Breastfeeding decreases the risk of developing psoriasis through to early adulthood.

BACKGROUND: Psoriasis is a genetically determined systemic skin disease, although environmental trigger factors are required for disease manifestation. Some of these triggers, such as stress, infections and drug exposure, have been identified. OBJECTIVES: To explore the role of early nutrition as a risk factor for the development of psoriasis. METHODS: Parents in the All Babies in Southeast Sweden (ABIS) prospective birth cohort (n = 16 415) answered questionnaires at birth and when their children were aged 1 and 3 years. A diagnosis of psoriasis was determined from the Swedish National Patient Register and National Drug Prescription Register. Statistical analyses were conducted using custom-written R scripts. RESULTS: Individuals breastfed for < 4 months and who received infant formula before 4 months of age had a higher risk of psoriasis [odds ratio (OR) 1.84 (P = 0.02) and OR 1.88 (P = 0.02), respectively]. At the 3-year follow-up, the increased consumption of fish, especially from the Baltic Sea, increased the risk of psoriasis (OR 9.61; P = 0.003). In addition, the risk of psoriasis increased following the consumption of a large volume of milk (OR 2.53; P = 0.04). CONCLUSIONS: Our study underscores, for the first time, the impact of very early nutrition on the manifestation of psoriasis through early adulthood. Exclusive breastfeeding for 4 months appears to be protective.

Early-life diet and risk of inflammatory bowel disease: a pooled study in two Scandinavian birth cohorts.

OBJECTIVE: We assessed whether early-life diet quality and food intake frequencies were associated with subsequent IBD. DESIGN: Prospectively recorded 1-year and 3-year questionnaires in children from the All Babies in Southeast Sweden and The Norwegian Mother, Father and Child Cohort Study were used to assess diet quality using a Healthy Eating Index and intake frequency of food groups. IBD was defined as >2 diagnoses in national patient registers. Cox regression yielded HRs adjusted (aHRs) for child's sex, parental IBD, origin, education level and maternal comorbidities. Cohort-specific results were pooled using a random-effects model. RESULTS: During 1 304 433 person-years of follow-up, we followed 81 280 participants from birth through childhood and adolescence, whereof 307 were diagnosed with IBD. Compared with low diet quality, medium and high diet quality at 1 year of age were associated with a reduced risk of IBD (pooled aHR 0.75 (95% CI=0.58 to 0.98) and 0.75 (95% CI=0.56 to 1.00)). The pooled aHR per increase of category was 0.86 (0.74 to 0.99). Pooled aHR for children 1 year old with high versus low fish intake was 0.70 (95% CI=0.49 to 1.00) for IBD, and showed association with reduced risk of UC (pooled aHR=0.46; 95% CI=0.21, 0.99). Higher vegetable intake at 1 year was associated with a risk reduction in IBD. Intake of sugar-sweetened beverages was associated with an increased risk of IBD. Diet quality at 3 years was not associated with IBD. CONCLUSION: In this Scandinavian birth cohort, high diet quality and fish intake in early life were associated with a reduced risk of IBD.

Early-Life Hygiene-Related Factors and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

BACKGROUND: We aimed to investigate whether early-life hygiene-related factors influenced the risk of inflammatory bowel disease (IBD) in a Scandinavian population and test the association's consistency across cohorts. METHODS: This study followed 117 493 participants in the All Babies in Southeast Sweden study and the Norwegian Mother, Father, and Child Cohort Study. IBD diagnoses were defined by national registers. Comprehensive data on hygiene-related exposures, such as having pets, rural living, daycare attendance, and siblings, were retrieved from questionnaires administered from pregnancy until child's age of 36 months. A multivariable Cox regression model yielded adjusted hazard ratios (aHRs) for IBD accounting for socioeconomic status and perinatal factors. Cohort-specific estimates were pooled using a random-effects model. RESULTS: In over 2 024 299 person-years of follow-up 451 participants developed IBD. In pooled estimates children attending daycare up to 36 months of life vs not attending daycare were less likely to develop Crohn's disease (aHR, 0.60; 95% confidence interval [CI], 0.37- 0.98). Children having 1 or more siblings had a modestly increased risk of IBD (aHR, 1.17; 95% CI, 0.96-1.42; aHR for each sibling, 1.12; 95% CI, 1.01-1.24). The other hygiene factors were not significantly linked to later IBD. In the Norwegian Mother, Father, and Child Cohort Study cohort, bed sharing was associated with an increased risk of IBD, most notably for ulcerative colitis (aHR, 1.67; 95% CI, 1.01-2.78). CONCLUSIONS: In this birth cohort study from 2 high-income Scandinavian countries, some early-life hygiene-related exposures were associated with IBD risk. The generalizability of these results to countries of other socioeconomic level is unknown.

Exposure to some hygiene factors during early childhood seems to be associated with the risk of later inflammatory bowel disease. The direction and magnitude of the associations need to be further studied before any clinical implications.

Physical activity in childhood and later risk of inflammatory bowel disease: A Scandinavian birth cohort study.

BACKGROUND AND OBJECTIVE: Retrospective data have linked adult physical activity (PA) to reduced risk of inflammatory bowel disease (IBD). We aimed to prospectively examine the association of PA and screen time (ST) in childhood with later risk of IBD, for which data are scarce. METHODS: Using two population-based birth cohorts (All Babies in Southeast Sweden [ABIS] and Norwegian Mother, Father, and Child Cohort Study [MoBa]), we retrieved parent-reported data on PA and ST degree at ages 3 and 8 years. Data were modelled as binary (high vs. low) and numerical (hours/day) exposures. Inflammatory bowel disease was defined as ≥2 diagnostic records in national health registers. Cox regression estimated hazard ratios adjusted for potential confounding from parental IBD, country of origin, education, and smoking habits (Adjusted hazard ratio (aHR)). Our 8-year analyses included a 2-year lag period to reduce the risk of reverse causation. Cohort-specific estimates were pooled using random-effects model. RESULT: Among 65,978 participants from ABIS (n = 8810) and MoBa (n = 57,168) with available data, 266 developed IBD. At 3 years, children with high versus low PA had an aHR of 1.12 for IBD (95%CI = 0.87-1.43); high versus low ST showed an aHR of 0.91 (95%CI = 0.71-1.17). Conversely, at 8 years, high versus low ST was associated with increased risk of later IBD (aHR = 1.51; 95%CI = 1.02-2.25), but PA at 8 years, was not linked to IBD (aHR = 1.19; 95%CI = 0.80-1.76). Subtype-specific analyses for Crohn's disease and ulcerative colitis did not differ appreciably. CONCLUSION: Acknowledging possible confounding variables, children with high versus low ST at 8 years were at increased risk of IBD. In contrast, PA degree was not linked to IBD at any age category.

Childhood Socioeconomic Characteristics and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

BACKGROUND: Ecological observations suggest a negative relationship between childhood socioeconomic status (SES) and inflammatory bowel disease (IBD) risk. Individual-level analyses have been inconsistent and mostly lacked refined assessments of SES. We aimed to comprehensively study the association between early-life SES and later IBD. METHODS: This study included 117 493 participants from the Norwegian Mother, Father and Child cohort and Swedish All Babies in Southeast Sweden cohorts. Participants were followed from birth (1997-2009) through 2021. IBD was identified through national patient registers. Questionnaire and register data were used to define parental educational level, employment, and household income level. Cox regression estimated adjusted hazard ratios (aHRs), accounting for other SES exposures and covariates (eg, parental IBD). Cohort-specific estimates were pooled using a random-effects model. RESULTS: During 2 024 299 person-years of follow-up, 451 participants were diagnosed with IBD (All Babies in Southeast Sweden cohort, n = 113 and Norwegian Mother, Father and Child cohort, n = 338). Early-life maternal, but not paternal, educational level was associated with later IBD (low vs high educational level; pooled aHR, 1.81; 95% confidence interval [CI], 1.16-2.82; and pooled aHR, 1.20; 95% CI, 0.80-1.80; respectively). Having a nonworking mother or father was not significantly associated with IBD (pooled aHR, 0.69; 95% CI, 0.47-1.02; pooled aHR, 0.79; 95% CI, 0.45-1.37). High vs low household income level yielded a pooled aHR of 1.33 (95% CI, 0.94-1.89). Overall, results were largely consistent across cohorts. CONCLUSIONS: In this prospective Scandinavian cohort study, low maternal educational level was, independent of other SES and covariates, significantly associated with later IBD in her child. Further research is needed to elucidate factors that may mediate this relationship.

In this Scandinavian birth cohort study with ≥117 000 participants, we used prospectively collected data to investigate the association between early-life socioeconomic status and later inflammatory bowel disease. We found low maternal educational level, independent of covariates, negatively associated with inflammatory bowel disease.

Epidemiology, validation, and clinical characteristics of inflammatory bowel disease: the ABIS birth cohort study.

BACKGROUND: Birth cohort studies with linked register-based data on inflammatory bowel disease (IBD) provide opportunities to prospectively study early-life determinants of the disease. However, register-based data often lack information on clinical characteristics and rely on diagnostic algorithms. Within the All Babies in Southeast Sweden (ABIS) cohort, we examined the validity of a register-based definition of IBD, its incidence, and clinical and therapeutic characteristics at diagnosis. METHODS: We followed 16,223 children from birth (1997-1999) until the end of 2020 for the diagnosis of IBD as defined by a minimum of two diagnostic codes for IBD in the Swedish National Patient Register (NPR). We described the incidence and cumulative incidence of IBD. Through a medical record review of cases diagnosed by the end of 2017, we examined the positive predictive value (PPV) for IBD and described its clinical characteristics and treatment. RESULTS: By 2020, at an average age of 22.2 years, 113 participants (0.74%, 95% confidence interval [CI] = 0.61-0.89) had a register-based diagnosis of IBD, corresponding to an incidence of 31.3 per 100,000 person-years of follow-up; the incidence for Crohn's disease (CD) was 11.1 per 100,000 person-years and 15.8 for ulcerative colitis (UC). Of 77 participants with a register-based definition of IBD by the end of 2017, medical records were identified for 61 participants, of whom 57 had true IBD (PPV = 93%; 95%CI = 0.87-1.00). While oral 5-aminosalicylic acid treatment was equally common in newly diagnosed CD and UC patients, biologics were more often used for newly diagnosed CD. The median faecal calprotectin levels were 1206 mg/kg at diagnosis and 93 mg/kg at the last follow-up (P < 0.001). CONCLUSIONS: In this population-based sample of Swedish children and young adults the cumulative IBD incidence was 0.74. The validity of register-based definition of IBD was high and supports using such data to identify IBD patients in cohort studies.

Reduction of systemic exposure and side effects by intra-articular injection of anti-inflammatory agents for osteoarthritis: what is the safer strategy?

Osteoarthritis (OA) is a chronic degenerative joint disease associated with pain, inflammation, and cartilage degradation. However, no current treatment can effectively halt the progression of the disease. Therefore, the use of NSAIDs and intra-articular corticosteroids is usually recommended as the primary treatment for OA-associated pain and inflammation. However, there is accumulating evidence that the long-term use of oral NSAIDs and intra-articular corticosteroids can lead to a myriad of negative side effects. Although numerous efforts have been made to develop intra-articular formulations for NSAIDs, the systemic exposure of intra-articular injection of NSAIDs and its potential side effects have not been explicitly investigated. To ascertain the evident and potential side effects of intra-articular injection of anti-inflammatory agents, we have summarised in this review the systemic exposure, local side effects, and systemic side effects of intra-articular injections of anti-inflammatory agents, including NSAIDs and corticosteroids. For developing a safer treatment to fulfil the unmet long-term use needs of patients, a new therapy, which combines the locally active drug and a sustained-release formulation, has been proposed in this review.

Methodological Approaches to Ketogenic Dietary Treatments in Glioma Patients from a Nutritional Point of View.

Ketogenic diets (KD) have received increasing interest in neuro-oncology based on their ability to inhibit glioma growth In Vitro and their established role in medically refractory seizures. This review analyses the methodological aspects of KD treatment alongside standard care for patients with gliomas from a nutritional point of view. A literature search was performed in March 2022 searching PubMed and Scopus. We identified 13 articles including 187 patients with a histological-new or recurrent-diagnosis of glioma and treated by KD during the course of the disease. Dietary treatments were categorized as the classical ketogenic diet (CKD), the Modified Atkins diet (MAD), and the medium-chain triglyceride (MCT) diet. We identified a large variation in dietary characteristics regarding restriction of carbohydrates, ketogenic ratio, and additional dietary support. This striking heterogenicity in the methodological approaches of KD treatments made it problematic to compare effects between the included studies. Therefore, a standardized definition of KD for patients with glioma and a consensus on methodological implementation is needed. It would also be desirable to further investigate to what extent KD treatment can be optimized to secure optimal nutrient status and patient satisfaction.

The interdependent transport of yeast vacuole Ca2+ and H+ and the role of phosphatidylinositol 3,5-bisphosphate.

Yeast vacuoles are acidified by the v-type H+-ATPase (V-ATPase) that is comprised of the membrane embedded VO complex and the soluble cytoplasmic V1 complex. The assembly of the V1-VO holoenzyme on the vacuole is stabilized in part through interactions between the VO a-subunit ortholog Vph1 and the lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). PI(3,5)P2 also affects vacuolar Ca2+ release through the channel Yvc1 and uptake through the Ca2+ pump Pmc1. Here, we asked if H+ and Ca2+ transport activities were connected through PI(3,5)P2. We found that overproduction of PI(3,5)P2 by the hyperactive fab1T2250A mutant augmented vacuole acidification, whereas the kinase-inactive fab1EEE mutant attenuated the formation of a H+ gradient. Separately, we tested the effects of excess Ca2+ on vacuole acidification. Adding micromolar Ca2+ blocked vacuole acidification, whereas chelating Ca2+ accelerated acidification. The effect of adding Ca2+ on acidification was eliminated when the Ca2+/H+ antiporter Vcx1 was absent, indicating that the vacuolar H+ gradient can collapse during Ca2+ stress through Vcx1 activity. This, however, was independent of PI(3,5)P2, suggesting that PI(3,5)P2 plays a role in submicromolar Ca2+ flux but not under Ca2+ shock. To see if the link between Ca2+ and H+ transport was bidirectional, we examined Ca2+ transport when vacuole acidification was inhibited. We found that Ca2+ transport was inhibited by halting V-ATPase activity with Bafilomycin or neutralizing vacuolar pH with chloroquine. Together, these data show that Ca2+ transport and V-ATPase efficacy are connected but not necessarily through PI(3,5)P2.

Dietary intake and meal patterns among young adults with high caries activity: a cross-sectional study.

BACKGROUND: Dental caries is a multifactorial disease that is highly dependent on diet, where a lower consumption and intake frequency of sugar would be favorable. The aims were (i) to examine dietary intake and meal patterns, more specifically sugar intake and foods high in sugar, among young adults with high caries activity, and (ii) to investigate the association between dietary and meal patterns consumption, and level of caries activity. METHODS: This study presents baseline data from an ongoing randomized controlled trial. A total of 50 young adults (aged 23.0 ± 3.0 years) with ≥ 2 decayed tooth surfaces were included. Dietary intake was captured with a 59-item food frequency questionnaire (FFQ) and a three-day food diary. Adherence to dietary guidelines was analyzed by comparing the dietary intake to the Nordic Nutritional Recommendations (NNR) 2012 and by using the Healthy Dietary Adherence score (HDAS). Participants were categorized into two groups: (i) the Caries group with 2-4 decayed surfaces, and (ii) the High caries group with ≥ 5 decayed surfaces. RESULTS: The High caries group reported a statistically significantly higher snack and total meal intake compared to the Caries group, as well as a sugar intake exceeding the Nordic nutritional recommendations. The majority of the participants reported a high intake frequency (> 2.5/day) of sweet foods and drinks and less than one intake of fruit and vegetables, respectively, per day. Similar results were found when analyzing adherence by using the HDAS, where the lowest adherence according to dietary guidelines was shown for the food groups of sugar, whole meal products, and fruit and vegetables. CONCLUSION: The results indicated a high intake of sugar and low intake of fruit, vegetables, and fiber in high caries-active individuals.

Shared decision-making in neurosurgery: a scoping review.

BACKGROUND: In modern neurosurgery, there are often several treatment alternatives, with different risks and benefits. Shared decision-making (SDM) has gained interest during the last decade, although SDM in the neurosurgical field is not widely studied. Therefore, the aim of this scoping review was to present the current landscape of SDM in neurosurgery. METHODS: A literature review was carried out in PubMed and Scopus. We used a search strategy based on keywords used in existing literature on SDM in neurosurgery. Full-text, peer-reviewed articles published from 2000 up to the search date February 16, 2021, with patients 18 years and older were included if articles evaluated SDM in neurosurgery from the patient's perspective. RESULTS: We identified 22 articles whereof 7 covered vestibular schwannomas, 7 covered spinal surgery, and 4 covered gliomas. The other topics were brain metastases, benign brain lesions, Parkinson's disease and evaluation of neurosurgical care. Different methods were used, with majority using forms, questionnaires, or interviews. Effects of SDM interventions were studied in 6 articles; the remaining articles explored factors influencing patients' decisions or discussed SDM aids. CONCLUSION: SDM is a tool to involve patients in the decision-making process and considers patients' preferences and what the patients find important. This scoping review illustrates the relative lack of SDM in the neurosurgical literature. Even though results indicate potential benefit of SDM, the extent of influence on treatment, outcome, and patient's satisfaction is still unknown. Finally, the use of decision aids may be a meaningful contribution to the SDM process.

Phosphatidylinositol 3,5-bisphosphate regulates Ca2+ transport during yeast vacuolar fusion through the Ca2+ ATPase Pmc1.

The transport of Ca2+ across membranes precedes the fusion and fission of various lipid bilayers. Yeast vacuoles under hyperosmotic stress become fragmented through fission events that requires the release of Ca2+ stores through the TRP channel Yvc1. This requires the phosphorylation of phosphatidylinositol-3-phosphate (PI3P) by the PI3P-5-kinase Fab1 to produce transient PI(3,5)P2 pools. Ca2+ is also released during vacuole fusion upon trans-SNARE complex assembly, however, its role remains unclear. The effect of PI(3,5)P2 on Ca2+ flux during fusion was independent of Yvc1. Here, we show that while low levels of PI(3,5)P2 were required for Ca2+ uptake into the vacuole, increased concentrations abolished Ca2+ efflux. This was as shown by the addition of exogenous dioctanoyl PI(3,5)P2 or increased endogenous production of by the hyperactive fab1T2250A mutant. In contrast, the lack of PI(3,5)P2 on vacuoles from the kinase dead fab1EEE mutant showed delayed and decreased Ca2+ uptake. The effects of PI(3,5)P2 were linked to the Ca2+ pump Pmc1, as its deletion rendered vacuoles resistant to the effects of excess PI(3,5)P2 . Experiments with Verapamil inhibited Ca2+ uptake when added at the start of the assay, while adding it after Ca2+ had been taken up resulted in the rapid expulsion of Ca2+ . Vacuoles lacking both Pmc1 and the H+ /Ca2+ exchanger Vcx1 lacked the ability to take up Ca2+ and instead expelled it upon the addition of ATP. Together these data suggest that a balance of efflux and uptake compete during the fusion pathway and that the levels of PI(3,5)P2 can modulate which path predominates.

Copper blocks V-ATPase activity and SNARE complex formation to inhibit yeast vacuole fusion.

The accumulation of copper in organisms can lead to altered functions of various pathways and become cytotoxic through the generation of reactive oxygen species. In yeast, cytotoxic metals such as Hg+ , Cd2+ and Cu2+ are transported into the lumen of the vacuole through various pumps. Copper ions are initially transported into the cell by the copper transporter Ctr1 at the plasma membrane and sequestered by chaperones and other factors to prevent cellular damage by free cations. Excess copper ions can subsequently be transported into the vacuole lumen by an unknown mechanism. Transport across membranes requires the reduction of Cu2+ to Cu+ . Labile copper ions can interact with membranes to alter fluidity, lateral phase separation and fusion. Here we found that CuCl2 potently inhibited vacuole fusion by blocking SNARE pairing. This was accompanied by the inhibition of V-ATPase H+ pumping. Deletion of the vacuolar reductase Fre6 had no effect on the inhibition of fusion by copper. This suggests that Cu2+ is responsible for the inhibition of vacuole fusion and V-ATPase function. This notion is supported by the differential effects of chelators. The Cu2+ -specific chelator triethylenetetramine rescued fusion, whereas the Cu+ -specific chelator bathocuproine disulfonate had no effect on the inhibited fusion.

Phosphatidylinositol 3,5-bisphosphate regulates the transition between trans-SNARE complex formation and vacuole membrane fusion.

Phosphoinositides (PIs) regulate a myriad of cellular functions including membrane fusion, as exemplified by the yeast vacuole, which uses various PIs at different stages of fusion. In light of this, the effect of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) on vacuole fusion remains unknown. PI(3,5)P2 is made by the PI3P 5-kinase Fab1 and has been characterized as a regulator of vacuole fission during hyperosmotic shock, where it interacts with the TRP Ca2+ channel Yvc1. Here we demonstrate that exogenously added dioctanoyl (C8) PI(3,5)P2 abolishes homotypic vacuole fusion. This effect was not linked to Yvc1, as fusion was equally affected using yvc1Δ vacuoles. Thus, the effects of C8-PI(3,5)P2 on fusion and fission operate through distinct mechanisms. Further testing showed that C8-PI(3,5)P2 inhibited vacuole fusion after trans-SNARE pairing. Although SNARE complex formation was unaffected, we found that C8-PI(3,5)P2 blocked outer leaflet lipid mixing. Overproduction of endogenous PI(3,5)P2 by the fab1T2250A hyperactive kinase mutant also inhibited the lipid mixing stage, bolstering the model in which PI(3,5)P2 inhibits fusion when present at elevated levels. Taken together, this work identifies a novel function for PI(3,5)P2 as a regulator of vacuolar fusion. Moreover, it suggests that this lipid acts as a molecular switch between fission and fusion.

Measuring patient flow in a children's hospital using a scorecard with composite measurement.

BACKGROUND: Although patient flow is a focus for improvement in hospitals, commonly used single or unaggregated measures fail to capture its complexity. Composite measures can account for multiple dimensions of performance but have not been reported for the assessment of patient flow. OBJECTIVES: To present and discuss the implementation of a composite measure system as a way to measure and monitor patient flow and improvement activities at an urban children's hospital. METHODS: A 5-domain patient flow scorecard with composite measurement was designed by an interdisciplinary workgroup using measures involved in multiple aspects of patient flow. RESULTS: The composite score measurement system provided improvement teams and administrators with a comprehensive overview of patient flow. It captured overall performance trends and identified operational domains and specific components of patient flow that required improvement. DISCUSSION: A patient flow scorecard with composite measurement holds advantages over a single or unaggregated measurement system, because it provides a holistic assessment of performance while also identifying specific areas in need of improvement.