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Background It is challenging to identify malnutrition, which is a risk factor for poor outcome in patients with liver cirrhosis. In the present study, we aimed to investigate the prevalence of malnutrition among patients listed for liver transplantation, as assessed by different methods, and also to relate dual-energy X-ray absorptiometry ( DXA) to short-term post-transplant outcomes. Methods In this retrospective cohort study, we reviewed the medical records of 106 patients who underwent liver transplantation in 2009-2012. Body composition was assessed by the fat-free mass index ( FFMI) and fat mass index ( FMI) obtained using DXA. Severe infections within 1 month, length of stay in intensive care unit and length of hospital stay were endpoints of primary interest. Results The prevalence of malnutrition was 2-20% depending on sex and the assessment method. Thirty-nine (37%) patients developed severe infections within 1 month after liver transplantation. In multivariate analysis with logistic regression, body composition was significantly associated with post-operative infection when measured with FFMI ( P = 0.043) but not with FMI ( P = 0.087). Post-operative dialysis ( P = 0.004) and post-operative infections ( P < 0.001) were significantly associated with length of stay in hospital. Post-operative bleeding ( P = 0.015), duration of mechanical ventilation ( P < 0.001) and the need for dialysis ( P < 0.001), but not body composition, were significant predictors of the length of stay in the intensive care unit. Conclusions The prevalence of malnutrition depends on assessment method. FFMI is an independent predictor for early post-transplant infections. Body composition measured by DXA during the pretransplant evaluation provides valuable information about nutritional status in patients with liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Individuals with primary sclerosing cholangitis (PSC) have expressed a need for more dietary information. The aim of this study was to evaluate the dietary intake of individuals with PSC and compare it with Nordic nutrition recommendations 2023 (NNR2023)., Methods: A cross-sectional assessment of dietary intake was performed using a food-frequency questionnaire among 120 individuals with PSC from five regions across Sweden. Macro- and micronutrient intake was compared to NNR2023. Dietary quality was evaluated using an index developed by the National Food Agency in Sweden., Results: The median age was 47 years (IQR 18), and median body mass index (BMI) was 25.2 kg/m 2 (IQR 5.9). Eight percent had a BMI < 20, and 13% had a BMI > 30. The average fibre intake was 18 g (IQR 18). Median energy distribution included 36% from fat (15% saturated, 4.6% polyunsaturated), 17% from protein and 43% from carbohydrates, highlighting an imbalanced diet with low carbohydrate, fibre and polyunsaturated fat intake and high saturated fat consumption. More than half reported suboptimal intake of zinc, selenium and vitamins C, D and K and > 30% suboptimal intake of vitamins A, B6, E, niacin, folate, potassium, magnesium and iron. Forty percent had poor dietary quality. Longer PSC duration and previous colectomy were associated with a lower dietary quality., Conclusions: Many individuals with PSC do not reach the recommended levels of various micronutrients, especially fat-soluble vitamins and report a poor dietary quality. The results highlight the need for a comprehensive approach to nutritional management in this population., Trial Registration: ClinicalTrials.gov identifier: NCT04133792., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Over the past 15 years, the D-statistic, a four-taxon test for organismal admixture (hybridization, or introgression) which incorporates single nucleotide polymorphism data with allelic patterns ABBA and BABA, has seen considerable use. This statistic seeks to discern significant deviation from either a given species tree assumption, or from the balanced incomplete lineage sorting that could otherwise defy this species tree. However, while the D-statistic can successfully discriminate admixture from incomplete lineage sorting, it is not a simple matter to determine the directionality of admixture using only four-leaf tree models. As such, methods have been developed that use five leaves to evaluate admixture. Among these, the DFOIL method ("FOIL", a mnemonic for "First-Outer-Inner-Last"), which tests allelic patterns on the "symmetric" tree S=(((1,2),(3,4)),5), succeeds in finding admixture direction for many five-taxon examples. However, DFOIL does not make full use of all symmetry, nor can DFOIL function properly when ancient samples are included because of the reliance on singleton patterns (such as BAAAA and ABAAA). Here, we take inspiration from DFOIL to develop a new and completely general family of five-leaf admixture tests, dubbed Δ-statistics, that can either incorporate or exclude the singleton allelic patterns depending on individual taxon and age sampling choices. We describe two new shapes that are also fully testable, namely the "asymmetric" tree A=((((1,2),3),4),5) and the "quasisymmetric" tree Q=(((1,2),3),(4,5)), which can considerably supplement the "symmetric" S=(((1,2),(3,4)),5) model used by DFOIL. We demonstrate the consistency of Δ-statistics under various simulated scenarios, and provide empirical examples using data from black, brown and polar bears, the latter also including two ancient polar bear samples from previous studies. Recently, DFOIL and one of these ancient samples was used to argue for a dominant polar bear → brown bear introgression direction. However, we find, using both this ancient polar bear and our own, that by far the strongest signal using both DFOIL and Δ-statistics on tree S is actually bidirectional gene flow of indistinguishable direction. Further experiments on trees A and Q instead highlight what were likely two phases of admixture: one with stronger brown bear → polar bear introgression in ancient times, and a more recent phase with predominant polar bear → brown bear directionality., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Dietary fatty acids (FA) affect metabolic risk factors. The aim of this study was to explore if changes in dietary fat intake during energy restriction were associated with plasma FA composition. The study also investigated if these changes were associated with changes in liver fat, liver stiffness and plasma lipids among persons with non-alcoholic fatty liver disease. Dietary and plasma FA were investigated in patients with non-alcoholic fatty liver disease ( n 48) previously enrolled in a 12-week-long open-label randomised controlled trial comparing two energy-restricted diets: a low-carbohydrate high-fat diet and intermittent fasting diet (5:2), to a control group. Self-reported 3 d food diaries were used for FA intake, and plasma FA composition was analysed using GC. Liver fat content and stiffness were measured by MRI and transient elastography. Changes in intake of total FA ( r 0·41; P = 0·005), SFA ( r 0·38; P = 0·011) and MUFA ( r 0·42; P = 0·004) were associated with changes in liver stiffness. Changes in plasma SFA ( r 0·32; P = 0·032) and C16 : 1 n -7 ( r 0·33; P = 0·028) were positively associated with changes in liver fat, while total n -6 PUFA ( r -0·33; P = 0·028) and C20 : 4 n -6 ( r -0·42; P = 0·005) were inversely associated. Changes in dietary SFA, MUFA, cholesterol and C20:4 were positively associated with plasma total cholesterol and LDL-cholesterol. Modifying the composition of dietary fats during dietary interventions causes changes in the plasma FA profile in patients with non-alcoholic fatty liver disease. These changes are associated with changes in liver fat, stiffness, plasma cholesterol and TAG. Replacing SFA with PUFA may improve metabolic parameters in non-alcoholic fatty liver disease patients during weight loss treatment.

Island systems provide important contexts for studying processes underlying lineage migration, species diversification, and organismal extinction. The Hawaiian endemic mints (Lamiaceae family) are the second largest plant radiation on the isolated Hawaiian Islands. We generated a chromosome-scale reference genome for one Hawaiian species, Stenogyne calaminthoides, and resequenced 45 relatives, representing 34 species, to uncover the continental origins of this group and their subsequent diversification. We further resequenced 109 individuals of two Stenogyne species, and their purported hybrids, found high on the Mauna Kea volcano on the island of Hawai'i. The three distinct Hawaiian genera, Haplostachys, Phyllostegia, and Stenogyne, are nested inside a fourth genus, Stachys. We uncovered four independent polyploidy events within Stachys, including one allopolyploidy event underlying the Hawaiian mints and their direct western North American ancestors. While the Hawaiian taxa may have principally diversified by parapatry and drift in small and fragmented populations, localized admixture may have played an important role early in lineage diversification. Our genomic analyses provide a view into how organisms may have radiated on isolated island chains, settings that provided one of the principal natural laboratories for Darwin's thinking about the evolutionary process., (© 2024. The Author(s).)

With populations of threatened and endangered species declining worldwide, efforts are being made to generate high quality genomic records of these species before they are lost forever. Here, we demonstrate that data from single Oxford Nanopore Technologies (ONT) MinION flow cells can, even in the absence of highly accurate short DNA-read polishing, produce high quality de novo plant genome assemblies adequate for downstream analyses, such as synteny and ploidy evaluations, paleodemographic analyses, and phylogenomics. This study focuses on three North American ash tree species in the genus Fraxinus (Oleaceae) that were recently added to the International Union for Conservation of Nature (IUCN) Red List as critically endangered. Our results support a hexaploidy event at the base of the Oleaceae as well as a subsequent whole genome duplication shared by Syringa, Osmanthus, Olea, and Fraxinus. Finally, we demonstrate the use of ONT long-read sequencing data to reveal patterns in demographic history., (© 2024. The Author(s).)

Subgenome dominance after whole-genome duplication generates distinction in gene number and expression at the level of chromosome sets, but it remains unclear how this process may be involved in evolutionary novelty. Here we generated a chromosome-scale genome assembly of the Asian pitcher plant Nepenthes gracilis to analyse how its novel traits (dioecy and carnivorous pitcher leaves) are linked to genomic evolution. We found a decaploid karyotype and a clear indication of subgenome dominance. A male-linked and pericentromerically located region on the putative sex chromosome was identified in a recessive subgenome and was found to harbour three transcription factors involved in flower and pollen development, including a likely neofunctionalized LEAFY duplicate. Transcriptomic and syntenic analyses of carnivory-related genes suggested that the paleopolyploidization events seeded genes that subsequently formed tandem clusters in recessive subgenomes with specific expression in the digestive zone of the pitcher, where specialized cells digest prey and absorb derived nutrients. A genome-scale analysis suggested that subgenome dominance likely contributed to evolutionary innovation by permitting recessive subgenomes to diversify functions of novel tissue-specific duplicates. Our results provide insight into how polyploidy can give rise to novel traits in divergent and successful high-ploidy lineages., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Inclusion of package leaflets in paper format is a legal requirement in European Union (EU), therefore the electronic package leaflet (ePL) is a relatively unknown phenomenon in medicinal products in Europe. Introduction of ePL only would be a more sustainable format of providing the product information than paper package leaflet. Furthermore, ePL would support health care professionals' comprehension of product use through electronic searchability and facilitate access to up-to-date product information in respective language used. It could also help us to tackle the availability issues and be a further step towards common packages. With this commentary, our aim is to review the ongoing ePL pilots in hospital settings in Europe and identify the benefits and challenges of ePL. Based on our review, there is a broad general support for the removal of paper package leaflets from hospital products. Packages without paper package leaflets are considered more sustainable due to savings in production and materials. Furthermore, ePL could be a facilitator for common packages in EU-countries with the benefit of reducing pharmaceutical waste and drug shortages. The most important benefit from both pharmaceutical industry and healthcare professionals' interest is that current and on-line updated product information is always electronically available, especially from drug safety perspective., (Copyright © 2023. Published by Elsevier B.V.)

Background & Aims: Intensive nutritional therapy is an essential component of burn care. Regarding post-minor burn injuries, the literature is lacking. The aim of this study was to evaluate documented nutritional therapy in relation to international guidelines after both minor and major burn injuries. The secondary aim of this study was to evaluate the adequacy of energy and protein intake compared to individual nutritional goals post-burn injury., Methods: A retrospective observational single-centre study including patients admitted between 2017 and 2019 at a burn centre in Sweden was performed. The patients included in the study were ≥18 years old and in need of hospital care for ≥72 h post-burn injury. Information about patients' demographics, nutritional therapy, and clinical characteristics of burn injury was collected. The patients were divided according to total body surface area burnt (TBSA %) into minor burn injuries (TBSA <20%) and major burn injuries (TBSA ≥20%). Descriptive statistics were used to analyse data. Adherence to guidelines was established by comparing 24 nutritional therapy recommendations to documented treatment. If documented nutritional treatment were in accordance with guidelines, adherence was considered high (≥80%), moderate (60-79.9%) or low (<59.9%)., Results: One hundred thirty-four patients were included, 90 patients with minor burn injuries and 44 patients with major burn injuries. Documented adherence to the nutritional guideline was overall low. After minor burn injury, 8% (2/24) of nutritional therapy recommendations had a high adherence (fat intake <35% of total energy intake and enteral nutrition as prioritized feeding route), 17% (4/24) a moderate adherence, and 75% (18/24) a low adherence. In patients treated after a major burn injury, there were two recommendations with documented high adherence (Vitamin C and Zinc); 25% (6/24) had moderate adherence, and 67% (16/24) had low adherence. In addition, quite a large amount of missing data was found. Adequacy of documented nutritional intake, compared to the individual documented goal, was 78% (±23%) for energy and 66% (±22%) for protein after minor burn injury. After major burn injury, the adequacy was 89% (±21%) for energy and 78% (±19%) for protein, respectively., Conclusions: This study revealed low adherence to nutritional guidelines in patients treated for minor and major burn injuries. Compared to major burn injuries, lower documented adequacy for both energy and proteins was found in minor burn injuries. Given the disparity between guidelines and documented nutritional therapy, and the lack of specific guidelines for minor burn injuries, there could be a considerable risk of inadequate nutritional therapy post-burn injury., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

During the Late Pleistocene, major parts of North America were periodically covered by ice sheets. However, there are still questions about whether ice-free refugia were present in the Alexander Archipelago along the Southeast (SE) Alaska coast during the last glacial maximum (LGM). Numerous subfossils have been recovered from caves in SE Alaska, including American black (Ursus americanus) and brown (U. arctos) bears, which today are found in the Alexander Archipelago but are genetically distinct from mainland bear populations. Hence, these bear species offer an ideal system to investigate long-term occupation, potential refugial survival and lineage turnover. Here, we present genetic analyses based on 99 new complete mitochondrial genomes from ancient and modern brown and black bears spanning the last ~45,000 years. Black bears form two SE Alaskan subclades, one preglacial and another postglacial, that diverged >100,000 years ago. All postglacial ancient brown bears are closely related to modern brown bears in the archipelago, while a single preglacial brown bear is found in a distantly related clade. A hiatus in the bear subfossil record around the LGM and the deep split of their pre- and postglacial subclades fail to support a hypothesis of continuous occupancy in SE Alaska throughout the LGM for either species. Our results are consistent with an absence of refugia along the SE Alaska coast, but indicate that vegetation quickly expanded after deglaciation, allowing bears to recolonize the area after a short-lived LGM peak., (© 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Objectives: Dietary composition may affect body composition during weight loss therapy. We tested the hypothesis of whether dietary macronutrient composition influences the reduction of total abdominal adipose tissue, subcutaneous adipose tissue (SAT), or visceral adipose tissue (VAT) during weight loss., Methods: Dietary macronutrient composition and body composition were analyzed as a secondary outcome of a randomized controlled trial of 62 participants with non-alcoholic fatty liver disease. Patients were randomly assigned to a calorie-restricted intermittent fasting (5:2), calorie-restricted low-carbohydrate high-fat (LCHF), or healthy lifestyle advice (standard-of-care) diet in a 12-wk intervention phase. Dietary intake was assessed by self-reported 3-d food diaries and by characterization of total plasma fatty acid profile. Percentage of energy intake (E%) from different macronutrients was calculated. Body composition was assessed by magnetic resonance imaging and anthropometric measurements., Results: The macronutrient composition differed significantly between the 5:2 (fat 36 E% and carbohydrates 43 E%) and the LCHF (fat 69 E% and carbohydrates 9 E%) groups (P < 0.001). Weight loss was similar in the 5:2 and LCHF groups (-7.2 [SD = 3.4] kg versus 8.0 [SD = 4.8] kg; P = 0.44) and significantly larger than for standard of care (-2.5 kg [SD = 2.3]; P < 0.001). The volume of total abdominal fat, adjusted for height, decreased on average by 4.7% (standard of care), 14.3% (5:2), and 17.7% (LCHF), with no significant differences between the 5:2 and LHCF groups (P = 0.32). VAT and SAT, adjusted for height, decreased on average by 17.1% and 12.7% for 5:2, respectively, and by 21.2% and 17.9% for LCHF, with no significant group differences (VAT [P = 0.16] and SAT [P = 0.10]). VAT was mobilized to a greater extent than SAT in all diets., Conclusions: The 5:2 and LCHF diets had similar effects on changes in intraabdominal fat mass and anthropometrics during weight loss. This might indicate that overall weight loss is more important than diet composition to achieve changes in total abdominal adipose tissue, VAT, or SAT. The results of the present study suggest that there is a need for further studies on the effect of diet composition on body composition changes during weight loss therapy., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many specifics of the population histories of the Indigenous peoples of North America remain contentious owing to a dearth of physical evidence. Only few ancient human genomes have been recovered from the Pacific Northwest Coast, a region increasingly supported as a coastal migration route for the initial peopling of the Americas. Here, we report paleogenomic data from the remains of a ∼3,000-year-old female individual from Southeast Alaska, named Tatóok yík yées sháawat ( TYYS ). Our results demonstrate at least 3,000 years of matrilineal genetic continuity in Southeast Alaska, and that TYYS is most closely related to ancient and present-day northern Pacific Northwest Coast Indigenous Americans. We find no evidence of Paleo-Inuit (represented by Saqqaq ) ancestry in present-day or ancient Pacific Northwest peoples. Instead, our analyses suggest the Saqqaq genome harbors Northern Native American ancestry. This study sheds further light on the human population history of the northern Pacific Northwest Coast., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Species radiations, despite immense phenotypic variation, can be difficult to resolve phylogenetically when genetic change poorly matches the rapidity of diversification. Genomic potential furnished by palaeopolyploidy, and relative roles for adaptation, random drift and hybridisation in the apportionment of genetic variation, remain poorly understood factors. Here, we study these aspects in a model radiation, Syzygium, the most species-rich tree genus worldwide. Genomes of 182 distinct species and 58 unidentified taxa are compared against a chromosome-level reference genome of the sea apple, Syzygium grande. We show that while Syzygium shares an ancient genome doubling event with other Myrtales, little evidence exists for recent polyploidy events. Phylogenomics confirms that Syzygium originated in Australia-New Guinea and diversified in multiple migrations, eastward to the Pacific and westward to India and Africa, in bursts of speciation visible as poorly resolved branches on phylogenies. Furthermore, some sublineages demonstrate genomic clines that recapitulate cladogenetic events, suggesting that stepwise geographic speciation, a neutral process, has been important in Syzygium diversification., (© 2022. The Author(s).)

Objectives: Head and neck cancers (HNCs) include various malignant tumors of the upper aerodigestive tract. Due to their anatomical location, HNCs can cause obstruction, odynophagia, or trismus, leading to dysphagia. In addition, this patient group may be vulnerable to treatment side effects both by surgery and oncological treatment, exposing the patients to an even higher risk of malnutrition. The risk of malnourishment is often resolved by applying a feeding gastrostomy tube. The present study aims to identify complication rates after percutaneous endoscopic gastrostomy (PEG) and open gastrostomy (OG) in patients treated for HNC in a high-volume center., Study Design: Retrospective cohort study., Methods: A retrospective cohort study of all patients treated for a new diagnosis of HNC at the Department of Otorhinolaryngology and Head and Neck Surgery at Karolinska University Hospital between January 1, 2000 and December 31, 2018 in whom gastrostomy was performed., Results: Regarding tumor location, 165 (56.7%) were in the pharynx, 68 (23.4%) in the oral cavity, 57 (19.6%) in the larynx, and 1 (0.3%) in the nasal cavity. PEG was performed in 240 (82.5%) and OG in 51 (17.5%) patients. The overall complication rate was 28.2%: 64 (26.7%) among PEG patients and 18 (35.3%) among OG patients. The incidence of major complications was 3.1%., Conclusions: Our study confirms that enteral feeding via gastrostomy is a safe method, regardless of the technique used (PEG or OG), with a low rate of major complications and no mortality linked to the procedure., Level of Evidence: 3 Laryngoscope, 132:1778-1784, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background/aim: Previous studies have demonstrated that NK cells present in PBMCs might explain why clinical trials conducted with NK-92 as well as CAR modified NK-92 cells have to a large extent failed. Two NK-92 clones with different NK target cell properties have been established and are described here., Materials and Methods: Two NK-92 cell clones, NK-92 clone 1 and clone 2, were established using the limiting dilution technique. A time-resolved fluorometric assay (TDA-labeled NK-92 clone 1, 2 or K562 as target cells) was used for measuring their sensitivities to NK cell-mediated cytolysis and their NKG2D expression was identified with immunoblotting., Results: A striking difference between the NK-92 clones in their cytotoxic capacity against K562 cells was observed. A clear correlation was noticed between these NK-92 clones when used as target cells and their ability to kill K562 cells. A 50:1 effector:target ratio (PBMCs:NK-92 clone 1) gave 6.50±5.44% lysis whereas the corresponding value was 39.9±10.0% with NK-92 clone 2 as target cells. Interestingly, incubating PBMCs in medium for longer times slightly potentiated their NK activity also against the NK-92 clone 1 (E:T ratio 50:1), from 2.5±0.88% lysis (24 h pre-incubation time) to 13.7±9.04% (48 h) and 13.8±6.89% (72 h). Immunoblotting with anti-NKG2D antibodies stained an approximately 34 kDa protein band in lysates prepared from NK-92 clone 1 cells, which corresponds to the NKG2D antigen. A very faint band of the same size was observed in lysates prepared from NK-92 clone 2 cells., Conclusion: The NK-92 clones 1 and 2, established and described here, might turn out to be very useful for finding possible solutions for using NK-92 and CAR NK-92 cells in future treatments of human malignant diseases., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The polar bear (Ursus maritimus) has become a symbol of the threat to biodiversity from climate change. Understanding polar bear evolutionary history may provide insights into apex carnivore responses and prospects during periods of extreme environmental perturbations. In recent years, genomic studies have examined bear speciation and population history, including evidence for ancient admixture between polar bears and brown bears (Ursus arctos). Here, we extend our earlier studies of a 130,000- to 115,000-y-old polar bear from the Svalbard Archipelago using a 10× coverage genome sequence and 10 new genomes of polar and brown bears from contemporary zones of overlap in northern Alaska. We demonstrate a dramatic decline in effective population size for this ancient polar bear’s lineage, followed by a modest increase just before its demise. A slightly higher genetic diversity in the ancient polar bear suggests a severe genetic erosion over a prolonged bottleneck in modern polar bears. Statistical fitting of data to alternative admixture graph scenarios favors at least one ancient introgression event from brown bears into the ancestor of polar bears, possibly dating back over 150,000 y. Gene flow was likely bidirectional, but allelic transfer from brown into polar bear is the strongest detected signal, which contrasts with other published work. These findings may have implications for our understanding of climate change impacts: Polar bears, a specialist Arctic lineage, may not only have undergone severe genetic bottlenecks but also been the recipient of generalist, boreal genetic variants from brown bears during critical phases of Northern Hemisphere glacial oscillations.

Objectives: Patients undergoing liver transplantation (LT) are at risk for eating difficulties. Adequate nutritional support is important to promote enhanced recovery and to reduce postoperative complications. The aim of this study was to evaluate two nutritional protocols and their effect on total protein intake during the first 7 d after LT., Methods: Adult patients were monitored daily for energy and protein intake during the first week after LT. Patients with ≥3 d of monitoring were included in the study. Two patient groups were studied: protocol A (pA) based on enteral nutrition (EN) provided from postoperative days 1 through 4 (historical control); and protocol B (pB), which was based on high volume of EN and high-protein oral nutritional supplements (ONS). Outcome measures were hospital length of stay and grade of complications according to Clavien-Dindo within the first 3 mo after transplantation., Results: Seventy patients were included in the study (pA n=34, pB n= 36). The median age was 59 y and 70% were men. During postoperative week 1, patients with pB had a higher daily protein intake (95 g versus 77 g, P < 0.01) and met a higher proportion of estimated protein requirements (80% versus 70%, P < 0.05). There were no differences in severe postoperative outcomes between the two groups., Conclusions: A nutritional protocol with a higher rate of EN and high-protein ONS resulted in a higher protein intake early after LT. However, there was no difference in severe postoperative outcomes between the two nutritional protocols., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Anti-D alloimmunization is the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). The management of pregnancies affected by less frequent red blood cell (RBC) antibodies poses a challenge to clinicians, and perinatal outcomes are less well described. This study aimed to describe the frequency of clinically significant RBC antibodies in our pregnant population and analyze the risk of prenatal and postnatal treatment for HDFN in relation to our national risk classification system and management guidelines., Material and Methods: A retrospective cohort study in the population of all alloimmunized singleton pregnancies in the Stockholm region 1990-2016. Descriptive summaries of different RBC antibodies and pregnancy outcomes were presented, the risks of intrauterine blood transfusion (IUT) and neonatal treatment for HDFN were estimated by type of antibodies., Results: Of the 1724 alloimmunized pregnancies, 1079 (63%) were at risk of HDFN and constituted our study cohort. Anti-D was detected in 492 (46%) pregnancies, followed by anti-E in 161 (15%), and anti-c in 128 (12%). Eighty-seven (8%) pregnancies had IUT, with the highest risk in pregnancies affected by anti-D combined with other antibodies. The maximum titer recorded before IUT was 64 or above, except for two pregnancies affected by anti-c, for which the maximum titers were 8 and 16. For the 942 (95%) live-born neonates from 992 alloimmunized pregnancies without IUT, the median gestational age at birth was 38 +5  weeks compared with 35 +5  weeks for those who had IUT. Neonatal treatment was most common in the anti-D alone and anti-D combined groups, with 136 (57%) and 21 (44%), respectively, treated with phototherapy and 35 (15%) and 9 (20%) receiving exchange transfusions, respectively. For pregnancies complicated by moderate- and low-risk antibodies, phototherapy was less frequent (32 [36%] and 21 [19%]) and exchange transfusion was rare (5 [6%] and 3 [3%])., Conclusions: Anti-D, especially in combination with other antibodies, presents the highest risk of severe HDFN. The classification of less frequent and less well-known RBC antibodies into risk groups can help clinicians in assessing the risk of HDFN and counseling alloimmunized pregnant women regarding the risk of prenatal and postnatal treatments., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Enteric glial cells (EGC) and mast cells (MC) are intimately associated with gastrointestinal physiological functions. We aimed to investigate EGC-MC interaction in irritable bowel syndrome (IBS), a gut-brain disorder linked to increased intestinal permeability, and MC., Methods: Parallel approaches were used to quantify EGC markers in colonic biopsies from healthy controls (HC) and patients with IBS. Data were correlated with MC, vasoactive intestinal polypeptide (VIP) and VIP receptors (VPAC1/VPAC2) expressions, and bacterial translocation through biopsies mounted in Ussing chambers. In addition, we investigated the effects of EGC mediators on colonic permeability and the pharmacological-induced responses of EGC and MC cell lines., Key Results: Immunofluorescence of IBS colonic mucosa, as well as Western blotting and ELISA of IBS biopsy lysates, revealed increased glial fibrillary intermediate filament (GFAP) expression, indicating EGC activation. Mucosal GFAP correlated with increased MC and VPAC1 + MC numbers and decreased VIP + MC, which seemed to control bacterial translocation in HC. In the contrary, EGC activation in IBS correlated with less MC and VPAC1 + MC numbers, and more VIP + MC. In vitro, MC and EGC cell lines showed intracellular calcium responses to each other's mediators. Furthermore, EGC mediators prevented VIP-induced MC degranulation, while MC mediators induced a reactive EGC phenotype. In Ussing chambers, EGC mediators decreased paracellular passage through healthy colonic biopsies., Conclusions & Inferences: Findings suggest the involvement of EGC and MC in the control of barrier function in the human colon and indicate a potential EGC-MC interaction that seems altered in IBS, with detrimental consequences to colonic permeability. Altogether, results suggest that imbalanced EGC-MC communication contributes to the pathophysiology of IBS., (© 2021 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Physiotherapists in primary health care are required to use patient reported outcome measures (PROMs) to manage patients with low back pain (LBP)., Objective: Our aim was to explore and describe how physiotherapists in primary care managing patients with LBP, experience the use of PROMs with a focus on facilitating and hindering factors., Methods: We undertook a qualitative study with semi-structured interviews. Fifteen physiotherapists (9 female and 6 male) were included. The interviews were audio-recorded and transcribed verbatim and analysed by inductive manifest content analysis., Results: Our findings resulted in eight main categories: PROMs give structure and increase patient involvement; Patients' motivations to use PROMs; Time and the physiotherapist's clinical priorities; Physiotherapists' routines steer their use of PROMs; Physiotherapists' competences in using PROMs; Organizations and managers steer the use of PROMs; Prerequisites for future use of PROMs; Using PROMs develops the physiotherapy profession., Conclusion: Our findings show that using PROMs gives structure and increases patient involvement, but the patient's motivation to use PROMs needs to be taken into consideration. Time and routines influence the use of PROMs and these factors depend on organizational and managerial levels. Using PROMs is believed to help develop the physiotherapy profession. Prerequisites for future use, such as digitalization and increased competence, need to be fulfilled. Future studies should focus on increasing physiotherapists' knowledge about relevant PROMs, and study implementation in clinical practice, thereby improving the physiotherapy profession's quality of care., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Background/aim: Recent studies have indicated that natural killer (NK) cells present in peripheral blood mononuclear cells (PBMCs) might be responsible for the somewhat poor outcome of clinical trials conducted with the NK cell line NK-92, as well as chimeric antigen receptor-modified NK-92 cells against leukemias and lymphomas. These NK cells and how their cytotoxic profiles can be altered by some common gamma chain receptor-dependent cytokines or by removal of CD4 + cells have been addressed herein., Materials and Methods: A time-resolved fluorometric assay using 2.2':6'.2"-terpyridine-6.6"-dicarboxylic acid-labeled NK-92 or K562 as target cells was used for measuring the cytotoxic activity of cytokine-treated PBMCs and purified NK cells., Results: Pre-incubation with 25 ng/ml interleukin 12 (IL-12), IL-15 or IL-21 for 72 h increased NK cell activity against K562 cells by more than 90% (1:25 target:effector ratio), whereas the corresponding NK cell activity against NK-92 cells was reduced by 15.9±0.1% by IL-12 and 50.6±2.9% by IL-15 compared to cells treated with medium alone. IL-7, on the other hand, increased NK activity against K562 to a much smaller extent (10.4±0.4%) and inhibited NK-92 cell lysis by 15.2±0.3%. Interestingly, similar amounts of IL-2 potentiated NK cell activity against both K562 and NK-92 cells by 50.9±0.5% and 14.3±0.9%, respectively. Purification of NK cells with magnetic beads demonstrated that NK cells indeed were responsible for the observed cytotoxic activity against both NK-92 cells (58.5±9.10%, 1:100 target:effector ratio) and K562 cells (81.6±9.57%, 1:100 target:effector ratio). Elimination of CD4+ cells from PBMCs did not alter the NK activity profile., Conclusion: This study highlights a problem that might arise with immune-based NK-92 and chimeric antigen receptor-transduced NK-92 cell therapies and pinpoints the need for evaluating new NK-like cell lines., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.

The oldest confirmed remains of domestic dogs in North America are from mid-continent archaeological sites dated approximately 9900 calibrated years before present (cal BP). Although this date suggests that dogs may not have arrived alongside the first Native Americans, the timing and routes for the entrance of New World dogs remain uncertain. Here, we present a complete mitochondrial genome of a dog from southeast Alaska, dated to 10 150 ± 260 cal BP. We compared this high-coverage genome with data from modern dog breeds, historical Arctic dogs and American precontact dogs (PCDs) from before European arrival. Our analyses demonstrate that the ancient dog belongs to the PCD lineage, which diverged from Siberian dogs around 16 700 years ago. This timing roughly coincides with the minimum suggested date for the opening of the North Pacific coastal (NPC) route along the Cordilleran Ice Sheet and genetic evidence for the initial peopling of the Americas. This ancient southeast Alaskan dog occupies an early branching position within the PCD clade, indicating it represents a close relative of the earliest PCDs that were brought alongside people migrating from eastern Beringia southward along the NPC to the rest of the Americas. The stable isotope δ C value of this early dog indicates a marine diet, different from the younger mid-continent PCDs' terrestrial diet. Although PCDs were largely replaced by modern European dog breeds, our results indicate that their population decline started approximately 2000 years BP, coinciding with the expansion of Inuit peoples, who are associated with traditional sled-dog culture. Our findings suggest that dogs formed part of the initial human habitation of the New World, and provide insights into their replacement by both Arctic and European lineages.13 C value of this early dog indicates a marine diet, different from the younger mid-continent PCDs' terrestrial diet. Although PCDs were largely replaced by modern European dog breeds, our results indicate that their population decline started approximately 2000 years BP, coinciding with the expansion of Inuit peoples, who are associated with traditional sled-dog culture. Our findings suggest that dogs formed part of the initial human habitation of the New World, and provide insights into their replacement by both Arctic and European lineages.

Background & Aims: The first-line treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction. Several diets have been proposed, with various effects specifically on liver steatosis. This trial compared the effects of intermittent calorie restriction (the 5:2 diet) and a low-carb high-fat diet (LCHF) on reduction of hepatic steatosis., Methods: We conducted an open-label randomised controlled trial that included 74 patients with NAFLD randomised in a 1:1:1 ratio to 12 weeks' treatment with either a LCHF or 5:2 diet, or general lifestyle advice from a hepatologist (standard of care; SoC). The primary outcome was reduction of hepatic steatosis as measured by magnetic resonance spectroscopy. Secondary outcomes included transient elastography, insulin resistance, blood lipids, and anthropometrics., Results: The LCHF and 5:2 diets were both superior to SoC treatment in reducing steatosis (absolute reduction: LCHF: -7.2% [95% CI = -9.3 to -5.1], 5:2: -6.1% [95% CI = -8.1 to -4.2], SoC: -3.6% [95% CI = -5.8 to -1.5]) and body weight (LCHF: -7.3 kg [95% CI = -9.6 to -5.0]; 5:2: -7.4 kg [95% CI = -8.7 to -6.0]; SoC: -2.5 kg [95% CI =-3.5 to -1.5]. There was no difference between 5:2 and LCHF ( p  = 0.41 for steatosis and 0.78 for weight). Liver stiffness improved in the 5:2 and SoC but not in the LCHF group. The 5:2 diet was associated with reduced LDL levels and was tolerated to a higher degree than LCHF., Conclusions: The LCHF and 5:2 diets were more effective in reducing steatosis and body weight in patients with NAFLD than SoC, suggesting dietary advice can be tailored to meet individual preferences., Lay Summary: For a person with obesity who suffers from fatty liver, weight loss through diet can be an effective treatment to improve the condition of the liver. Many popular diets that are recommended for weight reduction, such as high-fat diets and diets based on intermittent fasting, have not had their effects on the liver directly evaluated. This study shows that both a low-carb high-fat and the 5:2 diet are effective in treating fatty liver caused by obesity., Clinical Trials Registration: This study is registered at Clinicaltrials.gov (NCT03118310)., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)