Permanently infertile couples and family building-a cross-sectional survey in Denmark.

STUDY QUESTION: Which decision-making factors influence family building among permanently infertile couples? SUMMARY ANSWER: Ethical, legal, and financial considerations outweigh genetic relatedness in decision-making, favouring domestic gestational surrogacy, if this were possible, over international options. WHAT IS KNOWN ALREADY: Permanent infertility affects 4-5% of people in the fertile age. Their family-building options include adoption, surrogacy, uterus transplantation, foster care, and intentional multiple parenthood. However, in most countries, including Denmark, legal barriers constrain these methods due to surrogacy restrictions, suspended international adoptions, and the experimental status of uterus transplantation. Despite existing research on surrogacy, adoption, and specific causes of permanent infertility, a significant gap remains in our understanding of how couples with permanent infertility make family-building decisions within these limited frameworks. STUDY DESIGN, SIZE, DURATION: This cross-sectional study with 150 permanently infertile Danish participants was conducted from June to November 2023 using an online questionnaire. Multiple strategies, such as online forums, fertility clinics, hospital departments, and snowballing, were used to recruit a diverse sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included couples aged 26-50 years facing permanent infertility due to the following primary causes: women without a uterus (15%), women with a non-functional uterus (47%) or women for whom pregnancy would be life-threatening (9%), male couples (16%), transgender partner couples (2%), and other causes (11%). The survey collected data on demographics, reproductive history, family-building choices, and communication strategies. Closed questions were analysed using descriptive statistics. MAIN RESULTS AND THE ROLE OF CHANCE: Among 150 respondents, 41% had used transnational surrogacy, 27% adoption, 14% chose to remain childless, and 19% were undecided. Critical factors on family-building decisions were ethical, legal, and financial concerns which ranked higher than genetic relatedness. Despite the complexity of family building, most participants were open about their child's origin and received social support. If all family-building methods were legal and available in Denmark, domestic gestational surrogacy would be the preferred method, with uterus transplantation and remaining childless being least popular. LIMITATIONS, REASONS FOR CAUTION: The sample size is relatively small, despite the use of a variety of recruitment strategies. Nevertheless, this has ensured a diverse cohort representing the different reasons for infertility and family-building choices. It is important to note that the strategies may have favoured individuals achieving parenthood. WIDER IMPLICATIONS OF THE FINDINGS: The finding of our study reveals a notable gap between available family-building options in Denmark and the preferences of couples facing permanent infertility. These insights could be instrumental for organizations reviewing and developing family-building frameworks. Furthermore, for healthcare professionals guiding couples experiencing infertility issues in their attempts to build a family, an understanding of these preferences is essential to facilitate informed decisions about their future family plans. STUDY FUNDING/COMPETING INTEREST(S): The project was financed by the Independent Research Fund Denmark. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Human sperm cells can form paracetamol metabolite AM404 that directly interferes with sperm calcium signalling and function through a CatSper-dependent mechanism.

STUDY QUESTION: Do paracetamol (N-acetyl-para-aminophenol (APAP) or acetaminophen) and/or its metabolites affect human sperm Ca2+-signalling and function? SUMMARY ANSWER: While APAP itself does not interact with Ca2+-signalling in human sperm, its metabolite N-arachidonoyl phenolamine (AM404), produced via fatty acid amide hydrolase (FAAH), interferes with human sperm Ca2+-signalling and function through a suggested CatSper channel-dependent action. WHAT IS KNOWN ALREADY: Studies have shown that adult men with high urinary levels of over-the-counter mild analgesic APAP have impaired sperm motility and increased time-to-pregnancy. STUDY DESIGN, SIZE, DURATION: This study consists of (i) an in vivo human pharmaceutical APAP exposure experiment to understand to what degree APAP reaches the sperm cells in the seminal fluid; (ii) in vitro calcium imaging and functional experiments in freshly donated human sperm cells to investigate CatSper channel-dependent activation by APAP and its metabolites; and (iii) experiments to understand the in situ capabilities of human sperm cells to form APAP metabolite AM404. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three healthy young males participated in the in vivo human exposure experiment after prior consent. Human semen samples were provided by healthy young volunteer donors after prior consent on the day of the in vitro experiments. MAIN RESULTS AND THE ROLE OF CHANCE: Pharmaceutical APAP exposure reaches the seminal plasma in high micromolar concentrations and accumulates in the seminal plasma between 3 and 5 days of exposure (P-value 0.023). APAP and its primary metabolite 4-aminophenol (4AP) do not interact with human sperm Ca2+-signalling. Instead, the APAP metabolite AM404 produced via FAAH interferes with human sperm Ca2+-signalling through a CatSper-dependent action. Also, AM404 significantly increases sperm cell penetration into viscous mucous (P-value of 0.003). FAAH is functionally expressed in human sperm cells in the neck/midpiece region, as evidenced by immunohistochemical staining and the ability of human sperm cells to hydrolyse the fluorogenic FAAH substrate arachidonyl 7-amino, 4-methyl coumarin amide in an FAAH-dependent manner. Importantly, human sperm cells have the capacity to form AM404 in situ after exposure to 4AP (P-value 0.0402 compared to vehicle-treated sperm cells). LIMITATIONS, REASONS FOR CAUTION: The experiments were conducted largely in vitro. Future studies are needed to test whether APAP can disrupt human sperm function in vivo through the action of AM404. WIDER IMPLICATIONS OF THE FINDINGS: We hypothesize that these observations could, at least in part, be responsible for the negative association between male urinary APAP concentrations, sperm motility and time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): D.M.K. is funded by the Lundbeck Foundation, grant number R324-2019-1881, and the Svend Andersen Foundation. A.R. is funded by a BRIDGE-Translational Excellence Programme grant funded by the Novo Nordisk Foundation, grant agreement number: NNF18SA0034956. All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Effect of locally tailored labour management guidelines on intrahospital stillbirths and birth asphyxia at the referral hospital of Zanzibar: a quasi-experimental pre-post study (The PartoMa study).

OBJECTIVE: To evaluate effect of locally tailored labour management guidelines (PartoMa guidelines) on intrahospital stillbirths and birth asphyxia. DESIGN: Quasi-experimental pre-post study investigating the causal pathway through changes in clinical practice. SETTING: Tanzanian low-resource referral hospital, Mnazi Mmoja Hospital. POPULATION: Facility deliveries during baseline (1 October 2014 until 31 January 2015) and the 9th to 12th intervention month (1 October 2015 until 31 January 2016) [corrected]. METHODS: Birth outcome was extracted from all cases of labouring women during baseline (n = 3690) and intervention months (n = 3087). Background characteristics and quality of care were assessed in quasi-randomly selected subgroups (n = 283 and n = 264, respectively). MAIN OUTCOME MEASURES: Stillbirths and neonates with 5-minute Apgar score ≤5. RESULTS: Stillbirth rate fell from 59 to 39 per 1000 total births (RR 0.66, 95% CI 0.53-0.82), and subanalyses suggest that this was primarily due to reduction in intrahospital stillbirths. Apgar scores between 1 and 5 fell from 52 to 28 per 1000 live births (RR 0.53, 95% CI 0.41-0.69). Median time from last fetal heart assessment till delivery (or fetal death diagnosis) fell from 120 minutes (IQR 60-240) to 74 minutes (IQR 30-130) (Mann-Whitney test for difference, P < 0.01). Oxytocin augmentation declined from 22% to 12% (RR 0.54, 95% CI 0.37-0.81) and timely use improved. CONCLUSION: Although low human resources and substandard care remain major challenges, PartoMa guidelines were associated with improvements in care, leading to reductions in stillbirths and birth asphyxia. Findings furthermore emphasise the central role of improved fetal surveillance and restricted intrapartum oxytocin use in safety at birth. TWEETABLE ABSTRACT: #PartoMa guidelines aided in reducing stillbirths and birth asphyxia at a Tanzanian low-resource hospital PLAIN LANGUAGE SUMMARY: PartoMa guidelines help birth attendants in Tanzania to save lives Every year, 3 million babies die on the day of birth. The vast majority of these deaths occur in the poorest countries. If their mothers had received better care during birth, most babies would have survived. At Mnazi Mmoja Hospital, an East African referral hospital, the PartoMa study shows that use of locally developed guidelines helps birth attendants to deliver better quality of care, which has led to improved survival at birth. At the hospital studied, resources are scarce. Each birth attendant assists four to six birthing women simultaneously, and many have less than 1 year of professional experience. International guidelines are available, but they are often unachievable and seldom applied. The PartoMa guidelines were developed in close collaboration with the birth attendants and approved by seven international experts. The result is an 8-page pocket booklet providing locally achievable and simple decision support for care during birth. Use of the PartoMa guidelines began in February 2015. As the staff group frequently changes, quarterly seminars are conducted where birth attendants are welcomed after working hours to learn about the guidelines. The guidelines have been positively received, and seminar attendance remains high. Use of the PartoMa guidelines is associated with: A decrease by one-third in stillbirths (59 to 39 per 1000 total births) A nearly halving in the number of babies born in immediate poor medical condition (52 to 28 per 1000 live births) The results presented here derive from a comparison of births before using the PartoMa guidelines and during the 9th-12th month of use. Such a 'before-after' study cannot exclude the possibility of other causes of better survival at birth. However, the improved survival is consistent with improved care during birth, which is in line with the PartoMa guidelines.

Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis.

Mutants of Bacillus subtilis overproducing valine (B. subtilis VAL) could be an approach to supply pigs dietary valine (Val). In the study, 18 gilts were fed: (i) negative diet with a standardized ileal digestible (SID) Val:Lys of 0.63:1 (Neg); (ii) Neg added B. subtilis VAL (1.28 × 1011  cfu/kg as-fed) or; (iii) Neg added L-Val to a Val:Lys of 0.69:1. Using the Ussing chamber method, the study aimed to investigate whether (i) the diets affect intestinal transport of additions of 0, 5, 10 or 20 mmol Val/L from the mucosal to the serosal side and (ii) the B. subtilis VAL contributes to a net transport of Val produced in situ. The results showed that the Isc (ΔIscVal ) and release of Val to the serosal side solution (Srel ; µmol cm-2  min-1 ) increased with Val addition (linear and quadratic, p < .0001) but was similar for 5, 10 or 20 mmol Val/L and not affected by diet. No net transport of in situ produced Val by B. subtilis VAL was detected. In conclusion, feeding a Val-deficient diet with or without B. subtilis VAL or a Val sufficient diet did not affect the Val transport across intestinal epithelia. No in situ Val production by B. subtilis VAL was observed in the Ussing chambers.

Perspectives and unmet needs in polymyalgia rheumatica. Providing the fundamental framework for the development of new treatment regimes in polymyalgia rheumatica.

Polymyalgia rheumatica is effectively treated with glucocorticoids. However, glucocorticoid treatment can cause numerous and potentially serious side effects. Therefore, lowest effective dose and shortest duration to control disease is aimed for and glucocorticoid-sparing treatments are needed. Nevertheless, development of treatment regimens in PMR has been hampered by the lack of reliable classification criteria and evidence-based outcome measures. In this editorial, we discuss the need for valid classification criteria in PMR, the strengths and limitations of the ACR/EULAR 2012 provisional classification criteria for PMR and the need of validation and possible refining of the criteria.

Recombinant porcine factor VIII for high-risk surgery in paediatric congenital haemophilia A with high-titre inhibitor.

INTRODUCTION: High-titre factor VIII (FVIII) inhibitors complicate peri-operative haemostasis. Recombinant porcine FVIII (r-pFVIII) may provide an alternative haemostatic agent for high-risk procedures and allow FVIII activity monitoring. AIM: Devise an effective haemostatic plan for repair of a progressively symptomatic aortic coarctation in a 5-year-old male with immune tolerance induction (ITI) refractory high-titre FVIII inhibitors. METHODS: Preprocedure human FVIII inhibitor titre was 58 Bethesda Units mL-1 (BU) and cross-reacted to neutralize porcine FVIII at 30 BU. Daily ITI with plasma-derived FVIII concentrate was supplemented with anti-B-cell and anti-plasma cell immunotherapy to reduce FVIII inhibitor titres. Potential haemostatic agents were evaluated in comparative ex vivo thrombin generation assays (TGA). RESULTS: Four weeks after immunosuppression, human and porcine inhibitor titres declined to 16 and 2 BU respectively. TGA with r-pFVIII was less robust than with activated prothrombin complex concentrate (aPCC); however, r-pFVIII was selected for cardiac surgery to secure the ability to assay FVIII levels throughout this high-bleeding risk procedure. Haemostasis with r-pFVIII was excellent; initial trough FVIII activity levels ranged from 0.81-1.17 IU mL-1 . On postoperative day 3, peak and trough levels markedly declined suggesting a rising porcine inhibitor titre. Postprocedure prophylaxis was transitioned to aPCC, informed by TGA. CONCLUSIONS: R-pFVIII provided effective peri-procedural haemostasis with no adverse events. Rapid neutralization of r-pFVIII after the first 60 hours, despite intensive immune suppression, accentuates the importance of careful monitoring. Use of TGA can support bypassing agent selection for convalescence. The comparative cost of r-pFVIII may limit its use to high morbidity clinical scenarios.

A National Needs Assessment to Identify Technical Procedures in Vascular Surgery for Simulation Based Training.

OBJECTIVES AND BACKGROUND: Practical skills training in vascular surgery is facing challenges because of an increased number of endovascular procedures and fewer open procedures, as well as a move away from the traditional principle of "learning by doing." This change has established simulation as a cornerstone in providing trainees with the necessary skills and competences. However, the development of simulation based programs often evolves based on available resources and equipment, reflecting convenience rather than a systematic educational plan. The objective of the present study was to perform a national needs assessment to identify the technical procedures that should be integrated in a simulation based curriculum. DESIGN AND METHODS: A national needs assessment using a Delphi process was initiated by engaging 33 predefined key persons in vascular surgery. Round 1 was a brainstorming phase to identify technical procedures that vascular surgeons should learn. Round 2 was a survey that used a needs assessment formula to explore the frequency of procedures, the number of surgeons performing each procedure, risk and/or discomfort, and feasibility for simulation based training. Round 3 involved elimination and ranking of procedures. RESULTS: The response rate for round 1 was 70%, with 36 procedures identified. Round 2 had a 76% response rate and resulted in a preliminary prioritised list after exploring the need for simulation based training. Round 3 had an 85% response rate; 17 procedures were eliminated, resulting in a final prioritised list of 19 technical procedures. CONCLUSION: A national needs assessment using a standardised Delphi method identified a list of procedures that are highly suitable and may provide the basis for future simulation based training programs for vascular surgeons in training.

Short communication: Calving site selection of multiparous, group-housed dairy cows is influenced by site of a previous calving.

A calving cow and her newborn calf appear to have an attracting effect on periparturient cows, which may potentially influence the functionality of future motivation-based calving pen designs. In this pilot study we examined whether calving site selection of group-housed Holstein dairy cows was affected by the site of a previous calving. Ten multiparous cows moved to 1 of 2 group pens 11 (range = 4-27) d before calving were included. Each pen consisted of an open area (9 × 9 m) connected to 6 secluded areas (4.5 × 3 m each), where cows could move freely between all areas. Time of calving, location of the breaking of the amniotic sac, as well as the place of birth were recorded. In all but 1 case cows calved within a distance of 1 cow length from where the previous calving took place, suggesting that the cows did not select calving site at random. These preliminary observations indicate that choice of calving site may be affected by the site of a previous calving, potentially explained by the presence of amniotic fluids.

Vertebral fracture assessment by DXA is inferior to X-ray in clinical severe osteoporosis.

UNLABELLED: Spine fractures are diagnosed by X-ray or vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) scanning. The use of VFA evaluation by DXA is still debated. We demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine and therefore with a reduced diagnostic performance in detecting fractures. INTRODUCTION: Vertebral fracture assessment (VFA) by DXA has been evaluated for many years, and its use in clinical practice is still debated. In a cross-sectional setting, we aimed to compare VFA with traditional radiography in vertebral fracture (VF) diagnosis in severe osteoporotic patient. METHODS: A total of 207 patients referred to the outpatient clinic for teriparatide treatment were screened, out of whom 35 (16.9 %) severe osteoporotic patients were identified (mean age 67.5 ± 11.3 years and median T-score -3.2 interquartile range (IQR) (-1.9 to -3.7). VF diagnosis was performed independently using VFA and X-ray in accordance with the semiquantitative (SQ) approach. The same technician performed the primary interpretation on both sets of images, after which a radiologist and an endocrinologist reviewed the evaluation for a conclusive judgement. RESULTS: In total, 180 radiographic fractures were detected, corresponding to 5.1 fractures per individual. Using VFA, 18.5 % of vertebrae were considered unreadable, compared to 2.0 % on X-ray. The accuracy of VFA in VF detection using X-ray as a reference resulted in sensitivity and specificity of 75.5 and 86.7 %, respectively. Sensitivity decreased from the lumbar to thoracic level. Nevertheless, VFA only identified fractures consistently between Th11 and L3. CONCLUSION: Our data, based on a severe osteoporotic population, demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine, resulting in vertebrae not being assessable for analysis and a reduced diagnostic performance in detecting fractures. Improvements in DXA techniques are needed for it to be comparable with X-ray in VF diagnosis.

Selective complexation of divalent cations by a cyclic α,ß-peptoid hexamer: a spectroscopic and computational study.

We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and ß-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na+, K+, Ag+) but showed selectivity for divalent cations (Ca2+, Ba2+, Sr2+ and Mg2+). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca2+ and Ba2+), while 5-coordination is preferred for divalent cations with larger (Ba2+) or smaller ionic radii (Mg2+).

Characterization of an apparently synonymous F5 mutation causing aberrant splicing and factor V deficiency.

Coagulation factor V (FV) deficiency is a rare autosomal recessive bleeding disorder. We investigated a patient with severe FV deficiency (FV:C < 3%) and moderate bleeding symptoms. Thrombin generation experiments showed residual FV expression in the patient's plasma, which was quantified as 0.7 ± 0.3% by a sensitive prothrombinase-based assay. F5 gene sequencing identified a novel missense mutation in exon 4 (c.578G>C, p.Cys193Ser), predicting the abolition of a conserved disulphide bridge, and an apparently synonymous variant in exon 8 (c.1281C>G). The observation that half of the patient's F5 mRNA lacked the last 18 nucleotides of exon 8 prompted us to re-evaluate the c.1281C>G variant for its possible effects on splicing. Bioinformatics sequence analysis predicted that this transversion would activate a cryptic donor splice site and abolish an exonic splicing enhancer. Characterization in a F5 minigene model confirmed that the c.1281C>G variant was responsible for the patient's splicing defect, which could be partially corrected by a mutation-specific morpholino antisense oligonucleotide. The aberrantly spliced F5 mRNA, whose stability was similar to that of the normal mRNA, encoded a putative FV mutant lacking amino acids 427-432. Expression in COS-1 cells indicated that the mutant protein is poorly secreted and not functional. In conclusion, the c.1281C>G mutation, which was predicted to be translationally silent and hence neutral, causes FV deficiency by impairing pre-mRNA splicing. This finding underscores the importance of cDNA analysis for the correct assessment of exonic mutations.

Peripherally applied opioids for postoperative pain: evidence of an analgesic effect? A systematic review and meta-analysis.

BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity scores, consumption of supplemental analgesics and time to first analgesic were included. Trials with sample sizes of fewer than 10 patients per treatment group or trials with opioids administered intra-articularly or as peripheral nerve blocks were excluded. RESULTS: Data from 26 studies, including 1531 patients and 13 different surgical interventions were included. Clinical heterogeneity of the studies was substantial. Meta-analysis indicated statistically significant, but not clinically relevant, reductions in VAS score at 6-8 h (mean difference -4 mm, 95% CI: -6 to -2) and 12 h postoperatively (mean difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved postoperative analgesia. CONCLUSION: Evidence of a clinically relevant analgesic effect of peripherally applied opioids for acute postoperative pain is lacking. The analgesic effect of peripherally applied opioids may depend on the presence of preoperative inflammation.

Clinical features and management of haemophilic pseudotumours: a single US centre experience over a 30-year period.

Given the rarity of haemophilic pseudotumours, consensus on management is lacking. We describe the clinical features and management of haemophilic pseudotumours by retrospectively reviewing the medical records of haemophilia patients with a diagnosis of pseudotumour seen at our Hemophilia Center from 1981 to 2011. We recorded the following data: type and severity of haemophilia, documented aetiological antecedent, localization of the pseudotumour, presenting symptoms, management and outcome. We identified 12 pseudotumours in 11 patients over a 30-year period. Six patients had known inhibitors or a history of inhibitor. An aetiological antecedent leading to the development of pseudotumour was reported in nine cases. Localization of the pseudotumour was confined to soft tissue (n = 3) and bone (n = 8). Six of the 12 pseudotumours (50%) were not diagnosed at the time of initial presentation, with a delay ranging from 6 weeks to 6 years. In eight cases, surgical intervention (surgical drainage, n = 2; excision, n = 4; limb amputation, n = 2) was the initial treatment choice, with complete resolution in six cases. Conservative management with close monitoring occurred in three cases, with one case subsequently requiring surgical resection. We conclude that haemophilic pseudotumours still occur sporadically, and the diagnosis is frequently delayed. Surgical intervention is generally a safe and effective treatment, although conservative management may be appropriate in selected cases.

Sarcopenia and self-reported markers of physical frailty in patients with osteoporosis.

Bone and muscle impairment, named osteoporosis and sarcopenia, may co-occur with age, and patients with both disorders might exhibit physical frailty. One-hundred sixty-three patients were included. 14.2% had both disorders and presented more frequent with previous fall, reduced daily activity level, walk/balance challenges, and need of walking aid, indicating overall frailty. PURPOSE: In older adults, sarcopenia (muscle impairment) and physical frailty may accompany osteoporosis (bone brittleness), yet osteoporosis is typically assessed without evaluating these conditions, even though coexistence may contribute to exacerbated negative health outcomes. We aimed at evaluating the prevalence of sarcopenia and impaired muscle domains in osteoporotic patients and explore the risk of osteosarcopenia from markers of physical frailty. METHODS: In Copenhagen, Denmark, osteoporotic patients aged 65 + were assessed cross-sectionally in 2018-2019. Evaluations included muscle mass, strength, and function; bone mineral density; and self-reported physical activity, fall, balance challenges, dizziness, and the need of walking aid. Low bone mass, low-energy fracture, or treatment with anti-osteoporotic medication defined patient with osteoporosis, and sarcopenia was defined by low muscle strength and mass. Osteosarcopenia was defined from the coexistence of both conditions. RESULTS: One-hundred sixty-three patients with osteoporosis were included. Of those, 23 (14.2%) exhibited sarcopenia, hence osteosarcopenia. Hand-grip-strength, 30-s-chair-stand-test, relative-appendicular-lean-muscle-mass, and gait-speed were below cut-off levels in 21.0%, 30.9%, 28.8%, and 23.6% of the patients, respectively. Previous fall, activity level, walk and balance challenges, and need of walking aid were statistically (or borderline) significantly more often affected in the osteosarcopenic group compared with the solely osteoporotic. Logistic regression analysis, however, revealed that only the need for walking aid significantly increased the risk of an osteosarcopenia diagnosis (odds ratio 5.54, 95% CI (1.95-15.76), p < 0.01). CONCLUSIONS: Sarcopenia and impaired muscle domains were frequent in osteoporotic patients, as were markers of physical frailty, indicating the need of thorough examination of osteoporotic patients.

The prognostic importance of miR-21 in stage II colon cancer: a population-based study.

BACKGROUND: Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. The aim of the present study was to investigate the prognostic importance of miRNA-21 (miR-21), quantified by in situ hybridisation, in a unique, large population-based cohort. PATIENTS AND METHODS: The study included 764 patients diagnosed with stage II colon cancer in Denmark in the year 2003. One section from a representative paraffin-embedded tumour tissue specimen from each patient was processed for analysis of miR-21 and quantitatively assessed by image analysis. RESULTS: The miR-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumours. We found that patients expressing high levels of miR-21 had significantly inferior recurrence-free cancer-specific survival (RF-CSS): HR=1.26; 95% CI: 1.15-1.60; P<0.001. In Cox regression analysis, a high level of miR-21 retained its prognostic importance and was found to be significantly related to poor RF-CSS: HR=1.41; 95% CI: 1.19-1.67; P<0.001. CONCLUSION: The present study showed that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited.

Mobile phones as a health communication tool to improve skilled attendance at delivery in Zanzibar: a cluster-randomised controlled trial.

OBJECTIVE: To examine the association between a mobile phone intervention and skilled delivery attendance in a resource-limited setting. DESIGN: Pragmatic cluster-randomised controlled trial with primary healthcare facilities as the unit of randomisation. SETTING: Primary healthcare facilities in Zanzibar. POPULATION: Two thousand, five hundred and fifty pregnant women (1311 interventions and 1239 controls) who attended antenatal care at one of the selected primary healthcare facilities were included at their first antenatal care visit and followed until 42 days after delivery. All pregnant women were eligible for study participation. METHODS: Twenty-four primary healthcare facilities in six districts in Zanzibar were allocated by simple randomisation to either mobile phone intervention (n = 12) or standard care (n = 12). The intervention consisted of a short messaging service (SMS) and mobile phone voucher component. MAIN OUTCOME MEASURES: Skilled delivery attendance. RESULTS: The mobile phone intervention was associated with an increase in skilled delivery attendance: 60% of the women in the intervention group versus 47% in the control group delivered with skilled attendance. The intervention produced a significant increase in skilled delivery attendance amongst urban women (odds ratio, 5.73; 95% confidence interval, 1.51-21.81), but did not reach rural women. CONCLUSIONS: The mobile phone intervention significantly increased skilled delivery attendance amongst women of urban residence. Mobile phone solutions may contribute to the saving of lives of women and their newborns and the achievement of Millennium Development Goals 4 and 5, and should be considered by maternal and child health policy makers in developing countries.

Factors associated with work outcome for survivors from haematological malignancies--a systematic literature review.

Recent years have seen a growing number of survivors from haematological malignancies. As biology and treatment for these malignancies differ from other malignancies, we performed a systematic literature review of factors associated with work outcome for these survivors. A systematic literature search was conducted. Eight studies with different methodology and characteristics met the inclusion criteria. Three prospective studies agreed, to a high extent, on their findings, whereas results of five cross-sectional studies collectively were inconclusive. Overall, this review - like reviews on other cancer survivors - found no certain association of single factors with work outcome. However, based on possible explanations of the converging findings, this review pinpointed a number of issues that may inform future studies. The design should preferably be prospective, including comparison with age-paired cancer-free individuals. The role of co-morbidity and of differences between haematological diagnoses ought to be established, and work outcomes must be well defined and recorded with valid methods. To establish cause-effect relations, factors possibly associated to work outcome should be evaluated at an early time point after diagnosis. Such studies would assist identification of individuals at increased risk of encountering work-related problems and would hence help establish knowledge on which rehabilitation measures could rest.

Effects of quinoa hull meal on piglet performance and intestinal epithelial physiology.

Saponin-containing feed additives have shown positive effects on pig performance. Quinoa hull has high saponin content and may be of interest as a feed additive. This study aimed to evaluate quinoa hull meal (QHM) as a feed additive in a pig diet. The effects of QHM were assessed for three dosages of South American (SA) origin (100, 300 and 500 mg/kg) and one dosage of Danish (DK) quinoa (300 mg/kg). In addition, the effect of dietary SA-QHM and SA-QHM-extract on jejunal epithelial physiology was studied ex vivo in Ussing chambers. The experiment included 400 piglets weaned at 28 ± 2 days of age and the experimental period was 4 weeks. Piglets were weighed initially and finally and feed intake registered. The ex vivo studies were performed with epithelium from 40 pigs receiving control or SA-QHM. Epithelium from each pig was placed into eight Ussing chambers, where four concentrations of SA-QHM-extract were added. Epithelial permeability, Na(+)-dependent glucose transport and serotonin (5-HT) and theophylline-induced secretion were measured. The results showed that QHM had no influence on piglet's growth (p = 0.41) or feed intake (p = 0.17). In spite of a large difference in saponin content between SA-QHM and DK-QHM (28.7% and 2.0% w/w respectively) the source did not affect pig performance. The ex vivo studies revealed no effect (p > 0.05) of adding QHM-extract into the medium. The permeability and glucose induced absorption were highest (p = 0.003 and p = 0.04 respectively) in epithelium from pigs that consumed 100 or 300 mg/kg SA-QHM. The secretory response to 5-HT was not affected (p = 0.59) by dietary treatments, but the theophylline-induced secretion decreased (p = 0.02) with increasing dietary SA-QHM. The changes in epithelial physiology measured ex vivo did not affect animal performance in vivo in this study.