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Abstract Background Problem-solving interventions with workplace involvement (PSI-WPI) have been shown to reduce sick leave and increase return to work in an occupational health services context. However, many employees struggle with reduced work functioning, anxiety-, and depressive symptoms up to 12 months after a sick leave episode, and it is unclear if the intervention affects outcomes other than sick leave. The aim of this study is to investigate if a PSI-WPI added to care as usual (CAU) is superior to CAU with respect to self-reported sick leave, psychological symptoms, work ability, work performance, and health after RTW when provided in primary care. Methods Employed individuals aged 18–59 years on sick leave (2 to 12 weeks) diagnosed by a physician at a primary care center with mild to moderate depression, anxiety, or adjustment disorder were enrolled in a two-armed cluster-randomised trial evaluating the effectiveness of a PSI-WPI. Multiple outcomes were recorded at baseline, six months, 12 months, and every fourth week during the study period. Outcomes were categorised into psychological symptoms, health, work ability, work performance, and self-reported sick leave. Data were analysed using MANOVA, GEE (Generalized Estimating Equations), and cox regression. Results One hundred ninety-nine individuals responded to the invitation to participate; one participant withdrew, one was excluded as the employment ended, nine did not answer the baseline survey, and three were removed from the analysis due to missing data. The analysis included 81 subjects who received the intervention and 104 subjects who received the control. Baseline characteristics were similar across both groups. No differences between the groups were found among either variables except one. There was a significant difference between the groups in self-rated health (EQ5D) in favour of the CAU group from baseline to six-month follow-up, with a mean difference of -8.44 (-14.84, -2.04). Conclusions A problem-solving intervention with workplace involvement added to CAU did not result in statistically significant reductions in outcomes. Further research is needed to understand why problem-solving interventions appear to have an effect on sick leave in an occupational health services context and not in a primary care context. Trial registration NCT3346395, registration date 2017–11-17.

Abstract Background This study explores how the goals of collaboration in the return-to-work (RTW) process for people with common mental disorders are described by the stakeholders involved, and how they experience stakeholders’ roles and responsibilities in relation to these goals. Methods Interviews were conducted with 41 participants from three Swedish regions. Nine of the participants were workers, six employer representatives, four occupational health professionals, four social insurance officers, 18 RTW coordinators and five physicians. Thematic analysis was conducted. Results Three main themes and overarching goals when collaborating on RTW were identified. In the first theme, ‘creating an informative environment’, all stakeholders emphasised clear roles and responsibilities. The second theme, ‘striving for consensus in an environment of negotiations’, addressed negotiations about when and how to collaborate, on what and with whom, and reveal different views on stakeholders’ goals, roles and responsibilities in collaboration. The third theme identified goals for ‘creating a supportive environment’ for both workers and other stakeholders. Coordinators are found to have an important role in achieving a supportive environment, and in neutralising power imbalances between workers and their employers and social insurance officers. Conclusions Competing goals and priorities were identified as hindering successful collaboration, contributing to a spectrum of complex versus easy RTW collaboration. This study suggests some basic conditions for achieving a collaborative arena that is neutral in terms of power balance, where all stakeholders can share their views.

Abstract Background Desmin is a major cytoskeletal protein considered ubiquitous in mature muscle fibers. However, we earlier reported that a subgroup of muscle fibers in the soft palate of healthy subjects and obstructive sleep apnea patients (OSA) lacked immunoexpression for desmin. This raised the question of whether these fibers also lack messenger ribonucleic acid (mRNA) for desmin and can be considered a novel fiber phenotype. Moreover, some fibers in the OSA patients had an abnormal distribution and aggregates of desmin. Thus, the aim of the study was to investigate if these desmin protein abnormalities are also reflected in the expression of desmin mRNA in an upper airway muscle of healthy subjects and OSA patients. Methods Muscle biopsies from the musculus uvulae in the soft palate were obtained from ten healthy male subjects and six male patients with OSA. Overnight sleep apnea registrations were done for all participants. Immunohistochemistry, in-situ hybridization, and reverse transcription–quantitative polymerase chain reaction (RT–qPCR) techniques were used to evaluate the presence of desmin protein and its mRNA. Results Our findings demonstrated that a group of muscle fibers lacked expression for desmin mRNA and desmin protein in healthy individuals and OSA patients (12.0 ± 5.6% vs. 23.1 ± 10.8%, p = 0.03). A subpopulation of these fibers displayed a weak subsarcolemmal rim of desmin accompanied by a few scattered mRNA dots in the cytoplasm. The muscles of OSA patients also differed from healthy subjects by exhibiting muscle fibers with reorganized or accumulated aggregates of desmin protein (14.5 ± 6.5%). In these abnormal fibers, the density of mRNA was generally low or concentrated in specific regions. The overall quantification of desmin mRNA by RT–qPCR was significantly upregulated in OSA patients compared to healthy subjects (p = 0.01). Conclusions Our study shows evidence that muscle fibers in the human soft palate lack both mRNA and protein for desmin. This indicates a novel cytoskeletal structure and challenges the ubiquity of desmin in muscle fibers. Moreover, the observation of reorganized or accumulated aggregates of desmin mRNA and desmin protein in OSA patients suggests a disturbance in the transcription and translation process in the fibers of the patients.

Abstract Background Incorporating multiple perspectives and contexts in knowledge mobilisation for return-to-work after sick leave due to common mental disorders can promote interprofessional and organisational strategies for facilitating the return-to-work process. This study aimed to explore the facilitators of and barriers to return-to-work after common mental disorders. This exploration considered the perspectives of employees and managers and the realms of work and private life. Methods A qualitative approach was used with data from 27 semi-structured telephone interviews. The strategic sample consisted of employees who returned to work after sick leave due to common mental disorders (n = 17) and managers responsible for their return-to-work process (n = 10). Thematic analysis conducted in a six-step process was used to generate themes in the interview data. Results The analysis generated three main themes with subthemes, illustrating experiences of barriers to and facilitators of return-to-work positioned in the employees’ private and work contexts: (1) Getting along: managing personal difficulties in everyday life; (2) Belonging: experiencing social connectedness and support in work and private life; and (3) Organisational support: fostering a supportive work environment. The results contribute to a comprehensive understanding of the return-to-work process, including the challenges individuals face at work and in private life. Conclusions The study suggests that return-to-work after sick leave due to CMDs is a dynamic and ongoing process embedded in social, organisational, and societal environments. The results highlight avenues for an interprofessional approach and organisational learning to support employees and managers, including space for the employee to recover during the workday. Trial registration This study recruited employees from a two-armed cluster-randomised controlled trial evaluating a problem-solving intervention for reducing sick leave among employees sick-listed due to common mental disorders (reg. NCT3346395).

Abstract Background Physical activity is essential to improve health and reduce the risk of recurrence of stroke or transient ischemic attack (TIA). Still, people post stroke or TIA are often physically inactive and the availability of physical activity promotion services are often limited. This study builds on an existing Australian telehealth-delivered programme (i-REBOUND– Let’s get moving) which provides support for home-based physical activity for people post stroke or TIA. The aim of this study is to test the feasibility, acceptability, and preliminary effects of a mobile Health (mHealth) version of the i-REBOUND programme for the promotion of physical activity in people post stroke or TIA living in Sweden. Methods One hundred and twenty participants with stroke or TIA will be recruited via advertisement. A parallel-group feasibility randomised controlled trial design with a 1:1 allocation ratio to 1) i-REBOUND programme receiving physical exercise and support for sustained engagement in physical activity through behavioural change techniques, or 2) behavioural change techniques for physical activity. Both interventions will proceed for six months and be delivered digitally through a mobile app. The feasibility outcomes (i.e., reach, adherence, safety and fidelity) will be monitored throughout the study. Acceptability will be assessed using the Telehealth Usability Questionnaire and further explored through qualitative interviews with a subset of both study participants and the physiotherapists delivering the intervention. Clinical outcomes on preliminary effects of the intervention will include blood pressure, engagement in physical activity, self-perceived exercise self-efficacy, fatigue, depression, anxiety, stress and health-related quality of life and will be measured at baseline and at 3, 6 and 12 months after the baseline assessments. Discussion We hypothesise that the mHealth delivery of the i-REBOUND programme will be feasible and acceptable in people post stroke/TIA living in rural and urban regions of Sweden. The results of this feasibility trial will inform the development of full-scale and appropriately powered trial to test the effects and costs of mHealth delivered physical activity for people after stroke or TIA. Trial registration ClinicalTrials.gov Identifier: NCT05111951. Registered November 8, 2021.

Abstract Background The pressure difference between the eye and brain in upright postures may be affected by compartmentalization of the optic nerve subarachnoid space (ONSAS). Both pressure and deformation will depend on the microstructures of the ONSAS, and most likely also on ocular glymphatic clearance. Studying these factors could yield important knowledge regarding the translaminar pressure difference, which is suspected to play a role in normal-tension glaucoma. Methods A compartment model coupling the ONSAS with the craniospinal CSF system was used to investigate the effects of microstructures on the pressure transfer through the ONSAS during a posture change from supine to upright body postures. ONSAS distensibility was based on MRI measurements. We also included ocular glymphatic flow to investigate how local pressure gradients alter this flow with changes in posture. Results A compartmentalization of the ONSAS occurred in the upright posture, with ONSAS porosity (degree of microstructural content) affecting the ONSAS pressure (varying the supine/baseline porosity from 1.0 to 0.75 yielded pressures between − 5.3 and − 2 mmHg). Restricting the minimum computed porosity (occurring in upright postures) to 0.3 prevented compartmentalization, and the ONSAS pressure could equilibrate with subarachnoid space pressure (− 6.5 mmHg) in $$\le$$ ≤ 1 h. The ocular glymphatics analysis predicted that substantial intraocular-CSF flows could occur without substantial changes in the ONSAS pressure. The flow entering the ONSAS in supine position (both from the intraocular system and from the cranial subarachnoid space) exited the ONSAS through the optic nerve sheath, while in upright postures the flow through the ONSAS was redirected towards the cranial subarachnoid space. Conclusions Microstructures affect pressure transmission along the ONSAS, potentially contributing to ONSAS compartmentalization in upright postures. Different pathways for ocular glymphatic flow were predicted for different postures.

Abstract Background The impact of cardiorespiratory fitness (CRF) and other lifestyle-related factors on severe COVID-19 risk is understudied. The present study aims to investigate lifestyle-related and socioeconomic factors as possible predictors of COVID-19, with special focus on CRF, and to further study whether these factors may attenuate obesity- and hypertension-related risks, as well as mediate associations between socioeconomic factors and severe COVID-19 risk. Methods Out of initially 407,131 participants who participated in nationwide occupational health service screening between 1992 and 2020, n = 857 cases (70% men, mean age 49.9 years) of severe COVID-19 were identified. CRF was estimated using a sub-maximum cycle test, and other lifestyle variables were self-reported. Analyses were performed including both unmatched, n = 278,598, and sex-and age-matched, n = 3426, controls. Severe COVID-19 included hospitalization, intensive care or death due to COVID-19. Results Patients with more severe COVID-19 had significantly lower CRF, higher BMI, a greater presence of comorbidities and were more often daily smokers. In matched analyses, there was a graded decrease in odds for severe COVID-19 with each ml in CRF (OR = 0.98, 95% CI 0.970 to 0.998), and a two-fold increase in odds between the lowest and highest (

Abstract Background This study, undertaken in Rwanda, aimed to investigate health professionals’ experiences and views on the following topics: current clinical guidelines for ultrasound from second trimester at the clinic, regional and national levels, and adherence to clinical guidelines; medically indicated ultrasound examinations; non-medical use of ultrasound including ultrasounds on maternal request; commercialisation of ultrasound; the value of ultrasound in relation to other clinical examinations in pregnancy; and ultrasound and medicalisation of pregnancy. Methods A cross-sectional design was adopted. Health professionals providing antenatal care and delivery services to pregnant women in 108 health facilities were invited to complete a survey, which was developed based on the results of earlier qualitative studies undertaken as part of the CROss Country Ultrasound Study (CROCUS). Results Nine hundred and seven health professionals participated: obstetricians/gynecologists (3.2%,) other physicians (24.5%), midwives (29.7%) and nurses (42.7%). Few physicians reported the existence of clinical guidelines at clinic, regional or national levels in Rwanda, and guidelines were moderately adhered to. Three obstetric ultrasound examinations were considered medically indicated in an uncomplicated pregnancy. Most participants (73.0%) were positive about obstetric ultrasound examinations on maternal request. Commercialisation was not considered a problem, and the majority (88.5%) agreed that ultrasound had contributed to medicalisation of pregnancy. Conclusions Findings indicate that clinical guidelines for the use of obstetric ultrasound are limited in Rwanda. Non-medically indicated obstetric ultrasound was not considered a current problem at any level of the healthcare system. The positive attitude to obstetric ultrasound examinations on maternal request may contribute to further burden on a maternal health care system with limited resources. It is essential that limited obstetric ultrasound resources are allocated where they are most beneficial, and clearly stated medical indications would likely facilitate this.

Abstract Background Total sitting time is associated with a higher risk for cardio metabolic disease and mortality, while breaks in prolonged sitting attenuate these effects. However, less is known about associations of different specific domains and breaks of sitting on general health, back/neck pain and if physical activity could influence these associations. The aim was to investigate how workplace sitting and frequency of breaking up workplace sitting is associated with self-reported general health and self-reported back/neck pain. Methods 44,978 participants (42% women) from the Swedish working population, who participated in a nationwide occupational health service screening 2014–2019, were included in this cross-sectional study. Self-reported sitting duration and frequency of breaks from sitting at work, general health, back/neck pain, exercise, leisure time sitting, diet, smoking, stress and body mass index were assessed. Occupation was classified as requiring higher education qualifications or not. Logistic regression modelling was used to assess the association between workplace sitting/frequency of breaks in workplace sitting and poor general health and back/neck pain, respectively. Results Compared to sitting all the time at work, sitting ≤75% of the time showed significantly lower risks for poor general health (OR range 0.50–0.65), and sitting between 25 and 75% of the time showed significantly lower risks (OR 0.82–0.87) for often reported back/neck pain. For participants reporting sitting half of their working time or more, breaking up workplace sitting occasionally or more often showed significantly lower OR than seldom breaking up workplace sitting; OR ranged 0.40–0.50 for poor health and 0.74–0.81 for back/neck pain. Conclusions Sitting almost all the time at work and not taking breaks is associated with an increased risk for self-reported poor general health and back/neck pain. People sitting almost all their time at work are recommended to take breaks from prolonged sitting, exercise regularly and decrease their leisure time sitting to reduce the risk for poor health.

Abstract Background Communicating hydrocephalus is a disease where the cerebral ventricles are enlarged. It is characterized by the absence of detectable cerebrospinal fluid (CSF) outflow obstructions and often with increased CSF pulsatility measured in the cerebral aqueduct (CA). We hypothesize that the cardiac-related pulsatile flow over the CA, with fast systolic outflow and slow diastolic inflow, can generate net pressure effects that could source the ventriculomegaly in these patients. This would require a non-zero cardiac cycle averaged net pressure difference (ΔP net ) over the CA, with higher average pressure in the lateral and third ventricles. Methods We tested the hypothesis by calculating ΔP net across the CA using computational fluid dynamics based on prospectively collected high-resolution structural (FIESTA-C, resolution 0.39 × 0.39 × 0.3 mm3) and velocimetric (2D-PCMRI, in-plane resolution 0.35 × 0.35 mm2) MRI-data from 30 patients investigated for communicating hydrocephalus. Results The ΔP net due to CSF pulsations was non-zero for the study group (p = 0.03) with a magnitude of 0.2 ± 0.4 Pa (0.001 ± 0.003 mmHg), with higher pressure in the third ventricle. The maximum pressure difference over the cardiac cycle ΔP max was 20.3 ± 11.8 Pa and occurred during systole. A generalized linear model verified an association between ΔP net and CA cross-sectional area (p = 0.01) and flow asymmetry, described by the ratio of maximum inflow/outflow (p = 0.04), but not for aqueductal stroke volume (p = 0.35). Conclusions The results supported the hypothesis with respect to the direction of ΔP net , although the magnitude was low. Thus, although the pulsations may generate a pressure difference across the CA it is likely too small to explain the ventriculomegaly in communicating hydrocephalus.

Abstract Background The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. Methods Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. Results Desmin displayed a disorganized pattern in 21 ± 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 ± 12% vs. 14 ± 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 ± 18% vs. 14 ± 7%, p

Abstract Background Midwives are the main providers of routine antenatal care services including the routine ultrasound examination in Norway. The ultrasound examination can be perceived by expectant parents not only as a medical examination but also as a social event facilitating attachment to their fetus. This study explores Norwegian midwives’ experiences and views on the role of ultrasound in clinical management of pregnancy. Methods A qualitative study design was applied. Twenty-four midwives who all performed obstetric ultrasound examinations were recruited for focus group discussions and individual interviews. Data collection took place in 2015 in five hospitals in two different regions of Norway. Data were analyzed using qualitative content analysis. Results Midwives described obstetric ultrasound examinations as very valuable although doing ultrasounds placed high demands on their operational and counselling skills. Increasing requests for ultrasound from pregnant women were mentioned. Advancements in ultrasound diagnosis were considered to have put the fetus in the position of a patient, and that pregnant women declining ultrasound could be viewed as irresponsible by some health professionals. Ethical concerns were raised regarding the possibility of pregnancy termination when fetal anomalies were detected. Fears were also expressed that prenatal diagnoses including those following ultrasound, might create a society where only ‘perfect’ children are valued. However, participants stressed that their intention in performing ultrasound was to optimize pregnancy outcome and thereby assist expectant couples and their unborn children. Conclusions Midwives in Norwegian maternity care services describe obstetric ultrasound as very valuable, playing a central role in pregnancy management by optimizing pregnancy outcomes. Although high demands are placed on operators’ technical skills and counseling, midwives described performing obstetric ultrasound as very satisfying work. However, midwives believed that expectant parents’ approach to the ultrasound examination, both its medical value and the precious images obtained of the fetus, could put extra strain on the midwives performing ultrasounds. The potential of ultrasound to detect fetal anomalies and the possibility that this may lead to termination of pregnancy, seemed to create some ambivalent feelings in midwives towards its use.

Abstract Background Maternal vitamin D status has been associated with both gestational diabetes mellitus (GDM) and fetal growth restriction, however, the evidence is inconsistent. In Finland, maternal vitamin D status has improved considerably due to national health policies. Our objective was to compare maternal 25-hydroxy vitamin D concentrations [25(OH)D] between mothers with and without GDM, and to investigate if an association existed between maternal vitamin D concentration and infant birth size. Methods This cross-sectional study included 723 mother-child pairs. Mothers were of Caucasian origin, and infants were born at term with normal birth weight. GDM diagnosis and birth size were obtained from medical records. Maternal 25(OH)D was determined on average at 11 weeks of gestation in pregnancy and in umbilical cord blood (UCB) at birth. Results GDM was observed in 81 of the 723 women (11%). Of the study population, 97% were vitamin D sufficient [25(OH)D ≥ 50 nmol/L]. There was no difference in pregnancy 25(OH)D concentration between GDM and non-GDM mothers (82 vs 82 nmol/L, P = 0.99). Regression analysis confirmed no association between oral glucose tolerance test results and maternal 25(OH)D (P > 0.53). Regarding the birth size, mothers with optimal pregnancy 25(OH)D (≥ 80 nmol/L) had heavier newborns than those with suboptimal pregnancy 25(OH)D (P = 0.010). However, mothers with optimal UCB 25(OH)D had newborns with smaller head circumference than those with suboptimal 25(OH)D (P = 0.003), which was further confirmed as a linear association (P = 0.024). Conclusions Maternal vitamin D concentration was similar in mothers with and without GDM in a mostly vitamin D sufficient population. Associations between maternal vitamin D status and birth size were inconsistent. A sufficient maternal vitamin D status, specified as 25(OH)D above 50 nmol/L, may be a threshold above which the physiological requirements of pregnancy are achieved. Trial registration The project protocol is registered in ClinicalTrials.gov in November 8, 2012 ( NCT01723852 ).

Abstract Background Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P dural ). In the upright posture, P dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 ± 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results IJV area was 94.5 mm2 in supine and decreased to 6.5 ± 5.1 mm2 in sitting position, which agreed with the predicted IJV area of 8.7 ± 5.2 mm2 (equivalence limit ±5 mm2, one-sided t tests, p = 0.03, 33 IJVs). Conclusions The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P dural and consequently ICP in the upright posture.

Abstract Background Vitamin D is important for bone mass accrual during growth. Additionally, it is considered a requirement for a multitude of processes associated with, for example, the development of immunity. Many countries apply vitamin D supplementation strategies in infants, but the guidelines are not based on scientific evidence and aim at prevention of rickets. It remains unclear whether the recommended doses are sufficient for the wide array of other effects of vitamin D. The VIDI trial performed in Finland is the first large randomised controlled study for evaluation of the effects of different vitamin D supplemental doses in infancy on: 1. bone strength 2. infections and immunity 3. allergy, atopy and asthma 4. cognitive development 5. genetic regulation of mineral homeostasis Methods/Design VIDI, a randomised controlled double-blinded single-centre intervention study is conducted in infants from the age of 2 weeks to 24 months. Participants, recruited at Helsinki Maternity Hospital, are randomised to receive daily either 10 μg (400 IU) or 30 μg (1 200 IU) of vitamin D3 supplementation. Both groups are assessed at 6 months of age for calcium homeostasis, and at 12 and 24 months of age for parameters associated with bone strength, growth, developmental milestones, infections, immunity, atopy-related diseases, and genetic factors involved in these functions. Discussion The study enables evaluation of short and long term effects of supplemental vitamin D on growth, immune functions and skeletal and developmental parameters in infants, and the effects of genetic factors therein. The results enable institution of evidence-based guidelines for vitamin D supplementation in infancy. Trial registration ClinicalTrials.gov, NCT01723852 , registration date 6.11.2012.

Abstract Background The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients. Methods PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by western blot. Results In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (P = 0.03). No survival relationship in patients with RT was observed (P = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (P = 0.68)/inner tumour area (P = 0.49). In patients with RT, strong PINCH expression was related to a higher grade of LVD (lymphatic vessel density) (P = 0.01) Conclusions PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.

Abstract Background Genes and culture are believed to interact, but it has been difficult to find direct evidence for the process. One candidate example that has been put forward is lactase persistence in adulthood, i.e. the ability to continue digesting the milk sugar lactose after childhood, facilitating the consumption of raw milk. This genetic trait is believed to have evolved within a short time period and to be related with the emergence of sedentary agriculture. Results Here we investigate the frequency of an allele (-13910*T) associated with lactase persistence in a Neolithic Scandinavian population. From the 14 individuals originally examined, 10 yielded reliable results. We find that the T allele frequency was very low (5%) in this Middle Neolithic hunter-gatherer population, and that the frequency is dramatically different from the extant Swedish population (74%). Conclusions We conclude that this difference in frequency could not have arisen by genetic drift and is either due to selection or, more likely, replacement of hunter-gatherer populations by sedentary agriculturalists.

Abstract Background Geographic distribution of the genetic diversity in domestic animals, particularly mitochondrial DNA, has often been used to infer centers of domestication. The underlying presumption is that phylogeographic patterns among domesticates were established during, or shortly after the domestication. Human activities are assumed not to have altered the haplogroup frequencies to any great extent. We studied this hypothesis by analyzing 24 mtDNA sequences in ancient Scandinavian dogs. Breeds originating in northern Europe are characterized by having a high frequency of mtDNA sequences belonging to a haplogroup rare in other populations (HgD). This has been suggested to indicate a possible origin of the haplogroup (perhaps even a separate domestication) in central or northern Europe. Results The sequences observed in the ancient samples do not include the haplogroup indicative for northern European breeds (HgD). Instead, several of them correspond to haplogroups that are uncommon in the region today and that are supposed to have Asian origin. Conclusion We find no evidence for local domestication. We conclude that interpretation of the processes responsible for current domestic haplogroup frequencies should be carried out with caution if based only on contemporary data. They do not only tell their own story, but also that of humans.