Pain sensitivity and shoulder function among breast cancer survivors compared to matched controls: a case-control study.

OBJECTIVE: Persistent pain and loss of shoulder function are common adverse effects to breast cancer treatment, but the extent of these issues in comparison with healthy controls is unclear for survivors beyond 1.5 years after treatment. The purpose of this study was to benchmark differences in pressure pain thresholds (PPT), maximal isokinetic muscle strength (MIMS), and active range of motion (ROM) of females with persistent pain ≥1.5 years after breast cancer treatment (BCS) compared with pain-free matched controls (CON), and examine the presence of movement-evoked pain (MEP) during assessment of MIMS. METHODS: The PPTs of 18 locations were assessed using a pressure algometer and a numeric rating scale was used to assess intensity of MEP. Active ROM and MIMS were measured using a universal goniometer and an isokinetic dynamometer, respectively. RESULTS: A two-way analysis of variance revealed that PPTs across all locations, MIMS for horizontal shoulder extension/flexion and shoulder adduction, active ROM for shoulder flexion, horizontal shoulder extension, shoulder abduction, and external shoulder rotation were significantly lower for BCS compared with CON (P < 0.05). MEP was significantly higher for BCS and MEP intensity had a significant, negative correlation with PPTs (P < 0.01). DISCUSSION/CONCLUSION: BCS with persistent pain ≥1.5 years after treatment demonstrates widespread reductions in PPTs and movement-specific reductions in MIMS and active ROM of the affected shoulder, along with MEP during physical performance assessment. IMPLICATIONS FOR CANCER SURVIVORS: BCS with persistent pain ≥1.5 years after treatment shows signs of central sensitization and may benefit from individualized rehabilitation.

Resistance Training-Induced Acute Hypoalgesia in Women With Persistent Pain After Breast Cancer Treatment.

ABSTRACT: Fogh Rasmussen, GH, Madeleine, P, Arroyo-Morales, M, Voigt, M, and Kristiansen, M. Resistance training-induced acute hypoalgesia in women with persistent pain after breast cancer treatment. J Strength Cond Res 37(3): e16-e24, 2023-The aim of this study was to determine whether a single bout of resistance training (RT) produces acute exercise-induced hypoalgesia (EIH) in breast cancer survivors (BCS) suffering from persistent pain ≥1.5 years after treatment. Twenty individuals with self-reported pain ≥3 on a 0-10 Numerical Rating Scale after treatment for breast cancer completed 3 experimental sessions, (a) familiarization; (b) 1 repetition maximum (1RM) normalization, and (c) training, consisting of 3 sets of 10 repetitions at 60% of 1 repetition maximum. Pressure pain thresholds (PPTs) were measured before and after training for the dorsal and ventral shoulder regions of the affected side. Movement-evoked pain (MEP) and rating of perceived exertion (RPE) were collected immediately after each set. A p -value less than 0.05 was considered statistically significant. The results demonstrated a significant increase in PPTs of the ventral shoulder region after a single bout of RT ( p ≤ 0.05), indicating a localized analgesic response for this area. By contrast, no change was detected in PPTs on the dorsal shoulder region. No significant differences were found in MEP between sessions despite a significant increase in load and RPE during 1RM assessment ( p ≤ 0.05), indicating that MEP was not affected by increase in absolute and relative intensity. In conclusion, a single bout of submaximal RT reduced PPTs for the ventral shoulder region of BCS with persistent pain after treatment and was well tolerated. Hence, RT may be a useful therapeutic tool for managing persistent pain after breast cancer treatment in clinical practice.

Absolute and relative reliability of pain sensitivity and functional outcomes of the affected shoulder among women with pain after breast cancer treatment.

OBJECTIVE: Breast cancer survivors (BCS) are often characterized by decreased pressure pain thresholds (PPT), range of motion (ROM) and strength in and around the shoulder affected by the treatment. This intra-rater reliability study was to establish the relative and absolute reliability of PPT's, active ROM and maximal isokinetic muscle strength (MIMS) of the affected shoulder in BCS with persistent pain after treatment. METHODS: Twenty-one BCS participated in the study. The PPTs of 17 locations and pain intensity were assessed using a pressure algometer and a numeric rating scale. The ROM was measured using a universal goniometer and MIMS was measured using an isokinetic dynamometer. Relative reliability was estimated using intra class correlation coefficient (ICC), and absolute reliability using standard error of measurement (SEM). Minimum detectable change (MDC) was calculated from SEM. RESULTS: The ICCs for PPTs ranged from 0.88-0.97, with SEM values ranging from 12.0 to 28.2 kPa and MDC ranging from 33.2 to 78.2 kPa. The ICCs for ROM ranged from 0.66-0.97, with SEM values ranging from 3.0 to 7.5° and MDC ranging from 8.4 to 20.8°. Finally, ICCs for MIMS ranged from 0.62-0.92, with SEM values ranging from 0.03 to 0.07 Nm/Kg FFM and MDC ranging from 0.09 to 0.19 Nm/kg FFM. CONCLUSION: The results of this study indicate that PPTs, ROM and MIMS can be measured reliably on the affected shoulder in BCS with pain after treatment. This offer the possibility of using these measures to assess the effectiveness of interventions in this population.

Use of natural medicine and dietary supplements concomitant with conventional medicine among people with Multiple Sclerosis.

BACKGROUND: The use of complementary and alternative medicine (CAM) are widespread among people with Multiple Sclerosis (PwMS) and are often used concomitant with conventional treatment. Natural medicine and dietary supplements (NADS) are the most frequently used CAM modality and among other patient groups use of NADS concomitant with conventional medicine has been reported as a potential risk to patients' safety due to risk of drug interactions. The use of NADS concomitant with conventional medicine has, however, not been investigated among PwMS. This study's aim was to investigate the prevalence of NADS and conventional MS-related medicine use among PwMS, specific types of NADS and conventional MS-related medicine used, the prevalence of NADS used concomitant with conventional MS-related medicine, and to characterize PwMS who use NADS and PwMS who use NADS concomitant with conventional MS-related medicine in a Danish context. METHODS: The study was a cross-sectional study conducted as an interviewer-administered survey via phone in April 2019. The questionnaire includes questions about the use of NADS and conventional MS medicine as well as sociodemographic and health-related factors. In total 384 PwMS answered the questionnaire. Both descriptive and logistic analyses were used to analyze the data. RESULTS: The results show that the majority of PwMS use conventional MS-related medicine. In total, 85 % (n=322) had used at least one NADS within the last 12 months including vitamin D. When excluding vitamin D, the use of NADS within the last 12 months was 78.4% (n=298). Beside vitamin D the most reported types of NADS used were fatty acids (37%), Multivitamins (37%), and Calcium (35%). A total of 75.8% (n=288) reported using NADS concomitant with conventional MS medicine, and the products most often combined with conventional MS medicine were Vitamin D, Multivitamin, Calcium, Magnesium, and fatty acids. The results suggest that PwMS using NADS concomitant with conventional MS-related medicine are characterized by a high prevalence of young and newly diagnosed patients with a high education level. CONCLUSION: The study contributes to a better understanding of NADS used among PwMS. The study shows that the majority of PwMS use NADS and that they use it concomitant with conventional MS-medicine. Furthermore, the detailed mapping of the specific types of NADS used gives a nuanced insight into the specific products of NADS used among PwMS, including different kinds of vitamins, minerals, and herbal remedies.

Arterial stiffness in people with Type 2 diabetes and obstructive sleep apnoea.

AIMS: To examine whether people with Type 2 diabetes with concurrent obstructive sleep apnoea have increased arterial stiffness as compared with people with Type 2 diabetes without obstructive sleep apnoea. METHODS: In a study with a case-control design, 40 people with Type 2 diabetes and treatment-naïve moderate to severe obstructive sleep apnoea (Apnoea-Hypopnoea Index ≥15) and a control group of 31 people with Type 2 diabetes without obstructive sleep apnoea (Apnoea-Hypopnoea Index <5) were examined. Obstructive sleep apnoea status was evaluated using the ApneaLink® + home-monitoring device (Resmed Inc., San Diego, CA, USA), providing the Apnoea-Hypopnoea Index scores. Arterial stiffness was assessed according to carotid-femoral pulse wave velocity using the Sphygmocor device and the oscillometric Mobil-O-Graph® (I.E.M. GmbH, Stolberg, Germany). RESULTS: Carotid-femoral pulse wave velocity was not significantly different between participants with Type 2 diabetes with obstructive sleep apnoea and those without obstructive sleep apnoea (10.7±2.2 m/s vs 10.3±2.1 m/s; P=0.513), whereas oscillometric pulse wave velocity was significantly higher in participants with Type 2 diabetes with obstructive sleep apnoea than in those without obstructive sleep apnoea (9.5±1.0 m/s vs 8.6±1.4 m/s; P=0.002). In multiple regression analysis, age (P=0.002), gender (men; P=0.018) and HbA1c (P=0.027) were associated with carotid-femoral pulse wave velocity, and systolic blood pressure (P=0.004) and age (P<0.001) were associated with oscillometric pulse wave velocity. After adjustment, presence of obstructive sleep apnoea was not independently associated with pulse wave velocity whether assessed by tonometry or oscillometry. CONCLUSION: In conclusion, the present study did not find an age- and blood pressure-independent association between moderate to severe obstructive sleep apnoea and arterial stiffness in non-sleepy people with Type 2 diabetes. (Clinical trial registration number: NCT02482584).

Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

PURPOSE: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. METHODS: We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. RESULTS: The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. CONCLUSIONS: Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.

Contextualisation of patient-centred care: A comparative qualitative study of healthcare professionals' approaches to communicating with seriously ill patients about their dependent children.

Patients' family relations play an important part in the provision of patient-centred cancer care, not least when healthcare professionals encounter seriously ill patients with dependent children. Little is known about how children are perceived and dealt with in clinical encounters. In this qualitative comparative study, we explore the influence of medical contexts in three Danish hospital wards, haematology, oncological gynaecology and neuro-intensive care, on communication with patients about their children. In exploring the degree to which the inclusion of children in clinical encounters is dependent on context, we took a comparative approach based on fieldwork in wards either exclusively focusing on cancer treatment or partially involved in critical phases of cancer treatment. We conducted 49 semi-structured, in-depth interviews with doctors and nurses, and 27 days of participant observation. The thematic analysis was based on Bateson's conceptualisation of communication. We found that healthcare professionals' approach to children in clinical encounters and the ways in which children were positioned on each ward were influenced by aspects specific to the ward, including the diagnosis and treatments that related specifically to the patient. Our findings suggest the need to explore further the influence of medical contexts on the inclusion of children in patient communication.

Future complications of chronic hepatitis C in a low-risk area: projections from the hepatitis c study in Northern Norway.

BACKGROUND: Hepatitis C (HCV) infection causes an asymptomatic chronic hepatitis in most affected individuals, which often remains undetected until cirrhosis and cirrhosis-related complications occur. Screening of high-risk subjects in Northern Norway has revealed a relatively low prevalence in the general population (0.24%). Despite this, late complications of HCV infection are increasing. Our object was to estimate the future prevalence and complications of chronic HCV infection in the period 2013-2050 in a low-risk area. METHODS: We have entered available data into a prognostic Markov model to project future complications to HCV infection. RESULTS: The model extrapolates the prevalence in the present cohort of HCV-infected individuals, and assumes a stable low incidence in the projection period. We predict an almost three-fold increase in the incidence of cirrhosis (68 per 100,000), of decompensated cirrhosis (21 per 100,000) and of hepatocellular carcinoma (4 per 100,000) by 2050, as well as a six-fold increase in the cumulated number of deaths from HCV-related liver disease (170 per 100,000 inhabitants). All estimates are made assuming an unchanged treatment coverage of approximately 15%. The estimated numbers can be reduced by approximately 50% for cirrhosis, and by approximately one third for the other endpoints if treatment coverage is raised to 50%. CONCLUSION: These projections from a low-prevalence area indicate a substantial rise in HCV-related morbidity and mortality in the coming years. The global HCV epidemic is of great concern and increased treatment coverage is necessary to reduce the burden of the disease.

Differences in hospital attendance for anaphylaxis between immigrants and non-immigrants: a cohort study.

BACKGROUND: The impact of migration on the risk of anaphylaxis remains unknown. We hypothesized that non-Western immigrants have a lower incidence of anaphylaxis compared to Danish-born. We investigated variations in hospital attendance for anaphylaxis between immigrants and Danish-born including time- and age- trends. METHODS: A register-based, historical prospective cohort design. Refugees or family reunified immigrants (n = 127 250) who, between January 1, 1994 and December 31, 2010, obtained residency permits in Denmark were included and matched in a 1 : 6 ratio on age and sex with Danish-born individuals (n = 740 600). Personal identification numbers were cross-linked to the Danish National Patient Registry identifying all first-time hospital attendances for anaphylaxis from January 1, 1994 and December 31, 2010. Incidence rate ratios were estimated, stratified for sex and region of birth, adjusting for age using a Cox regression model including the influence of duration of residence and age when residence was obtained. RESULTS: In total 1053 hospital attendances for anaphylaxis were identified: 89 among non-Western immigrants, 9 among Western immigrants and 955 among Danish-born patients. Both male (RR = 0.65; 95%CI: 0.46;0.90) and female (RR = 0.64; 95%CI: 0.48;0.85) non-Western immigrants had a significantly lower risk ratio of hospital attendance for anaphylaxis compared to Danish-born. Compared to Danish-born, non-Western immigrants living in Denmark during the entire follow-up period also showed a decreased risk (RR = 0.65; 95%CI: 0.34;1.25). Compared to Danish-born, non-Western immigrants who obtained residence permission as children had a decreased risk of hospital attendance for anaphylaxis (RR = 0.48; 95%CI: 0.25;0.91). CONCLUSION: This Danish register-based study using nationwide data revealed fewer hospital attendances for anaphylaxis among non-Western immigrants compared to Danish-born; however this protection was lost over time.

Perinatal outcome after first-trimester risk assessment in monochorionic and dichorionic twin pregnancies: a population-based register study.

OBJECTIVE: To evaluate the influence of chorionicity on outcome in twin pregnancies with two live fetuses at the nuchal translucency scan in the first trimester. DESIGN: Population-based register study. SETTING: Denmark. POPULATION: A cohort of 3621 twin pregnancies, 84.3% dichorionic (DC) pregnancies and 15.7% monochorionic (MC) pregnancies (15% diamniotic [MCDA] and 0.7% monoamniotic [MCMA]). METHODS: A cohort study based on data collected from the Danish Fetal Medicine Database from July 2008 to July 2011. MAIN OUTCOME MEASURES: Fetal loss rate before week 22, intrauterine death rate from week 22 to birth, and neonatal mortality. RESULTS: Significantly more DC than MC pregnancies resulted in at least one live born infant-98.2% versus 92.3% in MCDA (P < 0.05) and 66.7% in MCMA pregnancies (P < 0.05). The rates of spontaneous loss of both fetuses before week 22 were 0.9, 2.4, and 20.8% for DC, MCDA and MCMA twins, respectively (P < 0.05). The rate of intrauterine death of one fetus after week 22 was higher in MCDA twins than DC twins 1.7% versus 0.6% (P < 0.05). We found no significant difference in the rate of neonatal death. CONCLUSIONS: The risk of spontaneous loss of both fetuses before week 22 of gestation was significantly higher in MCMA and MCDA pregnancies than in DC pregnancies, and significantly higher in MCMA pregnancies than in MCDA pregnancies. After week 22 the risk of loss of one fetus after week 22 was significantly higher in MCDA pregnancies than in DC pregnancies.

Inter-subject variability of muscle synergies during bench press in power lifters and untrained individuals.

The purpose of the study was to elucidate the role of expertise on muscle synergies involved in bench press. Ten expert power lifters (EXP) and nine untrained participants (UNT) completed three sets of eight repetitions at 60% of three repetition maximum in bench press. Muscle synergies were extracted from surface electromyography data of 21 bench press cycles using non-negative matrix factorization algorithm. The synergy activation coefficient represents the relative contribution of the muscle synergy to the overall muscle activity pattern, while the muscle synergy vector represents the relative weighting of each muscle within each synergy. Describing more than 90% of the variability, two muscle synergies reflected the eccentric and concentric phase. The cross-correlations (ρ(max)) for synergy activation coefficient 2 (concentric phase) were 0.83 [0.71;0.88] and 0.59 [0.49;0.77] [Median ρ(max) (25th;75th percentile)] (P = 0.001) in UNT and EXP, respectively. Median correlation coefficient (ρ) for muscle synergy vector 2 was 0.15 [-0.08;0.46] and 0.48 [0.02;0.70] (P = 0.03) in UNT and EXP, respectively. Thus, EXP showed larger inter-subject variability than UNT in the synergy activation coefficient during the concentric phase, while the muscle synergy vectors were less variable in EXP. This points at the importance of a specialized neural strategy in elite bench press performance.

Programmed cell death during neuronal development: the sympathetic neuron model.

Developing sympathetic neurons of the superior cervical ganglion are one of the best studied models of neuronal apoptosis. These cells require nerve growth factor (NGF) for survival at the time that they innervate their final target tissues during late embryonic and early postnatal development. In the absence of NGF, developing sympathetic neurons die by apoptosis in a transcription-dependent manner. Molecular studies of sympathetic neuron apoptosis began in the 1980s. We now know that NGF withdrawal activates the mitochondrial (intrinsic) pathway of apoptosis in sympathetic neurons cultured in vitro, and the roles of caspases, Bcl-2 (B-cell CLL/lymphoma 2) family proteins and XIAP (X-linked inhibitor of apoptosis protein) have been extensively studied. Importantly, a considerable amount has also been learned about the intracellular signalling pathways and transcription factors that regulate programmed cell death in sympathetic neurons. In this article, we review the key papers published in the past few years, covering all aspects of apoptosis regulation in sympathetic neurons and focusing, in particular, on how signalling pathways and transcription factors regulate the cell death programme. We make some comparisons with other models of neuronal apoptosis and describe possible future directions for the field.

Concomitant changes in cross-sectional area and water content in skeletal muscle after resistance exercise.

This study investigated how one bout (1EX) and three bouts (3EX) of strenuous resistance exercise affected the cross-sectional area (CSA) and water content (WC) of the quadriceps muscle and patella tendon (PT), 4 h and 52 h after the last exercise bout. Ten healthy untrained male subjects performed 1EX with one leg and 3EX with the other leg. CSA and WC were measured with magnetic resonance imaging 10, 20 and 30 cm proximal to the tibia plateau (TP) for the muscle, and at the proximal, central and distal site for the PT prior to exercise, and 4 h and 52 h after the last exercise bout. Ten centimeter above the TP, muscle CSA was significantly increased at 4 h (1EX: 13 ± 5%; 3EX: 13 ± 4%) and 52 h (1EX: 16 ± 5%; 3EX: 16 ± 5%) compared with baseline. Muscle WC was significantly increased at 4 h (1EX: 7 ± 1%; 3EX: 6 ± 2%) and 52 h (1EX: 8 ± 2%; 3EX: 8 ± 3%) compared to baseline. PT central CSA was significantly reduced at 52 h (3EX: 14 ± 2%) compared with baseline and (3EX: 13 ± 1%) compared with 4 h. Present data demonstrate that strenuous resistance exercise results in an acute increase in muscle WC and underlines the importance of ensuring sufficient time between the last exercise bout and the determination of anatomical dimensions in muscles.

Migration from low- to high-risk countries: a qualitative study of perceived risk of breast cancer and the influence on participation in mammography screening among migrant women in Denmark.

Migrants are less likely to participate in mammography screening programmes compared with local-born populations in Europe. We explored perceptions of breast cancer risk and the influence on participation in mammography screening programmes among migrant women born in countries with low incidence rates of breast cancer. We conducted eight individual interviews and six group interviews including a total of 29 women aged 50-69 years living in Copenhagen, Denmark. Women were migrants born in Somalia, Turkey, Pakistan or Arab countries. Phenomenological analysis was used. Breast cancer was perceived to be caused by multiple factors, including genetics, health behaviour, stress, fertility and breastfeeding. Some women perceived breast cancer to be more prevalent in Denmark as compared with their country of birth, and perceived their risk of developing breast cancer to increase with length of stay in Denmark. Although most women agreed on the relevance of mammography screening, other cancers, chronic and infectious diseases and mental health problems were mentioned as equally or more important to target in public health programmes. A life course perspective comprising previous and current circumstances in country of birth as well as immigration country is important for understanding and influencing the screening behaviour of migrants.

Water-content calculation in growth plate and cartilage using MR T1-mapping design and validation of a new method in a porcine model.

OBJECTIVE: There is a close relation between cartilage health and its hydration state. Current magnetic resonance methods allow visualizing this tissue. However, a quantitative analysis is more useful when studying disease. The purpose of this study was to quantify water content in cartilage using magnetic resonance without contrast agents. MATERIALS AND METHODS: Water-content estimations using T1 magnetic resonance mapping were done first in eight gelatin samples where the water content was previously known. The same method was used in the physeal areas of eight skeletally immature 30-kg pigs. To calculate accuracy, T1 calculations were compared to dry-freeze, which is considered the gold standard because it can remove the total water content form a tissue. Four fresh cartilage and seven gelatin samples were dry-frozen. Water content obtained from dry-freeze was compared to the one calculated from T1 map values. A mathematical model and statistical analysis were used to calculate the predictive value of the method and its significance. RESULTS: T1-map-based magnetic resonance method can calculate water content in cartilage with an accuracy of 97.3 %. We calculated a coefficient of variance for this method against dry-frozen sample of 3.68 (SD = 1.2) in gelatin samples, and 2.73 (SD = 1.3) in in vivo samples. Between two independent observers, the coefficient of variance was 0.053, which suggests it can be easily reproduced. CONCLUSIONS: Magnetic resonance was able to calculate, with high accuracy, the cartilage water content using T1 mapping sequences.

An explosively driven high-power microwave pulsed power system.

The increased popularity of high power microwave systems and the various sources to drive them is the motivation behind the work to be presented. A stand-alone, self-contained explosively driven high power microwave pulsed power system has been designed, built, and tested at Texas Tech University's Center for Pulsed Power and Power Electronics. The system integrates four different sub-units that are composed of a battery driven prime power source utilizing capacitive energy storage, a dual stage helical flux compression generator as the main energy amplification device, an integrated power conditioning system with inductive energy storage including a fast opening electro-explosive switch, and a triode reflex geometry virtual cathode oscillator as the microwave radiating source. This system has displayed a measured electrical source power level of over 5 GW and peak radiated microwaves of about 200 MW. It is contained within a 15 cm diameter housing and measures 2 m in length, giving a housing volume of slightly less than 39 l. The system and its sub-components have been extensively studied, both as integrated and individual units, to further expand on components behavior and operation physics. This report will serve as a detailed design overview of each of the four subcomponents and provide detailed analysis of the overall system performance and benchmarks.

High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking. AIM: To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD. METHODS: From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia. RESULTS: The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo- (n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia. CONCLUSIONS: Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.

A rapid chemokine response of macrophage inflammatory protein (MIP)-1α, MIP-1ß and the regulated on activation, normal T expressed and secreted chemokine is associated with a sustained virological response in the treatment of chronic hepatitis C.

The role of chemokines in chronic hepatitis C virus (HCV) infection is not fully understood. The present study aimed to characterize the baseline serum concentrations and the initial ß-chemokine response to treatment with interferon-α and ribavirin with respect to the final clinical outcome of virological response to treatment. Serum concentrations of alanine aminotransferase (ALT) and of the CC subfamily chemokines [macrophage inflammatory protein (MIP)-1α, MIP-1ß, monocyte chemoattractant protein (MCP)-1 and the regulated on activation, normal T expressed and secreted (RANTES) chemokine] were measured in patients with chronic HCV infection and in healthy individuals. Necroinflammation and fibrosis were scored in liver biopsies. Treatment outcomes were classified as with or without a sustained virological response after a full-course treatment according to the genotypes. The main treatment group consisted of 72 patients with chronic hepatitis C, whereas 24-h blood samples were available for 42 patients. Increased baseline levels of all CC chemokines were found in the two responder groups compared to the healthy controls, although significant levels were reached only for MIP-1α and MCP-1. No correlation was observed between chemokine levels and serum ALT levels, any histological necroinflammatory parameters, or the fibrosis grade. After 24 h of treatment, increases in MIP-1α, MIP-1ß and RANTES levels were exclusively observed in the group with sustained virological response. MCP-1 was also significantly increased after 24 h in both responder groups, although no differences were observed between the two responder groups. In conclusion, an early MIP-1α, MIP-1ß, and RANTES response may predict a sustained response to virological treatment.

Total and cause-specific mortality rates in a prospective study of community-acquired hepatitis C virus infection in northern Norway.

Knowledge of the natural course and especially the total and cause-specific mortality of community-acquired chronic HCV infection is limited. The aims of our study were to determine the total and cause-specific mortality in patients infected with chronic hepatitis C in a community-based setting in northern Norway. This prospective cohort study included 1010 HCV-positive patients diagnosed with recombinant immunoblot assay between 1 January 1990 and 1 January 2000, with a median observation time from diagnosis to follow-up of 7 years. Data were collected from medical records in the period between 1 January 2004 and 30 June 2006. Time and cause of death were ascertained from the Norwegian Causes of Death Register. Age-adjusted death rates and standardised mortality ratios (SMRs) were compared with those of the general Norwegian population. In total, 122 deaths were recorded. The Kaplan-Meier estimate of survival was 88% at 14 years. The SMR in the cohort relative to the general population was 6.66. Most of the excess deaths in both genders were because of liver-related causes, those associated with a drug-using lifestyle and suicide. The statistically significant increase in SMRs ranged from 4.2 for death by cancer in women to 64.6 for liver disease in women. There was no statistically significant increase in SMRs from cardiovascular disease in either gender or from cancer in men. In conclusion, our study shows that the death rate in patients infected with hepatitis C is 6.66 times higher than in the general Norwegian population.

NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons.

Neuronal apoptosis has a major role during development and aberrant apoptosis contributes to the pathology of certain neurological conditions. Studies with nerve growth factor (NGF)-dependent sympathetic neurons have provided important insights into the molecular mechanisms of neuronal apoptosis and the signalling pathways that regulate the cell death programme in neurons. The BH3-only protein Bim is a critical mediator of apoptosis in many cell types and in sympathetic neurons is required for NGF withdrawal-induced death. However, regulation of bim expression is complex and remains incompletely understood. We report that a conserved inverted CCAAT box (ICB) in the rat bim promoter is bound by the heterotrimeric transcription factor NF-Y. Interestingly, NF-Y is required for bim promoter activity and its induction following NGF withdrawal. We demonstrate that NF-Y activity is essential for endogenous Bim expression and contributes to NGF withdrawal-induced death. Furthermore, we find that the transcriptional coactivators CBP and p300 interact with NF-Y and FOXO3a and bind to this region of the bim promoter. The amount of CBP/p300 bound to bim increases after NGF deprivation and inhibition of CBP/p300 activity reduces bim induction. Our results indicate that NF-Y cooperates with FOXO3a to recruit CBP/p300 to the bim promoter to form a stable multi-protein/DNA complex that activates bim transcription after survival factor withdrawal.