Gut immune maturation depends on colonization with a host-specific microbiota.

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression--all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.

Sphingosine 1-phosphate receptor signaling.

The sphingosine 1-phosphate (S1P) receptor signaling system is a productive model system. A hydrophobic zwitterionic lysophospholipid ligand with difficult physical properties interacts with five high-affinity G protein-coupled receptors to generate multiple downstream signals. These signals modulate homeostasis and pathology on a steep agonist concentration-response curve. Ligand presence is essential for vascular development and endothelial integrity, while acute increases in ligand concentrations result in cardiac death. Understanding this integrated biochemical system has exemplified the impact of both genetics and chemistry. Developing specific tools with defined biochemical properties for the reversible modulation of signals in real time has been essential to complement insights gained from genetic approaches that may be irreversible and compensated. Despite its knife-edge between life and death, this system, based in part on receptor subtype-selectivity and in part on differential attenuation of deleterious signals, now appears to be on the cusp of meaningful therapy for multiple sclerosis.

Risk of thrombosis and bleeding in gynecologic cancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L. METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty. RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. CONCLUSION: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.

Risk of thrombosis and bleeding in gynecologic noncancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis. STUDY ELIGIBILITY CRITERIA: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L. METHODS: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty. RESULTS: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures. CONCLUSION: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures.

Bone marrow metabolism is affected by body weight and response to exercise training varies according to anatomical location.

AIM: High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole-body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight. METHODS: We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co-twins 7.6 kg/m2 ; eight female pairs). Ten pairs completed the 6-month long training intervention. We measured lumbar vertebral and femoral BM insulin-stimulated glucose uptake (GU) using 18 F-FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers. RESULTS: At baseline, heavier co-twins had higher lumbar vertebral BM GU (p < .001) and lower bone turnover markers (all p < .01) compared with leaner co-twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole-body insulin sensitivity, aerobic capacity (both p < .05) and femoral BM GU (p = .008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p = .02), as GU tended to decrease in heavier co-twins (p = .06) while there was no change in leaner co-twins. CONCLUSIONS: In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co-twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity.

Relative risk of second malignant neoplasms highest among young adult cancer patients - a population-based registry study in Finland.

BACKGROUND AND PURPOSE: The objective of this study was to explore the incidence of second malignant neoplasms (SMNs) among adult cancer patients in Finland diagnosed with their first primary cancer (FPC) in 1992-2021. MATERIAL AND METHODS: The study used data from the population-based Finnish Cancer Registry (FCR). Risk estimates were calculated using the standardised incidence ratio (SIR), the ratio of observed second cancers compared to the expected numbers assuming the same cancer incidence as the corresponding sex-age-calendar year -split of the general population. RESULTS: A total of 573,379 FPCs were diagnosed during 1992-2021. During the follow-up, 60,464 SMNs were diagnosed. Male cancer patients had neither a decreased nor an increased risk (SIR 1.00 [95% CI, 0.99-1.01]) and female patients had an 8% increased risk (SIR 1.08 [95% CI, 1.06-1.09]) of developing any SMN compared to a FPC in the general population. The highest SIR of any SMN was observed in patients aged 20-39 -years at FPC diagnosis, and the SIR decreased by increasing age at diagnosis. Patients with lymphoid and haematopoietic tissue neoplasms, cancers of the mouth and pharynx, endocrine glands, respiratory and intrathoracic organs, skin, and urinary organs had the highest SIRs, while patients with cancers of the male genital organs and the female breast had the lowest SIRs. INTERPRETATION: Elevated SIRs were observed in cancer patients diagnosed at an early age and for FPCs known to be in large part attributable to lifestyle factors, which highlights the importance of monitoring and encouraging lifestyle changes.

Health-related quality of life after hip fracture: effects of a 12-month home-based exercise intervention-secondary analyses of an RCT.

PURPOSE: In this randomized controlled trial, we analyzed the effects of a 12-month home-based exercise intervention on the health-related quality of life (HRQoL) of patients with a hip fracture. METHODS: Participants (n = 121) aged ≥ 60 years, with a Mini-Mental State Examination (MMSE) score of ≥ 12 and an operated hip fracture, were placed into Exercise (n = 61) or Usual care (n = 60) groups. Physiotherapist-supervised, home-based training was given twice a week over 12 months. HRQoL was assessed using the 15D instrument at baseline and at 3, 6, and 12 months. The total 15D scores and dimension scores were analyzed and compared to national age- and sex-matched reference data. RESULTS: The participants' mean age was 81 years (SD 7), 75% were women, and 61% had a femoral neck fracture. The mean within-group change in total 15D score over 12 months was 0.023 (95% CI: -0.003 to 0.048) in the Usual care group, and 0.028 (CI: 0.003 to 0.054) in the Exercise group (between-group p = 0.76). We found a statistically significant change in total 15D score in the Exercise group, as well as in the dimension scores of mobility and usual activities in both groups. All 15D scores remained below the general population reference level. CONCLUSION: Exercise training for 12 months did not enhance the HRQoL of home-dwelling patients with hip fractures any more than usual care. In addition, HRQoL remained below the population level in both groups.

Familial aggregation of early-onset cancers in early-onset breast cancer families.

The risk of early-onset (EO) breast cancer is known to be increased in relatives of EO breast cancer patients, but less is known about the familial risk of other EO cancers. We assessed familial risks of EO cancers (aged ≤40 years) other than breast cancer in 54 753 relatives of 5562 women with EO breast cancer (probands) by using a population-based cohort from Finland. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were estimated by using gender-, age- and period-specific cancer incidences of the general population as reference. The risk of any cancer excluding breast cancer in first-degree relatives was comparable to population cancer risk (SIR 0.99, 95% CI: 0.84-1.16). Siblings' children of women with EO breast cancer were at an elevated risk of EO testicular and ovarian cancer (SIR = 1.74, 95% CI: 1.07-2.69 and 2.69, 95% CI: 1.08-5.53, respectively). The risk of EO pancreatic cancer was elevated in siblings of the probands (7.61, 95% CI: 1.57-22.23) and an increased risk of any other cancer than breast cancer was observed in children of the probands (1.27, 95% CI: 1.03-1.55). In conclusion, relatives of women with EO breast cancer are at higher familial risk of certain discordant EO cancers, with the risk extending beyond first-degree relatives.

Association between PIRCHE-II scores and de novo allosensitization after reduction of immunosuppression during SARS-CoV-2 infection in kidney transplant recipients.

BACKGROUND: Before the availability of mRNA vaccines, many transplant centers chose to significantly reduce maintenance immunosuppression in kidney transplant recipients (KTRs) with SARS-CoV-2 infection. The extent to which this increases the risk of allosensitization is unclear. METHODS: In this observational cohort study, we analyzed 47 KTRs from March 2020 to February 2021 who underwent substantial reduction of maintenance immunosuppression during SARS-CoV-2 infection. KTRs were followed at 6 and 18 months concerning the development of de novo donor-specific anti-HLA (human leukocyte antigen) antibodies (DSA). The HLA-derived epitope mismatches were calculated using the predicted indirectly recognizable HLA-epitopes (PIRCHE-II) algorithm. RESULTS: In total, 14 of 47 KTRs (30%) developed de novo HLA antibodies after the reduction of maintenance immunosuppression. KTRs with higher total PIRCHE-II scores and higher PIRCHE-II scores for the HLA-DR locus were more likely to develop de novo HLA antibodies (p = .023, p = .009). Furthermore, 4 of the 47 KTRs (9%) developed de novo DSA after reduction of maintenance immunosuppression, which were exclusively directed against HLA-class II antigens and also showed higher PIRCHE-II scores for HLA-class II. The cumulative mean fluorescence intensity of 40 KTRs with preexisting anti-HLA antibodies and 13 KTRs with preexisting DSA at the time of SARS-CoV-2 infection remained stable after the reduction of maintenance immunosuppression (p = .141; p = .529). CONCLUSIONS: Our data show that the HLA-derived epitope mismatch load between donor and recipient influences the risk of de novo DSA development when immunosuppression is temporarily reduced. Our data further suggest that reduction in immunosuppression should be made more cautiously in KTRs with high PIRCHE-II scores for HLA-class II antigens.

Cochlear implantation in single-sided deafness: a single-center experience of 138 cases.

OBJECTIVES: Assess the outcomes in patients who underwent cochlear implant (CI) for single-sided deafness (SSD). METHODS: All patients affected by SSD who underwent CI at Gruppo Otologico, Piacenza, from October 2012 to May 2022 with at least 6 months of follow-up were selected in the study group. The analysis included subjective and objective measures performed pre-operative and up to 24 months after surgery. Hearing threshold on both sides was evaluated with a weighted four-frequency average (PTA [0.5 kHz + 1 kHz + 2 kHz + 4 kHz]/4) on pure tone audiometry and speech audiometry (Speech Discrimination Score, SDS). The Speech Spatial and Qualities of Hearing scale (SSQ Questionnaire) for binaural hearing benefits and sound localization, the Tinnitus Handicap Inventory Questionnaire (THI) and Dizziness Handicap Inventory Questionnaire (DHI) were used for subjective assessment. RESULTS: Data from 138 patients, 69 males and 69 females, (mean age 49 years, range 17-77 years) underwent CI for SSD were examined. Single-sided hearing deprivation average before undergoing CI surgery was 2.5 years (range 3 months-35 years). There was a significant reduction of THI and DHI scores compared to pre-operative scores alongside a referred improvement in social, physical, and emotional well-being through the SSQ questionnaire. CONCLUSIONS: To the best of our knowledge, this paper descried the largest cohort of SSD who underwent CI in a single institution. According to our findings CI in patients affected by SSD represents a valuable tool for an overall improvement of tinnitus and dizziness but also quality of life, after at least 6 months of follow-up. Further studies are desirable to improve rehabilitation pathways and possibly set new standards of care of this condition.

Preventing Disordered Eating in Teenage Ballet Students: Evaluation of DancExcellent, a Combined CBT and Nutrition Education Intervention.

BACKGROUND: Disordered eating (DE) behaviors are relatively common among high-level dancers, especially in classical ballet. At the same time, interventions aimed at reducing DE behaviors in this population are scarce. METHODS: An 8-week exploratory preventive intervention for DE behaviors was carried out in a high-level ballet school for 40 teenagers aged 12-15 years (77.5% female). Both risk factors (perfectionism) and potentially protective factors (self-esteem, self-compassion) for the development of DE behaviors were considered. The intervention was created specifically for this study and consisted of five cognitive behavior therapy (CBT) workshops and four nutrition workshops. Additional components included newsletters for pupils and educational sessions and social media interactions with staff and parents. The intervention comprised two phases (control and intervention periods), with students acting as their own controls. Standardized questionnaires were completed before and after both phases. RESULTS: Questionnaire results did not indicate any changes in reported perfectionism, self-esteem, or self-compassion, nor were symptoms of DE affected during either the control or intervention periods. CONCLUSIONS: The intervention did not yield any discernible impact. However, it was affected by the onset of the COVID-19 pandemic, which limits our ability to draw conclusions about intervention effectiveness. Evaluations with pupils offer several considerations for future improvements.

Effects of Bifidobacterium animalis ssp. lactis 420 on gastrointestinal inflammation induced by a nonsteroidal anti-inflammatory drug: A randomized, placebo-controlled, double-blind clinical trial.

AIMS: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the gastric and duodenal mucosa. Some probiotics have proven useful in ameliorating the harmful side-effects of NSAIDs. Our aim was to evaluate whether oral administration of Bifidobacterium animalis ssp. lactis 420 (B420) can attenuate the increase of calprotectin excretion into faeces induced by intake of diclofenac sustained-release tablets. METHODS: A double-blind, parallel-group, placebo-controlled and randomized clinical study was performed in 50 healthy male and female volunteers aged 20-40 years, in Finland. Study participation consisted of 4 phases: run-in, intervention with B420 or placebo, B420 or placebo + NSAID treatment, and follow-up. The primary outcome was the concentration of calprotectin in faeces. Secondary outcomes were haemoglobin and microbial DNA in faeces and blood haemoglobin levels. RESULTS: Intake of diclofenac increased the faecal excretion of calprotectin in both groups. The observed increases were 48.19 ± 61.55 µg/g faeces (mean ± standard deviation) in the B420 group and 31.30 ± 39.56 µg/g in the placebo group (difference estimate 16.90; 95% confidence interval: -14.00, 47.77; P = .276). There were no significant differences between the treatment groups in changes of faecal or blood haemoglobin. Faecal B. lactis DNA was much more abundant in the B420 group compared to the placebo group (ANOVA estimate for treatment difference 0.85 × 109 /g faeces; 95% confidence interval: 0.50 × 109 , 1.21 × 109 ; P < .0001). CONCLUSIONS: Short-term administration of the probiotic B420 did not protect the healthy adult study participants from diclofenac-induced gastrointestinal inflammation as determined by analysis of faecal calprotectin levels.

Effects of Home-Based Physical Exercise on Days at Home, Health Care Utilization, and Functional Independence Among Patients With Hip Fractures: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of a physical exercise program on days lived at home, the use and costs of health care and social services, mortality, and functional independence among patients with hip fractures. DESIGN: Randomized controlled trial with a parallel 2-group design consisting of a 12-month intervention and 12-month registry follow-up. SETTING: Home-based intervention. PARTICIPANTS: Patients aged ≥60 years (N=121) with operated hip fracture and who were living at home were randomized into physical exercise (n=61) and usual care (n=60) groups. INTERVENTIONS: Supervised physical exercise twice a week. MAIN OUTCOME MEASURES: The primary outcome was the number of days lived at home over 24 months. Secondary outcomes were the use and costs of health care and social services, mortality over 24 months, and Functional Independence Measure (FIM) over 12 months. RESULTS: Over 24 months, there was no significant difference between the groups in terms of days lived at home (incidence rate ratio, 1.01; 95% confidence interval [CI], 0.90-1.14) or mortality (hazard ratio, 1.01; 95% CI, 0.42-2.43). The mean total costs of health care and social services did not differ between the groups. The costs per person-year were 1.26-fold (95% CI, 0.87-1.86) greater in the physical exercise group than in the usual care group over 12 months and 1.08-fold (95% CI, 0.77-1.70) over 24 months. The mean difference between the change in FIM of the groups over 12 months was 4.5 points (95% CI, 0.5-8.5; P=.029) in favor of the physical exercise group. CONCLUSIONS: Long-term home-based physical exercise had no effect on the number of days lived at home over 24 months among patients with hip fractures. The intervention was cost neutral over these 24 months. The FIM scores improved in both groups over 12 months, but the improvement was significantly greater in the physical exercise group than in the usual care group.

Top-Down Proteomics of Human Saliva Discloses Significant Variations of the Protein Profile in Patients with Mastocytosis.

Mastocytosis is a myeloproliferative neoplasm causing abnormal clonal mast cell accumulation in different tissues, such as skin and bone marrow. A cutaneous subtype (CM) is distinguished from a systemic one (SM); SM patients can be grouped into SM with (SM+C) or without (SM-C) additional cutaneous lesions, and their classification is often challenging. This study was purposed to highlight variations in the salivary proteome of patients with different mastocytosis subtypes and compared to healthy controls. A top-down proteomics approach coupled to a label-free quantitation revealed salivary profiles in patients different from those of controls and a down-regulation of peptides/proteins involved in the mouth homeostasis and defense, such as statherin, histatins, and acidic proline-rich proteins (aPRPs), and in innate immunity and inflammation, such as the cathepsin inhibitors, suggesting a systemic condition associated with an exacerbated inflammatory state. The up-regulation of antileukoproteinase and S100A8 suggested a protective role against the disease status. The two SM forms were distinguished by the lower levels of truncated forms of aPRPs, statherin, P-B peptide, and cystatin D and the higher levels of thymosin ß4 and α-defensins 1 and 4 in SM-C patients with respect to SM+C. Data are available via ProteomeXchange with identifier PXD017759.

Familial aggregation of early-onset cancers.

This registry-linkage study evaluates familial aggregation of cancer among relatives of a population-based series of early-onset (≤40 years) cancer patients in Finland. A cohort of 376,762 relatives of early-onset cancer patients diagnosed between 1970 and 2012 in 40,538 families was identified. Familial aggregation of early-onset breast, colorectal, brain and other central nervous system (CNS) cancer and melanoma was explored by standardized incidence ratios (SIR), stratified by relatedness. Gender-, age- and period-specific population cancer incidences were used as reference. Cumulative risks for siblings and offspring of the proband up to age ≤40 years were also estimated. Almost all early-onset cancers were sporadic (98% or more). Among first-degree relatives, SIR was largest in colorectal cancer (14, 95% confidence interval 9.72-18), and lowest in melanoma (1.93, 1.05-3.23). Highest relative-specific SIRs were observed for siblings in families, where also parent had concordant cancer, 90 (43-165) for colorectal cancer and 29 (11-64) for CNS cancer. In spouses, all SIRs were at population level. Cumulative risk of colorectal cancer by age 41 was 0.98% in siblings and 0.10% in population, while in breast cancer the corresponding risks were 2.05% and 0.56%. In conclusion, early-onset cancers are mainly sporadic. Findings support high familial aggregation in early-onset colorectal and CNS cancers. Familial aggregation in multiplex families with CNS cancers was mainly attributed to neurofibromatosis and in colorectal cancer to FAP- and HNPCC-syndromes. The pattern of familial aggregation of early-onset breast cancer could be seen to support very early exposure to environmental factors and/or rare genetic factors.

My Migraine Voice survey: disease impact on healthcare resource utilization, personal and working life in Finland.

BACKGROUND: A global My Migraine Voice survey was conducted in 31 countries among 11,266 adults who suffered from ≥4 monthly migraine days (MMD). The aim of this retrospective observational survey-based study was to analyse the country specific results in Finland in order to understand the impact of migraine based on disease severity. METHODS: The included participants (3%, n = 338/11,266) were stratified by mean MMDs into 4 ≤ MMD < 8 (n = 133), 8 ≤ MMD < 15 (n = 139) and MMD ≥ 15 (n = 66) subgroups. Comorbidities, migraine-related emotional burden and impact on daily living and work productivity and activity impairment (WPAI) were assessed. Subgroup analysis on healthcare resource utilization (HCRU) due to migraine was assessed by visits to healthcare practitioners (HCPs) during the past 6 months and by hospitalizations and emergency room (ER) visits during the past 12 months. The group difference was tested using the one-way ANOVA and for categorical variables using the Chi-squared test. The association between HCRU and MMD and number of comorbidities was assessed using negative binomial regression analysis. RESULTS: Mean age was 44 years, 93% were women and 67% (n = 227) were employed. Chronic migraine (CM, MMD ≥ 15) was reported in 19.5% of the respondents. The negative impact on daily functioning and emotional burden increased significantly by migraine frequency. Mean number of comorbidities was 2.4, and mean number of HCP visits during the previous 6 months was 5.9. Increase in migraine frequency and comorbidities was associated with higher HCRU. Eighty-eight percent of the respondents reported negative impact on working life and 52% experienced overall work productivity impairment. Over previous month, the mean number of missed working days for all respondents was 2.8 days of which 54% were paid sick leave days, and in CM up to 6.0 days and 30%, respectively. Both absenteeism and presenteeism were higher in the CM group. CONCLUSIONS: The emotional and functional burden was high, and the societal burden increased by frequency and severity of migraine, as shown by higher HCRU and reduced work productivity. There is a need to improve quality of care in migraine and improve migraine management related issues in both healthcare and society in Finland.

Lack of interleukin-13 receptor α1 delays the loss of dopaminergic neurons during chronic stress.

BACKGROUND: The majority of Parkinson's disease (PD) cases are sporadic and idiopathic suggesting that this neurodegenerative disorder is the result of both environmental and genetic factors. Stress and neuroinflammation are among the factors being investigated for their possible contributions to PD. Experiments in rodents showed that severe chronic stress can reduce the number of dopaminergic neurons in the substantia nigra pars compacta (SNc); the same cells that are lost in PD. These actions are at least in part mediated by increased oxidative stress. Here, we tested the hypothesis that the interleukin-13 receptor alpha 1 (IL-13Rα1), a cytokine receptor whose activation increases the vulnerability of dopaminergic neurons to oxidative damage, participates in the stress-dependent damage of these neurons. METHODS: Mice were subject to daily sessions of 8 h (acute) stress for 16 weeks (5 days a week), a procedure previously showed to induce loss of dopaminergic neurons in the SNc. The source and the kinetics of interleukin-13 (IL-13), the endogenous ligand of IL-13Rα1, were evaluated 0, 1, 3, 6, and 8 h and at 16 weeks of stress. Identification of IL-13 producing cell-type was performed by immunofluorescent and by in situ hybridization experiments. Markers of oxidative stress, microglia activation, and the number of dopaminergic neurons in IL-13Rα1 knock-out animals (Il13ra1 Y/ - ) and their wild-type littermates (Il13ra1 Y/+ ) were evaluated at 16 weeks of stress and at 20 weeks, following a 4 week non-stressed period and compared to non-stressed mice. RESULTS: IL-13 was expressed in microglial cells within the SN and in a fraction of the tyrosine hydroxylase-positive neurons in the SNc. IL-13 levels were elevated during daily stress and peaked at 6 h. 16 weeks of chronic restraint stress significantly reduced the number of SNc dopaminergic neurons in Il13ra1 Y/+ mice. Neuronal loss at 16 weeks was significantly lower in Il13ra1 Y/- mice. However, the loss of dopaminergic neurons measured at 20 weeks, after 4 weeks of non-stress following the 16 weeks of stress, was similar in Il13ra1 Y/+ and Il13ra1 Y/- mice. CONCLUSIONS: IL-13, a cytokine previously demonstrated to increase the susceptibility of SNc dopaminergic neurons to oxidative stress, is elevated in the SN by restraint stress. Lack of IL-13Rα1 did not prevent nor halted but delayed neuronal loss in the mouse model of chronic restraint stress. IL-13/IL-13Rα1 may represent a target to reduce the rate of DA neuronal loss that can occur during severe chronic restraint stress.

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

WHAT IS KNOWN AND OBJECTIVE: Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia. METHODS: We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses. Of these, 59 patients were with G6PD-. All patients underwent fluoroquinolone prophylaxis and were transfused according to our single-unit transfusion policy. The principal endpoint was the incidence of acute haemolytic anaemia. Secondary endpoints included the incidence of febrile neutropenia, microbiologically and clinically documented infection (MDI and CDI) and the incidence of Gram-positive or Gram-negative infections. RESULTS AND DISCUSSIONS: No episode of acute haemolytic anaemia was observed in the entire cohort. The incidence of MDI and CDI was similar, but the incidence of invasive fungal disease (IFD; P<.0001, HR 11.4, 95%CI 3.5-37.05) and Candida sepsis (P=.008, HR 37, 95%CI 2.01-680.9) was higher in patients with G6PD-. Interestingly, we observed a reduced incidence of febrile neutropenia in patients with G6PD- (P=.01, HR 0.46, 95%CI 0.25-0.8). WHAT IS NEW AND CONCLUSIONS: Our data suggest that fluoroquinolone prophylaxis in patients with G6PD-, treated with intensive chemotherapy, is feasible and safe. Our findings on the incidence of IFD and febrile neutropenia suggest that G6PD may be important in susceptibility to opportunistic pathogens and host response in neutropenic patients.

Methanotrophy induces nitrogen fixation during peatland development.

Nitrogen (N) accumulation rates in peatland ecosystems indicate significant biological atmospheric N2 fixation associated with Sphagnum mosses. Here, we show that the linkage between methanotrophic carbon cycling and N2 fixation may constitute an important mechanism in the rapid accumulation of N during the primary succession of peatlands. In our experimental stable isotope enrichment study, previously overlooked methane-induced N2 fixation explained more than one-third of the new N input in the younger peatland stages, where the highest N2 fixation rates and highest methane oxidation activities co-occurred in the water-submerged moss vegetation.

Mycobacteriosis caused by Mycobacterium marinum in reared mullets: first evidence from Sardinia (Italy).

Mycobacterium marinum is a slow-growing non-tuberculous mycobacterium, and it is considered the most common aetiologic agent of mycobacteriosis in wild and cultured fish. The diagnosis is principally made by histology when positive Ziehl-Neelsen stain granulomas are detected. The aim of this study was to investigate the occurrence of mycobacteriosis in extensively cultured Mugilidae of two lagoons (Cabras and San Teodoro) from Sardinia by the use of histology, microbiology, PCR and DNA sequencing. Nine of 106 mullets examined were affected by mycobacteriosis, and the spleen was the most affected organ. The histology detected higher rate (100%) of infection in spleen than the culture and PCR (75% and 62.5%, respectively). The sequencing of hsp65 gene identified M. marinum as the primary cause of mycobacteriosis in the mullets examined. Mullets affected by mycobacteriosis were mainly fished in the San Teodoro lagoon characterized by critical environmental conditions. Histology remains the most common method in detecting fish affected by mycobacteriosis, and PCR-based methods are essential for species identification. Our finding are worthy of attention because mycobacteriosis caused by M. marinum in reared mullets was evidenced for the first time in Sardinia, suggesting that this disease may be underestimated also in other cultured fish species.