Machine learning evaluation for identification of M-proteins in human serum.

Serum electrophoresis (SPEP) is a method used to analyze the distribution of the most important proteins in the blood. The major clinical question is the presence of monoclonal fraction(s) of antibodies (M-protein/paraprotein), which is essential for the diagnosis and follow-up of hematological diseases, such as multiple myeloma. Recent studies have shown that machine learning can be used to assess protein electrophoresis by, for example, examining protein glycan patterns to follow up tumor surgery. In this study we compared 26 different decision tree algorithms to identify the presence of M-proteins in human serum by using numerical data from serum protein capillary electrophoresis. For the automated detection and clustering of data, we used an anonymized data set consisting of 67,073 samples. We found five methods with superior ability to detect M-proteins: Extra Trees (ET), Random Forest (RF), Histogram Grading Boosting Regressor (HGBR), Light Gradient Boosting Method (LGBM), and Extreme Gradient Boosting (XGB). Additionally, we implemented a game theoretic approach to disclose which features in the data set that were indicative of the resulting M-protein diagnosis. The results verified the gamma globulin fraction and part of the beta globulin fraction as the most important features of the electrophoresis analysis, thereby further strengthening the reliability of our approach. Finally, we tested the algorithms for classifying the M-protein isotypes, where ET and XGB showed the best performance out of the five algorithms tested. Our results show that serum capillary electrophoresis combined with decision tree algorithms have great potential in the application of rapid and accurate identification of M-proteins. Moreover, these methods would be applicable for a variety of blood analyses, such as hemoglobinopathies, indicating a wide-range diagnostic use. However, for M-protein isotype classification, combining machine learning solutions for numerical data from capillary electrophoresis with gel electrophoresis image data would be most advantageous.

Maternal pheochromocytoma and childbirth in Sweden 1973-2015: a population-based study on short and long-term outcome.

PURPOSE: Data guiding management of pheochromocytoma and paraganglioma (PPGL) in pregnant women is limited, and long-term effects on the child are unknown. The aim of this retrospective registry-based case-cohort study was to assess how maternal PPGL and treatment impacts maternal and fetal outcome, including long-term outcome for the child. The main outcomes were maternal and fetal mortality and morbidity at delivery and relative healthcare consumption in children born by mothers with PPGL during pregnancy. METHODS: The National Birth Register identified 4,390,869 pregnancies between 1973-2015. Data was crosslinked with three Swedish national registers to identify women diagnosed with pheochromocytoma or paraganglioma within one year before or after childbirth. Hospital records were reviewed and register data was collected for five age-matched controls for each child until age 18. RESULTS: 21 women and 23 children were identified (incidence 4.8/1.000.000 births/year), all women with adrenal pheochromocytomas (Pc). The majority (71%) were diagnosed post-partum. Nine women (43%) were hypertensive during pregnancy. Preterm delivery was more common in Pc patients compared to controls (30% vs 6%, p < 0.001). There was no maternal or fetal mortality. Timing of tumor removal did not affect gestational weight or APGAR scores. There was no observed difference in hospital admissions between children affected by maternal Pc and controls. CONCLUSION: Pc was commonly diagnosed after delivery and raised the risk of pre-term delivery, suggesting a need for an increased awareness of this diagnosis. However, reassuringly, there was no fetal or maternal mortality or any observed long-term impact on the children.

Child-Adult Contract for Prevention of Tobacco Use: "As-Treated" Analysis of a Cluster Randomized Controlled Trial (the TOPAS Study) at 3-Year Follow-Up.

To estimate the effect of a 3-year commitment to remain tobacco free on tobacco uptake among high school students in Sweden. The commitment is developed in the form of a contract between a child and a significant adult, constituting the core component of Tobacco-free Duo (T-Duo), a Swedish school-based tobacco prevention program. Secondary analysis of data from a cluster randomized controlled trial. Participants were 586 students in high schools assigned to the intervention arm of T-Duo. At inception, participants attended grade 7 (i.e., age 12-13). Only students who were tobacco naïve at baseline for the respective outcome and participated in all follow-ups were included. The exposure was defined as signing a 3-year contract with a significant adult, categorized as "stable contract" (3 years contract with the same contract partner), "unstable" (signed a contract sometime during follow-up but this was not sustained over time and/or with the same partner), and "no contract" at all during the intervention period. The primary outcome was having never tried cigarette smoking at the end of grade 9. Exposure and outcomes were self-reported in yearly questionnaires. Of 586 students, 321 (55%) held a stable contract, 204 (35%) an unstable contract, and 61 (10%) did not sign a contract at all. At the end of grade 9 (age 15-16), the relative risk (RR) to remain cigarette free was 1.11 (95% CI 1.00-1.22) (Number Needed to Treat = 10) among students in any type of contract compared to students that did not write a contract at all. The RRs for remaining tobacco free (secondary outcomes) ranged from 1.07 (0.98-1.16) for regular snus use to 1.16 (1.00-1.35) for any type of tobacco use. A commitment to remain tobacco free through a child-adult contract seems to exert a preventive effect on the uptake of tobacco use among Swedish adolescents over 3 school years. The current findings apply to a selected sample of both schools and students. Registration: Current Controlled Trials ISRCTN52858080 Date: January 4, 2019, retrospectively registered.

Case report: Bilateral damage to the immature optic radiation and secondary massive loss of retinal ganglion cells causing tunnel vision.

We describe the case of a 30-year-old woman, who needed a formal report on her visual impairment to seek support from society. She was born preterm, and during her neonatal period, she suffered from bilateral intraventricular hemorrhage (IVH) grade 3, a condition that can cause cerebral visual impairment (CVI) due to damage to the retro-geniculate visual pathways. Individuals with such brain damage of this severity are often restricted by cerebral palsy (CP) and intellectual disability, and thus have a limited ability to cooperate in the assessment of visual function. However, our patient was capable of providing reliable test results, and she manifested only a small island of central vision in each eye, with additional reduced visual acuities. She cooperated well in examinations involving MRI of the brain, optical coherence tomography (OCT) of retinal ganglion cells, and multi-focal visual evoked potentials, with each test providing information about potential limitations in the structural prerequisites for visual function. What distinguishes our case is the severity of the damage to the optic radiations and the massive secondary loss of most of her retinal ganglion cells (GCs). However, there is some measurable visual function, which may be due to developmental neuroplasticity during early development, when surviving GCs prioritize the central visual field. Despite her visual difficulties, she is a keen portrait painter. Our patient may be representative of, and a spokesperson for, other individuals with extensive brain damage of the same etiology, who are unable to perform perimetric tests and therefore run the risk of not being recognized as severely visually impaired, and consequently, not being given the best conditions for habilitation. OCT may serve as a helpful diagnostic tool. Aim: This study aims to describe visual behavior and practical applications of visual function in relation to structural prerequisites for visual function.

The prognostic implication of visual acuity at the time of uveal melanoma diagnosis.

BACKGROUND: Visual outcomes after primary tumour treatment of uveal melanoma (UM) have been investigated repeatedly. This study evaluates the correlation between best-corrected visual acuity (BCVA) before treatment with clinicopathological factors and patient survival. SUBJECTS/METHODS: Pre-treatment BCVA was examined in relation to tumour dimensions and location, and survival in a retrospective cohort of 1809 patients who underwent plaque brachytherapy. BCVA was also correlated to tumour histological factors in a second cohort of 137 enucleated eyes. RESULTS: The mean BCVA of the tumour eye prior to plaque brachytherapy was LogMAR 0.42 (SD 0.46). Patients with low BCVA (LogMAR ≥ 1.00) did not differ in age (p = 0.19) and had similar frequency of ciliary body involvement (p = 0.99) but had tumours with greater apical thickness (p < 0.0001), greater diameter (p < 0.0001) and shorter distance to the optic disc and fovea (p < 0.0001). There were no significant relations between low BCVA and any of 13 examined tumour histological factors at a Bonferroni-corrected significance level (p > 0.004). Patients with low BCVA had greater incidence of UM-related mortality in competing risk analysis (p = 0.0019) and shorter overall survival (p < 0.0001). Low BCVA was also associated with increased hazard ratio (HR) for UM-related mortality in univariate analysis (HR 1.5, 95% confidence interval 1.2 to 1.9), but not in multivariate analysis with tumour size and location as covariates. CONCLUSIONS: UM patients with low BCVA before primary tumour treatment have a worse prognosis, likely related to increased tumour dimensions. Future studies should examine the prognostic significance of BCVA in relation to macula-involving retinal detachment and genetic factors.

Optical Coherence Tomography Identifies Visual Pathway Involvement Earlier than Visual Function Tests in Children with MRI-Verified Optic Pathway Gliomas.

This study investigates whether optical coherence tomography (OCT) could add useful information in the examination of children with optic pathway glioma (OPG) at high risk of developing vision loss. For this purpose, the relationship between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, evaluated with tests of visual acuity (VA) and visual field (VF), as well as tumor site according to magnetic resonance imaging (MRI), were examined in a geographically defined group of children with OPG. METHODS: Children aged <18 years with OPG underwent ophthalmic examination including VA, VF (Zeiss HFA perimetry) and OCT imaging (Zeiss Cirrus HD-OCT). RESULTS: Out of 51 patients included, 45 provided 77 eyes with MRI-verified OPG, and 19 patients provided 25 eyes without OPG. Significant correlations were found between GC-IPL, VF and VA (p < 0.001). The GC-IPL pattern loss corresponded in 95% to VF defects and in 92% to MRI findings. CONCLUSIONS: Our study indicates that GC-IPL measures could serve as an early marker of vision-threatening changes related to OPG and as a valuable link between MRI and visual function tests. Thinning of GC-IPL and differences in topography between eyes are strong indicators of and predictive of vision loss related to OPG.

Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice.

A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.

Evaluation of the Swedish school-based program "tobacco-free DUO" in a cluster randomized controlled trial (TOPAS study). Results at 2-year follow-up.

Friends' and parents' tobacco use are strong predictors of tobacco uptake among adolescents, however the effectiveness of interventions based on public commitments and agreements to remain tobacco-free are not established. Here, we evaluated the effectiveness of the school-based Swedish program Tobacco-Free Duo (T-Duo) in preventing adolescents from initiating tobacco use (TOPAS study). T-Duo is a multi-component intervention witha formal agreement between a student and an adult partner to remain tobacco-free during the entire 3-year study period as core component. The standardized educational component of the same program was used as comparator (control). Primary outcome was the probability to "remain a non-user" of i) cigarettes and secondary outcomes ii) other types of tobacco at second (21-month) follow-up. Analysis was conducted according to Intention To Treat. In total 1776 adolescents (51% female) aged 12-13 in grade 7 from 34 participating high schools in Sweden were included at baseline in 2018, of which 1489 were retained after 21 months. The Risk Ratio (RR) of not having tried cigarettes 21-months after initiation of the intervention was 1.03(CI 0.98-1.08), Bayes Factor(BF) = 0.93, Absolute Risk Difference(ARD) = 3.1%. Similar associations were found for never smoked a whole cigarette and never use of other tobacco/nicotine products. There was a minimal reduction of tobacco use initiation among Swedish adolescents assigned to a multi-component intervention (T-Duo) compared to those assigned to standardized classroom education after 2 schoolyears. However, for most outcomes' findings were inconclusive and not reliably different from zero. Trial registration: ISRCTN5285808 (doi:https://doi.org/10.1186/ISRCTN52858080); Study protocol: DERR1-https://doi.org/10.2196/21100. Registration: Current Controlled Trials ISRCTN52858080 Date: January 4, 2019, retrospectively registered. Protocol: Galanti, M.R., Pulkki-Brännström, A.-M., Nilsson, M., 2020. Tobacco-free duo adult-child contract for prevention of tobacco use among adolescents and parents: protocol for a mixed-design evaluation. JMIR Res. Protoc. 9, e21100. doi:10.2196/21100.

Protocol for the evaluation of cost-effectiveness and health equity impact of a school-based tobacco prevention programme in a cluster randomised controlled trial (the TOPAS study).

INTRODUCTION: Despite a long-term downward trend in smoking prevalence, tobacco remains the number one risk factor for death and disability in Sweden. Globally, tobacco use generates a substantial economic burden for health systems and is also a major driver of socioeconomic inequalities in health. This article describes the planned cost-effectiveness and health equity impact evaluation of a multicomponent school-based programme to prevent the onset of tobacco use in adolescents. METHODS AND ANALYSIS: Cost-effectiveness of the multicomponent Tobacco-Free Duo programme will be evaluated against the educational component of the same programme only. An incremental cost-effectiveness ratio (ICER) will be calculated in terms of the cost per case prevented using the trial primary outcome and within-trial payer costs. If the ICER is negative, an incremental net benefit ratio will be calculated. Robustness of the results will be assessed through one-way sensitivity analyses. The slope index of inequality will be computed to assess the potential impact of the Tobacco-free Duo programme on education-related inequalities in the onset of smoking and in adult smoking cessation, comparing the two trial arms. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Regional Ethics Review Board, Umeå (registration number 2017/255-31). The Public Health Agency of Sweden commissioned the study. The findings will be disseminated internationally within academia and to national and local policy-makers. TRIAL REGISTRATION NUMBER: ISRCTN52858080; Pre-results.

Tobacco-Free Duo Adult-Child Contract for Prevention of Tobacco Use Among Adolescents and Parents: Protocol for a Mixed-Design Evaluation.

BACKGROUND: Universal tobacco-prevention programs targeting youths usually involve significant adults, who are assumed to be important social influences. Commitment not to use tobacco, or to quit use, as a formal contract between an adolescent and a significant adult is a preventive model that has not been widely practiced or explored and has been formally evaluated even less. In this paper, we present the rationale and protocol for the evaluation of the Swedish Tobacco-free Duo program, a multicomponent school-based program the core of which rests on a formal agreement between an adolescent and an adult. The adolescent's commitment mainly concerns avoiding the onset of any tobacco use while the adult commits to support the adolescent in staying tobacco free, being a role model by not using tobacco themselves. OBJECTIVE: To assess (1) whether Tobacco-free Duo is superior to an education-only program in preventing smoking onset among adolescents and promoting cessation among their parents, (2) whether exposure to core components (adult-child agreement) entails more positive effects than exposure to other components, (3) the impact of the program on whole school tobacco use, (4) potential negative side effects, and (5) school-level factors related to fidelity of the program's implementation. METHODS: A mixed-design approach was developed. First, a cluster randomized controlled trial was designed with schools randomly assigned to either the comprehensive multicomponent program or its educational component only. Primary outcome at the adolescent level was identified as not having tried tobacco during the 3-year junior high school compulsory grades (12-15 years of age). An intention-to-treat cohort-wise approach and an as-treated approach complemented with a whole school repeated cross-sectional approach was devised as analytical methods of the trial data. Second, an observational study was added in order to compare smoking incidence in the schools participating in the experiment with that of a convenience sample of schools that were not part of the experimental study. Diverse secondary outcomes at both adolescent and adult levels were also included. RESULTS: The study was approved by the Umeå Regional Ethics Review Board (registration number 2017/255-31) in 2017. Recruitment of schools started in fall 2017 and continued until June 2018. In total, 43 schools were recruited to the experimental study, and 16 schools were recruited to the observational study. Data collection started in the fall 2018, is ongoing, and is planned to be finished in spring 2021. CONCLUSIONS: Methodological, ethical, and practical implications of the evaluation protocol were discussed, especially the advantage of combining several sources of data, to triangulate the study questions. The results of these studies will help revise the agenda of this program as well as those of similar programs. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 52858080; https://doi.org/10.1186/ISRCTN52858080. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21100.

Proteo-Transcriptomic Analysis Identifies Potential Novel Toxins Secreted by the Predatory, Prey-Piercing Ribbon Worm Amphiporus lactifloreus.

Nemerteans (ribbon worms) employ toxins to subdue their prey, but research thus far has focused on the small-molecule components of mucus secretions and few protein toxins have been characterized. We carried out a preliminary proteotranscriptomic analysis of putative toxins produced by the hoplonemertean Amphiporus lactifloreus (Hoplonemertea, Amphiporidae). No variants were found of known nemertean-specific toxin proteins (neurotoxins, cytotoxins, parbolysins or nemertides) but several toxin-like transcripts were discovered, expressed strongly in the proboscis, including putative metalloproteinases and sequences resembling sea anemone actitoxins, crown-of-thorn sea star plancitoxins, and multiple classes of inhibitor cystine knot/knottin family proteins. Some of these products were also directly identified in the mucus proteome, supporting their preliminary identification as secreted toxin components. Two new nemertean-typical toxin candidates could be described and were named U-nemertotoxin-1 and U-nemertotoxin-2. Our findings provide insight into the largely overlooked venom system of nemerteans and support a hypothesis in which the nemertean proboscis evolved in several steps from a flesh-melting organ in scavenging nemerteans to a flesh-melting and toxin-secreting venom apparatus in hunting hoplonemerteans.

[Patient blood management - to transfuse blood on appropriate indications]. / Transfusionsstrategi ­ att ge blod på rätt indikation - I Sverige ges fler blodtransfusioner än i jämförbara länder ­ restriktiv policy ger inte sämre vårdresultat.

During the last decade, the varying use and the lack of consistent indications for blood transfusions have been questioned. Comparisons of liberal and restrictive transfusion policies, most often support a restrictive policy. This has led to an evidence-based approach to optimizing the care of patients who might need transfusion, Patient Blood Management (PBM). There is evidence that both anemia and allogeneic blood transfusions are independently associated with increased morbidity and mortality. In elective surgery it is possible to adapt the three pillars of PBM in a structured way; i.e. optimization of red blood cell mass, reduction of blood loss and bleeding, and optimization of the patient's physiological tolerance towards anemia. These activities should be included in the pre-peri- and postoperative routines, in all surgical units.

Children report positive experiences of animal-assisted therapy in paediatric hospital care.

AIM: To evaluate children's experiences of and responses to animal-assisted therapy using a therapy dog as complementary treatment in paediatric hospital care. METHODS: The study was performed using mixed methods, by means of qualitative and quantitative data. Fifty children in a paediatric surgery ward, at a tertiary hospital in Sweden, were included between February 2016 to May 2017. Children answered questions about feelings of well-being and experiences of the hospital stay before and after animal-assisted therapy, and experiences of their interaction with a therapy dog. RESULTS: The children's well-being increased from moderately good before to very good after animal-assisted therapy, and the children assessed the hospital stay as better after than before. The vast majority of the children (93%) assessed the interaction with the dog as very good. The children described mixed experiences before and mainly positive aspects of joy, satisfaction and pain relief after animal-assisted therapy. CONCLUSION: The children's responses before interaction, of both a positive and negative nature, show a focus shift after the interaction with a therapy dog to mainly positive nature regarding self-reported feeling of well-being and experiences of the hospital stay. Using a therapy dog in paediatric hospital care is suitable complementary treatment.

Retrophylogenomics in rorquals indicate large ancestral population sizes and a rapid radiation.

BACKGROUND: Baleen whales (Mysticeti) are the largest animals on earth and their evolutionary history has been studied in detail, but some relationships still remain contentious. In particular, reconstructing the phylogenetic position of the gray whales (Eschrichtiidae) has been complicated by evolutionary processes such as gene flow and incomplete lineage sorting (ILS). Here, whole-genome sequencing data of the extant baleen whale radiation allowed us to identify transposable element (TE) insertions in order to perform phylogenomic analyses and measure germline insertion rates of TEs. Baleen whales exhibit the slowest nucleotide substitution rate among mammals, hence we additionally examined the evolutionary insertion rates of TE insertions across the genomes. RESULTS: In eleven whole-genome sequences representing the extant radiation of baleen whales, we identified 91,859 CHR-SINE insertions that were used to reconstruct the phylogeny with different approaches as well as perform evolutionary network analyses and a quantification of conflicting phylogenetic signals. Our results indicate that the radiation of rorquals and gray whales might not be bifurcating. The morphologically derived gray whales are placed inside the rorqual group, as the sister-species to humpback and fin whales. Detailed investigation of TE insertion rates confirm that a mutational slow down in the whale lineage is present but less pronounced for TEs than for nucleotide substitutions. CONCLUSIONS: Whole genome sequencing based detection of TE insertions showed that the speciation processes in baleen whales represent a rapid radiation. Large genome-scale TE data sets in addition allow to understand retrotransposition rates in non-model organisms and show the potential for TE calling methods to study the evolutionary history of species.

Taking a Stand: An Untapped Strategy to Reduce Waterpipe Smoking in Adolescents.

INTRODUCTION: Waterpipe use amongst adolescents is on the rise globally. Thus, there is a need to understand adolescents 'attitudes towards and perceptions of waterpipe use in order to develop specific interventions against this form of tobacco use. METHODS: Focus group interviews were conducted among 37 Swedish adolescents (14 boys and 23 girls) from grades 10 to 12. Waterpipe users and nonusers were interviewed separately, with two groups each for users and nonusers. Interviews were audiotaped, transcribed, and thematically analyzed using content analysis. RESULTS: Six themes emerged including taking a stand, weighing the risks, Lack of knowledge, Social context, Waterpipe new and unknown, and Family influence. Taking a stand was about being able to stand up for one's owns views rather than giving in to peer pressure to smoke waterpipe. Participants feared harming others via secondhand smoke and expressed criticism of the tobacco industry. Participants considered the health consequences and feared addiction. Lack of knowledge concerning health effects of waterpipe smoking due to the unavailability of credible information was also reported. Waterpipe smoking was considered a social event carried out in the company of friends. Perceived as novel and fun, waterpipe was smoked out of curiosity. Parents' and siblings' smoking behaviors influenced adolescent waterpipe use. CONCLUSION: Adolescents reported lacking information about the possible health effects of waterpipe smoking and that gaining such knowledge would make it easier for them to take a stand and refuse smoking waterpipe. Prevention strategies should focus on providing adolescents with factual information about the dangers of waterpipe use.

Injuries to the Immature Optic Radiation Show Correlated Thinning of the Macular Ganglion Cell Layer.

Injuries to the immature optic radiation (OR) are associated with thinning of the retinal nerve fiber layer and corresponding visual field (VF) defects. The aim of the current study was to seek evidence for causal retrograde trans-synaptic degeneration by exploring the correspondence between the localization and extension of the injury to the OR and the structure of the macular ganglion cell complex, and the relation to VF function. Seven adults (age range 18-35) with visual dysfunction secondary to white-matter damage of immaturity and six healthy adults (age range 22-33) underwent magnetic resonance imaging (MRI). Fiber tractography was used to generate the geniculate projections to the dorsal and ventral striate cortex, delineated by retinotopic functional MRI mapping. The structure of the macular ganglion cell complex was measured with optical coherence tomography. The tractography showed overlaps between the dorsal and ventral geniculo-striate projections. However, in four patients with inferior VF defects, the dorsal projections were to a large extent traversing the space normally solely occupied by ventral projections. This is consistent with structural changes to the OR and suggests of re-organization upon injury. Diffusion parameters were significantly different between patients and controls, and most pronounced in the dorsal geniculo-striate projections, with a pattern indicating primary injury. The macular ganglion cell complex was significantly thinner in the patients and most pronounced in the superior sectors; a pattern particularly evident in the four patients with inferior VF defects. The ratio of the mean thickness of the macular ganglion cell complex in the superior and inferior sectors significantly correlated with the axial and mean diffusivities in the contra- and ipsilateral dorsal striate projections. The results suggest a causal link between injuries to the superior portion of the immature OR and secondary thinning in the macular ganglion cell complex, resulting in inferior VF defects.

Waterpipe use in adolescents in Northern Sweden: Association with mental well-being and risk and health behaviours.

AIMS: There is a lack of studies examining the association between waterpipe smoking and mental well-being among adolescents. This study sought to determine whether waterpipe smoking is associated with mental well-being and other risk and health behaviours in adolescents. METHODS: A questionnaire was distributed to 1006 adolescents in grades 9-12 (with a response rate of >95%), containing questions on measures of stress, mental energy and sleep. In addition, the questionnaire assessed risk and health behaviours, including use of a waterpipe, cigarettes, e-cigarettes, snus, alcohol, narcotics, gambling and exercise. Logistic regression was used to assess factors associated with waterpipe use. RESULTS: Thirty-seven per cent ( n=371) of the participants had used a waterpipe at some point. Waterpipe use was associated with lower mental energy (odds ratio [OR] = 0.90, 95% confidence interval [CI] 0.81-0.99), higher stress (OR = 1.10, 95% CI 1.02-1.20) and use of cigarettes (OR = 3.82, 95% CI 2.33-6.03), e-cigarettes (OR = 3.26, 95% CI 2.12-4.99), snus (OR = 2.29, 95% CI 2.12-4.99), alcohol (OR = 1.92, 95% CI 1.07-3.44) and narcotics (OR = 3.64, 95% CI 1.75-7.58). Waterpipe use was not significantly associated with gambling, exercise or sleep quality. CONCLUSIONS: Waterpipe use in adolescents is associated with worse mental well-being, as well as use of other nicotine products, alcohol and narcotics. Prospective studies are needed to delineate causal and temporal relationships further between waterpipe use and mental well-being and its relationship to other risky behaviours in order to design effective prevention programs.

Prostate tumors downregulate microseminoprotein-beta (MSMB) in the surrounding benign prostate epithelium and this response is associated with tumor aggressiveness.

BACKGROUND: Microseminoprotein-beta (MSMB) is a major secretory product from prostate epithelial cells. MSMB synthesis is decreased in prostate tumors in relation to tumor grade. MSMB levels are also reduced in the circulation and MSMB is therefore used as a serum biomarker for prostate cancer. We hypothesized that cancers induce a reduction in MSMB synthesis also in the benign parts of the prostate, and that the magnitude of this response is related to tumor aggressiveness. Reduced levels of MSMB in the circulation could therefore be a consequence of reduced MSMB expression not only in tumor tissue but also in the benign prostate tissue. METHODS: MSMB expression was analyzed in prostatectomy specimens from 36 patients using immunohistochemistry and qRT-PCR. MSMB expression in the benign prostate tissue was analyzed in relation to Gleason score, tumor stage, and distance to the tumor. Furthermore, Dunning rat prostate tumors with different aggressiveness were implanted into the prostate of Copenhagen rats to study if this affected the MSMB expression in the tumor-adjacent benign rat prostate tissue. RESULTS: In prostatectomy specimens, MSMB expression was reduced in prostate tumors but also in the tumor-adjacent benign parts of the prostate. The reduction in tumor MSMB was related to tumor grade and stage, and the reduction in the benign parts of the prostate to tumor grade, stage, and distance to the tumor. Implantation of Dunning cancer cells into the rat prostate resulted in reduced MSMB protein levels in the tumor-adjacent benign prostate tissue. Rapidly growing and metastatic MatLyLu tumors had a more pronounced effect than slow-growing non-metastatic G tumors. CONCLUSION: Our data suggest that aggressive prostate tumors suppress MSMB synthesis in the benign prostate and that this could explain why serum levels of MSMB are decreased in prostate cancer patients. This study suggests that markers for aggressive cancer can be found among factors altered in parallel in prostate tumors and in the adjacent benign tissue.