Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases

Therapeutic emails

BACKGROUND: In this paper, we show how counselors and psychologists can use emails for online management of substance abusers, including the anatomy and content of emails that clinicians should send substance abusers. Some investigators have attempted to determine if providing mental health services online is an efficacious delivery of treatment. The question of efficacy is an empirical issue that cannot be settled unless we are explicitly clear about the content and nature of online treatment. We believe that it is not the communications via internet that matters, but the content of these communications. The purpose of this paper is to provide the content of our online counseling services so others can duplicate the work and investigate its efficacy. RESULTS: We have managed nearly 300 clients online for recovery from substance abuse. Treatment included individual counseling (motivational interviewing, cognitive-behavior therapy, relapse prevention assignments), participation in an electronic support group and the development of a recovery team. Our findings of success with these interventions are reported elsewhere. Our experience has led to development of a protocol of care that is described more fully in this paper. This protocol is based on stages of change and relapse prevention theories and follows a Motivational Interviewing method of counseling. CONCLUSION: The use of electronic media in providing mental health treatment remains controversial due to concerns about confidentiality, security and legal considerations. More research is needed to validate and generalize the use of online treatment for mental health problems. If researchers have to build on each others work, it is paramount that we share our protocols of care, as we have done in this paper

Universal emission intermittency in quantum dots, nanorods, and nanowires

Virtually all known fluorophores, including semiconductor nanoparticles, nanorods and nanowires exhibit unexplainable episodes of intermittent emission blinking. A most remarkable feature of the fluorescence intermittency is a universal power law distribution of on- and off-times. For nanoparticles the resulting power law extends over an extraordinarily wide dynamic range: nine orders of magnitude in probability density and five to six orders of magnitude in time. The exponents hover about the ubiquitous value of -3/2. Dark states routinely last for tens of seconds, which are practically forever on quantum mechanical time scales. Despite such infinite states of darkness, the dots miraculously recover and start emitting again. Although the underlying mechanism responsible for this phenomenon remains an enduring mystery and many questions remain, we argue that substantial theoretical progress has been made.Comment: 9 pages, 2 figures, Accepted versio

Gender differences in patients with dizziness and unsteadiness regarding self-perceived disability, anxiety, depression, and its associations

BACKGROUND: It is known that anxiety and depression influence the level of disability experienced by persons with vertigo, dizziness or unsteadiness. Because higher prevalence rates of disabling dizziness have been found in women and some studies reported a higher level of psychiatric distress in female patients our primary aim was to explore whether women and men with vertigo, dizziness or unsteadiness differ regarding self-perceived disability, anxiety and depression. Secondly we planned to investigate the associations between disabling dizziness and anxiety and depression. METHOD: Patients were recruited from a tertiary centre for vertigo and balance disorders. Participants rated their global disability as mild, moderate or severe. They filled out the Dizziness Handicap Inventory and the two subscales of the Hospital Anxiety Depression Scale (HADS). The HADS was analysed 1) by calculating the median values, 2) by estimating the prevalence rates of abnormal anxiety/depression based on recommended cut-off criteria. Mann-Whitney U-tests, Chi-square statistics and odds ratios (OR) were calculated to compare the observations in both genders. Significance values were adjusted with respect to multiple comparisons. RESULTS: Two-hundred and two patients (124 women) mean age (standard deviation) of 49.7 (13.5) years participated. Both genders did not differ significantly in the mean level of self-perceived disability, anxiety, depression and symptom severity. There was a tendency of a higher prevalence of abnormal anxiety and depression in men (23.7%; 28.9%) compared to women (14.5%; 15.3%). Patients with abnormal depression felt themselves 2.75 (95% CI: 1.31-5.78) times more severely disabled by dizziness and unsteadiness than patients without depression. In men the OR was 8.2 (2.35-28.4). In women chi-square statistic was not significant. The ORs (95% CI) of abnormal anxiety and severe disability were 4.2 (1.9-8.9) in the whole sample, 8.7 (2.5-30.3) in men, and not significant in women. CONCLUSIONS: In men with vertigo, dizziness or unsteadiness emotional distress and its association with self-perceived disability should not be underestimated. Longitudinal surveys with specific pre-defined co-variables of self-perceived disability, anxiety and depression are needed to clarify the influence of gender on disability, anxiety and depression in patients with vertigo, dizziness or unsteadiness

Manual therapy with and without vestibular rehabilitation for cervicogenic dizziness: a systematic review

<p>Abstract</p> <p>Background</p> <p>Manual therapy is an intervention commonly advocated in the management of dizziness of a suspected cervical origin. Vestibular rehabilitation exercises have been shown to be effective in the treatment of unilateral peripheral vestibular disorders, and have also been suggested in the literature as an adjunct in the treatment of cervicogenic dizziness. The purpose of this systematic review is to evaluate the evidence for manual therapy, in conjunction with or without vestibular rehabilitation, in the management of cervicogenic dizziness.</p> <p>Methods</p> <p>A comprehensive search was conducted in the databases Scopus, Mantis, CINHAL and the Cochrane Library for terms related to manual therapy, vestibular rehabilitation and cervicogenic dizziness. Included studies were assessed using the Maastricht-Amsterdam criteria.</p> <p>Results</p> <p>A total of fifteen articles reporting findings from thirteen unique investigations, including five randomised controlled trials and eight prospective, non-controlled cohort studies were included in this review. The methodological quality of the included studies was generally poor to moderate. All but one study reported improvement in dizziness following either unimodal or multimodal manual therapy interventions. Some studies reported improvements in postural stability, joint positioning, range of motion, muscle tenderness, neck pain and vertebrobasilar artery blood flow velocity.</p> <p>Discussion</p> <p>Although it has been argued that manual therapy combined with vestibular rehabilitation may be superior in the treatment of cervicogenic dizziness, there are currently no observational and experimental studies demonstrating such effects. A rationale for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is presented.</p> <p>Conclusion</p> <p>There is moderate evidence to support the use of manual therapy, in particular spinal mobilisation and manipulation, for cervicogenic dizziness. The evidence for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is lacking. Further research to elucidate potential synergistic effects of manual therapy and vestibular rehabilitation is strongly recommended.</p

The 2024 Outline of Fungi and fungus-like taxa

With the simultaneous growth in interest from the mycological community to discover fungal species and classify them, there is also an important need to assemble all taxonomic information onto common platforms. Fungal classification is facing a rapidly evolving landscape and organizing genera into an appropriate taxonomic hierarchy is central to better structure a unified classification scheme and avoid incorrect taxonomic inferences. With this in mind, the Outlines of Fungi and fungus-like taxa (2020, 2022) were published as an open-source taxonomic scheme to assist mycologists to better understand the taxonomic position of species within the Fungal Kingdom as well as to improve the accuracy and consistency of our taxonomic language. In this paper, the third contribution to the series of Outline of Fungi and fungus-like taxa prepared by the Global Consortium for the Classification of Fungi and fungus-like taxa is published. The former is updated considering our previous reviews and the taxonomic changes based on recent taxonomic work. In addition, it is more comprehensive and derives more input and consensus from a larger number of mycologists worldwide. Apart from listing the position of a particular genus in a taxonomic level, nearly 1000 notes are provided for newly established genera and higher taxa introduced since 2022. The notes section emphasizes on recent findings with corresponding references, discusses background information to support the current taxonomic status and some controversial taxonomic issues are also highlighted. To elicit maximum taxonomic information, notes/taxa are linked to recognized databases such as Index Fungorum, Faces of Fungi, MycoBank and GenBank, Species Fungorum and others. A new feature includes links to Fungalpedia, offering notes in the Compendium of Fungi and fungus-like Organisms. When specific notes are not provided, links are available to webpages and relevant publications for genera or higher taxa to ease data accessibility. Following the recent synonymization of Caulochytriomycota under Chytridiomycota, with Caulochytriomycetes now classified as a class within the latter, based on formally described and currently accepted data, the Fungi comprises 19 Phyla, 83 classes, 1,220 families, 10,685 genera and ca 140,000 species. Of the genera, 39.5% are monotypic and this begs the question whether mycologists split genera unnecessarily or are we going to find other species in these genera as more parts of the world are surveyed? They are 433 speciose genera with more than 50 species. The document also highlights discussion of some important topics including number of genera categorized as incertae sedis status in higher level fungal classification. The number of species at the higher taxonomic level has always been a contentious issue especially when mycologists consider either a lumping or a splitting approach and herein we provide figures. Herein a summary of updates in the outline of Basidiomycota is provided with discussion on whether there are too many genera of Boletales, Ceratobasidiaceae, and speciose genera such as Colletotrichum. Specific case studies deal with Cortinarius, early diverging fungi, Glomeromycota, a diverse early divergent lineage of symbiotic fungi, Eurotiomycetes, marine fungi, Myxomycetes, Phyllosticta, Hymenochaetaceae and Polyporaceae and the longstanding practice of misapplying intercontinental conspecificity. The outline will aid to better stabilize fungal taxonomy and serves as a necessary tool for mycologists and other scientists interested in the classification of the Fungi