Recent Updates on the Development of Therapeutics for the Targeted Treatment of Alzheimer's Disease.
Alzheimer's disease (AD) is a complicated, multifaceted, irreversible, and incurable neurotoxic old age illness. Although NMDA (N-methyl D-aspartate)-receptor antagonists, cholinesterase repressors, and their pairings have been approved for the treatment, they are useful for short symptomatic relief. Researchers throughout the globe have been constantly working to uncover the therapy of Alzheimer's disease as new candidates must be determined, and newer treatment medicines must be developed. The aim of this review is to address recent advances in medication research along with new Alzheimer's disease therapy for diverse targets. Information was gathered utilizing a variety of internet resources as well as websites, such as ALZFORUM (alzforum.org) and clinicaltrials.gov. In contrast to other domains, the proposed medicines target amyloids (secretases, A42 generation, neuroinflammation, amyloid precipitation, and immunization), tau proteins (tau phosphorylation/aggregation and immunotherapy), and amyloid deposition. Despite tremendous advancement in our understanding of the underlying pathophysiology of Alzheimer's disease, the FDA (Food and Drug Administration) only approved aducanumab for diagnosis and treatment in 2003. Hence, novel treatment tactics are needed to find and develop therapeutic medicines to combat Alzheimer's disease.


Doctors' beliefs and knowledge on corticosteroid-induced osteoporosis: identifying barriers to improve prevention.
Despite the availability of effective treatments for the management of corticosteroid-induced osteoporosis (CIOP), the condition is undertreated. Our objective was to assess prescribers' knowledge and likely prescribing patterns concerning the diagnosis and treatment of CIOP. Another goal was to identify key barriers to the use of preventive therapy in patients using long-term corticosteroids. We used a postal survey of general practitioners (GPs) and specialists in the Netherlands. The survey comprised of questions on: demographic data, perceived barriers to the use of preventive therapy for CIOP, and knowledge of diagnosis and treatment of CIOP. Case scenarios were questioned to assess practice patterns. Responding prescribers correctly answered an average of 55% of knowledge questions and 69% of case scenarios. Multiple questions and cases showed that knowledge on the use of bone mineral density (BMD) determination was poor. BMD was determined in patients who, according to the national osteoporosis guideline, should be treated with bisphosphonates independent of BMD. Moreover, only 18% of doctors correctly answered that the BMD cutoff in CIOP patients is a T-score of ≤-1 or ≤-1·5. Key barriers identified were: (i) GPs, significantly more than specialists, consider prescription of preventive therapy the responsibility of another doctor; (ii) discontinuation of anti-resorptive medication due to adverse effects and (iii) the reluctance to prescribe preventive therapy in patients already prescribed multiple medications. Doctors did not identify many barriers to the prescribing of anti-resorptive therapies. Lack of knowledge, especially concerning use of BMD-results, likely led to the under-treatment of the presented patients.


Atopic dermatitis in West Highland white terriers - Part III: early life peripheral blood regulatory T cells are reduced in atopic dermatitis.
Regulatory T (Treg) cells are involved in homeostasis of immune regulation and suppression of inflammation and T-cell polarisation. Current knowledge regarding the role of Treg cells in the initiation of allergic disease is limited for both people and dogs. To explore the role of circulating Treg cells and their possible influencing factors, on the development of atopic dermatitis (AD). This study followed part of a birth cohort of West Highland white terrier dogs and classified them according to eventual clinical signs of AD (i.e. allergic versus healthy). The Treg phenotypes were assessed longitudinally by flow cytometry at 3, 3-12 and 12-36 months of age, and associated with development of AD. Different early life antigenic factors [endotoxins and allergens in house dust, Toxocara canis-specific immunoglobulin (Ig)E/IgG, allergen-specific and total IgE, skin microbiota] were measured at three months of age, and a possible association with Treg cell levels was assessed. The percentages of CD4+ CD25+ Foxp3+ Treg cells in healthy dogs were significantly higher at in 3-month-old (mean 4.5% healthy versus 3.3% allergic; P = 0.021) and <1-year-old (4.0% healthy versus 2.9% allergic; P = 0.028) dogs when compared to percentages of Treg cells in dogs that developed AD. There was a significantly positive correlation between the relative abundance of Lachnospiraceae on the skin and CD4+ CD25+ Foxp3+ Treg cells in puppies that became allergic (r = 0.568, P = 0.017). Further large-scale studies are needed to identify the practical value of these findings in AD diagnosis, treatment and prevention.


Pathways to psychiatric care in Ethiopia.
Understanding the pathways to psychiatric care and recognition of delay points are crucial for the development of interventions that aim to improve access to mental health-care services. Over a 2-month period in 2003, a total of 1044 patients at the commencement of new episodes of care at Amanuel Specialized Mental Hospital in Addis Ababa, Ethiopia were interviewed using the encounter form that was developed by the World Health Organization (WHO) for the study of pathways to psychiatric care. The mental hospital was contacted directly by 41% of patients. The remaining patients sought care from up to four different caregivers before arriving at the psychiatric hospital. Where the initial service was not received at the psychiatric hospital, 30.9% of patients sought care from priests/holy water/church. The median delay between onset of illness and arrival at the psychiatric hospital was 38 weeks. The longest delays before arriving at the mental hospital were associated with having no formal education, joblessness, and diagnoses of epilepsy and physical conditions. Implementing a robust referral system and establishing a strong working relationship with both traditional and modern health-care providers, as well as designing a service delivery model that targets particular segments of the population, such as those who are uneducated, jobless and/or suffer from epilepsy and somatic conditions, should be the most important strategies towards improving mental health service delivery and shortening of undue delay for patients receiving psychiatric care in Ethiopia.


Recombinant Laminin-511 Fragment (iMatrix-511) Coating Supports Maintenance of Human Nucleus Pulposus Progenitor Cells In Vitro.
The angiopoietin-1 receptor (Tie2) marks specific nucleus pulposus (NP) progenitor cells, shows a rapid decline during aging and intervertebral disc degeneration, and has thus sparked interest in its utilization as a regenerative agent against disc degeneration. However, the challenge of maintaining and expanding these progenitor cells in vitro has been a significant hurdle. In this study, we investigated the potential of laminin-511 to sustain Tie2+ NP progenitor cells in vitro. We isolated cells from human NP tissue (n = 5) and cultured them for 6 days on either standard (Non-coat) or iMatrix-511 (laminin-511 product)-coated (Lami-coat) dishes. We assessed these cells for their proliferative capacity, activation of Erk1/2 and Akt pathways, as well as the expression of cell surface markers such as Tie2, GD2, and CD24. To gauge their regenerative potential, we examined their extracellular matrix (ECM) production capacity (intracellular type II collagen (Col2) and proteoglycans (PG)) and their ability to form spherical colonies within methylcellulose hydrogels. Lami-coat significantly enhanced cell proliferation rates and increased Tie2 expression, resulting in a 7.9-fold increase in Tie2-expressing cell yields. Moreover, the overall proportion of cells positive for Tie2 also increased 2.7-fold. Notably, the Col2 positivity rate was significantly higher on laminin-coated plates (Non-coat: 10.24% (±1.7%) versus Lami-coat: 26.2% (±7.5%), p = 0.010), and the ability to form spherical colonies also showed a significant improvement (Non-coat: 40.7 (±8.8)/1000 cells versus Lami-coat: 70.53 (±18.0)/1000 cells, p = 0.016). These findings demonstrate that Lami-coat enhances the potential of NP cells, as indicated by improved colony formation and proliferative characteristics. This highlights the potential of laminin-coating in maintaining the NP progenitor cell phenotype in culture, thereby supporting their translation into prospective clinical cell-transplantation products.


Identifying causes of disagreement between self-reports and spouse ratings of personality.
Self-reports and spouse ratings of personality traits typically show less-than-perfect agreement, but powerful moderators of agreement have not yet been identified. In Study 1, 47 married couples completed the Revised NEO Personality Inventory to describe themselves and their spouses. Extent of agreement was not consistently moderated by response sets; the age, intelligence, or education of the respondent; or the length or quality of the relationship. In Study 2 these couples were interviewed about reasons for substantial disagreements, and an audiotape was content-analyzed. Sixteen reasons were reliably coded, including idiosyncratic understanding of items, reference to different time frames or roles, and unavailability of covert experience to the spouse. Faking good, assumed similarity, and other variables prominent in the psychometric literature were relatively unimportant. Findings (1) suggest that attempts to improve the validity of self-reports and ratings may need to be refocused and (2) underscore the desirability of routinely obtaining multiple sources of information on personality.


Maternal exposure to fine particulate matter over the first trimester and umbilical cord insertion abnormalities.
Our hypothesis was that exposure to fine particulate matter (PM2.5) is related to abnormal cord insertion, which is categorized as a form of placental implantation abnormality. We investigated the association between exposure to total PM2.5 and its chemical components over the first trimester and abnormal cord insertion, which contributes to the occurrence of adverse birth outcomes. From the Japan Perinatal Registry Network database, we used data on 83 708 women who delivered singleton births at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). We collected PM2.5 on a filter and measured daily concentrations of carbon and ion components. Then, we calculated the average concentrations over the first trimester (0-13 weeks of gestation) for each woman. A multilevel logistic-regression model with the hospital as a random effect was used to estimate the odds ratios (ORs) of abnormal cord insertion. Among the 83 708 women (mean age at delivery = 33.7 years), the frequency of abnormal cord insertion was 4.5%, the median concentration [interquartile range (IQR)] of total PM2.5 was 16.1 (3.61) μg/m3 and the OR per IQR for total PM2.5 was 1.14 (95% confidence interval = 1.06-1.23). In the total PM2.5-adjusted models, total carbon, organic carbon, nitrate, ammonium and chloride were positively associated with abnormal insertion. Organic carbon was consistently, and nitrate tended to be, associated with specific types of abnormal insertion (marginal or velamentous cord insertion). Exposure to total PM2.5 and some of its components over the first trimester increased the likelihood of abnormal cord insertion.


Cloning and characterization of the 82 kDa tyrosine-rich sexual stage glycoprotein, GAM82, and its role in oocyst wall formation in the apicomplexan parasite, Eimeria maxima.
The sexual (macrogamete/macrogametocyte) stage antigen, GAM82, in the apicomplexan parasite Eimeria maxima, has an apparent molecular mass of 82 kDa, and has been implicated in protective immunity against coccidiosis in poultry. The gene encoding this protein, gam82, was cloned and sequenced. It is a single-copy, intronless gene, which localizes to a 2145 bp transcript, and is first detected at 130 h post-infection. The gene predicts two distinct domains rich in the residues tyrosine and serine, amino acids that have been implicated in oocyst wall formation in other Eimeria spp., and in the extraorganismic sclerotization of structural proteins throughout the animal kingdom. A high number of small amino acids, predominantly alanine and proline, were detected in the intervening sequence between these two domains. The inference that GAM82 is involved in oocyst wall formation in Eimeria was confirmed when it was shown that a specific antibody to a recombinant version of GAM82 recognized the wall forming bodies in macrogametes, and the walls of oocysts in E. maxima. A closer biochemical analysis of the role of GAM82 in oocyst wall formation by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting showed that the antibodies to the recombinant version of GAM82 recognized an 82 kDa protein in macrogametocyte extracts, and a 30 kDa protein in unsporulated and sporulated oocyst extracts, as well as in purified oocyst wall fragments. Together, these findings indicate that the 82 kDa macrogametocyte antigen, GAM82, is a tyrosine and serine rich precursor protein that is proteolytically processed during development to give rise to a 30 kDa protein, that is incorporated into the oocyst wall. In addition, these findings provide evidence that the oocyst wall of Eimeria species is composed of a family of tyrosine rich proteins, that arise from precursor proteins found in the wall forming bodies of macrogametes.


Elevational homogenization of mountain parasitoids across six decades.
Elevational gradients are characterized by strong environmental changes within small geographical distances, providing important insights on the response of biological communities to climate change. Mountain biodiversity is particularly sensitive to climate change, given the limited capacity to colonize new areas and the competition from upshifting lowland species. Knowledge on the impact of climate change on mountain insect communities is patchy, but elevation is known to influence parasitic interactions which control insect communities and functions within ecosystems. We analyzed a European dataset of bristle flies, a parasitoid group which regulates insect herbivory in both managed and natural ecosystems. Our dataset spans six decades and multiple elevational bands, and we found marked elevational homogenization in the host specialization of bristle fly species through time. The proportion of specialized parasitoids has increased by ca. 70% at low elevations, from 17 to 29%, and has decreased by ca. 20% at high elevations, from 48 to 37%. As a result, the strong elevational gradient in bristle fly specialization observed in the 1960s has become much flatter over time. As climate warming is predicted to accelerate, the disappearance of specialized parasitoids from high elevations might become even faster. This parasitoid homogenization can reshape the ecological function of mountain insect communities, increasing the risk of herbivory outbreak at high elevations. Our results add to the mounting evidence that symbiotic species might be especially at risk from climate change: Monitoring the effects of these changes is urgently needed to define effective conservation strategies for mountain biodiversity.


What does local tenderness say about the origin of pain? An investigation of cervical zygapophysial joint pain.
Mechanical pain sensitivity is assessed in every patient with pain, either by palpation or by quantitative pressure algometry. Despite widespread use, no studies have formally addressed the usefulness of this practice for the identification of the source of pain. We tested the hypothesis that assessing mechanical pain sensitivity distinguishes damaged from healthy cervical zygapophysial (facet) joints. Thirty-three patients with chronic unilateral neck pain were studied. Pressure pain thresholds (PPTs) were assessed bilaterally at all cervical zygapophysial joints. The diagnosis of zygapophysial joint pain was made by selective nerve blocks. Primary analysis was the comparison of the PPT between symptomatic and contralateral asymptomatic joints. The secondary end points were as follows: differences in PPT between affected and asymptomatic joints of the same side of patients with zygapophysial joint pain; differences in PPT at the painful side between patients with and without zygapophysial joint pain; and sensitivity and specificity of PPT for 2 different cutoffs (difference in PPT between affected and contralateral side by 1 and 30 kPa, meaning that the test was considered positive if the difference in PPT between painful and contralateral side was negative by at least 1 and 30 kPa, respectively). The PPT of patients was also compared with the PPT of 12 pain-free subjects. Zygapophysial joint pain was present in 14 patients. In these cases, the difference in mean PPT between affected and contralateral side (primary analysis) was -6.2 kPa (95% confidence interval: -19.5 to 7.2, P = 0.34). In addition, the secondary analyses yielded no statistically significant differences. For the cutoff of 1 kPa, sensitivity and specificity of PPT were 67% and 16%, respectively, resulting in a positive likelihood ratio of 0.79 and a diagnostic confidence of 38%. When the cutoff of 30 kPa was considered, the sensitivity decreased to only 13%, whereas the specificity increased to 95%, resulting in a positive likelihood ratio of 2.53 and a diagnostic confidence of 67%. The PPT was significantly lower in patients than in pain-free subjects (P < 0.001). Assessing mechanical pain sensitivity is not diagnostic for cervical zygapophysial joint pain. The finding should stimulate further research into a diagnostic tool that is widely used in the clinical examination of patients with pain.


Ginkgo biloba Extract 761: A Review of Basic Studies and Potential Clinical Use in Psychiatric Disorders.
Ginkgo biloba extract 761 (EGb 761) is a well-defined extract obtained from Ginkgo biloba leaves according to a standardized method. It has been used extensively for the treatment of diseases related to the central nervous system including neurosensory disturbances, cerebrovascular insufficiency, peripheral vascular disturbances, and degenerative dementia. The potential use of EGb 761 has also been suggested for the treatment of psychiatric disorders such as anxiety and depression, which is discussed in the current review. These disorders constitute a global epidemic with serious economic and social consequences. Current available treatments with synthetic drugs may have some disadvantages and undesired side effects. There are diverse natural extracts that have been used for the treatment of psychiatric disorders due to their therapeutic action and low rate of side effects, such as EGb 761. EGb 761 has the ability to produce neuroprotection due to its chemical composition and the synergy of its components. We describe several neuroprotective mechanisms of action of EGb 761 such as antioxidant effects, modulation of neurotransmission, neuroendocrine regulation, and upregulation of neurotrophic factors, which underlie its potential therapeutic effect on psychiatric disorders. Furthermore, we discuss the therapeutic effects of EGb 761 both in animal models of psychiatric disorders and in clinical studies that include these pathologies. We focus on depression, anxiety, and schizophrenia, as well as the therapeutic action of EGb 761 on dementia in comorbidity with psychiatric disorders. In the current review, we propose thef potential use of EGb 761, alone or combined with current medication treatment, for psychiatric disorders.


Alterations in fucosyl oligosaccharides of glycoproteins during rat liver regeneration.
[3H]Fucose-labelled glycopeptides in the slices of liver 24h after partial hepatectomy were fractionated on Sephadex G-50. Glycopeptides from regenerating liver contained a higher proportion of lower-Mr components than did controls. Regenerating liver contained a higher proportion of glycopeptides that were bound to concanavalin A-Sepharose and were subsequently eluted with 20mM-methyl alpha-D-glucopyranoside than did controls. Concanavalin A-bound glycopeptides from each source were entirely bound to a lentil lectin-Sepharose column. Both the concanavalin A-bound and -unbound fractions from regenerating liver were indistinguishable from the respective controls by Bio-Gel P6 column chromatography and neuraminidase digestion. These results show that fucosyl glycopeptides from regenerating liver contain a higher proportion of biantennary species with core fucose residues than do controls. Glycopeptides from regenerating livers 12h, 72h and 144h after partial hepatectomy were also examined; however, the difference was not significant. These observations suggest that the alterations in fucosyl glycopeptides may be related to rapid growth of hepatocytes 24h after partial hepatectomy. No significant difference was found in either [3H]mannose- or [3H]fucose-labelled glycoproteins from regenerating liver and from controls by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, suggesting that the alteration in glycopeptides should depend on some differences in the late stage of oligosaccharide processing.


The burden of service for faculty of color to achieve diversity and inclusion: the minority tax.
The exclusion of Blacks/African-Americans, Latinx/Hispanics, and Indigenous people from science has resulted in their underrepresentation in the biomedical workforce, especially in academia. Faculty diversity at academic institutions is unacceptably low (<6%) and has remained unchanged in the past 20 years. Despite low representation, faculty of color are disproportionately tasked with service to enhance diversity and inclusion of the academy, often to the detriment of their research and academic success. This essay offers a perspective on the undue burden of service placed on underrepresented faculty to achieve institutional diversity and inclusion. I reflect on the challenges that faculty of color face trying to maintain a competitive research program while serving the needs of the academy, often in a capacity greater than that of their well-represented peers. I also discuss opportunities for faculty of color to leverage related diversity and inclusion work to boost their career progression and academic advancement.


Cognitive performance-altering effects of electronic medical records: An application of the human factors paradigm for patient safety.
According to the human factors paradigm for patient safety, health care work systems and innovations such as electronic medical records do not have direct effects on patient safety. Instead, their effects are contingent on how the clinical work system, whether computerized or not, shapes health care providers' performance of cognitive work processes. An application of the human factors paradigm to interview data from two hospitals in the Midwest United States yielded numerous examples of the performance-altering effects of electronic medical records, electronic clinical documentation, and computerized provider order entry. Findings describe both improvements and decrements in the ease and quality of cognitive performance, both for interviewed clinicians and for their colleagues and patients. Changes in cognitive performance appear to have desirable and undesirable implications for patient safety as well as for quality of care and other important outcomes. Cognitive performance can also be traced to interactions between work system elements, including new technology, allowing for the discovery of problems with "fit" to be addressed through design interventions.


Maternal Obesity and the Uterine Immune Cell Landscape: The Shaping Role of Inflammation.
Inflammation is often equated to the physiological response to injury or infection. Inflammatory responses defined by cytokine storms control cellular mechanisms that can either resolve quickly (i.e., acute inflammation) or remain prolonged and unabated (i.e., chronic inflammation). Perhaps less well-appreciated is the importance of inflammatory processes central to healthy pregnancy, including implantation, early stages of placentation, and parturition. Pregnancy juxtaposed with disease can lead to the perpetuation of aberrant inflammation that likely contributes to or potentiates maternal morbidity and poor fetal outcome. Maternal obesity, a prevalent condition within women of reproductive age, associates with increased risk of developing multiple pregnancy disorders. Importantly, chronic low-grade inflammation is thought to underlie the development of obesity-related obstetric and perinatal complications. While diverse subsets of uterine immune cells play central roles in initiating and maintaining healthy pregnancy, uterine leukocyte dysfunction as a result of maternal obesity may underpin the development of pregnancy disorders. In this review we discuss the current knowledge related to the impact of maternal obesity and obesity-associated inflammation on uterine immune cell function, utero-placental establishment, and pregnancy health.


Suicidal ideation modulates the reduction in serotonin transporter availability in male military conscripts with major depression: A 4-[18F]-ADAM PET study.
Suicide is an important issue in the military service, since it can influence military morale and create dangerous situations for other personnel. The serotonin transporter (SERT) has been suggested to be involved in the pathophysiology of depression and suicidal behaviours. The aims of this study were to examine whether the brain SERT availability differs between military conscripts with depression and control subjects, and whether suicidal ideation is correlated with SERT availability. We used N,N-dimethyl-2-(2-amino-4-[(18)F]-fluorophenylthio)benzylamine (4-[(18)F]-ADAM) as a radioligand for positron emission tomography (PET) imaging. All participants completed the Hamilton Depression Rating Scale and Beck Scale for Suicide Ideation (BSS) prior to PET imaging. The effect of major depression and BSS scores had an interaction on SERT availability. After adjusting for the BSS score, subjects with depression had lower SERT availability than control subjects (F1,17 = 23.85, P < 0.001). A positive correlation between SERT availability and BSS scores was observed in the depression group (F1,8 = 30.67, P = 0.001). The status of depression and intensity of suicidal ideation exert opposite effects on SERT availability. The extent of suicidal ideation may moderate the reduction effect in SERT binding observed in major depression in male military conscripts.


Impact of bladder volume on treatment planning and clinical outcomes of radiotherapy for patients with cervical cancer.
This study aimed to investigate the impact of bladder volume on treatment planning and clinical outcomes of radiotherapy for patients with cervical cancer. One hundred and sixty-six patients with locally advanced cervical cancer were selected in this retrospective study. The patients were divided into four groups according to their average bladder volume during radiotherapy (external beam radiation therapy and intracavitary brachytherapy): group A: V<100 mL, group B: 100 mL≤V≤150 mL, group C: 150 mL<V≤200 mL, group D: V>200 mL. The bladder volume and the cumulative dose to planning target (D90), bladder (D2cc), rectum (D2cc), and sigmoid (D2cc) were calculated using the treatment planning system. Treatment outcomes including late adverse events (the maximum grade of radiation-induced proctitis and cystitis), the objective response rate of tumor and lymph node, overall survival (OS), and progression-free survival (PFS) were collected. Additionally, the correlation between bladder volume and the irradiated dose of organs at risk and treatment outcomes was analyzed. The median follow-up time was 28 months. The D90 and D2cc of the rectum in group A were the highest (P<0.05). The D2cc of the bladder in group D was the highest (P<0.05). There was no significant difference in the tumor and lymph node regression rate, OS, and PFS among the groups. The difference in the late radiation-induced proctitis and cystitis maximum grade among the four groups was statistically significant (P<0.001, P=0.022, respectively), with group A the most serious and group B the mildest. For patients with cervical cancer, the bladder volume significantly affected the delivered dose to target, rectum, and bladder. When the bladder volume range was 100-150 mL, the rate of late radiation-induced proctitis and cystitis was low and the degree of reaction was mild. This is thought to be the optimum bladder volume for patients with cervical cancer during radiotherapy.


Overestimation of complication rates in evaluations of Chlamydia trachomatis screening programmes--implications for cost-effectiveness analyses.
Cost-effectiveness analyses of screening programmes for asymptomatic Chlamydia trachomatis infection suggest that screening at low prevalences in the population is cost-effective. However, the decision models in these studies are based on assumptions about the risk of complications, which are derived from the literature. Incorrect assumptions may lead to under- or overestimation of the effectiveness of screening. The first objective of this paper is to evaluate the assumptions about the probability of complications after an asymptomatic C. trachomatis infection. The second objective is to calculate alternative rates by using available data on the incidence of complications. We identified cost-effectiveness studies via Medline, and evaluated these for the evidence for the quoted probabilities. In addition, the probability of complications was calculated for Amsterdam from available registration data. In the three studies that were identified, the assumptions for the rates of pelvic inflammatory disease (PID) (clinical and subclinical) after C. trachomatis infection varied from 15% to 80%, and for ectopic pregnancy, tubal factor infertility, and chronic pelvic pain after PID from 5-25%, 10-20%, and 18-30%, respectively. The assumptions were based on data from high-risk populations, case-control data, and data not accounting for misdiagnoses. Using data obtained from local registrations, we estimated the probability of a clinical PID (0.43%), ectopic pregnancy (0.07%), and tubal factor infertility (0.02%) for women with a current infection. These estimates were consistently lower than the estimates based on the literature. We argue that an overestimation of the current complication rates is likely. The effect of overestimation is potentially the greatest in populations with a low prevalence, since the currently assumed cost savings associated with screening may disappear when using more realistic estimates for complications.


A child in shock: carotid blowout syndrome.
Paediatricians commonly encounter neck lumps during their routine clinical practice; vascular abnormalities, such as (pseudo)aneurysms, are a rare cause of these. Pseudoaneurysms of the carotid artery in children are usually the result of blunt or penetrating trauma, infection or vasculitis/connective tissue disorders. They can present with a variety of symptoms including neck pain, as a pulsatile neck mass or with compressive symptoms (for example, cranial nerve palsies or dyspnoea). Pseudoaneurysms carry a risk of rupture in which case they are fatal, unless immediate treatment is provided.We report a 17-month-old male child with idiopathic carotid artery blowout syndrome presenting with acute oropharyngeal haemorrhage leading to asystolic cardiac arrest. He was successfully resuscitated and emergency embolisation controlled the bleeding. Despite extensive left hemispheric infarct, he has survived.Carotid artery blowout syndrome needs to be recognised as a potential cause of major haemorrhage in childhood. The purpose of this case report is to remind readers of the differential diagnosis and work-up of a child presenting with a neck lump, to highlight important aspects of the acute management of major haemorrhage and massive blood transfusion in paediatrics, to describe the aetiology, presentation and management of carotid artery pseudoaneurysm in children and to discuss long term rehabilitation in patients with consequent neurological sequelae (including the need for input from multiple specialty teams).


Non-melanoma skin cancer diagnosis: a comparison between dermoscopic and smartphone images by unified visual and sonification deep learning algorithms.
Non-melanoma skin cancer (NMSC) is the most frequent keratinocyte-origin skin tumor. It is confirmed that dermoscopy of NMSC confers a diagnostic advantage as compared to visual face-to-face assessment. COVID-19 restrictions diagnostics by telemedicine photos, which are analogous to visual inspection, displaced part of in-person visits. This study evaluated by a dual convolutional neural network (CNN) performance metrics in dermoscopic (DI) versus smartphone-captured images (SI) and tested if artificial intelligence narrows the proclaimed gap in diagnostic accuracy. A CNN that receives a raw image and predicts malignancy, overlaid by a second independent CNN which processes a sonification (image-to-sound mapping) of the original image, were combined into a unified malignancy classifier. All images were histopathology-verified in a comparison between NMSC and benign skin lesions excised as suspected NMSCs. Study criteria outcomes were sensitivity and specificity for the unified output. Images acquired by DI (n = 132 NMSC, n = 33 benign) were compared to SI (n = 170 NMSC, n = 28 benign). DI and SI analysis metrics resulted in an area under the curve (AUC) of the receiver operator characteristic curve of 0.911 and 0.821, respectively. Accuracy was increased by DI (0.88; CI 81.9-92.4) as compared to SI (0.75; CI 68.1-80.6, p < 0.005). Sensitivity of DI was higher than SI (95.3%, CI 90.4-98.3 vs 75.3%, CI 68.1-81.6, p < 0.001), but not specificity (p = NS). Telemedicine use of smartphone images might result in a substantial decrease in diagnostic performance as compared to dermoscopy, which needs to be considered by both healthcare providers and patients.


Comparison of volatiles, phenolics, sugars, antioxidant vitamins, and sensory quality of different colored carrot varieties.
Four different colored carrots, orange, purple with orange core, yellow, and white, were examined for their content of phenolics, antioxidant vitamins, and sugars as well as their volatiles and sensory responses. A total of 35 volatiles were identified in all carrots, 27 positively. White carrot contained the highest content of volatiles, followed by orange, purple, and yellow. In total, 11, 16, 10, and 9 phenolic compounds were determined for the first time in orange, purple, yellow, and white carrots, respectively. Of these, chlorogenic acid was the most predominant phenolic compound in all carrot varieties. Differences (p < 0.05) in relative sweetness, the contents of vitamin C and alpha- and beta-carotenes, and certain flavor characteristics were observed among the colored carrot varieties examined. Purple carrots contained 2.2 and 2.3 times more alpha- and beta-carotenes (trace in yellow; not detected in white) than orange carrots, respectively. Purple carrot may be used in place of other carrot varieties to take advantage of its nutraceutical components.


A learning perspective on individual differences in skilled reading: Exploring and exploiting orthographic and semantic discrimination cues.
The goal of the present study is to understand the role orthographic and semantic information play in the behavior of skilled readers. Reading latencies from a self-paced sentence reading experiment in which Russian near-synonymous verbs were manipulated appear well-predicted by a combination of bottom-up sublexical letter triplets (trigraphs) and top-down semantic generalizations, modeled using the Naive Discrimination Learner. The results reveal a complex interplay of bottom-up and top-down support from orthography and semantics to the target verbs, whereby activations from orthography only are modulated by individual differences. Using performance on a serial reaction time (SRT) task for a novel operationalization of the mental speed hypothesis, we explain the observed individual differences in reading behavior in terms of the exploration/exploitation hypothesis from reinforcement learning, where initially slower and more variable behavior leads to better performance overall. (PsycINFO Database Record


Baicalein protects tert‑butyl hydroperoxide‑induced hepatotoxicity dependent of reactive oxygen species removal.
Baicalein (BA), one of the major bioactive flavonoids isolated from Scutellariae Radix, possesses various pharmacological activities. The present study aimed to investigate the protective effects of BA on tert‑butyl hydroperoxide (t‑BHP)‑induced hepatotoxicity, and to investigate the potential mechanisms in LO2 cells. BA was demonstrated to possess protective properties against t‑BHP injury in LO2 cells, as evidenced by MTT and lactate dehydrogenase assays. BA significantly prevented t‑BHP‑induced depolarization of mitochondrial membrane potential (MMP), decreased the percentage of apoptotic cells caused by t‑BHP, and prevented intracellular reactive oxygen species (ROS) generation in LO2 cells. Furthermore, BA slightly triggered autophagy in LO2 cells, as evidenced by the elevation of LC3‑II expression, while BA combined treatment with an autophagy inhibitor (chloroquine) or activator (rapamycin) did not alter the hepatoprotective properties. In conclusion, BA may possess a hepatoprotective effect against t‑BHP‑induced liver cell injury, dependent on ROS removal. Therefore, BA may represent a potential drug candidate in protecting hepatotoxicity.


Intramolecular-rotation driven triplet-to-singlet upconversion and fluctuation induced fluorescence activation in linearly connected donor-acceptor molecules.
Thermally activated triplet-to-singlet upconversion is attractive from both fundamental science and exciton engineering, but controlling the process from molecular configuration is still unrevealed. In particular, the flexibility of the freedom of molecular geometry is of major importance to understand the kinetics of the phonon-induced upconversion. Here, we focus on two linearly connected donor-acceptor molecules, 9,9-dimethyl-9,10-dihydroacridine-2,4,6-triphenyl-1,3,5-triazine (DMAC-TRZ) and hexamethylazatriangulene-2,4,6-triphenyl-1,3,5-triazine (HMAT-TRZ), as the model system. While DMAC-TRZ possesses a rotational degree of freedom in the dihedral angle between the donor and acceptor moieties, i.e., C-N bond in tertiary amine, the rotation is structurally restricted in HMAT-TRZ. The rotationally flexible DMAC-TRZ showed significant triplet-to-singlet upconversion caused by thermal activation. On the other hand, the rotation-restricted HMAT-TRZ showed negligible thermal upconversion efficiency. We elaborate on the origin of the photophysical properties from the viewpoint of the geometries in the excited states using time-resolved infrared spectroscopy and quantum chemical calculations. We uncovered that the structural restriction of the intramolecular flexibility significantly affects the optimized geometry and phonon modes coupled to the spin conversion. As a result of the rotation restriction, the spin flipping in HMAT-TRZ was coupled to bending motion instead of the rotation. In contrast, the free rotation fluctuation in the DMAC-TRZ mixes local-excitation and charge-transfer characters, leading to successful activation of the delayed fluorescence as well as the reverse intersystem crossing. Our discovery sheds light on the mechanism of the triplet-to-singlet upconversion, providing a microscopic strategy to control the optoelectronic properties from a molecular viewpoint.


Double calcaneal osteotomy with percutaneous Steinmann pin fixation as part of treatment for flexible flatfoot deformity: a review of consecutive cases highlighting our experience with pin fixation.
Surgical correction of flexible flatfoot deformity and posterior tibial tendon dysfunction has been extensively reported in published studies. When appropriate, calcaneal osteotomies for flatfoot correction have been a favorite of foot and ankle surgeons because of the corrective power achieved without the need to fuse any rearfoot joints. The medial displacement calcaneal osteotomy and Evans calcaneal osteotomy, together termed the double calcaneal osteotomy, have been reported several times by various investigators with a wide variety of fixation options. We undertook an institutional review board-approved retrospective review of 9 consecutive patients (11 feet), who had undergone double calcaneal osteotomy with 2 percutaneous Steinmann pin fixation for the correction of flexible flatfoot deformity, with or without posterior tibial tendon dysfunction. All patients had radiographic evidence of bone healing of the posterior calcaneal osteotomy and incorporation of the Evans osteotomy bone graft at 6 weeks and demonstrated clinical healing at 6 weeks. All patients had 2 percutaneous Steinmann pins placed through both osteotomies, and these were removed an average of 6 weeks postoperatively. No patient developed pin site complications. The only complication noted was sural neuritis, which was likely incision related. No patients had delayed union or nonunion, and we did not identify any graft shifting postoperatively. The present retrospective series highlights our experience with 2 percutaneous Steinmann pin fixation, demonstrating equal or better results than many previous published fixation methods for double calcaneal osteotomy. It is cost-effective and minimizes the potential risk of iatrogenic Achilles pathologic features associated with screw fixation.


Potential Drug-Drug Interactions in Patients With Urinary Tract Infections: A Contributing Factor in Patient and Medication Safety.
Introduction: Hospitalized patients with urinary tract infections (UTIs) often present with comorbid illnesses and are subsequently prescribed multiple medications, which increases the likelihood of drug-drug interactions. Therefore, this study aimed to explore the prevalence, levels, risk factors, and clinical relevance of potential drug-drug interactions (pDDIs) in hospitalized patients with UTIs. Secondly, we aimed to develop management guidelines and identify monitoring parameters for the most frequent interactions. Methods: A retrospective cross-sectional study was conducted in internal medicine wards of two tertiary care hospitals in Peshawar, Khyber Pakhtunkhwa, Pakistan. The clinical profiles of 422 patients with UTIs were reviewed for pDDIs using the Micromedex Drug-Reax®. Logistic regression was applied to assess the association of pDDIs with various risk factors. The clinical relevance of frequent pDDIs was identified by assessing the potential adverse outcomes of pDDIs including patients' signs, symptoms, and abnormal laboratory findings. Results: Of 422 patients, at least one pDDI was identified in 62.3% patients, while 40% patients had at least one major pDDI. A total of 1,086 pDDIs were identified, of which 53.4% and 39.3% were of moderate and major severity, respectively. Patients with most frequent pDDIs were presented with hypoglycemia, hepatotoxicity, nephrotoxicity, hypertension, and decreased therapeutic response. These adverse events were more prevalent in patients taking higher doses of interacting drugs. Multivariate regression analysis revealed significant association of pDDIs with six or more medicines (p < 0.001), diabetes mellitus (p < 0.001), ischemic heart disease (p = 0.02), and congestive cardiac failure (p = 0.04). Conclusions: Patients with UTIs present with a considerable number of clinically important pDDIs. Polypharmacy, diabetes mellitus, ischemic heart disease, and congestive cardiac failure increase the risk of pDDIs. Knowledge about the most frequent pDDIs will enable healthcare professionals to implement optimized monitoring and management strategies regarding associated adverse consequences in order to ensure patient safety. Most of the interactions can be managed by considering alternative therapy and dose reduction.


Distinct hemodynamic responses to (pyr)apelin-13 in large animal models.
This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure (P = 0.59), dP/dtmax (P = 0.26), or dP/dtmin (P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% (P < 0.01), which was accompanied by a significant increase in coronary blood flow (P < 0.05) and reductions in left ventricular end-diastolic volume and stroke volume (P < 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow (P = 0.83) or vasorelaxation in isolated, endothelium-intact (P = 0.89) or denuded (P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs (P < 0.001; R2 = 0.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species (P < 0.001; R2 = 0.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs.NEW & NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion.


Small bowel enteroscopy in undiagnosed gastrointestinal blood loss.
Sixty five of 70 consecutive patients with undiagnosed gastrointestinal blood loss were examined using the new technique of small bowel enteroscopy. Using a balloon driven sonde enteroscope (SIF-SW) extended views of the small bowel were obtained as far as the distal ileum. Medium length of small bowel examined was 140 cm (range (30-200 cm). All patients studied had a normal upper gastrointestinal endoscopy. Nineteen (41%) of 46 anaemic rheumatoid arthritis patients taking non-steroidal antiinflammatory drugs (NSAID) and three (27%) of 11 patients with unexplained iron deficiency, were found to have small bowel lesions to account for their anaemia. Small bowel lesions were found in a further three of eight (37%) patients with acute gastrointestinal bleeding. The procedure failed or was terminated in five patients. Small bowel enteroscopy has considerable potential in the investigation of undiagnosed gastrointestinal blood loss and deserves more widespread application.


Different Routes to Inhibit Fatty Acid Amide Hydrolase: Do All Roads Lead to the Same Place?
There is robust evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of eCBs degradation by fatty acid amide hydrolase (FAAH) blockade, is the best-known option to increase N-acyl-ethanolamines-(NAEs)-mediated signaling. Here, we investigated the hypothesis that intranasal delivery is an effective route for different FAAH inhibitors, such as URB597 and PF-04457845. URB597 and PF-04457845 were subchronically administered in C57BL/6 male mice every other day for 20 days for overall 10 drug treatment, and compared for their ability to inhibit FAAH activity by the way of three different routes of administration: intranasal (i.n.), intraperitoneal (i.p.) and oral (p.o.). Lastly, we compared the efficacy of the three routes in terms of URB597-induced increase of NAEs levels in liver and in different brain areas. Results: We show that PF-04457845 potently inhibits FAAH regardless the route selected, and that URB597 was less effective in the brain after p.o. administration while reached similar effects by i.n. and i.p. routes. Intranasal URB597 delivery always increased NAEs levels in brain areas, whereas a parallel increase was not observed in the liver. By showing the efficacy of intranasal FAAH inhibition, we provide evidence that nose-to-brain delivery is a suitable alternative to enhance brain eCB tone for the treatment of neurodegenerative disorders and improve patients' compliance.


Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression.
To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control. This is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with ≥1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau. HIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200-350 blood CD4+ T cells/μL and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.


Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells.
Oral squamous cell carcinoma is an aggressive neoplasm with serious morbidity and mortality, which typically spreads through local invasive growth. Lysophosphatidic acid (LPA) is involved in a number of biological processes, and may have a role in cancer cell migration and invasiveness. LPA is present in most tissues and can activate cells through six different LPA receptors (LPAR1-6). Although LPA is predominantly promigratory, some of the receptors may have antimigratory effects in certain cells. The signalling mechanisms of LPA are not fully understood, and in oral carcinoma cells the specific receptors and pathways involved in LPA-stimulated migration are unknown. The oral carcinoma cell lines E10, SCC-9, and D2 were investigated. Cell migration was studied in a scratch wound assay, and invasion was demonstrated in organotypic three dimensional co-cultures. Protein and mRNA expression of LPA receptors was studied with Western blotting and qRT-PCR. Activation of signalling proteins was examined with Western blotting and isoelectric focusing, and signalling mechanisms were further explored using pharmacological agents and siRNA directed at specific receptors and pathways. LPA stimulated cell migration in the two oral carcinoma cell lines E10 and SCC-9, but was slightly inhibitory in D2. The receptor expression profile and the effects of specific pharmacological antagonist and agonists indicated that LPA-stimulated cell migration was mediated through LPAR3 in E10 and SCC-9. Furthermore, in both these cell lines, the stimulation by LPA was dependent on PKC activity. However, while LPA induced transactivation of EGFR and the stimulated migration was blocked by EGFR inhibitors in E10 cells, LPA did not induce EGFR transactivation in SCC-9 cells. In D2 cells, LPA induced EGFR transactivation, but this was associated with slowing of a very high inherent migration rate in these cells. The results demonstrate LPA-stimulated migration in oral carcinoma cells through LPAR3, mediated further by PKC, which acts either in concert with or independently of EGFR transactivation.


Discriminative fusion of moments-aligned latent representation of multimodality medical data.
Fusion of multimodal medical data provides multifaceted, disease-relevant information for diagnosis or prognosis prediction modeling. Traditional fusion strategies such as feature concatenation often fail to learn hidden complementary and discriminative manifestations from high-dimensional multimodal data. To this end, we proposed a methodology for the integration of multimodality medical data by matching their moments in a latent space, where the hidden, shared information of multimodal data is gradually learned by optimization with multiple feature collinearity and correlation constrains. We first obtained the multimodal hidden representations by learning mappings between the original domain and shared latent space. Within this shared space, we utilized several relational regularizations, including data attribute preservation, feature collinearity and feature-task correlation, to encourage learning of the underlying associations inherent in multimodal data. The fused multimodal latent features were finally fed to a logistic regression classifier for diagnostic prediction. Extensive evaluations on three independent clinical datasets have demonstrated the effectiveness of the proposed method in fusing multimodal data for medical prediction modeling.&#xD.


Detection of baroreceptor activity in rat vagal nerve recording using a multi-channel cuff-electrode and real-time coherent averaging.
Electrical stimulation of afferent nerve fibers originating from pressure sensors can trigger the baroreflex to reduce blood pressure and might be an alternative to treat patients with hypertension. In this study, baroreceptor compound activity was detected using multi-channel cuff-electrode recordings on rat vagal nerve. In order to isolate the vagal nerve signals from external potentials (such as ECG- and EMG-coupling), a tripolar measuring technique was applied. To eliminate noise and neural signals corresponding to other organs, coherent averaging was used. The baroreceptor-correlated signals appear predominantly in one of the electrode channels, presumably close to the corresponding neural substrate. This localization was done in real-time.


Abscisic Acid Treatment in Patients with Prediabetes.
to evaluate the effects of abscisic acid (ABA), contained in dwarf peaches, on the regression of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) conditions. sixty-five patients with IFG or IGT were randomized to take ABA or placebo for 3 months. We evaluated: fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile and high sensitivity C-reactive protein (Hs-CRP). At baseline, and after 3 months, all patients underwent an oral glucose tolerance test (OGTT), an euglycemic hyperinsulinemic clamp, and a glucagon test. a significant reduction of HbA1c, FPG, PPG, FPI and HOMA-IR was observed in the ABA group. After 3 months, 26.7% of patients returned to a normal glycemic status in the ABA group versus zero patients in placebo group; 20.0% were classified as IFG and 53.3% as IGT in the nutraceutical group versus 33.3% and 63.3% in the placebo group. The M value was higher in the ABA group at the end of the treatment. Finally, Hs-CRP was reduced after 3 months of ABA consumption. abscisic acid can be effective in ameliorating glyco-metabolic compensation and in reducing inflammatory status in patients with IFG or IGT.


Outcomes of operative versus nonoperative treatment of displaced pediatric clavicle fractures.
Current literature proposes relative and absolute indications for surgical treatment of clavicle fractures in adults. However, few studies have evaluated these fractures in children. The current study examined short- and long-term outcomes of pediatric patients with displaced clavicle fractures. Outcomes assessed included radiographic healing, full active range of motion, and return to activity. The authors' hypothesis was that open reduction and internal fixation of displaced clavicle fractures would lead to better outcomes than nonoperative treatment. The authors retrospectively reviewed the charts of pediatric patients treated for clavicle fractures between January 2001 and October 2011. The nonoperative group included 32 patients, and the operative group included 46 patients. Mean time to return to activity was 12.24 weeks in the nonoperative group and 12.70 weeks in the operative group (P=.67). Mean time to full active range of motion was 7.85 weeks in the nonoperative group and 8.74 weeks in the operative group (P=.24). Mean time to radiographic evidence of healing was 12.02 weeks in the nonoperative group and 11.90 weeks in the operative group (P=.90). Average Disabilities of the Arm, Shoulder and Hand (DASH) score was 0.04 in the nonoperative group (range, 0-0.08) and 1.17 in the operative group (range, 0-8.3), with no significant difference between groups. No significant difference between operative treatment and nonoperative treatment was found in any of the authors' outcome measures. Thus, the authors propose that unless the patient's injury is an absolute indication for surgery, conservative management provides equivalent immediate and long-term clinical results.


[Predominant pulmonary manifestations in leptospirosis icterohemorrhagica].
14 cases of leptospirosis ictero-haemorrhagica observed on Reunion island with predominant or isolated pulmonary symptoms are described. Hospitalisation was motivated in every case by haemoptysis, at times profuse, which occurred in patients with fever and myalgia. The chest radiographs revealed an alveolar and/or a bilateral alveolar pattern of variable severity. In spite of the importance of chest radiography port raying an extensive and serious pneumonia in one case out of every two, the outcome was favourable with a mean time lag of one week. In three cases, an adult respiratory distress syndrome (ARDS) was seen requiring assisted ventilation and one death occurred. The diagnosis of leptospirosis may be considered, even in countries of low endemicity, in a case pneumonia with extensive haemoptysis or an adult respiratory distress syndrome whose cause is not established by the usual tests.


Morphological evaluation of full-thickness idiopathic macular holes by optical coherence tomography.
To assess the efficacy of optical coherence tomography (OCT) for the morphological evaluation of idiopathic full-thickness macular holes and for detecting any morphological changes with time. Serial sagittal tomographs through the macula were taken by OCT in a consecutive series of 34 eyes of 34 patients with diagnosis of idiopathic full-thickness macular hole. The patients were divided into two groups on the basis of "recent" (group 1, 25 patients) or "not-recent" (group 2, 9 patients) onset of symptoms related to the macular hole. Fourteen of the 25 patients in group 1 and all nine in group 2 underwent vitrectomy. The 11 in group 1 who refused surgery were observed by OCT examination with follow-up from 6 to 13 months. In most eyes OCT scans revealed two different anatomical features of macular holes depending on the time of onset of symptoms. Eleven of the 14 "recent-onset" holes that underwent surgery showed "sharp", undermining edges at preoperative OCT; the other three had "rounded" edges. Seven of the nine eyes operated for long-standing full-thickness macular holes had preoperative "rounded" edges, while the edges in the remaining two eyes were "sharp". OCT of eight of the 11 non-operated eyes in group 1 showed a morphological evolution of the macular hole edges from a "sharp" to a "rounded" contour and an increase in the diameter of the hole. OCT can help in the morphological evaluation of idiopathic full-thickness macular holes and in the detection of morphological changes with time.


Accuracy of BMI and waist circumference cut-off points to predict obesity in older adults.
The main objectives were to analyse the validity and accuracy of Body Mass Index (BMI) and Waist Circumference (WC) to evaluate obesity by excess of body fat in older adults and to identify more adequate cut-off points for this age group. The recommended cut-off points for BMI (25, 27 or 30 kg/m2) and WC (≥ 102 cm for men and ≥ 88 cm for women or ≥ 90cm for men and ≥ 80 cm for women) were compared to the total body densitometry. BF was defined by a value higher than the 90th percentile. Out of the 132 participants, 61% were women and aged between 60 and 91 years. The recommended cut-off points of BMI ≥ 25kg/m2 and BMI ≥ 27 kg/m2 showed similar performances. BMI ≥ 30 kg/m2 showed high specificity but low sensitivity to identify BF in men and better performance in women. Conventional WC cut-off points showed low sensitivity and specificity. Based on our analyses, new cut-off points for BMI (25 kg/m2 for men and 26.6 kg/m2 for women) and WC (98.8 cm for men and 77.8cm for women) were proposed. The new cut-off points showed sensitivity and specificity values > 74% and accuracy > 76%. The areas under the curve (ROC) were > 0.86. The new BMI and WC cut-off points proposed in the present study for the diagnosis of obesity in older adults showed the best levels of sensitivity and specificity for this age group.


Use of Picosecond Laser for Melasma Treatment: A Narrative Review.
Background: Melasma results from the imbalance of the mechanisms that regulate skin pigmentation, causing the appearance of hyperpigmented patches. Treatment includes topical and oral agents, chemical peelings, microneedling, and laser therapy. The picosecond laser was developed to minimize pain and skin discoloration, which can sometimes be associated with laser treatments. It emits short pulses of energy that last from 300 to 500 picoseconds, leading to a more significant fragmentation of melanin, with miniminal risk of scarring and thermal lesions in the surrounding skin. Objective: The authors aimed to review the use of picosecond laser in the treatment of melasma and further provide an overview of the other current available options. Conclusions: While the use of picosecond laser for the treatment of melasma has yielded good results, further studies with longer follow-up periods and a higher number of patients are needed.


Insights into the structures and properties of dyes in the Fenton catalytic process for treating wastewater effluent.
A notable level of apprehension exists over the adverse impacts of dye pollution on aquatic ecosystems and human well-being. The primary objective of this research is to assess the effectiveness of Fenton catalytic reactions in degrading 14 different commercial azo dyes (both single and double) present in aqueous solutions. The investigation focused on the function of dye structures, using a combination of experimental data and examination of theoretical factors. Dye degradation process was carried out at pH 3, and the concentrations of Fe2+ (10-4 mol/L), H2 O2 (2 × 10-3 mol/L), and dye (0.05 g/L). The findings revealed that dyes with a larger molecular weight were more effective at degrading (D%), with the overall degradation efficiency varying from 0% to 94%. Functional groups played an important role in degradation efficiency; for example, dyes with higher aromatic rings led to less D%, while a higher number of sulfonic, methyl, and nitro groups was responsible for better D%. Notably, the presence of OH groups in the backbone of dyes (AB 24, ABE 113, and MB 9) formed the Fe complex during the catalytic process, and the D% was minimal. On the other hand, theoretical quantum calculations such as the greater the JCLogP, highest occupied molecular orbital, and Dipole moment value, the higher the degradation efficiency. And dyes with low lowest unoccupied molecular orbital tended to have a better degradation efficiency. To some extent, UV-Vis spectral analysis was investigated to determine the degradation pathway, and the pseudo-second-order kinetic model fitted better in the degradation process. The overall experimental and theoretical findings suggested that dye degradation efficiency by the Fenton process is structure-dependent. PRACTITIONER POINTS: Insights into the role of azo dye structures-properties on degradation efficiency. Higher molecular weight and sulfonic groups containing dyes showed better degradation efficiency. Hydroxyl groups play the formation of the Fe complex during the degradation process. Higher values of HOMO and lower values of LUMO enhanced degradation efficiency. The pseudo-second-order (PSO) kinetic model obeyed the Fenton process.


Breast cancer risk associated with ovulation-stimulating drugs.
Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.


Comparison of cost-effectiveness and postoperative outcomes following integration of a stiff shaft glidewire into percutaneous nephrolithotripsy.
To analyze the cost effectiveness of integrating a stiff shaft glidewire (SSGW) in percutaneous nephrolithotripsy (PCNL) relative to standard technique (ST). This is prudent because healthcare providers are experiencing increased pressure to improve procedure-related cost containment. ST for PCNL at our institution involves a hydrophilic glidewire during initial percutaneous access and then two new stiff shaft wires. The SSGW is a hydrophilic wire used for initial access and the remainder of the procedure. We collected operating room (OR) costs for all primary, unilateral PCNL cases over a 5-month period during which ST for PCNL was used at a single institution with a single surgeon and compared with a 6-month period during which a SSGW was used. Mean costs for each period were then compared along with stone-free rates and complications. We included 17 total cases in the ST group and 22 in the SSGW group. The average operating room supply cost for the ST group was $1937.32 and $1559.39 in the SSGW group. The net difference of $377.93 represents a nearly 20% decrease in cost. This difference was statistically significant (p = 0.031). There was no difference in postoperative stone-free rates (82.4% versus 86.4%, p = 1.0, respectively) or complications (23.5% versus 13.6%, p = 0.677, respectively) between ST and SSGW groups. Transitioning to a SSGW has reduced OR supply cost by reducing the number of supplies required. The change in wire did not affect stone-free rates or complications.


Decoding multiple sound categories in the human temporal cortex using high resolution fMRI.
Perception of sound categories is an important aspect of auditory perception. The extent to which the brain's representation of sound categories is encoded in specialized subregions or distributed across the auditory cortex remains unclear. Recent studies using multivariate pattern analysis (MVPA) of brain activations have provided important insights into how the brain decodes perceptual information. In the large existing literature on brain decoding using MVPA methods, relatively few studies have been conducted on multi-class categorization in the auditory domain. Here, we investigated the representation and processing of auditory categories within the human temporal cortex using high resolution fMRI and MVPA methods. More importantly, we considered decoding multiple sound categories simultaneously through multi-class support vector machine-recursive feature elimination (MSVM-RFE) as our MVPA tool. Results show that for all classifications the model MSVM-RFE was able to learn the functional relation between the multiple sound categories and the corresponding evoked spatial patterns and classify the unlabeled sound-evoked patterns significantly above chance. This indicates the feasibility of decoding multiple sound categories not only within but across subjects. However, the across-subject variation affects classification performance more than the within-subject variation, as the across-subject analysis has significantly lower classification accuracies. Sound category-selective brain maps were identified based on multi-class classification and revealed distributed patterns of brain activity in the superior temporal gyrus and the middle temporal gyrus. This is in accordance with previous studies, indicating that information in the spatially distributed patterns may reflect a more abstract perceptual level of representation of sound categories. Further, we show that the across-subject classification performance can be significantly improved by averaging the fMRI images over items, because the irrelevant variations between different items of the same sound category are reduced and in turn the proportion of signals relevant to sound categorization increases.


New low bandgap dithienylbenzothiadiazole vinylene based copolymers: synthesis and photovoltaic properties.
Two new low-bandgap block copolymers derived from dithienylbenzothiadiazole (DTBT) and different electron-rich functional groups (dioctoxyl benzene and N-octyl-diphenylamine), poly(1,4-dioctoxyl-2,5-divinylbenzene-co-4,7-dithiophene-2'-yl-2,1,3-benzothiadiazole) (PPV-DTBT), poly(3,8-divinyl-N-octyl-diphenylamine-co-4,7-dithiophene-2'-yl-2,1,3-benzothiadiazole) (PDPAV-DTBT), were synthesized by Heck cross-coupling polymerization. PPV-DTBT and PDPAV-DTBT are easily soluble in common organic solvents such as o-dichlorobenzene and chloroform. DSC and TGA results indicate that these copolymers possess good thermal stabilities. PPV-DTBT and PDPAV-DTBT films exhibit broad absorption bands at 300-765 nm (with an optical bandgap of 1.62 eV) and 300-733 nm (with an optical bandgap of 1.69 eV), respectively. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of PPV-DTBT were estimated by cyclic voltammetry to be -5.43 and -3.74 eV, respectively, and the HOMO and LUMO of PDPAV-DTBT were -5.37 and -3.7 eV, respectively. Preliminary photovoltaic cells based on the composite structure of ITO/PEDOT: PSS/PPV-DTBT:PCBM (1: 2, w/w)/Al showed an open-circuit voltage of 0.75 V, a power conversion efficiency of 0.6%, and a short circuit current of 1.7 mA · cm(-2) .


Comparison of Health-related Behaviors in Pregnant Women and Breast-feeding Mothers vs Non-pregnant Women.
The aim of this study was to assess health-related behavior of pregnant women and breastfeeding mothers by investigating relevant risk factors. Data of 10,396 women (age 19 to 49 years) from the Korea National Health and Nutrition Examination Survey report from 2007 to 2012 was used to analyze factors associated with health-related behavior. The subjects were divided into pregnant women; breastfeeding mothers; and non-pregnant women. Bottle feeding mothers were excluded. Current smoking rate including self-reported smoker and/or positive cotinine urine test were lower for pregnant or breast-feeding group than non-pregnant group. Heavy-drinking was not different among groups while monthly drinking rate was higher in non-pregnant group. Rate of stress recognition was lower in pregnant and breast-feeding group than non-pregnant group. Rate of experience for depressive symptoms and rate of suicidal ideation were not different among groups. Pregnant women and breast-feeding mothers maintain a good pattern of health-related behavior compared to non-pregnant women. However, substantial proportion of pregnant women and breast-feeding mothers continue to drink and smoke. This shows the need for a plan that will modify health-related behavior.


Factors associated with pediatrician attitudes over the use of complementary and traditional medicine on children in Muscat, Oman.
This study aimed to evaluate the attitude of pediatricians toward the use of complementary and Traditional Medicine (TM) on children in Muscat, Oman. A cross-sectional survey was performed using a self-completed questionnaire during the year 2012. A total of 67 pediatricians, comprising of 30 males (44.8%) and 37 females (55.2%) participated in the study. The majority of the studied group (83.5%) was of the opinion that most types of complementary and TM are not safe for children, except spiritual healing, to which 53.7% considered as safe. About one third (29.9%) of the participants reported that they might recommend complementary and TM for sick children in the future. Almost half the participants (52.2%) acknowledged personal use of complementary and TM in the past and 67.2% reported that their family members used these medicines. Herbal therapy was found to be the most commonly used method (38.9%) followed by spiritual (33.9%), cautery (20.2%) and Curucoma (15.7%). Other methods, which include; acupuncture, bone healing and Chinese healing were also found to be in use but in rare manner. Knowledge level of TM and complementary medicine of most of the doctors was found to be low but one third of them acknowledged that they may recommend these treatments to their patients in future. Therefore, training pediatricians on the types, benefits and side effects of complementary and TM is recommended.


Correlations between detectors allow violation of the Heisenberg noise-disturbance principle for position and momentum measurements.
Heisenberg formulated a noise-disturbance principle stating that there is a tradeoff between noise and disturbance when a measurement of position and a measurement of momentum are performed sequentially, and another principle imposing a limitation on the product of the uncertainties in a joint measurement of position and momentum. We prove that the former, the Heisenberg sequential noise-disturbance principle, holds when the detectors are assumed to be initially uncorrelated from each other, but that it can be violated for some properly correlated initial preparations of the detectors.


Impact of FUTON and NAA bias on visibility of research.
To determine whether availability of journals on MEDLINE as FUTON (full text on the Net) affects their impact factor. A comprehensive search identified 324 cardiology, nephrology, and rheumatology/immunology journals on-line until May 2003. The status of these journals was ascertained in MEDLINE as having FUTON, abstracts only, and NAA (no abstract available). Impact factors for all available journals from the Institute for Scientific Information (ISI) were abstracted. Of the 324 Journals, 124 (38.3%) were FUTON, 138 (42.6%) had abstracts only, and 62 (19.1%) had NAA. The mean (+/-SEM) impact factor was 3.24 (+/-0.32), 1.64 (+/-0.30), and 0.14 (+/-0.45), respectively. Of the 324 current journals, 159 existed in both the pre- and the post-Internet era. An analysis of the change (ie, delta) in impact factor from the pre- to post-Internet era revealed a trend between journals with FUTON and abstracts only (P=.17, Wilcoxon rank sum test). Similar analyses of the delta of cardiology journals revealed a statistically significant difference between Journals with FUTON and abstracts only (P=.04, Wilcoxon rank sum test). FUTON bias is the tendency to peruse what is more readily available. This is the first study to show that on-line availability of medical literature may increase the impact factor and that such increase tends to be greater in FUTON journals. Failure to consider this bias may affect a journal's impact factor. Also, it could limit consideration of medical literature by ignoring relevant NAA articles and thereby influence medical education akin to publication or language bias.


Cranial computed tomography in disorders of complex carbohydrate metabolism and related storage diseases.
Computed tomography (CT) was performed on 34 children with different disorders of complex carbohydrate metabolism and related storage diseases to obtain data on the degree of cerebral involvement. The main findings on CT were cerebral atrophy and hypodensity of the white matter. There was a great variability in these CT findings, even in siblings. Among the patients there were several in whom CT was normal, so a negative study does not exclude one of these disorders. These findings show that CT features such as cerebral atrophy or hypodensity are helpful in the evaluation of these disorders, though a diagnosis cannot be made on the basis of CT alone.


Changes in bone density after exposure to oral anticoagulants: a meta-analysis.
Oral anticoagulants are putative risk factors for osteoporosis, but observational cross-sectional studies describing their effects on bone mineral density have reported conflicting results, prospective studies are not available, and randomized trials are not feasible. To determine the association between exposure to oral anticoagulants and changes in bone density, we systematically reviewed nine original cross-sectional studies on the effect of long-term exposure to any oral anticoagulant on bone density in adults. The effect size was assessed by standardized mean difference (SMD, exposed minus unexposed) and pooled by skeletal site; results are reported in standard deviation units. Bone density was significantly decreased among exposed subjects in the ultradistal radius (SMD, -0.39; 95% CI, -0.67 to -0.10) but not in the distal radius (SMD, -0.47; 95% CI, -0.97 to 0.04), lumbar spine (SMD, -0.27; 95% CI, -0.59 to 0.05), femoral neck (SMD, 0.03; 95% CI, -0.22 to 0.29) or femoral trochanter (SMD, -0.18; 95% CI, -0.48 to 0.11). The evidence should be considered with caution, but it is consistent with a negative association of oral anticoagulants with bone density in the ultradistal radius, although not in the spine or hip. This suggests that long-term oral anticoagulation might be associated with no more than a modest increase in osteoporotic fracture risk, but this should be verified in future longitudinal studies.


Physical, chemical and functional changes following platelet activation in normal and "giant" platelets.
Unactivated discocytes in healthy human donors have mean volumes of approximately 6.0 microns3 (range 3.8-7.5 microns3), while mean values for similarly-shaped discocytes obtained from donors with the hereditary "giant" platelet syndromes were either normal (one Bernard-Soulier syndrome (BSS) and all five members of a family with the Montreal platelet syndrome (MPS) or, on average, up to twice normal (range 6.4-13.8 microns3). This apparent heterogeneity is complicated by the much more consistent and significant observation that both BSS and MPS platelets undergo a defective hypervolumetric shape change following activation which is prolonged indefinitely, in contrast to a transient hypervolumetric change measureable in 1-5 s following ADP addition to normal platelets. It is suggested that the hypervolumetric shape change in both normal and "giant" platelets is accompanied by an increase in externalized plasma membrane surface area, with the most probable source being surface-connected canalicular system. Membrane glycoprotein I abnormalities were not detectable in platelets for 2/3 sibling MPS donors. The precise relation of these membrane changes to altered platelet functions is compared for normal and "giant" platelets, but largely remains to be experimentally determined. Early shape change appears tightly associated with early microscopically-measured aggregation (PA), with both PA and turbidimetrically-measured macroaggregation generally appearing normal to elevated for "giant" platelets.


Developing and Implementing a Professional Practice Model.
Professional practice models guide nursing practice by giving meaning to the work of nurses. They elevate the practice from tasks to theory, from skills to knowledge, and remind us that the patient and family are at the center of our practice. Professional practice models are one of the foundations of the Magnet Recognition Program. The purpose of this paper is to describe the development and implementation of a professional practice model in a healthcare system, which includes three hospitals and over 80 ambulatory practices in the New York City region.


An avian influenza H5N1 virus that binds to a human-type receptor.
Avian influenza viruses preferentially recognize sialosugar chains terminating in sialic acid-alpha2,3-galactose (SAalpha2,3Gal), whereas human influenza viruses preferentially recognize SAalpha2,6Gal. A conversion to SAalpha2,6Gal specificity is believed to be one of the changes required for the introduction of new hemagglutinin (HA) subtypes to the human population, which can lead to pandemics. Avian influenza H5N1 virus is a major threat for the emergence of a pandemic virus. As of 12 June 2007, the virus has been reported in 45 countries, and 312 human cases with 190 deaths have been confirmed. We describe here substitutions at position 129 and 134 identified in a virus isolated from a fatal human case that could change the receptor-binding preference of HA of H5N1 virus from SAalpha2,3Gal to both SAalpha2,3Gal and SAalpha2,6Gal. Molecular modeling demonstrated that the mutation may stabilize SAalpha2,6Gal in its optimal cis conformation in the binding pocket. The mutation was found in approximately half of the viral sequences directly amplified from a respiratory specimen of the patient. Our data confirm the presence of H5N1 virus with the ability to bind to a human-type receptor in this patient and suggest the selection and expansion of the mutant with human-type receptor specificity in the human host environment.


Matching asymmetry of tremor with asymmetry of postmortem cerebellar hemispheric changes in essential tremor.
Although the number of postmortem studies in essential tremor (ET) has grown in recent years, clinical-pathological correlations remain limited. We are unaware of a study that has assessed whether the pathological changes in ET, if asymmetric, lateralize to the cerebellar hemisphere that is ipsilateral to the arm with more severe action tremor, as one would predict if the lesions were tremor producing. We compared postmortem changes in the right vs. left cerebellar hemispheres in ET and examined how these correlated with asymmetry of tremor on neurological examination. Action tremor in each arm was quantified using a reliable and valid clinical rating scale. Cases were divided into three clinical groups: tremor more severe on right, tremor more severe on left, and tremor symmetric. Calbindin D28k immunohistochemistry was performed on 100 μm vibrotome sections from a standard tissue block of both right and left neocerebellums to quantify Purkinje cell linear density, torpedo counts, and a group of previously described changes in Purkinje cell axonal shape (thickened axonal profiles) and connectivity (axon recurrent collaterals, axonal branching, terminal axonal sprouting, arciform axons, extent of recurrent collateral plexus). ET cases were divided into three postmortem groups: findings greatest on right, findings greatest on left, and findings symmetric. In 18 (72.0 %) of 25 ET cases, clinical and pathological features were concordant (i.e., both clinically and pathologically right-predominant (one case), both clinically and pathologically left-predominant (five cases), or both clinically and pathologically symmetric (12 cases), p = 0.007). In the remaining seven (28.0 %) ET cases, clinical and pathological data were not concordant, and in none were they completely discordant (i.e., tremor was more severe on the right, and postmortem cerebellar changes were paradoxically more severe on the left or vice versa). Among the seven ET cases with >20 % side-to-side difference in tremor severity, six cases (85.7 %) had the expected pathological asymmetry, with quantified postmortem cerebellar changes more marked ipsilateral to the more clinically affected side. We also created continuous measures of asymmetry. For the entire sample, there was a positive correlation between the clinical asymmetry index and the pathological asymmetry index = 0.52, p = 0.01 (i.e., the right-left difference in clinical asymmetry was correlated with the right-left difference in postmortem changes). For the seven ET cases with clear clinical asymmetry, the correlation was even more robust (r = 0.78, p = 0.039). Clinical-pathological correlations are important in terms of understanding the significance of observed pathological changes. The correlation between clinical laterality or symmetry of tremor and pathological changes in the majority of ET cases provides additional evidence that the pathological changes in the cerebellum in ET are of patho-mechanistic importance.


Imatinib plasma levels during successful long-term treatment of metastatic-gastrointestinal stromal tumors.
To investigate whether imatinib dosage correlated with effective plasma levels and clinical characteristics for Japanese patients undergoing long-term (≥2 years) imatinib therapy for GISTs. Twenty-five patients who received imatinib for a metastatic pathologically diagnosed GISTs at our hospital were enrolled. Imatinib response was assessed according to Choi's criteria. Blood samples were collected 22–26 h after the previous imatinib dose before the next scheduled dose. Results: Fourteen patients were male and the median age was 65 years. The median duration of imatinib therapy was 3.8 years (range, 2.0–11.5 years). The median plasma level of imatinib was 1098 ng/ml and the minimal plasma level after ≥5 years of therapy was 789 ng/ml. Imatinib dosage was significantly correlated with history of gastrectomy. The minimum body surface area of patients who received 400-mg/day imatinib dosage was 1.560 m2. The minimum level in all patients showing response for ≥5 years of treatment was 789 ng/ml, suggesting an effective plasma imatinib level of ≥800 ng/ml. Our results suggest that imatinib dosage of 400 mg/day is recommended for a patient with a large BSA (≥1.56 m2) and that of 300 mg/day might be sufficient for patients who have undergone a gastrectomy.


Ethnic disparities in the perception of ethical risks from psychiatric genetic studies.
To examine if ethnic differences in concerns about unfavorable consequences from psychiatric genetic studies, existing between non-Hispanic Black and White populations, persist among participants in an actual genetic study of bipolar disorder. Historically, minority subjects have been less willing to participate in such studies. Participants in the US Bipolar Genome Study (BIGS) were assessed on six items of concerns in the Questionnaire on Genetic Risk (QGR). Each item had five response categories, ranging from "not at all" concerned to "very concerned." Responses from Black (N = 188) and White participants (N = 1,065) formed the base for this analysis. Concerns about unfavorable consequences of conducting psychiatric genetic studies were prevalent in the whole sample. Concern for medical insurance was most prevalent (63.4%), followed by job concern (58.8%) and stigma (57.4%). Racial discrimination was less prevalent (28.1%). Blacks endorsed significantly stronger concerns for all consequences except the medical insurance item (P < 0.008). The most significant ethnic disparity in concerns was for racial discrimination (P < 0.0001). Associations between levels of concern and ethnicity remained significant after adjustments for other factors in multivariate models. Ethnic differences (Blacks vs. Whites) in perceived concerns about unfavorable consequences from participation persist among participants in an actual psychiatric genetic study. This suggests that other factors may play a more critical role in the decision not to participate. Future studies should investigate more comprehensive sources of barriers to consenting for ongoing psychiatric genetic studies in representative samples, incorporating assessments from non-participants as well as participants.


[Magnetocardiography for assessment of fetal heart actions].
Magnetocardiography provides a new, alternative method for fetal surveillance. This method allows the registration of changes in the magnetic field produced by the fetal cardiac system. In comparison to fetal ECG, the fetal magnetocardiogram (fMCG) is not affected by intermediate tissue, in particular by the insulating effect of the vernix caseosa. Furthermore fMCG's with a good signal noise ratio can be obtained in the second trimester. A multichannel biomagnetometer allows the non-invasive measurement of the magnetic signals produced by the fetus. Examples of dta and evaluation techniques are given. Signal processing software allows the identification of all fetal beats in a data set, permitting the calculation of an averaged beat and the evaluation of signal morphology and cardiac time intervals. Furthermore it is possible to produce a beat to beat time series with high temporal resolution, making the evaluation of heart rate variability with measures from the time, frequency, and phase domain accessible. Particularly the latter are of interest in investigating changes in temporal complexity of the fetal cardiac system. Magnetocardiography thus holds the promise of improved antenatal surveillance as of the second trimester.


T1 Mapping for Myocardial Fibrosis by Cardiac Magnetic Resonance Relaxometry-A Comprehensive Technical Review.
Cardiac magnetic resonance (CMR) imaging has been widely used to assess myocardial perfusion and scar and is the non-invasive gold standard for identification of focal myocardial fibrosis. However, the late gadolinium enhancement technique is limited in its accuracy for absolute quantification and assessment of diffuse myocardial fibrosis by technical and pathophysiological features. CMR relaxometry, incorporating T1 mapping, has emerged as an accurate, reproducible, highly sensitive, and quantitative technique for the assessment of diffuse myocardial fibrosis in a number of disease states. We comprehensively review the physics behind CMR relaxometry, the evidence base, and the clinical applications of this emerging technique.


Prevalence of Prediabetes and Undiagnosed Diabetes in Patients with HFpEF and HFrEF and Associated Clinical Outcomes.
The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models. HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c < 6.0), 20 and 22% had prediabetes (HbA1c 6.0-6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63-1.65) for prediabetes, HR 1.18 (0.75-1.86) for undiagnosed diabetes and 2.75 (1.83-4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF. These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF.


[Carcinogenic risk in residents of the Techa riverside villages].
The paper summarizes carcinogenic risk estimates in residents of the Techa riverside villages who have been exposed for many years to radiation due to discharge of radioactive wastes from the Mayak Production Association into the Techa-Iset-Tobol-Ob river system. Analysis of cancer incidence and mortality data has shown a statistically significant dose-dependent increase in the risk of both malignant tumors and leukemia. The dependence of excess relative risk on exposure dose is well described by a linear model. No evidence has been obtained that carcinogenic risk resulting from low-rate radiation exposure is lower than that from acute exposure of A-bomb survivors. Difficulties of following up vital status due to population migration, incomplete data on mortality causes, and inaccurate dose estimates are believed to be key contributors to radiation risk uncertainties.


Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study.
Epidemiologic studies report a protective association between non-steroidal anti-inflammatory drug (NSAID) use and hormone receptor-positive breast cancer risk, a finding consistent with NSAID-mediated suppression of aromatase-driven estrogen biosynthesis. However, the association between NSAID use and breast cancer-specific mortality is uncertain and it is unknown whether this relationship differs by hormone receptor status. This study comprised 935 invasive breast cancer cases, of which 490 were estrogen receptor (ER)-positive, enrolled between 1996 and 2001 in the Carolina Breast Cancer Study. Self-reported NSAID use in the decade prior to diagnosis was categorized by duration and regularity of use. Differences in tumor size, stage, node, and receptor status by NSAID use were examined using Chi-square tests. Associations between NSAID use and breast cancer-specific mortality were examined using age- and race-adjusted Cox proportional hazards analysis. Tumor characteristics did not differ by NSAID use. Increased duration and regularity of NSAID use was associated with reduced breast cancer-specific mortality in women with ER-positive tumors (long-term regular use (≥8 days/month for ≥ 3 years) versus no use; hazard ratio (HR) 0.48; 95 % confidence interval (CI) 0.23-0.98), with a statistically significant trend with increasing duration and regularity (p-trend = 0.036). There was no association for ER-negative cases (HR 1.19; 95 %CI 0.50-2.81; p-trend = 0.891). Long-term, regular NSAID use in the decade prior to breast cancer diagnosis was associated with reduced breast cancer-specific mortality in ER-positive cases. If confirmed, these findings support the hypothesis that potential chemopreventive properties of NSAIDs are mediated, at least in part, through suppression of estrogen biosynthesis.