Comparison of quality of the surgical field after controlled hypotension using esmolol and magnesium sulfate during endoscopic sinus surgery.
Most vital aspect of Endoscopic Sinus Surgery (ESS) is an optimal visibility in the surgical field. This invariably requires controlled hypotension to facilitate surgical dissection and to decrease operative time. We used esmolol and magnesium sulfate to achieve controlled hypotension and assessed the quality of the surgical field in ESS. A total of 30 patients undergoing ESS, were enrolled in three parallel groups of 10 patients each in a prospective randomized double-blind study. "Magnesium Sulfate group" received magnesium sulfate 40 mg/kg intravenously (i.v.) as a bolus over 10 min before induction of anesthesia, followed by 15-30 mg/kg/h through infusion. "Esmolol group" received 0.5 mg/kg i.v. bolus over 10 min after induction followed by 150-300 μg/kg/min infusion and "control group" received normal saline in same volume schedule. The primary aim was to assess the quality of surgical field, using Fromme scale. Category Scale values of all the three groups were compared using Kruskal-Wallis analysis of variance (ANOVA) test. Hemodynamic data was compared using ANOVA test. Quality of the surgical field was better in both magnesium sulfate and esmolol groups as compared to the control group. Durations of anesthesia and surgery were significantly lower in esmolol group as compared to the control group. Blood loss was comparable in all the three groups. Quality of the surgical field was better in esmolol and magnesium sulfate groups as compared to control group. Duration of surgery was significantly less in esmolol group as compared to other two groups.


Genetic and environmental influences on internalizing psychopathology across age and pubertal development.
Symptoms of anxiety and depression are commonly comorbid and partially share a genetic etiology. Mean levels of anxiety and depression increase over the transition to adolescence, particularly in girls, suggesting a possible role of pubertal development in the activation of underlying genetic risks. The current study examined how genetic and environmental influences on anxiety and depression differed by chronological age and pubertal status. We analyzed composite scores from child self-reports and parent informant-reports of internalizing symptomology in a racially and socioeconomically diverse sample of 1,913 individual twins from 1,006 pairs (ages 8-20 years) from the Texas Twin Project. Biometric models tested age and pubertal status as moderators of genetic and environmental influences shared between and specific to anxiety and depression to determine whether etiology of internalizing symptomology differs across development as a function of age or puberty. Genetic influences did not increase as a function of age or puberty, but instead shared environmental effects decreased with age. In an exploratory model that considered the moderators simultaneously, developmental differences in etiology were reflected in genetic and environmental effects unique to depression. Results suggest that genetic variance in internalizing problems is relatively constant during adolescence, with environmental influences more varied across development. (PsycINFO Database Record


Polymorphism in the thymidylate synthase promoter enhancer region modifies the risk and survival of colorectal cancer.
Thymidylate synthase (TS) converts dUMP to dTMP, the rate-limiting nucleotide in DNA synthesis. It is also the target for 5-flurorouracil, the most common chemotherapy agent for treatment of colorectal cancer (CRC). We designed a nested case-control study within the prospective Physicians' Health Study to investigate whether TS polymorphisms independently predict risk of CRC and simultaneously the overall survival after the disease in the same population. We also investigated influences of this polymorphism on plasma folate and homocysteine levels. The study consists of 270 incident CRC and 454 control subjects. Risk of CRC was estimated by use of conditional multiple logistic regression analysis. Survival was analyzed by Cox proportional hazards regression analysis. Compared with the TS 3R/3R genotype, the multivariate-adjusted risk ratio was 0.86 (0.59-1.25) for the 2R/3R genotype and 0.59 (0.36-0.98) for the 2R/2R genotype with P for trend of 0.03. The TS 2R/2R genotype was also associated with better survival, although the results were not significant. Compared with those with either the 3R/3R or 2R/3R genotypes, the age-adjusted hazard ratio for the 2R/2R genotype was 0.57 (0.30-1.07). Individuals with the 2R/2R genotype had significantly lower plasma folate levels than those with the 3R/3R genotype, whereas their plasma homocysteine levels were unaffected by the TS promoter polymorphism. The deletion polymorphism at the TS 3'-untranslated region did not influence the CRC risk and survival, nor did it modify the plasma folate and total homocysteine levels. Given that individuals with high plasma folate had a better survival outcome with a hazard ratio of 0.68 (0.45-1.03) compared with those with low plasma folate, we conclude that the TS promoter polymorphism may modify both the risk and the survival of CRC; however, these effects do not appear to be mediated through its modulation of biological folate levels.


[The enhancement of the penetration of the human immunodeficiency virus into cells with the aid of a helper virus].
Penetration of human immunodeficiency virus (HIV) into the cells of lymphoblastoid T-cell line H9 was studied using 35S-methionine-labeled virus by demonstration of virus-specific proteins in the cytoplasm of the infected cells. Purification of the virus by ultracentrifugation through 30% glycerol was shown to lead to virus aggregation and its partial destruction manifested by the loss of gp120 protein, therefore unlabeled concentrated virus was used mainly with subsequent determination of virus-specific proteins by immune blotting. The addition of Sendai virus inactivated with UV rays to HIV increased the amount of HIV associated with cells as well as the amount of virus-specific proteins in the cytoplasm of the infected cells.


The Moderating Effect of Attention-Deficit Hyperactivity Disorder Symptoms on the Relationship Between Procrastination and Internalizing Symptoms in the General Adult Population.
Background: The symptoms of attention-deficit hyperactivity disorder (ADHD) are known to exacerbate the effect of cognitive-behavioral impairments on emotional burden. Although adults with ADHD frequently experience procrastination and internalizing symptoms such as depression and anxiety, few studies have examined whether the association between procrastination and internalizing symptoms differs by ADHD symptoms. Objective: This study aimed to examine the moderating effect of ADHD symptoms on the association between procrastination and internalizing symptoms. Method: A cross-sectional survey was conducted among 470 adults (mean age=26.57, standard deviation=2.93) using self-reported questionnaires: Adult ADHD Self-Report Scale, General Procrastination Scales, Patient Health Questionnaire-9, and State-Trait Anxiety Inventory. Conclusion: Participants with more substantial ADHD symptoms experienced more procrastination and internalizing symptoms than those with the less substantial ADHD symptoms. Therefore, procrastination constitutes the treatment target for those suffering from ADHD and comorbid internalizing symptoms. Alternatively, there was no enhancing effect of ADHD symptoms on the association between procrastination and internalizing symptoms. It is necessary to examine more precise and valid hypotheses and underlying mechanisms of procrastination in high and low ADHD symptom groups.


Economic burden of epilepsy in children: A population-based matched cohort study in Canada.
The economic burden of childhood epilepsy to the health care system remains poorly understood. This study aimed to determine phase-specific and cumulative long-term health care costs in children with epilepsy (CWE) from the health care payer perspective. This cohort study utilized linked health administrative databases in Ontario, Canada. Incident childhood epilepsy cases were identified from January 1, 2003 to June 30, 2017. CWE were matched to children without epilepsy (CWOE) on age, sex, rurality, socioeconomic status, and comorbidities, and assigned prediagnosis, initial, ongoing, and final care phase based on clinical trajectory. Phase-specific, 1-year and 5-year cumulative health care costs, attributable costs of epilepsy, and distribution of costs across different ages were evaluated. A total of 24 411 CWE were matched to CWOE. The costs were higher for prediagnosis and initial care than ongoing care in CWE. Hospitalization was the main cost component. The costs of prediagnosis, initial, and ongoing care were higher in CWE than CWOE, with the attributable costs at $490 (95% confidence interval [CI] = $352-$616), $1322 (95% CI = $1247-$1402), and $305 (95% CI = $276-$333) per 30 patient-days, respectively. Final care costs were lower in CWE than CWOE, with attributable costs at -$2515 (95% CI = -$6288 to $961) per 30 patient-days. One-year and 5-year cumulative costs were higher in CWE ($14 776 [95% CI = $13 994-$15 546] and $39 261 [95% CI = $37 132-$41 293], respectively) than CWOE ($6152 [95% CI = $5587-$6768] and $15 598 [95% CI = $14 291-$17 006], respectively). The total health care costs were highest in the first year of life in CWE for prediagnosis, initial, and ongoing care. Health care costs varied along the continuum of epilepsy care, and were mainly driven by hospitalization costs. The findings identified avenues for remediation, such as enhancing care around the time of epilepsy diagnosis and better care coordination for epilepsy and comorbidities, to reduce hospitalization costs and the economic burden of epilepsy care.


Combined Effect of Income and Medication Adherence on Mortality in Newly Treated Hypertension: Nationwide Study of 16 Million Person-Years.
Background Low socioeconomic status and poor medication adherence are known to be associated with increased morbidity and mortality among patients with hypertension, but their combined effects have not been studied. We therefore evaluated the joint association of household income and medication adherence with death and cardiovascular disease in patients newly treated for hypertension. Methods and Results This was a nationwide cohort study using the Korean National Health Insurance database. We included 1 651 564 individuals, aged 30 to 80 years, with newly treated hypertension and no prior cardiovascular disease and followed them for 10 years. Main exposures were household income in quintiles and adherence to antihypertensive medication, estimated by medication possession ratio: good (≥0.8), moderate (0.5 to <0.8), or poor (<0.5). The primary outcomes were all-cause and cardiovascular deaths. Higher mortality risk was observed in patients with low income (adjusted hazard ratio=1.50, 99% CI=1.46-1.53; lowest versus highest quintile) and poor medication adherence (adjusted hazard ratio=1.66, 99% CI=1.63-1.68; poor versus good adherence). When compared with the highest-income and good-adherence group, adjusted hazard ratio (99% CI) of death was 1.56 (1.52-1.61) for highest-income poor-adherers, 1.46 (1.41-1.51) for lowest-income good-adherers, and 2.46 (2.38-2.54) for lowest-income poor-adherers (P for interaction <0.001). Conclusions Low socioeconomic status and poor adherence to antihypertensive medication are associated with increased mortality and cardiovascular disease risks, but patients with low income are subject to larger excess risks by nonadherence. This highlights the potential importance of promoting medication adherence for risk reduction, especially in low-income patients with hypertension.


Health care practitioners' motivation for tobacco-dependence counseling.
Smoking cessation counseling by practitioners occurs at low rates in spite of strong evidence that counseling increases quit rates and reduces patient mortality. In a preliminary study, 1060 New York State physicians completed a survey concerning use of the Agency for Health Care Policy and Research (AHCPR) Guidelines, perceived autonomy and perceived competence for counseling, perceived autonomy support from insurers, and barriers to counseling. Considered together, perceived autonomy, perceived competence and perceived autonomy support predicted time devoted to counseling and use of the AHCPR guidelines. The primary, longitudinal study of 220 health care practitioners who attended a smoking cessation workshop predicted change in the practitioners' perceived autonomy and perceived competence for counseling as a function of the degree to which they experienced the workshop instructor as autonomy-supportive. In turn, change in perceived autonomy predicted change in time spent counseling and change in use of the AHCPR guidelines.


Nitric oxide-related toxicity in cultured astrocytes: effect of Bacopa monniera.
There is growing evidence that high concentrations of nitric oxide (NO), generated by activated astrocytes, might be involved in a variety of neurodegenerative diseases, such as Alzheimer's disease, ischemia and epilepsy. It has recently been suggested that glial cells may produce NO under superoxide radical stimulation by enzyme-independent mechanism. This suggests that also natural antioxidants may have therapeutical relevance in neurodegenerative diseases. Studies of Bhattacharya et al. have evidenced that Bacopa monniera (BM) (family Scrophulariaceae), an Ayurvedic medicinal plant clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative, is able to reduce the memory-dysfunction in rat models of Alzheimer's disease, but the molecular mechanisms of this action are yet to be determined. In the present study, we examined the effect of a methanolic extract of BM on toxicity induced by the nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP), in culture of purified rat astrocytes. Our results indicate that, after 18 h of treatment, SNAP induced an increase in the production of reactive species, but did not induce the rupture of cellular membrane. Conversely, this NO donor induced a fragmentation of genomic DNA compared to control astrocytes. The extract of BM inhibited the formation of reactive species and DNA damage in a dose dependent manner. This data supports the traditional use of BM and indicates that this medicinal plant has a therapeutic potential in treatment or prevention of neurological diseases.


Exploring opportunities for collaboration between the corporate sector and the dental education community.
The ultimate purpose of both dental industry and dental education is to improve the oral health of the public. This report provides background information on the different roles and objectives of the dental industry and dental education communities, the different operating environment of each sector and also areas of common interest where collaboration will be of mutual benefit. The report addresses five areas for potential collaboration between the dental industry and the dental education communities: 1. Contribution to joint activities. 2. Effectiveness and efficiency. 3. Workforce needs. 4. Middle- and low-income countries. 5. The future of International Federation of Dental Educators and Associations (IFDEA). The traditional areas of support and their limitations that have been provided by industry are outlined in the report and some new approaches for collaboration are considered. Industry-based research has been an important factor in developing new products and technologies and in promoting oral health. However there is a need to facilitate the introduction of these developments at an early stage in the education process. Industry has to operate in an efficient manner to remain competitive and maximise its returns and therefore survive. The academic sector operates in a different environment and under different governance structures; although some trends are noted towards adoption of greater efficiency and financial accountability similar to industry. Opportunities to jointly develop best business practices should be explored. Industry has responded well to the oral health needs of the public through the development of new products and technologies. The education community needs to respond in a similar way by examining different healthcare delivery models worldwide and developing programmes to train members of the dental team to cater for future needs and demands of communities in different regions of the world. The reputation of industry-based scientists and clinicians is high, and their role in contributing to the dental education process in practical ways needs to be explored and further developed. Closer relationships between industry scientists and faculty and students could assist industrys need and desire to develop new technologies for the broader dental care system. The corporate sector can play a key role in the future success of IFDEA by providing support and expertise in developing areas such as regional leadership institutes, a Global Faculty and Network and in collaborating in developing continuing education programmes as well as involvement in its governance. Thirteen recommendations are made in the report. These are considered to be important initial steps in developing the already strong relationship between the education and corporate sectors. Partnership and collaborating more effectively along the lines suggested should, almost certainly, generate mutually beneficial outcomes, whilst serving over the long term to elevate the publics oral health status on a global basis.


Inhibition of ERK1/2 improves lipid balance in rat macrophages via ABCA1/G1 and CD36.
ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), and macrophage scavenger receptor, cluster of differentiation (CD)36, function as key mediators of cholesterol efflux and influx from macrophages. In addition, they are associated with foam cell formation and the development of atherosclerosis (AS). The aim of the present study was to investigate the effects of extracellular signal-regulated kinases 1/2 (ERK1/2) inhibition on lipid balance in oxidized-low-density lipoprotein (Ox-LDL)-stimulated rat macrophages, and to examine the role of ERK1/2 inhibitors in AS. Rat peritoneal macrophages were treated with Ox-LDL alone or in combination with an ERK1/2 inhibitor, U0126, and untreated cells served as controls. Ox-LDL-induced lipid accumulation was detected by DiI fluorescence and oil red O staining. In addition, the mRNA and protein expression levels of ABCA1, ABCG1 and CD36 were determined using polymerase chain reaction and western blotting, respectively. Treatment with Ox-LDL significantly increased lipid accumulation and upregulated the mRNA and protein expression levels of ABCA1, ABCG1 and CD36 in macrophages. The addition of U0126 resulted in a marked reduction of lipid deposition, upregulation of ABCA1/G1 expression and suppression of CD36 expression in Ox-LDL-stimulated macrophages. The results of the present study indicated a novel association between ERK1/2 signaling and lipid metabolism, thus suggesting that inhibition of ERK1/2 may be considered a promising therapeutic strategy against AS.


The Effectiveness of Early Combined CO2 Ablative Fractional Laser and 595-nm Pulsed Dye Laser Treatment After Scar Revision.
Scars are significant complications of wound healing and associated with negative physical, psychological, and cosmetic effects. Scar revision and laser treatment have been used over the past century to improve many different types of scars. Here, we evaluated the effectiveness of early combined carbon dioxide ablative fractional laser (AFL) and pulsed dye laser (PDL) treatment after scar revision. Fourteen patients who underwent scar revision were enrolled. All patients were treated with both a 10,600-nm AFL and a 595-nm PDL commencing 2 weeks after scar revision and continuing at 4-week intervals for a total of 4 treatments. Vancouver Scar Scale scores were evaluated before treatment and 5 months after the final treatment. All Vancouver Scar Scale scores improved significantly except that of scar height. We encountered no adverse complications (wound disruption, or hyper- or hypopigmentation) during follow-up. Early combined carbon dioxide AFL and PDL treatment after scar revision effectively and safely minimized scar formation.


Incorporating plasticity of the interfibrillar matrix in shear lag models is necessary to replicate the multiscale mechanics of tendon fascicles.
Despite current knowledge of tendon structure, the fundamental deformation mechanisms underlying tendon mechanics and failure are unknown. We recently showed that a shear lag model, which explicitly assumed plastic interfibrillar load transfer between discontinuous fibrils, could explain the multiscale fascicle mechanics, suggesting that fascicle yielding is due to plastic deformation of the interfibrillar matrix. However, it is unclear whether alternative physical mechanisms, such as elastic interfibrillar deformation or fibril yielding, also contribute to fascicle mechanical behavior. The objective of the current work was to determine if plasticity of the interfibrillar matrix is uniquely capable of explaining the multiscale mechanics of tendon fascicles including the tissue post-yield behavior. This was examined by comparing the predictions of a continuous fibril model and three separate shear lag models incorporating an elastic, plastic, or elastoplastic interfibrillar matrix with multiscale experimental data. The predicted effects of fibril yielding on each of these models were also considered. The results demonstrated that neither the continuous fibril model nor the elastic shear lag model can successfully predict the experimental data, even if fibril yielding is included. Only the plastic or elastoplastic shear lag models were capable of reproducing the multiscale tendon fascicle mechanics. Differences between these two models were small, although the elastoplastic model did improve the fit of the experimental data at low applied tissue strains. These findings suggest that while interfibrillar elasticity contributes to the initial stress response, plastic deformation of the interfibrillar matrix is responsible for tendon fascicle post-yield behavior. This information sheds light on the physical processes underlying tendon failure, which is essential to improve our understanding of tissue pathology and guide the development of successful repair.


Estimation of Wound Area and Severity Level of Skin tear using Deep Learning Methods.
Skin tears occur mainly in older adults, making it difficult to identify the wound area and severity level when making care decision. We propose an algorithm for estimating the wound area and severity level of skin tears using a deep learning method. In this study, U-Net was used to estimate the skin tear area and VGG16 was used to estimate the severity level. The deep learning method shows an Intersection of Union (IoU) of 0.58 and 0.65 in estimating wound areas and purpura areas, and 62.2% accuracy in estimating severity levels. The proposed method outperforms the previous method using a classical machine learning method. This indicates that the proposed deep learning method is promising for image processing for skin tears, even if the skin tears include narrow wound edges and flaps, which are difficult to distinguish from the wound area.Clinical relevance-The proposed method can automatically estimate the area and severity level of skin tears to assist caregivers who are unfamiliar with skin tears.


Paper-Based Biosensors for COVID-19: A Review of Innovative Tools for Controlling the Pandemic.
The appearance and quick spread of the new severe acute respiratory syndrome coronavirus disease, COVID-19, brought major societal challenges. Importantly, suitable medical diagnosis procedures and smooth clinical management of the disease are an emergent need, which must be anchored on novel diagnostic methods and devices. Novel molecular diagnostic tools relying on nucleic acid amplification testing have emerged globally and are the current gold standard in COVID-19 diagnosis. However, the need for widespread testing methodologies for fast, effective testing in multiple epidemiological scenarios remains a crucial step in the fight against the COVID-19 pandemic. Biosensors have previously shown the potential for cost-effective and accessible diagnostics, finding applications in settings where conventional, laboratorial techniques may not be readily employed. Paper- and cellulose-based biosensors can be particularly relevant in pandemic times, for the renewability, possibility of mass production with sustainable methodologies, and safe environmental disposal. In this review, paper-based devices and platforms targeting SARS-CoV-2 are showcased and discussed, as a means to achieve quick and low-cost PoC diagnosis, including detection methodologies for viral genomic material, viral antigen detection, and serological antibody testing. Devices targeting inflammatory markers relevant for COVID-19 are also discussed, as fast, reliable bedside diagnostic tools for patient treatment and follow-up.


Oxygen therapy in chronic obstructive pulmonary disease.
Since the introduction of oxygen as a therapeutic agent 70 years ago, much has been learned regarding the detrimental effects of hypoxemia and the beneficial impact of oxygen therapy. It is projected that there are close to 800,000 patients receiving long-term oxygen therapy (LTOT) in the United States, at a cost of approximately $1.8 billion annually. The large numbers of patients receiving supplemental oxygen as treatment and the high costs incurred in providing oxygen therapy necessitate the practitioner to know the indications for LTOT as well its effects on survival, pulmonary hemodynamics, sleep, and exercise capacity. It is now recognized that the basis for LTOT prescription for all patients is founded on data that are over 25 years old and that only involve a very select cohort of patients. It is clear that further studies are required to assess the effects of oxygen on patients with chronic obstructive pulmonary disease with only mild hypoxemia, not only survival but also on neurocognitive function, quality of life, exercise physiology, and sleep quality. In addition, although proven to be safe when prescribed long term to individuals with lung disease, there are some concerns about worsening carbon dioxide retention and increased oxidant injury. The goals of this article are to briefly describe the indications for chronic oxygen administration, the physiologic effects of treatment, and potential toxicities, as well as its effect on morbidity and mortality.


The herpetofauna of Timor-Leste: a first report.
Fieldwork conducted throughout Timor-Leste in September 2004 and July 2009 resulted in a collection or recording of 263 herpetological specimens (100 amphibians, 163 reptiles), comprising at least seven species of frogs and toads, 20 species of lizards, seven species of snakes, two species of turtles, and one species of crocodile. Among the amphibians, the most frequently encountered species were toads (Duttaphrynus melanostictus), rice paddy frogs (genus Fejervarya), and rhacophorid treefrogs (Polypedates cf. leucomystax). All three variants of rice paddy frogs encountered represent undescribed species similar to Fejervarya verruculosa from neighboring Wetar Island. Records of Fejervarya cancrivora and Fejervarya limnocharis for Timor Island are apparently errors based on misidentification. We obtained voucher specimens for a total of 147 lizards and voucher photographs only for four specimens of Varanus timorensis. Aside from geckos frequently associated with human habitations (e.g., Gehyra mutilata, Gekko gecko, Hemidactylus frenatus, Hemidactylus platyurus), we discovered an as yet undescribed species of bent-toed gecko, genus Cyrtodactylus, in the Same valley. Our specimens of Hemidactylus platyurus are the first record of this species from Timor-Leste. Commonly encountered skinks included four-fingered skinks (genus Carlia), wedge skinks (genus Sphenomorphus), and night skinks (genus Eremiascincus). Notable among the 15 snakes collected was the frequency of pitvipers (Cryptelytrops insularis), which amounted to over 25% of all snakes. Our specimen of the wolfsnake Lycodon subcinctus is the first record of this species for Timor-Leste. Based on these findings, it appears that the biodiversity of amphibians and reptiles in this remote corner of Wallacea is much greater than previously thought, particularly with respect to scincid lizards. The detail we provide in the species accounts is designed to allow the use of this report as a preliminary field guide to the amphibians and reptiles of Timor-Leste. However, survey work is ongoing.


Infectious diseases among foreign prisoners: results of a hospital-based management model in Palermo.
Foreign prisoners have a high vulnerability in terms of morbidity and access to care in overcrowded Italian prisons. This paper presents and comments on the management model of infectious diseases in foreign prisoners at our outpatient clinic, in order to describe a model of management for these conditions. Overall, 133 subjects (mean age 35.5 years) from 29 countries were followed for a period of 15 years. The most commonly represented area of origin (54.1%) was the Maghreb region. HCV infection (40.6%), HIV (22.5%), HBV (9.8%) and co-infection (15%, HIV/HCV or HIV/HBV) were observed. Ten subjects had tuberculosis, and only 30% of them were compliant with the treatment. Only 46.3% of HCV mono-infected patients completed the entire diagnostic process and even a lower percentage (37%) of them took treatment regularly. 90% of HBV mono-infected patients and 84% of those HIV mono- and co-infected completed the diagnostic workout. 77% of patients in each group took therapy regularly. Overall, the results show limited effectiveness. Therefore, it would be necessary to improve communication between healthcare professionals and correctional systems. Moreover, it appears urgent to reduce overcrowding in prisons to limit morbidity in prisoners.


Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma.
Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness. In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT50)) ≥1/320 was the product of choice for the study. Between 2 May 2020 and 26 January 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median (interquartile range) volume of 884 (806-906) mL) convalescent plasma was administered and 80.68% of the units came from donors with neutralising antibody titres (NT50) ≥1/320. Median time from onset of symptoms to randomisation was 7 days. The proportion of patients alive and free of mechanical ventilation on day 15 was not different between both groups (convalescent plasma 83.74% (n=267) versus control 84.05% (n=137)) (OR 0.99, 95% CI 0.59-1.66; p=0.9772). The intervention did not change the natural course of antibody titres. The number of serious or severe adverse events was similar in both study arms and transfusion-related side-effects were reported in 19 out of 320 patients in the intervention group (5.94%). Transfusion of 4 units of convalescent plasma with high neutralising antibody titres early in hospitalised COVID-19 patients did not result in a significant improvement of clinical status or reduced mortality.


Shared goals for mental health research: what, why and when for the 2020s.
Mental health problems bring substantial individual, community and societal costs and the need for innovation to promote good mental health and to prevent and treat mental health problems has never been greater. However, we know that research findings can take up to 20 years to implement. One way to push the pace is to focus researchers and funders on shared, specific goals and targets. We describe a consultation process organised by the Department of Health and Social Care and convened by the Chief Medical Officer to consider high level goals for future research efforts and to begin to identify UK-specific targets to measure research impact. The process took account of new scientific methods and evidence, the UK context with a universal health care system (the NHS) and the embedded research support from the National Institute for Health Research Clinical Research Network, as well as the views of individual service users and service user organisations. The result of the consultation is a set of four overarching goals with the potential to be measured at intervals of three, five or ten years.


Inactivation of a fibronectin-binding TonB-dependent protein increases adhesion properties of Bacteroides fragilis.
Bacteroides fragilis is the Gram-negative strictly anaerobic bacterium most frequently isolated from clinical infections, including intra-abdominal abscess and bacteraemia. A number of factors can contribute to its virulence, including the expression of adhesins. Some of them are already characterized and can recognize and bind to extracellular matrix components, such as fibronectin. One of the molecules responsible for fibronectin-binding is an outer-membrane protein previously described by our group, which belongs to the TonB-dependent family. The aim of the present work was to characterize this protein. Initially, it was confirmed by fluorescence and electron microscopy that the fibronectin-binding molecules were located in the bacterial surface, but the distribution of these molecules on the surface was not uniform. To further evaluate the role of this protein, the gene bf1991, responsible for encoding this protein, was inactivated by a suicide vector and the mutant strains generated were used in several experiments to verify possible phenotypical alterations. In adherence assays with fibronectin immobilized on latex beads an increased adhesion was observed with the mutant strains compared with the wild-type strain. Western blot analysis in the mutant strain revealed the absence of the 120 kDa TonB-dependent outer-membrane protein and an alteration in the expression of an unknown 30 kDa protein. Killing assays using peritoneal macrophages were performed to evaluate the role of this protein as a virulence attribute and it was observed that the mutant strains were more efficiently internalized than the wild-type strains, with more internalization in the samples covered with fibronectin than in the samples not covered with it.


Observations on Osteoporosis in Three Generations of Descendants of Holocaust Survivors.
Throughout history, studies on episodes of famine have led to the discovery of metabolic abnormalities and hormonal aberrations as well as an increased incidence of cancer and mental health conditions. Starvation during early life is thought to nfluence the programming of childhood and adult bone metabolism, which may result in poor bone health in later life. This observational case series includes a small group (with no control group) of famine-exposed Holocaust survivors and their descendants. We proposed an investigational mechanism to determine any association between starvation and osteoporosis, both in the individual survivors and in their descendants.


[On the way to our 200th anniversary].
The Dutch Journal of Medicine celebrates 150 years of continuous publication and looks forward to the next 50 years, notwithstanding the hazards offorecasting. In the coming years, the practice of medicine will see more teamwork and more specialisation, but the core process will remain personal counselling by a physician who manages to address somatic and psychological factors. Medical research will continue to include patients as well as molecules, but clinical trials will be threatened by overregulation through bureaucracy and legalism. Despite easy access to search facilities in the digital era, the future of general medical journals in local languages seems assured, because physicians need to keep abreast of developments in other specialties; the only uncertainty is whether these journals will continue to be read on paper.


Which patients with inoperable vulvar cancer may benefit from brachytherapy in addition to external beam radiation? A Surveillance, Epidemiology, and End Results analysis.
It is unknown whether brachytherapy after external beam radiation (EBRT + BT) results in improved outcomes compared with EBRT alone for patients with inoperable vulvar cancer. The purpose of this study was to compare survival outcomes for patients who received these treatment modalities. Data between 1973 and 2011 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients with Federation of International Gynecologists and Obstetricians stage I-IVA vulvar cancer treated with definitive EBRT + BT or EBRT alone were included. Patients with prior surgical resection were excluded. Disease-specific survival (DSS) and overall survival were compared using the Kaplan-Meier method and Cox proportional hazard models. A total of 649 patients were analyzed, of which 617 received EBRT alone and 32 received EBRT + BT. Median follow-up was 33 months in surviving patients. The use of brachytherapy declined from 16% of cases treated in 1973-1980 to 4% in 2001-2011 (p = 0.04). EBRT + BT vs. EBRT alone was not significantly associated with improved DSS (45% vs. 33% at 5 years) or overall survival (34% vs. 24% at 5 years) on univariate or multivariate analyses. On post hoc subgroup analyses, brachytherapy consolidation was associated with higher 5-year DSS in a composite subgroup that included patients with stage IVA disease, tumor >4 cm, or node-positive disease (52% vs. 27%, p = 0.02). Utilization of BT consolidation with EBRT for vulvar cancer is declining in the United States. EBRT + BT is not associated with improved survival compared with EBRT alone in the overall group of patients. Certain subgroups of patients might benefit from brachytherapy, but this hypothesis requires validation in future studies.


Probiotic Bacillus amyloliquefaciens SC06 Prevents Bacterial Translocation in Weaned Mice.
Probiotic is a preparation containing microorganisms that confers beneficial effect to the host. This work assessed whether oral administration of Bacillus amyloliquefaciens SC06 (Ba) could decrease bacterial translocation in weaned mice. Weaned C57BL/6 were randomly allocated into three groups: group I as the control group, group II were treated with 0.85 % NaCl. Group III was administered with probiotic Ba 1 × 10(9) CFU/day dissolved in 100 μl of 0.85 % NaCl for 30 days. Mice were then sacrificed, and tissue were cultured to determine bacterial translocation. Meanwhile, splenic CD4(+)T cells, CD8(+)T cells, B cells, and macrophages were analysised by FACS. Our results showed that probiotic Ba significantly reduced bacteria translocation compared with the control group and 0.85 % NaCl group (P < 0.05), lower levels of bacteria were detected in the MLN, liver, spleen, and kidney of mice. Moreover, significant increase in percentage and number of macrophages were observed in the spleen of Ba-treated mice compared with the control and 0.85 % NaCl groups. Together, these data indicated that Ba could decrease bacterial translocation in weaned mice. This effect seems to be correlated with the changes of macrophage numbers.


Detection and Cryoprotective Activity of Dehydrin Proteins from Rice Bran and Soybean Whey.
Dehydrin proteins, group2 LEA proteins in rice bran and soybean whey were analyzed by two-dimensional (2D) electrophoresis, and the cryoprotective activity on freeze/thaw inactivation of lactate dehydrogenase was examined as a criterion of its function. Dehydrins in rice bran were detected by immunoblotting using antibody raised against a conserved lysine-rich motif sequence. In the water-soluble fraction of rice bran, 10 spots of 44 kDa and 23 kDa dehydrin-like polypeptides were detected on the immunoblotted membrane. Isoelectric points of the polypeptides were between 6.6 and 7.4. The 23 kDa dehydrin polypeptide was partially purified by ammonium sulfate fractionation and ion exchange column chromatography. CP50 value, protein amount necessary to keep 50% of enzyme activity, of the 23 kDa dehydrin was 0.78 μM (15.6 μg/mL), slightly lower than that of bovine serum albumin. Heat-soluble soybean whey proteins were analyzed by SDS-PAGE and 2D-electrophoresis. Dehydrin appeared to be the most abundant protein in the fraction. CP50 value for heat-soluble whey protein was estimated to be 15.8 μg/mL, while that of total whey was 355 μg/mL. The result indicated that simple heat fractionation is efficient to concentrate cryoprotective protein from soybean whey.


Effect heterogeneity and variable selection for standardizing causal effects to a target population.
The participants in randomized trials and other studies used for causal inference are often not representative of the populations seen by clinical decision-makers. To account for differences between populations, researchers may consider standardizing results to a target population. We discuss several different types of homogeneity conditions that are relevant for standardization: Homogeneity of effect measures, homogeneity of counterfactual outcome state transition parameters, and homogeneity of counterfactual distributions. Each of these conditions can be used to show that a particular standardization procedure will result in an unbiased estimate of the effect in the target population, given assumptions about the relevant scientific context. We compare and contrast the homogeneity conditions, in particular their implications for selection of covariates for standardization and their implications for how to compute the standardized causal effect in the target population. While some of the recently developed counterfactual approaches to generalizability rely upon homogeneity conditions that avoid many of the problems associated with traditional approaches, they often require adjustment for a large (and possibly unfeasible) set of covariates.


A New Microtia Reconstruction Method Using Delayed Postauricular Skin Flap.
This article presents a new microtia reconstruction method using a delayed postauricular skin flap. The surgery is scheduled in three stages, the first of which delays the postauricular skin flap and deals with the remnant auricle. Three weeks later, the second stage is carried out. An erect, three-dimensional ear framework fabricated from autogenous rib cartilage is inserted between two flaps. The anterior auricular surface of the framework is draped with the delayed skin flap, and the postauricular surface is draped with postauricular fascia and overlying grafted skin. Six months later, the third stage reconstructs the tragus and shapes a hollow mimicking the external auditory meatus, and locally improves the reconstructed auricle. Ninety-six cases of microtia were reconstructed using the delayed skin flap. All ear reconstructions were successful, with good locations, sizes, and shapes, with few complications. The authors' method enables an adequately large, thin skin flap with sufficient blood supply, and also appropriately manages the remnant auricle. A delayed postauricular skin flap with a three-dimensional autologous costal cartilage framework represents a promising approach to microtia reconstruction.


On the iterative methods of linearization, decrease of order and dimension of the Karman-type PDEs.
Iterative methods to achieve a suitable linearization as well as a decrease of the order and dimension of nonlinear partial differential equations of the eighth order into the biharmonic and Poisson-type differential equations with their simultaneous linearization are proposed in this work. Validity and reliability of the obtained results are discussed using computer programs developed by the authors.


Physicochemical characteristics of quinupramine in the EVA matrix.
Ethylene-vinyl acetate (EVA) is widely used as a membrane or matrix for transdermal drug delivery systems. In an attempt to determine the state of a drug in the EVA matrix, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and thermal analysis of the quinupramine-EVA matrix were carried out and the results were compared with those of a physical mixture of quinupramine and EVA at the same ratio. The 1:2 matrix of quinupramine with EVA was prepared using the casting method. The XRD pattern of the quinupramine test preparations revealed that the pure quinupramine was crystalline in nature, whereas the quinupramine in the EVA matrix was an amorphous form, which leads to increased drug release. The FT-IR spectra of quinupramine in the physical mixture showed absorption bands at around 3000-3050 cm(-1) whereas these absorption bands were not observed in the quinupramine-EVA matrix. The thermal studies of quinupramine in the physical mixture showed an endothermic peak at 154-156 degrees C, which is the melting point of the drug, but there was no such endothermic peak observed in the EVA matrix. In conclusion, the physicochemical interactions between quinupramine and EVA, might occur at the molecular level, and that quinupramine was not crystalline in the EVA matrix.


Regulation of fission yeast mating-type interconversion by chromosome imprinting.
Mating types of the fission yeast Schizosaccharomyces pombe interchange nonrandomly in a cell lineage so that only one cell among four granddaughters of a cell ever switches, and the sister of the newly switched cell switches efficiently in consecutive cell divisions, thereby producing chains of recurrent switching. The programme of cellular differentiation is mediated by inheritance of parental DNA chains at the mating type locus (mat1) by progeny cells. This review summarizes recent results suggesting that two types of imprinting events at the mat1 locus are required to generate the specific pattern of switching in a cell lineage. One of those is a site- and strand- specific event that is required before the mat1 locus can be cleaved in vivo. The other is a double-stranded break at mat1 that is healed by gene conversion in the progeny cells resulting in switching the mat1 locus.


Eruption of el chichon volcano, chiapas, Mexico, 28 march to 7 april 1982.
El Chichón volcano erupted at 2322 hours on 28 March 1982 after being dormant during historic times. Three major eruptions of tephra occurred between that date and 7 April, discharging approximately 0.3 cubic kilometer of andesitic pyroclastic material. The initial eruption produced crystal-rich tephra of higher silica and alkali content than the lithic pyroclastic materials of the second and third eruptions. The initial tephra consists of primarily juvenile materials, whereas the later eruptions produced both lithic and juvenile fractions.


Study of Electrophysiological Changes in Sensory Nerves Among Diabetic Smokers.
Neuropathy is one of the most troublesome complication affecting individuals with diabetes. The resultant loss of function in peripheral nerves causes loss of protective sensations and impairs patient's ability to perceive incipient or even apparent ulcerations in the feet. This study was undertaken to test the hypothesis of alteration in electrophysiological parameters of nerve before actual manifestations of neuropathy in type 2 diabetic patients and to analyse the effect of smoking on Sensory Nerve Conduction Velocity (SNCV) of diabetic subjects. One hundred and twenty diagnosed diabetics were taken as cases while 30 healthy non diabetics were taken as control. Case group was divided into diabetic non-smoker and diabetic smoker. Diabetic smoker were further subdivided into light smoker, moderate smoker and heavy smoker according to smoking index. After detailed history and physical examination SNCV of median and ulnar nerve in upper limb and sural nerve in lower limb was performed. On comparison of SNCV of median and ulnar nerve of upper limb and sural nerve of lower limb between control and diabetic non-smoker only sural nerve of diabetic non smoker showed significant bilateral decrease. There was significant bilateral decrease in SNCV of median and ulnar nerve of diabetic heavy smoker when compared to control and diabetic non smoker. Similarly, SNCV of sural nerve of diabetic heavy smoker was significantly decreased when compared with control, diabetic non-smoker, diabetic light and moderate smoker. A negative and statistically significant correlation was found between SNCV and smoking index. Present study indicates that nerves of lower limbs are more susceptible to diabetic assault as compared to upper limb suggesting that long nerves are commonly affected. Also, apart from duration and severity of diabetes, smoking itself is an independent factor for diabetic neuropathy.


Desmoid-type fibromatosis-associated Gardner fibromas: prevalence and impact on local recurrence.
Although Gardner fibroma is a precursor lesion of desmoid tumor, the prevalence and prognostic importance of Gardner fibroma associated with desmoid tumors has not been systematically studied in adults. From 129 patients with desmoid-type fibromatosis, 170 specimens were re-examined for the presence of an associated Gardner fibroma. Clinicopathologic features of Gardner fibroma-associated desmoid-type fibromatosis were compared to desmoid tumors without associated Gardner fibroma. Recurrence-free survival was compared using multivariate Cox proportional hazard regression to account for known confounding factors. Of 104 evaluable primary desmoid tumor resections, 25 (24%) had an associated Gardner fibroma. When previous incisional biopsies and resection specimens of locally recurrent desmoid tumors were also examined, the overall prevalence of associated Gardner fibroma was 37%. Desmoid tumors arising in high risk anatomic sites (extremities or deep soft tissues of the back and chest wall) were more often associated with Gardner fibroma than tumors at other sites. Median recurrence-free survival for patients with Gardner fibroma-associated desmoid-type fibromatosis was 3.2 years, whereas median survival for patients without associated Gardner fibroma was >25 years (hazard ratio 2.8; P = 0.001). Although the presence of Gardner fibroma had no impact on the recurrence rate of desmoid tumors arising at high risk anatomic sites, associated Gardner fibroma increased the risk of recurrence 4-fold for desmoid tumors at low risk anatomic sites. Associated Gardner fibroma is under-recognized in desmoid-type fibromatosis and increases the risk of local recurrence for a subgroup of patients.


Threats of global warming to the world's freshwater fishes.
Climate change poses a significant threat to global biodiversity, but freshwater fishes have been largely ignored in climate change assessments. Here, we assess threats of future flow and water temperature extremes to ~11,500 riverine fish species. In a 3.2 °C warmer world (no further emission cuts after current governments' pledges for 2030), 36% of the species have over half of their present-day geographic range exposed to climatic extremes beyond current levels. Threats are largest in tropical and sub-arid regions and increases in maximum water temperature are more threatening than changes in flow extremes. In comparison, 9% of the species are projected to have more than half of their present-day geographic range threatened in a 2 °C warmer world, which further reduces to 4% of the species if warming is limited to 1.5 °C. Our results highlight the need to intensify (inter)national commitments to limit global warming if freshwater biodiversity is to be safeguarded.


Preanalytical Quality Evaluation of Citrate Evacuated Blood Collection Tubes-Ultraviolet Molecular Absorption Spectrometry Confronted with Ion Chromatography.
We previously enabled a direct insight into the quality of citrate anticoagulant tubes before their intended use for specimen collection by introducing an easy-to-perform UV spectrometric method for citrate determination on a purified water model. The results revealed differences between the tubes of three producers, Greiner BIO-ONE (A), LT Burnik (B), and BD (C). It became apparent that tubes C contain an additive, which absorbs light in the ultraviolet range and prevents reliable evaluation of citrate anticoagulant concentration with the suggested method. In this research, we re-evaluate the quality of citrate-evacuated blood collection tubes by complementing UV spectrometry with ion chromatography. (1) Comparable results were obtained for tubes B at 220 nm. (2) Citrate concentrations determined with ion chromatography were lower for tubes A and C. Chromatograms reveal additional peaks for both. (3) Influences of heparin on absorption spectra and chromatograms of citrate were studied. Some similarities with the shape of the anticoagulant spectra of tubes A and C were observed, and the lithium heparin peak in chromatograms is close to them, but a confident judgment was not possible. (4) Contamination of anticoagulant solution with potassium, magnesium, and calcium was confirmed for all the brands, and contamination with lithium for B and C.


Matchplay characteristics of Grand Slam tennis: implications for training and conditioning.
The purpose of this study was to probe the sex-based differences in the stroke and movement dynamics of Grand Slam hard-court tennis. Player and ball tracking data were collated for 102 male and 95 female players during the 2012-2014 Australian Open tournaments. Serve, serve return, groundstroke and movement data were compared between sexes. Serve statistics were the subject of the largest differences, with males achieving significantly faster speeds, aces and unreturned serves while also winning a greater percentage of service points. When returning serve, women contacted the ball closer to the net, lower to the ground and achieved flatter ball trajectories than males. Groundstroke frequencies were similar between sexes, although males hit with greater speed, flatter trajectories and impacted more shots inside the baseline. Distance covered per set or during points won or lost was not sex dependent, yet men exhibited faster average movement speeds. These findings highlight the need for sex-specific training and practice designs that cater to the different stroke dynamics, particularly in relation to the first serve and serve-return, as well as movement speeds.


The association of physical activity and cardiorespiratory fitness with β-cell dysfunction, insulin resistance, and diabetes among adults in north-western Tanzania: A cross-sectional study.
Research on the associations of physical activity and cardiorespiratory fitness with β-cell dysfunction and insulin resistance among adults in Sub-Saharan Africa (SSA) is limited. We assessed the association of physical activity and cardiorespiratory fitness with β-cell function, insulin resistance and diabetes among people living with HIV (PLWH) ART-naïve and HIV-uninfected Tanzanian adults. In a cross-sectional study, we collected data on socio-demography, anthropometry, fat mass and fat free mass and C-reactive protein. Data on glucose and insulin collected during an oral glucose tolerance test were used to assess β-cell dysfunction (defined as insulinogenic index <0.71 (mU/L)/(mmol/L), HOMA-β index <38.3 (mU/L)/(mmol/L), and overall insulin release index <33.3 (mU/L)/(mmol/L)), oral disposition index <0.16 (mU/L)/(mg/dL)(mU/L)-1, insulin resistance (HOMA-IR index >1.9 (mU/L)/(mmol/L) and Matsuda index <7.2 (mU/L)/(mmol/L), prediabetes and diabetes which were the dependent variables. Physical activity energy expenditure (PAEE), sleeping heart rate (SHR), and maximum uptake of oxygen during exercise (VO2 max) were the independent variables and were assessed using a combined heart rate and accelerometer monitor. Logistic regressions were used to assess the associations. Of 391 participants, 272 were PLWH and 119 HIV-uninfected. The mean age was 39 ( ± 10.5) years and 60% (n=235) were females. Compared to lower tertile, middle tertile of PAEE was associated with lower odds of abnormal insulinogenic index (OR=0.48, 95%CI: 0.27, 0.82). A 5 kj/kg/day increment of PAEE was associated with lower odds of abnormal HOMA-IR (OR=0.91, 95%CI: 0.84, 0.98), and reduced risk of pre-diabetes (RRR=0.98, 95%CI: 0.96, 0.99) and diabetes (RRR=0.92, 95%CI: 0.88, 0.96). An increment of 5 beats per min of SHR was associated with higher risk of diabetes (RRR=1.06, 95%CI: 1.01, 1.11). An increase of 5 mLO2/kg/min of VO2 max was associated with lower risk of pre-diabetes (RRR=0.91, 95%CI: 0.86, 0.97), but not diabetes. HIV status did not modify any of these associations (interaction, p>0.05). Among Tanzanian adults PLWH and HIV-uninfected individuals, low physical activity was associated with β-cell dysfunction, insulin resistance and diabetes. Research is needed to assess if physical activity interventions can improve β-cell function and insulin sensitivity to reduce risk of diabetes and delay progression of diabetes in SSA.


Soft cup vacuum extraction: a comparison of outlet delivery.
One hundred eighteen nulliparous patients delivered under conduction anesthesia who met the standard criteria for low forceps delivery were randomly assigned to one of three groups to be delivered by low Tucker-McLane forceps, Silastic vacuum extraction system, or Mityvac vacuum extractor. Significant maternal soft tissue trauma was identified in 48.9% of the forceps group, 36.1% of the Silastic group, and 21.6% of the Mityvac group. Superficial fetal scalp changes were found in 71% of the forceps group, 44% of the Silastic group, and 46% of the Mityvac group. Of these, cephalhematomatas were noted in 2.2% of the forceps group, 13.9% of the Silastic group, and 16.2% of the Mityvac group. All three instruments were considered effective outlet delivery instruments.


A severe case of thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly syndrome with myocardial and skeletal muscle calcification despite hypocalcemia: a case report.
TAFRO (thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly) syndrome is a recently recognized disease with a variety of presentations of variable severity. In acute settings, this disease also involves organ dysfunction because of the associated systemic inflammation. However, cases of TAFRO syndrome with myocardial and/or skeletal muscle calcification have never been reported. A 24-year-old healthy young Asian man was admitted with intermittent epigastric pain and fever for 2 weeks. Computed tomography revealed pleural effusion, ascites and systemic lymphadenopathy. Laboratory tests showed thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, anemia and renal dysfunction. Based on these findings and bone marrow biopsy, we diagnosed his disease as TAFRO syndrome and commenced hemodialysis for the renal dysfunction. However, he developed refractory hypocalcemia with unstable vital signs, for which we administered calcium gluconate hydrate. Thereafter, myocardial and skeletal muscle calcification was revealed radiologically, with the myocardial calcification causing sick sinus syndrome. He was treated with tocilizumab and finally discharged in an ambulatory condition after prolonged hospitalization, with residual calcific lesions. This is the first report of a patient with TAFRO syndrome and the complication of organ calcification. The etiology of calcification in this case is not clear. Systemic inflammation with possible hypercytokinemia might have been involved in the unexpected complication of systemic calcification. It is important to carefully handle the general management of TAFRO syndrome because of the possibility of various complications.


Comparison of polyhexanide, cold atmospheric plasma and saline in the treatment of canine bite wounds.
To compare the efficacy of polyhexanide, cold argon plasma and saline in reducing bacterial bio-burden in dog bite wounds. Prospective blinded randomised clinical trial. Dogs were randomly assigned to one of the treatment groups by lottery and bacterial cultures obtained before and after treatment were compared. Bite wounds were surgically debrided and treated with polyhexanide, cold argon plasma or saline lavage. All wounds were cultured three times: directly after debridement, directly after prelavage with 2 mL/cm2 (saline in the saline and cold argon plasma group, or polyhexanide) and following the definitive lavage. Data were analysed using a generalised linear model for ordinal data. A total of 85 dogs were enrolled in this study (polyhexanide n=29, cold argon plasma n=28, saline n=28). Positive bacterial culture results after debridement were obtained in 53/85 (62.3%) wounds. Polyhexanide and saline lavage significantly reduced the bio-burden, while cold argon plasma treatment did not. This effect was evident after prelavage when polyhexanide performed significantly better than saline and cold argon plasma as well as after final treatment. No significant differences were detected after prelavage or main treatment between saline and cold argon plasma. Polyhexanide lavage achieved the best immediate and ultimate decontamination of bite wounds.


Origin of cortical microtubules organized at M/G1 interface: recruitment of tubulin from phragmoplast to nascent microtubules.
The origin of cortical microtubules (CMTs) was investigated in transgenic BY-2 cells stably expressing a GFP (green fluorescent protein) -tubulin fusion protein (BY-GT16). In a previous study, we found that CMTs were initially organized in the perinuclear regions but then elongated to reach the cell cortex where they formed bright spots, and that the appearance of parallel MTs from the bright spots was followed by the appearance of transverse MTs (Kumagai et al., Plant Cell Physiol. 42, 723-732, 2001). In this study, we investigated the migration of tubulin to the reorganization sites of CMTs at the M/G1 interface. After synchronization of the BY-GT16 cells by aphidicolin, the localization of GFP-tubulin was monitored and analyzed by deconvolution microscopy. GFP-tubulin was found to accumulate on the nuclear surface near the cell plate at the final stage of phragmoplast collapse. Subsequently, GFP-tubulin accumulated again on the nuclear surface opposite the cell plate, where nascent MTs elongated to the cell cortex. The significance of these observations on the mode of CMT organization is discussed.


Comorbid depressive and anxiety symptoms and the risk of type 2 diabetes: Findings from the Lifelines Cohort Study.
Prior studies indicate that depression is a risk factor for type 2 diabetes (T2D), though there is considerable heterogeneity in reported estimates. Identifying homogeneous subgroups of depression strongly associated with T2D may be beneficial. This study examined associations between depression and anxiety comorbidity with the risk of T2D. 78,025 participants from the Lifelines Cohort Study (age range = 30-75 years) without diabetes at baseline were included in this study. The Mini-International Neuropsychiatric Interview assessed depressive and anxiety symptoms at baseline. Incident T2D was assessed by self-report or hemoglobin A1c levels during an approximately 3.8-year follow-up period. Risk of T2D was compared across four groups (no depressive or anxiety symptoms, depressive symptoms alone, anxiety symptoms alone, comorbid depressive/anxiety symptoms) using mixed effects logistic regression analyses adjusted for sociodemographic, lifestyle, and cardiometabolic characteristics. 1,096 participants developed diabetes. Compared to those without depressive or anxiety symptoms (n = 74,467), those with comorbid depressive and anxiety symptoms (n = 743) were more likely to develop T2D (n = 28, OR = 2.12, 95% CI = 1.22-3.68). Depressive symptoms alone (n = 650) and anxiety symptoms alone (n = 2,165) were not significantly associated with T2D (n = 23 and n = 24, respectively, developed diabetes). Those with comorbid symptoms were also more likely to develop T2D compared to those with depressive symptoms alone (OR = 2.86, 95% CI = 1.25-6.54). Depressive and anxiety symptom assessments were based on a screening tool. Hemoglobin A1c data were only available for a subset of participants. Depression with comorbid anxiety may be a subgroup of depression that is strongly associated with the risk of T2D.


Relationships of iron metabolism with insulin resistance and glucose levels in young and healthy adults.
Several biomarkers within the iron metabolism pathway have been related to the occurrence of diabetes mellitus, but underlying mechanisms are unknown. The aim of our study was to investigate the differential relationships of iron metabolism with a broad range of diabetes markers in young and healthy adults. 2160 participants aged 25 to 41years were enrolled in a population-based study. Established cardiovascular disease, diabetes or a body mass index >35kg/m(2) were exclusion criteria. Multivariable linear regression models were built to assess the associations of ferritin and transferrin saturation (TSAT) with blood levels of glucagon-like peptide-1 (GLP-1), insulin, homeostatic model assessment-insulin resistance (HOMA-IR), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Median (interquartile range) age was 37 (31, 40) years. In multivariable linear regression analyses, β-coefficients (95% confidence intervals) per 1-SD increase in ferritin were 0.04 (0.02; 0.07, p=0.0008) for GLP-1, 0.06 (0.04; 0.08, p<0.0001) for insulin, 0.07 (0.04; 0.09, p<0.0001) for HOMA-IR, 0.004 (-0.00; 0.01, p=0.07) for FPG and -0.003 (-0.01; -0.00, p=0.07) for HbA1c. β-coefficients (95% CI) per 1-SD increase in TSAT were -0.07 (-0.09; -0.05, p<0.0001) for GLP-1, -0.06 (-0.08; -0.04, p<0.0001) for insulin, -0.07(-0.09; -0.05, p<0.0001) for HOMA-IR, -0.01 (-0.01; -0.00, p<0.0001) for FPG and -0.01 (-0.01; -0.00, p=0.0004) for HbA1c. Markers of insulin resistance are strongly related with markers of iron metabolism in healthy subjects. These relationships were inconsistent and weaker for short-term and long-term glucose levels. These results may provide insights in the relationships between iron metabolism and diabetes occurrence.


Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats.
Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries. These effects were similar to those of hCG, although in some cases they were less pronounced. TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis.


Predictors of mortality in patients with type 2 diabetes with or without diabetic nephropathy: a follow-up study.
To evaluate the prognostic significance of cardiovascular risk factors including 24-h ambulatory blood pressure level and rhythm for all-cause mortality in type 2 diabetic patients. In a prospective observational study, 104 patients with type 2 diabetes were followed: 51 patients with diabetic nephropathy and 53 patients with persistent normoalbuminuria. At baseline, 24-h ambulatory blood pressure, left ventricular hypertrophy, glomerular filtration rate and cardiac autonomic neuropathy were measured. Blood samples were taken and patients answered a World Health Organization questionnaire. Dipping was calculated as the average nocturnal reduction in systolic and diastolic blood pressure. Mean follow-up was 9.2 years (range 0.5-12.9). During follow-up, 54 of 104 patients died. Sixteen patients (15%) had higher blood pressure at night than during the day (reversed pattern); 14 of these patients died (88%), compared to 40 of 88 patients (45%) with reduced dipping or normal dipping; log rank P = 0.001. In a Cox regression analysis, predictors of all-cause mortality were: age, male sex, presence of left ventricular hypertrophy, glycated haemoglobin A1c (HbA1c), daytime systolic blood pressure, cardiac autonomic neuropathy, glomerular filtration rate and dipping (1% increase; hazard ratio 0.97, 95% confidence interval 0.94-0.998, P = 0.033). Type 2 diabetes patients with non-dipping of night blood pressure were at higher risk of death as compared to dippers, independent of known cardiovascular risk factors. Since non-dipping has a high prevalence in patients with diabetic nephropathy, 24-h ambulatory blood pressure should be used to assess a full risk profile and blood pressure-lowering therapy in these patients.


Benchmarking the lithium-thiophene complex.
The equilibrium geometry and the binding energy of the lithium-thiophene complex are determined by means of an accurate composite scheme. The scheme is based on approximate explicitly correlated coupled-cluster theory with single and double excitations extended by higher-level excitations. Core correlation effects as well as relativistic, diagonal Born-Oppenheimer, and counterpoise corrections are also taken into account. The best estimate of the binding energy amounts to D(e)=41.2 kJ mol(-1), with a 95% confidence interval of ±1.0 kJ mol(-1).


Exercise capacity and mortality in older men: a 20-year follow-up study.
Epidemiological findings, based largely on middle-aged populations, support an inverse and independent association between exercise capacity and mortality risk. The information available in older individuals is limited. Between 1986 and 2008, we assessed the association between exercise capacity and all-cause mortality in 5314 male veterans aged 65 to 92 years (mean+/-SD, 71.4+/-5.0 years) who completed an exercise test at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, Calif. We established fitness categories based on peak metabolic equivalents (METs) achieved. During a median 8.1 years of follow-up (range, 0.1 to 25.3), there were 2137 deaths. Baseline exercise capacity was 6.3+/-2.4 METs among survivors and 5.3+/-2.0 METs in those who died (P<0.001) and emerged as a strong predictor of mortality. For each 1-MET increase in exercise capacity, the adjusted hazard for death was 12% lower (hazard ratio=0.88; confidence interval, 0.86 to 0.90). Compared with the least fit individuals (< or =4 METs), the mortality risk was 38% lower for those who achieved 5.1 to 6.0 METs (hazard ratio=0.62; confidence interval, 0.54 to 0.71) and progressively declined to 61% (hazard ratio=0.39; confidence interval, 0.32 to 0.49) for those who achieved >9 METs, regardless of age. Unfit individuals who improved their fitness status with serial testing had a 35% lower mortality risk (hazard ratio=0.65; confidence interval, 0.46 to 0.93) compared with those who remained unfit. Exercise capacity is an independent predictor of all-cause mortality in older men. The relationship is inverse and graded, with most survival benefits achieved in those with an exercise capacity >5 METs. Survival improved significantly when unfit individuals became fit.


A cross-sectional study of musculoskeletal symptoms and risk factors in semiconductor workers.
As part of the cross-sectional component of the Semiconductor Health Study, we assessed prevalence of specific musculoskeletal symptoms and their association with possible ergonomic risk factors. A total of 3,175 persons (78% participation rate) from eight manufacturing sites across the U.S. completed a health and work questionnaire. Using logistic regression methods to adjust for nonoccupational factors, we compared musculoskeletal symptom (self report) prevalence among fabrication room (fab) and nonfab workers, among specific work process groups, and among workers exposed to selected ergonomic stressors. Overall, seven of 12 musculoskeletal outcomes were significantly more prevalent among fab workers. Distal upper-extremity symptoms were more common among fab than nonfab workers [relative risk (RR) = 1.44, 95% confidence interval (CI) = 1.26-1.63] and showed a dose-response effect with hours per day spent in the fab; increased risk was associated with frequency of lifting and with use of vacuum wands and projection aligners. Female sex and high somatization index score were associated with increased reporting for all musculoskeletal outcomes.


[Ectopic pregnancy in cesarean scar].
The ectopic pregnancy within a cesarean scar, is defined as the implantation of the blastocyst outside the endometrium in the site where the histerotomy was made in the previous cesarean. We report a case of a 35-year-old patient, which arrives to the emergency room with 11.3 weeks of gestation. With the diagnostic, prognostic and pleased parity we decide to do block hysterectomy. We describe this case because of its low frequency, but catastrophic consequences that put on danger mothers life. Prevalence is calculated on 1:1800-1226 of all pregnancies (0.15%) and represents 6.15% of de ectopic pregnancies in women with at least one cesarean. They have been published a mayor number of cases during the last decade, probably because of the world increment of cesarean delivery or the earliest diagnostic. We recommend interruption of pregnancy at the moment of diagnosis, to avoid complications.


Follicular mucinosis presenting as an acneiform eruption: a follow-up study.
It has been proposed by many authors that follicular mucinosis is directly associated with mycosis fungoides (MF). Follicular mucinosis may be classified into 3 main clinical variants: a benign idiopathic form in children and young adults, which includes an acneiform presentation; an idiopathic form in older patients with a benign course; and a third variant that occurs in adults and is associated with MF. Our goal was to study the relationship between the acneiform variant of follicular mucinosis and MF. Eight patients previously diagnosed with the acneiform variant of follicular mucinosis were identified. Biopsy specimens were reviewed to evaluate the histopathologic attributes that characterize the disease and the infiltrate's immunohistochemistry. Also, patient follow-up was assessed to evaluate the clinical course of the disease. Median age of onset of disease was 29.5 years; 95% of lesions were located in the head and neck region. Biopsy specimens showed a moderate to dense perivascular, perifollicular, and interstitial infiltrate of lymphocytes with mucinous deposits within the follicular epithelium. On immunohistochemistry, the infiltrate showed prominent leukocyte common antigen (LCA) positivity and a CD3-positive and CD4-positive infiltrate with rare CD20-positive cells. None of the study patients showed evidence of MF after a mean follow-up of 3 years. The benign course of disease demonstrated in the study patients suggests that the acneiform variant of follicular mucinosis probably represents a subpopulation of the benign idiopathic form of the disease. However, given that histopathologically this variant cannot be distinguished from the lymphoma-associated variant of follicular mucinosis, longitudinal evaluation is still warranted in these patients.


[Antibiotic resistance of bacteria Campylobacter sp].
Campylobacter is recognized as a major cause of human acute bacterial enteritis. The incidence of human Campylobacter infection has increased markedly in both developed and developing countries and, more significantly, so has rapid emergence of antibiotic-resistant Campylobacter strains. It is caused by improper applying antibiotics in treating people and too frequent applying these substances in the animal husbandry. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter spp. are discussed.


[Dirofilariasis in the Nizhny Novgorod Region].
The paper describes cases of dirofilariasis in the Nizhny Novgorod Region in 2006-2010. During this period 26 patients with dirofilariasis were registered. Their age was 20 to 68 years; the maximum cases (26.9%) were among those aged 50-59 years. Females constituted most cases (70%). In 73% of patients, the helminth was found in different areas of the head, with the predominant involvement of eye lesion (34.6%), in the temple (11.5%), cheek (8%), and nose (8%). Dirofilaria were randomly detected in 2 patients. Helminth migration occurred in 15.3% of cases. No clear seasonality for this helminthiasis was found. Local dirofilariasis was noted in most cases (92.3%). This infection was observed in 13 of 49 districts of the region and in 3 of 8 districts of Nizhny Novgorod. The Nizhny Novgorod Region is situated in a low infection transmission risk area (latitude 54-58 degrees North). However, among 11 areas located in this zone, the Nizhny Novgorod Region registered the maximum cases of dirofilariasis. Dirofilariasis in the Nizhny Novgorod Region shares the manifestations of this helminthiasis in the Russian Federation.


ARC is essential for maintaining pancreatic islet structure and β-cell viability during type 2 diabetes.
Pancreatic β-cell loss through apoptosis is an important disease mechanism in type 2 diabetes. Apoptosis Repressor with CARD (ARC) is a cell death inhibitor that antagonizes multiple death programs. We previously reported that ARC is abundant in pancreatic β-cells and modulates survival of these cells in vitro. Herein we assessed the importance of endogenous ARC in maintaining islet structure and function in vivo. While generalized loss of ARC did not result in detectable abnormalities, its absence in ob/ob mice, a model of type 2 diabetes, induced a striking pancreatic phenotype: marked β-cell death, loss of β-cell mass, derangements of islet architecture, and impaired glucose-stimulated insulin secretion in vivo. These abnormalities contributed to worsening of hyperglycemia and glucose-intolerance in these mice. Mechanistically, the absence of ARC increased levels of C/EBP homologous protein (CHOP) in wild type isolated islets stimulated with ER stress and in ob/ob isolated islets at baseline. Deletion of CHOP in ob/ob; ARC -/- mice led to reversal of β-cell death and abnormalities in islet architecture. These data indicate that suppression of CHOP by endogenous levels of ARC is critical for β-cell viability and maintenance of normal islet structure in this model of type 2 diabetes.


Variation in pediatric and adolescent firearm mortality rates in rural and urban US counties.
We examined whether firearm mortality rates among children varied across US counties along a rural-urban continuum. US vital statistics data were accessed for all pediatric (age: 0-19 years) firearm deaths from 1999 through 2006. Deaths were analyzed according to a modified rural-urban continuum code (based on population size and proximity to metropolitan areas) assigned to each county (3141 counties). In the 8-year study period, there were 23649 pediatric firearm deaths (15190 homicides, 7082 suicides, and 1377 unintentional deaths). Pediatric nonfirearm mortality rates were significantly higher in the most-rural counties (adjusted rate ratio: 1.36 [95% confidence interval [CI]: 1.13-1.64]), compared with the most-urban counties. The most-rural counties demonstrated virtually identical pediatric firearm mortality rates (adjusted rate ratio: 0.91 [95% CI: 0.63-1.32]), compared with the most-urban counties. The most-rural counties had higher rates of pediatric firearm suicide (adjusted rate ratio: 2.01 [95% CI: 1.43-2.83]) and unintentional firearm death (adjusted rate ratio: 2.19 [95% CI: 1.27-3.77]), compared with the most-urban counties. Pediatric firearm homicides rates were significantly higher in the most-urban counties (adjusted rate ratio: 3.69 [95% CI: 2.00-6.80]), compared with the most-rural counties. Children in the most-rural US counties had firearm mortality rates that were statistically indistinguishable from those for children in the most-urban counties. This finding reflects a greater homicide rate in urban counties counterbalanced by greater suicide and unintentional firearm death rates in rural counties. Nonfirearm mortality rates were significantly greater outside the most-urban US counties.


Poly(ethylene glycol)-modified gold nanorods as a photothermal nanodevice for hyperthermia.
Gold nanorods, which have a strong surface plasmon band at the near-infrared region, absorb light energy which is then converted to heat. Since near-infrared light can penetrate deeply into tissue, gold nanorods are expected to be useful as photosensitizers for photothermal therapy. In this study, the length of the poly(ethylene glycol) (PEG) chain was optimized in order to stabilize the gold nanorods in the blood circulation after intravenous injection. PEG(5000)- and PEG(10000)-modified gold nanorods showed higher stability in the blood circulation compared with PEG(2000)- and PEG(20000)-modified gold nanorods. As a demonstration of photothermal tissue damage, PEG(5000)-modified gold nanorods were injected into the muscle in the hind limbs of a mouse, and then irradiated with near-infrared pulsed laser light. Significant tissue damage was observed only in the presence of gold nanorods and laser irradiation. We next injected the gold nanorods directly into subcutaneous tumors in mice, and then irradiated the tumor with near-infrared pulsed laser light. Significant suppression of tumor growth was observed. In the case of the intravenous injection of gold nanorods, the suppression of tumor growth was weaker than for the case of direct injection, indicating that the targeted delivery of gold nanorods to the tumor tissue is an important key to improve the therapeutic effect.


Signal transduction events in human basophils. A comparative study of the role of protein kinase C in basophils activated by anti-IgE antibody and formyl-methionyl-leucyl-phenylalanine.
We have compared the transmembrane signals generated in human basophils by two distinct stimuli, anti-IgE antibody and FMLP (f-met peptide). Although both stimuli resulted in the activation of protein kinase C (PKC) and an increase in intracellular free calcium, there were substantial differences between the two which suggested that distinct signal transduction mechanisms were operating. We have confirmed an earlier observation that the cross-linking of IgE led to an increase in membrane PKC activity with no apparent concomitant loss of cytosolic PKC and established that in contrast, the univalent stimulus, f-met peptide, resulted in the canonical translocation of cytosolic PKC to the membrane. Furthermore, unlike anti-IgE-stimulated basophils, there was no clear relationship between the increase in PKC activity and the subsequent release of histamine. Two PKC inhibitors, staurosporine (0.1 to 1 nM) and sphingosine (25 to 50 microM), inhibited anti-IgE induced release, yet, potentiated the release of mediators after a challenge with 1 microM f-met peptide. Both stimuli led to an increase in the intracellular Ca2+ levels that correlated well with the release of histamine, however, the anti-IgE-induced responses were typically only 50% of those required to give equivalent histamine release when f-met peptide initiated release. Pharmacologic evidence suggested that the up-regulation of PKC was required for a full IgE-mediated Ca2+ response and that PKC contributed to the elevated Ca2+ levels that persist for up to 15 min after the addition of anti-IgE. In contrast, the PKC inhibitor, staurosporine, did not affect the initial increase in Ca2+ after the addition of f-met peptide but reduced the rate at which Ca2+ was removed from the cytosol. Experiments with the phorbol ester, PMA, suggested that substantial degranulation can occur in the absence of any increase in intracellular Ca2+. The addition of 10 ng/ml PMA 10 min before the addition of f-met peptide did not affect the magnitude of the initial Ca2+ transient but increased the rate at which Ca2+ levels returned to a stable baseline. Similar pretreatment with PMA almost completely abolished the anti-IgE antibody-induced Ca2+ response. These experiments, together with other previous data, suggest that the activation of PKC is a prodegranulatory component of the IgE-mediated signal transduction pathway, yet serves principally to modulate the Ca2+ signal when f-met peptide initiates release.


Early-stage primary bone lymphoma: a retrospective, multicenter Rare Cancer Network (RCN) Study.
Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score ≤1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.


[Pregnancy and possible complications in a patient with systemic sclerosis--a case report].
The report describes a case of a 28-year-old woman who, despite many problems with scleroderma, was able to conceive and deliver a healthy baby The main symptoms, problems, treatment and consequences of the disease that the patient experienced were presented. The authors paid attention to interdisciplinary medical care that such a patient should get. Apart from a gynecologist, a rheumatologist and a dermatologist should be involved in medical treatment. Although our patient did not demonstrate intensified symptoms of the main disease and did not need drugs, the authors showed problems, possible difficulties of treatment and consequences of sclerosis that every obstetrician can encounter in such cases. To increase the value of this article the authors included data from available literature to lay emphases on problems with scleroderma that can be met with a patient who needs treatment with a preconception, during pregnancy and afterwards, during lactation.


Management of Pregabalin Use Disorder: A Case Series.
Pregabalin is indicated for the treatment of partial epilepsy, generalized anxiety disorder, and neuropathic pain. The first reports on pregabalin use disorder have been published in Europe in 2010 and notified to the French Addictovigilance Network (FAN) in 2011. The management of pregabalin use disorder is challenging due to the risks associated with the abrupt withdrawal and lack of guidelines. In this retrospective observational study, the management of pregabalin use disorder was analyzed in eight cases reported to the addictovigilance center of Montpellier, France, between 2019 and 2020. Most of these patients had a history of illicit psychoactive substance use. During the withdrawal period, patients experienced mainly psychiatric problems, nervous system symptoms, general disorders, and gastrointestinal symptoms. Multiple strategies were proposed for these patients to manage pregabalin withdrawal, such as hospitalization and pregabalin gradual dose reduction with or without adjuvant medications. Two patients relapsed and the others were lost to follow up. Although other reports of pregabalin use disorder have been published, recommendations or guidelines for its management are not yet available. The current case series and the previous reports suggest that the use of adjunctive therapy may be useful to limit the risk of convulsions and anxiety.


Contact Transmission of COVID-19 in South Korea: Novel Investigation Techniques for Tracing Contacts.
In the epidemiological investigation of an infectious disease, investigating, classifying, tracking, and managing contacts by identifying the patient's route are important for preventing further transmission of the disease. However, omissions and errors in previous activities can occur when the investigation is performed through only a proxy interview with the patient. To overcome these limitations, methods that can objectively verify the patient's claims (medical facility records, Global Positioning System, card transactions, and closed-circuit television) were used for the recent ongoing coronavirus disease 2019 contact investigations in South Korea.


The changing role of hospital nurse managers: a literature review.
Hospitals in Canada and indeed throughout the world are in the midst of significant and even dramatic change. The impact of these changes on the role of the nurse manager is just beginning to be identified and research in this area is limited. As hospitals' structures and functions change, so must the roles of their managers and providers. The nurse manager is key in both facilitating patient care and in ensuring the quality of worklife of staff nurses. If the nurse manager role is to be maintained and more importantly, if the role is to develop as a significant one in the hospital infrastructure, more understanding, more study, and clear directions for the future are required. This article provides an overview of the literature on nurse managers, examines the roles, perspectives and needs of those managers and discusses the implications for future research in this area.


Comparison of four polymerase chain reaction methods for the rapid detection of human fecal pollution in marine and inland waters.
We compared the effectiveness of three PCR protocols for the detection of Bifidobacterium adolescentis and one PCR protocol for detecting Bacteroidales as indicators of human fecal pollution in environmental samples. Quantitative PCR indicated that a higher concentration of B. adolescentis DNA was recovered from sewage samples on the 0.2 mum filters compared to the 0.45 mum filters, and there was no evidence of qPCR inhibitors in the DNA extracts. With the Matsuki method (1999), B. adolescentis was detected only in undiluted sewage samples. The King method (2007) performed well and detected B. adolescentis in all of the sewage dilutions (from undiluted to 10(-4)). In contrast, the Bonjoch approach (2004) was effective at detecting B. adolescentis at lower dilutions (10(-3)) of sewage samples and it gave false positive results with some (3/8) pig fecal samples. Human-specific Bacteroidales (HuBacs) were detected in the lower diluents of sewage samples but was positive in pig (6/8) and cattle fecal samples. PCR detection of B. adolescentis in marine samples from Puerto Rico and freshwater samples from Georgia indicated that the PCR method of King et al. (2007) and the modified Layton method for HuBac were in agreement in detecting human fecal pollution in most sites.


The role of kidney transplantation as a component of integrated care for chronic kidney disease.
Kidney transplant provides superior outcomes to dialysis as a treatment for end-stage kidney disease. Therefore, it is essential that kidney transplantation be part of an integrated treatment and management plan for chronic kidney disease (CKD). Developing an effective national program of transplantation is challenging because of the requirement for kidney donors and the need for a multidisciplinary team to provide expert care for both donors and recipients. This article outlines the steps necessary to establish a national kidney transplant program, starting with the requirement for effective legislation that provides the legal framework for transplantation whilst protecting organ donors, their families, recipients, and staff and is an essential requirement to combat organ trafficking. The next steps involve capacity building with the development of a multiskilled workforce, the credentialing of transplant centers, and the reporting of outcomes through national or regional registries. Although it is accepted that most transplant programs will begin with living related kidney donation, it is essential to aspire to and develop a deceased donor program. This requires engagement with multiple stakeholders, especially the patients, the general community, intensivists, and health departments. Development of transplant centers should be undertaken in concert with the development of a dialysis program. Both are essential components of integrated care for CKD and both should be viewed as part of the World Health Organization's initiative for universal health coverage. Provisions to cover the costs of treatment for patients need to be developed taking into account the state of development of the overall health framework in each country.


Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4.
The vertebrate circulatory system is composed of arteries and veins. The functional and pathological differences between these vessels have been assumed to reflect physiological differences such as oxygenation and blood pressure. Here we show that ephrin-B2, an Eph family transmembrane ligand, marks arterial but not venous endothelial cells from the onset of angiogenesis. Conversely, Eph-B4, a receptor for ephrin-B2, marks veins but not arteries. ephrin-B2 knockout mice display defects in angiogenesis by both arteries and veins in the capillary networks of the head and yolk sac as well as in myocardial trabeculation. These results provide evidence that differences between arteries and veins are in part genetically determined and suggest that reciprocal signaling between these two types of vessels is crucial for morphogenesis of the capillary beds.


Evaluation of 99mTc-RP128 as a potential inflammation imaging agent: human dosimetry and first clinical results.
99mTc-RP128 is a bifunctional peptide chelate designed to target the tuftsin receptor, expressed by neutrophils, monocytes, and macrophages. Studies in animal models of both infectious and noninfectious inflammation have shown a positive correlation between accumulation of 99mTc-RP128 and quantitative measures of inflammation. A phase 1 trial was conducted with the objective of determining the safety, biodistribution, and human dosimetry of 99mTc-RP128 in eight healthy volunteers. For evaluation of the potential of 99mTc-RP128 for imaging sites of inflammation, 10 patients with active rheumatoid arthritis were studied. Normal biodistribution was determined using the conjugate view method up to 24 h after intravenous injection of 280 MBq 99mTc-RP128. Dosimetry calculations were based on standard MIRD methodology, using the International Commission on Radiological Protection model 30 of the gastrointestinal tract and a voiding bladder model with an interval of 4.8 h. For rheumatoid arthritis patients, whole-body scans and spot views of the hands, knees, and feet were obtained at 1 and 3 h after injection of 475 MBq 99mTc-RP128. 99mTc-RP128 was cleared rapidly from the blood by renal excretion, and no major organs showed significant accumulation. The synovia of the major joints were visualized for all subjects. The effective dose equivalent and the effective dose were calculated to be 0.011 and 0.0094 mSv/MBq, respectively. The highest dose was to the bladder wall, which received 0.076 mGy/MBq. In all rheumatoid arthritis patients, we observed a markedly increased uptake in several affected joints. Painful and swollen joints were detected with a sensitivity of 76% and 69%, respectively. Seventy-three percent of the joints with radiographic signs of erosion were scintigraphically positive. In some patients, lines of increased activity were observed and were considered to correspond to uptake in the synovium lining tendon sheaths in the wrists and hands. This study shows that 99mTc-RP128 is safe and can successfully be used to visualize clinically affected joints in patients with long-standing rheumatoid arthritis. A proposed radioactive dose of 450-500 MBq will produce an effective dose well within the range of effective doses for commonly used radiopharmaceuticals.