The PLATO trial: do you believe in magic?
The PLATO trial revealed a remarkable advantage of ticagrelor over clopidogrel in ACS patients. Unless the regulatory authorities discover serious flaws with the study, which is unlikely, the drug may substantially change the present landscape of oral antiplatelet therapy, especially in high-risk patients. Despite a somewhat unfavourable safety profile, ticagrelor has a lot of room to compensate for these well-defined side effects based on a documented absolute mortality reduction, solid prevention of MI, and convincing pattern of benefit growing over time.


Enriching CCL3 in the Tumor Microenvironment Facilitates T cell Responses and Improves the Efficacy of Anti-PD-1 Therapy.
Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.


The Radiotherapy Role in the Multidisciplinary Management of Locally Advanced Vulvar Cancer: A Multidisciplinary VulCan Team Review.
Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisciplinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients' age and comorbidities, in view of a better treatment personalization.


Testicular fluid content and scrotal surface temperature increase with rams' sexual activity.
Contact with oestrual ewes induces an increase in LH and testosterone concentrations in rams. LH provokes an increase in testicular capillary permeability in rodents and an increase in testicular fluid in rams. Therefore, the objectives of the present experiment were to determine whether contact with oestrual ewes, including courtship and mating, induces an increase in testicular fluid content and scrotal temperature in rams. During the breeding season, after 2 weeks isolated from females, a total of 18 tests were performed using one ram with one ewe. The rams were allowed to court and mate the ewes during 20 min. Testosterone blood concentrations were measured by RIA from blood samples taken before and immediately after each test. Rectal, scrotal surface and anal skin temperatures were measured before the test, at the end, and 30 min later. At the same moments, ultrasonographic examinations of the testes were performed. Testosterone concentrations increased after the tests (p = 0.016), and ultrasound images were darker at the end of the tests and 30 min later (p < 0.0001). Rectal, anal skin and scrotal temperatures increased at the end of the test, but decreased 30 min later to initials values. The stimulus of oestrual ewes determined an increase in testosterone secretion, which was associated with an increase in testicular fluid content. Fluid content remained increased at least for 30 min after the end of the ram-ewe contact. Contact with oestrual ewes triggered an increase in testicular fluid that remained higher after the end of the test.


Angiotensinogen gene variation in a population case-control study of preeclampsia/eclampsia in Australians and Chinese.
Preeclampsia/eclampsia (PE/E) is a common disease of human pregnancy with a strong genetic component. The etiology of PE/E is unknown. Two recent reports indicated that the angiotensinogen gene (AGT) could be involved in susceptibility to PE/E. We performed a population-based case-control study in Australian and Chinese populations to investigate whether AGT is a good candidate gene for PE/E. A microsatellite polymorphism within AGT was typed as well as a molecular variant T235 (Met-->Thr) of AGT using allele-specific PCR and allele-induced restriction site PCR. The allele distributions of the microsatellite and the variant T235 of AGT were significantly different between the two ethnic groups. However, no significant allele associations were found with disease when comparing PE/E patients and controls in Australian or Chinese populations, which is in contrast to the two earlier reports. The results suggest that the contribution of AGT to the occurrence of PE/E is small, if anything, and is not constant across populations.


Meta-analysis of the effectiveness of psychological and pharmacological treatments for binge eating disorder.
The aim of this study was to compute and compare mean effects of various treatments for binge eating disorder. A total of 38 studies with 1973 participants fulfilled the defined inclusion criteria. Effect sizes, odds ratios, and simple rates were integrated in fixed and random (mixed) effects categorical models. From randomized controlled trials, psychotherapy and structured self-help, both based on cognitive behavioral interventions, were found to have large effects on the reduction of binge eating. Regarding pharmacotherapy, mainly comprising antidepressants, randomized controlled trials revealed medium effects for the reduction of binge eating. Uncontrolled studies on weight-loss treatments demonstrated moderate reductions of binge eating. Combination treatments did not result in higher effects compared with single-treatment regimens. Except for weight-loss treatment, none of the interventions resulted in a considerable weight reduction. Psychotherapy and structured self-help, both based on cognitive-behavioral interventions, should be recommended as the first-line treatments.


Squamous cell carcinoma of the skin.
After studying this article, the participant should be able to: 1. Identify the subtypes of squamous cell carcinoma of the skin. 2. Identify factors that affect recurrence and/or metastasis. 3. Develop a surgical management plan for treating high-risk squamous cell carcinoma of the skin. In treating squamous cell carcinoma of the skin, a key concept in proper management is understanding why certain tumors are more prone to both recurrence and metastasis. When developing a surgical management plan, an understanding of "high risk" is essential. This article concentrates on identifying those tumor subtypes and factors that may serve as predictors of high-risk status as well as on providing management suggestions.


High virologic sustained response for former young intravenous drug users with chronic hepatitis C treated by pegylated interferon-alpha plus ribavirin.
The aim of this clinical study was to assess virological response at end-of -treatment (ETR), sustained virological (SVR) and biochemical response in former drug users with chronic hepatitis C treated with PEG-IFN-alpha and R. Ninety two former drug users (21 F, 71 M) average age 27 years (18 to 41 years) and previously not treated with IFN-alpha and R (naive patients, pts) were evaluated for their virological and biochemical response. Standard treatment regimen of either 24 or 48 weeks was applied in patients with genotype 3 or genotype 1, respectively. SVR was considered if viral tests (HCV RNA) were negative 24 weeks after the end of treatment. Overall SVR was attained in 87 (95%) of 92 treated patients, and therapy failed in 5 pts with genotype 1. In genotype 1 patients ETR and SVR were 81% and 86%, respectively (p < 0.001). In genotype 3 patients ETR and SVR were 98% and 100%, respectively (p < 0.001). ALT levels decreased significantly after 12 weeks of therapy (ALT 1.61 vs 0.64 micro/kat/l, p < 0.001) and were at normal levels during follow-up. Crucial predictive factors resulting in high SVR were the younger age in combination with low stage of liver fibrosis, relatively short duration of viral infection, high proportion of genotype 3 and excellent adherence of patients to treatment regimen than previously not treated with IFN-alpha and R (naive patients). High proportion of SVR in former drug users has been achieved in patients with genotype 3 (100%) and genotype 1 (86%). The most decisive prognostic factor which favors high therapeutic efficacy appears to be young age and early onset of anti-HCV treatment (Tab. 3, Fig. 1, Ref. 33). Full Text (Free, PDF) www.bmj.sk.


Moving science into state child and adolescent mental health systems: Illinois' evidence-informed practice initiative.
In 2005, the Illinois State Mental Health Authority embarked on an initiative to close the gap between research and practice in the children's mental health system. A stakeholder advisory council developed a plan to advance evidence informed practice through policy and program initiatives. A multilevel approach was developed to achieve this objective, which included policy change, stakeholder education, and clinician training. This article focuses on the evidence-informed training process designed following review of implementation research. The training involved in-person didactic sessions and twice-monthly telephone supervision across 6 cohorts of community based clinicians, each receiving 12 months of training. Training content initially included cognitive behavioral therapy and behavioral parent training and was adapted over the years to a practice model based on common element concepts. Evaluation based on provider and parent report indicated children treated by training clinicians generally showed superior outcomes versus both a treatment-as-usual comparison group for Cohorts 1 to 4 and the statewide child population as a whole after 90 days of care for Cohorts 5 to 6. The results indicated primarily moderate to strong effects for the evidence-based training groups. Moving a large public statewide child mental health system toward more effective services is a complex and lengthy process. These results indicate training of community mental health providers in Illinois in evidence-informed practice was moderately successful in positively impacting child-level functional outcomes. These findings also influenced state policy in committing resources to continuing the initiative, even in difficult economic times.


Efficacy and safety of immune checkpoint inhibitors-combined antiangiogenic drugs in the treatment of hepatocellular carcinoma: A systematic review and meta analysis.
Hepatocellular carcinoma is a pathological type of liver cancer and accounts for the majority of primary liver cancers. We conducted a meta-analysis to evaluate the efficacy and safety of immune checkpoint inhibitors in combination with antiangiogenic drugs in the treatment of hepatocellular carcinoma. We searched scientific literature databases and clinical trials databases through May 2022 for required studies. Progression-free survival was taken as the main outcome, and overall survival, response rate and adverse events as secondary outcomes. These data were extracted, combined and used for meta-analysis to compare the treatment effect and safety of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced/unresectable/metastatic hepatocellular carcinoma. This study included 3 randomized controlled trials and 6 single-arm trials of immune checkpoint inhibitors in combination with antiangiogenic drugs in hepatocellular carcinoma. Meta-analysis showed that compared with single use, combination of the two can significantly improve PFS (HR=5.93, 95% CI=5.41, 6.45) and OS (HR=15.84, 95% CI=15.39, 16.28). The ORR and DOR of patients with combination therapy were HR=19.11, 95% CI=15.99, 22.22 and HR=12.26, 95% CI=10.32, 14.21, respectively. Common adverse reactions to combination therapy included hypertension (26.8%), diarrhea (23.6%), fatigue (23.8%), decreased appetite (22.8%), hypothyroidism (9.9%), and rash (14.5%). In the treatment of advanced/unresectable/metastatic hepatocellular carcinoma, immune checkpoint inhibitors combined with antiangiogenic drugs achieved better survival benefits than alone. In addition, the combination therapy has tolerable safety.


Biomarker-based assessment of collagen cross-linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial.
The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial. Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean differencesspiro/control : -1.77 (95% confidence interval, CI -2.94 to -0.59) and -2.52 (95% CI -4.46 to -0.58) mL/m2 ; interaction pacross-tertiles = 0.005; interaction pthird tertile = 0.008] with a similar trend for N-terminal pro-B-type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross-linking tertile [mean differencesspiro/control : -0.47 (95% CI -0.66 to -0.28) and -0.31 (95% CI -0.59 to -0.04) ng/L; interaction pacross-tertiles = 0.09; interaction pthird tertile < 0.001]. These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).


MicroRNA-1236-3p inhibits human osteosarcoma growth.
Osteosarcoma (OS) is a common bone tumor with high mortality worldwide. The long-term survival rate of patients with metastatic or recurrent disease is <20%. The present study explored the biological role of microRNA (miRNA/miR)-1236-3p in OS. miRNA and mRNA expression levels were measured via reverse transcription-quantitative PCR. Fluorescence in situ hybridization was performed to determine miR-1236-3p expression levels in clinical specimens. Protein expression was measured via western blotting. Immunohistochemical analysis was used to detect Wnt target gene expression in tumor tissues. The interaction between the Wnt3a 3'untranslated region and miR-1236-3p was assessed via dual-luciferase reporter assays. Cell cycle, Transwell, Cell Counting Kit-8 and wound healing assays were conducted to evaluate the function of the miR-1236-3p/Wnt3a axis. Human OS (HOS) cells stably transfected with vector or miR-1236-3p sponge were injected subcutaneously into nude mice to assess the role of miR-1236-3p in vivo. miR-1236-3p expression was downregulated in OS tissues compared with chondroma tissues, and miR-1236-3p overexpression inhibited OS cell migration and proliferation compared with the negative control group. Furthermore, in vivo xenograft assays displayed enhanced tumour growth rates in the miR-1236-3p sponge group compared with the vector control group. In the present study, the results indicated that miR-1236-3p inhibited OS progression and Wnt3a was identified as a target of miR-1236-3p.


Anterior segment characteristics in normal and keratoconus eyes evaluated with a new type of swept-source optical coherence tomography.
This study aimed to evaluate and compare the discriminating ability of corneal elevation maps generated using a swept-source optical coherence tomography (SS-OCT) (SS-OCT ANTERION, Heidelberg Engineering, Heidelberg, Germany), which was estimated with different reference surfaces, to distinguish normal corneas from those with keratoconus and keratoconus suspect. A total of 126 eyes of patients, which comprised 43, 37, and 46 keratoconus, keratoconus suspects, and normal controls, respectively, were included in this study. The anterior and posterior elevations at the thinnest point under the best-fit sphere (BFS) and toric-ellipsoid (BFT), respectively, and other corneal parameters were measured using the SS-OCT. In addition, the receiver operating characteristic (ROC) curve analysis and cut-off value were calculated to evaluate the diagnostic ability of the corneal elevation values in differentiating keratoconus and keratoconus suspects from normal eyes. The mean total keratometric and corneal elevation values were significantly higher in the keratoconus group than in the other groups. Pachymetric parameters exhibited the lowest values for keratoconus. In addition, ROC curve analyses showed a high accuracy of the thinnest point anterior and posterior BFT for both keratoconus and keratoconus suspects and normal controls (area under the ROC were 0.969 and 0.961, respectively). Furthermore, the optimal cut-off point of the posterior elevation at the thinnest point under BFT was 16.44 μm (sensitivity and specificity of 86% and 98%, respectively) for differentiating keratoconus from normal and keratoconus suspect eyes. The elevation map using the BFS and BFT references measured with the anterior segment SS-OCT is considered an effective indicator for keratoconus diagnosis. Therefore, the anterior segment SS-OCT can effectively differentiate keratoconus from suspected keratoconus and normal corneas by measuring parameters such as posterior and anterior elevations, pachymetry, and keratometry.


Recurrent alternating stroke.
Recurrent alternating stroke, i.e., one time ischemic and the other hemorrhagic or vice versa, is an uncommon event. We report a series of eight patients who had recurrent alternating strokes, which were diagnosed by CT scans during the last four years. Infarcts preceded hemorrhage in six patients. In the remaining two patients, hemorrhage developed first and infarct followed. All ischemic strokes were the lacunar infarcts. The lesions of the two attacks were located in different sites in all cases except one. The mean age of the patients was 56.6 years at the time of the first attack and 57.5 years at the time of the second. The mean interval between attacks was 11.8 months. All patients were hypertensive on admission. After the first attack, the outcome was favorable in all patients. However, after the second attack the outcome deteriorated to moderate disability in three, severe disability in one and death in four. We discuss some possible reasons for the rarity of recurrent alternating stroke.


Human papillomavirus 'reflex' testing as a screening method in cases of minor cytological abnormalities.
The aim was to evaluate human papillomavirus (HPV) 'reflex genotyping' in cases of minor cytological abnormalities detected in the gynaecological screening programme in Stockholm, Sweden. Liquid-based cytology samples showing minor cytological abnormalities were analysed using HPV genotyping (Linear Array, Roche diagnostics). Colposcopically directed cervical biopsies were obtained and the HPV test results were correlated with the histological results. In all, 63% (70/112) of the samples were high-risk (HR) HPV (HR-HPV) positive. A statistically significant correlation was found between high-grade cervical lesions and HR-HPV (P=0.019), among which HPV 16, 18, and 31 were the most important. The negative predictive value of HR-HPV detection for histologically confirmed high-grade lesions was 100%. An age limit for HPV reflex testing may be motivated in cases of low-grade squamous intraepithelial neoplasia (LSIL), because of high HR-HPV prevalence among younger women. By using HPV reflex genotyping, additional extensive workup can safely be avoided in about 50% of all cases of atypical squamous cells of undetermined significance (ASCUS) and LSIL among women 30 years. This screening strategy could potentially reduce the total abnormal cytology-reporting rate in the Swedish screening programme by about 1% and provide more accurately directed follow-up, guided by cytological appearance and HPV test results.


[Play therapy in social work with children].
This article introduces the results of scientific research performed in 1995-1997 in Kaunas primary school with 1st and 2nd grade children exhibiting behavioral disorders. Play therapy, a quite novel method in the country, seeks better improvement and an achievement of a better relationship for disadvantaged children in educational process. Play group counseling, or play media counseling, is shown as an important method in working with early primary grade children, especially those who present behavioral problems in the classroom. Another important aspect of group play therapy is the concentrated relationship with the counselor. Primary school children, especially those who are disadvantaged respond more to warmth than to praise for being right and doing well. Data analysis allow us to assume that behavioral difficulties of primary school children are connected with a low rate of self-esteem and dissatisfaction with their vital activities. Main conclusions to correspond with hypothesis held for the research are: a) children exhibiting behavioral problems are less active in educational process; b) by means of systematic use of play group counseling method in school, problematic children are able to solve their difficulties and to optimize their academic improvement; c) there is a complementary relationship between child's self-esteem and his/her satisfaction with his/her vital activity.


Giant and complicated subcutaneous lipoma of the neck.
Although lipomas around the head and neck region are not uncommon, giant lipomas around the neck are rare. To report the case of a long standing giant lipoma of the neck which was managed easily by simple surgical excision. A case of giant subcutaneous lipoma of the neck is reported in a 70 year old woman who presented with dragging sensation and bleeding from the site of pressure ulceration as the major complaint. The patient was evaluated and definitive diagnosis was arrived at using Fine Needle Aspiration Cytology (FNAC). She had a successful Surgical excision and was subsequently discharged but never came back for follow up. Lipoma should always be considered in the differential diagnosis of pedunculated lesions around the neck.


Rational Design and Porosity of Porous Alumina Ceramic Membrane for Air Bearing.
Air bearing has been widely applied in ultra-precision machine tools, aerospace and other fields. The restrictor of the porous material is the key component in air bearings, but its performance is limited by the machining accuracy. A combination of optimization design and material modification of the porous alumina ceramic membrane is proposed to improve performance within an air bearing. Porous alumina ceramics were prepared by adding a pore-forming agent and performing solid-phase sintering at 1600 °C for 3 h, using 95-Al2O3 as raw material and polystyrene microspheres with different particle sizes as the pore-forming agent. With 20 wt.% of PS50, the optimum porous alumina ceramic membranes achieved a density of 3.2 g/cm3, a porosity of 11.8% and a bending strength of 150.4 MPa. Then, the sintered samples were processed into restrictors with a diameter of 40 mm and a thickness of 5 mm. After the restrictors were bonded to aluminum shells for the air bearing, both experimental and simulation work was carried out to verify the designed air bearing. Simulation results showed that the load capacity increased from 94 N to 523 N when the porosity increased from 5% to 25% at a fixed gas supply pressure of 0.5 MPa and a fixed gas film thickness of 25 μm. When the gas film thickness and porosity were fixed at 100 μm and 11.8%, respectively, the load capacity increased from 8.6 N to 40.8 N with the gas supply pressure having been increased from 0.1 MPa to 0.5 MPa. Both experimental and simulation results successfully demonstrated the stability and effectiveness of the proposed method. The porosity is an important factor for improving the performance of an air bearing, and it can be optimized to enhance the bearing's stability and load capacity.


Multipoint linkage analysis and homogeneity tests in 15 Dutch X-linked retinitis pigmentosa families.
Linkage analysis and homogeneity tests were carried out in 15 Dutch families segregating X-linked retinitis pigmentosa (X L R P). The study included segregation data for eight polymorphic DNA markers from the short arm of the human X chromosome. The results of both multipoint linkage analysis in individual families and heterogeneity analysis support the view that there are only two X L R P loci on the short arm of the human X chromosome, with one locus near the OTC gene and one in the vicinity of DXS255. Furthermore, our data confirm the hypothesis that a tapetal reflex in female carriers can be observed more frequently, if not exclusively, in X L R P families of the R P 3 type.


Women's mental health: implications for occupational therapy.
This article describes issues of sexism in the mental health profession. Theoretical bias in psychiatry and the sociopolitical status of women are both linked to the inappropriate mental health treatment of women. A relational model of women's psychological development is offered as an alternative theoretical perspective for understanding the mental health needs of women. Ways to integrate this perspective in occupational therapy practice are included.


Mycobacterium tuberculosis-Specific Antigen Rv3619c Effectively Alleviates Allergic Asthma in Mice.
Despite significant advances, asthma remains a cause of premature death, and current treatments are suboptimal. Antigen-specific Th2 cells and their cytokines are primary mediators of the pathophysiological changes seen in asthma. Studies in animal models have shown that mycobacteria can suppress the asthma phenotype by alteration of the Th1/Th2 cytokines ratio. In this study, utilizing a Th1 delivery system to modulate the allergic airway inflammation in a Th2-driven model of asthma, we evaluated the efficacy of immunization with Mycobacterium tuberculosis-specific antigen Rv3619c, either alone or in combination with low dose dexamethasone. The rv3619c gene was cloned in an expression plasmid pGES-TH-1, expressed in Escherichia coli, and the recombinant protein Rv3619c was purified to homogeneity using affinity chromatography. Mice were immunized with the recombinant protein emulsified in Freund's Incomplete Adjuvant (IFA) alone and in combination with low dose dexamethasone, and then challenged with ovalbumin (OVA). Airway inflammation was assessed by quantifying airway cytology, histological changes and Th2 cytokine (IL-5) secretion from splenocytes. OVA-specific IgE, IgG and IgG1 from sera was assessed, as well as pERK1/2 expression in the lung tissue. Immunization with recombinant Rv3619c alone inhibited the OVA-induced increase in total cell counts, eosinophil airway cell infiltration in BAL fluid, perivascular and peribronchial inflammation and fibrosis, and goblet cell hyper/metaplasia. In addition, Rv3619c/IFA inhibited the OVA-induced IL-5 in spleen cells, OVA-specific IgE, IgG, and IgG1 levels in sera, and pERK1/2 expression in lung tissue. Immunization with Rv3619c/IFA in combination with low dose dexamethasone resulted in an enhanced effect on some but not all the asthma features. Taken together, this study demonstrates that immunization with Rv3619c/IFA, alone or in combination with dexamethasone, may be an effective treatment strategy for the prevention of asthma.


The role of the basal ganglia in exploration in a neural model based on reinforcement learning.
We present a computational model of basal ganglia as a key player in exploratory behavior. The model describes exploration of a virtual rat in a simulated water pool experiment. The virtual rat is trained using a reward-based or reinforcement learning paradigm which requires units with stochastic behavior for exploration of the system's state space. We model the Subthalamic Nucleus-Globus Pallidus externa (STN-GPe) segment of the basal ganglia as a pair of neuronal layers with oscillatory dynamics, exhibiting a variety of dynamic regimes such as chaos, traveling waves and clustering. Invoking the property of chaotic systems to explore state-space, we suggest that the complex exploratory dynamics of STN-GPe system in conjunction with dopamine-based reward signaling from the Substantia Nigra pars compacta (SNc) present the two key ingredients of a reinforcement learning system.


Assessment of Financial Toxicity Among Patients With Advanced Lung Cancer in Western China.
Background: Lung cancer is the leading source of cancer-caused disability-adjusted life years. Medical cost burden impacts the well-being of patients through reducing income, cutting daily expenses, curtailing leisure activities, and depleting exhausting savings. The COmprehensive Score for Financial Toxicity (COST) was created and validated by De Souza and colleagues. Our study intends to measure the financial burdens of cancer therapy and investigate the link between financial toxicity and health-related quality of life (HRQoL) in an advanced lung cancer population. Methods: Patients aged ≥ 18 years with confirmed stage III to IV lung cancer were eligible. The COST questionnaire verified by de Souza et al. was used to identify financial toxicity. Multivariable linear regression analysis with log transformation univariate analysis and Pearson correlations were used to perform the analysis. Results: The majority of the patients (90.8%, n = 138/152) had an annual income of $50,000 ($7,775). The cohort's insurance situation was as follows: 64.5% of the cohort had social insurance, 20.4% had commercial insurance, and 22.0% had both. Patients who were younger age (50-59, P < 0.001), employed but on sick leave, and had lower income reported increased levels of financial toxicity (P < 0.05). The risk factors for high financial toxicity: (i) younger age (50-59), (ii) <1 month of savings, and (iii) being employed but on sick leave. Increased financial toxicity is moderately correlated with a decrease in QoL. Conclusion: Poorer psychological status and specific demographics are linked to increased financial toxicity (lower COST). Financial toxicity has a modest relationship with HRQoL and may have a clear link with HRQoL measurements.


Mutual Conversion of CO-CO2 on a Perovskite Fuel Electrode with Endogenous Alloy Nanoparticles for Reversible Solid Oxide Cells.
Reversible solid oxide cells (RSOCs) can efficiently render the mutual conversion between electricity and chemicals, for example, electrolyzing CO2 to CO under a solid oxide electrolysis cell (SOEC) mode and oxidizing CO to CO2 under a solid oxide fuel cell (SOFC) mode. Nevertheless, the development of RSOCs is still hindered, owing to the lack of catalytically active and carbon-tolerant fuel electrodes. For improving mutual CO-CO2 conversion kinetics in RSOCs, here, we demonstrate a high-performing and durable fuel electrode consisting of redox-stable Sr2(Fe, Mo)2O6-δ perovskite oxide and epitaxially endogenous NiFe alloy nanoparticles. The electrochemical impedance spectrum (EIS) and distribution of relaxation time (DRT) analyses reveal that surface/interface oxygen exchange kinetics and the CO/CO2 activation process are both greatly accelerated. The assembled single cell produces a maximum power density (MPD) of 443 mW cm-2 at 800 °C under the SOFC mode, with the corresponding CO oxidation rate of 5.524 mL min-1 cm-2. On the other hand, a current density of -0.877 A cm-2 is achieved at 1.46 V under the SOEC mode, equivalent to a CO2 reduction rate of 6.108 mL min cm-2. Furthermore, reliable reversible conversion of CO-CO2 is proven with no performance degradation in 20 cycles under SOEC (1.3 V) and SOFC (0.6 V) modes. Therefore, our work provides an alternative way for designing highly active and durable fuel electrodes for RSOC applications.


Immunoglobulin G autoantibodies against tissue-transglutaminase. A sensitive, cost-effective assay for the screening of celiac disease.
The characterization of target antigens in several autoimmune disorders has made it possible to develop antigen-specific immunoassays that are superior in terms of sensitivity, specificity, reproducibility and ease of standardization, compared to immunohistological methods that are highly subjective, rely on skilled technicians and are not applicable to large-scale studies. In the case of celiac disease (CD), tissue transglutaminase (tTGase) has been identified as a major autoantigen, and antibodies against this molecule are present in most CD patients before gluten is removed from diet. In general, anti-tTGase detection assays detect the presence of IgA class antibodies, but these immunoglobulins are absent among patients with IgA deficiency, a frequent condition in which CD is very prevalent. In this report, we have analyzed 64 patients at diagnosis of CD for the presence of antibodies against tTGase of both IgA (TGA) and IgG (TGG) classes, using anti-IgA antibodies or Protein A, respectively, for the immunoprecipitation of 35S labeled, in vitro transcribed and translated human recombinant tTGase. In our hands, the TGG assay matches TGA in terms of sensitivity (97%) and specificity (100%), and besides, the combination of both assays is able to detect antibodies in all patient samples. The method described uses only 6 microl of serum, can be adapted to automated large-scale analysis and, in combination with other antigens, can be used for the simultaneous screening of other autoimmune diseases, like type 1 diabetes mellitus.


Cost-effectiveness and budget impact analyses for the prioritisation of the four available rotavirus vaccines in the national immunisation programme in Thailand.
Rotavirus is a major cause of diarrhoea in children less than five years old in Thailand. Vaccination has been shown to be an effective intervention to prevent rotavirus infections but has yet to be enlisted in the national immunisation programme. This study aimed to assess the cost-utility of introducing rotavirus vaccines, taking all WHO-prequalified vaccines into consideration. A cost-utility analysis was performed using a transmission dynamic model to estimate, from a societal perspective, the costs and outcomes of four WHO-prequalified rotavirus vaccines: Rotarix®, RotaTeq®, ROTAVAC® and ROTASIIL®. The model was used to simulate the impact of introducing the vaccines among children aged < 1 year and compare this with no rotavirus vaccination. The vaccination programme was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of USD 5,110 per QALY gained. Overall, without the vaccine, the model predicted the average annual incidence of rotavirus to be 312,118 cases. With rotavirus vaccination at a coverage of more than 95%, the average number of rotavirus cases averted was estimated to be 144,299 per year. All rotavirus vaccines were cost-saving. ROTASIIL® was the most cost-saving option, followed by ROTAVAC®, Rotarix® and RotaTeq®, providing average cost-savings of USD 32, 31, 23 and 22 million per year, respectively, with 999 QALYs gained. All vaccines remained cost-saving with lower QALYs gained, even when ignoring indirect beneficial effects. The net saving to the healthcare system when implementing any one of these vaccines would be between USD 13 and 33 million per year. Rotavirus vaccines should be included in the national vaccination programme in Thailand. Implementing any one of these four WHO-prequalified vaccines would reduce government healthcare spending while yielding health benefits to the population.


How feedback and feed-forward mechanisms link determinants of social dominance.
In many animal societies, individuals differ consistently in their ability to win agonistic interactions, resulting in dominance hierarchies. These differences arise due to a range of factors that can influence individuals' abilities to win agonistic interactions, spanning from genetically driven traits through to individuals' recent interaction history. Yet, despite a century of study since Schjelderup-Ebbe's seminal paper on social dominance, we still lack a general understanding of how these different factors work together to determine individuals' positions in hierarchies. Here, we first outline five widely studied factors that can influence interaction outcomes: intrinsic attributes, resource value asymmetry, winner-loser effects, dyadic interaction-outcome history and third-party support. A review of the evidence shows that a variety of factors are likely important to interaction outcomes, and thereby individuals' positions in dominance hierarchies, in diverse species. We propose that such factors are unlikely to determine dominance outcomes independently, but rather form part of feedback loops whereby the outcomes of previous agonistic interactions (e.g. access to food) impact factors that might be important in subsequent interactions (e.g. body condition). We provide a conceptual framework that illustrates the multitude potential routes through which such feedbacks can occur, and how the factors that determine the outcomes of dominance interactions are highly intertwined and thus rarely act independently of one another. Further, we generalise our framework to include multi-generational feed-forward mechanisms: how interaction outcomes in one generation can influence the factors determining interaction outcomes in the next generation via a range of parental effects. This general framework describes how interaction outcomes and the factors determining them are linked within generations via feedback loops, and between generations via feed-forward mechanisms. We then highlight methodological approaches that will facilitate the study of feedback loops and dominance dynamics. Lastly, we discuss how our framework could shape future research, including: how feedbacks generate variation in the factors discussed, and how this might be studied experimentally; how the relative importance of different feedback mechanisms varies across timescales; the role of social structure in modulating the effect of feedbacks on hierarchy structure and stability; and the routes of parental influence on the dominance status of offspring. Ultimately, by considering dominance interactions as part of a dynamic feedback system that also feeds forward into subsequent generations, we will understand better the factors that structure dominance hierarchies in animal groups.


Comparison of amino acid compositions of peptides eluted from HLA-B27 molecules of healthy individuals and patients with ankylosing spondylitis.
HLA-B27 is a relative risk factor for ankylosing spondylitis (AS) and is present in about 10% in European populations but in 95% of AS patients. Various data suggest that the HLA-B27 molecule itself could be the strongest risk factor, but there is no explanation for this association. To define differential antigen presenting features of HLA-B27 in healthy individuals and AS patients, a question that cannot be addressed by biochemical studies on cell lines, the HLA-B27 protein was purified from peripheral blood lymphocytes of AS patients and healthy controls and pool sequencing of the bound peptides was performed. Results show that peptides are rich in proline (Pro) and the content of arginine (Arg) is much lower in comparison with sequences listed in the register of peptides eluted from cell cultures. Statistically significant differences were detected in frequencies of a subset of amino acids, predominantly at positions in the middle of the peptides. The frequency of Glu was increased and Gln was decreased in peptides from AS patients. Detailed analysis of purity of the immunoisolated HLA molecules excluded that the peptides might originate from any co-purified HLA molecules other than B27. We conclude that statistically significant increase in the Glu/Gln ratio of peptides from AS patients, consistent with increased deamidation in vivo, may account for differential antigenicity of HLA-B27 in patients. Source protein(s) of deamidated peptides remain unknown.


Chest drain removal.
This article provides a step-by-step approach to the removal of chest drains and offers a rationale for practice. It also discusses indications for chest drain removal and potential complications associated with the procedure.


Coronavirus Disease 2019 (COVID-19) Disease Severity: Pregnant vs Nonpregnant Women at 82 Facilities.
Pregnancy has been reported to be a risk factor for severe COVID-19. We evaluated the impact of pregnancy on severe COVID-19 and mortality in an electronic medical record (EMR) database that enabled exclusion of labor and delivery (L&D) encounters. In this retrospective cohort study, EMRs from 82 healthcare facilities in the Cerner COVID-19 Datamart were analyzed. The study comprised 38 106 individuals aged 18-45 years old with COVID-19 who had emergency department, urgent care, or inpatient encounters from December 2019 to September 2020. Subgroups were balanced through propensity score weights for age, race, smoking status, and number of comorbidities. The primary outcome was COVID-19-related mortality; secondary outcomes were markers of severe COVID-19: intubations, mechanical ventilation, use of vasopressors, diagnosis of sepsis, and diagnosis of acute respiratory distress syndrome. In comparing pregnant and nonpregnant women, no statistical differences were found for markers of severe COVID-19, after adjusting for age, smoking, race, and comorbidities. The adjusted odds of an inpatient encounter were higher for pregnant vs nonpregnant women (adjusted odds ratio [aOR], 13.2; 95% confidence interval [CI], 11.6-15.3; P < .001), but notably lower after excluding L&D encounters (aOR, 2.3; 95% CI, 1.89-2.88; P < .001). In comparison to women without L&D encounters, hospitalization was significantly more likely for men. We did not find an increased risk of severe COVID-19 or mortality in pregnancy. Hospitalization does not necessarily indicate severe COVID-19 in pregnancy, as half of pregnant patients with COVID-19 were admitted for L&D encounters in this study.


Cyclopentadienyl-Based Anticancer Drugs: Improvement of Cytotoxic Activity through Functionalisation of the π Ligand.
Cytotoxic complexes containing molybdenum are widely studied as a potential substitution for commercially used drugs that often suffer from pronounced side effects and cellular resistance. Compounds of the type [(η5 -Cp')Mo(CO)2 (N,N L)][BF4 ], where Cp is cyclopentadienyl and N,N L is a bidentate ligand, are well known for their strong anticancer activity. It is a generally accepted paradigm that the nature of the coordinated N,N L ligand has a major impact on the cytotoxicity. In this study, a series of new functionalised Cp complexes of molybdenum was synthesised from derivatised fulvenes as π-ligand precursors. Indeed, the coordination sphere's modulation by various N,N-chelating ligands afforded species active toward leukemic cell line MOLT-4 with IC50 values depending on the character of the N,N-chelator used. However, following study clearly showed that functionalisation of the Cp ring with an amine moiety considerably improved cytotoxicity. These results are of crucial importance for the future design of highly active cytotoxic drugs, as modification of cyclopentadienyl is believed to have a minor effect on biological activity.


Executive functioning of complicated-mild to moderate traumatic brain injury patients with frontal contusions.
Executive dysfunctions are among the most prevalent neurobehavioral sequelae of traumatic brain injuries (TBIs). Using culturally validated tests from the Delis-Kaplan Executive Function System (D-KEFS: Trail Making, Verbal Fluency, Design Fluency, Sorting, Twenty Questions, and Tower) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS: Rule Shift Cards, Key Search, and Modified Six Elements), the current study was the first to examine executive functioning in a group of Iranian TBI patients with focal frontal contusions. Compared with a demographically matched normative sample, the frontal contusion patients showed substantial impairments, with very large effect sizes (p ≤ .003, 1.56 < d < 3.12), on all the executive measures. Controlling for respective lower-level/fundamental conditions, the differences on the highest-level executive (cognitive switching) conditions were still significant. The frontal patients also committed more errors. Patients with lateral prefrontal (LPFC) contusions were qualitatively worst. For example, only the LPFC patients committed perseverative repetition errors. Altogether, our results support the notion that the frontal lobes, specifically the lateral prefrontal regions, play a critical role in cognitive executive functioning, over and above the contributions of respective lower-level cognitive abilities. The results provide clinical evidence for validity of the cross-culturally adapted versions of the tests.


Mapping the resistance-associated mobilome of a carbapenem-resistant Klebsiella pneumoniae strain reveals insights into factors shaping these regions and facilitates generation of a 'resistance-disarmed' model organism.
This study aims to investigate the landscape of the mobile genome, with a focus on antibiotic resistance-associated factors in carbapenem-resistant Klebsiella pneumoniae. The mobile genome of the completely sequenced K. pneumoniae HS11286 strain (an ST11, carbapenem-resistant, near-pan-resistant, clinical isolate) was annotated in fine detail. The identified mobile genetic elements were mapped to the genetic contexts of resistance genes. The blaKPC-2 gene and a 26 kb region containing 12 clustered antibiotic resistance genes and one biocide resistance gene were deleted, and the MICs were determined again to ensure that antibiotic resistance had been lost. HS11286 contains six plasmids, 49 ISs, nine transposons, two separate In2-related integron remnants, two integrative and conjugative elements (ICEs) and seven prophages. Sixteen plasmid-borne resistance genes were identified, 14 of which were found to be directly associated with Tn1721-, Tn3-, Tn5393-, In2-, ISCR2- and ISCR3-derived elements. IS26 appears to have actively moulded several of these genetic regions. The deletion of blaKPC-2, followed by the deletion of a 26 kb region containing 12 clustered antibiotic resistance genes, progressively decreased the spectrum and level of resistance exhibited by the resultant mutant strains. This study has reiterated the role of plasmids as bearers of the vast majority of resistance genes in this species and has provided valuable insights into the vital role played by ISs, transposons and integrons in shaping the resistance-coding regions in this important strain. The 'resistance-disarmed' K. pneumoniae ST11 strain generated in this study will offer a more benign and readily genetically modifiable model organism for future extensive functional studies.


Early human cultural and skeletal remains from guitarrero cave, northern peru.
An early man site in highland Peru yielded a rich cultural assemblage in stratigraphic association with faunal remains, botanical remains, and campfire remnants that furnished secure radiocarbon dates. A human mandible and teeth, showing interesting patterns of occlusal wear, were found in a stratum dated by a charcoal sample to 10,610 B.C., the oldest such date in South America.


Chikungunya Detection during Dengue Outbreak in Sumatra, Indonesia: Clinical Manifestations and Virological Profile.
Chikungunya fever (CHIK) is an acute viral infection caused by infection with chikungunya virus (CHIKV). The disease affects people in areas where certain Aedes species mosquito vectors are present, especially in tropical and subtropical countries. Indonesia has witnessed CHIK disease since the early 1970s with sporadic outbreaks occurring throughout the year. The CHIK clinical manifestation, characterized by fever, headache, and joint pain, is similar to that of dengue (DEN) disease. During a molecular study of a DEN outbreak in Jambi, Sumatra, in early 2015, DENV-negative samples were evaluated for evidence of CHIKV infection. Among 103 DENV-negative samples, eight samples were confirmed (7.8%) as positive for CHIKV by both molecular detection and virus isolation. The mean age of the CHIK patients was 21.3 ± 9.1 (range 11-35 years). The clinical manifestations of the CHIK patients were mild and mimicked DEN, with fever and headache as the main symptoms. Only three out of eight patients presented with classical joint pain. Sequencing of the envelope glycoprotein E1 gene and phylogenetic analysis identified all CHIKV isolates as belonging to the Asian genotype. Overall, our study confirms sustained endemic CHIKV transmission and the presence of multiple arboviruses circulating during a DEN outbreak in Indonesia. The co-circulation of arboviruses poses a public health threat and is likely to cause misdiagnosis and underreporting of CHIK in DEN-endemic areas such as Indonesia.


Residency Exposure to Emergency Medical Services Concepts Through Immersion, Interprofessional Collaboration and Assembly Line Education.
The use of innovative strategies for teaching, such as flipped classroom and assembly line education, has become increasingly popular to engage learners. Residency education has been incorporating these methods to master content, develop critical skills, and improve professionalism. We created a three-part immersion experience to teach Emergency Medical Services (EMS) concepts to emergency medicine residents. Residents participated in a mass casualty incident (MCI) in which they were tasked to triage patients and allocate resources in a hospital to treat 11 victims properly. The second portion was to manage a cardiac arrest scenario in the field with the tools our EMS colleagues had available. Lastly, they were asked to create short, high-yield lectures about topics related to EMS. Pre- and post-test surveys were used to assess the effectiveness of the experience in teaching residents core EMS topics. It was determined that residents not only felt more prepared for an MCI, but they also were more comfortable with their skills as a result of participating in this activity. Our study further highlights the benefits of non-traditional techniques in residency education. The use of immersion experiences was unique and overall a positive experience for learners. The techniques used in this activity allowed residents to gain confidence in more challenging topics for emergency physicians. This format could be applied to many more topics in the future as an innovative education technique.


Glucagon binding and lipolytic response in isolated adipocytes from streptozotocin-diabetic rats.
Evidence for pre-receptor, receptor and post-receptor glucagon defects was investigated in adipocytes from streptozotocin-diabetic rats. For this purpose male Wistar rats were injected by cardiac puncture with streptozotocin (65 mg/Kg body-weight) or saline solution and sacrificed after 7 and 15 days of drug administration. Increased glucagon levels and increased glucagon degradation in serum together with a decrease in glucagon binding were found in both groups of diabetic rats. The decrease in glucagon binding was related to a decrease in the number of glucagon receptors/cell rather than to a change in receptor affinity. The lipolytic response of glucagon was increased. However, the ability of glucagon to increase basal or theophylline-stimulated cAMP accumulation in the incubation medium of adipocytes from diabetic rats was decreased. Such alterations could represent a counter-regulatory mechanism of the hyperglucagonemia detected in streptozotocin-diabetic rats.


Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer.
A variety of pulmonary disorders, including cystic fibrosis, are potentially amenable to treatment in which a therapeutic gene is directly transferred to the bronchial epithelium. This is difficult to accomplish because the majority of airway epithelial cells replicate slowly and/or are terminally differentiated. Adenovirus vectors may circumvent this problem, since they do not require target cell proliferation to express exogenous genes. To evaluate the diversity of airway epithelial cell targets for in vivo adenovirus-directed gene transfer, a replication deficient recombinant adenovirus containing the Escherichia coli lacZ (beta-galactosidase [beta-gal]) gene (Ad.RSV beta gal) was used to infect lungs of cotton rats. In contrast to uninfected animals, intratracheal Ad.RSV beta gal administration resulted in beta-gal activity in lung lysate and cytochemical staining in all cell types forming the airway epithelium. The expression of the exogenous gene was dose-dependent, and the distribution of the beta-gal positive airway epithelial cells in Ad.RSV beta gal-infected animals was similar to the normal cell differential of the control animals. Thus, a replication deficient recombinant adenovirus can transfer an exogenous gene to all major categories of airway epithelial cells in vivo, suggesting that adenovirus vectors may be an efficient strategy for in vivo gene transfer in airway disorders such as cystic fibrosis.


Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer.
To investigate the effect of parthenolide on apoptosis and autophagy and to study the role of the PI3K/Akt signaling pathway in cervical cancer. Parthenolide inhibits HeLa cell viability in a dose dependent-manner and was confirmed by MTT assay. Parthenolide (6 µM) induces mitochondrial-mediated apoptosis and autophagy by activation of caspase-3, upregulation of Bax, Beclin-1, ATG5, ATG3 and down-regulation of Bcl-2 and mTOR. Parthenolide also inhibits PI3K and Akt expression through activation of PTEN expression. Moreover, parthenolide induces generation of reactive oxygen species that leads to the loss of mitochondrial membrane potential. Parthenolide induces apoptosis and autophagy-mediated growth inhibition in HeLa cells by suppressing the PI3K/Akt signaling pathway and mitochondrial membrane depolarization and ROS generation. Parthenolide may be a potential therapeutic agent for the treatment of cervical cancer.


[Bioinformatics technologies for the analysis of antigenic evolution of influenza viruses].
Human influenza viruses mutate from time to time, causing annual epidemics worldwide. The strong immune pressure in the human population selects a new variant every year, and the antigenic change is one of the primary reasons why vaccination is not a perfect measure to control seasonal influenza. Thus prediction of antigenic change of influenza A virus has been one of the major public health goals. In this review bioinformatics technologies that have been developed to achieve this goal were summarized.


Effect of Saffron (Fan Hong Hua) On the Readiness of The Uterine Cervix In Term Pregnancy: A Placebo-Controlled Randomized Trial.
Readiness of the cervix is required for successful induction of labor, and there are a number of ways in which this can be achieved. The aim of the present study was to assess whether taking saffron orally could have an effect on the cervical readiness (primary outcome) and some delivery and neonatal outcomes (secondary outcomes) in women in the stage of term pregnancy. In this double-blind trial, 50 women with a gestational age of 39 to 41 weeks, no indication of cesarean section, a Bishop's score of less than 4, who had plan to have vaginal delivery at Shohada hospital of Bonab, Iran were randomized into two groups receiving three 250mg saffron or placebo pills in 24 hours. The readiness of the cervix was assessed using the Bishop's score. The Mann-Whitney U test was used to compare the scores between the groups. There were no significant differences between the groups in terms of the Bishop's score at the baseline (P = 0.792) and 10-12 hours after starting the intervention (P = 0.159). The Bishop's score was significantly higher in the saffron group 20 - 24 hours after the intervention was started (P = 0.029) and just after onset of active uterine contractions (P = 0.003). In the saffron group, there was no cesarean section and 1 meconium staining of the fetus, but 3 and 4, respectively, in the placebo group. There was no statistically significant difference between the groups in terms of the timing of the onset of spontaneous active uterine contractions, the duration of the first and second stages of labor, the need for delivery augmentation, and the first and fifth minutes of neonatal Apgar (P > 0.05). No adverse event was reported in any of the groups. Saffron can increase the readiness of the cervix in term pregnancies. However, the study limitations do not allow for any definite conclusions for its use in clinical practice, and more research is needed to assess its effect on delivery and neonatal outcomes.


Association of the estimated 24-h urinary sodium excretion with albuminuria in adult koreans: the 2011 Korea National Health and Nutrition Examination Survey.
Sodium intake and albuminuria have important roles in blood pressure and renal progression. Although their relationship has been reported, the results have not been consistent and all studies have examined small populations. This study investigated the role of the estimated 24-h urinary sodium excretion as a marker of sodium intake and albuminuria. This investigation included 5,187 individuals age 19 years and older from a cross-sectional, nationally representative, stratified survey: The Korea National Health and Nutrition Examination Survey (KNHANES V-2), in 2011. Albuminuria was defined as a urinary albumin/creatinine ratio ≥30 mg/g. The 24-h urinary sodium excretion was estimated from a spot urine. On classifying our participants into quartiles based on the estimated 24-h urinary sodium excretion, the prevalence of albuminuria increased with the 24-h urinary sodium excretion (5.3, 5.7, 7.5, and 11.8% in the first through fourth quartiles, respectively, p for trend <0.001). Even after adjusting for age, sex, diabetes, obesity, and hypertension, the significance persisted. In a multiple logistic regression analysis, the second and third quartiles of the estimated 24-h urinary sodium excretion were not associated with the presence of albuminuria with the first quartile as a control. However, the fourth quartile was significantly associated with the presence of albuminuria (odds ratio 1.61 [95% confidence interval 1.71-2.21], p = 0.003) after adjusting for age, sex, diabetes, obesity, and hypertension. These findings suggest that salt intake is associated with the presence of albuminuria in the general Korean adult population.


Antiprotozoal and cytotoxic naphthalene derivatives from Diospyros assimilis.
Chemical investigation of the roots of Diospyros assimilis had led to the isolation and characterization of six naphthalene derivatives, two 2-naphthaldehyes, namely 4-hydroxy-3,5-dimethoxy-2-naphthaldehyde 1, 4-hydroxy-5-methoxy-2-naphthaldehye 2, its related isomer 5-hydroxy-4-methoxy-2-naphthaldehyde 3 and three commonly occurring naphthoquinones, diospyrin 4, 8'-hydroxyisodiospyrin 5 and the simple monomer, plumbagin 6. Their chemical structures were established by detailed NMR investigations including 1H and 13C NMR, HSQC, HMBC and NOESY experiments. In addition, the naphthalene derivatives 1-5 were evaluated for their in vitro antiprotozoal activity against protozoan parasites belonging to the genera Trypanosoma, Leishmania and Plasmodium. Among the tested compounds, naphthaldehyde 1 showed moderate inhibition of the growth of the parasites, T. brucei, T. cruzi, L. donovani with IC50 values of 19.82, 12.28 and 38.78 microM and displayed cytotoxicity towards rat skeletal myoblasts (L-6 cells) with IC50 of 174.94 microM, while 2 and 3 were found to be comparatively less active to 1. The dimeric quinones 4 and 5 exhibited good activity against T. brucei and L. donovani with IC50 of 1.12 and 8.82 microM and 12.94 and 16.66 microM respectively.


Pharmacotherapy for disordered sleep in post-traumatic stress disorder: a systematic review.
Sleep disorders, such as insomnia and nightmares, are common problems in post-traumatic stress disorder (PTSD), exert a strong negative influence on the quality of life and are a great challenge for clinical psychiatry. Several studies have reported on the efficacy of drugs for the treatment of PTSD-related sleep disorders. These studies have not been systematically reviewed. This is the first review on the effectiveness of sleep medication in PTSD. We performed a Medline, EMBASE and Cochrane Library Indexed search, using the keywords: PTSD, pharmacotherapy, therapy, sleep, nightmares, insomnia and review. From this database, English-language, human subject, data driven papers published after 1980 were selected. Forty eight articles are discussed. Open-label and case studies suggest efficacy for some antidepressants, anticonvulsants and atypical antipsychotics. Only a few placebo-controlled studies have been published. They show promising results for the atypical antipsychotic olanzapine, and the alpha1-adrenoceptor antagonist prazosin. In comparison to the incidence and impact of sleep complaints in PTSD, the pharmacotherapeutic armamentarium for PTSD-related sleep complaints remains poorly investigated. Some recent studies show promising results, especially for alpha1-adrenoceptor and 5-HT2 receptor antagonists. However, randomized controlled trials with larger populations need to be conducted.


[Demography and epidemiology facts in geriatric oncology].
For decades, the ageing of the French population is constant. It is about an important phenomenon with a clean active dynamics. In 2050, the persons of more than 60 years will represent 33% of the population, and the 85 years and more 7%. Jointly the incidence of the cancer increases considerably after 65 years. This conjunction makes that more than a cancer on two occurs in elderly patients. Mortality by cancer in this age bracket does not know the favorable evolution observed in young people. This is related to more advanced stages of the disease at the time of diagnosis, with the rarer use to active therapeutics. However the elderly would like as younger people to receive an effective treatment of their cancer. The general practitioner has a fundamental role to play in the early diagnosis and in the participation to the management of cancer patient.


Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group.
In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas--7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P = 0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31; 95 percent confidence interval, 0.12 to 0.78). Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.


Placebo-controlled, blind study of dietary manipulation therapy in rheumatoid arthritis.
In a blind, placebo-controlled study of dietary manipulation therapy in outpatients with rheumatoid arthritis there was significant objective improvement during periods of dietary therapy compared with periods of placebo treatment, particularly among "good responders". Possible explanations for improvement include reduced food intolerance, reduced gastrointestinal permeability, and benefit from weight loss and from altered intake of substrates for prostaglandin production. A proportion of the improvement was due to a placebo response, but this was not sufficient to explain the whole improvement.


Caesarean and post-partum hysterectomy 1968-1983.
There have been 47 caesarean or post-partum hysterectomies over a period of 15 years at Birmingham Maternity Hospital, a frequency of 7 per 10 000 deliveries. In 12 patients the procedure was performed electively for a gynaecological or haematological disorder. In the remainder, emergency hysterectomy was necessary as a life saving measure, in most instances to overcome uncontrollable haemorrhage. The commonest cause of uncontrollable bleeding was a morbidly adherent placenta which occurred in 1 per 4348 pregnancies, and was associated with previous uterine surgery particularly if combined with placenta praevia. Such patients require the presence of an experienced obstetrician to make an early decision to operate and perform a technically demanding operation.


Entropy of surface EMG reflects object weight in grasp-and-lift task.
Fingertip force coordination is crucial to the success of grasp-and-lift tasks. In the development of motor prosthesis for daily applications, the ability to accurately classify the desired grasp-and-lift from multi-channel surface electromyography (sEMG) is essential. In order to extract reliable indicators for fingertip force coordination, we searched an extensive set of sEMG features for the optimal subset of relevant features. Using mutual information based feature selection we found that a subset of not more than 10 sEMG features selected from over seven thousand, could effectively classify object weights in grasp-and-lift tasks. Average classification accuracies of 82.53% in the acceleration phase and 88.61% in the isometric contraction phase were achieved. Furthermore, sEMG features associated with object weights and common across individuals were identified. These time-domain features (entropy, mean/median absolute deviation, pNNx) can be calculated efficiently, providing possible new indicators.


What do patients know about ultrasound, CT and MRI?
To establish the level of patient knowledge of ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI); to describe patient information-seeking behaviour before attendance; and to assess patients' understanding of the main aspects of scanning examinations. Survey of people attending for ultrasound, CT and MRI using a questionnaire, including 12 statements on simple aspects of procedures, to be indicated as true or false. Radiology department of an acute teaching hospital NHS Trust in the north-east of Scotland. A convenience sample of 500 out-patient, non-emergency first time attenders for ultrasound (300), computed tomography (150), and magnetic resonance imaging (50). An 82% response rate to the questionnaire was achieved. Less than half the patients (48.9%, 182/372) indicated they knew the type of investigation they had been referred for. When responses were compared with referral letters, 64% (238/372) were incongruent. Few participants hadsought information (32%, 120/372), but of those who had the main source was family and friends (72%, 86/120). Seven participants searched the Internet. Eighty-two percent (308/372) of participants reported having been given an explanation of why an investigation was necessary. The majority of participants (67.8%, 251/372) expected to receive their results within 2 weeks. The mean score on the 12 true/false knowledge statements was 3.8, and 17% (65/372) answered 'Don't know' to all the statements. One person answered all questions correctly. Patients were not well informed regarding these investigations. This has significant implications for information-giving strategies and informed consent.


Using unsupervised analysis to constrain generalization bounds for support vector classifiers.
A crucial issue in designing learning machines is to select the correct model parameters. When the number of available samples is small, theoretical sample-based generalization bounds can prove effective, provided that they are tight and track the validation error correctly. The maximal discrepancy (MD) approach is a very promising technique for model selection for support vector machines (SVM), and estimates a classifier's generalization performance by multiple training cycles on random labeled data. This paper presents a general method to compute the generalization bounds for SVMs, which is based on referring the SVM parameters to an unsupervised solution, and shows that such an approach yields tight bounds and attains effective model selection. When one estimates the generalization error, one uses an unsupervised reference to constrain the complexity of the learning machine, thereby possibly decreasing sharply the number of admissible hypothesis. Although the methodology has a general value, the method described in the paper adopts vector quantization (VQ) as a representation paradigm, and introduces a biased regularization approach in bound computation and learning. Experimental results validate the proposed method on complex real-world data sets.


Cytotoxic Effect of Iranian Vipera lebetina Snake Venom on HUVEC Cells.
Envenomation by heamotoxic snakes constituted a critical health occurrence in the world. Bleeding is the most sever consequence following snake bite with viperid and crothalid snakes. It is believed that the degradation of vascular membrane caused hemorrhage; in contrast, some suggested that direct cytotoxicity has role in endothelial cell disturbances. This study was carried out to evaluate the direct toxicity effect of V. lebetina crude venom on Human Umbilical Vein Endothelial Cells (HUVECs). The effect of V. lebetina snake venom on HUVECs growth inhibition was determined by MTT assay and neutral red uptake assay. The integrity of cell membrane through LDH release was measured with the Cytotoxicity Detection Kit. Morphological changes of endothelial cells were also evaluated using a phase contrast microscope. In MTT assay, crude venom showed a cytotoxic effect on endothelial cells which was confirmed by the effect observed with neutral red assay. Also, crude venom caused changes in the integrity of cell membrane by LDH release. The morphological alterations enhanced in high concentration results in total cells number reduced. V. lebetina venom showed potential direct cytotoxic effects on human endothelial cells in a manner of concentration- dependent inhibition.


Pragmatic assessment of exercise in routine care using an MDHAQ: associations with changes in RAPID3 and other clinical variables.
Exercise is associated with major benefits in patients with rheumatic diseases for both cardiovascular and rheumatic status. However, information about exercise generally is not collected systematically in routine rheumatology care. A multidimensional health assessment questionnaire (MDHAQ), which was designed for busy clinical settings, includes a query about exercise status. We analyzed possible associations between change in MDHAQ exercise scores and other MDHAQ measures in patients with various rheumatic diseases over one year. In one rheumatology clinical setting, all patients, regardless of diagnosis, complete an MDHAQ before seeing a rheumatologist. The MDHAQ includes scores for physical function, pain, and patient global estimate, compiled into an index, routine assessment of patient index data (RAPID3), as well as a self-report joint count and a query about exercise. Patients were classified into four groups according to their exercise status at baseline and one year later as: EXER-Yes (regular exercise), EXER-Yes; EXER-No (no regular exercise), EXER-Yes; EXER-Yes, EXER-No; and EXER-No, EXER-No. These groups were compared using the chi square and Kruskal-Wallis tests and analysis of variance (ANOVA). Patients who reported regular exercise at baseline were younger, had higher formal education, and better clinical status than other patients. The EXER-No, EXER-Yes group had greater improvement in other MDHAQ variables than patients in the other three groups. By contrast, the EXER-Yes, EXER-No group was the only group with poorer status one year later. The MDHAQ exercise query indicates that regular exercise is associated with better clinical status. Patients in the EXER-No, EXER-Yes group reported the best clinical improvement, although it is not known whether exercise preceded or followed the improved clinical status.


Elasmobranchs as bioindicators of pollution in the marine environment.
Bioindicator species are increasingly valuable in environmental pollution monitoring, and elasmobranch species include many suitable candidates for that role. By measuring contaminants and employing biomarkers of effect in relevant elasmobranch species, scientists may gain important insights about the impacts of pollution in marine ecosystems. This review compiles biomarkers applied in elasmobranchs to assess the effect of pollutants (e.g., metals, persistent organic pollutants, and plastics), and the environmental changes induced by anthropogenic activities (e.g., shifts in marine temperature, pH, and oxygenation). Over 30 biomarkers measured in more than 12 species were examined, including biotransformation biomarkers (e.g., cytochrome P450 1A), oxidative stress-related biomarkers (e.g., superoxide anion, lipid peroxidation, catalase, and vitamins), stress proteins (e.g., heat shock protein 70), reproductive and endocrine biomarkers (e.g., vitellogenin), osmoregulation biomarkers (e.g., trimethylamine N-oxide, Na+/K+-ATPase, and plasma ions), energetic and neurotoxic biomarkers (e.g., lactate dehydrogenase, lactate, and cholinesterases), and histopathological and morphologic biomarkers (e.g., tissue lesions and gross indices).


Recurrent craniofacial dermatofibrosarcoma protuberans: long-term prognosis after close surgical removal.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm of the dermis that rarely manifests in the craniofacial area. In this retrospective analysis, we investigated the long-term survival of 7 patients with recurrent craniofacial DFSP. This study includes all patients in our department with recurrences of DFSP between 1989 and 2006. All patients were treated by radical surgery with 1-cm free safety margin in every direction and remained in routine long-term follow-up for tumor patients. Two of the 7 patients showed a local recurrence, which was again successfully treated surgically with the same technique. Advanced reconstruction with free full-thickness skin transfers, regional flaps, and forearm flaps, respectively, was required in 5 of the 7 patients. The other 2 patients were reconstructed locally. The long-term prognosis of craniofacial DFSP can be assessed optimistically even if the tumor already reoccurred. All 7 patients included in this study are still alive and so far not suffering from local recurrence. Advanced reconstructive techniques are often required in the management of reoccurring craniofacial DFSP. Late recurrences have been reported; therefore, a long-term follow-up for these patients should be considered.


Multiple channel bridges for spinal cord injury: cellular characterization of host response.
Bridges for treatment of the injured spinal cord must stabilize the injury site to prevent secondary damage and create a permissive environment that promotes regeneration. The host response to the bridge is central to creating a permissive environment, as the cell types that respond to the injury have the potential to secrete both stimulatory and inhibitory factors. We investigated multiple channel bridges for spinal cord regeneration and correlated the bridge structure to cell infiltration and axonal elongation. Poly(lactide-co-glycolide) bridges were fabricated by a gas foaming/particulate leaching process. Channels within the bridge had diameters of 150 or 250 microm, and the main body of the bridge was highly porous with a controllable pore size. Upon implantation in a rat spinal cord hemisection site, cells infiltrated into the bridge pores and channels, with the pore size influencing the rate of infiltration. The pores had significant cell infiltration, including fibroblasts, macrophages, S-100beta-positive cells, and endothelial cells. The channels of the bridge were completely infiltrated with cells, which had aligned axially, and consisted primarily of fibroblasts, S-100beta-positive cells, and endothelial cells. Reactive astrocytes were observed primarily outside of the bridge, and staining for chondroitin sulfate proteoglycans was decreased in the region surrounding the bridge relative to studies without bridges. Neurofilament staining revealed a preferential growth of the neural fibers within the bridge channels relative to the pores. Multiple channel bridges capable of supporting cellular infiltration, creating a permissive environment, and directing the growth of neural fibers have potential for promoting and directing spinal cord regeneration.


Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review.
In this exploratory, hypothesis-generating literature review, we evaluated potentially differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C in published studies of ω-3 fatty acid supplementation or prescription ω-3 fatty acid ethyl esters. Placebo-adjusted changes in mean lipid parameters were compared in randomized, controlled trials in subjects treated for ≥ 4 weeks with DHA or EPA. Of 22 studies identified, 6 compared DHA with EPA directly, 12 studied DHA alone (including 14 DHA-treated groups), and 4 examined EPA alone. In studies directly comparing EPA with DHA, a net increase in LDL-C of 3.3% was observed with DHA (DHA: +2.6%; EPA: -0.7%). In such head-to-head comparative studies, DHA treatment was associated with a net decrease in TG by 6.8% (DHA: -22.4%; EPA: -15.6%); a net increase in non-HDL-C by 1.7% (DHA: -1.2%; EPA -2.9%); and a net increase in HDL-C by 5.9% (DHA: +7.3%; EPA: +1.4%). Increases in LDL-C were also observed in 71% of DHA-alone groups [with demonstrated statistical significance (P < .05) in 67% (8 of 12) DHA-alone studies] but not in any EPA-alone studies. Changes in LDL-C significantly correlated with baseline TG for DHA-treated groups. The range of HDL-C increases documented in DHA-alone vs EPA-alone studies further supports the fact that HDL-C is increased more substantially by DHA than EPA. In total, these findings suggest that DHA-containing supplements or therapies were associated with more significant increases in LDL-C and HDL-C than were EPA-containing supplements or therapies. Future prospective, randomized trials are warranted to confirm these preliminary findings, determine the potential effects of these fatty acids on other clinical outcomes, and evaluate the generalizability of the data to larger and more heterogeneous patient populations.


The CD22-IGF2R interaction is a therapeutic target for microglial lysosome dysfunction in Niemann-Pick type C.
Lysosome dysfunction is a shared feature of rare lysosomal storage diseases and common age-related neurodegenerative diseases. Microglia, the brain-resident macrophages, are particularly vulnerable to lysosome dysfunction because of the phagocytic stress of clearing dying neurons, myelin, and debris. CD22 is a negative regulator of microglial homeostasis in the aging mouse brain, and soluble CD22 (sCD22) is increased in the cerebrospinal fluid of patients with Niemann-Pick type C disease (NPC). However, the role of CD22 in the human brain remains unknown. In contrast to previous findings in mice, here, we show that CD22 is expressed by oligodendrocytes in the human brain and binds to sialic acid–dependent ligands on microglia. Using unbiased genetic and proteomic screens, we identify insulin-like growth factor 2 receptor (IGF2R) as the binding partner of sCD22 on human myeloid cells. Targeted truncation of IGF2R revealed that sCD22 docks near critical mannose 6-phosphate–binding domains, where it disrupts lysosomal protein trafficking. Interfering with the sCD22-IGF2R interaction using CD22 blocking antibodies ameliorated lysosome dysfunction in human NPC1 mutant induced pluripotent stem cell–derived microglia-like cells without harming oligodendrocytes in vitro. These findings reinforce the differences between mouse and human microglia and provide a candidate microglia-directed immunotherapeutic to treat NPC.


Single nucleotide polymorphisms and breast cancer: not yet a success story.
Numerous studies have examined low penetrance susceptibility polymorphisms in candidate genes, with some reporting significant findings. However, for the most part these associations could not be replicated in subsequent studies, suggesting that the original observations were due to chance. The failure to identify meaningful common genetic variation in relation to breast cancer should give us pause for thought and make us reconsider our current research strategies. The most recent directions of pooling samples to increase statistical power and pursuing whole genome screens may overcome some obstacles while also creating new challenges. Future studies should perhaps also consider alternative designs such as using surrogate (preferably continuous) markers of breast cancer, focusing on high-risk populations, and defining pathologically distinct outcomes.


Recent research on polyphenolics in vision and eye health.
A long-standing yet controversial bioactivity attributed to polyphenols is their beneficial effects in vision. Although anecdotal case reports and in vitro research studies provide evidence for the visual benefits of anthocyanin-rich berries, rigorous clinical evidence of their benefits is still lacking. Recent in vitro studies demonstrate that anthocyanins and other flavonoids interact directly with rhodopsin and modulate visual pigment function. Additional in vitro studies show flavonoids protect a variety of retinal cell types from oxidative stress-induced cell death, a neuroprotective property of significance because the retina has the highest metabolic rate of any tissue and is particularly vulnerable to oxidative injury. However, more information is needed on the bioactivity of in vivo conjugates and the accumulation of flavonoids in ocular tissues. The direct and indirect costs of age-related vision impairment provide a powerful incentive to explore the potential for improved vision health through the intake of dietary polyphenolics.


Effect of contrast dose on diagnostic performance in DCE-MR breast imaging.
To assess the diagnostic performance of breast magnetic resonance (MR) imaging as a function of gadolinium contrast dose using a retrospective reader study. IRB approval was obtained prior to the start of this study and was HIPAA compliant. One-hundred and fifty MR breast examinations were included that were acquired between January 2001 and December 2006. Seventy-five patients received contrast doses (gadopentetate dimeglumine) by weight of 0.10 mmol/kg and 75 patients were imaged using fixed volumes of 20 ml. The images were assessed by two radiologists with performance calculated for each reader as well as a combined assessment. Dose response was measured by comparing performance between cases binned by dose: <=0.10; >0.10; and >0.13 mmol/kg. Statistical significance was calculated using a one-sided Z-test for differences in proportions with interobserver agreement calculated using Cohen's kappa statistics. In the combined reader assessment with equivocal lesions classified as negative, sensitivity rose from 66% (19/29) to 92% (24/26, P < 0.01) and 95% (18/19, P < 0.01) with the specificity also increasing from 65% (32/49) to 87% (40/46, P < 0.01) and 86% (32/37, P = 0.01) corresponding to doses <=0.10, >0.10, >0.13 mmol/kg. With equivocal lesions classified as positive, sensitivity rose from 79% (23/29) to 92% (24/26, P < 0.10) and 95% (18/19, P < 0.10) Specificity also increased from 53% (26/49) to 72% (33/46, P < 0.05) and 70% (26/37, P = 0.05) with increasing dose. Interobserver agreement also improved at the higher doses.


5-amino-2-mercapto-1,3,4-thidiazole modified single-use sensors for electrochemical DNA analysis.
In this study, single-use graphite electrodes modified with 5-amino-2-mercapto-1,3,4-thidiazole (AMT) were fabricated for electrochemical monitoring of DNA. The surfaces of AMT modified pencil graphite electrodes (PGEs) were characterized by scanning electron microscopy (SEM). Electrochemical behaviors of these electrodes were investigated using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The effects of pretreatment of PGE and immobilization time and concentration of AMT were studied to facilitate an effective immobilization on PGE surface. The efficiency of immobilization is verified by measuring the oxidation signals of either AMT itself or adenine base of DNA, immobilized onto AMT modified electrodes.


Vascular leiomyoma of foot.
Vascular leiomyomas of the foot are relatively rare benign soft tissue tumours which arise from the tunica media and present as painful or painless solitary subcutaneous nodules. We are reporting a rare case of vascular leiomyoma with a dystrophic calcification and a myxoid change.


Managing future Gulf War Syndromes: international lessons and new models of care.
After the 1991 Gulf War, veterans of the conflict from the United States, United Kingdom, Canada, Australia and other nations described chronic idiopathic symptoms that became popularly known as 'Gulf War Syndrome'. Nearly 15 years later, some 250 million dollars in United States medical research has failed to confirm a novel war-related syndrome and controversy over the existence and causes of idiopathic physical symptoms has persisted. Wartime exposures implicated as possible causes of subsequent symptoms include oil well fire smoke, infectious diseases, vaccines, chemical and biological warfare agents, depleted uranium munitions and post-traumatic stress disorder. Recent historical analyses have identified controversial idiopathic symptom syndromes associated with nearly every modern war, suggesting that war typically sets into motion interrelated physical, emotional and fiscal consequences for veterans and for society. We anticipate future controversial war syndromes and maintain that a population-based approach to care can mitigate their impact. This paper delineates essential features of the model, describes its public health and scientific underpinnings and details how several countries are trying to implement it. With troops returning from combat in Afghanistan, Iraq and elsewhere, the model is already getting put to the test.


Hemolytic Response of Iron Oxide Magnetic Nanoparticles at the Interface and in Bulk: Extraction of Blood Cells by Magnetic Nanoparticles.
Surface-active and water-soluble magnetic nanoparticles (NPs) were synthesized in the presence of a series of amphiphilic molecules of different functional groups to determine the hemolytic response and their ability to extract blood cells across the interface and aqueous bulk while maintaining minimum hemolysis. Amphiphilic molecules such as Gemini surfactants of strong hydrophobicity and low hydrophilic-lipophilic balance produced surface-active magnetic NPs, which were highly cytotoxic even when placed at the blood suspension (aqueous)-air interface. A similar behavior was shown by water-soluble magnetic NPs produced using monomeric ionic and nonionic surfactants and different amino acids. The NPs produced using mild biological surfactants and mono- and oligosaccharides of the same functional group proved to be excellent blood cell extractors with minimum hemolysis. α/β-cyclodextrin and dextrose-stabilized magnetic NPs induced negligible hemolysis and extracted more than 50% of blood cells. The results showed that nontoxic magnetic NPs are excellent blood cell extractors from the blood suspension when tagged with amphiphilic molecules possessing good biocompatibility with cell membranes without inducing hemolysis. The work highlights the biological applicability of nontoxic magnetic NPs at biointerfaces and in blood suspensions.


[Experimental study on the therapeutic mechanism of high dose intravenous immunoglobulin in treatment of immune-mediated peripheral neuropathy].
To explore the therapeutic basis of high dose intravenous immunoglobulin (IVIg) in treatment of peripheral neuropathy induced by Campylobacter jejuni lipopolysaccharide (CJ LPS). (1) IVIg (400 mg/kg x d) was given to the rats on the different days respectively during the immunization with CJ LPS. Histological study of sciatic nerve was performed on the 35 th day after immunization. The titer of anti-CJ LPS antibody in sera of immunized rats was measured by ELISA; IgG deposition was detected by immunohistochemistry and expression of TNF-alpha mRNA in the pathological nerves by in situ hybridization histochemistry. (2) When PBMCs were stimulated by CJ LPS in vitro, IVIg was added into culture medium at the doses of 1, 2.5, 5, and 10 mg/ml, respectively. Pathological examination of sciatic nerve was performed on the 7th day after perineural injection of the supernatants. Expression of TNF-alpha mRNA in PBMCs stimulated by CJ LPS in medium was detected by in situ hybridization histochemistry after adding IVIg. (1) The rate of abnormal fibers appearance in IVIg group (1.0%) was much lower than that of the control group (15.0%) after immunization with CJ LPS, P < 0.01. The titer of antibody in control group was 9 times higher than that of IVIg group. There was no expression of immunoglobulin and TNF-alphamRNA in peripheral nerves in IVIg group, but high expression was found in control group in which no IVIg was injected. (2) The expression rates of TNF-alphamRNA on the PBMCs in IVIg group (1.0%) was much lower than that of control group (9.5%). (3) When the PBMCs of normal rats were stimulated by CJ LPS, the expression rates of TNF-alphamRNA in PBMCs of 5 mg/ml IVIg group (3.0%) or 10 mg/ml IVIg group (2.0%) were much lower than that of 1 mg/ml IVIg group (15.0%) or 2.5 mg/ml IVIg group (11.5%), P < 0.01. The rate of abnormal fibers appearance in 5 mg/ml IVIg group (9.8%) or 10 mg/ml IVIg group (8.5%) was much lower than that of 1 mg/ml IVIg group (50.0%), 2.5 mg/ml IVIg group (41.0%) or control group (50.8%) after the perineural injection with the supernatants, respectively, P < 0.01. The therapeutic effect of high dose IVIg might be associated with inhibition of the humoral and cellular immunity simultaneously in peripheral neuropathy induced by CJ LPS.


Haemodynamic monitoring. Problems, pitfalls and practical solutions.
The synthesis of adenosine triphosphate (ATP) depends on the coordinated interaction of oxygen delivery and glucose breakdown in the Krebs cycle. Cellular oxygen depots are non-existent, therefore the peripheral cells are totally dependent on the circulation for sufficient oxygen delivery. Shock is the clinical manifestation of cellular oxygen craving. The commonly measured variables--blood pressure, heart rate, urinary output, cardiac output and systemic vascular resistance--are not sensitive or accurate enough to warn of impending death in acutely ill patients nor are they appropriate for monitoring therapy. Calculated oxygen transport and oxygen consumption parameters provide the best available measures of functional adequacy of both circulation and metabolism. In order to optimise oxygen delivery (DO2), 4 interacting factors must be taken into account: cardiac output, blood haemoglobin content, haemoglobin oxygen saturation and avidity of oxygen binding to haemoglobin. For viscosity reasons, the optimal haemoglobin concentration is in the vicinity of 90 to 100 g/L, but for optimising the oxygen transport 100 to 115 g/L or a haematocrit of 30 to 35% seems better. The p50 (the pO2 at which haemoglobin is 50% saturated) describes the oxygen-haemoglobin dissociation curve; normally its value is +/- 27 mm Hg. It can be influenced by attaining normal body temperature, pH, pCO2 and serum phosphorous levels. In order to obtain an arterial blood saturation (SaO2) of more than 90% with acceptable haemodynamics, the ventilation mode and inspired oxygen fraction (FiO2) must be adapted; care must be taken not to stress the labile circulation with haemodynamic compromising ventilation techniques [e.g. high positive end expiratory pressure (PEEP) levels, inverse-ratio ventilation, etc.]. The factor most amenable to manipulation is the cardiac output, with its 4 determinants--preload, afterload, contractility and heart rate. In daily clinical practice, heart rate should be between 80 and 120 beats/min; small variations are acceptable. Important deviations must be treated by chemically [isoprenaline (isoproterenol)] or electrically (pacing techniques) accelerating the heart, or with the different antiarrhythmic drugs. A wide variety of agents is available to decrease the preload: diuretics [especially furosemide (frusemide)], venodilators like nitroglycerin (glyceryl trinitrate), isosorbide dinitrate (sorbide nitrate) and sodium nitroprusside, ACE inhibitors, phlebotomy, and haemofiltration techniques (peritoneal or haemodialysis, continuous arteriovenous haemofiltration). To increase the preload, volume loading using a rigid protocol ('rule of 7 and 3'), preferably with colloids, or vasopressor agents [norepinephrine (noradrenaline), epinephrine (adrenaline), dopamine] are useful. Arterial vasopressors are needed to improve perfusion pressure of 'critical' (coronary and cerebral) arteries. Afterload can be decreased by arterial vasodilators. Predominantly arterial dilators are hydralazine and clonidine, while sodium nitroprusside, nitroglycerin and isosorbide dinitrate have combined arterial and venous dilating actions.(ABSTRACT TRUNCATED AT 400 WORDS)


Parasitic Diseases With Cutaneous Manifestations.
Parasitic diseases result in a significant global health burden. While often thought to be isolated to returning travelers, parasitic diseases can also be acquired locally in the United States. Therefore, clinicians must be aware of the cutaneous manifestations of parasitic diseases to allow for prompt recognition, effective management, and subsequent mitigation of complications. This commentary also reviews pharmacologic treatment options for several common diseases.