Factors associated with readmission in late-preterm infants: a matched case-control study.
The goal of this study was to evaluate risk factors for readmission among late-preterm (34-36 weeks' gestation) infants in clinical practice. This was a retrospective, matched case-control study of late-preterm infants receiving care across 8 regional hospitals in 2009 in the United States. Those readmitted within 28 days of birth were matched to non-readmitted infants at a ratio of 1:3 according to birth hospital, birth month, and gestational age. Step-wise modeling with likelihood ratio tests were used to develop a multivariable logistic regression model. A subgroup analysis of hyperbilirubinemia readmissions was also performed. Of 1861 late-preterm infants delivered during the study period, 67 (3.6%) were readmitted within 28 days of birth. These were matched to 201 control infants, for a final sample of 268 infants. In multivariable regression, each additional day in length of stay was associated with a significantly reduced odds ratio (OR) for readmission (0.57, P = .004); however, for those infants delivered vaginally, there was no significant association between length of stay and readmission (adjusted OR: 1.08, P = .16). A stronger inverse relationship was observed in subgroup analysis for hyperbilirubinemia readmissions, with the adjusted OR associated with increased length of stay 0.40 (P = .002) for infants born by cesarean delivery but 1.14 (P = .27) for those delivered vaginally. Infants born via cesarean delivery with longer length of hospital stay have a decreased risk for readmission. As hospitals implement protocols to standardize length of stay, mode of delivery may be a useful factor to identify late-preterm infants at higher risk for readmission.


Characteristics of a population of women with breast implants compared with women seeking other types of plastic surgery.
Several previous studies have shown that breast implant patients demonstrate a number of differences compared with the general population. However, studies have not compared patients with breast implants with women receiving other types of plastic surgery, of interest because this latter group has been proposed as a comparison group for assessing the long-term health effects experienced by breast implant patients. Questionnaire data obtained from 7447 breast implant patients and 2203 patients with other types plastic surgery were collected during the course of a retrospective cohort study, to determine whether implant patients demonstrate different characteristics compared with a more restricted group of patients. In contrast to previous investigations that compared implant patients with the general population, distinctive differences with respect to family income, number of pregnancies, alcohol consumption, cigarette smoking, or histories of previous gynecologic operations or operations for benign breast disease were not found. However, implant patients were significantly more likely than other plastic surgery patients to be white, have low levels of education, have early ages at first birth, be thin, and be screened frequently for breast disease. Furthermore, implant patients reported somewhat greater use of exogenous hormones and familial histories of rheumatoid arthritis. These results support the notion that other plastic surgery patients are a more appropriate comparison group than women in the general population for studies of the health effects of breast implants; however, there continue to be distinctive characteristics possessed by breast implant patients, which need to be taken into account in an assessment of what disease effects can be uniquely attributed to silicone breast implants.


Enhanced efficacy with azacytidine and oncolytic BHV-1 in a tolerized cotton rat model of breast adenocarcinoma.
Oncolytic viruses selectively replicate in cancer cells by exploiting biochemical differences between normal and tumor cells. Treatment with epigenetic modifiers such as 5-Azacytidine, a DNA methyltransferase inhibitor, increases the replication and cytotoxicity of oncolytic viruses in vivo and in vitro. The cotton rat is an attractive animal to study oncolytic viruses, as syngeneic models of breast adenocarcinoma and osteosarcoma are well established, and many features of primary and secondary tumor growth recapitulate human disease. Treatment of LCRT breast cancer cells with 5-Azacytidine increases bovine herpesvirus type 1 (BHV-1)-mediated cytotoxicity in vitro, with Chou-Talalay analysis indicating a very strong synergy. In vivo, BHV-1 monotherapy delayed tumor growth but did not improve survival of cotton rats with subcutaneous breast adenocarcinomas. However, combination therapy significantly decreased the incidence of secondary lesions, with enhanced tumor cell clearance and evidence of immune cell infiltration compared to BHV-1 monotherapy. Together, these results warrant further investigation of BHV-1 combination therapy with epigenetic modifiers for the treatment of breast cancer, particularly in the context of the prevention and treatment of secondary lesions.


Myositis Ossificans Traumatica, an Unusual Cause of Mandibular Hypomobility.
Myositis ossificans traumatica is a rare condition in which causes restriction of mandibular movement. In this entity, temporomandibular joint is depleted of any problems; although all the patients have the history of trauma to the mandible and the face. Myositis ossificans traumatica can involve other parts of the body like femoral region with higher incidence in compare to the maxillofacial area. Blunt trauma to the head and neck causes muscle contusion injury, hematoma formation in the injured muscles or nearby soft tissues. Calcification of hematoma and heterotopic bone formation in the muscle, soft tissue, or near bony structures causes progressive decrease in mouth opening. Surgical removal of calcified body has been the only and one method for treatment of this disorder but rate of recurrence is high in the literature. The authors want to introduce 2 new cases of myositis ossificans traumatica, and then discuss about etiology and different treatment modalities.


Progesterone and dexamethasone stimulate proliferation and differentiation of osteoprogenitors and progenitors for adipocytes and macrophages in cell populations derived from adult rat vertebrae.
We investigated the effects of the sex hormone progesterone (Prog) and the synthetic glucocorticoid dexamethasone (Dex) on proliferation and differentiation of progenitor cells of osteogenic, adipocytic, and hemopoietic lineages in cell populations derived from explants of adult female rat lumbar vertebrae. The cell populations were obtained by culturing bone explants in plasma clots immersed in alpha-minimum essential medium plus 10% fetal calf serum (standard medium) and then subculturing the outgrowth cells in standard medium plus 50 micrograms/ml of ascorbic acid, 5 mM beta-glycerophosphate, and with or without Prog or Dex. On day 6 of culture, these populations were analyzed for cAMP responses to parathyroid hormone (PTH), prostaglandin E2 (PGE2), and isoproterenol (IPT). Increases in intracellular cAMP were seen in response to PTH, PGE2, and IPT, and culturing in medium containing Prog increased these responses. At various time periods between days 4-27 of culture, the cultures were evaluated for the presence of bone nodules, alkaline phosphatase (AP)-positive colonies, adipocytes, monocytes, and macrophages. Prog and Dex increased the number of bone nodules and AP-positive colonies. The effect of Prog on bone nodule formation was smaller than that of Dex. In addition, the effect of Dex on bone nodule formation was evident after 10 days of culture, while the Prog-induced effects became significant at days 16-20 of culture. Both hormones also increased the number of Sudan IV-positive colonies (adipocytes), certain types of alpha-naphthyl butyrate esterase (alpha-NBE)-positive colonies (monocytes, macrophages, and T-lymphocytes), and ED2-positive colonies (macrophages). Prog-treated cultures contained more colonies of small spindle-shaped alpha-NBE-positive cells and fewer colonies of small round alpha-NBE-positive cells when compared with Dex-treated cultures. These data indicate that cell populations derived from adult rat lumbar vertebrae contain, among others, osteoprogenitors and progenitors for adipocytes and macrophages that are stimulated to proliferate and differentiate by Prog and Dex. The data also suggest that the effects of Prog and Dex differ qualitatively and quantitatively.


Meloxicam fails to augment the reno-protective effects of soluble epoxide hydrolase inhibition in streptozotocin-induced diabetic rats via increased 20-HETE levels.
The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n=6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months. Glomerular albumin permeability and urinary albumin and nephrin excretion levels were significantly elevated in diabetic rats together with decreased glomerular α3 integrin and nephrin expression levels. Inhibition of sEH reduced glomerular albumin permeability, albumin and nephrin excretion levels and restored the decrease in glomerular α3 integrin and nephrin expression in diabetic rats. Meloxicam failed to reduce renal injury or even to synergize the reno-protective effects of sEH inhibition in diabetic rats. Furthermore, inhibition of sEH reduced the elevation in renal collagen deposition and urinary MCP-1 excretion levels together with a reduction in the number of renal TUNEL positive cells in diabetic vs. control rats (P<0.05). Meloxicam did not reduce renal inflammation or apoptosis in diabetic rats or even exacerbate the anti-inflammatory and anti-apoptotic effects of sEH inhibition. Renal 20-hydroxyeicosatetranoic acid (20-HETE) levels were elevated in diabetic rats and meloxicam further exacerbated this elevation. In conclusion, our study suggests that inhibition of COX failed to provide renal protection or to augment the reno-protective effects of sEH inhibition in diabetic rats, at least in part, via increased inflammatory 20-HETE levels.


In vitro prion-like behaviour of TDP-43 in ALS.
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND), and >95% of familial and sporadic cases involve the deposition of insoluble aggregated, phosphorylated and cleaved TDP-43 protein. Accumulating clinical and biological evidence now indicates that ALS bears a number of similarities to the prion diseases, with TDP-43 acting as a misfolded 'prion-like' protein demonstrating similar underlying pathobiology. Here we systematically address the hypothesis that ALS is a prion-like disorder. First we demonstrate that TDP-43 demonstrates seeded polymerisation in vitro directly from both ALS brain and spinal cord. We next show that the seeding of TDP-43 results in the formation of characteristic insoluble, aggregated, and phosphorylated TDP-43 pathology that directly recapitulates the morphological diversity of TDP-43 inclusions detected in ALS patient CNS tissue. We next demonstrate that this reaction can be serially propagated to produce increasing amounts of phosphorylated TDP-43 pathology, and that aggregates can spread from cell to cell in an analogous fashion to that seen in the prion diseases. Finally, we reproduced our findings in a murine motor neuron-like cell line (NSC-34), where the seeding of TDP-43 induces the formation of TDP-43 oligomers and reduced cell viability. These findings may guide therapeutic strategies in this rapidly progressive and invariably fatal disease.


Performance of the automated multiplex PCR Unyvero implant and tissue infections system in the management of diabetic foot osteomyelitis.
We evaluated the performance of Unyvero implant and tissue infections system (ITI) application (Curetis) to diagnose Diabetic Foot Osteomyelitis (DFOM). The study was conducted in the Diabetic Foot reference center of Nîmes University Hospital (France) from 1 December 2016 to 31 May 2017. We compared the Unyvero ITI PCR to conventional culture and alternative molecular approaches. A total of 79 patients with DFOM were included: 177 microorganisms were isolated by culture, 146 detected by PCR, resulting in a concordance level of 66.7% (65.0-68.4). Discrepant results were obtained for 45 samples, with 59 microorganisms being detected by PCR only (18 samples) or by culture only (27 samples). Unyvero ITI PCR represents an interesting additional diagnosis solution to manage DFOM.


Early and late-onset syncope: insight into mechanisms.
Unexplained syncope is an important clinical challenge. The influence of age at first syncope on the final syncope diagnosis is not well studied. Consecutive head-up tilt patients (n = 1928) evaluated for unexplained syncope were stratified into age groups <30, 30-59, and ≥60 years based on age at first syncope. Clinical characteristics and final syncope diagnosis were analysed in relation to age at first syncope and age at investigation. The age at first syncope had a bimodal distribution with peaks at 15 and 70 years. Prodromes (64 vs. 26%, P < 0.001) and vasovagal syncope (VVS, 59 vs. 19%, P < 0.001) were more common in early-onset (<30 years) compared with late-onset (≥60 years) syncope. Orthostatic hypotension (OH, 3 vs. 23%, P < 0.001), carotid sinus syndrome (CSS, 0.6 vs. 9%, P < 0.001), and complex syncope (>1 concurrent diagnosis; 14 vs. 26%, P < 0.001) were more common in late-onset syncope. In patients aged ≥60 years, 12% had early-onset and 70% had late-onset syncope; older age at first syncope was associated with higher odds of OH (+31% per 10-year increase, P < 0.001) and CSS (+26%, P = 0.004). Younger age at first syncope was associated with the presence of prodromes (+23%, P < 0.001) and the diagnoses of VVS (+22%, P < 0.001) and complex syncope (+9%, P = 0.018). In patients with unexplained syncope, first-ever syncope incidence has a bimodal lifetime pattern with peaks at 15 and 70 years. The majority of older patients present only recent syncope; OH and CSS are more common in this group. In patients with early-onset syncope, prodromes, VVS, and complex syncope are more common.


Relationship between Mycobacterium tuberculosis phylogenetic lineage and clinical site of tuberculosis.
Genotyping of Mycobacterium tuberculosis has revealed 4 major phylogenetic lineages with differential distribution worldwide. It is not clear whether different lineages are associated with different sites of infection (eg, pulmonary tuberculosis versus extrapulmonary tuberculosis). We sought to determine whether M. tuberculosis lineage is associated with the site of tuberculosis disease. We conducted a cross-sectional analysis of all culture-confirmed cases of tuberculosis with routinely determined M. tuberculosis spoligotype-defined lineage reported to the US National Tuberculosis Surveillance System from 2004 through 2008. Odds ratios (ORs) were used to assess the relation between disease site and M. tuberculosis lineage, after adjustment for age, sex, human immunodeficiency virus infection status, region of birth, and race/ethnicity. Of 53972 reported culture-positive tuberculosis cases, 32000 (59.3%) were cases of M. tuberculosis that included complete spoligotype-based data on lineage. Of these, 23844 (74.5%) were exclusively pulmonary, 5085 (15.9%) were exclusively extrapulmonary, and 3071 (9.6%) were combined pulmonary and extrapulmonary. The percentages of tuberculosis cases that were exclusively extrapulmonary differed by lineage: East Asian, 13.0%; Euro-American, 13.8%; Indo-Oceanic, 22.6%; and East-African Indian, 34.3%. Compared with East Asian lineage, the odds of exclusively extrapulmonary tuberculosis relative to exclusively pulmonary tuberculosis were greater for Euro-American (adjusted OR, 1.3; 95% confidence interval [CI], 1.1-1.4), Indo-Oceanic (adjusted OR, 1.7; 95% CI, 1.5-1.9), and East-African Indian (adjusted OR, 1.6; 95% CI, 1.4-1.9) lineages. Phylogenetic lineage of M. tuberculosis is associated with the site of tuberculosis disease.


Practical synthesis of quinoxalinones via palladium-catalyzed intramolecular N-arylations.
A practical and highly efficient route to the synthesis of pharmaceutically interesting quinoxalinone scaffolds is reported. The key step involves an intramolecular palladium-catalyzed N-arylation under microwave irradiation. The developed methodology tolerates a variety of bromoanilides to afford a diverse collection of bicyclic and polycyclic quinoxalinones in high yield.


Modification of the adult Blakemore tube for use in children with bleeding esophageal varices.
A modification of the adult-sized Blakemore tube is described for emergency use in children with bleeding esophageal varices. Inexpensive, readily available, heat-labile tubing was used to adapt the esophageal balloon for use in small children, keeping possible complications at a minimum.


[Kahoot: Applications and Effects in Education].
Stimulating learning motivation and enhancing learning effectiveness are particularly difficult challenges for nursing educators in educating Generation Z learners, who are part of the first generation of true "digital natives". In response, teachers are beginning to integrate gamification techniques into their classrooms in order to motivate classroom participation and to conduct learning evaluation. Kahoot is a free, online quiz platform and instant feedback system that helps teachers create a fun competitive-gaming environment. Learners may access the platform using a mobile phone or tablet to answer multiple-choice questions. The platform may be introduced at different stages of learning activities or combined with the flipped classroom model in order to achieve various teaching goals. This article provides a brief introduction of the gamification of learning and then discusses the operational skills needed to use Kahoot and the effectiveness of this platform, including advantages, limitations, and user feedback. Finally, the authors share their Kahoot-related teaching designs and experiences. It is suggested that nurse educators may apply Kahoot in their innovative teaching practices.


Effect of Estrogen and Progesterone Hormones on the Expression of Angiotensin II Receptors in the Heart and Aorta of Male Rats.
Activation of the Angiotensin II type 1 receptor (AT1R) has been implicated in the pathogenesis of the cardiovascular disease, while activation of Angiotensin II type 2 receptor (AT2R) leads to effects that are opposite to those mediated by AT1R. The interaction between female sex hormones and the renin-angiotensin system was proven to play an essential role in the pathological changes in the cardiovascular system. To investigate the direct effect of estrogen and progesterone on arterial and cardiac AT1R and AT2R expression in vivo in male. Male adult rats were assigned into four groups: Group 1 (control), group 2 (progesterone treated group; 10mg/kg), group 3 (estrogen treated group; 20μg/kg) and group 4 (progesterone; 10mg/kg + estrogen; 20μg/kg treated group). All treatments were administrated subcutaneously every second day for 21days. Estrogen treatments increase the left ventricle (LV) protein expression of AT1R, and progesterone treatment decreased the LV protein expression of AT2R. In the aorta, estrogen treatment increased the mRNA expression levels of AT1R, while progesterone treatment increased the AT2R mRNA expression levels. Estrogen treatment decreases the LV and aortic endothelial nitric-oxide synthase (eNOS) mRNA levels while progesterone treatments decrease the LV eNOS mRNA levels but increase the aortic eNOS mRNA levels. The serum angiotensin II levels were increased by estrogen treatment only. Both estrogen and progesterone treatments appear to have a harmful effect on the male rat hearts, possibly by increasing the protein expression of AT1R (for estrogen), decrease the protein and mRNA expression of AT2R (for progesterone), and decrease the eNOS mRNA levels (for both). However, it seems that progesterone but not estrogen exerts a vascular protective effect in males.


Review of malaria risk and prevention for use in corporate travel.
Malaria continues to be a significant, life-threatening illness in many parts of the world. For corporate travelers from countries with low endemicity, the risk of infection is considerable. Many corporate travelers are unaware of their risk, unsure of the correct preventative measures, and receive incorrect advice regarding prevention or do not comply with advice they have received. This review addresses the risk of malaria to the nonimmune corporate traveler, disease transmission, and recommended means of prevention, including prevention of mosquito bites and antimalaria chemoprophylaxis.


The Aβ-clearance protein transthyretin, like neprilysin, is epigenetically regulated by the amyloid precursor protein intracellular domain.
Proteolytic cleavage of the amyloid precursor protein (APP) by the successive actions of β- and γ-secretases generates several biologically active metabolites including the amyloid β-peptide (Aβ) and the APP intracellular domain (AICD). By analogy with the Notch signalling pathway, AICD has been proposed to play a role in transcriptional regulation. Among the cohort of genes regulated by AICD is the Aβ-degrading enzyme neprilysin (NEP). AICD binds to the NEP promoter causing transcriptional activation by competitive replacement with histone deacetylases (HDACs) leading to increased levels of NEP activity and hence increased Aβ clearance. We now show that the Aβ-clearance protein transthyretin (TTR) is also epigenetically up-regulated by AICD. Like NEP regulation, AICD derived specifically from the neuronal APP isoform, APP695 , binds directly to the TTR promoter displacing HDAC1 and HDAC3. Cell treatment with the tyrosine kinase inhibitor Gleevec (imatinib) or with the alkalizing agent NH4 Cl causes an accumulation of 'functional' AICD capable of up-regulating both TTR and NEP, leading to a reduction in total cellular Aβ levels. Pharmacological regulation of both NEP and TTR might represent a viable therapeutic target in Alzheimer's disease.


N-Terminal peptide labeling strategy for incorporation of isotopic tags: a method for the determination of site-specific absolute phosphorylation stoichiometry.
Determining the phosphorylation stoichiometry at specific sites in a phosphoprotein is a very challenging task. We describe here a novel mass spectrometry based method that is capable of measuring the absolute phosphorylation stoichiometry at specific sites without the need for specific internal standards, phospho-site antibodies or radioactivity. The method is based on a gentle chemical labeling strategy which specifically and differentially labels the N-terminus of all peptides in a sample with either a D(5)- or D(0)-propionyl group and measures the ratio of the abundance of the D(5)/D(0) peptide pairs simultaneously using mass spectrometry. Using matrix-assisted laser desorption/ionization (MALDI), the method can measure absolute stoichiometry to within at least 10% and can be applied to both in vitro and in vivo phosphorylated peptides and proteins. Furthermore, this method can potentially be applied to the quantitative study of other types of protein post-translational modifications, and the profiling of protein expression on the proteome level.


Health Symptoms Related to Pesticide Use in Farmers and Laborers of Ecological and Conventional Banana Plantations in Ecuador.
Conventional banana farming is pesticide-intensive and leads to high exposure of farmworkers. Ecuador is the world's biggest exporter of bananas. In this field study in 5 communities in Ecuador, we recorded potentially pesticide-associated subjective health symptoms in farmworkers and compared pesticide users to workers in organic farming. With one exception, symptom rates were always higher in the pesticide-exposed group. Significance was reached in 8 out of 19 investigated symptoms with the highest odds ratios (and smallest p-values) for local irritation like skin and eye irritation (OR = 3.58, CI 1.10-11.71, and 4.10, CI 1.37-12.31, respectively) as well as systemic symptoms like dizziness (OR = 4.80, CI 1.55-14.87) and fatigue (OR = 4.96, CI 1.65-14.88). Moreover, gastrointestinal symptoms were reported more frequently by pesticide users: nausea (OR = 7.5, CI 1.77-31.77) and diarrhea (OR = 6.43, CI 1.06-30.00). The majority of farmworkers were not adequately protected from pesticide exposure. For example, only 3 of 31 farmworkers that had used pesticides recently reported using gloves and only 6 reported using masks during active spraying. Improved safety measures and a reduction in pesticide use are necessary to protect the health of banana farmworkers.


Prevalence of psychological distress in university students--implications for service delivery.
Mental health problems are one of the leading causes of disability in Australia. General practitioners are often the first and only point of service for people suffering mental health problems, while many do not access services at all. University students can face numerous stressors in addition to academic demands that can contribute to the development or exacerbation of mental health problems. The aim of this study was to identify the prevalence of psychological symptoms in students who were patients at a university health service to enable appropriate planning of services to meet the needs of students. Participants were 384 students attending a university health service in urban Queensland over a period of 4 weeks during semester. At their first visit, patients completed the Kessler Psychological Distress Scale, a measure of psychological distress. Results showed there were significantly more patients experiencing high levels of distress compared with the general population and, consistent with the general population, almost two-thirds had not sought assistance for this distress. Increased distress was associated with increased disability among students. Within a university setting, co-location of specialist mental health services can promote a team approach to mental health care, with GPs, psychiatrists and clinical psychologists working together to increase the availability of care to students in need. The recent introduction of Medicare items for psychological treatment also facilitates greater access to clinical psychologists and other mental health professionals.


[A case of a solitary splenic metastasis from gastric cancer].
A 69-year-old man was brought to our hospital's emergency room with a chief complaint of hematemesis, which had been caused by advanced gastric cancer on the lesser curvature of the stomach's upper body. Subsequently, total gastrectomy with lymph node dissection (D2) was performed. A pathological diagnosis of gastric adenocarcinoma, U, Less, type 2, 100×70mm, tub2, pT3, int, INFb, ly0, v0, pN0 (0/24), pPM0 (30mm), pDM0 (30mm), fStage IIA, was then established. After discharge, the patient was treated with S-1 as adjuvant chemotherapy at a dose of 120mg per day. However, a decrease in the platelet count prompted termination of chemotherapy, which lasted for three courses. Ten months after surgery, serum CEA levels increased to 116.6ng/ml, with enhanced CT showing a solitary splenic tumor with a diameter of 48×52mm suggestive of gastric cancer recurrence. PET/CT revealed no other tumors suggestive of gastric cancer recurrence. Given that only a solitary splenic metastatic tumor was detected, splenectomy was performed eleven months after surgery. Histological findings were the same as the previous gastric cancer, with peritoneal washing cytology being suspicious. Chemotherapy with the SOX regimen (S-1 at a dose of 120mg per day and oxaliplatin at a dose of 100mg/m2) was then started. The patient remained recurrence-free for a half year. Except during the terminal phase, only a few cases of a splenic metastasis from gastric cancer have been reported. We consider splenectomy to be potentially useful for patients with a solitary splenic metastasis from gastric cancer, through which prolonged prognosis could be expected.


An overview of Middle East respiratory syndrome coronavirus vaccines in preclinical studies.
Middle East respiratory syndrome coronavirus (MERS-CoV) causes high mortality in humans. No vaccines are approved for use in humans; therefore, a consistent effort to develop safe and effective MERS vaccines is needed. This review describes the structure of MERS-CoV and the function of its proteins, summarizes MERS vaccine candidates under preclinical study (based on spike and non-spike structural proteins, inactivated virus, and live-attenuated virus), and highlights potential problems that could prevent these vaccines entering clinical trials. It provides guidance for the development of safe and effective MERS-CoV vaccines. Although many MERS-CoV vaccines have been developed, most remain at the preclinical stage. Some vaccines demonstrate immunogenicity and efficacy in animal models, while others have potential adverse effects or low efficacy against high-dose or divergent virus strains. Novel strategies are needed to design safe and effective MERS vaccines to induce broad-spectrum immune responses and improve protective efficacy against multiple strains of MERS-CoV and MERS-like coronaviruses with pandemic potential. More funds should be invested to move vaccine candidates into human clinical trials.


Expression of the vascular endothelial growth factor receptor, KDR, in human placenta.
Vascular endothelial growth factor (VEGF) is a heparin-binding growth factor known to act directly on vascular endothelial cells by promoting cell proliferation and permeability. To date, 3 structurally related cell surface receptors for VEGF, Flt-1, Flt-4 and KDR, have been identified and shown to be human type III receptor tyrosine kinases. The establishment of a vascular network is crucial to the development of the placenta and occurs through both angiogenesis and vasculogenesis. The signals controlling these processes are unclear. Immunohistochemical and in situ hybridisation techniques have localised VEGF in the trophoblast layers and VEGF binding to placental vascular endothelial cells and haemangioblasts has been shown, suggesting a role for VEGF and its receptors in development of the vascular network. In this study we have used specific antibodies to localise KDR and endothelial cells in 1st and 3rd trimester human placenta. The staining showed a colocalisation of KDR with endothelial cells and haemangioblasts. No staining of trophoblast cells was observed, but strong staining of the endothelial cells was seen in the villous stroma adjacent to areas of trophoblast proliferation.


Cooperative amplification-based electrochemical sensor for the zeptomole detection of nucleic acids.
In this work, we developed a multiple-amplification-based electrochemical sensor for ultrasensitive detection of nucleic acids using a disease-related sequence of the p53 gene as the model target. A capture probe (CP) with a hairpin structure is immobilized on the electrode surface via thiol-gold bonding, while its stem is designed to contain a restriction site for EcoRI. In the absence of target DNA, the probe keeps a closed conformation and forms a cleavable region. After treatment with EcoRI, the target binding portion (loop) plus the biotin tag can be peeled off, suppressing the background current. In contrast, the CP is opened by the target hybridization, deforming the restriction site and forcing the biotin tag away from the electrode. On the basis of the biotin-streptavidin complexation, gold nanoparticles (GNPs) modified with a large number of ferrocene-signaling probes (Fc-SPs) are captured by the resulting interface, producing an amplified electrochemical signal due to the GNP-based enrichment of redox-active moieties. Furthermore, Fc tags can be dragged in close proximity to the electrode surface via hybridization between the signaling probes and the CP residues after EcoRI treatment, facilitating interfacial electron transfer and further enhancing the signal. With combination of these factors, the present system is demonstrated to achieve an ultrahigh sensitivity of zeptomole level and a wide dynamic response range of over 7 orders of magnitude.


Corrugation gratings for fast integrated complementary metal-oxide semiconductor photodetectors: implementation and diffraction analyses.
We present simulation experiments to show the feasibility of using a corrugation grating structure at the silicon-silicon dioxide interface to reduce photon-absorption depth and therefore to improve response times for shallow p-n junction photodiodes for use in the optical interconnection of very-large-scale-integrated circuits. A fabrication method that uses standard complementary metal-oxide semiconductor fabrication steps is presented for generating the grating structure. Simulations show reduction in 1/e photon-penetration depth to one half the value that is expected with no grating.


[Application of molecular descriptors for recognition of phosphorylation sites in amino acid sequences].
Recognition of the phosphorylation sites in proteins is required for reconstruction of regulatory processes in living systems. This task is complicated because the phosphorylation motifs in amino acid sequences are considerably degenerated. To improve the prediction efficacy researchers often use additional descriptors, which should reflect physicochemical features of site-surrounding regions. We have evaluated the reasonability of this approach by applying molecular descriptors (MNA) for structural presentation of the peptide segments. Comparative testing was performed using the prognostic method PASS and two input data types: sets of the MNA descriptors represented peptides as chemical structures and amino acid sequences written using a one-letter code. Training sets were classified in accordance with the established types of the enzymes (protein kinases), modifying corresponding phosphorylation sites. The accuracy estimates obtained by prognosis validation for various classes of substrates were significantly different with both the letters and molecular descriptors. In case of the letter description, the prognosis accuracy demonstrated less dependence on the length of peptides in the training set, while in the case of structural descriptors the accuracy level was determined by the peptide size and descriptor characteristics (MNA levels). The maximal prognosis accuracy related to various kinase families was achieved at different sizes of molecular fragments covered by the MNA descriptors of corresponding levels. This obviously reflected structural differences in surroundings of phosphorylation sites modified by various protein kinases. The use of molecular descriptors provided the prognostic results comparable with the results obtained using traditional letter representation. The prognosis accuracy demonstrated less dependence on the method describing site-surrounding peptides at higher accuracy rates. Applying the MNA descriptors it is possible to achieve better accuracy in the cases when the letter description cannot provide acceptable accuracy.


Model process for removal of caseins from milk of transgenic animals.
We describe a method for selective removal of caseins from milk. The method was developed as a model for transgenic milk processing. Raw cow milk spiked with nonmilk proteins was chosen as the model to resemble transgenic animal milk containing recombinant proteins. The most important elements of the process are (1) "deconstruction" of casein micelles in milk by destroying their Ca(2+) core using a chelating agent (EDTA), thus freeing any protein that might be entrapped in casein aggregates, and (2) "reconstruction" of micelles by providing them with a new Ca(2+) core, thus precipitating them away from the whey proteins, and the protein of interest. Calcium phosphate particles (CAP) were used to reform the disrupted casein micelles. The crystal clear supernatant fraction generated by this method provided >90% recovery and 6- to 13-fold concentration of the desired protein. Product-rich supernatant contained no detectable casein residues, as silver-stained SDS-PAGE and Western blot analyses demonstrated.


Characterization of germline mutations in familial lung cancer from the Chinese population.
Compared with numerous studies of somatic mutations using sporadic lung cancer, the research into germline mutations using familial lung cancer (FLC) is limited. In the present study, we used FLC samples obtained from the Chinese population in highly air-polluted regions to screen for novel germline mutations in lung cancer. Through a whole genome sequencing (WGS) analysis of the nine subjects (four lung cancer patients and five normal family members of FLC), we obtained a whole genome dataset of DNA alterations in FLC samples. A total of 1218 genes were identified with mutations of multiple types. Subsequently, the top 12 highly mutated genes were selected for validation by polymerase chain reaction and DNA sequencing in an expanded sample set including FLC, sporadic lung cancer, and healthy population. Mutations of the five genes (ARHGEF5, ANKRD20A2, ZNF595, ZNF812, MYO18B) may be potential germline mutations of lung cancer. We also analyzed specific mutations within the 12 genes and found that some specific mutations within the MUC12, FOXD4L3 and FOXD4L5 genes showed higher frequencies in the samples of FLC and/or lung cancer tissue, compared with the healthy population. Moreover, some genes with copy number variation may be potentially associated with a predisposition to lung cancer. Furthermore, non-coding DNA alterations of the WGS data in FLC were systematically analyzed and arranged. Interestingly, we found that germline mutations also occurred in many genes of non-coding RNA. This study uncovered the mutation spectrum in FLC and provided important clues for the evaluation of the genetic susceptibility to lung cancer.


Understanding the Colloidal Stability of Nanoparticle-Ligand Complexes: Design, Synthesis, and Structure-Function Relationship Studies of Amphiphilic Small-Molecule Ligands.
For effective application of nanoparticles, their amenability to in-solution processing must be addressed, and stable, homogeneous solvent conditions are required. Although organic ligands have been used as surface-modifying reagents for nanoparticles to increase their colloidal stability and homogeneity in solution, the structure-function relationships of nanoparticle-ligand complexes remain elusive and controversial. Herein, a series of novel amphiphilic small-molecule ligands were designed, synthesized, and applied as surface-modifying reagents for aqueous, transparent TiO2 and ZrO2 nanoparticles. The colloidal stability of the resulting nanoparticle-ligand complexes was found to depend not only on the chain length, but also on the relative balance between hydrophobicity and hydrophilicity. The structure of the ligands can be fine-tuned to achieve "flexible colloidal stability", thus significantly increasing complex stability in a variety of organic solvents.


Coregulator proteins and corticosteroid action in the brain.
The corticosteroid hormones cortisol and corticosterone are secreted by the adrenal gland in response to stress. They have profound effects on brain function, which are mediated by the related mineralocorticoid (MR) and glucocorticoid (GR) receptors. The MR and GR are ligand-activated transcription factors and exert different, sometimes opposing effects on the brain. The balance between these two receptor activities is considered essential for appropriate corticosteroid signalling and health. An exciting recent insight in steroid biology is that the nature and magnitude of steroid receptor-mediated responses depend not only on ligand and receptor availability, but also in a critical manner on the presence of downstream mediator proteins (coregulators), such as the steroid receptor coactivators and nuclear receptor corepressors. Members of the coregulator families differ in their specific interactions with steroid receptors, as well as in their distribution throughout the brain and pituitary. The activity of these proteins can be regulated both at the expression level, and by post-translational modifications. These characteristics make coregulator proteins of outstanding interest as determinants of receptor, cell and state-dependent effects of MR and GR signalling (and steroid receptor signalling in general) in the brain.


Role of kinetics in the selective surface oxidations of transition metal carbides.
The different oxidation behavior of TiC and VC(100) surfaces by molecular oxygen has been investigated by density functional theory with a slab model. From the thermodynamic stability of the final states that involve dissociated O(2), one cannot well explain the experimental observations. Two different oxidation pathways of TiC and VC(100) surfaces have been explored in this work, and the results indicate that two channels share the same precursor state. However, from the precursor, only the pathway leading to the formation of a C-O bond is energetically feasible for the TiC(100) surface, while on VC(100) the O atoms tend to occupy the metal surface sites due to a smaller energy barrier for this channel. Further band structure calculations reveal that the additional d electron of V atom favors the stability of the molecularly adsorbed species. The oxidation mechanism unveiled from the present calculations clearly evidences that the kinetic effects introduced by one additional d electron of the V atom play a crucial role in explaining the different surface chemistry between TiC and VC (100) surfaces.


Thermalization and relaxation mediated by phonon management in tin-lead perovskites.
Understanding and control of ultrafast non-equilibrium processes in semiconductors is key to making use of the full photon energy before relaxation, leading to new ways to break efficiency limits for solar energy conversion. In this work, we demonstrate the observation and modulation of slow relaxation in uniformly mixed tin-lead perovskites (MASnxPb1-xI3 and CsSnxPb1-xI3 nanocrystals). Transient absorption measurements reveal that slow cooling mediated by a hot phonon bottleneck effect appears at carrier densities above ~1018 cm-3 for tin-lead alloy nanocrystals, and tin addition is found to give rise to suppressed cooling. Within the alloy nanoparticles, the combination of a newly introduced high-energy band, screened Fröhlich interaction, suppressed Klemens decay and reduced thermal conductivity (acoustic phonon transport) with increased tin content contributes to the slowed relaxation. For inorganic nanocrystals where defect states couple strongly with carriers, sodium doping has been confirmed to benefit in maintaining hot carriers by decoupling them from deep defects, leading to a decreased energy-loss rate during thermalization and an enhanced hot phonon bottleneck effect. The slow cooling we observe uncovers the intrinsic photophysics of perovskite nanocrystals, with implications for photovoltaic applications where suppressed cooling could lead to hot-carrier solar cells.


Crucial lncRNAs associated with adipocyte differentiation from human adipose-derived stem cells based on co-expression and ceRNA network analyses.
Injection of adipose-derived stem cells (ASCs) is a promising treatment for facial contour deformities. However, its treatment mechanisms remain largely unknown. The study aimed to explain the molecular mechanisms of adipogenic differentiation from ASCs based on the roles of long noncoding RNAs (lncRNAs). Datasets of mRNA-lncRNA (GSE113253) and miRNA (GSE72429) expression profiling were collected from Gene Expression Omnibus database. The differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs) between undifferentiated and adipocyte differentiated human ASCs were identified using the Linear Models for Microarray Data method. DELs related co-expression and competing endogenous RNA (ceRNA) networks were constructed. Protein-protein interaction (PPI) analysis was performed to screen crucial target genes. A total of 748 DEGs, 17 DELs and 51 DEMs were identified. A total of 13 DELs and 279 DEGs with Pearson correlation coefficients > 0.9 and p-value < 0.01 were selected to construct the co-expression network. A total of 151 interaction pairs among 112 nodes (10 DEMs; eight DELs; 94 DEGs) were obtained to construct the ceRNA network. By comparing the lncRNAs and mRNAs in two networks, five lncRNAs (SNHG9, LINC02202, UBAC2-AS1, PTCSC3 and myocardial infarction associated transcript (MIAT)) and 32 genes (i.e., such as phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), protein tyrosine phosphatase receptor type B (PTPRB)) were found to be shared. PPI analysis demonstrated PIK3R1 , forkhead box O1 (FOXO1; a transcription factor) and estrogen receptor 1 (ESR1) were hub genes, which could be regulated by the miRNAs that interacted with the above five lncRNAs, such as LINC02202-miR-136-5p-PIK3R1, LINC02202-miR-381-3p-FOXO1 and MIAT-miR-18a-5p-ESR1. LINC02202 also could directly co-express with PIK3R1. Furthermore, PTPRB was predicted to be modulated by co-expression with LINC01119. MIAT, LINC02202 and LINC01119 may be potentially important, new lncRNAs associated with adipogenic differentiation of ASCs. They may be involved in adipogenesis by acting as a ceRNA or co-expressing with their targets.


Chewing the Fat with Microbes: Lipid Crosstalk in the Gut.
It is becoming increasingly important for any project aimed at understanding the effects of diet on human health, to also consider the combined effect of the trillions of microbes within the gut which modify and are modified by dietary nutrients. A healthy microbiome is diverse and contributes to host health, partly via the production and subsequent host absorption of secondary metabolites. Many of the beneficial bacteria in the gut rely on specific nutrients, such as dietary fiber, to survive and thrive. In the absence of those nutrients, the relative proportion of good commensal bacteria dwindles while communities of opportunistic, and potentially pathogenic, bacteria expand. Therefore, it is unsurprising that both diet and the gut microbiome have been associated with numerous human diseases. Inflammatory bowel diseases and colorectal cancer are associated with the presence of certain pathogenic bacteria and risk increases with consumption of a Western diet, which is typically high in fat, protein, and refined carbohydrates, but low in plant-based fibers. Indeed, despite increased screening and better care, colorectal cancer is still the 2nd leading cause of cancer death in the US and is the 3rd most diagnosed cancer among US men and women. Rates are rising worldwide as diets are becoming more westernized, alongside rising rates of metabolic diseases like obesity and diabetes. Understanding how a modern diet influences the microbiota and how subsequent microbial alterations effect human health will become essential in guiding personalized nutrition and healthcare in the future. Herein, we will summarize some of the latest advances in understanding of the three-way interaction between the human host, the gut microbiome, and the specific class of dietary nutrients, lipids.


Pseudotumor Cerebri Syndrome (PTCS), Clinico-Radiological Profile: A Prospective Study.
The aim of the study was to classify patients of Pseudotumor Cerebri Syndrome (PTCS) on the basis of newer classification along with its clinico-radiological correlations. A prospective study was conducted at a tertiary care teaching hospital. A total of 25 consecutive patients who fulfilled the new diagnostic criteria for PTCS were enrolled after taking informed written consent. A thorough clinical history, neurological examination and neuroimaging was carried out. Patients were classified into Primary and Secondary PTCS followed by Definite, Probable and Suggested as per new nomenclature. Out of 25 patients, there were 9 patients in the primary PTCS group and 16 in the secondary PTCS group. Mean duration of symptoms was 40.84 ± 45.68 days. Primary PTCS group patients were significantly overweight and had higher BMI as compared to the secondary group with significant number of patients reporting recent rapid weight gain. The CSF pressure and protein were non-significantly higher in the primary PTCS group. We could classify 17 (68%) patients in our study as definite PTCS, 7 (28%) as probable PTCS and suggested PTCS in one patient. In secondary PTCS group there were 16 (64%) patients. APLA positivity was found to be the most common etiology for secondary PTCS with statistical significance (P = 0.025). Early recognition along with appropriate classification and prompt treatment can prevent vision loss in PTCS. Apart from obesity, recent weight gain is also closely related with primary PTCS.


Amiloride delays the ischemia-induced rise in cytosolic free calcium.
An increase in cytosolic free calcium (Cai) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Cai may occur as a result of exchange of Nai for Cao, which occurs as a result of an increase in Nai arising from exchange of Nao for H+i. The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Cai, Nai, ATP, and pHi during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Cai was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Nai was measured using 23Na NMR, and the shift reagent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetramethylenephosph onate (Tm[DOTP]-5) was used to separate Nai and Nao. ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Nai and Cai. After 20 minutes of ischemia, time-averaged Cai was 1.0 +/- 0.2 microM (mean +/- SEM) in amiloride-treated hearts compared with 2.3 +/- 0.9 microM in nontreated hearts. After 20 minutes of ischemia, Nai in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Nai was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Cai during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Quantitative analysis of low-resistance junctions between cultured cells and correlation with gap-junctional areas.
Electrophysiological studies of low-resistance junctions between Novikoff hepatoma cells grown in suspension cultures were carried out and correlated with gap-junctional areas per inferface determined by freeze-fracture. The mean coupling coefficient between isolated cell pairs was 0.773 +/- 0.025 (SEM) in 67G medium and 0.653 +/- 0.028 in M67 medium; the respective means for the central pairs of four-cell chains were 0.714 +/- 0.034 and 0.595 +/- 0.026. Mean estimates of nonjunctional resistances for cell pairs were 3.0 +/- 0.32 x 10(7) ohm (67G) and 2.01 +/- 0.01 x 10(7) ohm (M67), and the respective estimates for specific nonjunctional resistances were 158.6 +/- 8.1 ohm-cm2 (67G) and 133.0 +/- 812 ohm-cm2 (M67). Mean estimates of junctional conductances were 0.409 +/- 0.058 x 10(-6) mho (67G) and 0.211 +/- 0.018 x 10(-6) mho (M67) for pairs and 0.291 +/- 0.063 x 10(-6) mho (67G) and 0.212 +/- 0.04 mho (M67) for four-cell chains. The mean area of gap junction per interface for separate cell populations was 0.187 +/- 0.049 micron 2 and 0.269 +/- 0.054 micron 2 for cells fixed in loose pellets and in suspension, respectively. When compared with the mean junctional conductance, these values gave specific junctional conductance estimates of 1.13 x 10(2) mho/cm2 and 0.78 x 10(2) mho/cm2, respectively. These values are higher than most previous estimates, but are consistent with the hypothesis that gap-junctional particles contain central hydrophilic channels, about 2 nm in diameter, which have cytoplasmic resistivity.


The Benefits and Risks of Statin Therapy in Ischemic Stroke: A Review of the Literature.
Statins are effective cholesterol-lowering drugs for reducing the risks of mortality and morbidity of cardiovascular diseases. Increasing evidence has shown that statin use is associated with a significant beneficial effect in patients with ischemic stroke. Both pre-stroke and post-stroke statin use has been found to be beneficial in ischemic stroke. Furthermore, good adherence is associated with a better clinical outcome, and statin withdrawal is associated with a poor functional outcome in patients with ischemic stroke. High-intensity statin therapy is advocated for the treatment of ischemic stroke. However, there are concerns regarding the adverse effects associated with statin use in ischemic stroke such as intracranial hemorrhage. In this review, we summarize the beneficial effect of statin use in ischemic stroke and discuss the potential risks associated with statin therapy.


Effective killing of cancer cells and regression of tumor growth by K27 targeting sulfiredoxin.
Cancer cells have been suggested to be more susceptible to oxidative damages and highly dependent on antioxidant capacity in comparison with normal cells, and thus targeting antioxidant enzymes has been a strategy for effective cancer treatment. Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of sulfinylated peroxiredoxins and thereby reactivates them. In this study we developed a Srx inhibitor, K27 (N-[7-chloro-2-(4-fluorophenyl)-4-quinazolinyl]-N-(2-phenylethyl)-β-alanine), and showed that it induces the accumulation of sulfinylated peroxiredoxins and oxidative stress, which leads to mitochondrial damage and apoptotic death of cancer cells. The effects of K27 were significantly reversed by ectopic expression of Srx or antioxidant N-acetyl cysteine. In addition, K27 led to preferential death of tumorigenic cells over non-tumorigenic cells, and suppressed the growth of xenograft tumor without acute toxicity. Our results suggest that targeting Srx might be an effective therapeutic strategy for cancer treatment through redox-mediated cell death.


Discrimination between SRP- and SecA/SecB-dependent substrates involves selective recognition of nascent chains by SRP and trigger factor.
Besides SecA and SecB, Escherichia coli cells possess a signal recognition particle (SRP) to target exported proteins to the SecY translocon. Using chemical and site-specific cross-linking in vitro, we show that SRP recognizes the first signal anchor sequence of a polytopic membrane protein (MtlA) resulting in cotranslational targeting of MtlA to SecY and phospholipids of the plasma membrane. In contrast, a possible interaction of SRP with the secretory protein pOmpA is prevented by the association of trigger factor with nascent pOmpA. Trigger factor also prevents SecA from binding to the first 125 amino acids of pOmpA when they are still associated with the ribosome. Under no experimental conditions was SecA found to interact with MtlA. Likewise, virtually no binding of trigger factor to ribosome-bound MtlA occurs even in the complete absence of SRP. Collectively, our results indicate that at the stage of nascent polypeptides, polytopic membrane proteins are selected by SRP for co-translational membrane targeting, whereas secretory proteins are directed into the SecA/SecB-mediated post-translational targeting pathway by means of their preferential recognition by trigger factor.


High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening. Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up. Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.


Healthier options for public schoolchildren program improves weight and blood pressure in 6- to 13-year-olds.
Childhood obesity and related health consequences continue to be major clinical and public health issues in the United States. Schools provide an opportunity to implement obesity prevention strategies to large and diverse pediatric audiences. Healthier Options for Public Schoolchildren was a quasiexperimental elementary school-based obesity prevention intervention targeting ethnically diverse 6- to 13-year-olds (kindergarten through sixth grade). Over 2 school years (August 2004 to June 2006), five elementary schools (four intervention, one control, N=2,494, 48% Hispanic) in Osceola County, FL, participated in the study. Intervention components included integrated and replicable nutrition, physical activity, and lifestyle educational curricula matched to state curricula standards; modified school meals, including nutrient-dense items, created by registered dietitians; and parent and staff educational components. Demographic, anthropometric, and blood pressure data were collected at baseline and at three time points over 2 years. Repeated measures analysis showed significantly decreased diastolic blood pressure in girls in the intervention group compared to controls (P<0.05). Systolic blood pressure decreased significantly for girls in the intervention group compared to controls during Year 1 (fall 2004 to fall 2005) (P<0.05); while not statistically significant the second year, the trend continued through Year 2. Overall weight z scores and body mass index z scores decreased significantly for girls in the intervention group compared to controls (P<0.05 and P<0.01, respectively). School-based prevention interventions, including nutrition and physical activity components, show promise in improving health, particularly among girls. If healthy weight and blood pressure can be maintained from an early age, cardiovascular disease in early adulthood may be prevented.


Traversing Excitonic and Ionic Landscapes: Reduced-Dimensionality-Inspired Design of Organometal Halide Semiconductors for Energy Applications.
At the very heart of the global semiconductor industry lies the omnipresent push for new materials discovery. New materials constantly rise and fall out of fashion in the scientific literature, with those passing an initial phase of research scrutiny becoming hotbeds of characterization and optimization efforts. Yet, innumerable hours of painstaking research have been devoted to materials that have ultimately fallen by the wayside after crossing over an indefinable threshold, whereupon historical optimism is met with newfound skepticism. Materials have to perform well, and they have to do it quickly. In the past decade, metal-halide perovskites (MHPs) have garnered widespread attention. The hegemonic view in both academic and industrial circles is that these materials could be engineered to meet the demands of the semiconductor industry. Their promise as inexpensive solar cell devices is highly attractive, and it has been nothing short of remarkable that efficiencies have risen from 3.8% in 2009 to more than 25.5% in 2021. Moreover, MHPs are poised to be revolutionary materials in more ways than one. The highest MHP LED efficiency was recently reported (23.4%), and MHPs have demonstrated promise in photodetectors, memristors, and transistors. However, the many excellent properties of MHPs are contrasted by longstanding stability and reproducibility limitations that have hindered their commercialization. Overcoming the limitations of MHPs is ultimately a materials engineering problem, which should be solved by mapping more precise relationships between structure, composition, and device performance. In 1958, Francis Crick famously developed the central dogma of molecular biology which describes the unidirectional flow of information in biological systems. In the words of Crick, "nature has devised a unique instrument in which an underlying simplicity is used to express great subtlety and versatility." In this Account, taking inspiration from the hierarchical organization of nature, we describe a hierarchical approach to materials engineering of organic metal-halide semiconductors. We demonstrate that organo-metal halide semiconductors' dimensionality, composition, and morphology dictate their optoelectronic properties and can be exploited in defining more explicit relationships between structure and function. Here, we traverse three-dimensional (3D), two-dimensional (2D), and one-dimensional (1D) organo-metal halide semiconductors, detailing the morphological and compositional differences in each and the implications that can be drawn within each domain on the engineering process. Control over ion migration pathways via morphology engineering as well as control over charge formation in organic-inorganic semiconductors is demonstrated. Fundamental insights into the amount of static and dynamic disorder in the MHP lattice are provided, which can be continuously tuned as a function of composition and morphology. Using electroabsorption spectroscopy on 2D MHPs, a disorder-induced dipole moment in the exciton proportional to the summed value of static and dynamic disorder is measured. Spectroscopic isolation of exciton features in 2D MHP electroabsorption spectra allows us to obtain precise, model-independent measurements of exciton binding energies to study the effect of chemical substitutions, such as Sn2+ → Pb2+, on the value of the exciton binding energy. Finally, we conclude that this multidimensional platform, with the aid of machine learning and robotics, will be foundational in accurately predicting structure-property-device relationships in organo-metal halide semiconductors in the future.


Immunohistochemical localization of cells containing nerve growth factor receptors in the different regions of the adult rat forebrain.
Conditions have been optimized for an immunohistochemical procedure for the localization of nerve growth factor receptor-containing cells in the brain. Using this immunohistochemical procedure, the normal morphology and distribution of the nerve growth factor receptor-containing neurons of the adult rat forebrain have been studied, and the findings compared with observations on the choline acetyltransferase-positive neurons present either in the immediately-adjacent sections or in the medially-divided half of the same section. Unlike in the peripheral nervous system, only neurons showed immunoreactivity to the nerve growth factor receptor in the brain. Both the nerve growth factor receptor- and choline acetyltransferase-immunoreactive cells appear to form a continuous anteroposterior band, which includes the olfactory tubercle, the medial septal nucleus, the vertical and horizontal limbs of the diagonal band and the basal nucleus. In each subdivision of the basal forebrain, the topographic organization, the localization, the intensity of the immunoreaction and the total cell number of nerve growth factor receptor- and of choline acetyltransferase-immunoreactive neurons were strikingly similar, indicating that nearly all nerve growth factor receptor-containing cells were cholinergic neurons. However, in the striatum, only about half the number of the choline acetyltransferase-positive cells showed immunopositive reactions to the nerve growth factor receptor, and, also, in the nerve growth factor receptor-containing neurons the intensity of the reaction product was much less than the choline acetyltransferase immunoreactivity. In the neurons of the basal forebrain nuclei, the choline acetyltransferase immunoreaction product was uniformly distributed on the cell bodies, while the nerve growth factor receptor immunoreaction product was present also as intensely stained granules on the cell somata and the dendrites. The mean diameter and the mean cross-sectional area of the nerve growth factor receptor-containing neurons were least in the medial septal nucleus and were greatest in the basal nucleus, and showed a gradation in cell size going from the medial septal nucleus through the nucleus of the diagonal band and extending more posteriorly to the basal nucleus.


Real-Life Effectiveness of Mepolizumab on Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity in Patients with Severe Eosinophilic Asthma.
Severe eosinophilic asthma (SEA) is associated with high peripheral blood and airway eosinophilia, recurrent disease exacerbations and severe airflow limitation. Eosinophilic inflammation is also responsible for small airway disease (SAD) development. SEA patients experience poor disease control and response to standard therapy and are prime candidates for anti-IL5 biologicals, such as mepolizumab, but the effect of treatment on SAD is unclear. We investigated the effect of mepolizumab on lung function in SEA patients, focusing on SAD parameters, and searched for an association between patients' phenotypic characteristics and changes in small airways function. In this real-life study, data from 105 patients with SEA were collected at baseline and after 6, 12 and 18 months of mepolizumab treatment. Along with expected improvements in clinical and lung function parameters brought by Mepolizumab treatment, FEF2525-75% values showed a highly significant, gradual and persistent increase (from 32.7 ± 18.2% at baseline to 48.6 ± 18.4% after 18 months) and correlated with ACT scores at 18 months (r = 0.566; p ≤ 0.0001). A patient subgroup analysis showed that changes in FEF25-75% values were higher in patients with a baseline peripheral blood eosinophil count ≥400 cells/μL and oral corticosteroid use. Mepolizumab significantly improves small airway function. This effect correlates with clinical benefits and may represent an accessible parameter through which to evaluate therapeutic response. This study provides novel insights into the phenotypic characteristics associated with the improved functional outcome provided by mepolizumab treatment.


Transformation of monothioarsenate by haloalkaliphilic, anoxygenic photosynthetic purple sulfur bacteria.
Thioarsenates are the dominant arsenic species in arsenic-rich, alkaline, and sulfidic waters, but bacterial interactions with these compounds have only recently been examined. Previous studies have shown that microorganisms play a role in the transformation of monothioarsenate to arsenate, including use of monothioarsenate as a chemolithotrophic electron donor coupled with oxygen as an electron acceptor. We obtained enrichment cultures from two saline, alkaline lakes (Mono Lake, CA and Big Soda Lake, NV) that are able to use monothioarsenate as the sole electron donor for anoxygenic photosynthesis. These anoxic cultures were able to convert a 1 mM mixture of thioarsenates completely to arsenate in c. 13 days and 4 mM monothioarsenate to arsenate in c. 17 days. This conversion was light dependent; thus, monothioarsenate can be used as the sole electron donor for anoxygenic photosynthesis. Both of the Mono Lake and Big Soda Lake enrichment cultures were dominated by an organism closely related to Ectothiorhodospira species. We tested additional strains of purple sulfur bacteria and found widespread ability to use monothioarsenate as an electron donor. The ability of bacteria to transform thioarsenates directly via anoxygenic photosynthesis adds a new perspective to the well-studied arsenic and sulfur cycles.


Successful retrieval of dislodged paclitaxel-eluting stent with a nitinol loop snare: a case report.
Coronary stent dislodgment or embolization before deployment is a rare but challenging complication in interventional cardiology. Intracoronary embolization of the dislodged stent is associated with a high risk of coronary occlusion, due to thrombus formation and subsequent myocardial infarction. Furthermore, systemic embolization may cause severe cerebrovascular events. Nonsurgical retrieval strategies for this complication have been suggested, but bailout cardiac surgery may be indicated if percutaneous retrieval attempts fail. To our knowledge, this is the first case report of intracoronary drug-eluting stent dislodgment, and successful retrieval was accomplished by a loop snare technique. With the increasing trend of using drug-eluting stents in percutaneous coronary intervention, the likelihood of stent dislodgment or embolization may increase. It should be kept in mind, especially by coronary interventionists, how to manage this complication.


On the pleiotropic structure of the genotype-phenotype map and the evolvability of complex organisms.
Analyses of effects of mutants on many traits have enabled estimates to be obtained of the magnitude of pleiotropy, and in reviews of such data others have concluded that the degree of pleiotropy is highly restricted, with implications on the evolvability of complex organisms. We show that these conclusions are highly dependent on statistical assumptions, for example significance levels. We analyze models with pleiotropic effects on all traits at all loci but by variable amounts, considering distributions of numbers of traits declared significant, overall pleiotropic effects, and extent of apparent modularity of effects. We demonstrate that these highly pleiotropic models can give results similar to those obtained in analyses of experimental data and that conclusions on limits to evolvability through pleiotropy are not robust.


Microvessel density as a prognostic factor in bladder cancer: a systematic review of literature and meta-analysis.
Many studies have shown that microvessel density (MVD) could play a potential value as prognostic biomarkers of tumors. The aim of this systematic review and meta-analysis is to evaluate the association between MVD and survival in patients with bladder cancer. Relevant literature was identified using PubMed and EMBASE. The eligible studies were assessed for quality using REMAPK (REporting recommendations for tumor MARKer prognostic studies (REMARK)). The patients' clinical characteristics and survival outcomes in eligible studies were extracted. And then, data were synthesized to evaluate the prognostic role of the MVD in bladder cancer with hazard ratio (HR), while the heterogeneity among studies was examined using the I<formula>^{2}</formula>. This meta-analysis included 10 eligible studies conducted between 1998 and 2011 dealing with bladder cancer. The combined HRs and 95% confidence interval [95% CI] for disease-free survival (DFS) was 2.24 [1.20,4.17], for overall survival (OS) was 1.16 [1.02,1.33] and 1.68 [1.15,2.45] for disease-specific survival (DSS).There was evidence heterogeneity between studies, and the disease stage was a key factor for heterogeneity in subgroup analysis. Our studies suggested that high MVD was significantly associated with poor survival and MVD could serve as a prognostic biomarker in patients with bladder cancer.


Anti-Galectin-2 Antibody Treatment Reduces Atherosclerotic Plaque Size and Alters Macrophage Polarity.
Galectins have numerous cellular functions in immunity and inflammation. Short-term galectin-2 (Gal-2) blockade in ischemia-induced arteriogenesis shifts macrophages to an anti-inflammatory phenotype and improves perfusion. Gal-2 may also affect other macrophage-related cardiovascular diseases. This study aims to elucidate the effects of Gal-2 inhibition in atherosclerosis. ApoE -/- mice were given a high-cholesterol diet (HCD) for 12 weeks. After 6 weeks of HCD, intermediate atherosclerotic plaques were present. To study the effects of anti-Gal-2 nanobody treatment on the progression of existing atherosclerosis, treatment with two llama-derived anti-Gal-2 nanobodies (clones 2H8 and 2C10), or vehicle was given for the remaining 6 weeks. Gal-2 inhibition reduced the progression of existing atherosclerosis. Atherosclerotic plaque area in the aortic root was decreased, especially so in mice treated with 2C10 nanobodies. This clone showed reduced atherosclerosis severity as reflected by a decrease in fibrous cap atheromas in addition to decreases in plaque size.The number of plaque resident macrophages was unchanged; however, there was a significant increase in the fraction of CD206+ macrophages. 2C10 treatment also increased plaque α-smooth muscle content, and Gal-2 may have a role in modulating the inflammatory status of smooth muscle cells. Remarkably, both treatments reduced serum cholesterol concentrations including reductions in very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein while triglyceride concentrations were unchanged. Prolonged and frequent treatment with anti-Gal-2 nanobodies reduced plaque size, slowed plaque progression, and modified the phenotype of plaque macrophages toward an anti-inflammatory profile. These results hold promise for future macrophage modulating therapeutic interventions that promote arteriogenesis and reduce atherosclerosis.


Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum.
The release of endogenous glutamate (GLU) elicited by depolarization of rat cerebellum synaptosomes was inhibited potently (pEC30 = 9.77) by 5-hydroxytryptamine (5-HT). The 5-HT action was antagonized by methiothepin (pA2 = 10.37); ketanserin, methysergide, cinanserin and spiperone were ineffective. Exogenous 5-HT also inhibited the release of [3H]-5-HT from cerebellar synaptosomes (pEC30 = 8.73). Methiothepin, but not ketanserin, methysergide, cinanserin or spiperone counteracted the inhibition (pA2 = 9.28). The receptors involved (presynaptic 5-HT heteroreceptors and autoreceptors) were activated by the 5-HT1 agonist RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole) which showed comparable activity at the two receptor systems. (-)-Propranolol, used as a 5-HT1 antagonist, shifted to the right (pA2 = 8.05) the dose-response curve of 5-HT at the autoreceptors, but was ineffective at the receptors regulating GLU release. On the contrary, the 5-HT1A agonist 8-hydroxy-2-di-N-propylamino)tetralin activated the presynaptic heteroreceptors (pEC30 = 7.98), but was ineffective as a 5-HT autoreceptor agonist. The results allow the following major conclusions: 5-HT receptors are located on GLU terminals in rat cerebellum where they may modulate in an inhibitory way the release of GLU; 5-HT autoreceptors possibly involved in a negative feedback regulation of 5-HT release are present on cerebellar 5-HT nerve endings; 5-HT autoreceptors and heteroreceptors can be pharmacologically differentiated and appear to represent subtypes of the 5-HT1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of cytoplasmic calcium concentration in the bleaching adaptation of salamander cone photoreceptors.
1. In order to study the possible involvement of Ca2+ in the bleaching adaptation of cones isolated from the retina of the salamander Ambystoma tigrinum, changes in cytoplasmic calcium concentration ([Ca2+]i were opposed by exposing the outer segment to a low-Ca(2+)-O Na+ solution designed to minimize Ca2+ fluxes across the outer segment membrane. 2. When a cone was exposed in normal Ringer solution to bright light bleaching a significant fraction of the photopigment, the circulating current was initially suppressed completely and then recovered to a maintained value less than the value in darkness before the bleach. When the outer segment of the cone was stepped to low-Ca(2+)-O Na+ solution before the bleach was delivered, the circulating current recovered more slowly or (for large bleaches) remained completely suppressed for the duration of the solution exposure. 3. If, during the period for which the current was suppressed in low-Ca(2+)-O Na+ solution, the cone outer segment was exposed to the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), the circulating current was restored. The dim flash response recorded under these conditions exhibited kinetics and integration times similar to those recorded in low-Ca(2+)-O Na+ solution in darkness before the bleach. If, instead, the outer segment was returned to Ringer solution after the bleach, thereby allowing [Ca2+]i to fall from its dark-adapted level to the appropriate bleach-adapted level, the kinetics of the response in low-Ca(2+)-O Na+ solution were greatly accelerated, and the integration time considerably reduced. This was true regardless of whether or not the low-Ca(2+)-O Na+ solution included IBMX. 4. The role of Ca2+ in bleaching adaptation appeared to resemble its role in background adaptation, since in both cases exposure to low-Ca(2+)-O Na+ solution suppressed the acceleration of response kinetics. Responses recorded from cones in low-Ca(2+)-O Na+ solution were nearly identical in waveform and sensitivity during background light or after bleaches, provided that IBMX was used to restore sufficient photocurrent so that responses to flashes could be recorded, and sensitivity was corrected for loss in quantum catch. 5. These results indicate that the fall in [Ca2+]i in cones after a bleach is necessary both for the acceleration of the flash response and the adaptational decrease in sensitivity, as is the case for adaptation by background light.


Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse.
Leopard complex spotting is a group of white spotting patterns in horses caused by an incompletely dominant gene (LP) where homozygotes (LP/LP) are also affected with congenital stationary night blindness. Previous studies implicated Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) as the best candidate gene for both CSNB and LP. RNA-Seq data pinpointed a 1378 bp insertion in intron 1 of TRPM1 as the potential cause. This insertion, a long terminal repeat (LTR) of an endogenous retrovirus, was completely associated with LP, testing 511 horses (χ(2)=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ(2)=43, p<<0.0005). The LTR was shown to disrupt TRPM1 transcription by premature poly-adenylation. Furthermore, while deleterious transposable element insertions should be quickly selected against the identification of this insertion in three ancient DNA samples suggests it has been maintained in the horse gene pool for at least 17,000 years. This study represents the first description of an LTR insertion being associated with both a pigmentation phenotype and an eye disorder.


Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model.
Tumor immunosuppression is commonly braided with chronic inflammation during tumor development. However, the relationship between immunosuppression and inflammation in tumor microenvironment is still unclear. We have demonstrated that mast cells are accumulated and exacerbate the inflammation and immunosuppression in tumor microenvironment via SCF/c-kit signaling pathway. Here, we further elucidate the underlying mechanism, which involves both myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells. Our data showed that mast cells mobilized the infiltration of MDSCs to tumor and induced the production of IL-17 by MDSCs; MDSCs-derived IL-17 indirectly attracted Treg cells, enhanced their suppressor function, and induced the IL-9 production by Treg cells; in turn, IL-9 strengthened the survival and protumor effect of mast cells in tumor microenvironment. Our findings disclose a closed loop among mast cells, MDSCs and Treg cells in tumor microenvironment, which provides a new insight into the paralleled developments of inflammation and immunosuppression in tumor microenvironment. Based on these findings, we propose that targeting tumor inflammation might be a potential strategy to reverse the immunosuppression of tumor microenvironment, thus facilitating cancer immunotherapy.


Cerebral white matter lesions and subjective cognitive dysfunction: the Rotterdam Scan Study.
To determine the relationship between cerebral white matter lesions (WML) and subjective cognitive dysfunction. Subjective cognitive dysfunction is present when a person perceives failures of cognitive function. When annoying enough, these failures will be expressed as complaints. Subjective cognitive dysfunction may be a prelude to or coincide with objective cognitive impairment. WML have been related to objective cognitive impairment and dementia, but their relationship with subjective cognitive dysfunction is not clear. Previous population-based studies on the latter relationship have been limited in sample size, recording of subjective cognitive function, and assessment of WML severity. We randomly sampled 1,049 elderly nondemented participants from the general population. Data on subjective cognitive dysfunction and its progression were derived from a 15-item questionnaire. Objective cognitive performance was assessed using a series of neuropsychological tests. WML were scored on MRI for periventricular and subcortical regions separately. WML were associated with more subjective cognitive failures. WML were more severe for participants reporting progression of these failures compared with participants without these failures, especially within participants with better than average cognitive performance (p = 0.008, for periventricular WML). Participants with severe WML reported progression of cognitive failures more than twice as often than did those with little or no WML. The relationship between the severity of WML and subjective cognitive failures was present for periventricular and subcortical WML. WML are associated with subjective cognitive failures and in particular with reporting progression of these failures, even in the absence of objective cognitive impairment.


Heritability of blood pressure increases during mental stress.
We studied the influence of mental stress on the contributions of genes and environment to individual variation in systolic (SBP) and diastolic (DBP) blood pressure by structural equation modelling in 320 adolescent male and female twins. Blood pressure data were collected during rest and during a reaction time and a mental arithmetic task. Univariate analyses of SBP and DBP showed familial aggregation for blood pressure. A genetic explanation for this resemblance was most likely, although during rest conditions a model that attributed familial resemblance to shared environmental factors, also fitted the data. There was no evidence for sex differences in heritabilities. Multivariate analyses showed significant heterogeneity between sexes for the intercorrelations of the blood pressure data measured under different rest and task conditions. Multivariate genetic analyses were therefore carried out separately in males and females. For SBP and DBP in females and for SBP in males an increase in heritabilities was seen for blood pressure measured during stress, as compared to rest measurements. The influence of shared environmental factors decreased during stress. For DBP in males no significant contributions of shared environment were found. The multivariate analyses indicated that the same genetic and environmental influences are expressed during rest and stress conditions.


Siderophore production by pathogenic Neisseria spp.
Previous studies have established the importance of iron acquisition to the growth and virulence of Neisseria meningitidis and Neisseria gonorrhoeae. Although preliminary evidence that the Neisseria spp. produce siderophores has been presented, the exact mechanism of iron acquisition has remained obscure. Siderophore production by N. gonorrhoeae and N. meningitidis was induced in two different low-iron media. The iron-reactive siderophores, "gonobactin" and "meningobactin," were partially purified by ion exchange chromatography followed by extraction with phenol-chloroform-ether or by gel filtration. The compounds were of low molecular weight, their synthesis was repressed by iron in the medium, and they appeared to be hydroxamic acids since they were stimulatory for Arthrobacter flavescens JG-9 (a hydroxamate auxotroph) and gave a positive Csáky reaction for bound hydroxylamine. In the iron form, the compounds had an absorption maximum of approximately 420 nm. Although meningobactin stimulated growth of the gonococcus in low-iron media and vice versa, the homologous activity was more marked, indicating that the compounds, though similar, were probably not identical. As determined by A. flavescens assay the meningococcus produced three to five times more siderophore than did the gonococcus; however, the amount of siderophore present in the culture fluids of even the meningococcus was 100- to 1,000-fold lower than the concentration of hydroxamate siderophores reported to be produced by Bacillus megaterium or Aerobacter aerogenes. Virulent, colony type 1 N. gonorrhoeae produced significantly more gonobactin than did the avirulent colony type 3 gonococci.


Morphological and physiological responses of the lungs of dogs to acute decompression.
The lung's response to decompression was studied in dogs anesthetized with pentobarbital sodium. Arterial pressure, hematocrit, right ventricular pressure, left ventricular end-diastolic pressure (LVEDP), dynamic compliance (CL), pulmonary resistance (RL), and arterial PO2, PCO2, and pH were measured prior to and for 3 h after a simulated air dive to 300 feet of seawater. Bronchoscopy was performed predive and at 3 h postdive. At 3 h animals were killed, and sections of lung were excised for histological examination. The decompression profile used regularly produced pulmonary hypertension, systemic hypotension, hemoconcentration, and arterial hypoxemia. CL fell in all but one dived animal. RL was more variable but remained unchanged postdive in most animals. The decompression stress did not alter the bronchoscopic and histological appearance of the airway mucosa. Pulmonary edema was regularly observed in histological sections and occurred without elevations of LVEDP. We concluded that noncardiac pulmonary edema is the principal response of the lung to decompression stress.


Palliative radiotherapy for thoracic spine metastases: Dosimetric advantage of three-dimensional conformal plans.
The aim of the present study was to investigate the dosimetric advantages of three-dimensional conformal radiation therapy (3DCRT) for thoracic spine metastases and compare it with conventional two-dimensional (2D) plans. Radiation therapy (RT) planning data of 10 patients with mid-to-low thoracic spine metastases were analyzed. Computed tomography simulation was performed and the planning target volume (PTV), heart, esophagus, lung and spinal cord were contoured. The 3DCRT plan comprised one posteroanterior (PA) field and two posterior oblique fields. The 2D plans used a single PA field or opposed anteroposterior (AP)/PA fields. The prescription dose of radiation was 30 Gy in 10 fractions. All comparisons of the maximum or mean doses to the organs at risk or the PTV, between two of the three RT plans, demonstrated statistically significant differences (P<0.05), with the exception of the mean esophageal doses between the single PA vs. AP/PA (P=0.285) plans. The mean heart doses were 15.0±3.1 Gy in single PA, 17.3±4.3 Gy in AP/PA and 8.5±1.7 Gy using 3DCRT. The median reduction rates using 3DCRT were 38.9% compared with single PA (range, 29.4-58.5%) or 47.5% relative to AP/PA (range, 34.5-67.1%). The mean esophageal doses were 17.9±2.3 Gy in single PA, 18.2±2.2 Gy in AP/PA and 15.3±1.9 Gy in 3DCRT. The median reduction rate using 3DCRT was 12.8% compared with single PA or 15.6% relative to AP/PA. Compared with the single PA or AP/PA 2D plan, 3DCRT reduced the median dose by 13.7 or 1.9% of the maximum spinal cord dose, respectively, and 14.7 or 2.9% of the maximum PTV dose, respectively. The mean lung doses were 2.7±0.7 Gy in single PA, 2.6±0.7 Gy in AP/PA and 5.1±1.0 Gy in 3DCRT. In conclusion, 3DCRT for mid-to-low thoracic spine metastases demonstrated significant dosimetric advantages by reducing the unnecessary irradiation of critical organs, particularly the heart, and by achieving a homogeneous target dose.


Insufficient expression of Fas antigen on helper T cells in Behçet's disease.
To investigate the lack of equilibrium in the regulatory mechanism of the immune system in Behçet's disease (BD), the expression of Fas antigen, an apoptosis related antigen, on peripheral blood lymphocytes from BD patients was analysed. Twenty one BD patients were the subjects in this study. Ten healthy adults were examined as controls. Cell surface antigens of lymphocytes were analysed with flow cytometry. There was a significant (p < 0.01) difference in the proportion of CD4 positive cells with CD25 between BD patients with active uveoretinitis (27.6% (SD 8.4%)) and the controls (14.7% (2.3%)), but no significant difference in the proportion of CD4 or CD45RO positive cells with Fas. On the other hand, the proportion of CD8 positive cells with Fas was significantly (p < 0.01) higher in BD patients with active uveoretinitis (45.6% (11.6%)) than in those with inactive uveoretinitis (23.8% (8.1%)) or in the controls (24.4% (2.5%)). The proportion of CD19 positive cells with Fas was also significantly (p < 0.01) higher in BD patients with active uveoretinitis (13.0% (5.0%)) than in the controls (5.1% (2.1%)). The insufficient expression of Fas on activated CD4 positive T cells and its high expression on CD8 positive T cells seem to play an important role in the chronic inflammation in BD.


Glomus jugulare tumor presentation and management: a case study.
Glomus jugulare tumors are rare, normally benign, paragangliomas located in and around the jugular foramen at the base of the skull. They may cause significant lower cranial nerve deficits due to mass effect, and as part of the chromaffin cell system (including pheochromocytomas), they may also actively secrete catecholamines. Resection, while frequently difficult, is the treatment of choice. Nurses caring for patients with glomus jugulare tumors need to be skilled in recognizing lower cranial nerve deficits and complications that may arise related to inappropriate catecholamine release or due to disruption of cerebral venous return by tumor or surgery.


Local control of squamous cell carcinoma following marginal and segmental mandibulectomy.
The records of 130 consecutive patients undergoing marginal or segmental mandibulectomy for squamous cell carcinoma of the oral cavity or oropharynx were reviewed. An attempt was made to correlate incidence of recurrence with characteristics of the primary tumor and extent of mandibulectomy. The local recurrence rate was 19% following marginal mandibulectomy and 6% following segmental mandibulectomy. The incidence of local recurrence was independent of the size of the primary tumor or the extent of lymph node metastases. Neither mandibular invasion by tumor nor the addition of radiotherapy influenced local recurrence. Ten of 15 patients recurring locally after marginal mandibulectomy were salvaged by further surgery. This study suggests that local control following marginal mandibulectomy is comparable to that following segmental mandibulectomy regardless of the size of the tumor. Segmental mandibulectomy should be reserved for those tumors invading deeply into the mandible or wrapping around it.


Evaluation of CpG-ODN-Adjuvanted Toxoplasma Gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations.
Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4+ and CD8+ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.


Examining the Consequences of the "Prevalent Life Events" of Arrest and Incarceration among an Urban African-American Cohort.
The life course perspective has traditionally examined prevalent adult life events, such as marriage and employment, and their potential to redirect offending trajectories. However, for African Americans, the life events of arrest and incarceration are becoming equally prevalent in young adulthood. Therefore, it is critical to understand how these "standard" criminal justice practices, which are designed to deter as well as punish, affect deviance among this population. This study evaluates the long-term consequences of criminal justice intervention on substance use and offending into midlife among an African American community cohort using propensity score matching and multivariate regression analyses. The results largely point to a criminogenic effect of criminal justice intervention on midlife deviance with a particularly strong effect of young adult arrest on rates of violent and property arrest counts into midlife. The theoretical and policy implications of the findings are discussed.


Mood congruent tuning of reward expectation in positive mood: evidence from FRN and theta modulations.
Positive mood broadens attention and builds additional mental resources. However, its effect on performance monitoring and reward prediction errors remain unclear. To examine this issue, we used a standard mood induction procedure (based on guided imagery) and asked 45 participants to complete a gambling task suited to study reward prediction errors by means of the feedback-related negativity (FRN) and mid-frontal theta band power. Results showed a larger FRN for negative feedback as well as a lack of reward expectation modulation for positive feedback at the theta level with positive mood, relative to a neutral mood condition. A control analysis showed that this latter result could not be explained by the mere superposition of the event-related brain potential component on the theta oscillations. Moreover, these neurophysiological effects were evidenced in the absence of impairments at the behavioral level or increase in autonomic arousal with positive mood, suggesting that this mood state reliably altered brain mechanisms of reward prediction errors during performance monitoring. We interpret these new results as reflecting a genuine mood congruency effect, whereby reward is anticipated as the default outcome with positive mood and therefore processed as unsurprising (even when it is unlikely), while negative feedback is perceived as unexpected.


A study of the association of fraenal attachment, lip coverage, and vestibular depth with plaque and gingivitis.
The effects of fraenal attachment, upper lip coverage, and mandibular vestibular depth on plaque and bleeding indices in the maxillary and mandibular anterior segments were studied in a group of 1015 school children aged 11.5 to 12.5 years. The position of the mandibular labial fraenum was relatively unimportant to plaque and mandibular gingivitis, but anterior fraenal attachment in the maxilla appeared to affect the retention of plaque and the degree of gingivitis. Maxillary and mandibular plaque and bleeding scores increased with decreasing upper lip coverage at rest. In the mandibular anterior segment, plaque and bleeding indices decreased with increasing vestibular depth. Further analysis demonstrated that fraenal attachment and vestibular depth and fraenal attachment and lip coverage were significantly associated. However, two-way analysis of variance indicated that the influence of fraenal attachment, vestibular depth, and lip coverage on plaque and gingivitis was independent. The influences of these soft tissue variables on plaque accumulation and gingivitis were of small clinical significance and not in themselves a justification for mucogingival surgery.