Implications of changes in households and living arrangements for future home-based care needs and costs for disabled elders in China.
To better understand future home-based care needs and costs for disabled elders in China. To further develop and apply the ProFamy extended cohort-component method and the most recent census and survey data. (a) Chinese disabled elders and the annual growth rate of the percentage of national gross domestic product (GDP) devoted to home-based care costs for disabled elders will increase much more rapidly than the growth of total elderly population; (b) home-based care needs and costs for disabled oldest-old aged 80+ will increase much faster than that for disabled young-old aged 65-79 after 2030; (c) disabled unmarried elders living alone and their home-based care costs increase substantially faster than those disabled unmarried elders living with children; (d) percent of rural disabled oldest-old will be substantially higher than that of rural population after 2030; (e) sensitivity analyses show that possible changes in mortality and elderly disability status are the major direct factors affecting home-based care needs and costs; (f) caregivers resources under the universal two-child policy will be substantially better than that under the rigorous fertility policy unchanged. We discuss policy recommendations concerning pathways to healthy aging with relatively reduced care costs, including reductions of the prevalence of disability, gender equality, the universal two-child policy and resources of caregivers, encouragements of rural-to-urban family migration and elder's residential proximity to their adult children, and remarriages of not-married elders.


Buprenorphine has a concentration-dependent cytotoxic effect on equine chondrocytes in vitro.
To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro. Primary cultured equine articular chondrocytes from 3 healthy adult horses. Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-soluble tetrazolium salt-8 (WST-8) cytotoxic assay, LDH assay, and flow cytometry. All continuous variables were evaluated with a mixed ANOVA with treatment, time, and their interactions as the fixed effects and each horse as the random effect. Buprenorphine showed a concentration-dependent chondrotoxic effect. The viability of chondrocytes was significantly decreased with exposure to HBUPRE and BUPI compared to CON, MOR, and LBUPRE. Negligible chondrotoxic effects were observed in healthy cultured equine chondrocytes exposed to 0.05 mg/mL of buprenorphine, whereas higher concentrations (0.12 mg/mL) showed a marked cytotoxic effect. Based on these results, low concentrations of buprenorphine appear to be safe for intra-articular administration. Further evaluation of this dose in vivo is needed before recommending its clinical use.


Immunochemically identical hydrophilic and amphiphilic forms of the bovine adrenomedullary dopamine beta-hydroxylase.
By means of a monospecific antibody, dopamine beta-hydroxylase was monitored immunoelectrophoretically in various extracts of chromaffin granules. Approximately one-third of the dopamine beta-hydroxylase present was located in the membrane fraction and could only be liberated with detergent. The dopamine beta-hydroxylases of the buffer and membrane fractions were antigenically identical, but differed in their amphiphilicity, as demonstrated by the change in precipitation patterns on removal of Triton X-100 from the gel, on charge-shift crossed immunoelectrophoresis and on crossed hydrophobic interaction immunoelectrophoresis with phenyl-Sepharose. Furthermore, immunoelectrophoretic analysis in the presence of Triton X-100 plus the cationic detergent cetyltrimethylammonium bromide indicates additional heterogeneity of the membrane-bound dopamine-beta-hydroxylase. By limited proteolysis with chymotrypsin and thermolysin the amphiphilic form could be convered into its hydrophilic counterpart.


Aspects of manual wheelchair configuration affecting mobility: a review.
Many aspects relating to equipment configuration affect users' actions in a manual wheelchair, determining the overall mobility performance. Since the equipment components and configuration determine both stability and mobility efficiency, configuring the wheelchair with the most appropriate set-up for individual users' needs is a difficult task. Several studies have shown the importance of seat/backrest assembly and the relative position of the rear wheels to the user in terms of the kinetics and kinematics of manual propulsion. More recently, new studies have brought to light evidence on the inertial properties of different wheelchair configurations. Further new studies have highlighted the handrim as a key component of wheelchair assembly, since it is the interface through which the user drives the chair. In light of the new evidence on wheelchair mechanics and propulsion kinetics and kinematics, this article presents a review of the most important aspects of wheelchair configuration that affect the users' actions and mobility.


The Gp1ba-Cre transgenic mouse: a new model to delineate platelet and leukocyte functions.
Conditional knockout (KO) mouse models are invaluable for elucidating the physiological roles of platelets. The Platelet factor 4-Cre recombinase (Pf4-Cre) transgenic mouse is the current model of choice for generating megakaryocyte/platelet-specific KO mice. Platelets and leukocytes work closely together in a wide range of disease settings, yet the specific contribution of platelets to these processes remains unclear. This is partially a result of the Pf4-Cre transgene being expressed in a variety of leukocyte populations. To overcome this issue, we developed a Gp1ba-Cre transgenic mouse strain in which Cre expression is driven by the endogenous Gp1ba locus. By crossing Gp1ba-Cre and Pf4-Cre mice to the mT/mG dual-fluorescence reporter mouse and performing a head-to-head comparison, we demonstrate more stringent megakaryocyte lineage-specific expression of the Gp1ba-Cre transgene. Broader tissue expression was observed with the Pf4-Cre transgene, leading to recombination in many hematopoietic lineages, including monocytes, macrophages, granulocytes, and dendritic and B and T cells. Direct comparison of phenotypes of Csk, Shp1, or CD148 conditional KO mice generated using either the Gp1ba-Cre or Pf4-Cre strains revealed similar platelet phenotypes. However, additional inflammatory and immunological anomalies were observed in Pf4-Cre-generated KO mice as a result of nonspecific deletion in other hematopoietic lineages. By excluding leukocyte contributions to phenotypes, the Gp1ba-Cre mouse will advance our understanding of the role of platelets in inflammation and other pathophysiological processes in which platelet-leukocyte interactions are involved.


Human nail cortisol as a retrospective biomarker of chronic stress: A systematic review.
Cortisol is the primary glucocorticoid produced by the activation of the hypothalamic pituitary adrenal (HPA) axis after a psychological or physiological stressor. The dysregulation of the HPA axis by chronic stress has been associated with psychiatric disorders. Although hair is currently the main validated source of chronic cortisol concentrations, cortisol is also bound to human nails, another keratinised matrix. Therefore, nail cortisol has the potential to be an alternative retrospective chronic measure of HPA activation. The aim of this systematic review was to assess the temporal resolution, methodological issues, HPA correlates, and target populations in nail cortisol investigations. A qualitative synthesis was performed to assess current literature exploring cortisol concentrations from human nails. A total of 18 eligible human studies extracted from Medline (PubMed and Ovid), ProQuest (PsycINFO), and Scopus found that immunoassays and mass spectrometry were the two primarily methods of analysis. However, methodological variability remained evident between studies. Nail cortisol correlated with saliva and hair in some studies and was investigated across multiple developmental periods. Finally, when applied as an outcome measure in health disorders, higher nail cortisol concentrations have been shown to be associated with acute coronary syndrome and depression. In conclusion, nail cortisol may serve as a retrospective biomarker of chronic stress; however, the ability to track how much cortisol is accumulating within nail clippings is complex and may represent a large timespan. Further, very few studies have reported effect sizes and investigated the effects of covariates, such as age, sex, ethnicity, and nail characteristics, which limits the validation of this measure. Further studies are required to validate the utility of nail cortisol as a biomarker of chronic stress across the human lifespan.


Ethanol wet-bonding challenges current anti-degradation strategy.
The long-term effectiveness of chlorhexidine as a matrix metalloproteinase (MMP) inhibitor may be compromised when water is incompletely removed during dentin bonding. This study challenged this anti-bond degradation strategy by testing the null hypothesis that wet-bonding with water or ethanol has no effect on the effectiveness of chlorhexidine in preventing hybrid layer degradation over an 18-month period. Acid-etched dentin was bonded under pulpal pressure simulation with Scotchbond MP and Single Bond 2, with water wet-bonding or with a hydrophobic adhesive with ethanol wet-bonding, with or without pre-treatment with chlorhexidine diacetate (CHD). Resin-dentin beams were prepared for bond strength and TEM evaluation after 24 hrs and after aging in artificial saliva for 9 and 18 mos. Bonds made to ethanol-saturated dentin did not change over time with preservation of hybrid layer integrity. Bonds made to CHD pre-treated acid-etched dentin with commercial adhesives with water wet-bonding were preserved after 9 mos but not after 18 mos, with severe hybrid layer degradation. The results led to rejection of the null hypothesis and highlight the concept of biomimetic water replacement from the collagen intrafibrillar compartments as the ultimate goal in extending the longevity of resin-dentin bonds.


A key role for tetrahydrobiopterin-dependent endothelial NOS regulation in resistance arteries: studies in endothelial cell tetrahydrobiopterin-deficient mice.
The cofactor tetrahydrobiopterin (BH4) is a critical regulator of endothelial NOS (eNOS) function, eNOS-derived NO and ROS signalling in vascular physiology. To determine the physiological requirement for de novo endothelial cell BH4 synthesis for the vasomotor function of resistance arteries, we have generated a mouse model with endothelial cell-specific deletion of Gch1, encoding GTP cyclohydrolase 1 (GTPCH), an essential enzyme for BH4 biosynthesis, and evaluated BH4-dependent eNOS regulation, eNOS-derived NO and ROS generation. The reactivity of mouse second-order mesenteric arteries was assessed by wire myography. High performance liquid chromatography was used to determine BH4, BH2 and biopterin. Western blotting was used for expression analysis. Gch1fl/fl Tie2cre mice demonstrated reduced GTPCH protein and BH4 levels in mesenteric arteries. Deficiency in endothelial cell BH4 leads to eNOS uncoupling, increased ROS production and loss of NO generation in mesenteric arteries of Gch1fl/fl Tie2cre mice. Gch1fl/fl Tie2cre mesenteric arteries had enhanced vasoconstriction to U46619 and phenylephrine, which was abolished by L-NAME. Endothelium-dependent vasodilatations to ACh and SLIGRL were impaired in mesenteric arteries from Gch1fl/fl Tie2cre mice, compared with those from wild-type littermates. Loss of eNOS-derived NO-mediated vasodilatation was associated with increased eNOS-derived H2 O2 and cyclooxygenase-derived vasodilator in Gch1fl/fl Tie2cre mesenteric arteries. Endothelial cell Gch1 and BH4-dependent eNOS regulation play pivotal roles in maintaining vascular homeostasis in resistance arteries. Therefore, targeting vascular Gch1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of microvascular dysfunction in patients with cardiovascular disease.


Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors.
Occasional glomus tumors display unusual features, such as large size, deep location, infiltrative growth, mitotic activity, nuclear pleomorphism, and necrosis. Although a small number of purportedly malignant glomus tumors have been described, histologic criteria for malignancy in glomus tumors have never been elaborated. The authors studied 52 unusual glomus tumors (retrieved from their consultation files) previously diagnosed as "atypical" or "malignant" by virtue of nuclear atypia, infiltrative growth, or mitotic activity. They evaluated size, depth, growth pattern, cellularity, nuclear grade, number of mitotic figures per 50 high-power fields (HPF), atypical mitotic figures, vascular space involvement, and necrosis to define criteria for malignancy in glomus tumors. Estimated relative risk was calculated and the Fisher exact test was used for statistical analysis. The 27 female patients and the 25 male patients ranged in age from 8 to 83 years (median age, 43 years). The tumors measured from 0.2 to 12 cm (median size, 2 cm) and occurred predominantly in the extremities, in both the superficial (n = 35) and deep (n = 17) soft tissues. Atypical features were usually observed centrally with a rim of benign-appearing glomus tumor. Follow-up information (n = 35; range, 5 months-23 years; mean 5.5 years) showed seven recurrences, eight metastases, and seven deaths from disease. Five-year cumulative metastatic risk increased significantly for tumors with a deep location (p = 0.005), with a size of more than 2 cm (p = 0.004), and with atypical mitotic figures (p = 0.004). Mitotic activity of more than 5 mitoses/50 HPF, high cellularity, the presence of necrosis, and moderate to high nuclear grade approached but did not reach significance. High nuclear grade alone, infiltrative growth, and vascular space involvement were not associated with metastasis. The authors propose the following classification scheme and criteria. Malignant glomus tumor: Tumors with a deep location and a size of more than 2 cm, or atypical mitotic figures, or moderate to high nuclear grade and > or =5 mitotic figures/50 HPF. Symplastic glomus tumor: Tumors with high nuclear grade in the absence of any other malignant feature. Glomus tumor of uncertain malignant potential: Tumors that lack criteria for malignant glomus tumor or symplastic glomus tumor but have high mitotic activity and superficial location only, or large size only, or deep location only. Glomangiomatosis: Tumors with histologic features of diffuse angiomatosis and excess glomus cells. Using this classification scheme, metastasis was observed in 38% of tumors fulfilling the criteria for malignancy. In contrast, metastatic disease was not seen in any specimen classified as symplastic glomus tumor, glomus tumor of uncertain malignant potential, or glomangiomatosis.


Oscillation Phase Locking and Late ERP Components of Intracranial Hippocampal Recordings Correlate to Patient Performance in a Working Memory Task.
In working memory tasks, stimulus presentation induces a resetting of intracranial temporal lobe oscillations in multiple frequency bands. To further understand the functional relevance of this phenomenon, we investigated whether working memory performance depends on the phase precision of ongoing oscillations in the hippocampus. We recorded intra-hippocampal local field potentials in individuals performing a working memory task. Two types of trials were administered. For high memory trials presentation of a list of four letters ("List") was followed by a single letter memory probe ("Test"). Low memory load trials, consisting of four identical letters (AAAA) followed by a probe with the same letter (A), were interspersed. Significant phase locking of ongoing oscillations across trials, estimated by the Pairwise Phase Consistency Index (PPCI) was observed in delta (0.5-4 Hz), theta (5-7 Hz), and alpha (8-12 Hz) bands during stimulus presentation and recall but was increased in low memory load trials. Across patients however, higher delta PPCIs during recall in the left hippocampus were associated with faster reaction times. Because phase locking could also be interpreted as a consequence of a stimulus evoked potential, we performed event related potential analysis (ERP) and examined the relationship of ERP components with performance. We found that both amplitude and latency of late ERP components correlated with both reaction time and accuracy. We propose that, in the Sternberg task, phase locking of oscillations, or alternatively its ERP correlate, synchronizes networks within the hippocampus and connected structures that are involved in working memory.


An investigation in the possible effect of chronic headache on neuropsychological function in aCL-negative patients with SLE.
Controversy exists as to whether patients with migraine may suffer cortical damage. We investigate the possible association between impaired cognitive function and chronic headache in lupus patients. Sixty one patients with systemic lupus erythematosus but without the antiphospholipid (Hughes) syndrome were questioned about headaches and formally assessed for cognitive function. They were also subjected to magnetic resonance imaging (MRI). Twenty one patients denied any significant headaches, 19 reported migrainous headaches and 11 experienced an aura. Eleven patients experienced headaches with features of migraine but did not fulfill the criteria, and seven patients had tension headaches. All patients had stable lupus; there was no difference in the incidence of hypertension, age or previous episodes of neuropsychiatric lupus. Patients with migrainous headaches without aura had marginally shorter duration of disease. There was no difference between the groups with respect to eight different cognitive tests or the ventriculo brain index on MRI. We failed to detect cognitive impairment in lupus patients with chronic headaches including migrainous headaches.


Investigations of modal instabilities in fiber amplifiers through detailed numerical simulations.
We present detailed numerical simulations of modal instabilities in high-power Yb-doped fiber amplifiers using a time-dependent temperature solver coupled to the optical fields and population inversion equations. The temperature is computed by solving the heat equation in polar coordinates using a 2D second-order alternating direction implicit method. We show that the higher-order modal content rises dramatically in the vicinity of the threshold and we recover the three power-dependent regions that are characteristic of the transfer of energy. We also investigate the dependence of the threshold on the seed power and the modal content ratio of the seed. The latter has a minimal effect on the threshold while it is shown that for the fiber configuration investigated, the modal instability threshold scales linearly over a wide range with the seed power. In addition, two different gain-tailored core designs are investigated and are shown to have higher thresholds than that of a uniformly doped core. Finally, we show that this full time-dependent model which does not assume a frequency offset between the modes a priori, predicts a reduced threshold when the seed is modulated at the KHz level. This is in agreement with the steady-periodic approach to this phenomenon.


The lived experience of depression among culturally Deaf adults.
Culturally Deaf adults lost hearing at early ages, communicate primarily in American Sign Language (ASL), and self-identify as culturally Deaf. Communication barriers lead to isolation, low self-esteem, abuse, and inadequate health care. Screening Deaf patients for depressive symptoms poses challenge. Nurses are rarely familiar with ASL, and depression screening tools aren't easily translated from English to ASL. Consequently, Deaf adults are not adequately screened for depression. Qualitative interviews were conducted with culturally Deaf adults, and certified interpreters helped to enhance understanding. Text was generated from interview transcriptions and researcher observations. No novel depressive symptoms were described. Various ASL signs were used to represent depression; two participants used a unique gesture that had no meaning to others. Childhood experiences leading to depression included sexual or physical abuse, feeling ostracized from family and like a burden. Suicidal gestures communicated severity of depression. Adults felt interpreters were unwelcome during mental health encounters. No participants were asked about depressive symptoms despite frank manifestations of depression. Study describes antecedents and consequences of depressive symptoms among Deaf adults. Understanding symptom manifestations and challenges experienced by Deaf patients helps identify those at risk for depression, thereby reducing morbidity and mortality.


Alleviation of infectious-bursal-disease-virus-induced bursal injury by betaine is associated with DNA methylation in IL-6 and interferon regulatory factor 7 promoter.
Infectious bursal disease virus (IBDV) often infects young chickens and causes severe immunosuppression and inflammatory injury. Betaine is an antiviral and anti-inflammatory ingredient that may exert functions through epigenetic regulation. However, the effects of betaine on an IBDV-induced bursal injury and their underlying mechanisms have not been investigated. In this study, betaine was supplemented to the drinking water of newly hatched commercial broilers for 3 wk. Afterward, the chickens were infected with the IBDV. After 5 D of infection, the bursal lesions were examined. The mRNA expression levels of IBDV VP2 gene, pro-inflammatory cytokines, and interferons were detected. Furthermore, the 5-methylcytosine level of the CpG island in the promoter region of IL-6 and interferon regulatory factor 7 (IRF7) were determined. The IBDV induced the depletion of lymphocytes and inflammation in the bursal follicles. IBDV infection considerably elevated the mRNA levels of VP2, IL-6, types I (IFNα and IFNβ) and II (IFNγ) interferons, and IRF7. The CpG island methylation in the promoter regions of IL-6 and IRF7 were substantially decreased after IBDV infection. Betaine administration attenuated the IBDV-induced bursal lesions. Meanwhile, the IBDV-induced mRNA expression levels of IL-6, IFNβ, and IRF7 were suppressed by betaine consumption. Furthermore, the hypomethylation effects of IBDV infection to the promoter regions of IL-6 and IRF7 genes were eliminated and relieved by betaine administration. Our results indicated that the IBDV-induced expression levels of IL-6 and IRF7 genes are associated with the suppression of methylation in the promoter region. Betaine administration through drinking water may alleviate the IBDV-induced bursal injury via epigenetic regulation.


Emerging role of epigenetics in stroke: part 1: DNA methylation and chromatin modifications.
Epigenetic mechanisms refer to the complex and interrelated molecular processes that dynamically modulate gene expression and function within every cell in the body. These regulatory systems represent the long-sought-after molecular interfaces that mediate gene × environment interactions. Changes in the epigenome throughout life are responsible not only for controlling normal development, adult homeostasis, and aging but also for mediating responses to injury. Emerging evidence implicates a spectrum of epigenetic processes in the pathophysiology of stroke. In this review, we describe conventional epigenetic mechanisms (including DNA methylation, histone code modifications, nucleosome remodeling, and higher-order chromatin formation) and highlight the emerging roles each of these processes play in the pathobiology of stroke. We suggest that understanding these mechanisms may be important for discovering more sensitive and specific biomarkers for risk, onset, and progression of stroke. In addition, we highlight epigenetic approaches for stroke therapy, including the inhibition of DNA methyltransferase and histone deacetylase enzyme activities. These therapeutic approaches are still in their infancy, but preliminary results suggest that contemporary agents targeting these pathways can regulate the deployment of stress responses that modulate neural cell viability and promote brain repair and functional reorganization. Indeed, these agents even appear to orchestrate sophisticated cognitive functions, including learning and memory.


Behavioural discrimination of noxious stimuli in infants is dependent on brain maturation.
Changes in facial expression are an essential form of social communication and in nonverbal infants are often used to alert care providers to pain-related distress. However, studies of early human brain development suggest that premature infants aged less than 34 weeks' gestation do not display discriminative brain activity patterns to equally salient noxious and innocuous events. Here we examine the development of facial expression in 105 infants, aged between 28 and 42 weeks' gestation. We show that the presence of facial expression change after noxious and innocuous stimulation is age-dependent and that discriminative facial expressions emerge from approximately 33 weeks' gestation. In a subset of 49 infants, we also recorded EEG brain activity and demonstrated that the temporal emergence of facial discrimination mirrors the developmental profile of the brain's ability to generate discriminative responses. Furthermore, within individual infants, the ability to display discriminative facial expressions is significantly related to brain response maturity. These data demonstrate that the emergence of behavioural discrimination in early human life corresponds to our brain's ability to discriminate noxious and innocuous events and raises fundamental questions as to how best to interpret infant behaviours when measuring and treating pain in premature infants.


The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells.
We analyzed expression status of the recently identified tumor suppressor geneRASSF1A in primary prostate carcinomas and in prostate cell lines. We found complete methylation of the RASSF1A promoter in 63% of primary microdissected prostate carcinomas (7 of 11 samples). The remaining 4 samples (37%) were partially methylated, possibly because of contamination with normal cells. No promoter methylation was observed in matching normal prostate tissues. High levels of RASSF1A transcript and no methylation of RASSF1A promoter were found in explanted primary normal prostate epithelial and stromal cells. Complete silencing and methylation of RASSF1A promoter was observed in five widely used prostate carcinoma cell lines, which acquired the ability to grow in culture spontaneously, including LNCaP, PC-3, ND-1, DU-145, 22Rv1, and one primary prostate carcinoma immortalized by overexpression of the human telomerase catalytic subunit (RC-58T/hTERT). However, no silencing of RASSF1A was found in four other prostate carcinoma cell lines, which were adapted for cell culture after transformation with human papillomaviral DNA. Suppression of cell growth in vitro was demonstrated after the reintroduction of RASSF1A-expressing construct into LNCaP prostate carcinoma cells. Our data implicate the RASSF1A gene in human prostate tumorigenesis.


CD56bright natural killer cells preferentially kill proliferating CD4+ T cells.
Human CD56br natural killer (NK) cells represent a small subset of CD56+ NK cells in circulation and are largely tissue-resident. The frequency and number of CD56br NK cells in blood has been shown to increase following administration of low-dose IL-2 (LD-IL2), a therapy aimed to specifically expand CD4+ regulatory T cells (Tregs). Given the potential clinical application of LD-IL-2 immunotherapy across several immune diseases, including the autoimmune disease type 1 diabetes, a better understanding of the functional consequences of this expansion is urgently needed. In this study, we developed an in vitro co-culture assay with activated CD4+ T cells to measure NK cell killing efficiency. We show that CD56br and CD56dim NK cells show similar efficiency at killing activated CD4+ conventional T (Tconv) and Treg cell subsets. However, in contrast to CD56dim cells, CD56br NK cells preferentially target highly proliferative cells. We hypothesize that CD56br NK cells have an immunoregulatory role through the elimination of proliferating autoreactive CD4+ Tconv cells that have escaped Treg suppression. These results have implications for the interpretation of current and future trials of LD-IL-2 by providing evidence for a new, possibly beneficial immunomodulatory mechanism of LD-IL-2-expanded CD56br NK cells.


Habituation of single CO2 laser-evoked responses during interictal phase of migraine.
A reduced habituation of averaged laser-evoked potential (LEP) amplitudes was previously found in migraine patients. The aim of the present study was to assess the habituation of single LEP responses and pain sensation during the interictal phase in migraine patients. Fourteen migraine patients were compared with ten control subjects. The pain stimulus was laser pulses, generated by CO2 laser, delivered to right supraorbital zone. Patients were evaluated during attack-free conditions. The LEP habituation was studied by measuring the changes of LEP amplitudes across and within three consecutive repetitions of 21 non-averaged trials. In migraine patients the N2-P2 wave amplitudes did not show a tendency toward habituation across and, above all, within the three repetitions. Anomalous behaviour of nociceptive cortex during the interictal phase of migraine may predispose patients to headache occurrence and persistence.


Physicians, Primary Caregivers and Topical Repellent: All Under-Utilised Resources in Stopping Dengue Virus Transmission in Affected Households.
Primary health care facilities frequently manage dengue cases on an ambulatory basis for the duration of the patient's illness. There is a great opportunity for specific messaging, aimed to reduce dengue virus (DENV) transmission in and around the home, to be directly targeted toward this high-risk ambulatory patient group, as part of an integrated approach to dengue management. The extent however, to which physicians understand, and can themselves effectively communicate strategies to stop focal DENV transmission around an ambulatory dengue case is unknown; the matter of patient comprehension and recollection then ensues. In addition, the effectiveness of N,N-diethyl-3-methylbenzamide (DEET)-based insect repellent in protecting dengue patients from Aedes aegypti mosquitoes' bites has not been investigated. A knowledge, attitude and practice (KAP) survey, focusing on the mechanisms of DENV transmission and prevention, was performed using semi-structured questionnaires. This survey was targeted towards the patients and family members providing supportive care, and physicians routinely involved in dengue patient management in Southern Vietnam. An additional clinical observational study was conducted to measure the efficacy of a widely-used 13% DEET-based insect repellent to repel Ae. aegypti mosquitoes from the forearms of dengue cases and matched healthy controls. Among both the physician (n = 50) and patient (n = 49) groups there were several respondents lacking a coherent understanding of DENV transmission, leading to some inappropriate attitudes and inadequate acute preventive practices in the household. The application of insect repellent to protect patients and their relatives from mosquito bites was frequently recommended by majority of physicians (78%) participating in the survey. Nevertheless, our tested topical application of 13% DEET conferred only ~1hr median protection time from Ae. aegypti landing. This is notably shorter than that advertised on the manufacturer's label. No differences in landing time between febrile dengue cases or matched healthy controls (n = 19 experiments) were observed. Our study identifies missed opportunities for primary care physicians to improve public health through communication of strategies that could prevent focal dengue transmission in and around a case household. We advocate better access to more efficient communication methods for physicians and auxilliary health workers, supporting to educate those at high risk of DENV transmission. Our empirical testing of a widely-available 13% DEET-based repellent was limited in its protective efficacy against Ae. aegypti mosquito bites, and therefore DENV transmission, suggesting more frequent application is necessary to be beneficial.


Mitigating the health effects of disasters for medically underserved populations: electronic health records, telemedicine, research, screening, and surveillance.
The Regional Coordinating Center for Hurricane Response (RCC) collaborated with the EXPORT Centers (Centers of Excellence in Partnerships for Community Outreach, Research on Health Disparities and Training) to rebuild, revitalize, and improve the health care infrastructure in the Gulf Coast states damaged by Hurricanes Katrina and Rita. This initiative aims to enhance the provision of health care by installing Electronic Health Records and Telepsychiatry systems throughout the Gulf Coast. Through the EXPORT Centers, the RCC plans to perform screening and surveillance projects within the communities and develop research projects focused on eliminating health disparities affecting underserved populations in the region. Another goal is to establish partnerships with EXPORT Centers, Community Health Centers, and other essential primary care practices in hurricane-ravaged communities. Through these partnerships, the overarching goal is to create a balanced health care system model that academic institutions can integrate into preventive care for emergency planning and research.


Gene ontology function prediction in mollicutes using protein-protein association networks.
Many complex systems can be represented and analysed as networks. The recent availability of large-scale datasets, has made it possible to elucidate some of the organisational principles and rules that govern their function, robustness and evolution. However, one of the main limitations in using protein-protein interactions for function prediction is the availability of interaction data, especially for Mollicutes. If we could harness predicted interactions, such as those from a Protein-Protein Association Networks (PPAN), combining several protein-protein network function-inference methods with semantic similarity calculations, the use of protein-protein interactions for functional inference in this species would become more potentially useful. In this work we show that using PPAN data combined with other approximations, such as functional module detection, orthology exploitation methods and Gene Ontology (GO)-based information measures helps to predict protein function in Mycoplasma genitalium. To our knowledge, the proposed method is the first that combines functional module detection among species, exploiting an orthology procedure and using information theory-based GO semantic similarity in PPAN of the Mycoplasma species. The results of an evaluation show a higher recall than previously reported methods that focused on only one organism network.


One- and two-photon quantum interferences in parametric four-wave mixing.
We report the observation of the interferometric response in parametric four-wave mixing in rubidium atoms excited by a pair of ultrashort pulses. For pulses with orthogonal polarizations and in the presence of the two-photon transition 5S-5D reveals a one-photon quantum interference, in contrast to the optical interference observed when the pulses have parallel polarization. For opposite circular polarizations no interference is observed in the fluorescence of the two-photon transition, in contrast to the one- and two-photon interferences exhibited in the nonlinear process.


Coevolution Slows the Disassembly of Mutualistic Networks.
Important groups of mutualistic species are threatened worldwide, and identifying factors that make them more or less fragile in the face of disturbance is becoming increasingly critical. Although much research has focused on identifying the ecological factors that favor the stability of communities rich in mutualists, much less has been devoted to understanding the role played by historical and contemporary evolution. Here we develop mathematical models and computer simulations of coevolving mutualistic communities that allow us to explore the importance of coevolution in stabilizing communities against anthropogenic disturbance. Our results demonstrate that communities with a long history of coevolution are substantially more robust to disturbance, losing individual species and interactions at lower rates. In addition, our results identify a novel phenomenon-coevolutionary rescue-that mitigates the impacts of ongoing anthropogenic disturbance by rewiring the network structure of the community in a way that compensates for the extinction of individual species and interactions.


The Time Out Procedure: have we changed our practice?
A preoperative surgical safety checklist was implemented into three major hospitals performing elective operations in Christchurch (New Zealand) in 2004. A prospective analysis of the results of this "Time Out Procedure" (TOP) was performed upon its implementation and 4 years later. All members of the surgical team who participated in the TOP were recorded, as were the details of any discrepancies encountered during the TOP. The results of the initial prospective analysis from September 2004 until April 2005 (Phase 1, 10,330 procedures) were compared to a further prospective study 4 years later from October 2008 until September 2009 (Phase 2, 25,086 procedures). Surgeons' attitudes towards the TOP were analysed with a questionnaire. There were no wrong site operations in either phases of the study. Completion of the TOP improved in Phase 2 (98% compared to 87%, p<0.001). The overall discrepancies observed increased, (7.7% in Phase 1 and 9.3% in Phase 2, p<0.001) with surgeon being absent at the TOP resulting in 73% of the discrepancies observed. Only 86% of surgeons believed that TOP was valuable in reducing wrong site operation. This study suggests that surgical checklists such as the TOP are a useful tool in identification and prevention of wrong site surgery. Our practice with consent and limb marking has improved over the two study periods. However, there continues to be surgeon resistance to these checklists, and further research will help to identify the reasons and possible solutions to this phenomenon.


In vivo role of adenosine-5'-phosphosulfate reductase in the purple sulfur bacterium Allochromatium vinosum.
Adenosine-5'-phosphosulfate (APS) reductase participates in the oxidation of sulfite to APS in Allochromatium vinosum. Oxidation of sulfite via the APS pathway yields ATP through substrate-level phosphorylation. An alternative enzyme for the oxidation of sulfite to sulfate, sulfite:acceptor oxidoreductase, has also been reported in Ach. vinosum. Oxidation of sulfite through this enzyme does not yield ATP. APS reductase is expressed constitutively in Ach. vinosum, suggesting that it performs an important role in this organism. However, studies carried out with batch cultures of an APS reductase mutant showed little or no differences in growth or in the rates of substrate oxidation when compared to the wild-type, therefore questioning the role of this enzyme. In an attempt to establish whether the ATP gain derived from APS-reductase-mediated oxidation of sulfite is relevant for energy-limited cultures, we compared growth of the wild-type SM50 and the APS-reductase-deficient mutant D3 when grown in continuous culture under different degrees of illumination. Little differences in the specific growth rates of the two strains were observed at light-limiting irradiances, suggesting that the ATP gained during sulfite oxidation through the APS reductase pathway does not constitute a significant energy input. However, at saturating irradiances, wild-type Ach. vinosum grew considerably faster than the mutant. Increasing the irradiance even further resulted in inhibition of the wild-type strain down to the level of the APS reductase mutant. The implications of these results are discussed.


Periprosthetic tibial fractures after cementless low contact stress total knee arthroplasty.
Periprosthetic fractures are a recognized complication of total knee arthroplasty. Fractures may occur intraoperatively or postoperatively, and risk factors have been identified that may predispose an individual to such a complication. We report 7 cases of periprosthetic tibial fractures after low contact stress total knee arthroplasty, a complication encountered by the senior author (D.E.B.) only after a change in practice from a cemented implant to a cementless one. In light of this previously unreported complication in our unit, we attempted to identify common features within this group of patients that may have contributed to fracture occurrence. Statistical analysis revealed a highly significant (P<.005) risk of periprosthetic tibial fracture in patients with a preoperative neutral or valgus knee. Age, gender, and diagnosis did not appear to increase the risk of fracture significantly. All patients displayed evidence of reduced bone mineral density in the lumbar spine and femoral neck regions on dual-energy x-ray absorptiometry scanning. Patients with a preoperative neutral or valgus knee and local evidence of osteopenia represent a high-risk group, in whom particular care in alignment should be taken. In this group, it may be preferable to have the tibial component inserted with cement fixation.


The independent predictive value of peritraumatic dissociation for PTSD symptomatology after type I trauma: a systematic review of prospective studies.
We conducted a systematic review of prospective studies examining the independent predictive value of peritraumatic dissociation (PD) for posttraumatic stress disorder (PTSD) symptomatology following single traumatic events. Insight into the independent predictive value may help to identify victims at risk for PTSD symptomatology. For this purpose a literature search was carried out using the online databases PsycINFO, Medline/Pubmed, and PILOTS. Studies were included if they were published in peer-reviewed journals (before 2007), focused on more or less single traumatic events (Type I trauma), assessed PD within 1 month, had follow-ups 3 months or later, and which controlled for mental health problems at the time PD was assessed. The majority of the 17 identified studies showed no or only weak indications of an independent predictive value of PD for PTSD symptomatology following type I traumas. Only 3 of the 6 studies with positive results reported a strong independent predictive value of PD. Although bivariately associated with PTSD symptomatology, there is no general consensus across prospective Type I trauma studies that PD qualifies as an important independent predictor of PTSD symptomatology. Results indicate that initial mental health problems, among other factors, are better predictors of PTSD symptomatology than PD.


Matching different inorganic compounds as mixture of electron donors to improve CO2 fixation by nonphotosynthetic microbial community without hydrogen.
The dominant bacteria in nonphotosynthetic microbial community (NPMC) isolated from the ocean were identified by PCR-DGGE. The results revealed that the dominant microorganisms in cultures of NPMC differed when Na(2)S, Na(2)S(2)O(3), and NaNO(2) were used as the electron donor to reduce CO(2). These findings implied that different microorganisms in the NPMC respond to different inorganic compound as suitable electron donor, indicating that matching of Na(2)S, Na(2)S(2)O(3), and NaNO(2) may provide mixed electron donors that increase the ability of NPMC to fix CO(2). Accordingly, the central composite response surface method (RSM) was used to predict the optimal concentration and match of Na(2)S, Na(2)S(2)O(3), and NaNO(2) as mixed electron donors to improve CO(2) fixation efficiency under aerobic and anaerobic conditions without hydrogen. The results indicated that 0.46% NaNO(2), 0.50% Na(2)S(2)O(3), and 1.25% Na(2)S were the optimal match under aerobic conditions, while 1.04% NaNO(2), 1.07% Na(2)S(2)O(3), and 0.98% Na(2)S were the optimal match under anaerobic conditions. Under these conditions, the fixed CO(2) by NPMC was determined to be 387.51 and 512.57 mg/L, respectively, which obviously exceeded those values obtained prior to optimization (5.94 and 7.14 mg/L, respectively), as well as that obtained when hydrogen was used as the electron donor (91.60 mg/L).


Oxidative damage and phosphatidylserine expression of red blood cells in cattle experimentally infected with Theileria sergenti.
In order to elucidate the mechanism of anemia in Japanese bovine theileriosis, we investigated the oxidative alteration of red blood cells (RBCs) in cattle infected with Theileria sergenti. As an index of RBC oxidation, the levels of 2',7'-dichlorofluorescin-diacetate (DCFH) oxidation and malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS), and phosphatidylserine (PS) expression accompanying anemia were examined in experimentally infected cattle. Before the development of anemia, the concentrations of DCFH oxidation and MDA-TBARS were low, and PS expression on the surfaces of RBCs was hardly seen. However, during the onset of anemia, these levels began to increase remarkably in proportion to the decrease of packed cell volume and the increase of parasitemia in all infected cattle. During the serious stage of anemia, these oxidative indices reached their maximum values. Our findings indicate that oxidative damage and loss of membrane asymmetry in RBCs are related to the development of anemia in T. sergenti infection. This oxidative damage to the RBCs might play an important role in the pathogenesis of anemia in Japanese bovine theileriosis.


When helping helps: autonomous motivation for prosocial behavior and its influence on well-being for the helper and recipient.
Self-determination theory posits that the degree to which a prosocial act is volitional or autonomous predicts its effect on well-being and that psychological need satisfaction mediates this relation. Four studies tested the impact of autonomous and controlled motivation for helping others on well-being and explored effects on other outcomes of helping for both helpers and recipients. Study 1 used a diary method to assess daily relations between prosocial behaviors and helper well-being and tested mediating effects of basic psychological need satisfaction. Study 2 examined the effect of choice on motivation and consequences of autonomous versus controlled helping using an experimental design. Study 3 examined the consequences of autonomous versus controlled helping for both helpers and recipients in a dyadic task. Finally, Study 4 manipulated motivation to predict helper and recipient outcomes. Findings support the idea that autonomous motivation for helping yields benefits for both helper and recipient through greater need satisfaction. Limitations and implications are discussed.


Parasitic infections and medical expenses according to Health Insurance Review Assessment claims data in South Korea, 2011-2018.
In South Korea, Health Insurance Review and Assessment claims data contain comprehensive information on healthcare services for almost the entire population. The present study used claims data on parasitic diseases from 2011 to 2018, and associated medical expenses to investigate infection trends associated with endemic parasitic diseases in South Korea, including those not monitored by Korea Centers for Disease Control and Prevention. Basic data regarding each parasitic disease were curated from the Healthcare Bigdata Hub (http://opendata.hira.or.kr). Ten endemic parasitic diseases, three pandemic protozoan diseases, and three ectoparasitic diseases were evaluated between 2011 and 2018. Data on each parasitic disease included the number of patients of each sex, age range within 5 years, province, and total medical expenses. Heatmap and principal component analysis were performed to visualize the incidence pattern of parasitic diseases by provinces. Clonorchiasis and pinworm infections decreased remarkably from 6,097 and 4,018 infections in 2011 to 3,008 and 1,988 infections in 2018, respectively. Other endemic parasitic diseases mostly declined or remained steady over the 8-year period, except for anisakiasis, which doubled from 409 in 2011 to 818 in 2018. Provinces close to North Korea had a higher frequency of claims for Plasmodium vivax infection. The highest rate of clonorchiasis was in Gyeongsangnam-do, while that of anisakiasis was in southern Korea. Jeju province had the highest number of claims for cysticercosis, anisakiasis, pinworm infection, and soil-transmitted helminth infections. The total medical expense for anisakiasis was 65 million Korean won (57,000 US$) in 2011, rising to 237 million Korean won (206,000 US$) in 2018. The medical expense for trichomoniasis was 6,063 million won and for scabies was 1,669 million won in 2018. Since the claims data include only data reported by healthcare providers, some discrepancies might have occurred. Our findings provide the basis for a health policy to reduce further infections and medical expense.


Outcome of surgery for toxic goitres in Maiduguri: a single teaching hospital's perspective.
Thyrotoxicosis a common endocrine disorder of the thyroid gland in Nigeria is commonly treated surgically. The outcome of thyroidectomy for toxic goiters in Maiduguri Nigeria is evaluated. Over the last 5 years (Jan 2005-July 2010) , in a prospective review, the demographic, and clinical data of patients operated for toxic goiters in our department was entered, into a predesigned proforma and analyzed. The objective of the study is to review our experience with subtotal and near-total thyroidectomy as treatment for benign toxic goiters. Seventy-eight patients, 11 males (14.1%) and 67 females (85.9%), with male: female ratio of 1:6.1 and the mean age of 30 ± 10.9 (range, 17-65 years), underwent thyroidectomy for toxic goiters. The mean duration of symptoms was 41.9 (range 3-126 months). There were 53 patients with toxic diffuse goiters (Grave's disease) with their mean age of 27.6 ± 6.93 (range 17-38 years), 23 with toxic multinodular goiters, the mean age of 43.7 ± 15.68 (range 17-65 years) and two with toxic nodule. There was no case of permanent recurrent laryngeal nerve palsy or permanent hypocalcemia. Transient hypocalcemia occurred in 9 (11.5%) patients and hemorrhage with hematoma, requiring exploration in 4 (5.1%). There were two cases of wound infection and no postoperative mortality. The mean hospital stay was 7.6 ± 2.34 (range 5-15 days). There was no disease recurrence over a mean follow-up of 20.7 (range 2-48) months. Subtotal thyroidectomy is an effective procedure for the treatment of thyrotoxicosis with few postoperative complications and majority of patients being euthyroid after long follow-up.


Quantitative Measurement of Local Infrared Absorption and Dielectric Function with Tip-Enhanced Near-Field Microscopy.
Scattering-type scanning near-field optical microscopy (s-SNOM) and Fourier transform infrared nanospectroscopy (nano-FTIR) are emerging tools for nanoscale chemical material identification. Here, we push s-SNOM and nano-FTIR one important step further by enabling them to quantitatively measure local dielectric constants and infrared absorption. Our technique is based on an analytical model, which allows for a simple inversion of the near-field scattering problem. It yields the dielectric permittivity and absorption of samples with 2 orders of magnitude improved spatial resolution compared to far-field measurements and is applicable to a large class of samples including polymers and biological matter. We verify the capabilities by determining the local dielectric permittivity of a PMMA film from nano-FTIR measurements, which is in excellent agreement with far-field ellipsometric data. We further obtain local infrared absorption spectra with unprecedented accuracy in peak position and shape, which is the key to quantitative chemometrics on the nanometer scale.


Not a simple relationship between Neptune's migration speed and Kuiper belt inclination excitation.
We present numerical simulations of giant planet migration in our solar system and examine how the speed of planetary migration affects inclinations in the resulting population of small bodies (test particles) scattered outward and subsequently captured into Neptune's 3:2 mean motion resonance (the Plutinos) as well as the hot classical Kuiper belt population. We do not find a consistent relationship between the degree of test particle inclination excitation and e-folding planet migration timescales in the range 5 - 50 Myr. Our results present a counter-example to Nesvorný (2015)'s finding that the Plutino and hot classical inclinations showed a marked increase with increasing e-folding timescales for Neptune's migration. We argue that these differing results are likely due to differing secular architectures of the giant planets during and after migration. Small changes in the planets' initial conditions and differences in the numerical implementation of planet migration can result in different amplitudes of the planets' inclination secular modes, and this can lead to different final inclination distributions for test particles in the simulations. We conclude that the observed large inclination dispersion of Kuiper belt objects does not require Neptune's migration to be slow; planetary migration with e-folding timescales of 5, 10, 30, and 50 Myr can all yield inclination dispersions similar to the observed Plutino and hot classical populations, with no correlation between the degree of inclination excitation and migration speed.


Concomitant DNA copy number amplification at 17q and 22q in dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans (DFSP) is a tumor of low or intermediate malignant potential with a tendency for recurrence, but low rate of metastasis. The tumorigenesis of DFSP has recently been shown to be associated with the fusion of the collagen type I alpha 1 (COL1A1) and platelet-derived growth factor B-chain (PDGFB) genes, often as a consequence of translocation t(17;22)(q22;q13). Cytogenetically, DFSP is often characterized by supernumerary ring chromosomes containing material from chromosomes 17 and 22. A subset of DFSPs undergo fibrosarcomatous transformation de novo or upon recurrence, and contain components indistinguishable from fibrosarcoma (FS-DFSP). The fibrosarcomatous transformation appears to carry an increased risk for recurrence and metastasis, and is considered to represent tumor progression. The molecular cytogenetic events contributing to tumor progression are unknown. We used comparative genomic hybridization to analyze DNA copy number changes in 11 cases of typical DFSP and 10 cases of FS-DFSP. All cases in both groups were found to exhibit a gain or high-level amplification on chromosome 17q and the majority also on 22q. This finding is in line with previous studies, and suggests further that not only the COL1A1/PDGFB fusion gene formation but also the role of DNA copy number gains in the 17q and 22q regions is crucial per se in the pathogenesis of DFSP. Even though FS-DFSPs displayed a trend toward increase in the number of DNA copy number changes, the difference was not statistically significant, which indicates that mechanisms other than copy number changes are important in the transformation process of DFSP.


Evaluation of the Ontario Mandatory Working-at-Heights Training Requirement in Construction, 2012‒2019.
The province of Ontario, Canada, implemented mandatory day-long training for construction workers required to use fall-protection equipment. More than 400 000 training sessions were completed by 2017 when the requirement took full effect. The lost-time workers' compensation claim incidence rate attributable to falls targeted by the training was 19% lower in 2017-2019 than in 2012-2014. Rates for two comparator injuries increased or stayed the same. The decline in targeted fall claim incidence rate of the other Canadian provinces was 6%. (Am J Public Health. 2024;114(1):38-41. https://doi.org/10.2105/AJPH.2023.307440).


Persistent recurrence of hypomania and prosopoaffective agnosia in a patient with right thalamic infarct.
The authors report a 63-year-old man with a history of brief isolated manic episodes who became persistently hypomanic after a small right thalamic infarct. Detailed behavioral and neuropsychologic assessment were performed 18 months after the stroke and revealed a prosopoaffective agnosia as the foremost cognitive disorder, i.e., an impairment in the identification of emotional facial expressions with preserved discrimination of facial identity. Difficulties in reasoning on humorous material and other signs of mild right hemisphere dysfunction were present, but other perceptual, frontal and abstract-reasoning cognitive functions were unimpaired. Prosopoaffective agnosia has not been reported previously in thalamic lesions or in primary or secondary mania. The authors discuss the hypothetical relationships between a right hemisphere deficit in processing emotions and relapsing of the patient's hypomanic behavior.


The coincidence of two ultra-rare hereditary eye diseases: gyrate atrophy and Kjer optic atrophy - a surprising diagnosis based on next-generation sequencing.
Genetically determined ophthalmic diseases form a numerous and heterogenic group of disorders. Making the accurate clinical diagnosis of genetic eye disease is often a challenge for an ophthalmologist. In many cases, only genetic testing enables the establishment of the proper clinical diagnosis. Here we describe two ultra-rare diseases: gyrate atrophy of the choroid and retina (GACR) and Kjer-type optic atrophy coexisting in a 39-year-old Polish patient with severe visual impairment including a significant reduction of visual acuity and night blindness. Atrophic pigmented changes with large pigment deposits and chorioretinal atrophy with the retina's disturbed structure (with atrophic scarring changes and the epiretinal membrane) of both eyes were observed. Electroretinography (ERG) revealed extinguished responses. A Next-Generation Sequencing (NGS) panel comprising 275 retinal genes revealed a presence of potentially pathogenic variants in two genes: a homozygous variant c.1058G>A (p.Gly353Asp) in the OAT gene and a heterozygous variant c.1886C>G (p.Ser629Ter) in the OPA1 gene. The diagnosis established based on NGS is surprising because initially, several different diagnoses have been made, including high degenerative myopia, choroideremia, Leber congenital amaurosis, and severe, atypical retinitis pigmentosa. This report provides the unquestioned diagnostic value of the combination of chorioretinal imaging and the NGS technique. To our knowledge, this is the first and the only description of the coincidence of gyrate atrophy and Kjer-type optic atrophy.


Effects of the Consumption of Prickly Pear Cacti (Opuntia spp.) and its Products on Blood Glucose Levels and Insulin: A Systematic Review.
Background and Objectives: There is confusion as to which component of the Opuntia spp. cacti has demonstrated anti-hyperglycemic effects or anti-diabetic properties. It is important to clarify these health benefits due to the increasing need for prevention and treatment of chronic diseases. The aim of this review is to identify the effects of Opuntia spp. cacti consumption on biomedical measures; glucose and insulin with consideration of its' components; fruit, leaf and combined or unidentified Opuntia spp. products. Materials and Methods: Prior to commencing the searches, this systematic review was registered with PROSPERO (CRD42018108765). Following the PRISMA 2009 guidelines, six electronic databases (Food Science and Technology Abstracts (EBSCO), Medline, Scopus, CINAHL, Web of Science and Cochrane) were searched for articles investigating the effect of Opuntia spp. consumption on glucose and insulin in humans. Results: Initially, 335 articles were sourced and filtered by exclusion criteria (human interventions, control trials and articles published in English) resulting in 20 relevant articles. The included studies were characterized by such plant components as fruit (n = 4), cladode (n = 12), and other Opuntia spp. products (n = 4), further separated by clinical populations ('healthy', hyperlipidemic, hypercholesterolemic, Type 2 Diabetes Mellitus). The findings of this review indicate variations in effects between cacti components and products. Cladode and select Opuntia spp. products predominately demonstrated significant reductions in serum glucose and insulin, indicating potential as a functional food candidate. Prickly Pear fruit was predominately reported to have no significant effects on glucose or insulin. The quality of evidence appeared to vary based on the type of Opuntia spp. product used. Studies that used specifically the fruit or cladode had high risk of bias, whereas studies which used combined Opuntia spp. products had a lower risk of bias. Numerous mechanisms of action were proposed where positive findings were reported, with emphasis on dualistic glucose-dependent and independent actions, however, mechanisms require further elucidation. Conclusion: Currently, there is a lack of evidence to support the recommendation of using Opuntia spp. fruit products as an alternative or complementary therapy in the reduction of risk or management of Type 2 Diabetes Mellitus. The Cladode does however show promise in potential glucose-lowering effects which warrant further investigation.


Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics.
During 2010 and 2012, California and Vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. To overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. Through the use of combined next-generation sequencing technologies, this study compared de novo, single-contig genome assemblies from 31 out of 33 Bordetella pertussis isolates collected during two separate pertussis statewide epidemics and 2 resequenced vaccine strains. Final genome architecture assemblies were verified with whole-genome optical mapping. Sixteen distinct genome rearrangement profiles were observed in epidemic isolate genomes, all of which were distinct from the genome structures of the two resequenced vaccine strains. These rearrangements appear to be mediated by repetitive sequence elements, such as high-copy-number mobile genetic elements and rRNA operons. Additionally, novel and previously identified single nucleotide polymorphisms were detected in 10 virulence-related genes in the epidemic isolates. Whole-genome variation analysis identified state-specific variants, and coding regions bearing nonsynonymous mutations were classified into functional annotated orthologous groups. Comprehensive studies on whole genomes are needed to understand the resurgence of pertussis and develop novel tools to better characterize the molecular epidemiology of evolving B. pertussis populations. IMPORTANCE Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen, B. pertussis strains circulating during epidemics exhibit diversity visible on a genome structural level, previously undetectable by traditional sequence analysis using short-read technologies. For the first time, we combine short- and long-read sequencing platforms with restriction optical mapping for single-contig, de novo assembly of 31 isolates to investigate two geographically and temporally independent U.S. pertussis epidemics. These complete genomes reshape our understanding of B. pertussis evolution and strengthen molecular epidemiology toward one day understanding the resurgence of pertussis.


A replication study of obsessional followers and offenders with mental disorders.
The purpose of this study was to compare certain demographic, clinical, and criminal variables within subgroups of obsessional followers, and compare them to a group of offenders with mental disorders to attempt to replicate earlier findings. A static group archival design utilized a non-random group of convenience and a randomly selected comparison group. Sixty-five obsessional followers and 65 offenders with mental disorders were evaluated by psychiatrists and psychologists for court ordered reasons during their criminal proceedings. Both groups were evaluated during the same period, in the same court diagnostic clinic, and generally for sentencing determinations. The obsessional followers were measured on demographic, diagnostic, pursuit, victim, threat, violence, emotional, motivational, and defense variables. Inferential comparisons that used parametric and nonparametric statistics were done within and between groups on select variables. The obsessional followers had significantly greater estimated IQ than the offenders with mental disorders, but were neither older nor better educated. There were no significant differences in the high prevalence of both DSM-IV Axis I and II diagnoses. Obsessional followers who stalked prior sexual intimates were significantly more likely to have a substance abuse or dependence diagnosis. Obsessional followers who stalked strangers or acquaintances were more likely to be delusional. The majority of the obsessional followers, primarily motivated by anger, both threatened and were violent toward person or property. The modal obsessional follower is an average or above IQ, unemployed, unmarried male in his fourth decade of life. chronically pursuing a prior sexually intimate female. He is diagnosed with substance abuse or dependence and a personality disorder NOS, and has a prior psychiatric, criminal and substance abuse history. He is angry, likely to threaten her, and assault her person or property without causing serious injury.


miR-204 is dysregulated in metastatic prostate cancer in vitro.
During cancer progression, the genome instability incurred rearrangement could possibly turn some of the tumor suppressor micro-RNAs into pro-oncogenic ones. We aimed to investigate miR-204 in the context of prostate cancer progression using a cell line model of different levels of genome instability (LNCaP, PC3, VCaP and NCI H660), as demonstrated by the availability of ERG fusion. We studied the effect of miR-204 modulation on master transcription factors important for lineage development, cell differentiation and prostate cancer bone marrow metastasis. We followed c-MYB, ETS1 and RUNX2 transcript and protein expression and the miR-204 affected global proteome. We further investigated if these transcription factors exert an effect on miR-204 expression (qPCR, luciferase reporter assay) by silencing them using esiRNA. We found dualistic miR-204 effects, either acting as a tumor suppressor on c-MYB, or as an oncomiR on ETS1. RUNX2 and ETS1 regulation by miR-204 was ERG fusion dependent, demonstrating regulatory circuitry disruption in advanced metastatic models. miR-204 also differentially affected mRNA splicing and protein stability. miR-204 levels were found dependent on cancer hypermethylation and supported by positive feedback induced by all three transcription factors. In this regulatory circuitry among miR-204, c-MYB, RUNX2 and ETS1, the c-MYB was found to induce all three other members, but its expression was differentially affected by the methylation status in lymph node vs. bone metastasis. We demonstrate that not only tumor suppressor micro-RNA loss, but also significant genome rearrangement-driven regulatory loop perturbations play a role in the advanced cancer progression, conferring better pro-survival and metastatic potential.


Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent.
An increasing number of broadly neutralizing antibodies (bnAbs) are considered leads for HIV-1 vaccine development and novel therapeutics. Here, we systematically explored the capacity of bnAbs to neutralize HIV-1 prior to and post-CD4 engagement and to block HIV-1 cell-cell transmission. Cell-cell spread is known to promote a highly efficient infection with HIV-1 which can inflict dramatic losses in neutralization potency compared to free virus infection. Selection of bnAbs that are capable of suppressing HIV irrespective of the transmission mode therefore needs to be considered to ascertain their in vivo activity in therapeutic use and vaccines. Employing assay systems that allow for unambiguous discrimination between free virus and cell-cell transmission to T cells, we probed a panel of 16 bnAbs for their activity against 11 viruses from subtypes A, B and C during both transmission modes. Over a wide range of bnAb-virus combinations tested, inhibitory activity against HIV-1 cell-cell transmission was strongly decreased compared to free virus transmission. Activity loss varied considerably between virus strains and was inversely associated with neutralization of free virus spread for V1V2- and V3-directed bnAbs. In rare bnAb-virus combinations, inhibition for both transmission modes was comparable but no bnAb potently blocked cell-cell transmission across all probed virus strains. Mathematical analysis indicated an increased probability of bnAb resistance mutations to arise in cell-cell rather than free virus spread, further highlighting the need to block this pathway. Importantly, the capacity to efficiently neutralize prior to CD4 engagement correlated with the inhibition efficacy against free virus but not cell-cell transmitted virus. Pre-CD4 attachment activity proved strongest amongst CD4bs bnAbs and varied substantially for V3 and V1V2 loop bnAbs in a strain-dependent manner. In summary, bnAb activity against divergent viruses varied depending on the transmission mode and differed depending on the window of action during the entry process, underscoring that powerful combinations of bnAbs are needed for in vivo application.


Ccr4 contributes to tolerance of replication stress through control of CRT1 mRNA poly(A) tail length.
In Saccharomyces cerevisiae, DNA replication stress activates the replication checkpoint, which slows S-phase progression, stabilizes slowed or stalled replication forks, and relieves inhibition of the ribonucleotide reductase (RNR) complex. To identify novel genes that promote cellular viability after replication stress, the S. cerevisiae non-essential haploid gene deletion set (4812 strains) was screened for sensitivity to the RNR inhibitor hydroxyurea (HU). Strains bearing deletions in either CCR4 or CAF1/POP2, which encode components of the cytoplasmic mRNA deadenylase complex, were particularly sensitive to HU. We found that Ccr4 cooperated with the Dun1 branch of the replication checkpoint, such that ccr4Delta dun1Delta strains exhibited irreversible hypersensitivity to HU and persistent activation of Rad53. Moreover, because ccr4Delta and chk1Delta exhibited epistasis in several genetic contexts, we infer that Ccr4 and Chk1 act in the same pathway to overcome replication stress. A counterscreen for suppressors of ccr4Delta HU sensitivity uncovered mutations in CRT1, which encodes the transcriptional repressor of the DNA-damage-induced gene regulon. Whereas Dun1 is known to inhibit Crt1 repressor activity, we found that Ccr4 regulates CRT1 mRNA poly(A) tail length and may subtly influence Crt1 protein abundance. Simultaneous overexpression of RNR2, RNR3 and RNR4 partially rescued the HU hypersensitivity of a ccr4Delta dun1Delta strain, consistent with the notion that the RNR genes are key targets of Crt1. These results implicate the coordinated regulation of Crt1 via Ccr4 and Dun1 as a crucial nodal point in the response to DNA replication stress.


Candesartan augments ischemia-induced proangiogenic state and results in sustained improvement after stroke.
We have shown that acute treatment with candesartan in an experimental model of stroke resulted in vascular protection and improved outcomes at 24 hours poststroke, but the mechanisms are unknown. We now examine effects of candesartan on proangiogenic factors and 7-day outcomes using the same treatment paradigm. Male Wistar rats underwent 3 hours of middle cerebral artery occlusion followed by reperfusion. A single dose of 1 mg/kg candesartan intravenously was given at reperfusion. Animals received neurobehavioral testing before middle cerebral artery occlusion, at 24 hours after middle cerebral artery occlusion, and at 7 days. Blood pressure was measured by telemetry. Animals euthanized at 24 hours had brain tissue and cerebrospinal fluid collected for matrix metalloproteinase activity, vascular endothelial growth factor expression, and tube formation assay. Neurobehavioral testing included elevated body swing test, Bederson, beam walk, and paw grasp. Cerebrovascular density was quantified using immunohistochemistry at 24 hours and 7 days. Matrix metalloproteinase-2 activity and vascular endothelial growth factor expression were higher (P=0.035, P=0.042, respectively) and cerebrospinal fluid was significantly more proangiogenic (5x tube formation; P=0.002) in the candesartan group at 24 hours. Although no difference was seen in infarct size at 7 days, treatment improved Bederson scores (2.1 versus 2.9, P=0.0083), elevated body swing test (22.9 versus 39.4, P=0.021), and paw grasp (1.29 versus 2.88, P=0.0001) at 7 days. Candesartan treatment resulted in increased vascular density in the striatum at 7 days (P=0.037). Candesartan after reperfusion augments ischemia-induced angiogenic state and provides long-term benefits. The beneficial effects may involve vascular protection and enhancement of early angiogenic remodeling.


Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry.
Pleuropulmonary blastoma (PPB) has 3 subtypes on a tumor progression pathway ranging from type I (cystic) to type II (cystic/solid) and type III (completely solid). A germline mutation in DICER1 is the genetic cause in the majority of PPB cases. Patients confirmed to have PPB by central pathology review were included, and their clinical characteristics and outcomes were reported. Germline DICER1 mutations were sought with Sanger sequencing. There were 435 cases, and a central review confirmed 350 cases to be PPB; 85 cases (20%) were another entity. Thirty-three percent of the 350 PPB cases were type I or type I regressed (type Ir), 35% were type II, and 32% were type III or type II/III. The median ages at diagnosis for type I, type II, and type III patients were 8, 35, and 41 months, respectively. The 5-year overall survival (OS) rate for type I/Ir patients was 91%; all deaths in this group were due to progression to type II or III. OS was significantly better for type II versus type III (P = .0061); the 5-year OS rates were 71% and 53%, respectively. Disease-free survival (DFS) was also significantly better for type II versus type III (P = .0002); the 5-year DFS rates were 59% and 37%, respectively. The PPB type was the strongest predictor of outcome. Metastatic disease at the diagnosis of types II and III was also an independent unfavorable prognostic factor. Sixty-six percent of the 97 patients tested had a heterozygous germline DICER1 mutation. In this subset, the DICER1 germline mutation status was not related to the outcome. Cystic type I/Ir PPB has a better prognosis than type II, and type II has a better outcome than type III. Surveillance of DICER1 carriers may allow the earlier detection of cystic PPB before its progression to type II or III PPB and thereby improve outcomes.


[Immunocorrection in combined prevention of early postoperative complications in patients with systemic vasculitis].
The authors studied peculiarities of the immune status in angiosurgical patients with systemic vasculitis, as well as possibilities of immunodiagnosis and immunocorrection in prevention of early coagulopathic and reparative complications after angiosurgical interventions in this cohort of patients. A total of 172 angiosurgical patients presenting with systemic vasculitis were subdivided into two groups depending on the preoperative preparation methods used. In Group One (Study Group) comprising 81 patients preoperative preparation was carried out using immunosuppressive therapy with hormones and cytostatics according to the rheumatologist's indications. In Group Two (n=91) hormones and/or cytostatics were replaced by the proposed four-component immunocorrection including various combinations of correcting the lifestyle, use of antioxidative-activity immunomodulators, plasmapheresis and intravenous administration of immunoglobulins. It was determined that using this method of correction made it possible to achieve a good anti-inflammatory effect in angiosurgical patients with systemic vasculitis, thus avoiding negative aftermaths of immunosuppression. The developed method of immunocorrection makes it possible to decrease the rate of early postoperative coagulopathic and reparative complications in angiosurgical patients as compared to therapy with hormones and/or cytostatics.


The person-affecting restriction, comparativism, and the moral status of potential people.
Traditional ethical theories have paradoxical implications in regards to questions concerning procreation and our moral duties to future people. It has been suggested that the crux of the problem resides in an all too 'impersonal' axiology and that the problems of population axiology can be solved by adopting a 'Person Affecting Restriction' which in its slogan form states that an outcome can only be better than another if it is better for people. This move has been especially popular in the context of medical ethics where many of the problems of population axiology are actualized. Examples are embryo or egg selection, pre-implantation genetic testing, assisted reproduction programmes, abortion, just to mention a few. I discuss a number of different interpretations of the Restriction and in particular one interpretation which I call Comparativism. According to this view, we should draw a distinction between uniquely and non-uniquely realizable people. The former people only exist in one out of two possible outcomes, whereas the latter exist in both of the compared outcomes. The idea is that we should give more weight to the well-being of non-uniquely realizable people or take it into account in a different way as compared to the well-being of uniquely realizable people. I argue that the different versions of the Person Affecting Restriction and Comparativism either have counterintuitive implications of their own or are compatible with traditional theories such as Utilitarianism.


Detectionof reverse transcriptase activity in live attenuated virus vaccines.
Safety considerations require that biological products for human use are free from any agent that might pose a potential health hazard. One method to detect the presence of retroviral particles is the reverse transcriptase (RT) assay. This assay is capable of detecting all infectious retrovirus particles, irrespective of genome or protein composition. Recently, a family of ultrasensitive RT tests, named product-enhanced reverse transcriptase (PERT) assays, has been designed with a detection limit that is 10(6) - 10(7) times lower than that of conventional RT tests. To investigate with the PERT assay whether RT activity is detectable in live attenuated virus vaccines and to characterize eventual RT activities. A total of 12 different monovalent and one trivalent virus vaccines containing live attenuated viruses were tested for RT activity with the PERT assay and a conventional RT test. RT activities were investigated with respect to their susceptibility to RT inhibitors, association with physical particles, and their possible origin. One trivalent and five different monovalent vaccines contained RT activity when tested with the PERT assay, but were negative in a conventional RT assay. All lots tested of these vaccines showed RT activity. The activity in all vaccines was sensitive to AZT-triphosphate and ddTTP and at least part of it was associated with particles. Mg(2+)-dependent RT activity banded at a density of 1.14 g/ml. All positive vaccines were produced using chicken cells. The data indicate the systematic presence of partially particle-associated retroviral reverse transcriptase in attenuated live virus vaccines that are produced in chicken-derived cells. The identification and further characterization of these particles, as well as the elucidation of possible interactions with the human organism are imperative goals despite the fact that these vaccines have been safely used for many years.


Distinguishing asthma from sarcoidosis: an approach to a problem that is not always solvable.
Because pulmonary sarcoidosis often affects the airway, it is commonly confused with asthma. This article reviews the mechanisms of airflow obstruction in sarcoidosis, the symptoms associated with this phenomenon, and the approach to distinguish sarcoidosis from asthma. Because asthma is highly likely in a patient with wheeze, cough, and chest tightness, sarcoidosis is usually not considered unless the patient has extrapulmonary manifestations of sarcoidosis or a family history of the disease. When pulmonary sarcoidosis is a consideration, a chest radiograph should be performed. A chest radiograph should also be performed in an asthmatic patient when the presentation is atypical, or fails to respond to standard asthma treatment; chest radiography should be performed in this situation to consider not only pulmonary sarcoidosis but also other possible cardiopulmonary disorders. In a patient with confirmed pulmonary sarcoidosis, the diagnosis of concomitant asthma is problematic. The symptoms associated with the two disorders are often identical. Airflow obstruction is common in sarcoidosis so that pulmonary function testing is unlikely to differentiate these two diseases. Demonstration of airway hyperreactivity may fail to distinguish these disorders as this is common in sarcoidosis. Serum IgE, serum angiotensin-converting enzyme levels, sputum eosinophilia, and exhaled nitric oxide measurements show promise as distinguishing tests, although they have not been studied specifically. Pulmonary imaging is probably of limited value unless baseline studies are available for comparison. We suspect that historical information will be more useful in distinguishing these two diseases. Not infrequently, it may be impossible to exclude or confirm an asthmatic component in a confirmed pulmonary sarcoidosis patient. Fortunately, exacerbations of both these diseases are often treated with systemic corticosteroids initially. Significant variability in pulmonary symptoms and airflow obstruction suggest that an asthma component is present, and inhaled corticosteroids and bronchodilators should be considered in these cases, Asthma and sarcoidosis share many of the same symptoms, as sarcoidosis commonly affects the airways. Therefore, it is problematic to distinguish these two diseases. In this article, we have outlined an approach to assess the presence of each of these diseases and an approach to therapy.


First population-level effectiveness evaluation of a national programme to prevent HIV transmission from mother to child, South Africa.
There is a paucity of data on the national population-level effectiveness of preventing mother-to-child transmission (PMTCT) programmes in high-HIV-prevalence, resource-limited settings. We assessed national PMTCT impact in South Africa (SA), 2010. A facility-based survey was conducted using a stratified multistage, cluster sampling design. A nationally representative sample of 10 178 infants aged 4-8 weeks was recruited from 565 clinics. Data collection included caregiver interviews, record reviews and infant dried blood spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine ≤10 weeks; 2b: incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information. Findings were adjusted for non-response, survey design and weighted for live-birth distributions. Nationally, 32% of live infants were HEI; early mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total 29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had missing ARV information (3b). Controlling for other factors groups, 1b and 2a had similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a, 1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to 18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to 5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively). SA, a high-HIV-prevalence middle income country achieved <5% MTCT by 4-8 weeks post partum. The long-term impact on PMTCT on HIV-free survival needs urgent assessment.


Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum.
Monolayers of human erythrocytes (E) infected with Plasmodium falciparum were briefly fixed with 1% glutaraldehyde and air dried. They were then exposed to sera from patients with P. falciparum malaria or from donors immune to this parasite and tested in an indirect immunofluorescence assay (IFA). Parasites in infected E were made visible by counterstaining with ethidium bromide. Immunofluorescence (IF) was restricted to the surface of infected E. No antibody binding was detected unless the E were dried, suggesting that the relevant antigens were not available on the outer layers of the E surface. Staining over large parts of the E surface was seen already when the merozoite penetrated noninfected cells and was strong in E containing early stages of the parasite (rings, trophozoites). It was weak or absent from E containing schizonts. Antibodies in sera from different parts of Africa, Colombia, or Sweden reacted similarly with E infected with a Tanzanian P. falciparum strain kept in culture for many years and with parasitized E freshly drawn from African, Swedish, or Colombian patients. All sera from residents of a holoendemic area (Liberia) were IFA positive. In contrast, some sera from Colombian or Swedish patients with primary infection gave negative results. The results of the IFA and of an enzyme-linked immunosorbent assay in which fixed and dried E were the targets were well-correlated, suggesting that the same antibodies were detected by these assays. The antigens involved in the IFA were susceptible to pronase but not to trypsin or neuraminidase. E surface IF was inhibited by lysates of infected E, merozoite extracts, or soluble antigens present in P. falciparum culture supernatants but not by lysates of normal E or ghost extracts. The inhibitory antigens were heat stable (100 degrees C, 5 min). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting of either antigen-enriched preparations from culture supernatants or merozoite extracts showed that antibodies eluted from monolayers of infected E reacted consistently with a predominant polypeptide of Mr 155,000 and two to four minor polypeptides of lower molecular weights. Metabolic labeling of the parasites with 75Se-methionine indicated that these antigens were parasite derived. We conclude that the antigens involved in these reactions are released from bursting schizonts or merozoites and are deposited in the E membrane in the course of invasion.(ABSTRACT TRUNCATED AT 400 WORDS)


BPA Alters Estrogen Receptor Expression in the Heart After Viral Infection Activating Cardiac Mast Cells and T Cells Leading to Perimyocarditis and Fibrosis.
Myocarditis is an inflammatory heart disease that leads to dilated cardiomyopathy (DCM) and heart failure. Sex hormones play an important role in the development of myocarditis with testosterone driving disease in males and estrogen being cardioprotective in females. The human population is widely exposed to the endocrine disruptor bisphenol A (BPA) from plastics such as water bottles, plastic food containers, copy paper, and receipts. Several clinical and numerous animal studies have found an association between elevated BPA levels and cardiovascular disease. A recent report found elevated levels of BPA in the serum of patients with DCM compared to healthy controls. In this study we examined whether exposure to BPA for 2 weeks prior to viral infection and leading up to myocarditis at day 10 altered inflammation in female BALB/c mice housed in standard plastic cages/water bottles with soy-free food and bedding. We found that a human relevant dose of BPA (25 μg/L) in drinking water, with an estimated exposure of 5 μg BPA/kg BW, significantly increased myocarditis and pericarditis compared to control water without altering viral genome levels in the heart. BPA exposure activated ERα and ERβ in the spleen 24 h after infection and phosphorylated ERα and ERβ during myocarditis, but decreased ERα and increased ERβ mRNA in the heart as measured by qRT-PCR. Exposure to BPA significantly increased CD4+ T cells, IFNγ, IL-17A, TLR4, caspase-1, and IL-1β in the heart. BPA exposure also increased cardiac fibrosis compared to controls. Mast cells, which are associated with cardiac remodeling, were found to increase in number and degranulation, particularly along the pericardium. Interestingly, plastic caging/water bottle exposure alone led to increased mast cell numbers, pericardial degranulation and fibrosis in female BALB/c mice compared to animals housed in glass cages/water bottles with soy-free food and bedding. These data suggest that BPA exposure may increase the risk of developing myocarditis after a viral infection in women.


Brainstem disconnection: two additional patients and expansion of the phenotype.
Brainstem disconnection (BD) is a rare posterior fossa abnormality defined by the nearly complete absence of a brainstem segment with the rostral and caudal brainstem portions connected only by a thin cord of tissue. The outcome is poor and the majority of children die within the first 2 months of life without achieving developmental milestones. We report on the cases of two children with BD and a prolonged spontaneous survival. Neither patient required intubation or mechanical ventilation and each survived longer than 2 months (one child died at the age of 8 months, the other is alive at the age of 4.5 years). In addition, patient 1 is the only child with BD reported so far who achieved some developmental milestones. Although the long-term neurodevelopmental outcome of BD remains unfavorable, the expansion of the phenotypic spectrum may be important in terms of counseling.


Cognitive versus functional approaches to rehabilitation after traumatic brain injury: commentary on a randomized controlled trial.
I describe the findings of one of the largest randomized controlled trials (RCTs) of rehabilitation after traumatic brain injury (TBI) ever conducted, examine the theoretical relationship between cognitive and functional rehabilitation after TBI, and describe the historical preference for cognitive (top-down) rather than functional (bottom-up) interventions. I also contrast the goals and principles of cognitive rehabilitation and of the neurofunctional approach of Giles and Clark-Wilson (1993; Giles, 2005)--a bottom-up approach. Findings of the RCT provide empirical support for both functional and cognitive interventions following acute TBI. In addition, they provide evidence that each type of intervention offers significant advantages for a specific subpopulation. The clinical implications of these findings for occupational therapy practitioners are discussed.


Assessing the perceived prevalence of research fraud among faculty at research-intensive universities in the USA.
Survey-based studies on research fraud often feature narrow operationalizations of misbehavior and use limited samples. Such factors potentially hinder the development of strategies aimed at reducing the frequency of wrongdoing among researchers. This study asked full-time faculty members in the natural, social, and applied sciences how frequently six types of research fraud (i.e., data fabrication, plagiarism, data falsification, authorship fraud, publication fraud, and grant fraud) occur in their field of study. These data come from mail and online surveys that were administered to a stratified random sample of tenured and tenure-track faculty members (N = 613) at the top 100 research universities in the United States. Factor-analytic modeling demonstrated that the survey items load on the hypothesized latent constructs and also confirmed the presence of a second-order factor. A specific type of authorship fraud - gift authorship - was perceived to be the most prevalent overall. The least common fraud was a form of data fabrication (i.e., creating data from a study that was never actually conducted). The results were largely consistent with previous studies indicating that serious forms of fraud like data fabrication are relatively rare. Future survey-based studies should pay careful attention to the multidimensional nature of research fraud.


Error-free demodulation of pixelated carrier frequency interferograms.
Recently, pixelated spatial carrier interferograms have been used in optical metrology and are an industry standard nowadays. The main feature of these interferometers is that each pixel over the video camera may be phase-modulated by any (however fixed) desired angle within [0,2pi] radians. The phase at each pixel is shifted without cross-talking from their immediate neighborhoods. This has opened new possibilities for experimental spatial wavefront modulation not dreamed before, because we are no longer constrained to introduce a spatial-carrier using a tilted plane. Any useful mathematical model to phase-modulate the testing wavefront in a pixel-wise basis can be used. However we are nowadays faced with the problem that these pixelated interferograms have not been correctly demodulated to obtain an error-free (exact) wavefront estimation. The purpose of this paper is to offer the general theory that allows one to demodulate, in an exact way, pixelated spatial-carrier interferograms modulated by any thinkable two-dimensional phase carrier.


Intermittent versus continuous cerebrospinal fluid drainage management in adult severe traumatic brain injury: assessment of intracranial pressure burden.
There is clinical equipoise regarding whether neurointensive care unit management of external ventricular drains (EVD) in severe traumatic brain injury (TBI) should involve an open EVD, with continuous drainage of cerebrospinal fluid (CSF), versus a closed EVD, with intermittent opening as necessary to drain CSF. In a matched cohort design, we assessed the relative impact of continuous versus intermittent CSF drainage on intracranial pressure in the management of adult severe TBI. Sixty-two severe TBI patients were assessed. Thirty-one patients managed by open EVD drainage were matched by age, sex, and injury severity (initial Glasgow Coma Scale (GCS) score) to 31 patients treated with a closed EVD drainage. Patients in the open EVD group also had a parenchymal intracranial pressure (ICP) monitor placed through an adjacent burr hole, allowing real-time recording of ICP. Hourly ICP and other pertinent data, such as length of stay in intensive care unit (LOS-ICU), Injury Severity Score, and survival status, were extracted from our prospective database. With age, injury severity (initial GCS score), and neurosurgical intervention adjusted for, there was a statistically significant difference of 5.66 mmHg in mean ICP (p < 0.0001) between the open and the closed EVD groups, with the closed EVD group exhibiting greater mean ICP. ICP burden (ICP ≥ 20 mmHg) was shown to be significantly higher in the intermittent EVD group (p = 0.0002) in comparison with the continuous EVD group. Continuous CSF drainage via an open EVD seemed to be associated with more effective ICP control in the management of adult severe TBI.


Optically thin terahertz metamaterials.
Resonant properties of optically thin metamaterials are studied by terahertz time-domain spectroscopy. Both the lower energy inductor-capacitor (LC) and the higher energy dipole resonances of the planar double split-ring resonators (SRRs) exhibit characteristic evolution with various sub-skin-depth thicknesses of the constituent Pb film. The signature of the LC resonance begins to emerge at a critical thickness near 0.15 skin depth. The resonances reveal a characteristic enhancement; they are strengthened remarkably with increasing SRR thicknesses at sub-skin-depth level and then gradually saturate beyond the skin depth.