Bombardment induced ion transport--part III: experimental potassium ion conductivities in poly(para-xylylene).
The bombardment induced ion transport (BIIT) technique has been employed for studying the ionic conductivity of thin poly(p-xylylene) (PPX) films. The experiment is based on bombarding a PPX film with a c.w. potassium ion beam. The transport of ions through the film - which follows the laws of electrodiffusion - is detected as a neutralization current on the backside electrode on which the film has been deposited. This backside current scales quadratically with the acceleration potential of the ion beam and inversely cubically with the thickness of the film. This confirms theoretical predictions made in part I of this mini-series (Phys. Chem. Chem. Phys., 2011, 13, 20112-20122). This characteristic is markedly different from the Ohm-like current-voltage properties of a solid electrolyte, e.g. an ion conducting glass. The diffusion coefficient for K(+) in PPX is determined to be 8.528 × 10(-16) cm(2) s(-1) at 333 K. From the temperature dependence of the diffusion coefficient we conclude that a hopping mechanism with an activation energy of 2.74 eV ± 0.18 eV is operative.


Inflammaging as a major characteristic of old people: can it be prevented or cured?
Widespread aging at the population level is a recent phenomenon that emerged in affluent societies. Inflammation is necessary to cope with damaging agents and is crucial for survival, particularly to cope with acute inflammation during our reproductive years. But chronic exposure to a variety of antigens, especially to some viruses such as cytomegalovirus, for a period much longer than that predicted by evolution, induces a chronic low-grade inflammatory status that contributes to age-associated morbidity and mortality. This condition carries the proposed name "inflammaging". Centenarians are unique in that, despite high levels of pro-inflammatory markers, they also exhibit anti-inflammatory markers that may delay disease onset. The key to successful aging and longevity is to decrease chronic inflammation without compromising an acute response when exposed to pathogens.


Motor functioning and associated cognitive outcomes in pediatric survivors of acute lymphoblastic leukemia.
Pediatric acute lymphoblastic leukemia survivors are at risk for developing neurocognitive late effects following intensive medical treatment. Motor impairments have been highlighted as a common neurocognitive late effect, including fine-, gross-, and visual-motor skills. The severity of these motor deficits is variable in the existing literature, warranting additional investigations with more homogenous samples. In addition, there is an even greater paucity regarding the interrelations between motor deficits and the impact motor challenges may have on other domains of functioning, such as academics. Therefore, the present study aimed to characterize motor functioning in children who were treated for acute lymphoblastic leukemia with chemotherapy (n = 13) in comparison to healthy controls (n = 13). Additionally, this study investigated the relationship between primary (e.g., visual-spatial, fine-motor), secondary (e.g., visual-motor), and tertiary (e.g., academics) skills. The results revealed that oncology survivors had significantly lower fine- and gross-motor skills compared to healthy controls. No significant differences were observed between the groups on visual-perception and visual-motor tasks. Fine-motor functioning was significantly associated with visual-motor functioning in ALL survivors. Motor skills were not related to academic outcomes. The present findings provide evidence for motor impairments in pediatric ALL survivors, along with initial findings highlighting the cascading effect of primary motor impairments on other cognitive domains. This research sheds light on the need for clinical screening and intervention of motor skills in the survivorship population. Future research is warranted to examine the effect of motor deficits on cognitive and psychosocial functioning in pediatric oncology.


The effect of uterine motion and uterine margins on target and normal tissue doses in intensity modulated radiation therapy of cervical cancer.
In intensity modulated radiation therapy (IMRT) of cervical cancer, uterine motion can be larger than cervix motion, requiring a larger clinical target volume to planning target volume (CTV-to-PTV) margin around the uterine fundus. This work simulates different motion models and margins to estimate the dosimetric consequences. A virtual study used image sets from ten patients. Plans were created with uniform margins of 1 cm (PTV(A)) and 2.4 cm (PTV(C)), and a margin tapering from 2.4 cm at the fundus to 1 cm at the cervix (PTV(B)). Three inter-fraction motion models (MM) were simulated. In MM1, all structures moved with normally distributed rigid body translations. In MM2, CTV motion was progressively magnified as one moved superiorly from the cervix to the fundus. In MM3, both CTV and normal tissue motion were magnified as in MM2, modeling the scenario where normal tissues move into the void left by the mobile uterus. Plans were evaluated using static and percentile DVHs. For a conventional margin (PTV(A)), quasi-realistic uterine motion (MM3) reduces fundus dose by about 5 Gy and increases normal tissue volumes receiving 30-50 Gy by ∼5%. A tapered CTV-to-PTV margin can restore fundus and CTV doses, but will increase normal tissue volumes receiving 30-50 Gy by a further ∼5%.


[Gout management: an update].
Gout is the most frequent arthritis worldwide. Despite progress in therapeutic options the majority of gout patients are still insufficiently treated. International guidelines (ACR, EULAR, 3e initiative) clearly specify treatment targets: keep the patient flare-free and maintain a low urate serum level (< 360 µmol/l). The treat to target strategy includes therapy of flares, urate lowering treatment (ULT) and prophylaxis of flares. Evolution of gout guidelines over several years shows a broader indication for ULT, mandatory prophylaxis of flares during the initiation of ULT over several months and an earlier start of ULT in patients with flares as soon as symptoms have diminished. Colchicine is the preferred specific flare treatment, Caution has to be taken especially in patients with kidney disease, patients with hepatic dysfunction or in patients with interacting comedication. Low dose oral colchicine is nowadays the standard flare treatment. NSAIDs and prednisone are valuable alternatives. Interleukin-1 blockers offer a quick resolution of flares and may be an option in patients with chronic gout and severe kidney disease. Xanthinoxidase inhibitors (XOI) are the mainstay of ULT, with allopurinol still being the preferred XOI. The recently approved XOI febuxostat is eliminated mostly by the liver and can induce a faster lowering of urate. Uricosuric drugs such as probenecid are recommended in patients with sufficient renal function in whom the treatment goals cannot be reached with XOI. In Switzerland, only the two gout-lowering drugs allopurinol and probenecid are available, which reduces the therapeutic possibilities. Treatment success is often hampered by malcompliance. Recent guidelines stress the importance of patient education to ameliorate compliance. Comorbidities such as metabolic syndrome, cardiovascular and kidney disease are often found in gout patients. Patients with severe kidney disease are the most difficult to treat: the choice of antiinflammatory treatment is narrowed, ULT has to be uptitrated very carefully and patients often suffer from repeated flares. Another factor associated with treatment failure is the low physician's adherence towards the guidelines. Therapeutic failure can lead to chronic and refractory gout (polyarticular gout, uncontrolled flare activity, chronic synovitis, destructive tophi) which makes the further management very difficult. Most gout patients are treated in primary care settings. Patients with chronic gout or at high risk for development of chronic gout (in particular patients with severe kidney disease or patients transplanted) should be additionally treated by a rheumatologist.


On the fate of sexual traits under asexuality.
Environmental shifts and life-history changes may result in formerly adaptive traits becoming non-functional or maladaptive. In the absence of pleiotropy and other constraints, such traits may decay as a consequence of neutral mutation accumulation or selective processes, highlighting the importance of natural selection for adaptations. A suite of traits are expected to lose their adaptive function in asexual organisms derived from sexual ancestors, and the many independent transitions to asexuality allow for comparative studies of parallel trait maintenance versus decay. In addition, because certain traits, notably male-specific traits, are usually not exposed to selection under asexuality, their decay would have to occur as a consequence of drift. Selective processes could drive the decay of traits associated with costs, which may be the case for the majority of sexual traits expressed in females. We review the fate of male and female sexual traits in 93 animal lineages characterized by asexual reproduction, covering a broad taxon range including molluscs, arachnids, diplopods, crustaceans and eleven different hexapod orders. Many asexual lineages are still able occasionally to produce males. These asexually produced males are often largely or even fully functional, revealing that major developmental pathways can remain quiescent and functional over extended time periods. By contrast, for asexual females, there is a parallel and rapid decay of sexual traits, especially of traits related to mate attraction and location, as expected given the considerable costs often associated with the expression of these traits. The level of decay of female sexual traits, in addition to asexual females being unable to fertilize their eggs, would severely impede reversals to sexual reproduction, even in recently derived asexual lineages. More generally, the parallel maintenance versus decay of different trait types across diverse asexual lineages suggests that neutral traits display little or no decay even after extended periods under relaxed selection, while extensive decay for selected traits occurs extremely quickly. These patterns also highlight that adaptations can fix rapidly in natural populations of asexual organisms, in spite of their mode of reproduction.


Scanning electron microscopy and immunohistochemical observations of the vascular nerve plexuses in the dental pulp of rat incisor.
The innervation of rat incisors, which are continuously erupting teeth, is quite unique. Although many reports have documented the neural control of the pulpal blood flow, only a few studies have examined the structure and distribution of vascular nerves in the rat incisors. This study examined the nerve plexuses and the spatial relationship of nerve terminals to smooth muscle cells of the pulp vessels of rat incisors. The innervation of the pulp vessels of rat incisors was studied using immunohistochemical evaluations of calcitonin gene-related peptide (CGRP) and neuropeptide-Y (NPY). The three-dimensional ultrastructure of nerve meshworks and terminals on smooth muscle cells of pulp arterioles were examined by scanning electron microscopy (SEM) with a KOH digestion method. The blood vessels were associated with many nerve fibers immunoreactive for CGRP and NPY. Some NPY and frequent CGRP-immunoreactive nerve fibers were observed in the labial odontoblast layer. Three different morphologies of nerve fibers could be distinguished: fine nerve fibers with numerous terminal varicosities, medium-sized fibers associated with occasional or much scarcer varicosities, and thick fibers that had no varicosity and sometimes ran apart from blood vessels. The SEM observations identified five vascular segment types: terminal arterioles, precapillary arterioles, capillaries, postcapillary venules, and muscular venules. Nerve meshworks were observed around the large terminal arterioles; these meshworks were very comparable to those revealed by immunohistochemistry. The vascular smooth muscle cells were closely attached by one or more terminal varicosities. It has become evident that the large terminal arterioles in the rat incisors receive a dense nerve supply and provide well-developed wall architecture, suggesting an important role of neuronal regulation on the vessels.


Evans blue antagonizes both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and kainate receptors and modulates receptor desensitization.
The biphenyl derivative of 1,3-naphthalene disulfonic acid, known as Evans blue (EB), has been shown previously to specifically antagonize currents mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors (1). In contrast, we demonstrate herein that EB potently inhibits glutamate-evoked currents mediated by the kainate-type receptor GluR6 (IC50 150 nM) as well as the AMPA-type receptor GluR1 (IC50 = 220 nM) in whole-cell patch clamp recordings from transfected human embryonic kidney 293 cells. In addition to diminishing GluR6-mediated peak current amplitude, EB significantly altered receptor desensitization by slowing the rate of onset by approximately 2-fold (1 microM EB), slowing the rate of recovery by approximately 2-fold (0.1 microM EB), and increasing the steady state to peak current amplitude ratio by approximately 50-fold (1 microM EB). Interestingly, relatively little EB inhibition of GluR6 currents was observed in recordings from cells pretreated with the lectin concanavalin A, which eliminates kainate receptor desensitization. Similarly, currents recorded from GluR1-transfected cells were also relatively insensitive to EB inhibition if desensitization was first blocked by cyclothiazide. Moreover, for both GluR6 and GluR1, EB inhibition of agonist-evoked current was largely reversed if transfected cells were subsequently exposed to concanavalin A or cyclothiazide, respectively. Although EB may not be as selective an antagonist as previously believed, the relationship between EB-induced peak current inhibition and effects on receptor desensitization may be useful in further elucidating structures or mechanisms involved in the rapid desensitization of AMPA- and kainate-type glutamate receptors.


A Qualitative Study Exploring Yoga in Veterans with PTSD Symptoms.
Quantitative studies of yoga have reported reduced posttraumatic stress disorder (PTSD) symptoms in veterans, but little is known about how and why veterans are attracted to and stick with a yoga practice. Guided by the Health Belief Model, this study examined veterans' perceptions of the benefits, barriers, and motivations to continue practicing trauma-sensitive yoga. Interviews were conducted with nine individuals, five of whom completed a 6-week trauma-sensitive yoga intervention designed for veterans and four who did not complete the intervention. Transcripts were analyzed for themes. The benefits identified by veterans were finding mental stillness, body awareness, and social connection. The barriers were perceptions that yoga is socially unacceptable, especially for men, and physically unchallenging. Understanding these benefits and barriers can help to make yoga more attractive to service members and veterans. For example, medical personnel can refer service members and veterans to yoga not only for PTSD symptoms, but also to address back pain and to reduce isolation. Access to male yoga instructors, especially those who are themselves service members or veterans, could be expanded, and classes could be integrated into physical activity routines required of active-duty personnel. Promotional materials can feature male service members and veterans with captions related to yoga as a way to increase resiliency, self-sufficiency, and physical and mental mission readiness. Findings from this study can help the Department of Defense and the Veterans Health Administration implement yoga as an adjunct or alternative treatment for veterans with PTSD symptoms.


Community-centred oral healthcare for adults experiencing homelessness in Australia: Perceptions and experiences of key stakeholders.
The objective of the study was to identify whether creating a responsive, respectful and trustworthy environment that provides free dental care for clients who are homeless using volunteer dental professionals was effective in meeting their oral health needs in Fremantle, Western Australia. Qualitative research conducted between October 2018 and August 2019 was guided by a social constructivist paradigm to gather and analyse data. Semi-structured interviews were conducted with adults experiencing homelessness accessing a community dental clinic and health providers and other stakeholders involved in its establishment, management and service delivery. An inductive approach to analysis was used to organise themes under the categories of 'establishing the oral health clinic' (OHC) and 'responses to the implementation of the clinic' Thirty-nine semi-structured interviews were conducted across eight participant groups: clients, executive management, the oral health clinical reference group, volunteer dentists, employed staff, nursing students, volunteer staff and other stakeholders. Key findings across all groups included positive responses to the establishment and implementation of the OHC, the quality of care and the safe and respectful environment in which services were delivered. Challenges related to sustainability include uncertainty around ongoing funding and recruitment of dental professionals. Whilst volunteer dental services fill a gap in meeting the complex needs of this population group, mainstream services must consider and address issues of equity in this context. Findings can be used to guide this process that includes creating environments of respect and trust where adults who are homeless or at risk of homelessness feel safe, welcomed and more likely to return to the service.


RS9, a novel Nrf2 activator, attenuates light-induced death of cells of photoreceptor cells and Müller glia cells.
The retina is highly sensitive to oxidative stress because of its high consumption of oxygen associated with the phototransductional processes. Recent findings have suggested that oxidative stress is involved in the pathology of age-related macular degeneration, a progressive degeneration of the central retina. A well-known environmental risk factor is light exposure, as excessive and continuous light exposure can damage photoreceptors. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that controls antioxidative responses and phase 2 enzymes. Thus, we hypothesized that RS9, a specific activator of Nrf2, decreases light-induced retinal cell death in vivo and in vitro. Nrf2 was detected in the nucleus of the 661W cells exposed to RS9 and also after light exposure, and the Nrf2-antioxidant response element binding was increased in 661W cells after exposure to RS9. Consequentially, the expression of the phase 2 enzyme's mRNAs of Ho-1, Nqo-1, and Gclm genes was increased in 661W cells after exposure to RS9. Furthermore, RS9 decreased the light-induced death of 661W cells (2500 lux, 24 h), and also reduced the functional damages and the histological degeneration of the nuclei in the outer nuclear layer or the retina in the in vivo studies (8000 lux, 3 h). Heme oxygenase-1 was increased after light exposure, and Nrf2 was translocated into the nucleus after light exposure in vivo. Silencing of Ho-1 reduced the protective effects of RS9 against light-induced death of 661W cells. These findings indicate that RS9 has therapeutic potential for retinal diseases that are aggravated by light exposure.


Treatment of megacolon and megarectum.
Patients presenting with megacolon and megarectum require extensive specialized testing to distinguish underlying Hirschsprung's disease from other secondary causes. Diagnostic testing and long-term treatment are best initiated after disimpaction has been achieved, by large-volume tap water enemas and/or oral colonic lavage with polyethylene glycol. With intensive treatment (including biofeedback if pelvic floor dysfunction is present), at lease one half of patients can avoid surgery. Maintenance therapy relies on daily use of osmotic laxatives. Stimulant laxatives are used intermittently as rescue treatments if there has not been a satisfactory bowel movement in 3 days. Patients with idiopathic megacolon or megarectum may require surgery if they have refractory symptoms. Depending on age, pelvic floor, and anal sphincter function, patients who have isolated megacolon can be treated with either subtotal colectomy with ileorectostomy or diverting loop ileostomy. Patients with isolated megarectum can be treated with either proctectomy and coloanal anastomosis or vertical reduction rectoplasty. Patients who have combined megacolon and megarectum can be offered diverting loop ileostomy or, if pelvic floor function is normal and they wish to avoid stoma, total proctocolectomy with ileal pouch-anal anastomosis.


Carrier-mediated uptake of lucifer yellow in skate and rat hepatocytes: a fluid-phase marker revisited.
Uptake of lucifer yellow (LY), a fluorescent disulfonic acid anionic dye, was studied in isolated skate (Raja erinacea) perfused livers and primary hepatocytes to evaluate its utility as a fluid-phase marker in these cells. However, our findings demonstrated that LY is transported across the plasma membrane of skate hepatocytes largely via carrier-mediated mechanisms. Isolated perfused skate livers cleared 50% of the LY from the recirculating perfusate within 1 h of addition of either 22 or 220 microM LY, with only 4.5 and 9% of the LY remaining in the perfusate after 7 h, respectively. Most of the LY was excreted into bile, resulting in high biliary LY concentrations (1 and 10 mM at the two doses, respectively), indicating concentrative transport into bile canalicular lumen. LY uptake by freshly isolated skate hepatocytes was temperature sensitive, exhibited saturation kinetics, and was inhibited by other organic anions. Uptake was mediated by both sodium-dependent [Michaelis-Menten constant (K(m)), 125 +/- 57 microM; maximal velocity (V(max)), 1.5 +/- 0.2 pmol. min(-1). mg cells(-1)] and sodium-independent (K(m), 207 +/- 55 microM; V(max), 1.7 +/- 0.2 pmol. min(-1). mg cells(-1)) mechanisms. Both of these uptake mechanisms were inhibited by various organic anions and transport inhibitors, including furosemide, bumetanide, sulfobromophthalein, rose bengal, probenecid, N-ethylmaleimide, taurocholate, and p-aminohippuric acid. Fluorescent imaging techniques showed intracellular vesicular compartmentation of LY in skate hepatocyte clusters. Studies in perfused rat livers also indicated that LY is taken up against a concentration gradient and concentrated in bile. LY uptake in isolated rat hepatocytes was saturable, but only at high concentrations, and demonstrated a K(m) of 3.7 +/- 1.0 mM and a V(max) of 1.75 +/- 0.16 nmol. min(-1). mg wet wt(-1). These results indicate that LY is transported into skate and rat hepatocytes and bile largely by carrier-mediated mechanisms, rather than by fluid-phase endocytosis.


Antipsychotic drugs and the elderly.
Antipsychotic agents can be useful in the treatment of elderly patients who manifest psychotic signs and symptoms. Geropsychiatric disorders in which these drugs may be indicated include chronic schizophrenia persisting into late life, paraphrenia, dementia, and delirium. Unfortunately, antipsychotic drugs are more difficult to use in elderly patients than in younger psychotic patients. A clearly positive clinical response is less likely to occur in elderly patients, particularly in those who have an underlying dementia. In addition, the incidence of adverse effects in elderly patients is high. However, if these cautions are kept in mind, the clinician can select the appropriate antipsychotic based on a patient's particular medical status and, thus, reduce the patient's disability and enhance the patient's quality of life.


A branched biosynthetic pathway is involved in production of roquefortine and related compounds in Penicillium chrysogenum.
Profiling and structural elucidation of secondary metabolites produced by the filamentous fungus Penicillium chrysogenum and derived deletion strains were used to identify the various metabolites and enzymatic steps belonging to the roquefortine/meleagrin pathway. Major abundant metabolites of this pathway were identified as histidyltryptophanyldiketopiperazine (HTD), dehydrohistidyltryptophanyldi-ketopiperazine (DHTD), roquefortine D, roquefortine C, glandicoline A, glandicoline B and meleagrin. Specific genes could be assigned to each enzymatic reaction step. The nonribosomal peptide synthetase RoqA accepts L-histidine and L-tryptophan as substrates leading to the production of the diketopiperazine HTD. DHTD, previously suggested to be a degradation product of roquefortine C, was found to be derived from HTD involving the cytochrome P450 oxidoreductase RoqR. The dimethylallyltryptophan synthetase RoqD prenylates both HTD and DHTD yielding directly the products roquefortine D and roquefortine C without the synthesis of a previously suggested intermediate and the involvement of RoqM. This leads to a branch in the otherwise linear pathway. Roquefortine C is subsequently converted into glandicoline B with glandicoline A as intermediates, involving two monooxygenases (RoqM and RoqO) which were mixed up in an earlier attempt to elucidate the biosynthetic pathway. Eventually, meleagrin is produced from glandicoline B involving a methyltransferase (RoqN). It is concluded that roquefortine C and meleagrin are derived from a branched biosynthetic pathway.


3D Accuracy of a Conventional Method Versus Three Digital Scanning Strategies for Completely Edentulous Maxillary Implant Impressions.
To compare the 3D accuracy of three scanning strategies and conventional impressions using an edentulous model with six implants. An edentulous maxillary master model was fabricated with six equigingival internal connection implants at 0 degrees of angulation. Ten conventional open-tray splinted implant-level impressions were made and poured in stone. A master model and conventional casts were digitized with a reference scanner. Digital impressions were made by calibrated clinicians with a TRIOS 3 intraoral scanner ([IOS] 3Shape) according to three scanning strategies: DIG1 (occlusal-palatal-lingual), DIG2 (S-type motion from buccal to palatal), and DIG3 (scanning two half arches and connecting them at the midline). Each technique was repeated 10 times on the master model. Deviations from the STL datasets (N = 40) were compared to those of the reference master model using the Hexagon Metrology software system PC-DMIS CAD++. Linear distortions (dX, dY, dZ), global linear distortion (dR), and angular distortions (Absdθx, Absdθy) were calculated. Kruskal-Wallis test and mixed linear and logistic regression models were used to compare the original and binary distortion measures between the techniques. The mean dR ranged from 91 μm (conventional method) to 183 μm (DIG1). The mean angular distortion ranged from 0.20 degrees (Absdθx for DIG2) to 0.69 degrees (Absdθy for DIG3). No scan pattern resulted in a more accurate reproduction in any of the measured parameters than the conventional impression method. There were significant differences between the methods for all distortion measures. No group reproduced the 3D position of the six-implant master model below the thresholds for both global linear and angular distortions. All the digital strategies tested were less accurate than the conventional open-tray splinted implant-level impression technique.


Pulmonary surfactant protein A-mediated uptake of phosphatidylcholine by alveolar type II cells.
Pulmonary surfactant protein A (SP-A)-mediated uptake of phosphatidylcholine (PC) by alveolar type II cells was investigated. SP-A enhanced the uptake of liposomes containing dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC), or 1,2-dihexadecyl-sn-glycero-3-phosphocholine (DPPC-ether), a diether analogue of DPPC, but about twice as much DPPC was taken up by type II cells as PLPC or DPPC-ether. When subcellular distribution was analyzed, 51.3 +/- 2.9% (mean +/- SD, n = 3) of cell-associated radiolabeled DPPC was recovered in the lamellar body-rich fraction in the presence of SP-A, whereas only 19.3 +/- 1.9% (mean +/- SD, n = 3) was found to this fraction in the absence of SP-A. When type II cells were incubated either with DPPC at 0 degree C or with DPPC-ether at 37 degrees C, or no cells were included, low proportions of the cell-associated lipids were present in the fractions corresponding to lamellar bodies even in the presence of SP-A. Anti-SP-A antibody significantly reduced the radioactivity incorporated into the lamellar body fraction. Phosphatidylcholine that had been incorporated into lamellar bodies remained largely intact when SP-A was present. Subcellular fractionations of type II cells with radiolabeled SP-A and DPPC revealed that the sedimentation characteristics of cell-associated SP-A are different from those of DPPC, although a small broad peak of radiolabeled SP-A was found in the lamellar body fraction.(ABSTRACT TRUNCATED AT 250 WORDS)


Latino migrants' healthcare use in the US and perceived immigration laws and consequences: A multivariable analysis.
Using healthcare, whether for routine preventative examinations, chronic condition management, or emergent conditions, is an essential element of achieving and maintaining health. Over 44 million migrants live in the US today and nearly half (44.6 %) are Latino. To the extent that immigration law-related concerns deter US Latino migrants from using healthcare, they jeopardize the health of a substantial though marginalized US subpopulation. A multistate sample (N = 1750) of noncitizen adult, Spanish speaking Latino migrants (both undocumented and documented) living in the US completed a cross-sectional survey comprising a scale assessing perceptions of immigration laws and consequences related to healthcare use and whether they had received and/or needed but did not receive healthcare in the previous 12-months. Participants were recruited in community settings and by word-of-mouth. Univariate analyses examined associations among study outcomes and common predictors of healthcare use. Multivariable analyses examined the relative contribution of perceived immigration laws and consequences on healthcare use and unmet need. Perceptions of immigration laws and immigration consequences were a significant predictor of not having received healthcare in the previous 12-months and having needed and not received healthcare in the same period, even when considered relative to common predictors of healthcare use. Immigration documentation status and preferred language predicted healthcare use in univariate analyses but not in the multivariable model. Perceived immigration laws and consequences related to healthcare use may influence migrants' healthcare use. Effective interventions should be developed to address immigration-related concerns.


Dr Arthur Wakefield on Mount Everest in 1922: "this has not been by any manner of means a picnic".
In 1922 Dr Arthur Wakefield, a general practitioner from Cumbria, reached the North Col of Mt Everest at 23,000 feet as a member of the first British team to attempt the summit. As well as being a climber, he provided medical care to his comrades, who included George Leigh Mallory and George Finch. Yet, in their accounts of the expedition, several climbers portrayed him as a nervous old man and a "complete passenger". However, his letters home and a small daily diary suggest he was a wise and caring physician. His motivation for joining this expedition at the age of 46 was somewhat different from that of his companions.


Left ventricular hypertrophy in obese hypertensives: is it really eccentric? (An echocardiographic study).
In order to study left ventricular hypertrophy patterns in obese hypertensives, we examined 132 patients with essential hypertension by 2D, M-mode and Doppler echocardiography. The patients were classified in four comparable groups, corresponding to the values of Quetelet's body mass index (BMI) and grades of obesity. More obese hypertensives had on average larger left ventricles with thicker walls and larger left atria than less obese, or lean ones. Left ventricular mass increased significantly and progressively with advancing grades of obesity, but relative wall thickness (wall thickness/cavity size ratio) did not diminish. Doppler echocardiography revealed significantly higher prevalence of left ventricular diastolic dysfunction among obese than among lean hypertensives. In the second part of our study, we analyzed the subgroups defined by the severity of hypertension and the age of the patients. The correlation of the indices of left ventricular and left atrial hypertrophy with the BMI values was considerably better in the group of moderate than in the group of mild hypertension. The r values were 0.62 vs. 0.22 for left ventricular mass and 0.64 vs. 0.26 for left atrial dimension. The group of patients with severe hypertension was characterized by left ventricular cavity enlargement in correlation with increasing BMI values, but without corresponding left ventricular wall thickening. So called left ventricular "eccentricity index", as the reverse value of relative wall thickness, correlated well (r = 0.76) with the BMI values. The indices of left ventricular hypertrophy correlated with the BMI values slightly better in middle age groups than in the groups of the youngest (< or = 30 years) or the eldest (> or = 61 years) hypertensives. In conclusion, eccentric left ventricular hypertrophy does not seem to be a distinctive feature of hypertensive heart disease in obesity. There is only some tendency toward the "eccentricity" of left ventricular geometry which becomes more apparent in more severe forms of hypertension, especially in very obese persons.


Catharanthus roseus Combined with Ursolic Acid Attenuates Streptozotocin-Induced Diabetes through Insulin Secretion and Glycogen Storage.
Catharanthus roseus (C. roseus) and ursolic acid (UA) are ayurvedic medicines with multiple pharmacological activities including antidiabetic activity, but till date, no study is available on their combination. This study documented the antidiabetic efficacy of the combination of C. roseus and UA in rats. Rats were divided into six groups. All groups were given a single dose of Streptozotocin (STZ) at a dose of 50 mg/kg by intraperitoneal route for induction of diabetes, except the normal control group. Group 1 was treated as a normal control (NC) group and fed with saline water, Group 2 as a Diabetes Control group, Group 3 as a STZ+C. roseus ethanolic extract (CREE) group at 50 mg/kg p.o., Group 4 as a STZ+UA group orally at 50 mg/kg, Group 5 as a STZ+CREE (25 mg/kg p.o.)+UA (25 mg/kg p.o.) group, and Group 6 as a STZ+Glimepiride (0.1 mg/kg) group. Diabetes was confirmed after 72 hours by estimation of blood glucose level, and then treatment was given for the next 28 days. During the course of treatment, plasma insulin and blood glucose were measured regularly at the interval of 7 days. At the end of the protocol, blood was collected and animals were sacrificed. The glucose level, insulin level, liver glycogen storage level, and antioxidant enzymes (LPO, CAT, SOD, GPx, GST) were measured. The blood glucose level in Group 5 significantly (P < 0.001) reduced to 98.35 ± 2.45 mg/dl in comparison with that in Group 2 (321.75 ± 5.46 mg/dl). The level of plasma insulin in Group 5 increased (13.65 ± 0.10 μU/ml) significantly (P < 0.01) as compared with that in Group 2 (05.93 ± 0.31 μU/ml). In Group 5, the level of glycogen in liver was significantly (P < 0.01) increased as compared with that in Group 2 rats. The level of antioxidant enzymes in Group 5 restored toward normal values significantly (P < 0.01; P < 0.001) as compared with that in Group 2 animals. These findings suggest that low-dose combination of CREE and UA is effective in the treatment of diabetes.


Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression.
Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective. Biological markers of early-onset MDD could increase diagnostic specificity, but no such biomarker exists. Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD. We carried out unbiased analyses of this combined set of 26 candidate blood transcriptomic markers in a sample of 15-19-year-old subjects with MDD (N=14) and subjects with no disorder (ND, N=14). A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths. These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies.


Reduction in acute rejections decreases chronic rejection graft failure in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
Chronic rejection accounted for 32% of all graft losses in 7123 pediatric transplants. In a previous study acute, multiple acute and late acute rejections were risk factors for the development of chronic rejection. We postulated that the recent decrease in acute rejections would translate into a lower risk for chronic rejection among patients with recent transplants. We reviewed our data on patients transplanted from 1995 to 2000, and using multivariate analysis and a proportional hazards model developed risk factors for patients whose grafts had failed due to chronic rejection. A late initial rejection increased the risk of chronic rejection graft failure 3.6-fold (p < 0.001), while a second rejection resulted in further increase of 4.2-fold (p < 0.001). Recipients who received less than 5 mg/kg of cyclosporine at 30 days post-transplant had a relative risk (RR) of 1.9 (p = 0.02). Patients transplanted from 1995 to 2000 had a significantly lower risk (RR = 0.54, p < 0.001) of graft failure from chronic rejection than those who received their transplants earlier (1987-94). Since we were able to demonstrate that there is a decreased risk of chronic rejection graft failure in our study cohort, we would conclude that the goal of future transplants should be to minimize acute rejections.


Automated event detection algorithm for two squatting protocols.
Squatting biomechanics assessed using motion analysis relies on the identification of specific events: start of descent, transition between descent/ascent and end of ascent. Automated identification reduces the time needed to process trials while allowing consistency across studies. The purpose of this study was to develop criteria for the identification of events and apply them to two squatting protocols in pathological patient and typically developing (TD) groups. Thirty-four subjects with hip dysplasia and 41 TD subjects were enrolled in this study. While instrumented with a full-body Plug-In-Gait marker set, participants performed two squatting protocols: a hold squat, where subjects paused for a count of three at their lowest squat depth, and a traditional squat, where the descent phase was immediately followed by the ascent phase. Reviewers analyzed the kinematic/kinetic waveforms of a subset of trials to develop criteria for events. Sagittal plane knee and vertical center of mass velocities were used to identify events and absolute vs. relative thresholds of the peak knee velocity were compared. These criteria were incorporated into an automatic event detection code. Using a relative threshold algorithm, events were automatically identified in 244 of 259 total trials (94%). For the trials requiring manual placement of events (n=15 trials), there was perfect inter-rater reliability between research personnel. The criteria developed for the automatic detection of squatting events was highly successful for both protocols in each participant group and was also highly reliable for research personnel to follow in the few instances where manual placement was necessary.


Rhythmic firing of medial septum non-cholinergic neurons.
The presence of theta rhythm (5-10 Hz) in the hippocampus has been shown to enable long-term potentiation, a synaptic mechanism which has been proposed to underlie learning and memory. Medial septum cholinergic and GABAergic neurons that project to the hippocampus have been hypothesized to play conjointly a major role in the genesis of this rhythm. Building upon previous studies that have established the electrophysiological criteria for distinguishing cholinergic and non-cholinergic neurons in this area, it is demonstrated here that medial septum non-cholinergic neurons, putatively GABAergic, have the ability to discharge in rhythmic clusters of action potentials occurring at frequencies ranging from 1 to 8 Hz. Within the clusters, the firing frequency of action potentials varied between 13 and 57 Hz in a voltage-dependent manner. In addition, small voltage-dependent subthreshold membrane potential oscillations (16-54 Hz) were observed between clusters. Both subthreshold oscillations and clusters were eliminated by tetrodotoxin at 1 microM. These results indicate that non-cholinergic medial septum neurons could convey to the hippocampus not only theta but also higher frequency rhythmicity in the beta-gamma range (20-60 Hz).


Shortening increases spontaneous contractility in myometrium from pregnant women at term.
The purpose of this study was to determine whether shortening alters spontaneous contractility in myometrial strips that are obtained from pregnant women. Isometric contractions were measured in myometrial strips that were obtained at cesarean delivery from 14 pregnant women at term. After 2 hours of stretching, the strip lengths were decreased by 4%, 6%, or 8%. Spontaneous contractility was measured for 120 minutes with or without prostaglandin synthase inhibitor indomethacin (10 -5 mol/L), and the cumulative concentration response to oxytocin was determined. Contractility was increased by 29% and 34% in strips that shortened by 4% and 6%, respectively. Preincubation with indomethacin increased contractility by 15% in stretched strips and decreased contractility by 30% and 19% in 4% and 6% strips, respectively. Contraction frequency was increased by 26% and 53% for the strips that were shortened to 6% and 8%, respectively. These increases were prevented by indomethacin. The oxytocin responses were similar at all lengths. Shortening of myometrial strips from pregnant women at term increases spontaneous contractility by a mechanism that apparently involves prostaglandins.


The emerging determinants of replication fork stability.
A universal response to replication stress is replication fork reversal, where the nascent complementary DNA strands are annealed to form a protective four-way junction allowing forks to avert DNA damage while replication stress is resolved. However, reversed forks are in turn susceptible to nucleolytic digestion of the regressed nascent DNA arms and rely on dedicated mechanisms to protect their integrity. The most well studied fork protection mechanism involves the BRCA pathway and its ability to catalyze RAD51 nucleofilament formation on the reversed arms of stalled replication forks. Importantly, the inability to prevent the degradation of reversed forks has emerged as a hallmark of BRCA deficiency and underlies genome instability and chemosensitivity in BRCA-deficient cells. In the past decade, multiple factors underlying fork stability have been discovered. These factors either cooperate with the BRCA pathway, operate independently from it to augment fork stability in its absence, or act as enablers of fork degradation. In this review, we examine these novel determinants of fork stability, explore the emergent conceptual underpinnings underlying fork protection, as well as the impact of fork protection on cellular viability and cancer therapy.


Glucosamine sulfate and cartilage type II collagen degradation in patients with knee osteoarthritis: randomized discontinuation trial results employing biomarkers.
To determine whether glucosamine sulfate has an effect on cartilage type II collagen degradation in patients with knee osteoarthritis (OA). A randomized, double blind, placebo controlled glucosamine discontinuation trial was conducted in 137 subjects with knee OA, who had had at least moderate relief of knee pain after starting glucosamine. Subjects were randomized to glucosamine at prestudy dose or placebo at an equivalent dose. Treatment was continued to Week 24 or disease flare, whichever occurred first. Serum and urine samples were collected at Weeks 0, 4, 12, and 24 or flare visit. Samples were analyzed in triplicate for 2 type II collagen degradation biomarkers: C2C epitope (COL2-3/4C(long)) and C1,2C epitope (COL2-3/4C(short)). The primary outcome was the mean change in serum and urine C1,2C/C2C ratio in the glucosamine and placebo groups from baseline to final (flare or Week 24) visit. Linear regression analyses were conducted to adjust for potential confounders. Due to non-normal distributions, the data were log-transformed (lnC1,2C/C2C). Secondary outcomes included comparison of mean change scores at final visit compared to baseline for serum and urine C1,2C and C2C in the 2 treatment groups and in Flare versus No-Flare groups. Baseline and final visit samples were available in 130 subjects for serum analysis and 126 subjects for urinalysis. No significant difference was seen between placebo and glucosamine groups in the serum C1,2C/C2C ratio, with a mean (SD) change from baseline to final visit of 0.8 (27.8) and -0.1 (1.8), respectively (mean difference 0.9; 95% CI -6.0, 7.7, p = 0.80). Similarly, no differences between treatment groups were seen for mean change in urine C1,2C/C2C (p = 0.82), or for mean change in C2C or C1,2C. In linear regression analysis, after adjustment for sex, radiographic severity, baseline lnC1,2C/C2C ratio, WOMAC function, and flare status, treatment was not a significant predictor of final serum or urine lnC1,2C/C2C ratio. When those who experienced flare were contrasted with those without flare, there was a nonsignificant trend toward a difference in mean baseline to final visit change score for serum C1,2C/C2C ratio (p = 0.12). In addition, in the multivariable linear regression analysis, flare status showed a borderline association with final visit serum lnC1,2C/C2C ratio (p = 0.16). No statistically significant effect of glucosamine sulfate on type II collagen fragment levels in serum or urine was observed for knee OA over 6 months. Further research is necessary to elucidate which biopathologic systems, if any, are affected by glucosamine treatment. While collagen degradation products may be of value in predicting progression, at least as defined by clinical flare, a larger dataset would be needed to prove this.


Innovative approach for the in vitro research on biomedical scaffolds designed and customized with CAD-CAM technology.
Studies on biomaterials involve assays aimed to assess the interactions between the biomaterial and the cells seeded on its surface. However, the morphology of biomaterials is heterogeneous and it could be tricky to standardize the results among different biomaterials and the classic plastic plates. In this light, we decided to create, by means of computer-aided design (CAD) technology, a standardized sample model, with equal shape and sizes, able to fit into a classic shape of a 96-wells tissue culture plate (TCP). The design of this sample consists of a hole in the top in order to allow the injected cells to settle without them being able to slip from the sides of the sample to the bottom of the TCP wells. This CAD project is made using the software Pro-Engineer. The sample will totally fill the wells of the 96-well TCP. Dental pulp stem cells have been used to assess the ability of the different sample to support and promote the cell proliferation. Twelve titanium, 12 gold-palladium, and 12 zirconium oxide customized samples were designed by means of the software cam powermill, by importing the .stl file created in Pro-Engineer software. The proliferation rate of the tested scaffolds showed to be similar to the control in the group with the customized shape. We think that our method can be useful to test different types of scaffolds when a greater accuracy of the measurements is desirable in order to verify the cell behavior of these scaffolds. Our innovative method can improve the standardization process in the evaluation of cell behavior on different biomaterials to open the way to more reliable tests on biomatrices functionalized with drugs or growth factors applied to the future regenerative medicine.


Treatment of nonalcoholic fatty liver: present and emerging therapies.
Treatment of patients with nonalcoholic fatty liver has typically been focused on the management of associated conditions such as obesity, diabetes mellitus, and hyperlipidemia as well as discontinuation of potentially hepatotoxic drugs. Nonalcoholic fatty liver associated with obesity may resolve with weight reduction, although the benefits of weight loss have been inconsistent. Appropriate metabolic control for patients with diabetes mellitus or hyperlipidemia is always recommended but not always effective in reversing nonalcoholic fatty liver. Promising results of pilot studies evaluating ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, and alpha-tocopherol suggest that these medications may be of potential benefit in the treatment of patients with nonalcoholic fatty liver. These medications, however, need first to be tested in well-controlled trials with clinically relevant end points and extended follow-up. A better understanding of the pathogenesis and natural history of this condition will help to identify the subset of patients with nonalcoholic fatty liver at risk of progressing to advanced liver disease and, hence, the subgroup of patients who should derive the most benefit from medical therapy. In this article, we review (1) the existing medical therapy for patients with nonalcoholic fatty liver, (2) the emerging data from clinical trials evaluating potentially useful medications, and (3) the potential therapeutic implications of recent studies on the pathogenesis of this liver disease.


Constitutional translocation breakpoint mapping by genome-wide paired-end sequencing identifies HACE1 as a putative Wilms tumour susceptibility gene.
Localisation of the breakpoints of chromosomal translocations has aided the discovery of several disease genes but has traditionally required laborious investigation of chromosomes by fluorescent in situ hybridisation approaches. Here, a strategy that utilises genome-wide paired-end massively parallel DNA sequencing to rapidly map translocation breakpoints is reported. This method was used to fine map a de novo t(5;6)(q21;q21) translocation in a child with bilateral, young-onset Wilms tumour. Genome-wide paired-end sequencing was performed for approximately 6 million randomly generated approximately 3 kb fragments from constitutional DNA containing the translocation, and six fragments in which one end mapped to chromosome 5 and the other to chromosome 6 were identified. This mapped the translocation breakpoints to within 1.7 kb. Then, PCR assays that amplified across the rearrangement junction were designed to characterise the breakpoints at sequence-level resolution. The 6q21 breakpoint transects and truncates HACE1, an E3 ubiquitin-protein ligase that has been implicated as a somatically inactivated target in Wilms tumourigenesis. To evaluate the contribution of HACE1 to Wilms tumour predisposition, the gene was mutationally screened in 450 individuals with Wilms tumour. One child with unilateral Wilms tumour and a truncating HACE1 mutation was identified. These data indicate that constitutional disruption of HACE1 likely predisposes to Wilms tumour. However, HACE1 mutations are rare and therefore can only make a small contribution to Wilms tumour incidence. More broadly, this study demonstrates the utility of genome-wide paired-end sequencing in the delineation of apparently balanced chromosomal translocations, for which it is likely to become the method of choice.


Use of health care services by inner-city infants in an early discharge program.
To assess the use of health care services by inner-city infants enrolled in an early discharge program who received care in tertiary care children's hospital primary care clinic. Retrospective cohort study. Large, metropolitan university hospital and a children's hospital. Term infants cared for in a single full-term nursery, before and after implementation of a coordinated early discharge program, who received primary care at the children's hospital. The coordinated Early Discharge Program was characterized by in-hospital visits by hospital-based coordinating nurses, home visits by nurses from a home nursing agency, and communication with physicians for necessary adjustments in postdischarge care. After linking birth hospital records and the children's hospital medical records, a retrospective chart review was performed to obtain maternal demographic information and birth hospital length of stay, as well as the infants' attendance at primary care clinic, immunizations, emergency department visits, and rehospitalization. Number of primary care visits in the first 3 months of life, completion of one series of immunizations by 3 months of life, and number of emergency department visits and rehospitalization during the first 3 months of life. The early discharge group (n = 253) had a significantly shorter birth hospital length of stay (35 +/- 24 hours, mean +/- SD) when compared with the control group (n = 212) (52 +/- 14 hours). The early discharge group was also younger than the control group at the first primary care visit, with significantly more infants visiting the primary care clinic in the first month of life. There was also a significant difference between the groups in the mean number of emergency department visits (early discharge = .61 visits/patient, control = .79 visits/patient) and the proportion of patients with no emergency department visits during the first 3 months of life (early discharge = 57%, control = 43%). There was no difference between the two groups in the proportion of infants completing one series of immunizations or in the number of infants rehospitalized during the study period. Coordinated early discharge with home nursing visits for inner-city infants may result in earlier use of primary care services. Furthermore, there is a significant decrease in use of the emergency department during the first 3 months of life, and no increase in rehospitalization.


Rare cause of odynophagia: Giant esophageal ulcer.
Gastrointestinal complications are a frequent cause of morbidity after transplantation and may affect up to 40% of kidney transplant recipients. Here we report a rare case of idiopathic giant esophageal ulcer in a kidney transplant recipient. A 37-year-old female presented with a one-week history of odynophagia and weight loss. Upon admission, the patient presented cold sores, and a quantitative cytomegalovirus polymerase chain reaction was positive (10(5) copies/mL). An upper endoscopy demonstrated the presence of a giant ulcer. Serological test and tissue biopsies were unable to demonstrate an infectious origin of the ulcer. Immunosuppression was reduced and everolimus was introduced. An empirical i.v. therapy with acyclovir was started, resulting in a dramatic improvement in symptoms and complete healing of the ulcer. Only two cases of idiopathic giant esophageal ulcer in kidney transplant recipients have been reported in the literature; in both cases, steroid therapy was successful without recurrence of symptoms or endoscopic findings. However, this report suggests that correction of immune imbalance is mandatory to treat such a rare complication.


Oral immunization with a recombinant malaria protein induces conformational antibodies and protects mice against lethal malaria.
The increasing death toll from malaria, due to the decreasing effectiveness of current prophylactic and therapeutic regimens, has sparked a search for alternative methods of control, such as vaccines. Although several single proteins have shown some promise as subunit vaccines against sexual blood stages in experimental systems, it is clear that multicomponent vaccines are required. Many logistic difficulties make such an approach prohibitively expensive. In an effort to try to overcome some of these issues, we examined the possibility of oral immunization as a route for inducing host protective immunity. We report here that oral feeding of a malaria protein induced serum antibody levels similar to those induced by intraperitoneal immunization with Freund's adjuvant. Further, responses to conformational epitopes were induced. In the rodent challenge system, significant levels of protection to lethal challenge with malaria were induced in mice. The protective efficacy was highly correlated with antibody levels, which depended on the antigen dosage and required cholera toxin subunit B as an oral adjuvant. These findings offer new approaches to the development of a malaria vaccine and provide justification for the investigation of transgenic plants as a means of vaccine delivery.


Association between Stress and the HPA Axis in the Atopic Dermatitis.
The hypothalamic-pituitary-adrenal (HPA) axis is one of the body's neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are essential for cutaneous homeostasis. Atopic dermatitis (AD) is a condition typically characterized by a chronic relapsing course that often results in PS. HPA dysfunction is present in AD patients by the decreased response of GCs elevation to stress as compared to those unaffected by AD. Nevertheless, in skin, acute PS activates several metabolic responses that are of immediate benefit to the host. During the acute phase of PS, increased endogenous GCs have been shown to provide benefit rather than by aggravating cutaneous inflammatory dermatoses. However, a chronic T helper cell type 2 (Th2) predominant cytokine profile acts as a negative feedback loop to blunt the HPA axis response in AD. In this article, we reviewed the role of CRF, pro-opiomelanocortin (POMC)-derived peptides, GCs of the HPA, and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in AD, with a discussion of the pathogenetic mechanisms of inflammation and skin barrier functions, including antimicrobial defense, and their association with PS.


Fast 2D NMR Spectroscopy for In vivo Monitoring of Bacterial Metabolism in Complex Mixtures.
The biological toolbox is full of techniques developed originally for analytical chemistry. Among them, spectroscopic experiments are very important source of atomic-level structural information. Nuclear magnetic resonance (NMR) spectroscopy, although very advanced in chemical and biophysical applications, has been used in microbiology only in a limited manner. So far, mostly one-dimensional 1H experiments have been reported in studies of bacterial metabolism monitored in situ. However, low spectral resolution and limited information on molecular topology limits the usability of these methods. These problems are particularly evident in the case of complex mixtures, where spectral peaks originating from many compounds overlap and make the interpretation of changes in a spectrum difficult or even impossible. Often a suite of two-dimensional (2D) NMR experiments is used to improve resolution and extract structural information from internuclear correlations. However, for dynamically changing sample, like bacterial culture, the time-consuming sampling of so-called indirect time dimensions in 2D experiments is inefficient. Here, we propose the technique known from analytical chemistry and structural biology of proteins, i.e., time-resolved non-uniform sampling. The method allows application of 2D (and multi-D) experiments in the case of quickly varying samples. The indirect dimension here is sparsely sampled resulting in significant reduction of experimental time. Compared to conventional approach based on a series of 1D measurements, this method provides extraordinary resolution and is a real-time approach to process monitoring. In this study, we demonstrate the usability of the method on a sample of Escherichia coli culture affected by ampicillin and on a sample of Propionibacterium acnes, an acne causing bacterium, mixed with a dose of face tonic, which is a complicated, multi-component mixture providing complex NMR spectrum. Through our experiments we determine the exact concentration and time at which the anti-bacterial agents affect the bacterial metabolism. We show, that it is worth to extend the NMR toolbox for microbiology by including techniques of 2D z-TOCSY, for total "fingerprinting" of a sample and 2D 13C-edited HSQC to monitor changes in concentration of metabolites in selected metabolic pathways.


Patent ductus arteriosus during high-frequency ventilation for hyaline membrane disease.
The cardiovascular effects of a patent ductus arteriosus (PDA) in a premature baboon model of hyaline membrane disease treated with conventional positive-pressure ventilation (CPPV) or high-frequency ventilation (HFV) were studied. Twenty-seven (84%) of 32 infant baboons delivered at 75% gestation had positive retrograde aortograms at one hour of life. Eleven (34%) of these infant baboons had persisting evidence for retrograde flow over the first 24 h by Doppler examination. Significantly higher fluid requirements and bicarbonate requirements were present in the animals with a persisting PDA. Mean aortic BP values were significantly lower in these same animals. No significant differences were found between groups when mean airway pressure, heart rate, urine output, or form of ventilation were compared. The only significant differences found between the conventional and high-frequency ventilated animals with PDA were higher peak airway pressures and lower PEEP levels in the conventionally ventilated infants. The premature baboons can be a useful primate model to study the PDA. There appears to be no significant difference regarding the clinical effects of HFV and CPPV on PDA.


Malignant rhabdoid tumors of the liver: an exceptional tumor in adults - a case report and literature review.
Malignant rhabdoid tumor (MRT) is a very rare liver tumor, with only a few cases reported in the literature. MRT generally occurs in pediatric patients and prognosis is usually very poor. Here we report a very rare case of MRT occurring in a young adult who is still alive with no sign of recurrence at 41 months of follow-up. MRI and computed tomography scans revealed a voluminous heterogeneous mass in the left liver with no specific pattern. The mass included necrotic and fibrous components. Histology showed fusiform, loosely cohesive cells with abundant eosinophilic cytoplasm resulting in eccentric nuclei, thus creating the characteristic rhabdoid appearance. Immunohistochemical studies revealed a lack of nuclear INI1 protein expression. The patient's treatment included a major left liver resection associated with chemotherapy. A thorough search of the literature revealed one case of MRT in a young adult who died at 48 months of follow-up. A less malignant nature of the tumor in young adults may be suspected, but a longer disease-free survival may also be the fruit of aggressive surgical and oncological treatment.


[A carcinoid tumor in a mature thymic teratoma].
A description of a carcinoid in the mature thymic teratoma in a 43-year-old woman. Teratoma was represented by the skin with appendages, intestinal and respiratory epithelium, salivary gland, fat tissue, islands of cartilage and ependyma. A carcinoid of alveolo-trabecular type consisting of cells with argyrophilic and argentaffinic properties was found in the area of submucous glands of a respiratory tube. Serotonin and neurotensin were found by means of PAP method in carcinoid cells.


Corpus callosotomy for treatment of drug-resistant epilepsy: a review of 16 pediatric cases in northern Vietnam.
The aim of this study was to evaluate postoperative seizure outcome in children with drug-resistant epilepsy not eligible for focal resection who underwent corpus callosotomy. The study included 16 patients undergoing corpus callosotomy between September 2015 and May 2018. Seizure semiology and frequency, psychomotor status, and video electroencephalography and imaging findings were evaluated for all patients. Of the 16 patients who underwent callosotomy during the study period, 11 underwent complete callosotomy and 5 underwent anterior only. Seizure improvement greater than 75% was achieved in 37.5% of patients, and another 50% of patients had seizure improvement of 50%-75%. No sustained neurological deficits were observed in these patients. There were no significant complications. Duration of postoperative follow-up ranged from 12 to 44 months. Corpus callosotomy is an effective treatment for selected patients with drug-resistant epilepsy not eligible for focal resection in resource-limited settings. Fostering and developing international epilepsy surgery centers should remain a high priority for the neurosurgical community at large.


Regulation of Rous sarcoma virus RNA splicing and stability.
Only a fraction of retroviral primary transcripts are spliced to subgenomic mRNAs; the unspliced transcripts are transported to the cytoplasm for packaging into virions and for translation of the gag and pol genes. We identified cis-acting sequences within the gag gene of Rous sarcoma virus (RSV) which negatively regulate splicing in vivo. Mutations were generated downstream of the splice donor (base 397) in the intron of a proviral clone of RSV. Deletion of bases 708 to 800 or 874 to 987 resulted in a large increase in the level of spliced RSV RNA relative to unspliced RSV RNA. This negative regulator of splicing (nrs) also inhibited splicing of a heterologous splice donor and acceptor pair when inserted into the intron. The nrs element did not affect the level of spliced RNA by increasing the rate of transport of the unspliced RNA to the cytoplasm but interfered more directly with splicing. To investigate the possible role of gag proteins in splicing, we studied constructs carrying frameshift mutations in the gag gene. While these mutations, which caused premature termination of gag translation, did not affect the level of spliced RSV RNA, they resulted in a large decrease in the accumulation of unspliced RNA in the cytoplasm.


Translocation of glutamate transporter subtype excitatory amino acid carrier 1 protein in kainic acid-induced rat epilepsy.
Glutamate excitotoxicity has been implicated in the pathophysiology of epilepsy. Systemic injection of kainic acid (KA) in the rat produces an animal model of human temporal lobe epilepsy. We examined the temporal expression of the sodium-dependent neuronal glutamate transporter, excitatory amino acid carrier 1 (EAAC1), in KA-induced rat epilepsy. As an early alteration, perinuclear deposits of EAAC1 protein were found mainly in the large pyramidal neurons at the hippocampus, neocortex, piriform cortex, and amygdala with the reduction of neuropil staining 6 hours after KA injection. Immunoelectron microscopic study revealed that the perinuclear EAAC1 immunoreactivity corresponded to the translocation to the Golgi complex. At this time point, EAAC1 mRNA was down-regulated. The intracellular aggregation of EAAC1 primarily disappeared by 24 hours. In vitro studies indicated that internalization of EAAC1 from the plasma membrane to the intracellular compartment by KA treatment was associated with the reduction of electrogenic transporter currents. Our results suggest that the transient EAAC1 internalization participates in the modulation of the transporter function preventing excessive glutamate uptake to pyramidal neurons during the early stage of epilepsy.


Autostimulation of growth by human myelogenous leukemia cells (HL-60).
We have studied the effects of medium conditioned by the human progranulocytic leukemia cell line, HL-60, on the subsequent growth of new inocula of HL-60 cells. When HL-60 cells were cultured at high cell density, optimal growth rate occurred in liquid suspension and confluent colony growth was observed in viscous medium without the addition of conditioned medium. However, when cells were cultured at lower cell density, growth rate was reduced and colony growth was nil unless conditioned medium from HL-60 culture was added. All HL-60 populations studied, including the earliest available passage, 9, both elaborated and responded to HL-60 CM. HL-60 CM did not stimulate normal human or mouse granulocyte-monocyte colony-forming cell (CFU-GM) growth. Conditioned media from other human cell lines varied in the ability to stimulate HL-60 cell and CFU-GM proliferation. Some, such as GCT CM, stimulated both HL-60 cells and normal CFU-GM, whereas others, like HL-60 CM, stimulated only HL-60 growth. The majority of cell line CMs tested did not stimulate either HL-60 or CFU-GM. Chromatography of HL-60 CM on Ultrogel AcA54 showed a single peak of HL-60 stimulating activity of apparent molecular weight 13,000. The ability of HL-60 cells to elaborate this activity provides a possible explanation for their proliferation at higher cell densities. Autostimulation may prove to be important in the high growth potential of other cell populations that undergo unrepressed proliferation.


The apparent preferential interaction of human plasma high density apolipoprotein A-I with gel-state phospholipids.
The enthalpy, entropy and free energy of activation was measured for the transfer of the tryptophan residues of apolipoprotein A-I from a more hydrophobic environment of a lipoprotein particle containing dimyristoylphosphatidylcholine (with or without 12% cholesterol) to an aqueous solvent in the presence of varying concentrations of guanidinium chloride. The free energy of activation was approximately 25 kcal/mol at 50 degrees C for all the conditions studied. The enthalpy of activation was greatest under conditions where a large degree of unfolding occurs when the protein dissociated from lipid. However, under these conditions the unfavourable activation enthalpy was compensated for by a favourable activation entropy resulting in the insensitivity of the free energy of activation to the condition of measurement. Apolipoprotein A-I has an apparent affinity for gel-state lipid which results from the very slow rate of dissociation of the lipoprotein particle below 40 degrees C. It is unlikely that the association of apolipoprotein A-I with dimyristoylphosphatidylcholine is thermodynamically stable only in the temperature region of the phase transition but that the association exhibits a large kinetic stability, especially at lower temperatures or in the absence of guanidinium chloride.


Comparison of Anthropometry and Body Composition Using Air Displacement Plethysmography in Term Small for Gestational Age and Appropriate for Gestational Age Neonates.
Small for gestational age (SGA) neonates are prone to growth deficits in early life, which may be associated with later life metabolic abnormalities. To compare anthropometry and body composition using air-displacement plethysmography (ADP) in term SGA and appropriate for gestational age (AGA) neonates, and assess if sexual dimorphism existed in estimates of body composition. Cross-sectional analytical study. 413 term neonates (91 SGA and 322 AGA) at birth (≤7days). Neonatal anthropometry and body composition were measured using ADP. Length corrected fat mass index (FMI) and fat free mass index (FFMI) were calculated. Anthropometry and body composition estimates of SGA and AGA neonates, segregated by sex. The mean (SD) birth weight of SGA and AGA neonates was 2.5 (0.2) kg and 3.1 (0.3) kg, respectively. SGA neonates had significantly lower % body fat (BF) (2.0%), fat mass (94.4 g), fat free mass (FFM) (349.7 g), FMI (0.34 kg/m2), and FFMI (0.76 kg/m2), but higher %FFM (2.0%) compared to AGA neonates (P<0.001). Males had significantly higher %FFM [91.2 (3.1) vs 90.2 (3.5); P=0.001], FFM [2604 (280) vs 2442 (233) g; P<0.001], and FFMI [11.1 (0.8) vs 10.8 (0.8) kg/m2; P=0.005], but lower % BF [8.8 (3.1) vs 9.8 (3.5); P=0.001] and FMI [1.1(0.4) vs 1.2 (0.5) kg/m2; P=0.008], compared to females. Accurate estimates of body composition in neonates at birth suggest significantly lower body fat and fat free mass in SGA compared to AGA, with sexual dimorphism.


Supervised machine learning and active learning in classification of radiology reports.
This paper presents an automated system for classifying the results of imaging examinations (CT, MRI, positron emission tomography) into reportable and non-reportable cancer cases. This system is part of an industrial-strength processing pipeline built to extract content from radiology reports for use in the Victorian Cancer Registry. In addition to traditional supervised learning methods such as conditional random fields and support vector machines, active learning (AL) approaches were investigated to optimize training production and further improve classification performance. The project involved two pilot sites in Victoria, Australia (Lake Imaging (Ballarat) and Peter MacCallum Cancer Centre (Melbourne)) and, in collaboration with the NSW Central Registry, one pilot site at Westmead Hospital (Sydney). The reportability classifier performance achieved 98.25% sensitivity and 96.14% specificity on the cancer registry's held-out test set. Up to 92% of training data needed for supervised machine learning can be saved by AL. AL is a promising method for optimizing the supervised training production used in classification of radiology reports. When an AL strategy is applied during the data selection process, the cost of manual classification can be reduced significantly. The most important practical application of the reportability classifier is that it can dramatically reduce human effort in identifying relevant reports from the large imaging pool for further investigation of cancer. The classifier is built on a large real-world dataset and can achieve high performance in filtering relevant reports to support cancer registries.


Evaluation of bidirectional relationships between risk preference and mood disorders: A 2-sample Mendelian randomization study.
Risk preference is often defined as the tendency to engage in risky activities. Increasing evidence shows that risk preference is associated with mood disorders. However, the causality and direction of this association are not clear. Genome-wide association study summary data of risk preference in 939,908 participants from UK Biobank and 23andMe were used to identify general risk preference. Data for 413,466 individuals taken from The Psychiatric Genomics Consortium were used to identify bipolar disorder (BP). Data for 807,553 individuals taken from The Psychiatric Genomics Consortium were used to identify major depressive disorder (MDD). The weighted median, inverse-variance weighting, and Mendelian randomization-Egger methods were used for the Mendelian randomization analysis to estimate a causal effect and detect directional pleiotropy. GWAS summary data were obtained from three combined samples, containing 939,908, 413,466 and 807,553 individuals of European ancestry. Mendelian randomization evidence suggested that risk preference increased the onset of BP, and BP also increased risk preference (P < 0.001). In contrast, there were no reliable results to describe the relationship of risk preference with MDD (P > 0.05). Furthermore, there was no significant relationship between MDD and risk preference. Using large-scale GWAS data, robust evidence supports a mutual relationship between risk preference and BP, but no relationship between risk preference and MDD was observed. This study indicates a potential marker for the early identification of MDD and BP. Additionally, it shows that reducing risk preferences for patients with BP may be a valuable intervention for treating BP.


Chemical Genetics Screen Identifies Epigenetic Mechanisms Involved in Dopaminergic and Noradrenergic Neurogenesis in Zebrafish.
The cell type diversity and complexity of the nervous system is generated by a network of signaling events, transcription factors, and epigenetic regulators. Signaling and transcriptional control have been easily amenable to forward genetic screens in model organisms like zebrafish. In contrast, epigenetic mechanisms have been somewhat elusive in genetic screens, likely caused by broad action in multiple developmental pathways that masks specific phenotypes, but also by genetic redundancies of epigenetic factors. Here, we performed a screen using small molecule inhibitors of epigenetic mechanisms to reveal contributions to specific aspects of neurogenesis in zebrafish. We chose development of dopaminergic and noradrenergic neurons from neural progenitors as target of epigenetic regulation. We performed the screen in two phases: First, we tested a small molecule inhibitor library that targets a broad range of epigenetic protein classes and mechanisms, using expression of the dopaminergic and noradrenergic marker tyrosine hydroxylase as readout. We identified 10 compounds, including HDAC, Bromodomain and HAT inhibitors, which interfered with dopaminergic and noradrenergic development in larval zebrafish. In the second screening phase, we aimed to identify neurogenesis stages affected by these 10 inhibitors. We analyzed treated embryos for effects on neural stem cells, growth progression of the retina, and apoptosis in neural tissues. In addition, we analyzed effects on islet1 expressing neuronal populations to determine potential selectivity of compounds for transmitter phenotypes. In summary, our targeted screen of epigenetic inhibitors identified specific compounds, which reveal chromatin regulator classes that contribute to dopaminergic and noradrenergic neurogenesis in vivo.


Diazoxide attenuates glucose-induced defects in first-phase insulin release and pulsatile insulin secretion in human islets.
Humans with type-2 diabetes mellitus (TTDM) have hyperglycemia ( approximately 11 mM) and impaired glucose-mediated insulin secretion characterized by impaired first-phase insulin release (FPIR) and pulsatile insulin release. Culture of islets from nondiabetic humans in very high glucose concentrations ( approximately 20-30 mM) for 96 h causes impaired FPIR. We sought to determine 1). whether human islets cultured at a glucose concentration of approximately 11 mM (comparable to TTDM) recapitulates impaired insulin secretion in TTDM, specifically impaired FPIR and insulin pulse mass with an increased proinsulin/insulin (PI/I) secretion ratio; and 2). whether these changes can be attenuated by addition of diazoxide to islets cultured with 11 mM glucose. Islets cultured with 11 mM glucose for 96 h had 75% depleted insulin stores (P < 0.05), decreased FPIR and insulin pulse mass (P < 0.05), and an approximately 3-fold increase in the ratio of PI/I islet content and in secretion ratio (P < 0.05). Addition of diazoxide to islets cultured with 11 mM glucose decreased insulin secretion during static incubation, leading to relative preservation of insulin stores and enhanced insulin secretion during subsequent perifusion; FPIR increased by 162% (P < 0.05) and insulin pulse mass by 150% (P < 0.05) vs. no diazoxide. The mean islet PI/I content and islet PI/I secretion ratio were also decreased by approximately 70% (P < 0.05) by prior addition of diazoxide to islets during culture with 11 mM glucose. FPIR and insulin pulse mass were related to islet insulin stores (P < 0.001 for FPIR and P < 0.001 for pulse amplitude). In conclusion, the pattern of defects of insulin secretion present in TTDM (impaired FPIR and pulsatile insulin secretion, increased PI/I ratio) can be recapitulated in human islets cultured with 11 mM glucose for 96 h. These defects can be at least partially offset by concurrent inhibition of insulin secretion by diazoxide, which also preserves insulin stores. Defective insulin secretion in TTDM may be, at least in part, due to depletion of available insulin stores secondary to chronic increased demand (insulin resistance and hyperglycemia) in the setting of a decreased beta-cell mass.


Evolution of functional diversification within quasispecies.
According to quasispecies theory, high mutation rates limit the amount of information genomes can store (Eigen's Paradox), whereas genomes with higher degrees of neutrality may be selected even at the expenses of higher replication rates (the "survival of the flattest" effect). Introducing a complex genotype to phenotype map, such as RNA folding, epitomizes such effect because of the existence of neutral networks and their exploitation by evolution, affecting both population structure and genome composition. We reexamine these classical results in the light of an RNA-based system that can evolve its own ecology. Contrary to expectations, we find that quasispecies evolving at high mutation rates are steep and characterized by one master sequence. Importantly, the analysis of the system and the characterization of the evolved quasispecies reveal the emergence of functionalities as phenotypes of nonreplicating genotypes, whose presence is crucial for the overall viability and stability of the system. In other words, the master sequence codes for the information of the entire ecosystem, whereas the decoding happens, stochastically, through mutations. We show that this solution quickly outcompetes strategies based on genomes with a high degree of neutrality. In conclusion, individually coded but ecosystem-based diversity evolves and persists indefinitely close to the Information Threshold.


Multilevel Sleep Surgery Including the Palate in Nonsyndromic, Neurologically Intact Children with Obstructive Sleep Apnea.
To examine the effects of multilevel sleep surgery, including palate procedures, on obstructive sleep apnea parameters in the pediatric population. A case series with chart review was conducted to identify nonsyndromic, neurologically intact pediatric patients who underwent either uvulectomy or uvulopalatopharyngoplasty as part of multilevel sleep surgery from 2011 through 2017. A tertiary care, university children's hospital. Unpaired Student t test was used to compare average pre- and postsurgical apnea-hypopnea index (AHI) and oxygen saturation nadir (OSN). Paired Student t test was used to compare the mean pre- and postsurgical AHI and OSN within the same patient for the effects of adenotonsillectomy (T&A) vs multilevel sleep surgery. In patients who underwent T&A previously, multilevel sleep surgery, including palate procedures, resulted in improved OSA severity in 6 (86%) patients and worsened OSA in 1 (14%) patient. Multilevel sleep surgery, including palate procedures, significantly decreased mean AHI from 37.98 events/h preoperatively to 8.91 events/h postoperatively (P = .005). However, it did not significantly decrease OSN. This study includes one of the largest populations of children in whom palate procedures as a part of multilevel sleep surgery have been performed safely with no major complications and a low rate of velopharyngeal insufficiency. Therefore, palatal surgery as a part of multilevel sleep surgery is not necessarily the pariah that we have traditional thought it is in pediatric otolaryngology.


Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide: evaluation with a microcirculatory model, including free radicals, laser doppler flux, and PO2/PCO2 measurements.
In 32 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of the local application of a hydrogen peroxide cream (Crystacide) applied onto the skin was evaluated using a complex, proportional, microcirculatory model to assess and quantify venous microangiopathy after local treatment. A comparative group treated without Crystacide was included. Laser Doppler flowmetry was used to assess skin perfusion (flux and venoarteriolar response) in association with transcutaneous PO2 and PCO2 measurements. Local plasma free radicals were evaluated in the area surrounding the venous ulcer using the D-Roms test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatments. PO2 was increased (improved, P < .05), and plasma free radicals, PCO2, and laser Doppler flowmetry were decreased (improving toward normal values, P < .05). Also, the ulcerated area was significantly smaller at 10 days in the Crystacide group in comparison with controls (P < .05). In the proportional microcirculatory model, all parameters indicated an important level of improvement significantly larger than in controls. In conclusion, in chronic venous insufficiency and venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals, thus improving healing.


Assortative fertilization and selection at larval stage in the mussels Mytilus edulis and M. galloprovincialis.
Assortative mating (prezygotic isolation) and reduced hybrid fitness (postzygotic isolation) are typically invoked to explain the stability of hybrid zones. In the tension zone model, these factors work in opposition to migration, which promotes genetic homogeneity. Many marine animals migrate over long distances through a planktonic larval stage. Therefore, strong reproductive isolation is needed to maintain stable marine hybrid zones. However, surprisingly little is known about mating preferences and hybrid fitness in marine organisms. Smooth-shelled mussels (Mytilus spp.) form a well-known species complex, with hybridization over extensive areas such as the contact zone of M. edulis and M. galloprovincialis around European Atlantic coasts. This paper reports direct experimental evidence of assortative fertilization, hybrid larval inviability, and early heterosis for growth rate in M. edulis and M. galloprovincialis. Four crosses between pure M. edulis and M. galloprovincialis were analyzed with a new polymerase-chain-reaction-based diagnostic marker. Gamete competition between taxa was allowed in two out of the four crosses. Genotype frequencies observed at an early stage (36 h after fertilization) unambiguously revealed assortative fertilization when gamete competition was allowed. A significant reduction in hybrid viability was subsequently observed during the larval stage. At the same stage an antagonistic effect, heterosis, was observed on growth rate. However, even if heterosis is observed in the F1, it is expected to vanish in subsequent hybrid generations. Although specialization for different habitats and asynchronous spawning have been mentioned as factors contributing to the maintenance of the blue mussel hybrid zone in Europe, we argue that assortative fertilization and reduced hybrid fitness are important factors that also contribute to the stabilization of this zone. These results emphasize that multiple factors may act concomitantly in a barrier to gene flow, especially in complex life cycles. Furthermore, they show that assortative mating through gamete preference, as already demonstrated for sea urchins, may play a role in speciation processes taking place in the sea.


[Citrobacter freundii endocarditis].
Infection by Citrobacter appears in man only in certain circumstances, since it usually acts as contaminant or colonizer. Bacteraemia by this bacillus can affect immunodeficient people, elderly people or those patients who have undergone invasive hospital processes. Although incidence of bacteraemia is low (0.3-0.9%), the death rate is very high, about 48%. This bacillus is seldom the cause of endocarditis. That is why we describe a case of endocarditis by Citrobacter freundii, in an aged person with previous valvulopathy.


Environmental and Personal Protective Equipment Contamination during Simulated Healthcare Activities.
Providing care to patients with an infectious disease can result in the exposure of healthcare workers (HCWs) to pathogen-containing bodily fluids. We performed a series of experiments to characterize the magnitude of environmental contamination-in air, on surfaces and on participants-associated with seven common healthcare activities. The seven activities studied were bathing, central venous access, intravenous access, intubation, physical examination, suctioning and vital signs assessment. HCWs with experience in one or more activities were recruited to participate and performed one to two activities in the laboratory using task trainers that contained or were contaminated with fluorescein-containing simulated bodily fluid. Fluorescein was quantitatively measured in the air and on seven environmental surfaces. Fluorescein was quantitatively and qualitatively measured on the personal protective equipment (PPE) worn by participants. A total of 39 participants performed 74 experiments, involving 10-12 experimental trials for each healthcare activity. Healthcare activities resulted in diverse patterns and levels of contamination in the environment and on PPE that are consistent with the nature of the activity. Glove and gown contamination were ubiquitous, affirming the value of wearing these pieces of PPE to protect HCW's clothing and skin. Though intubation and suctioning are considered aerosol-generating procedures, fluorescein was detected less frequently in air and at lower levels on face shields and facemasks than other activities, which suggests that the definition of aerosol-generating procedure may need to be revised. Face shields may protect the face and facemask from splashes and sprays of bodily fluids and should be used for more healthcare activities.


Fly ash lung: a new pneumoconiosis?
A laborer who worked in a steel mill and in a shipyard developed a nonspecific pulmonary interstitial fibrosis. Postmortem samples of his lung were digested, and the inorganic material present was extracted and examined using transmission electron microscopy, electron diffraction, and electron microprobe analysis. Uncoated asbestos fibers were present (1.4 X 10(5)/g wet lung), but the surprising finding was the presence of a large number of fly ash particles (6 X 10(6)/g wet lung). Fly ash, the particulate material produced during coal combustion, has not previously been reported to be present in human lung tissue. Although the contribution of the asbestos to this man's lung disease is uncertain, we believe, based on previous studies implicating aluminum silicates in pneumoconiosis, that the fly ash, an aluminum silicate, may be a contributing factor.


Assessing competence: the European Survey on Aging Protocol (ESAP).
The main goal of this research project was to translate and adapt the European Survey on Ageing Protocol (ESAP) to 7 European countries/cultures. This article presents preliminary results from the ESAP, the basic assessment instrument of EXCELSA (European Longitudinal Study of Aging). 672 individuals aged 30-85, selected through quota sampling (by age, gender, education and living conditions), participated in this study, with 96 subjects from each of the 7 European countries. The basic research protocol for assessing competence and its determinants was designed to be administered in a 90-min in-home face-to-face interview. It contains a series of questions, instruments, scales and physical tests assessing social relationships and caregiving, mental abilities, well-being, personality, mastery and perceived control, self-reported health, lifestyles, anthropometry, biobehavioral measures and sociodemographic variables. 84% of ESAP measures are age-dependent and 75% of them discriminate between education levels. Minor differences were found due to gender, and between people living in rural and urban areas. Exploratory factor analysis yielded 10 factors accounting for 67.85% of total variance, one of which was identified as cognitive and physical 'competence'. This factorial structure was tested across countries through concordance coefficients. Finally, using structural equation modeling, our data were fitted into a model of competence. When the sample was split into younger groups (aged 30-49 years) and older ones (50 and more years), the same model was appropriate for our data. The results are discussed in accordance with other findings on psychosocial, biophysical and sociodemographic components of competence, and also in accordance with theories on competence and successful aging.


Nasopharyngeal carriage of Haemophilus influenzae type b: attempted eradication by cefaclor or rifampin.
The efficacy of cefaclor and rifampin in eradicating Haemophilus influenzae type b (HITB) from the nasopharynx of day care center and household contacts of children with HITB meningitis was evaluated. In 38/50 children treated with cefaclor, the carrier state persisted, a failure rate of 76%. Although cefaclor failed to eradicate HITB from many carriers, an appreciable reduction in the intensity of colonization following treatment was noticed. When rifampin was used in 17 children who had failed to respond to cefaclor, persistence of the carrier state with HITB was found in only two children, a failure rate of only 12%. During the study, two episodes of invasive HITB disease were documented to be acquired from sources other than the index cases or from children who were screened, which suggested the need to reevaluate the usually recommended strategy to screen for carriage and to treat only the immediate contacts 6 years of age and younger. Furthermore, the most appropriate agent for eradicating nasopharyngeal carriage of HITB awaits additional studies.


Morphology of bovine viral diarrhea virus.
The morphology of bovine viral diarrhea virus (BVDV) was studied by electron microscopy. The NADL strain of BVDV was plaque purified 3 times, concentrated by polyethylene glycol precipitation, and purified by centrifugation to equilibrium in continuous potassium tartrate density-gradients. The virus was examined by negative-stain electron microscopy in the presence or absence of specific antiserum. The density of BVDV was between 1.101 g/cm3 and 1.174 g/cm3, with the peak at maximum infectivity at 1.122 g/cm3. Oval to pleomorphic viral particles, 120 ( +/- 30) nm in diameter, were enriched in the peak of maximum infectivity. The detailed structure of virions was revealed: a 5- to 7-microns thick unit membrane-like envelope layer with numerous projecting knobs, 4 to 5 nm in diameter, surrounding an interior core-like structure. Viral particles measuring 120 ( +/- 30) nm were found in large aggregates in the presence of specific antiserum.


Zonation of glucose and fatty acid metabolism in the liver: mechanism and metabolic consequences.
The liver is generally considered as a relatively homogeneous organ containing four different cell types. It is however well-known that the liver is not homogeneous and consists of clearly demarcated metabolic zones. Hepatocytes from different zones show phenotypical heterogeneity in metabolic features, leading to zonation of metabolic processes across the liver acinus. Zonation of processes involved in glucose and fatty acid metabolism is rather flexible and therefore prone to change under (patho)physiological conditions. Hepatic zonation appears to play an important role in the segregation of the different metabolic pathways in the liver. As a consequence, perturbations in metabolic zonation may be a part of metabolic liver diseases. The metabolic syndrome is characterized by the inability of insulin to adequately suppress hepatic gluconeogenesis, leading to hyperglycemia, hyperinsulinemia and eventually to type II diabetes. As insulin promotes lipogenesis through the transcription factor sterol regulatory element binding protein (SREBP)-1c, one would expect that lipogenesis should also be impaired in insulin-resistant states. However, in the metabolic syndrome hepatic de novo lipogenesis is increased, leading to hyperlipidemia and hepatosteatosis, primarily in the pericentral zone. These observations suggest the co-existence of insulin resistant glucose metabolism and insulin sensitive lipid metabolism in the metabolic syndrome. Here we provide a theoretical framework to explain this so-called 'insulin signaling paradox' in the context of metabolic zonation of the liver.