[Impact of robotic assistance on the use and the outcomes of nephron-sparing surgery: A single center experience].
The aim of this study was to assess the impact of the acquisition of a Da Vinci® robot on the use and outcomes of partial nephrectomy (PN). It was a single center retrospective study including 280 patients who underwent PN from January 2006 to May 2013. The number of PN, tumors and patients' characteristics and perioperative outcomes have been assessed over 3 periods defined according to the main surgical approach: 2006-2008 (open PN), 2008-2010 (laparoscopic PN) and 2010-2013 (robotic PN). Over the study period, the surgical approach has changed significantly in favor of minimally-invasive surgery and especially robotic approach. The PN/nephrectomy rate has also evolved to a higher proportion of PN over radical nephrectomy (P=0.002). No significant difference was noted between the three periods in terms of tumor size but there was a higher rate of highly complex tumors (RENAL score≥10) during the last period (10.7%; 18.6% and 33.2%; P=0.04). Warm ischemia time increased from 2006-2008 to 2008-2010 (26 vs. 23minutes) but decreased thereafter during the robotic era (14.5minutes; P<0.001). Regarding postoperative outcomes, the only change was a decreased length of stay over time (P=0.003). In this single center series, the robotic approach was associated with a spread of PN and with an improvement of nephron-sparing surgery outcomes. 4.


Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to ocreotide therapy and do not correlate with tumor histology.
The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx). (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immuno histology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically non-functioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake: G1, uptake comparable to normal pituitary; G2, increased uptake: G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n = 10) vs G2/3 (n = 8): 3.6 +/- 1.9 vs 10.5 +/- 6.5 cm3 (mean +/- S.E.), P = 0.051), but not in NF-A (G0/1 (n = 12) vs G2/3 (n = 12): 17.0 +/- 10.1 vs 14.3 +/- 3.6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-1 in GH-A did not correlate with SRS results (G0/1 (n = 17) vs G2/3 (n = 8), GH: 32.3 +/- 18.2 vs 29.3 +/- 7.4 micrograms/l IGF-I: 851 +/- 80 vs 1038 +/- 153 micrograms/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or alpha-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify post-operative tumor remnants not visible on MRI.


Heterogeneity in Military Trauma Casualty Care.
Military combat casualty care is at the forefront of military medical readiness, but there is little data on current proficiency of deployed personnel. A previous study identified a potential performance gap in military trauma teams. This study aims to evaluate a subsequent team to determine if heterogeneity of teams exists and to determine if this level of efficiency persists or can be improved. Military trauma teams at the Role 3 hospital in Bagram, Afghanistan, were evaluated over the course of a single deployment between April and October 2018. Trauma teams were directly observed and performance of the ATLS primary trauma survey timed. These results were compared to previously published times from Kandahar and Bagram Role 3 sites from Oct 2016 to Apr 2017. Time to completion of the primary survey in 2018 was statistically faster than the times reported from the Role 3 sites from Oct 2016 to Apr 2017 (344.75 s vs. 482.8 s, p < 0.05). The greatest improvements of efficiency were in the time periods between assessing the airway and breathing, evaluating the patient's circulation, and completing of the primary survey. Trauma teams can vary significantly in their efficiency in evaluating trauma patients. Whether this is clinically significant is currently debatable, but it highlights a possible readiness gap for deploying military personnel and the heterogeneity of military combat casualty care.


Single DNA molecule analysis: applications of molecular combing.
Dynamic changes to the genomic structure and to the DNA replication programme are important determinants of normal and abnormal cell development. To understand these changes and how they vary from cell to cell, single DNA molecules from both normal and abnormal cell populations must be examined and compared. Physical characterisation of single genomes at the kilobase level of resolution over large genomic regions is possible with molecular combing technology. An array of combed single DNA molecules is prepared by stretching molecules attached by their extremities to a silanised glass surface with a receding air-water meniscus. By performing fluorescent hybridisation on combed DNA, genomic probe position can be directly visualised, providing a means to construct physical maps and detect micro-rearrangements. Single-molecule DNA replication can also be monitored through fluorescent detection of incorporated nucleotide analogues on combed DNA molecules. These and other single-molecule applications of molecular combing are discussed in this paper and future developments of the technology are considered.


High-extinction virtually imaged phased array-based Brillouin spectroscopy of turbid biological media.
Brillouin microscopy has recently emerged as a powerful technique to characterize the mechanical properties of biological tissue, cell, and biomaterials. However, the potential of Brillouin microscopy is currently limited to transparent samples, because Brillouin spectrometers do not have sufficient spectral extinction to reject the predominant non-Brillouin scattered light of turbid media. To overcome this issue, we combined a multi-pass Fabry-Perot interferometer with a two-stage virtually imaged phased array spectrometer. The Fabry-Perot etalon acts as an ultra-narrow band-pass filter for Brillouin light with high spectral extinction and low loss. We report background-free Brillouin spectra from Intralipid solutions and up to 100 μm deep within chicken muscle tissue.


Genome-Wide Identification of TCP Transcription Factors Family in Sweet Potato Reveals Significant Roles of miR319-Targeted TCPs in Leaf Anatomical Morphology.
Plant-specific TCP transcription factors play vital roles in the controlling of growth, development, and the stress response processes. Extensive researches have been carried out in numerous species, however, there hasn't been any information available about TCP genes in sweet potato (Ipomoea batatas L.). In this study, a genome-wide analysis of TCP genes was carried out to explore the evolution and function in sweet potato. Altogether, 18 IbTCPs were identified and cloned. The expression profiles of the IbTCPs differed dramatically in different organs or different stages of leaf development. Furthermore, four CIN-clade IbTCP genes contained miR319-binding sites. Blocking IbmiR319 significantly increased the expression level of IbTCP11/17 and resulted in a decreased photosynthetic rate due to the change in leaf submicroscopic structure, indicating the significance of IbmiR319-targeted IbTCPs in leaf anatomical morphology. A systematic analyzation on the characterization of the IbTCPs together with the primary functions in leaf anatomical morphology were conducted to afford a basis for further study of the IbmiR319/IbTCP module in association with leaf anatomical morphology in sweet potato.


Generalization and articulation instruction.
Three young children were taught correct articulation of an error phoneme on a program administered by their mothers in their homes. During the course of the treatment program each child was periodically brought into the speech clinic where the generalization of correct articulation learned in the home treatment setting could be measured in a series of four settings which differed from the treatment setting in varying degrees. Stimulus words which had not been taught during the home articulation program were also included in generalization testing. The results indicated (1) that correct articulation generalized to a high extent to the nontreatment settings investigated; and (2) that responses to new stimulus words were less adequate than responses to words which had received previous training. The clinical implications of these findings are discussed.


ACE I/D Polymorphism in Hypertensive Patients of Kashmiri Population.
The angiotensin-converting enzyme (ACE) gene in humans has an insertion-deletion (I/D) polymorphic state in intron 16 on chromosome 17q23. This polymorphism has been widely investigated in different diseases. In this study we aimed to investigate the ACE I/D genotype frequency in hypertensive cases in Kashmiri population. We designed a case control study, where 52 hypertensive cases were studied for ACE I/D polymorphism against 150 age/sex matched controls taken from general population. The polymorphisms of ACE gene were investigated using polymerase chain reaction for detection of ACE I/D genotype. Fisher's Chi square test was used for calculation of P value and OR. We found the frequency of ACE DD genotype to be 46.15% (24/52), II 23.07% (12/52) and DI 30.77% (16/52) in 52 hypertensive cases. The ACE I/D genotype is positively associated with hypertension in our population.


Liquid chromatography and chemometric-assisted spectrophotometric methods for the analysis of two multicomponent mixtures containing cough suppressant drugs.
Three methods were applied for the analysis of 2 multicomponent mixtures containing dextromethorphan hydrobromide, phenylephrine hydrochloride, chlorpheniramine maleate, methylparaben, and propylparaben, together with either sodium benzoate (Mix 1) or ephedrine hydrochloride and benzoic acid (Mix 2). In the first method, liquid chromatography was used for their simultaneous determination using an ODS column with a mobile phase consisting of acetonitrile-phosphate buffer, pH 2.7 (40 + 60, v/v), containing 5mM heptanesulfonic acid sodium salt and ultraviolet (UV) detection at 214 nm. Also, 2 chemometric methods, principal component regression, and partial least squares were used. For both chemometric calibrations, a concentration set of the mixture consisting of each compound in each mixture was prepared in distilled water. The absorbance data in the UV spectra were measured for the 76 or 71 wavelength points in the spectral region 210-240 or 210-224 nm considering the intervals of deltagamma = 0.4 or 0.2 nm for Mix 1 and Mix 2, respectively. The 2 chemometric methods did not require any separation step. These methods were successfully applied for the analysis of the 2 multicomponent combinations in synthetic mixtures and in commercial syrups, and the results were compared with each other.


Motor and visuomotor skills of children with Asperger's disorder: preliminary findings.
While motor clumsiness is frequently described as an associated feature of Asperger's Disorder, little research has examined specific motor skills and the relation among aspects of motor performance in this population. The present purpose was to present preliminary findings for three aspects of Asperger's: the presence and magnitude of gross motor and fine motor deficits, the presence and magnitude of visuomotor deficits, and the relation between motor functioning and visuomotor skills. 17 boys, 6 to 13 years old, with Asperger's were tested using standardized measures of gross, fine, and visuomotor skills. Statistically significant deficits were found for the sample's scores compared with values for the general population (using one-sample t tests), but none for fine motor vs gross motor skills (using a dependent sample t test). Significant positive correlations were found for gross motor skills with visuomotor skills (.73) and for fine motor skills with visuomotor skills (.71). Tentative suggestions for clinical assessment were proposed.


Direct and indirect activation of nerve cells by electrical pulses applied extracellularly.
1. The mode of activation of nerve cells by extracellular stimuli was investigated while recording from a selected cell with one electrode, and applying current pulses around this cell with another electrode. The analysis was done on motoneurones and on spinal border cells from lower lumbar segments in the cat. 2. Directly evoked action potentials were defined by their appearance in an all-or-none fashion with stable latencies of less than 0-5 ms. The lowest thresholds for their generation were 0-15-0-20 muA in the spinal border cells and 0-35-0-40 muA in the motoneurones. In the main series on motoneurones a correlation has been established between different positions of the extracellular stimulating electrode in relation to the cells and the thresholds for the direct excitation of these cells. The position of the electrode were defined on the basis of an analysis of the IS and SD components of the action potentials recorded extracellularly around the cell when evoked by current pulses applied through the intracellular electrode; both the amplitudes of these IS and SD components and their timing with the IS and SD spikes, which were simultaneously recorded with the intracellular electrode, were then taken into account. The lowest thresholds (less than 2 muA) for the direct activation of cells were found nearest the initial segment of the axon. Their values increased to about 5 mu A at near-soma positions and to greater than 10 muA at near-dendrites positions about 150 mum away. 3. Transsynaptically evoked action potentials which were clearly set up by the preceding e.p.s.p.s appeared with latencies greater than 0-7 ms. When single current pulses were used, the lowest thresholds for transsynaptic spike activation were usually greater than 5-10 muA but they considerably decreased with repetitive stimuli. These thresholds were higher than the thresholds for the direct activation of cells within the region of the initial segment, of the same order of magnitude near the soma, and lower when the stimulating electrode was nearer the dendrites than the soma and generally at all larger distances from the cells. 4. All the observations on direct excitation of cells by extracellular stimuli (generation of the IS spike before the SD spike, lowest thresholds near the region of the initial segment of the axon, similar rates of increase in these thresholds with distance as for fibres) lead to the conclusion that the effects of the extracellular stimuli are exerted primarily via spread of current to the initial segment of the axon and its depolarization. 5. Late extracellular negativities presumably related to dendritic activation were observed in a few cells. These negativities were synchronous with late components of the intracellulary recorded action potentials.


Web-based information on orthodontic clear aligners: a qualitative and readability assessment.
Data regarding the quality of information (QOI) related to orthodontic clear aligners (OCAs) on the internet are lacking. The aim of the present investigation was to assess the quality and readability of websites providing information regarding OCAs to prospective patients. Three search terms were entered separately into three search engines. Four validated QOI instruments were used to determine the QOI and readability of the content contained within the websites that satisfied predetermined criteria. Descriptive statistical analyses and intrarater testing for DISCERN scores were calculated. Forty-nine websites satisfied inclusion/exclusion criteria. General dentists (44.9%) and specialist orthodontists (26.5%) authored the majority of websites. One website contained the Health on the Net (HON) code seal. Cohen's kappa for DISCERN scores was good (0.87). The overall mean (SD) DISCERN score was 38.55 (8.00)/80, range 26-60. The websites authored by 'Direct-to-consumer' OCA providers recorded the lowest DISCERN mean score (33/80). One website contained all four Journal of the American Medical Association (JAMA) benchmarks. The mean (SD) Flesch Reading Ease score was 53.92 (9.08), range 36-82.5. The QOI of the website content related to OCAs is poor and is 'fairly difficult' to read. Website authors should consider using QOI instruments and readability tools to enable the delivery of evidence-based and easily readable information regarding OCAs to prospective patients.


Multiple Myeloma and the Role of Bisphosphonates in Its Management.
An aberrant growth of plasma cells in the bone marrow characterizes the hematological neoplasm known as multiple myeloma, which is typically accompanied by increased bone pain and skeletal-related events such as pathological fractures and/or spinal cord compression. Changes in the bone marrow microenvironment brought on by increased osteoclastic activity and/or decreased osteoblastic activity as a result of myeloma bone disease have a detrimental effect on quality of life. Bone-modifying medications such as bisphosphonates or denosumab are used to treat myeloma bone disease. These substances can lessen bone pain and the chance of pathological fracture, but they do not stimulate the growth of new bone or heal already damaged bone. In order to conduct this study, we searched the PubMed, Google Scholar, and Cochrane databases for complete free papers published in English and studied people over the previous five years, starting in 2018. The search covered randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and conventional reviews. Twenty-five publications are picked after using quality evaluation techniques to determine the type of study. These papers' full-text articles are investigated, examined, and tallied. We spoke about the various treatments for bone damage in multiple myeloma. It was discovered that bisphosphonates lessen the frequency and severity of bone problems. However, we are unsure of their contribution to survival. Although these medicines enhance life quality, it is unknown if they also increase overall survival. The focus of this study is on several kinds of bone-modifying drugs, their processes of action, the point at which therapy is started, how long it lasts, and any possible mortality advantages.


Risk factors for HIV infection among young adult men in northern Thailand.
To determine the sociodemographic and behavioral risk factors associated with human immunodeficiency virus (HIV) infection in two cohorts of young men selected for military service in northern Thailand. Military conscripts were studied cross-sectionally after conscription in May 1991 and November 1991. Risk factors were assessed by interview with trained nonmilitary interviewers. Two military training bases in Chiang Mai, Thailand. A total of 2417 young men aged 19 to 23 years (mean age, 21 years) conscripted by lottery into military service in the Royal Thai Army or Royal Thai Air Force from six provinces in northern Thailand. Human immunodeficiency virus seroprevalence by enzyme-linked immunosorbent assay confirmed by Western blot and univariate and multivariate analyses of sociodemographic and behavioral risk factors associated with HIV seroprevalence. Overall, 289 (12.0%) of 2417 men were HIV-seropositive at baseline. The strongest associations with being HIV positive were heterosexual activities. History of sex with a female commercial sex worker (CSW) was frequent (96.5% of men who were HIV-positive and 79.0% of men who were HIV-negative) and strongly associated with HIV infection on univariate and multivariate analyses (adjusted odds ratio, 1.60 to 2.07, depending on the frequency of CSW contact). Also, sexually transmitted diseases were common and associated with HIV infection in both univariate and multivariate analyses (adjusted odds ratio, 3.36). Sex with other males and injection drug use were uncommon and not associated with HIV infection. Condom use was reported in 61.5% of men at last sex with a CSW but was not shown to be protective of prevalent HIV infection. The epidemic of HIV infection has spread widely among young men in northern Thailand, despite reported frequent and recent use of condoms during sex with female CSWs. Control of HIV infection in this population will probably require more regular and effective use of condoms, prevention and treatment of sexually transmitted diseases, and reduction in the frequency of CSW contact.


Accumulated Angle Factor-Based Beamforming to Improve the Visualization of Spinal Structures in Ultrasound Images.
In recent years, ultrasound has been increasingly used to guide needle insertion procedures for spinal anesthesia. The primary anatomical targets are facet joints and epidural spaces. For these procedures, accurate visualization of the spine anatomy is of critical importance. Challenges arising from the interactions between the ultrasound beam and spinal structures including tilt caused by specular reflections, off-axis interference, and reverberations often result in weakened and blurred vertebra surfaces. Previously, adaptive beamforming methods have been proposed to improve the resolution and contrast. However, most of these methods are not specialized for improving the contrast of specular targets like bones. In this paper, we propose an accumulated angle factor (AAF)-based beamforming method customized for bone surface enhancement. This approach applies a Hilbert transform on delay compensated channel data across the receive aperture. The accumulated phase change across the receive aperture is then calculated and utilized as the weight in the beamforming output. We compared our method with classical delay and sum (DAS) beamforming method and adaptive beamforming methods such as Wiener, phase coherence factor (PCF), CF, and generalized CF (GCF) beamforming. In 12 volunteer data sets, the mean contrast ratio between the vertebrae surface and the surrounding tissue for DAS, Wiener, PCF, CF, GCF, and the proposed AAF methods are 0.49, 0.64, 0.82, 0.77, 0.76, and 0.91, respectively. The contrast is significantly improved in the proposed method.


Glucose transporters and FDG uptake in untreated primary human non-small cell lung cancer.
PET imaging of malignant tumors with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) as a tracer is a noninvasive diagnostic and prognostic tool that measures tumor metabolism. In this study, we assessed the relationships between FDG uptake and the expression of facilitative glucose transporters, the sizes of populations of proliferating cells and infiltrating macrophages in patients with primary non-small cell lung cancers (NSCLC). FDG uptake and the expression of five glucose transporters and the proportions of proliferating cell and macrophage populations were studied in paraffin sections from untreated primary lung cancers by immunohistochemistry. The patients were imaged with FDG PET before surgery. All tumors could be detected by FDG PET. Uptake was correlated with tumor size (P = 0.004). FDG uptake was lower in adenocarcinomas (ACs) than in squamous cell carcinomas (SQCs) (P = 0.03) or large cell carcinomas (P = 0.002) [standardized uptake value corrected for lean body mass (SUL) = 5.42 +/- 2.77, 8.04 +/-3.25 and 10.42 +/- 4.54, respectively]. Glut-1 expression was significantly higher than that of any other transporter. All tumors tested (n = 23) were Glut-1-positive (70.8% +/- 26.1% of tumor cell area was positive and staining intensity was 2.8 +/- 1.2). Glut-1 expression was higher in SQCs (78% +/- 17.8% and 3.5 +/-0.6) than in ACs (47.5% +/- 30.3% and 1.6 +/- 1.1; P = 0.044 for positive tumor cell area and P = 0.005 for staining intensity). Proliferating cells constituted 15.3% +/- 13.1% of the cancer cells, and the average number of macrophages was 7.8% +/- 6.3%; neither correlated with FDG uptake. In this population of patients with NSCLC, Glut-1 is the major glucose transporter expressed. Both FDG uptake and Glut-1 expression appear to be associated with tumor size. No association was found between FDG uptake and either macrophage or proliferative cell populations.


Ligand-Based Virtual Screening in a Search for Novel Anti-HIV-1 Chemotypes.
In a search for new anti-HIV-1 chemotypes, we developed a multistep ligand-based virtual screening (VS) protocol combining machine learning (ML) methods with the privileged structures (PS) concept. In its learning step, the VS protocol was based on HIV integrase (IN) inhibitors fetched from the ChEMBL database. The performances of various ML methods and PS weighting scheme were evaluated and applied as VS filtering criteria. Finally, a database of 1.5 million commercially available compounds was virtually screened using a multistep ligand-based cascade, and 13 selected unique structures were tested by measuring the inhibition of HIV replication in infected cells. This approach resulted in the discovery of two novel chemotypes with moderate antiretroviral activity, that, together with their topological diversity, make them good candidates as lead structures for future optimization.


PRAF2 stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma.
Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein with four transmembrane-spanning domains that belongs to the PRAF protein family. Neuroblastoma (NB) is the most common malignant extracranial solid tumor of childhood that originates in primitive cells of the developing sympathetic nervous system. We investigated the correlation of PRAF2 mRNA expression to NB clinical and genetic parameters using Affymetrix expression analysis of a series of 88 NB tumors and examined the functional role of PRAF2 in an NB cell line using RNA interference. We found that high PRAF2 expression is significantly correlated to several unfavorable NB characteristics: MYCN amplification, high age at diagnosis, poor outcome and high INSS stage. The shRNA-mediated PRAF2 downregulation in the SK-N-SH NB cell line resulted in decreased cellular proliferation, migration and matrix-attachment. These findings were confirmed in NB patient tumor samples, where high PRAF2 expression is significantly correlated to bone and bone marrow metastasis, the main cause of death in NB patients. The present study shows that PRAF2 plays an essential role in NB tumorigenesis and metastasis.


Detection in noise by spectro-temporal pattern analysis.
Detectability of a 400-ms, 1000-Hz pure-tone signal was examined in bandlimited noise where different spectral regions were given similar waveform envelope characteristics. As expected, in random noise the threshold increased as the noise bandwidth was increased up to a critical bandwidth, but remained constant for further increases in bandwidth. In the noise with envelope coherence however, threshold decreased when the noise bandwidth was made wider than the critical bandwidth. The improvement in detectability was attributed to a process by which energy outside the critical band is used to help differentiate signal from masking noise, provided that the waveform envelope characteristics of the noise inside and outside the critical band are similar. With flanking coherent noise bands either lower or higher in frequency than a noise band centered on the signal, it was next determined that the frequency relation and remoteness of the coherent noise did not particularly influence the magnitude of the unmasking effect. An interpretation in terms of nonsimultaneous masking was reconciled with some aspects of the data, and with an interpretation in terms of across-frequency temporal pattern analysis. This paradigm, in which detection is based upon across-frequency temporal envelope coherence, was termed "comodulation masking release." Comodulation offers a controlled way to investigate some of the mechanisms which permit signals to be detected at adverse signal-to-noise ratios.


Balance ability in patients with benign paroxysmal positional vertigo.
The purpose of the study was to investigate the balance ability of the patients with benign paroxysmal positional vertigo (BPPV). Twenty-three patients (63.3 +/- 9.2 years of age) with a diagnosis of unilateral posterior semicircular canal BPPV were recruited. Static balance was measured in 4 conditions with eyes open and eyes closed: stance on firm surface, stance on foam surface, left leg stance, and right leg stance. Dynamic balance was measured in tandem walk test. Data of the patients with BPPV were compared to age-matched norm values of the healthy adults. The patients with BPPV demonstrated greater sway velocity in stance on foam surface with eyes closed (P < 0.05), in single leg stance with eyes closed (P < 0.001), and in tandem walk test (P < 0.05) compared to the healthy adults. Patients with BPPV demonstrated impaired static and dynamic balance ability particularly when depriving visual and changing proprioceptive inputs. Clinically, in addition to canalith repositioning maneuver, balance retraining on different conditions may be a useful adjunct to treatment for patients with BPPV.


[Changes of immunocytes in livers of chronic hepatitis C patients treated with IFN alpha-2b and ribavirin].
To investigate the immunocytodynamic changes in the livers of chronic hepatitis C patients treated with IFN alpha-2b and ribavirin and to find new bases for an effective immune regulation therapy. Forty-two chronic hepatitis C patients were treated with combined IFN alpha-2b and ribavirin and their peripheral blood and liver tissues were collected before the treatment for analyses. After the treatment, peripheral blood and liver tissue specimens were obtained from only 11 patients. All the specimens were exposed to three monoclonal antibody fluorescence dyes, and the CD45+ cells with triple colors were analyzed using flow cytometry. Compared to the control groups, the positive rates of CD56+, CD57+, CD161+ cells in the livers of those with chronic hepatitis C sharply decreased (Probability value less than 0.01), and CD56+T cells had decreased mildly; CD28 from the CD56+T cells decreased mildly, but the expression of CD152 increased (P<0.05); the positive rates of CD83+CD1a+ cells had decreased mildly, and the positive rates of CD80+CD11c+ and the CD86+CD11c+ cells significantly decreased (P<0.01). After the treatment, the CD56+, CD161+, CD56+T, CD161+T, CD80+CD11c+, CD86+CD11c+ cells in the responding group increased. Combined interferon alpha-2b and ribavirin treatment can improve the suppressed cell immunity function.


XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans.
The molecular architecture of the mature N-glycome is dynamic, with consequences for both normal and pathologic processes. Elucidating cellular mechanisms that modulate the N-linked glycome is, therefore, crucial. The unfolded protein response (UPR) is classically responsible for maintaining proteostasis in the secretory pathway by defining levels of chaperones and quality control proteins. Here, we employ chemical biology methods for UPR regulation to show that stress-independent activation of the UPR's XBP1s transcription factor also induces a panel of N-glycan maturation-related enzymes. The downstream consequence is a distinctive shift toward specific hybrid and complex N-glycans on N-glycoproteins produced from XBP1s-activated cells, which we characterize by mass spectrometry. Pulse-chase studies attribute this shift specifically to altered N-glycan processing, rather than to changes in degradation or secretion rates. Our findings implicate XBP1s in a new role for N-glycoprotein biosynthesis, unveiling an important link between intracellular stress responses and the molecular architecture of extracellular N-glycoproteins.


Phase function effects on the retrieval of oceanic high-spectral-resolution lidar.
A semianalytic Monte Carlo model is developed to simulate oceanic high-spectral-resolution lidar (HSRL) signals with multiple scattering. The phase function effects on oceanic HSRL retrieval are studied, e.g., the effective particulate 180° volume scattering function (VSF) and lidar attenuation coefficient that describe characteristics of backscatter and attenuation, respectively. The results demonstrate that the particulate backward and forward phase functions both have a significant influence on δ1, which is the relative difference between the effective and true particulate 180° VSF. The values of |δ1| are typically quite small for all phase functions at the water surface and increase with depth up to ~17% for the Fournier and Forand (FF) phase function but up to ~40% for the two-term Henyey-Greenstein (TTHG) phase function and ~75% for the one-term Henyey-Greenstein (OTHG) phase function. The reason that δ1 is not zero is due to broadening of backscattering angles from 180° caused by multiple scattering and uneven backward phase function. Also, the reason that maximum TTHG and OTHG |δ1| are larger than FF is due to less sharply increasing feature of FF in the backward direction. In addition, the particulate forward phase functions are closely related to δ2, which is the relative deviation between the lidar attenuation coefficient and the sum of the absorption and backscattering coefficients. The values of δ2 are small for all phase functions at the water surface and increase with depth up to ~12% for TTHG but up to ~26% for FF and ~31% for OTHG, due to the less peaked forward phase functions that result in more angular spread of the beam with depth and therefore result in less photons within the field of view of the lidar.


Trauma precipitating thyroid storm.
A 40 year old male victim of a road traffic accident presented to our emergency trauma services with multiple limb injuries and a Glasgow Coma Score (GCS) of 15/15. Soon after admission, he became confused, stuporous, febrile and tachycardic. A clinical diagnosis of thyrotoxic crisis precipitated by trauma was confirmed by relevant investigations, with appropriate therapeutic response. A review of the clinical features and management of this rare medical emergency, with only few cases reported worldwide, is presented.


Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome.
Memantine is a partial NMDA receptor antagonist that has been shown to improve learning and memory in several animal models, and is approved for the treatment of Alzheimer's disease (AD). Chronic treatments using memantine in animal models of Alzheimer's disease show disease-modifying effects and suggest a potential neuroprotective function. The present study assessed the effects of both short- and long-term memantine treatment in a mouse model of Down syndrome (DS), the Ts65Dn mouse. The Ts65Dn mouse contains a partial trisomy of murine chromosome 16, and exhibits hippocampal-dependent memory deficits, as well as progressive degeneration of basal forebrain cholinergic neurons (BCFNs). Ts65Dn mice were treated with memantine for a period of 6 months, beginning at 4 months of age. At the end of treatment the mice underwent memory testing using novel object recognition and water radial arm maze tasks, and then histologically analyzed for markers of neurodegeneration. Memantine treatment improved spatial and recognition memory performance in the Ts65Dn mice, though not to the level of normosomic littermate controls. Despite these memory improvements, histological analysis found no morphological signs of neuroprotection of basal forebrain cholinergic or locus coeruleus neurons in memantine-treated Ts65Dn mice. However, memantine treatment of Ts65Dn mice gave rise to elevated brain-derived neurotrophic factor expression in the hippocampus and frontal cortex, suggesting a mechanism of behavioral modification. Thus, our findings provide further evidence for memory facilitation of memantine, but suggest pharmacological rather than neuroprotective effects of memantine both after acute and chronic treatment in this mouse model.


Arthroscopic Single-Bundle Anterior Cruciate Ligament Reconstruction Using the Quadrupled Hamstring Tendon Graft: A Single-Institution Experience From North-Eastern India.
Background There is a lack of literature regarding the arthroscopic approach to a single-bundle anterior cruciate ligament (ACL) reconstruction using the quadrupled hamstring tendon graft in the north-eastern Indian population. Methodology A prospective, single-center study was planned for patients with ACL tears according to the eligibility criteria and with a defined surgical protocol. Patients were followed up from the preoperative period for at least one year, and knee function was evaluated using the International Knee Documentation Committee (IKDC) subjective knee score and the Lysholm knee score. Results A total of 29 patients were followed up for a mean of 14.6 months (12-22 months). The mean age of patients was 26.83 ± 7.50 years, with a male:female ratio of 4.8:1 and almost equal involvement of both knees. There was statistically significant improvement (p<0.001) in results in the Lachman test, anterior drawer test, pivot shift test, IKDC score, and Lysholm score. No intraoperative or postoperative complications were found in the present study. Discussion The study shows that arthroscopic anatomical single-bundle ACL reconstruction using quadrupled hamstring tendon grafts is a minimally invasive, safe, and effective procedure that provides anteroposterior and rotational stability and good to excellent functional outcomes.


Saturation-transfer electron paramagnetic resonance detection of anisotropic motion by sickle hemoglobin molecules in the polymer state.
The motional behavior of spin-labeled deoxygenated sickle hemoglobin has been studied by using both 9- and 35-GHz saturation-transfer electron paramagnetic resonance (EPR). Using spectral subtraction techniques and saturation-transfer EPR parameter correlation plots, we find that the saturation-transfer EPR spectra for the sickle hemoglobin gel state at high temperature and high hemoglobin concentration cannot be described as a simple superposition of spectra from immobilized hemoglobin plus solution-state hemoglobin but instead suggest that the individual sickle hemoglobin molecules exhibit limited, anisotropic, rotational oscillation within the polymer fiber. The spectra also imply that the symmetry axis for sickle hemoglobin rotational oscillation is approximately coincident with the nitroxide z axis of the covalently attached spin-label. We suggest that this anisotropic rotational motion may be produced by one or two of the known intermolecular contact sites within the sickle hemoglobin fiber acting as strong intermolecular binding sites, and producing "motional alignment" within the fiber; determining the location of the strong binding site should be important in focusing the future development of antisickling agents.


[Testicular microlithiasis--are biopsy and follow-up necessary?].
Improvement in the technology of ultrasound has made it possible to visualise small calcifications in the testes, known in the literature as testicular microlithiasis (TM). TM is described in otherwise healthy men, but is also found related to cancer and CIS. Here we will discuss the evaluation and follow up of patients with diagnosed TM. The study comprises 14 patients in whom TM was diagnosed sonographically in the period from December 1997 to May 2000. Ultrasound indicated cancer in two patients. Pathology showed germ cell cancer in both. In 12 patients, ultrasound showed only TM, no suspicion of cancer. Biopsies taken in eight of these patients were all benign. The prevalence of TM is still unknown, as is its aetiology. TM is somehow correlated to testicular cancer, as microliths are found much more often in testes with cancer than in those without malignancy. However, in the vast majority of patients, evidence of cancer or CIS cannot be found. Development of cancer in patients formerly diagnosed with TM is rarely described. In the case of TM and no sonographic signs of cancer, we therefore believe biopsies can be limited to patients at increased risk of testicular cancer, for instance those with retained or small atrophic testes, and also possibly to patients known to have developed TM between repeated ultrasound examinations. If a biopsy shows no signs of malignancy or CIS, we see no need for follow up. If biopsy is not indicated, we recommend a clinical check up, followed by further investigations if these are indicated.


Practices and Perspectives of Traditional Bone Setters in Northern Tanzania.
Traditional health practitioners remain a critical source of care in Tanzania, more than 50% of Tanzanians frequently using their services. With a severe shortage of orthopaedic surgeons (1:3.3 million Tanzanians) traditional bone setters (TBSs) could potentially expand access to musculoskeletal care and improve outcomes for morbidity as a result of trauma. We sought to identify the advantages and disadvantages of traditional bone setting in Tanzania and to assess potential for collaboration between TBSs and allopathic orthopaedic surgeons. Between June and July 2017 we interviewed six TBSs identified as key informants in the regions of Kilimanjaro, Arusha, and Manyara. We conducted semi-structured interviews about practices and perspectives on allopathic healthcare, and analyzed the data using a deductive framework method. The TBSs reported that their patients were primarily recruited from their local communities via word-of-mouth communication networks. Payment methods for services included bundling costs, livestock barter, and sliding scale pricing. Potentially unsafe practices included lack of radiographic imaging to confirm reduction; cutting and puncturing of skin with unsterile tools; and rebreaking healed fractures. The TBSs described past experience collaborating with allopathic healthcare providers, referring patients to hospitals, and utilizing allopathic techniques in their practice. All expressed enthusiasm in future collaboration with allopathic hospitals. TBSs confer the advantages of word-of-mouth communication networks and greater financial and geographic accessibility. However, some of their practices raise concerns relating to infection, fracture malunion or nonunion, and iatrogenic trauma from manipulating previously healed fractures. A formal collaboration between TBSs and orthopaedic surgeons, based on respect and regular communication, could alleviate concerns through the development of care protocols and increase access to optimal orthopaedic care through a standardized triage and follow-up system.


Efficient Super-Resolution Method for Targets Observed by Satellite SAR.
This study presents an efficient super-resolution (SR) method for targets observed by satellite synthetic aperture radar (SAR). First, a small target image is extracted from a large-scale SAR image and undergoes proper preprocessing. The preprocessing step is adaptively designed depending on the types of movements of targets. Next, the principal scattering centers of targets are extracted using the compressive sensing technique. Subsequently, an impulse response function (IRF) of the satellite SAR system (IRF-S) is generated using a SAR image of a corner reflector located at the calibration site. Then, the spatial resolution of the IRF-S is improved by the spectral estimation technique. Finally, according to the SAR signal model, the super-resolved IRF-S is combined with the extracted scattering centers to generate a super-resolved target image. In our experiments, the SR capabilities for various targets were investigated using quantitative and qualitative analysis. Compared with conventional SAR SR methods, the proposed scheme exhibits greater robustness towards improvement of the spatial resolution of the target image when the degrees of SR are high. Additionally, the proposed scheme has faster computation time (CT) than other SR algorithms, irrespective of the degree of SR. The novelties of this study can be summarized as follows: (1) the practical design of an efficient SAR SR scheme that has robustness at a high SR degree; (2) the application of proper preprocessing considering the types of movements of targets (i.e., stationary, moderate motion, and complex motion) in SAR SR processing; (3) the effective evaluation of SAR SR capability using various metrics such as peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), focus quality parameters, and CT, as well as qualitative analysis.


"Minimal metabolism": A key concept to investigate the origins and nature of biological systems.
The systems view on life and its emergence from complex chemistry has remarkably increased the scientific attention on metabolism in the last two decades. However, during this time there has not been much theoretical discussion on what constitutes a metabolism and what role it actually played in biogenesis. A critical and updated review on the topic is here offered, including some references to classical models from last century, but focusing more on current and future research. Metabolism is considered as intrinsically related to the living but not necessarily equivalent to it. More precisely, the idea of "minimal metabolism", in contrast to previous, top-down conceptions, is formulated as a heuristic construct, halfway between chemistry and biology. Thus, rather than providing a complete or final characterization of metabolism, our aim is to encourage further investigations on it, particularly in the context of life's origin, for which some concrete methodological suggestions are provided. Also see the video abstract here: https://youtu.be/DP7VMKk2qpA.


Initial single-center experience with a new external support device for the creation of the forearm native arteriovenous fistula for hemodialysis.
To assess and compare the maturation rate of the native radiocephalic arteriovenous fistula (RC-AVF) created with and without a nitinol external support (VasQ™ Laminate Medical Technologies Ltd, Tel Aviv, Israel). Data of all consecutive patients who underwent the creation of native RC-AVFs at our center between October 2018 and January 2020 was prospectively collected and retrospectively analyzed.Selected patients who had a suitable vein and a radial artery with triphasic flow at preoperative duplex ultrasound exam and were selected for the creation of a radiocephalic fistula were included. Exclusion criteria were: malignant tumors, acute renal failure, previous upper limb revascularization, and septic status. Patency and maturation, vein, and artery diameter and blood flow rate were assessed at the following intervals: post-operatively, 24 h post-operatively, 1 month, 3 months, and 6 months post-operatively. Forty-nine patients (31 males, mean age 65.7 years old) were included. Patients who received VasQ™ devices were 25 (VasQ group), the other 24 formed the control group. All patients underwent radio-cephalic AVF placement (21 on the wrist, 20 on the forearm, 8 on the proximal forearm). There were no perioperative complications and fatalities. At 1, 3, and 6 months, primary patency rates were 96 ± 4%, 96 ± 4%, 91 ± 6% (VasQ group) versus 87 ± 7%, 87 ± 7%, 80 ± 9% (control group, P 0.17), secondary patency rates were 96 ± 4%, 96 ± 4%, 91 ± 6% (VasQ group) versus 95 ± 4%, 90 ± 7%, 90 ± 7% (control group, P 0.79). A significantly larger vein diameter increase postoperatively (P 0.009) and a greater maturation rate (96% vs 74%, p 0.044) were found in the VasQ group compared to the control group. The use of the VasQ™ device was associated with higher maturation rates and larger vein diameters postoperatively. The patency rates were slightly higher but not significantly. Further studies are needed to confirm these findings.


Histological findings on jaw osteonecrosis associated with bisphosphonates (BONJ) or with radiotherapy (ORN) in humans.
To describe the histological features of bone tissue harvested from patients affected by jaw osteonecrosis associated with bisphoshponates (BONJ) or with radiotherapy (ORN), in undecalcified ground sections. Sixteen bone tissue samples from 14 patients with BONJ and two patients with ORN were processed in order to obtain both ground, undecalcified sections and decalcified sections. The sections underwent histometric and morphometric analysis. Bone tissue samples obtained from patients with BONJ or ORN of the jaws shared some histological characteristics. Common histological features included the loss of bone architecture, the absence of a proper Haversian system and proper marrow spaces, the presence of necrotic spots of non-mineralized tissue, areas of empty osteocytic lacunae next to areas of hypercellularity, the presence of resorption pits with rare osteoclast-like cells and the presence of bacteria and of an inflammatory infiltrate. A violet rib of tissue characterized by large resorption pits facing was frequently observed between the mineralized bone and the inflammatory infiltrate. The histological features of BONJ and ORN are similar and resemble those of osteomyelitis. Even though it is not clear whether infection is the cause or consequence of bone exposure, inflammatory cells, bacteria or their products may have a massive, direct lytic effect on bone tissue challenged by bisphosphonates.


Macronutrient composition and sarcopenia in the oldest-old men: The Helsinki Businessmen Study (HBS).
Sarcopenia is associated with increased risk for several adverse health outcomes including frailty, disability, loss of independence, and mortality. We examined cross-sectional associations between sarcopenia and detailed dietary macronutrient composition in community-living oldest-old men (mean age 87). Participants were invited to a clinic visit in 2017/2018 including assessments of sarcopenia status using European Working Group on Sarcopenia in Older People's 2 (EWGSOP2) criteria and detailed macronutrient, vitamin D and food intakes retrieved from 3-day food diaries. Of the 126 participants, 48 had probable sarcopenia and 27 sarcopenia. Sarcopenia was associated with lower energy (p = 0.020), total protein (p = 0.019), plant (p = 0.008) and fish proteins (p = 0.041), total fat (p = 0.015), monounsaturated fatty acids (MUFA) (p = 0.011), polyunsaturated fatty acids (p = 0.002), vitamin D intakes (p = 0.005) and, of fat quality indicators, MUFA: saturated fatty acid-ratio (p = 0.042). These findings suggest that sufficient energy and protein intakes, but also fat quality may be important along with healthy dietary patterns for prevention of sarcopenia in the oldest-old.


Neurobiological mechanisms of aggression and stress coping: a comparative study in mouse and rat selection lines.
Aggression causes major health and social problems and constitutes a central problem in several psychiatric disorders. There is a close relationship between the display of aggression and stress coping strategies. In order to gain more insight into biochemical pathways associated with aggression and stress coping, we assessed behavioral and neurobiological responses in two genetically selected rodent models, namely wild house mice selectively bred for a short (SAL) and long (LAL) attack latency and Wistar rats bred for high (HAB) or low (LAB) anxiety-related behavior. Compared to their line counterparts, the SAL mice and the LAB rats display a high level of intermale aggression associated with a proactive coping style. Both the SAL mice and the LAB rats show a reduced hypothalamic-pituitary-adrenal (HPA) axis response to non-social stressors. However, when exposed to social stressors (resident-intruder, sensory contact), SAL mice show an attenuated HPA response, whereas LAB rats show an elevated HPA response. In both rodent lines, the display of aggression is associated with high neuronal activation in the central amygdala, but reduced neuronal activation in the lateral septum. Furthermore, in the lateral septum, SAL mice have a reduced vasopressinergic fiber network, and LAB rats show a decreased vasopressin release during the display of aggression. Moreover, the two lines show several indications of an increased serotonergic neurotransmission. The relevance of these findings in relation to high aggression and stress coping is discussed. In conclusion, exploring neurobiological systems in animals sharing relevant behavioral characteristics might be a useful approach to identify general mechanisms of action, which in turn can improve our understanding of specific behavioral symptoms in human psychiatric disorders.


Thermal adaptation and phenotypic plasticity in a warming world: Insights from common garden experiments on Alaskan sockeye salmon.
An important unresolved question is how populations of coldwater-dependent fishes will respond to rapidly warming water temperatures. For example, the culturally and economically important group, Pacific salmon (Oncorhynchus spp.), experience site-specific thermal regimes during early development that could be disrupted by warming. To test for thermal local adaptation and heritable phenotypic plasticity in Pacific salmon embryos, we measured the developmental rate, survival, and body size at hatching in two populations of sockeye salmon (Oncorhynchus nerka) that overlap in timing of spawning but incubate in contrasting natural thermal regimes. Using a split half-sibling design, we exposed embryos of 10 families from each of two populations to variable and constant thermal regimes. These represented both experienced temperatures by each population, and predicted temperatures under plausible future conditions based on a warming scenario from the downscaled global climate model (MIROC A1B scenario). We did not find evidence of thermal local adaptation during the embryonic stage for developmental rate or survival. Within treatments, populations hatched within 1 day of each other, on average, and among treatments, did not differ in survival in response to temperature. We did detect plasticity to temperature; embryos developed 2.5 times longer (189 days) in the coolest regime compared to the warmest regime (74 days). We also detected variation in developmental rates among families within and among temperature regimes, indicating heritable plasticity. Families exhibited a strong positive relationship between thermal variability and phenotypic variability in developmental rate but body length and mass at hatching were largely insensitive to temperature. Overall, our results indicated a lack of thermal local adaptation, but a presence of plasticity in populations experiencing contrasting conditions, as well as family-specific heritable plasticity that could facilitate adaptive change.


Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective.
Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif (182CWAIC186) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), which is known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included RSV r19F because it induces mucus production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wild-type (wt) virus, mice infected with CX4C had a 0.7 to 1.2 log10-fold lower virus titer in the lung at 5 days postinfection (p.i.) and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucus production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1-biased T cell memory response at 75 days p.i. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.IMPORTANCE RSV binds to the corresponding chemokine receptor, CX3CR1, through a CX3C chemokine motif (182CWAIC186) in the G protein. RSV binding to CX3CR1 contributes to disease pathogenesis; therefore, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), known to block binding to CX3CR1, might decrease disease. The effect of this mutation and treatment with the F(ab')2 form of the anti-RSV G 131-2G monoclonal antibody (MAb) show that mutating the CX3C motif to CX4C blocks much of the disease and immune modulation associated with the G protein and should improve the safety and efficacy of a live attenuated RSV vaccine.


Current patterns of bacterial infection in myelomatosis.
Bacterial infections were registered in 39 patients with myelomatosis during 18 months in a prospective study. The infection incidence was 0.80 infections per patient year. 81% of a total of 32 isolates were gram-negative. Urinary tract infections due to Escherichia coli were the most frequent infections. Pneumonia due to Streptococcus pneumoniae were infrequently seen compared to previous studies. Hence, the etiologic spectrum has clearly shifted from gram-positive to gram-negative bacteria in these patients. 53% of all infections were hospital-acquired, and most of these were preceded by instrumentation of the urinary tract or indwelling venous catheters. The infections were nosocomial in 7/9 cases of septicemia registered. All 4 patients who died of infection, suffered from hospital-acquired infections. Patients who attracted infections had significantly higher serum creatinine levels and higher mortality compared to the rest of the patients.


Development of fibrocartilage layers in Achilles tendon enthesis in rabbits.
Objective: The details regarding the development of fibrocartilage layers in Achilles tendon (AT) enthesis are unknown. Therefore, we evaluated the development of fibrocartilage layers in AT enthesis using a rabbit model. Materials and Methods: Forty-eight male Japanese white rabbits were used in this study. Six of them were euthanized at different stages (day 1, and 1, 2, 4, 6, 8, 12, and 24 weeks of age). The proliferation, apoptosis, Sox9-positivity rates, and chondrocyte number were evaluated. Additionally, safranin O-stained glycosaminoglycan (GAG) areas, width of AT enthesis, and calcaneus length were assessed. All parameters were compared to those at 24 weeks of age. Results: The level of chondrocyte apoptosis was high from 1 to 8 weeks of age, and high expression level of Sox9 was maintained from day 1 to 6 weeks of age, which decreased gradually. Safranin O-stained GAG areas increased up to 12 weeks, calcaneus length increased up to 6 weeks, and the width of AT enthesis increased up to 1 week of age. Conclusion: The changes in chondrocyte and extracellular matrix were completed by 8 and 12 weeks of age, respectively. The development of fibrocartilage layers in AT enthesis was completed by 12 weeks of age. Our results contribute to the administration of appropriate treatments based on age and aid in the development of novel methods for regenerating AT enthesis.


Knowledge, Attitude, and Practice Regarding Zika Among Travelers to Brazil: Qatar's Airport Study 2017.
Background The Zika virus has become an international health issue and poses a systematic risk for a growing number of travelers. Qatar is no exception to this status, where its Hamad International Airport (HIA) has become an important hub for many travelers to and from affected countries. Thus, it is a national necessity to determine the knowledge, attitude, and practice of travelers' regarding this emerging disease in the State of Qatar. Methods This was a cross-sectional study that employed a self-administered questionnaire (n=100) and was conducted at Hamad International Airport. Descriptive and inferential statistical tests were applied to analyze the data using the Statistical Package for the Social Sciences (SPSS) (IBM SPSS Statistics 21, IBM Corporation, Armonk, NY, USA, 2014). Results The majority of travelers (75%) reported hearing about the Zika disease prior to their current flight, mainly from the media (73%) and the internet (46%). The majority of participants (69%) knew about the vector-borne transmission and symptomatology of a Zika infection while more than half (54%) correctly identified effective methods to prevent infection. Regarding their attitude, less than two-thirds (58%) of the participants agreed that pregnant women must postpone their travel to any Zika-affected area. Regarding their practice, only a quarter of the sampled travelers (24%) sought pre-travel medical advice before going to Brazil. Comparing the knowledge score among different education levels, we found that high-school students scored significantly better than those with diplomas and bachelors, p=0.042 and p=0.012, respectively. Conclusion The survey findings revealed that the knowledge of Zika infection is low among travelers to Brazil. Thus, stronger efforts to educate travelers about Zika are recommended. It is also vital that travelers be encouraged to seek proper medical advice prior to travel.


Positive affect and the complex dynamics of human flourishing.
Extending B. L. Fredrickson's (1998) broaden-and-build theory of positive emotions and M. Losada's (1999) nonlinear dynamics model of team performance, the authors predict that a ratio of positive to negative affect at or above 2.9 will characterize individuals in flourishing mental health. Participants (N=188) completed an initial survey to identify flourishing mental health and then provided daily reports of experienced positive and negative emotions over 28 days. Results showed that the mean ratio of positive to negative affect was above 2.9 for individuals classified as flourishing and below that threshold for those not flourishing. Together with other evidence, these findings suggest that a set of general mathematical principles may describe the relations between positive affect and human flourishing.


Short-term exposure to an odor increases its subsequent preference in preweanling rats: a descriptive profile of the phenomenon.
Five experiments assessed the change in preference for an ambient odor after a brief period of exposure to that odor. Three minutes of exposure to a novel odor consistently increased subsequent preference for that odor. This effect occurred in preweanling rats 10 and 15 days of age even though, relative to the nest, the conditions of exposure were probably aversive tactually and thermally. There was relatively little variation in this effect between the ages of 10 Days postnatal and adulthood and over exposure durations ranging between 3 and 81 min. Substantial retention of this exposure effect was found for the 10-day-old rat, with no decline in induced preference over a 24-hr period. The effect was unchanged by brief familiarization with the testing situation, but was eliminated by prior aversive experience with the testing situation. These results have implications for the design and interpretation of experiments that test learning and memory of odors, and emphasize generally the facility of the developing rat for processing olfactory information.


[Laparoscopic surgery in the treatment of adrenal pathology: experience with 200 cases].
We report our experience in laparoscopic adrenalectomy, after adopting the laparoscopic technique for 10 years as a primary option for suprarenal surgery. We included 200 laparoscopic adrenal surgeries performed consecutively in 183 patients with surgical adrenal pathology between November 1994 and November 2005. Sixty-seven (36.6%) patients were male and 116 (63.4%) were female, with an average age of 49.1 years (age range 8 months to 78 years). The most frequents clinical diagnosis were hyperaldosteronism (17.5%), metastatic cancer (15.8%), pheochromocytoma (15.3%), Cushing syndrome (7.1%), adrenal cyst (4.9%) and myelolipoma (2.7%). A total of 164 total adrenalectomies, 29 partial adrenalectomies and 7 marsupializations of adrenal cysts were performed. Mean surgical time was 82.6 minutes (range 25 to 240 minutes) and mean hospitalization time was 2.5 days (range 1-10 days). The size of the suprarenal gland and/or tumor varied between 1 and 14 cm (average 5.6 cm). The rate of complication was 6%. In 8 of the patients, there was another laparoscopic procedure besides the adrenal surgery: cholecystectomies (2), marsupialization of a renal cyst (2), block nephrectomy (2), partial nephrectomy for a tumor (1) and pancreatic cystectomy (1). One patient underwent a right laparoscopic adrenalectomy and an ipsilateral percutaneous nephrolithotomy. The accumulated experience with 200 laparoscopic adrenal procedures has allowed the management of endocrine pathologies, such as, aldosteroma, pheochromocytoma, Cushing syndrome and rare entities, such as, cysts, myelolipomas in a suitable manner. Additionally, it has permitted us to extend the benefits of a minimally invasive procedure for large adrenal masses and selected oncology cases.


Clinical features of Fitz-Hugh-Curtis Syndrome in the emergency department.
Fitz-Hugh-Curtis Syndrome (FHCS) is a clinical entity characterized by inflammation of the liver capsule associated with genital tract infection. The aim of this study is to provide physicians with clinical suggestions for diagnostic approaches based on a series of patients who were diagnosed with FHCS. We conducted a retrospective study of patients who were diagnosed with FHCS after presenting to the emergency department (ED). The symptoms, physical examinations, laboratory findings, radiological findings, and progress of the patients were reviewed. During the four-year study period, a total of 82 female patients received a final diagnosis of FHCS in the ED. Chlamydia trachomatis was identified as a pathogen in 89% of the patients. Their clinical characteristics and laboratory findings were described. Fifty-two patients (63.4%) were admitted to the hospital. All of the admitted patients improved after treatment combining antibiotic therapy with conservative care. FHCS should be considered as a differential diagnosis for female patients of childbearing age with right upper abdominal pain. Timely diagnosis using biphasic computed tomography (CT) with arterial and portal phases may help ensure adequate medical treatment as well as avoid invasive procedures.


Atypical coverage in community-acquired pneumonia after outpatient beta-lactam monotherapy.
In adults hospitalized with community-acquired pneumonia (CAP) after >48 h of outpatient beta-lactam monotherapy, coverage of atypical pathogens is recommended based on expert opinion. In a post-hoc analysis of a large study of CAP treatment we included patients who received beta-lactam monotherapy for >48 h before hospitalization. Length of hospital stay (LOS), 30-day mortality, and number of treatment escalations were compared for those that continued beta-lactam monotherapy and those that received atypical coverage at admission. Of 179 patients (median age 66 years (IQR 50-78), 100 (56%) male), 131 (73%) received additional atypical coverage at admission. These patients were younger, had less comorbidities, and longer symptom duration, compared to those that continued beta-lactam monotherapy. In crude analysis, median (IQR) LOS was 6 (4-8) and 6 (4-9) days, mortality was 2% and 4%, and treatment escalations occurred in 8 (17%) and 11 (8%) patients without and with atypical coverage, respectively. Adjusted effect ratios for absence of atypical coverage on LOS, mortality, and treatment escalation were 0.77 (95% CI 0.61-0.97), 0.37 (0.04-3.67), and 2.75 (0.94-8.09), respectively. In adults hospitalized with CAP after >48 h of outpatient beta-lactam monotherapy, not starting antibiotics with atypical coverage was associated with a trend towards more treatment escalations, without evidence of increased LOS or mortality.


Prevalence of Past-Year Mental Disorders in the Canadian Armed Forces, 2002-2013.
More than 40,000 Canadian Armed Forces (CAF) personnel have deployed in support of the mission in Afghanistan since 2002. Over the same period, the CAF strengthened its mental health system. This article explores the effect of these events on the prevalence of past-year mental disorders over the period 2002-2013. The data sources were 2 highly comparable population-based mental health surveys of CAF Regular Force personnel done in 2002 and 2013 (n = 5155 and 6996, respectively). Data were collected via in-person interviews with Statistics Canada personnel using the World Health Organization's Composite International Diagnostic Interview to assess past-year disorders. In 2013, 16.5% had 1 or more of the 6 past-year disorders assessed in the survey, with the most common conditions being major depressive episode (MDE), posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD), which affected 8.0%, 5.3%, and 4.7%, respectively. The prevalence of PTSD, GAD, and panic disorder has increased significantly since 2002 (adjusted odds ratios from logistic regression models = 2.1, 3.0, and 1.9, respectively), while no change was seen for MDE. The comorbidity of mood and anxiety disorders increased significantly over time, being seen in 27.4% and 41.0% of those with mental disorders in 2002 and 2013, respectively. There has been an increase in the prevalence of PTSD and other anxiety disorders and of the extent of comorbidity of mood and anxiety disorders in CAF personnel over the period 2002-2013.


Intraoperative Fracture of a Dual Modular Delta Ceramic Femoral Head During Total Hip Arthroplasty: A Case Report.
A 39-year-old man with cerebral palsy and hip dysplasia status post right Chiari osteotomy presented with right hip osteoarthritis in consultation for total hip arthroplasty (THA). During THA, a Delta ceramic head was misaligned on the taper, but this was obscured by an overlying dual modular polyethylene shell. When we attempted to tap the head onto the taper, fracture occurred requiring revision to a cobalt-chromium head due to slight taper damage. To our knowledge, this is the first reported case of intraoperative fracture of a BIOLOX Delta dual modular head.


Amino acid digestibility of chemically treated and extruder cooked defatted rice polishing.
Rice polishing is a by-product of rice milling. It is a good source of energy and an assortment of amino acids. The anti-nutritive factors associated with rice polishing reduce the availability of amino acids and other nutrients to poultry. Defatted rice polishing (DRP) was chemically treated with 0.4N HCl and 6% H2O2 solutions by soaking in ratio of 1:1.5. After the chemical treatments, one portion of each was further cooked with an extruder cooker maintained at 130oC for 10 seconds. The amino acid digestibility trial of untreated and treated DRP was done using precision fed cockerel assay. Thirty White Leghorn cockerels of 24 weeks of age, having uniform weight, were selected for the experiment and divided into five groups of six cockerels each. Three birds in each group were force-fed treated DRPs @ 25g per bird through crop intubation with the help of a funnel and plunger passed via the oesophagus. The other three were kept without feed throughout the experimental period to measure the endogenous amino acids excreted in the faeces. The excreta voided during 24 hours following force-feeding was collected at 12-hour intervals. The excreta of different groups were weighed, oven-dried and used for amino acid analysis. The results indicated that chemical or chemical plus extrusion cooking decreased the total amino acids present in DRP. The content of several amino acids were reduced as a result of chemical treatment. Further reduction of the amino acid content was observed when the chemically treated DRP were subjected to extrusion cooking. However, the acid (0.4N HCl), acid plus extrusion cooking and 6% H2O2 treatments improved the amino acid digestibility. On the other hand, treating DRP with 6% H2O2 plus extrusion cooking reduced the amino acids digestibility.


Kinetics of corneal transplant rejection in the rat penetrating keratoplasty model.
Kinetic changes of inflammatory cells and major histocompatibility (MHC) antigenic markers in syngeneic and allogeneic corneal grafts in rats were studied. Syngeneic grafts demonstrated mild inflammation in the first week with macrophages and T-helper/inducer cells found in a 2:1 ratio. By week 2 fewer macrophages were seen, and by week 4 no inflammatory cells were seen in the central graft. Central keratocytes and endothelium were negative for class II MHC expression. Significant inflammation persisted adjacent to the wound with macrophages and T-helper/inducer cells seen surrounding the sutures. Allogeneic grafts in the first week demonstrated mild inflammation with macrophages and T-helper/inducer cells in a 2:1 ratio. The central graft in week 2 had increased numbers of T-helper/inducer cells and T-suppressor/cytotoxic cells. By the third and fourth week, the T-suppressor/cytotoxic cells had become the major infiltrating cell. MHC class II antigens were seen on inflammatory cells, keratocytes, donor, and recipient endothelium.


Collisional granular flow as a micropolar fluid.
We show that a micropolar fluid model successfully describes collisional granular flows on a slope. A micropolar fluid is the fluid with internal structures in which coupling between the spin of each particle and the macroscopic velocity field is taken into account. It is a hydrodynamical framework suitable for granular systems which consists of particles with macroscopic size. We demonstrate that the model equations can quantitatively reproduce the velocity and the angular velocity profiles obtained from the numerical simulation of the collisional granular flow on a slope using a simple estimate for the parameters in the theory.


Membrane targeting of ATP-sensitive potassium channel. Effects of glycosylation on surface expression.
Oligosaccharides play significant roles in trafficking, folding, and sorting of membrane proteins. Sulfonylurea receptors (SURx), members of the ATP binding cassette family of proteins, associate with the inward rectifier Kir6.x to form ATP-sensitive potassium channels (K(ATP)). These channels are found on the plasma membrane in many tissues and play a pivotal role in synchronizing electrical excitability with cell metabolic state. Trafficking defects resulting from three independent SUR1 mutations involved in the disease persistent hyperinsulinemic hypoglycemia of infancy have been described. Two of these mutations displayed notable decreases in glycosylation. Here we have investigated the relationship between the two N-linked glycosylation sites (Asn(10) and Asn(1050)) and SUR1 trafficking. Using patch clamp analysis, surface biotinylation, and immunofluorescence microscopy, we demonstrate a significant decrease in surface expression of SUR1 single or double glycosylation site mutants (N10Q,N1050Q) when co-expressed with Kir6.2. Additionally, we show prominent retention within the ER of the SUR1 double glycosylation mutant under the same conditions. Further investigation revealed that mutation of the ER retention signal was able to partially restore surface expression of the SUR1 double glycosylation mutant. These studies suggest that SUR1 glycosylation is a key element for the proper trafficking and surface expression of K(ATP) channels.


Preliminary pharmacological study of the pterocarpans macckian and trifolirhizin isolated from the roots of Ononis vaginalis.
Preliminary pharmacological study was conducted for the pterocarpans macckian (Mac) and trifolirhizin (Trif). The two compounds isolated from Ononis vaginalis were tested for their hepatoprotective effects against CCl4 induced hepatotoxicity in rats. Activity was accessed by measuring liver enzymes and NP-SH groups. Estrogenic activity was expressed as increase in uterine weight of young female rats. Rat paw edema as a model of acute inflammation induced in Wistar rats using carragenan was used to evaluate the anti-inflammatory activity. Percentage inhibition of the aggregation induced by adenosine diphosphate (ADP) to platelets-rich plasma (PRP) obtained from rats was used as measure for antiplatelet aggregation effect. The aglycone Mac was only more active than the glycoside Trif in the anti-inflammatory assay. It resulted in 65.7% reduction in carregeenan induced rat paw edema compares with 79.8% reduction by indomethacin at the same molar concentration. The activity of Trif was about half of that of silymarin in reducing the elevated levels of liver enzymes at the same molar concentration. About 10 fold molar concentration of Trif produced about half fold increase in uterine weight produced by 17beta-estradiol.


Pneumothorax complicating isolated clavicle fracture.
Isolated clavicle fractures are among the commonest of traumatic fractures in the emergency department. Complications of isolated clavicle fractures are rare. Pneumothorax has been described as a complication of a fractured clavicle only rarely in English literature. In all the reported cases, the pneumothorax was treated by a thoracostomy and the clavicle fracture was treated conservatively. In our case, the pneumothorax required a chest drain insertion and the clavicle fracture was treated surgically with good result.


Relationship between Frequency of Sugary Food and Drink Consumption with Occurrence of Dental Caries among Preschool Children in Titiwangsa, Kuala Lumpur.
Dental caries are attributed to various factors including diet. The present crosssectional study determined the frequency of sugary food and drink consumption and defined its relationship to dental caries among preschool children. A total of 50 preschoolers (aged 5-6 years) in three kindergartens of the Department of Community Development (KEMAS) in Titiwangsa, Kuala Lumpur participated in this study. A set of structured questionnaires was used to assess the frequency of sugary food and drink consumption. Dental check ups were performed by a dentist. The dft index (decayed, filled teeth) was used to describe incidence of caries in subjects. Results showed that 62% of the subjects had dental caries. with the mean dft score being 3.72. The frequency of sugary food consumption by the majority of subjects was 2 times a day, while the frequency of sugary drink consumption was more than 3 times a day. There was no significant relationship between frequency of sugary food and drink consumption with incidence of caries. Subjects with high dft scores were more likely to report dental pain. The prevalence of dental caries in preschoolers in this study was high, indicating a need for effective dental health promotion to improve dental health status of this age group.


Inflammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection.
Nine patients with inflammatory demyelinating polyneuropathies (IDP) were found to have human T-cell lymphotropic virus type III (HTLV-III) infection. The 8 men, 6 of whom were homosexual, and 1 woman, a former intravenous drug user, presented with progressive weakness. Two had lymphadenopathy but all were otherwise asymptomatic. Six had chronic IDP and 3 had Guillain-Barré syndrome. In addition to an elevated cerebrospinal fluid (CSF) protein level (mean, 193 mg/dl), most patients had cerebrospinal fluid pleocytosis (mean, 23 cells/mm3), a distinctive feature. All had reduced T4:T8 T-cell ratios. Results of nerve conduction studies were characteristic of demyelination. Nerve biopsies revealed intense inflammatory cell infiltrates and macrophage-mediated demyelination. The patients recovered either spontaneously or following treatment with corticosteroids or plasmapheresis. During a mean interval of 20 months after presentation, only 1 patient had developed acquired immune deficiency syndrome. Patients with HTLV-III infection have disordered immune function, and the mechanism of the development of the IDP is likely to be immunopathogenic. As a result of our experience, we suggest that all patients with IDP be tested for evidence of HTLV-III infection. We also found, although in uncontrolled trials, that treatment with either prednisone or plasmapheresis was followed by clinical improvement; since plasmapheresis is not likely to further depress cell-mediated immunity, we suggest that it be the initial therapy.


Differentiated Fractionation of Various Biomass Resources by p-Toluenesulfonic Acid at Mild Conditions.
Biomass is the ideal substitute for petrochemical resources because of its renewable and abundant sources. p-Toluenesulfonic acid (p-TsOH) can effectively separate lignin from biomass under mild conditions, so it is highly expected in biomass fractionation to improve the utilization efficiency. In this study, we investigated the effect of p-TsOH differentiated fractionation of poplar sawdust, eucalyptus sawdust, and rice straw below 100 °C. According to the experimental results, upon pretreatment by p-TsOH of the three kinds of raw biomass, most of the lignin and hemicellulose of poplar sawdust and eucalyptus sawdust were removed, whereas the cellulose was retained, but most of the hemicellulose and cellulose of rice straw were kept, whereas the lignin was removed at similar conditions. The structures and compositions of pretreatment residues, lignin, and hemicellulose extracted from raw biomass were characterized by XRD, FTIR, HSQC-NMR, XPS, and SEM. The differentiated fractionation mechanism of biomass was analyzed. A better recognition and understanding of the factors affecting biomatrix opening and fractionation will allow for the identification of new pretreatment strategies that improve biomass utilization and permit the rational enzymatic hydrolysis of cellulose.


[Small cell lung cancer associated with multiple paraneoplastic syndromes].
We report the case of a patient presenting with multiple severe electrolyte disturbances who was subsequently found to have small cell lung cancer. Upon further evaluation, she demonstrated three distinct paraneoplastic processes, including the syndrome of inappropriate antidiuretic hormone, Fanconi syndrome, and an inappropriate elevation in fibroblast growth factor-23 (FGF23). The patient underwent one round of chemotherapy, but she was found to have progressive disease. After 36 days of hospitalization, the patient made the decision to enter hospice care and later she expired.


Intravesicular cidofovir for BK hemorrhagic cystitis in pediatric patients after hematopoietic stem cell transplant.
BK virus hemorrhagic cystitis is a complication of HCST. Response to IV cidofovir is unpredictable, and treatment carries risk of toxicity. We report the largest series of pediatric patients with BKHC after HSCT successfully treated with intravesicular cidofovir. There was no significant decrease in urine or plasma BK PCR. There was significant decrease in pain score on days 3 and 7, with associated decrease in morphine use. No patients experienced toxicities associated with IV cidofovir. Intravesicular cidofovir appears to be safe and effective for symptomatic treatment of BKHC in pediatric patients after HSCT.


Physician assistant education in Germany.
The first physician assistant (PA) program in Germany began in 2005. As of 2013 there are three PA programs operational, with a fourth to be inaugurated in the fall of 2013. The programs have produced approximately 100 graduates, all with a nursing background. The PA model of shifting tasks from medical doctors to PAs appears to be growing among senior physicians and hospital administrators. While the development of a German PA movement is in its nascent stage, the training, deployment, and evolution of PA training programs appears underway.


Observation of magnetocoriolis waves in a liquid metal Taylor-Couette experiment.
The first observation of fast and slow magnetocoriolis (MC) waves in a laboratory experiment is reported. Rotating nonaxisymmetric modes arising from a magnetized turbulent Taylor-Couette flow of liquid metal are identified as the fast and slow MC waves by the dependence of the rotation frequency on the applied field strength. The observed slow MC wave is damped but the observation provides a means for predicting the onset of the magnetorotational instability.


Aging in dense suspensions of soft thermosensitive microgel particles studied with particle-tracking microrheology.
Using particle tracking microrheology, we studied the glass transition in dense suspensions of thermosensitive microgel particles. These suspensions can be tuned reversibly between the glass state at low temperature and the liquid state at high temperature. In the glass state, the ensemble averaged mean squared displacements (MSDs) of added fluorescent tracer particles depend on the age of the suspension. We also determine the local viscoelastic moduli, G' and G", from the MSDs using the Generalized Stokes-Einstein Relation and compare them to the bulk moduli, measured using conventional rheometry. With particle tracking, one probes the viscoelastic moduli in a lower frequency range than with macrorheology, which makes it possible to determine the mean relaxation time that is inaccessible with macrorheology. In the glass state, the mean relaxation time increases linearly with the age of the sample and the short time particle displacement distributions are non-Gaussian, indicating inhomogeneity of the system. The observed difference between conventional and microrheology is explained quantitatively assuming that the tracer particles are surrounded by a viscoelastic liquid shell, different from the bulk.


Asthma and viruses: is there a relationship?
Asthma is a multifactorial disease in which many factors play a role in its development and exacerbations. Viral infections are known to be the main cause of asthmatic exacerbations and are often the first manifestation of asthma in preschool age. However, there is much evidence suggesting a role of viral infections even in asthma development. Respiratory Syncytial Virus (RSV). has been first associated with an increased risk to develop asthma, but recently new viruses have been proposed to be involved in asthma pathogenesis. Further studies will be needed to demonstrate a causative role of viral infections in asthma development, in order to implement preventive strategies in high-risk children.


Draft Genome Sequences of 256 Salmonella enterica subsp. enterica Serovar Enteritidis Strains Isolated from Humans, Food, Chickens, and Farm Environments in Brazil.
Salmonella enterica subsp. enterica serovar Enteritidis emerged in the late 1980s as the most isolated Salmonella serovar worldwide. Here, we report the draft genomes of 256 S Enteritidis strains isolated from humans, food, chickens, and farm environments in Brazil. These draft genomes will help enhance our understanding of this serovar in Brazil.


Simple assay of estrogen in urine during pregnancy by means of latex agglutination inhibition reaction.
A simple and rapid method, latex agglutination inhibition reaction (LAIR), using anti-estriol-16-glucuronide coupled with BSA for estimating estrogen in urine has been developed. Agglutination of the latex reagent by the antiserum occurs within 3 min. The agglutination, however, was completely inhibited by 100 ng/ml or more of estriol. There was a good correlation in results obtained by LAIR and by colorimetry, RIA and GLC. Urine samples (3329) obtained at various gestational weeks were assayed. The samples from 94% of the normal pregnant patients in the third trimester revealed 10 micrograms/ml or more of estrogens. Although the assay is semiquantitative, it may be useful in screening for fetal well-being in high-risk pregnancies.


Fetal micrognathia: associated anomalies and outcome.
The purpose of this study was to evaluate the spectrum of sonographic findings, karyotypic abnormalities, and clinical outcome in cases of fetal micrognathia. Twenty fetuses with sonographically identified micrognathia were identified between 15 weeks' gestation and term. Five of 20 fetuses (25%) had abnormal karyotypes, including three with trisomy 18 and one each with trisomy 13 and trisomy 9. Sixteen of the 20 fetuses (80%) did not survive: Ten died in utero or during the neonatal period, and six pregnancies were terminated electively. Three of 20 fetuses (15%) had micrognathia as the sole sonographic finding. Two of these fetuses survived, one with growth retardation and one with Pierre Robin syndrome. Thirteen of 20 pregnancies were complicated by polyhydramnios. The diversity of the syndromes represented in our cases of micrognathia indicates a wide breadth of possible diagnoses when micrognathia is encountered prenatally. The poor prognosis and associated karyotypic and lethal anomalies are remarkable, with survival of only four of 20 fetuses in this report.


Ganoderic acid targeting nuclear factor erythroid 2-related factor 2 in lung cancer.
Lung cancer causes huge mortality worldwide, and targeting new pathway may provide an alternative in modulating signaling in cancer. Nuclear factor erythroid 2-related factor 2 is the major regulator of endogenous and exogenous stress by activating numerous antioxidant genes critical in cancer, Alzheimer's, Parkinson's, and inflammatory bowel diseases. Ganoderic acid is a triterpene from basiodiomycetes fungus Ganoderma lucidum with numerous therapeutic effects. In this study, ganoderic acid and its 50 isomers and natural activators were docked by receptor-based molecular docking using Maestro 9.6 (Schrödinger Inc.) in the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 signaling pathway. The receptor-based molecular docking reveals the best binding interaction of nuclear factor erythroid 2-related factor 2 and ganoderic acid A with GScore (-9.69) (kcal/mol), Lipophilic EvdW (-1.83), Electro (-0.72), Glide emodel (-73.369), H bond (-1.1), molecular mechanics/generalized Born surface area (-75.541) with Leu 718, Asp 800, Cys 797 residues involved in hydrogen bonding. The calculated docking energy highlights the lipophilic, hydrogen bonding, pi-pi stacking interactions, and non-covalent bonding. Analysis showed the involvement of cysteine and serine residues which were crucial in the activation and translocation from cytoplasm to the nucleus in the nuclear factor erythroid 2-related factor 2 signaling process. The molecular docking tool QikProp analyzed the absorption, distribution, metabolism, excretion, and toxicity but needs some modifications in their structure to satisfy Lipinski's rule. Ganoderic acid A is a best docked isoform which inhibits the cell proliferation, viability, migration, and reactive oxygen species and messenger RNA expression of nuclear factor erythroid 2-related factor 2 in H460 cells.


Chronopharmacokinetic study of gentamicin in dogs.
The purpose of this experiment was to determine whether the time of day of single intravenous doses of gentamicin affects the drug's pharmacokinetics in dogs maintained under a 12 h light (08:00 to 20:00 h), 12 h dark (20:00 to 08:00 h) cycle. Using a crossover design, 6 mixed-breed male dogs received a single dose of 2 mg/kg of gentamicin at 8:00 or 20:00 h. Serial blood samples were collected and pharmacokinetic parameters were calculated following each timed dose. The concentration of the antibiotic was lower following the 08:00 h compared to the 20:00 h administration. When gentamicin was administered at 20:00 h, the initial concentration, mean residence time, and area under the disposition curve were significantly higher (p < 0.05) and the apparent volume of distribution of the central compartment, apparent volume of distribution, apparent volume of distribution at steady-state, and total body clearance (1.73+/-0.55 at 20:00 h versus 3.31+/-0.67 L/min/kg at 08:00 h) were significantly lower than for the 08:00 h administration (p < 0.05). Our results show that the pharmacokinetics of gentamicin exhibits significant temporal variation when administered to dogs at different times of day.


Targeting dendritic cells for priming cellular immune responses.
The cardinal role of dendritic cells (DC) in priming adaptive immunity and in orchestrating immune responses against all classes of pathogens and also against tumors is well established. Their unique potential both to maintain self-tolerance and to initiate protective immune responses against foreign and/or dangerous structures is based on the functional diversity and flexibility of these cells. Tissue DC lining antigenic portals such as mucosal surfaces and the skin are specialized to take up a wide array of compounds including proteins, lipids, carbohydrates, glycoproteins, glycolipids and oligonucleotides, particles carrying such structures and apoptotic or necrotic cells. This process is facilitated by specialized receptors with high endocytic capacity, which provides potential targets for delivering designed molecules. The best route for targeting B- and/or T cell epitopes, however, is still the subject of intense investigation. Immature DC, which reside in various tissues, can be activated by pathogens, stress and inflammation or modified metabolic products, which induce mobilization of cells to draining lymph nodes where they act as highly potent professional antigen presenting cells. This is brought about by the ability to present their accumulated intracellular content for both CD4+ helper (Th) and CD8+ cytotoxic/cytolytic T lymphocytes (Tc/CTL). Engulfed proteins are processed intracellularly and their peptide fragments are transported to the cell surface in the context of major histocompatibility complex encoded class I and II molecules for presentation to Th cells and CTLs, respectively. The T cell priming capacity of DC, however, depends not only on antigen presentation but also on other features of DC. Human monocyte-derived DC provide an excellent tool to study the internalizing, antigen-presenting and T cell-activating functions of DC at their immature and activated differentiation states. These biological activities of DC, however, are highly dependent on their migratory potential from the peripheral non-lymphoid tissues to the lymph nodes, on the expression of adhesion molecules, which support the interaction of DC with T lymphocytes, and the cytokines secreted by DC, which polarize immune responses to Th1-mediated cellular or Th2-mediated antibody responses. These results altogether demonstrate that monocyte-derived DC are useful candidates for in vitro or in vivo targeting of antigens to induce efficient adaptive immune responses against pathogens and also against tumors.


XMRV and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Appears Unreliable.
A few years ago, a highly significant association between the xenotropic murine leukemia virus-related virus (XMRV) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a complex debilitating disease of poorly understood etiology and no definite treatment, was reported in Science, raising concern for public welfare. Successively, the failure to reproduce these findings, and the suspect that the diagnostic PCR was vitiated by laboratory contaminations, led to the retraction of the paper. Notwithstanding, XMRV continued to be the subject of researches and public debates. Occasional positivity in humans was also detected recently, even if the data always appeared elusive and non-reproducible. In this study, we discuss the current status of this controversial association and propose that a major role in the unreliability of the results was played by the XMRV genomic composition in itself. In this regard, we present bioinformatic analyses that show: (i) aspecific, spurious annealings of the available primers in multiple homologous sites of the human genome; (ii) strict homologies between whole XMRV genome and interspersed repetitive elements widespread in mammalian genomes. To further detail this scenario, we screen several human and mammalian samples by using both published and newly designed primers. The experimental data confirm that available primers are far from being selective and specific. In conclusion, the occurrence of highly conserved, repeated DNA sequences in the XMRV genome deeply undermines the reliability of diagnostic PCRs by leading to artifactual and spurious amplifications. Together with all the other evidences, this makes the association between the XMRV retrovirus and CFS totally unreliable.