Occupational health in Egypt.
This review aims to evaluate current occupational health services (OHS) in Egypt. The authors begin with a background on the geography, population, and economy, and then briefly describe the labor force. They discuss the legislative aspects of OHS (including health insurance) and the environment; OHS training and education; and activities such as research, inspection, environmental monitoring, and management of occupational diseases. Occupational accidents and diseases, registered during 2000, are analyzed. Problems with OHS administration in Egypt are presented, along with relevant countermeasures. Various promotion and support measures for administrative policy are prioritized and discussed.


Follow-up of Prostatectomy versus Observation for Early Prostate Cancer.
We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality. From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and the main secondary outcome, prostate-cancer mortality. We describe disease progression, treatments received, and patient-reported outcomes through January 2010 (original follow-up). During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364 men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation (absolute difference in risk, 5.5 percentage points; 95% confidence interval [CI], -1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, -0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, -10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, -11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression. Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years. After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression. (Funded by the Department of Veterans Affairs and others; PIVOT ClinicalTrials.gov number, NCT00007644 .).


Elevated levels of AST, ALT, and CPK · no family history of liver disease · Dx?
A 26-year-old healthy male veteran with bipolar disorder and post-traumatic stress disorder was referred for a gastroenterology consultation after a routine laboratory evaluation revealed elevated levels of aspartate aminotransferase, 1040 IU/L (normal range, 10-40 IU/L), and alanine aminotransferase, 334 IU/L (normal range, 7-56 IU/L). He had been taking divalproex and ziprasidone for the previous 2 years, during which time liver test results had been normal.


Postmortem MRI and histopathology of white matter changes in Alzheimer brains. A quantitative, comparative study.
To evaluate whether magnetic resonance imaging (MRI) of white matter changes in Alzheimer's disease either under- or overestimates the findings on neuropathology. Postmortem MRI and neuropathological examination were performed on 6 brains from elderly individuals with a postmortem diagnosis of AD. Using a specially designed brain slicer, the brains were cut corresponding to the MRI images, and stained by Luxol Fast Blue. Quantitative analysis of white matter changes on MRI and neuropathology was performed using stereological principles. Measures from MRI and pathology were highly correlated (r(2) = 0.71). However, pathology showed significantly more extensive changes than did MRI in all cases, with a mean of 54% larger areas. The lesions not identified with MRI represented, however, only minor changes with lower intensity of myelin staining and with an accentuation of the distance between fibres but with preserved axonal network and glial cell density.


Transcriptional activation of mouse mast cell Protease-7 by activin and transforming growth factor-beta is inhibited by microphthalmia-associated transcription factor.
Previous studies have revealed that activin A and transforming growth factor-beta1 (TGF-beta1) induced migration and morphological changes toward differentiation in bone marrow-derived cultured mast cell progenitors (BMCMCs). Here we show up-regulation of mouse mast cell protease-7 (mMCP-7), which is expressed in differentiated mast cells, by activin A and TGF-beta1 in BMCMCs, and the molecular mechanism of the gene induction of mmcp-7. Smad3, a signal mediator of the activin/TGF-beta pathway, transcriptionally activated mmcp-7. Microphthalmia-associated transcription factor (MITF), a tissue-specific transcription factor predominantly expressed in mast cells, melanocytes, and heart and skeletal muscle, inhibited Smad3-mediated mmcp-7 transcription. MITF associated with Smad3, and the C terminus of MITF and the MH1 and linker region of Smad3 were required for this association. Complex formation between Smad3 and MITF was neither necessary nor sufficient for the inhibition of Smad3 signaling by MITF. MITF inhibited the transcriptional activation induced by the MH2 domain of Smad3. In addition, MITF-truncated N-terminal amino acids could associate with Smad3 but did not inhibit Smad3-mediated transcription. The level of Smad3 was decreased by co-expression of MITF but not of dominant-negative MITF, which resulted from proteasomal protein degradation. The changes in the level of Smad3 protein were paralleled by those in Smad3-mediated signaling activity. These findings suggest that MITF negatively regulates Smad-dependent activin/TGF-beta signaling in a tissue-specific manner.


Focal 123I-MIBG Uptake in the Medial Segment of the Normal Liver.
An 84-year-old man with parkinsonism was referred for I-MIBG scintigraphy. Abnormal uptake in the right upper abdomen was incidentally seen in planar image, and SPECT revealed focal uptake in the medial segment (S4) of the liver. Subsequent triple-phase contrast-enhanced CT showed no evidence of hepatic tumors, although in the arterial phase, there were an enhanced region corresponding to the uptake area and the enhanced vein of Sappey that flowed into S4. In this case, the focal I-MIBG uptake would be attributable to hemodynamic change in the liver.


Vibratory patterns of the vocal folds during pulse register phonation.
The purpose of the present study was to investigate the vibratory patterns of the vocal folds during pulse register phonation. Glottal area-time functions were calculated from three high speed laryngeal films (4000 frames/second) obtained during phonation of the schwa vowel in pulse register by a normally hearing and speaking adult female. The results for the first film indicated that each of 35 consecutive vibratory cycles of the vocal folds consisted of a single opening/closing gesture followed by a lengthy closed phase. The analysis of the second film revealed that each of 33 consecutive vibratory cycles consisted of a double opening/closing vocal fold pattern, followed by a long closed phase. For the third film, the results indicated that each of 26 consecutive vibratory cycles of the vocal folds consisted of either a double or triple opening/closing gesture followed by a lengthy closed period. From these data, it appears that one of the physiological descriptors of pulse phonation is multiple, as well as single, vocal fold vibratory patterning.


Epidemiology of preterm birth and its clinical subtypes.
Preterm birth (<37 weeks) complicates 12.5% of all deliveries in the USA, and remains the leading cause of perinatal mortality and morbidity, accounting for as many as 75% of perinatal deaths. Despite the recent temporal increase in preterm birth, efforts to understand the problem of prematurity have met with little success. This may be attributable to the under-appreciation of the etiologic heterogeneity of preterm birth as well as the heterogeneity in its underlying clinical presentations--spontaneous onset of labor, preterm premature rupture of membranes, and medically indicated preterm birth. In this paper, we review data regarding preterm births with particular focus on its incidence, temporal trends, and recurrence. Studies of births from the USA indicate that the recent temporal increase in the overall preterm birth rate is driven by an impressive concomitant increase in medically indicated preterm birth. However, the largest temporal decline in perinatal mortality has also occurred among medically indicated preterm births (relative to other clinical subtypes), suggesting that these obstetric interventions at preterm gestational ages are associated with a reduction in perinatal mortality. Recent data indicate that spontaneous preterm birth is not only associated with increased recurrence of spontaneous, but also medically indicated, preterm birth, and vice versa. This suggests that the clinical subtypes may share common underlying etiologies. Since medically indicated preterm birth accounts for as many as 40% of all preterm births, efforts to understand the reasons for such interventions and their impact on short- and long-term morbidity in newborns is compelling. Further research is necessary in order to understand the mechanisms and etiology of preterm birth, thus leading to the possibility of effective preventive or therapeutic strategies.


Optimizing Time Resolution Electronics for DMAPs.
Depleted Monolithic Active Pixel Sensors (DMAPSs) are foreseen as an interesting choice for future high-energy physics experiments, mainly because of the reduced fabrication costs. However, they generally offer limited time resolution due to the stringent requirements of area and power consumption imposed by the targeted spatial resolution. This work describes a methodology to optimize the design of time-to-digital converter (TDC)-based timing electronics that takes advantage of the asymmetrical shape of the pulse at the output of the analog front-end (AFE). Following that methodology, a power and area efficient implementation fully compatible with the RD50-MPW3 solution is proposed. Simulation results show that the proposed solution offers a time resolution of 2.08 ns for a range of energies from 1000 e- to 20,000 e-, with minimum area and zero quiescent in-pixel power consumption.


Jorunnamycin A from Xestospongia sp. Suppresses Epithelial to Mesenchymal Transition and Sensitizes Anoikis in Human Lung Cancer Cells.
Metastasis is a key driving force behind the high mortality rate associated with lung cancer. Herein, we report the first study revealing the antimetastasis activity of jorunnamycin A, a bistetrahydroisoquinolinequinone isolated from a Thai blue sponge Xestospongia sp. evidenced by its inhibition of epithelial to mesenchymal transition (EMT), sensitization of anoikis, and suppression of anchorage-independent survival in human lung cancer cells. Treatment with jorunnamycin A (0.05-0.5 μM) altered the expression of p53 and Bcl-2 family proteins, particularly causing the down-regulation of antiapoptosis Bcl-2 and Mcl-1 proteins. Under detachment conditions for 12 h, jorunnamycin A-treated cells exhibited diminution of pro-survival proteins p-Akt and p-Erk as well as the survival-promoting factor caveolin-1. Corresponding with the inhibition on the Akt and Erk pathway as well as activation of p53, there was an increase in the epithelial marker E-cadherin and a remarkable decrease of EMT markers and associated proteins including vimentin, snail, and claudin-1. As the loss of anchorage dependence is an important barrier to metastasis, the observed inhibitory effects of jorunnamycin A on the coordinating networks of EMT and anchorage-independent growth emphasize the potential development of jorunnamycin A as an effective agent against lung cancer metastasis.


Subunit composition of neurotransmitter receptors in the immature and in the epileptic brain.
Neuronal activity is critical for synaptogenesis and the development of neuronal networks. In the immature brain excitation predominates over inhibition facilitating the development of normal brain circuits, but also rendering it more susceptible to seizures. In this paper, we review the evolution of the subunit composition of neurotransmitter receptors during development, how it promotes excitation in the immature brain, and how this subunit composition of neurotransmission receptors may be also present in the epileptic brain. During normal brain development, excitatory glutamate receptors peak in function and gamma-aminobutiric acid (GABA) receptors are mainly excitatory rather than inhibitory. A growing body of evidence from animal models of epilepsy and status epilepticus has demonstrated that the brain exposed to repeated seizures presents a subunit composition of neurotransmitter receptors that mirrors that of the immature brain and promotes further seizures and epileptogenesis. Studies performed in samples from the epileptic human brain have also found a subunit composition pattern of neurotransmitter receptors similar to the one found in the immature brain. These findings provide a solid rationale for tailoring antiepileptic treatments to the specific subunit composition of neurotransmitter receptors and they provide potential targets for the development of antiepileptogenic treatments.


Comprehensive portrait of recurrent glioblastoma multiforme in molecular and clinical characteristics.
Glioblastoma multiforme is the most common primary malignant brain tumor in adults. In addition to poor response to treatment, a high recurrence rate contributes to the poor prognosis. The purpose of this study was to investigate the genetical and clinical characteristics of recurrent glioblastoma. We used whole transcriptome sequencing data to examine the distribution of molecular subtypes and gene signatures in 22 recurrent glioblastoma taken from the Chinese population, and further analyzed biological progression of the tumors, when compared with primary glioblastoma. The proportion of the classical subtype in recurrent ones (22%) was lower than that in primary glioblastoma (36%). The frequency of IDH1 mutations in recurrent glioblastomas was nearly twice that in primary glioblastomas. TP53 mutations were fewer in proneural recurrent glioblastomas (20%) but frequent in classical recurrent glioblastomas (80%). The most common sites of recurrent glioblastomas were the temporal lobe (41%). In patients diagnosed with recurrent glioblastoma multiforme, 64% were younger than 50 years. Gene set enrichment analysis revealed that chromatin fracture, repair, and remodeling genes were enriched in recurrent glioblastoma. Our results highlight the differences in clinical features, molecular subtypes and gene alterations between primary and recurrent glioblastoma and may be helpful for targeted therapy for recurrent glioblastoma.


Vibrationally inelastic collisions in H+ +CO system: comparing quantum calculations with experiments.
State-resolved cross beam experiments [H. Udseth et al., J. Chem. Phys. 60, 3051 (1974); J. Krutein and F. Linder, J. Chem. Phys. 71, 599 (1979); G. Niedner-Schatteburg and J. P. Toennies, Adv. Chem. Phys. LXXXII, 553 (1992)], coupled with proton energy loss spectroscopy for the inelastic scattering of H(+) from CO in the collision range of 10-30 eV show very low vibrational excitation of the target molecule. Stimulated by the experimentally observed low vibrational inelasticity in the system the ground and the first two low-lying excited electronic potential-energy surfaces have been computed using the ab initio multireference configuration interaction method. Quantum dynamics has been performed on the ground potential energy surface in the framework of vibrational close-coupling rotational infinite-order sudden approximation. The various computed dynamical attributes such as differential and integral cross sections, and average vibrational energy transfer are analyzed in detail, and compared successfully with the available experimental results.


Triplet superconductivity in 3D Dirac semi-metal due to exchange interaction.
Conventional phonon-electron interaction induces either triplet or one of two (degenerate) singlet pairing states in time reversal and inversion invariant 3D Dirac semi-metal. Investigation of the order parameters and energies of these states at zero temperature in a wide range of values of chemical potential μ, the effective electron-electron coupling constant λ and Debye energy TD demonstrates that when the exchange interaction is neglected the singlet always prevails, however, in significant portions of the (μ, λ, TD) parameter space the energy difference is very small. This means that interactions that are small, but discriminate between the spin singlet and the spin triplet, are important in order to determine the nature of the superconducting order there. The best candidate for such an interaction in the materials under consideration is the exchange (the Stoner term) characterized by constant λex. We show that at values of λex, much smaller than ones creating Stoner instability to ferromagnetism λex ∼ 1, the triplet pairing becomes energetically favored over the singlet ones. The 3D quantum critical point at μ = 0 is considered in detail. This can be realized experimentally in optically trapped cold atom systems.


Systematic sequencing of cDNA clones using the transposon Tn5.
In parallel with the production of genomic sequence data, attention is being focused on the generation of comprehensive cDNA-sequence resources. Such efforts are increasingly emphasizing the production of high-accuracy sequence corresponding to the entire insert of cDNA clones, especially those presumed to reflect the full-length mRNA. The complete sequencing of cDNA clones on a large scale presents unique challenges because of the generally small, yet heterogeneous, sizes of the cloned inserts. We have developed a strategy for high-throughput sequencing of cDNA clones using the transposon Tn5. This approach has been tailored for implementation within an existing large-scale 'shotgun-style' sequencing program, although it could be readily adapted for use in virtually any sequencing environment. In addition, we have developed a modified version of our strategy that can be applied to cDNA clones with large cloning vectors, thereby overcoming a potential limitation of transposon-based approaches. Here we describe the details of our cDNA-sequencing pipeline, including a summary of the experience in sequencing more than 4200 cDNA clones to produce more than 8 million base pairs of high-accuracy cDNA sequence. These data provide both convincing evidence that the insertion of Tn5 into cDNA clones is sufficiently random for its effective use in large-scale cDNA sequencing as well as interesting insight about the sequence context preferred for insertion by Tn5.


Effect of blood viscosity decrease on exercise ST segment depressions in hyperlipidemia.
In order to study the possible relation between blood viscosity and exercise ST segment depressions in hyperlipidemia the former was lowered by infusion of dextran and by treatment with clofibrate 1 g twice daily. Acute decrease of blood viscosity with dextran infusion in two cases increased the ST segment depressions during work. Nine subjects with asymptomatic hyperlipidemia, hyperfibrinogenemia and exercise ST segment depressions were treated with clofibrate in order to lower plasma fibrinogen and serum lipids. This did not influence the area of ST segment depression with either Frank leads or CH leads as determined by computer estimation. As the plasma fibrinogen level is of major importance for the blood viscosity it is concluded that the ischaemic ST segment depression seen in hyperlipidemia is not due to increased blood viscosity but more likely to a premature subclinical coronary atherosclerosis.


Extrapolation of water and formaldehyde harmonic and anharmonic frequencies to the B3LYP/CBS limit using polarization consistent basis sets.
The harmonic and anharmonic frequencies of fundamental vibrations in formaldehyde and water were successfully estimated using the B3LYP Kohn-Sham limit. The results obtained with polarization- and correlation-consistent basis sets were fitted with a two-parameter formula. Anharmonic corrections were obtained by a second order perturbation treatment (PT2). We compared the performance of the PT2 scheme on the two title molecules using SCF, MP2 and DFT (BLYP, B3LYP, PBE and B3PW91 functionals) methods combined with polarization consistent pc-n (n = 0, 1, 2, 3, 4) basis sets, Dunning's basis sets (aug)-cc-pVXZ where X = D, T, Q, 5, 6 and Pople's basis sets up to 6-311++G(3df,2pd). The influence of SCF convergence level and density grid size on the root mean square of harmonic and anharmonic frequency deviations from experimental values was tested. The wavenumber of formaldehyde CH(2) anharmonic asymmetric stretching mode is very sensitive to grid size for large basis sets; this effect is not observed for harmonic modes. BLYP-calculated anharmonic frequencies consistently underestimate observed wavenumbers. On the basis of formaldehyde anharmonic frequencies, we show that increasing the Pople basis set size does not always lead to improved agreement between anharmonic frequencies and experimental values.


Effect of chronic theophylline therapy on brain blood flow and function in adult asthmatics.
The impact of theophylline therapy on neuropsychological (NP) function in adult asthmatics is unclear. Additionally, whether the previously demonstrated acute reduction in cerebral blood flow (CBF) persists with continued administration of theophylline, or whether accommodation develops, has not been previously reported. We examined the effects of chronic theophylline administration on CBF and NP function in adults with mild to moderate asthma. Sixty adult patients with mild to moderate asthma were entered into this double-blind, placebo-controlled, crossover, random sequence study. Subjects received theophylline or placebo for 6 wk interposed with a 2-wk washout period. At the conclusion of Week 1 and Week 6 of each drug phase, patients received NP testing, and CBF was determined using the 133Xenon washout method. Forty-three patients completed the study. Theophylline administration was associated with small (6%), but statistically significant, reductions in CBF after both 1 and 6 wk of treatment. No differences consequent to theophylline administration were observed in any of the tests of NP function after 1 or 6 wk of therapy. While CBF was decreased after theophylline, the changes were small compared with previously reported decrements in CBF immediately after theophylline administration.


Surface roughness of various packable composites.
Packable composite restorations have become a popular alternative to dental amalgam restorations in posterior teeth. A drawback inherent to composites is their difficulty in polishing, which often results in a dull or rough surface. This study compared the surface roughness of a resin-based hybrid composite material and five packable resin-based composites polished with either aluminum oxide disks or a rubber polishing system. Sixteen specimens of each of the six composite materials were polished with either Sof-Lex XT disks or Enhance rubber polishers followed by fine and superfine polishing pastes. The specimens were evaluated for surface roughness using surface profilometry. Mean values were calculated for each material type and method of polishing. Data were subjected to a two-way ANOVA. Post hoc comparison was accomplished using Tukey's HSD. No significant difference in surface roughness was detected among polishing techniques (p=0.067); however, a strong trend-that aluminum oxide disks provided a smoother surface than rubber polishers in five out of six materials-was noted.


Evaluation of berberine pellet effect on clinical recovery time in COVID-19 outpatients: A pilot clinical trial.
Severe disease onset of COVID-19 may result in alveolar injury and respiratory failure. Apoptosis and inflammation are the main causes of respiratory distress syndrome. Berberine is used in medicine as an analgesic, anti-asthmatic, anti-inflammatory, and antiviral. In the current investigation, the effect of berberine on COVID-19 outpatients was studied. The present clinical trial was performed on 40 outpatients who were randomly assigned to berberine (300 mg, TID, 2 weeks) (n=19) or placebo groups (n=21). Both groups received standard therapy and they were monitored on days 3, 7, and 14 after the beginning of the therapy for clinical symptoms' improvement, quantitative CRP, lymphopenia, CBC, and SpO2. The severity and frequency of these symptoms and the level of the parameters were statistically compared between the two groups. On days (0, 3, 7, and 14, there was no significant difference between the berberine and placebo groups in the improvement of clinical symptoms (cough, shortness of breath, nausea, loss of smell and taste, diarrhea, dizziness, sore throat, stomachache, body aches, and body temperature), quantitative CRP, lymphopenia, WBC, neutrophils, platelets, or SpO2. Berberine (300 mg, TID, two weeks) is ineffective in treating COVID-19. More research with a larger sample size is needed to investigate different berberine dosages in other pharmaceutical formulations.


Efficacy and safety of LASIK in 10,052 eyes of 5081 myopic Chinese patients.
To analyze the outcomes and incidence of postoperative complications in a large series of patients undergoing LASIK for myopia. All 5081 patients (10,052 eyes) diagnosed with myopia at The Third Hospital of Handan, China, from September 2003 through March 2005 were studied. All study eyes underwent LASIK with 1-month follow-up. Spherical equivalent refraction, best spectacle-corrected visual acuity (BSCVA), and uncorrected visual acuity (UCVA) were measured before and after surgery and intra- and postoperative complications were recorded. Uncorrected visual acuity at 1-month follow-up of 9555 (95.1%) eyes reached or exceeded the preoperative BSCVA. Hemorrhage of corneal limbus during surgery occurred in 1060 (10.5%) eyes, Sands of Sahara syndrome occurred in 232 (2.3%) eyes, interface infection responsive to treatment occurred in 4 (0.04%) eyes, and epithelial ingrowth occurred in 1 (0.01%) eye. LASIK is a safe and effective method for the treatment of myopia.


Radiation-induced renal damage: the effects of hyperfractionation.
The response of mouse kidneys to multifraction irradiation was assessed using three nondestructive functional end points. A series of schedules was investigated giving 1, 2, 4, 8, 16, 32, or 64 equal X-ray doses, using doses per fraction in the range of 0.9 to 16 Gy. The overall treatment time was kept constant at 3 weeks. Kidney function was assessed from 19 to 48 weeks after irradiation by measuring changes in isotope clearance, urine output, and hematocrit. The degree of anemia (assessed from the hematocrit measurements) is a newly developed assay which is an early indicator of the extent of renal damage after irradiation. All three assays yielded steep dose-effect curves from which the repair capacity of kidney could be estimated by comparing the isoeffective doses in different schedules. There was a marked influence of fractionation, with increasing dose being required to achieve the same level of damage for increasing fraction number, even between 32 and 64 fractions. The data are well fitted by a linear quadratic dose-response equation, and analysis of the data in this way yields low values (approximately 3.0 Gy) for the ratio alpha/beta. This would suggest that hyperfractionation , using extremely small X-ray doses per fraction, would spare kidneys relative to tumors and acutely responding tissues.


Tick-borne flaviviruses alter membrane structure and replicate in dendrites of primary mouse neuronal cultures.
Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, detailed mechanisms of viral replication in the brain and features of viral pathogenesis remain poorly understood. We carried out a comparative analysis of replication of neurotropic flaviviruses: West Nile virus, Japanese encephalitis virus and tick-borne encephalitis virus (TBEV), in primary cultures of mouse brain neurons. All the flaviviruses multiplied well in primary neuronal cultures from the hippocampus, cerebral cortex and cerebellum. The distribution of viral-specific antigen in the neurons varied: TBEV infection induced accumulation of viral antigen in the neuronal dendrites to a greater extent than infection with other viruses. Viral structural proteins, non-structural proteins and dsRNA were detected in regions in which viral antigens accumulated in dendrites after TBEV replication. Replication of a TBEV replicon after infection with virus-like particles of TBEV also induced antigen accumulation, indicating that accumulated viral antigen was the result of viral RNA replication. Furthermore, electron microscopy confirmed that TBEV replication induced characteristic ultrastructural membrane alterations in the neurites: newly formed laminal membrane structures containing virion-like structures. This is the first report describing viral replication in and ultrastructural alterations of neuronal dendrites, which may cause neuronal dysfunction. These findings encourage further work aimed at understanding the molecular mechanisms of viral replication in the brain and the pathogenicity of neurotropic flaviviruses.


Angiopoietins and their role in colon cancer angiogenesis.
Tumor angiogenesis is a complicated process that is regulated by numerous factors simultaneously and in a coordinated fashion. Angiogenic factors drive the process of neovascularization, but the initiation of angiogenesis involves priming of endothelial cells so that they will respond to mitogenic stimuli. The angiopoietins (Ang) -1 and -2 mediate endothelial cell stability through binding to their endothelial cell-specific receptor, Tie-2. Ang-1 leads to endothelial cell stability, and, in vivo, to an actual decrease in angiogenesis. This is likely due to its ability to enhance adhesion to the perivascular tissues. In contrast, Ang-2 leads to endothelial cell instability and may be an initiating factor in angiogenesis, priming endothelial cells for mitogenic signals. Thus, a novel antiangiogenic strategy may be one that leads to enhanced endothelial cell stability, thereby protecting endothelial cells from standard angiogenic stimuli. This may ultimately lead to tumor dormancy by transforming a rapidly growing tumor into an indolent tumor.


A retrospective evaluation of treatments with implant-supported maxillary overdentures.
Considerably lower success rates have been presented for implant-supported overdentures in the maxilla compared with the mandible. The aim of the study was to report the outcome of implant-supported maxillary overdentures from one clinic. All patients treated with implant-supported maxillary overdentures in the Department of Prosthetic Dentistry, Central Hospital, Skövde, Sweden, between 1993 and 2002 were identified from patient charts and included in the study. All patients had a rigid cast gold alloy bar designed with ball attachments retaining an overdenture. Twenty-seven subjects were included, of whom 13 were originally planned for overdenture treatment (group 1) and the other 14 for a fixed prosthesis (group 2). The mean observation period was 5.7 years for subjects in group 1 and 5.5 years for those in group 2. One hundred forty-five implants were placed, and the majority of the failures were diagnosed as early ones and were found in group 2. The cumulative implant survival rate after 5 years was 77% in group 1 and 46% in group 2. The probability of having implant failure was almost three times higher among subjects in group 2 compared with subjects in group 1. Most technical and biologic complications were related to the retention system. Maxillary implant-supported overdentures show a high implant failure rate, but fewer implant failures occurred for patients originally planned for overdenture treatment.


Advance care planning after lung transplantation: a case of missed opportunities.
After lung transplantation, recipients are regularly evaluated by the transplant team and often require multiple hospitalizations. The primary focus of care during this time is on detecting and treating complications and may not necessarily include advance care planning discussions. This focus may leave clinicians unaware of the recipient's treatment preferences and place a burden on families trying to decide whether to undergo or forgo life-sustaining treatment when the recipient's medical condition deteriorates. We report the case of a woman with bronchiolitis obliterans who was admitted to the transplant center 37 times and died in the intensive care unit. Although progressive deterioration of her medical condition was well documented, her medical records revealed no evidence of advance care planning discussions with the patient and family. Incorporating timely advance care planning and integrating palliative care in the ongoing posttransplant clinical management may benefit patients, families, and clinicians as recipients approach the final stage of their illness.


Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages.
Meiosis pairs and segregates homologous chromosomes and thereby forms haploid germ cells to compensate the genome doubling at fertilization. Homologue pairing in many eukaryotic species depends on formation of DNA double strand breaks (DSBs) during early prophase I when telomeres begin to cluster at the nuclear periphery (bouquet stage). By fluorescence in situ hybridization criteria, we observe that mid-preleptotene and bouquet stage frequencies are altered in male mice deficient for proteins required for recombination, ubiquitin conjugation and telomere length control. The generally low frequencies of mid-preleptotene spermatocytes were significantly increased in male mice lacking recombination proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice with only one copy of the telomere length regulator Terf1. The bouquet stage was significantly enriched in Atm(-/-), Spo11(-/-), Mei1(m1Jcs/m1Jcs), Mlh1(-/-), Terf1(+/-) and Hr6b(-/-) spermatogenesis, but not in mice lacking recombination proteins DMC1 and HOP2, the non-homologous end-joining DNA repair factor KU80 and the ATM downstream effector GADD45a. Mice defective in spermiogenesis (Tnp1(-/-), Gmcl1(-/-), Asm(-/-)) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11(-/-)Atm(-/-) spermatogenesis suggests that DSBs contribute to the Atm(-/-)-correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1(-/-), Hop2(-/-)) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis.


Repurposing Old Drugs into New Epigenetic Inhibitors: Promising Candidates for Cancer Treatment?
Epigenetic alterations, as a cancer hallmark, are associated with cancer initiation, progression and aggressiveness. Considering, however, that these alterations are reversible, drugs that target epigenetic machinery may have an inhibitory effect upon cancer treatment. The traditional drug discovery pathway is time-consuming and expensive, and thus, new and more effective strategies are required. Drug Repurposing (DR) comprises the discovery of a new medical indication for a drug that is approved for another indication, which has been recalled, that was not accepted or failed to prove efficacy. DR presents several advantages, mainly reduced resources, absence of the initial target discovery process and the reduced time necessary for the drug to be commercially available. There are numerous old drugs that are under study as repurposed epigenetic inhibitors which have demonstrated promising results in in vitro tumor models. Herein, we summarize the DR process and explore several repurposed drugs with different epigenetic targets that constitute promising candidates for cancer treatment, highlighting their mechanisms of action.


Convergence Circuit Mapping: Genetic Approaches From Structure to Function.
Understanding the complex neural circuits that underpin brain function and behavior has been a long-standing goal of neuroscience. Yet this is no small feat considering the interconnectedness of neurons and other cell types, both within and across brain regions. In this review, we describe recent advances in mouse molecular genetic engineering that can be used to integrate information on brain activity and structure at regional, cellular, and subcellular levels. The convergence of structural inputs can be mapped throughout the brain in a cell type-specific manner by antero- and retrograde viral systems expressing various fluorescent proteins and genetic switches. Furthermore, neural activity can be manipulated using opto- and chemo-genetic tools to interrogate the functional significance of this input convergence. Monitoring neuronal activity is obtained with precise spatiotemporal resolution using genetically encoded sensors for calcium changes and specific neurotransmitters. Combining these genetically engineered mapping tools is a compelling approach for unraveling the structural and functional brain architecture of complex behaviors and malfunctioned states of neurological disorders.


Detection of clinical mastitis with the help of a thermal camera.
Increasing dairy farm size and increase in automation in livestock production require that new methods are used to monitor animal health. In this study, a thermal camera was tested for its capacity to detect clinical mastitis. Mastitis was experimentally induced in 6 cows with 10 microg of Escherichia coli lipopolysaccharide (LPS). The LPS was infused into the left forequarter of each cow, and the right forequarters served as controls. Clinical examination for systemic and local signs and sampling for indicators of inflammation in milk were carried out before morning and evening milking throughout the 5-d experimental period and more frequently on the challenge day. Thermal images of experimental and control quarters were taken at each sampling time from lateral and medial angles. The first signs of clinical mastitis were noted in all cows 2 h postchallenge and included changes in general appearance of the cows and local clinical signs in the affected udder quarter. Rectal temperature, milk somatic cell count, and electrical conductivity were increased 4 h postchallenge and milk N-acetyl-beta-D-glucosaminidase activity 8 h postchallenge. The thermal camera was successful in detecting the 1 to 1.5 degrees C temperature change on udder skin associated with clinical mastitis in all cows because temperature of the udder skin of the experimental and control quarters increased in line with the rectal temperature. Yet, local signs on the udder were seen before the rise in udder skin and body temperature. The udder represents a sensitive site for detection of any febrile disease using a noninvasive method. A thermal camera mounted in a milking or feeding parlor could detect temperature changes associated with clinical mastitis or other diseases in a dairy herd.


Corneroboletus, a new genus to accommodate the southeastern Asian Boletus indecorus.
Corneroboletus was erected in the Boletaceae to accommodate Boletus indecorus originally described from southeastern Asia. The mucilaginous surface of the basidioma, the ixohyphoepithelium pileipellis and the irregularly warty to irregularly bacillate ornamentation of basidiospores distinguish this fungus from other described species in Boletaceae. Phylogenetic placement of this fungus was investigated further with molecular data including LSU rRNA and concatenated alignment of nrLSU, 5.8S rRNA and rpb2 genes, and an independent lineage among existing genera of Boletaceae was suggested by our phylogenetic results. Consequently a description, illustrations and a comparison of Corneroboletus with allied taxa are presented.


Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III.
Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families.


CT scan in severe diffuse head injury: physiological and clinical correlations.
CT scan findings, clinical features and intracranial pressure were studied in patients with severe diffuse head injury. Compression of the 3rd ventricle and basal cisterns closely correlated with an intracranial pressure greater than 20 mmHg, with clinical signs of midbrain dysfunctions and worse prognosis. These CT scan findings can indicate whether intracranial pressure monitoring is appropriate.


Dietary treatment of childhood atopic eczema/dermatitis syndrome (AEDS).
This review summarizes the research and clinical evidence in favour of dietary intervention aimed at eliminating allergenic foods in the management of atopic eczema/dermatitis syndrome (AEDS). The data source was PubMed, using a search algorithm selecting for clinical studies of AEDS, diet therapy and food allergy in all children to October 2003. Also included is a commentary based on the authors' clinical experience in the allergy unit of a university hospital in Italy. Fourteen prospective studies matched the entry criteria. Diverse trial designs, diagnostic criteria, types of dietary intervention and length of observation periods precluded meta-analytic methods. Allergenic food exclusion claimed efficacy in 13 of the 14 studies and was most useful in infants, in patients with elevated immunoglobulin E levels and/or multiple food sensitization and in patients with a diagnosis of food allergy. Dietary intervention in the form of an elimination diet is efficacious in children with AEDS when a specific diagnosis of food allergy has been made. Diagnostic evaluation of food allergy should be performed in all children with eczema, particularly in younger children and those with severe forms of the disease.


Expression of the Emx-1 and Dlx-1 homeobox genes define three molecularly distinct domains in the telencephalon of mouse, chick, turtle and frog embryos: implications for the evolution of telencephalic subdivisions in amniotes.
Homologies between vertebrate forebrain subdivisions are still uncertain. In particular the identification of homologs of the mammalian neocortex or the dorsal ventricular ridge (DVR) of birds and reptiles is still a matter of dispute. To get insight about the organization of the primordia of the main telencephalic subdivisions along the anteroposterior axis of the neural tube, a fate map of the dorsal prosencephalon was obtained in avian chimeras at the 8- to 9-somite stage. At this stage, the primordia of the pallium, DVR and striatum were located on the dorsal aspect of the prosencephalon and ordered caudorostrally along the longitudinal axis of the brain. Expression of homeobox-containing genes of the Emx, Dlx and Pax families were used as markers of anteroposterior developmental subdivisions of the forebrain in mouse, chick, turtle and frog. Their expression domains delineated three main telencephalic subdivisions in all species at the onset of neurogenesis: the pallial, intermediate and striatal neuroepithelial domains. The fate of the intermediate subdivisions diverged, however, between species at later stages of development. Homologies between forebrain subdivisions are proposed based on the conservation and divergence of these gene expression patterns.


Imaging fluorescence correlation spectroscopy studies of dye diffusion in self-assembled organic nanotubes.
The rate and mechanism of diffusion by anionic sulforhodamine B (SRB) dye molecules within organic nanotubes self-assembled from bolaamphiphile surfactants were investigated by imaging fluorescence correlation spectroscopy (imaging-FCS). The inner and outer surfaces of the nanotubes are terminated with amine and glucose groups, respectively; the former allow for pH-dependent manipulation of nanotube surface charge while the latter enhance their biocompatibility. Wide-field fluorescence video microscopy was used to locate and image dye-doped nanotubes dispersed on a glass surface. Imaging-FCS was then used to spatially resolve the SRB transport dynamics. Mobilization of the dye molecules was achieved by immersion of the nanotubes in buffer solution. Experiments were performed in pH 6.4, 7.4 and 8.4 buffers, at ionic strengths ranging from 1.73 mM to 520 mM. The results show that coulombic interactions between cationic ammonium ions on the inner nanotube surface and the anionic SRB molecules play a critical role in governing mass transport of the dye. The apparent dye diffusion coefficient, D, was found to generally increase with increasing ionic strength and with increasing pH. The D values obtained were found to be invariant along the nanotube length. Mass transport of the SRB molecules within the nanotubes is concluded to occur by a desorption-mediated Fickian diffusion mechanism in which dye motion is slowed by its coulombic interactions with the inner surfaces of the nanotubes. The results of these studies afford information essential to the use of organic nanotubes in controlled drug release applications.


Detection by near-infrared spectroscopy of large lipid core plaques at culprit sites in patients with acute ST-segment elevation myocardial infarction.
This study sought to describe near-infrared spectroscopy (NIRS) findings of culprit lesions in ST-segment elevation myocardial infarction (STEMI). Although autopsy studies demonstrate that most STEMI are caused by rupture of pre-existing lipid core plaque (LCP), it has not been possible to identify LCP in vivo. A novel intracoronary NIRS catheter has made it possible to detect LCP in patients. We performed NIRS within the culprit vessels of 20 patients with acute STEMI and compared the STEMI culprit findings to findings in nonculprit segments of the artery and to findings in autopsy control segments. Culprit and control segments were analyzed for the maximum lipid core burden index in a 4-mm length of artery (maxLCBI(4mm)). MaxLCBI(4mm) was 5.8-fold higher in STEMI culprit segments than in 87 nonculprit segments of the STEMI culprit vessel (median [interquartile range (IQR)]: 523 [445 to 821] vs. 90 [6 to 265]; p < 0.001) and 87-fold higher than in 279 coronary autopsy segments free of large LCP by histology (median [IQR]: 523 [445 to 821] vs. 6 [0 to 88]; p < 0.001).Within the STEMI culprit artery, NIRS accurately distinguished culprit from nonculprit segments (receiver-operating characteristic analysis area under the curve = 0.90). A threshold of maxLCBI(4mm) >400 distinguished STEMI culprit segments from specimens free of large LCP by histology (sensitivity: 85%, specificity: 98%). The present study has demonstrated in vivo that a maxLCBI(4mm) >400, as detected by NIRS, is a signature of plaques causing STEMI.


Supporting Regularized Logistic Regression Privately and Efficiently.
As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large-scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc.


Volkmann's ischemic contracture. A case report.
A case is presented illustrating some of the basic principles in the development and repair of Volkmann's ischemic contracture following a supracondylar fracture. The etiology, initial signs, prevention, and possible treatments of the contracture are discussed. Early fasciotomy is the best treatment for impending contracture, while neurolysis with infarct excision, a flexor pronator slide, and tendon transfer can return much function following established contracture of the forearm.


Radionuclide-based theranostics - a promising strategy for lung cancer.
This review aims to provide a comprehensive overview of the latest literature on personalized lung cancer management using different ligands and radionuclide-based tumor-targeting agents. Lung cancer is the leading cause of cancer-related deaths worldwide. Due to the heterogeneity of lung cancer, advances in precision medicine may enhance the disease management landscape. More recently, theranostics using the same molecule labeled with two different radionuclides for imaging and treatment has emerged as a promising strategy for systemic cancer management. In radionuclide-based theranostics, the target, ligand, and radionuclide should all be carefully considered to achieve an accurate diagnosis and optimal therapeutic effects for lung cancer. We summarize the latest radiotracers and radioligand therapeutic agents used in diagnosing and treating lung cancer. In addition, we discuss the potential clinical applications and limitations associated with target-dependent radiotracers as well as therapeutic radionuclides. Finally, we provide our views on the perspectives for future development in this field. Radionuclide-based theranostics show great potential in tailored medical care. We expect that this review can provide an understanding of the latest advances in radionuclide therapy for lung cancer and promote the application of radioligand theranostics in personalized medicine.


Intradermal Low-Fat Spindle Cell Lipoma: A Case Report.
Spindle cell lipoma is a rare benign neoplasm that features a mixture of evenly aligned spindle cells, mature adipocytes, and ropey collagen. Most cases of spindle cell lipoma are found in the subcutaneous tissue, and intradermal spindle cell lipoma is rarely reported. We present a case of intradermal spindle cell lipoma in a 46-year-old female who presented with a 0.7-cm flesh-colored and dome-shaped nodule on the right temple that had developed 6 years ago. This mass was excised, and upon histopathologic examination, an unencapsulated lesion was located in the dermis, which consisted of bland spindle cells, scanty mature adipocytes, rare lipoblasts, and ropey collagen bundles with prominent basophilic myxoid stroma. Immunohistochemical staining showed diffuse positivity for CD34, negativity for the S-100 protein, and loss of retinoblastoma protein expression. Based on these features, intradermal low-fat spindle cell lipoma was diagnosed. No evidence of local recurrence was observed 4 months after excision. Intradermal low-fat spindle cell lipomas are extremely rare and can easily be mistaken for tumors that have similar clinical and histopathological findings. Herein, we report a globally rare case of an intradermal low-fat spindle cell lipoma.


Anti-anginal and anti-ischemic effects of mibefradil, a new T-type calcium channel antagonist.
Mibefradil is the first of a new class of calcium antagonists (CAs), the tetralol derivatives, that selectively blocks the T-type calcium channel. The anti-anginal and anti-ischemic efficacy of mibefradil in patients with chronic stable angina pectoris was established in five placebo-controlled trials (2 monotherapy trials, 3 trials with background beta-blocker or long-acting nitrate therapy). At the recommended doses of 50 and 100 mg, mibefradil treatment was associated with a significant dose-related increase in exercise test variables regardless of demographic subpopulation or background therapy. Significant reductions in weekly anginal attacks, silent ischemic parameters, heart rate (HR) and rate-pressure product were also observed. Two active-controlled trials compared mibefradil 100 mg with amlodipine 10 mg or diltiazem SR 120 mg b.i.d., respectively. Patients receiving mibefradil showed significantly larger improvements than did those treated with amlodipine and similar improvements as those treated with diltiazem SR in all variables measured. In both studies, treatment with mibefradil was associated with a greater decrease in HR and rate-pressure product. Mibefradil was found to be well tolerated and safe; this held true for patients on chronic anti-anginal background therapy. The overall incidences of adverse events and premature withdrawals were only slightly higher than those of placebo-treated patients. Asymptomatic sinus bradycardia and first-degree atrioventricular block were the most frequently occurring mibefradil dose-related ECG changes. Mibefradil was better tolerated than amlodipine (mainly with regard to leg edema) and similarly well tolerated as diltiazem CD.


Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269).
Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x) (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously reported biphenyl-based inhibitors that would provide additional interactions with the protein. These compounds were assayed for the ability to inhibit the binding of sialyl Lewis(x) (sLe(x), 2) bearing HL-60 cells to E-, P-, and L-selectin fusion proteins. We report that dimeric or trimeric compounds containing multiple components of simple nonoligosaccharide selectin antagonists inhibit sLe(x)-dependent binding with significantly enhanced potency over the monomeric compound. The enhanced potency is consistent with additional binding interactions within a single selectin lectin domain; however, multivalent interaction with multiple lectin domains as a possible alternative cannot be ruled out. Compound 15e (TBC1269) showed optimal in vitro activity from this class of antagonists and is currently under development for use in the treatment of asthma.


[Combined radiotherapy and chemotherapy: pulmonary side effects (author's transl)].
Systemic chemotherapy and lung irradiation have very similar effects on lung tissue. Several mechanisms are involved, mainly: --cytotoxic effects on lung cells (type II pneumocytes, capillary endothelial cells, and connective tissue); --enhancement of infection; --hypersensitivity and auto-immune phenomena. Acute pneumonitis or chronic lung sclerosis develops which may or may not be compatible with life, depending on the lung volume involved and the clinical course. These effects are dose dependent for radiotherapy, and for most of the chemotherapeutic drugs. In some cases however, the dose-effect relationship is not clear, especially with some drugs such as methotrexate, and sometimes with radiotherapy even when it can be assumed that there is no mistake in dose calculation. It must be stressed that we will lack basic knowledge on the pharmacokinetics and actual concentration of drugs in lung tissue. Additive or supra-additive effects are likely when chemotherapy is combined with lung irradiation, but current relevant data does not allow any firm conclusions to be drawn on the quantitative changes resulting from the association. Prevention of lung complications is however possible if the tolerance doses and the optimal distribution of each agent with time are respected. Combined lung irradiation and bleomycin administration must be avoided.


The Host Factor Early Growth Response Gene (EGR-1) Regulates Vaccinia virus Infectivity during Infection of Starved Mouse Cells.
Evolution has equipped poxvirus genomes with the coding capacity for several virus-host interaction products which interfere with host cell gene expression and protein function, creating an adequate intracellular environment for a productive infection. We show here that Vaccinia virus (VACV) induces the expression of the cellular transcription factor EGR-1 (early growth response-1) in Mouse Embryonic Fibroblasts (MEFs) through the MEK (mitogen-activated protein kinase (MAPK)/ERK)/ERK (extracellular signal-regulated kinases) pathway, from 3 to 12 h post infection (h.p.i.). By using starved egr-1 knockout (egr-1-/-) MEFs, we demonstrate that VACV replication is reduced by ~1 log in this cell line. Although western blotting and electron microscopy analyses revealed no difference in VACV gene expression or morphogenesis, the specific infectivity of VACV propagated in egr-1-/- MEFs was lower than virus propagated in wild type (WT) cells. This lower infectivity was due to decreased VACV DNA replication during the next cycle of infection. Taken together, these results revealed that EGR-1 appears to facilitate VACV replication in starved fibroblasts by affecting viral particles infectivity.


[Drug-resistant headache: is it the end?].
Chronic primary headache often cause significant interference with function and quality of life despite acute and preventive medicines. New treatments are emerging for pharmacologically intractable cluster headache and migraine. Occipital nerve stimulation in chronic cluster headache and botulinum toxin in chronic migraine represent the most promising therapies.


Approaches to isozyme-specific inhibitors. 16. A novel methyl-C5' covalent adduct of L-ethionine and beta,gamma-imido-ATP as a potent multisubstrate inhibitor of rat methionine adenosyltransferases.
N6,N6-Dibenzoyl-2',3'-O-isopropylideneadenosine, which is readily synthesized by one-pot 5'-O-trimethylsilylation, N6-benzoylation, and desilylation, was converted to the corresponding 5'-aldehyde. This was treated with CH2 = CHMgBr to afford, after debenzoylation, a 1:3 mixture of the 5'S and 5'R epimers, respectively, of 5'-C-vinyl-2',3'-O-isopropylideneadenosine. The configurations were established by single-crystal X-ray diffraction analysis of the 5'R epimer. Hydroboration of the 5'-O-tetrahydropyranyl derivative of the mixed epimeric 5'-C-vinyl nucleosides readily furnished 5'(S,R)-C-(2-hydroxyethyl)-2',3'-O-isopropylideneadenosine. Treatment of the 5'(S,R)-C-(2-O-tosyl) derivative of this with disodium L-homocysteinate permitted facile introduction of the L-ethionine system. By means of methods developed earlier in the synthesis of homologous methionine-ATP adducts, the alpha-amino acid group was protected, a beta,gamma-imidotriphosphoryl group was introduced at O5', and blocking groups were removed to give the title adduct as a 2:3 mixture of its two 5' epimers. It was a powerful inhibitor [KM(ATP)/Ki = 520 and 340] of the M-2 (normal tissue) and M-T (hepatoma tissue) forms, respectively, of the title enzyme and displayed predominantly competitive kinetics with the two substrates L-methionine and MgATP. It inhibited M-2 and M-T slightly less effectively than its homologue possessing one less CH2 between sulfur and C5' and gave kinetic evidence of an increased tendency to form L-methionine-enzyme-adduct and MgATP-enzyme-adduct complexes.


Ternary-Metal Sn-Pb-Zn Perovskite to Reconstruct Top Surface for Efficient and Stable Less-Pb Perovskite Solar Cells.
Though Sn-Pb alloyed perovskite solar cells (PSCs) achieved great progress, there is a dilemma to further increase Sn for less-Pb requirement. High Sn ratio (>70%) perovskite exhibits nonstoichiometric Sn:Pb:I at film surface to aggravate Sn2+ oxidation and interface energy mismatch. Here, ternary metal alloyed (FASnI3 )0.7 (MAPb1- x Znx I3 )0.3 (x = 0-3%) is constructed for Pb% < 30% perovskite. Zn with smaller ionic size and stronger ionic interaction than Sn/Pb assists forming high-quality perovskite film with ZnI6 4- enriched at surface to balance Sn:Pb:I ratio. Differing from uniform bulk doping, surface-rich Zn with lower lying orbits pushes down the energy band of perovskite and adjusts the interface energy for efficient charge transfer. The alloyed PSC realizes efficiency of 19.4% at AM1.5 (one of the highest values reported for Pb% < 30% PSCs). Moreover, stronger bonding of Zn─I and Sn─I contributes to better durability of ternary perovskite than binary perovskite. This work highlights a novel alloy method for efficient and stable less-Pb PSCs.


Placebo interventions for all clinical conditions.
Placebo interventions are often claimed to improve patient-reported and observer-reported outcomes, but this belief is not based on evidence from randomised trials that compare placebo with no treatment. To assess the effect of placebo interventions. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2002), MEDLINE (1966 to 2002), EMBASE (1980 to 2002), Biological Abstracts (1986 to 2002), and PsycLIT (1887 to 2002). We contacted experts on placebo research, and read references in the included trials. We included randomised placebo trials with a no-treatment control group investigating any health problem. Two reviewers independently assessed trial quality and extracted data. We contacted study authors for additional information. Outcome data were available in 156 out of 182 included trials, investigating 46 clinical conditions. We found no statistically significant pooled effect of placebo in 38 studies with binary outcomes (4284 patients), relative risk 0.95 (95% confidence interval (CI) 0.89 to 1.01). The pooled relative risk for patient-reported outcomes was 0.95 (95% CI 0.88 to 1.03) and for observer-reported outcomes 0.91 (95% CI 0.81 to 1.03). There was heterogeneity (P=0.01) but the funnel plot was symmetrical. There was no statistically significant effect of placebo interventions in the four clinical conditions investigated in three trials or more: pain, nausea, smoking, and depression, but confidence intervals were wide. We found an overall effect of placebo treatments in 118 trials with continuous outcomes (7453 patients), standardised mean difference (SMD) -0.24 (95% CI -0.31 to -0.17). The SMD for patient-reported outcomes was -0.30 (95% CI -0.38 to -0.21), whereas no statistically significant effect was found for observer-reported outcomes, SMD -0.10 (95% CI -0.20 to -0.01). There was heterogeneity (P<0.001) and large variability in funnel plot results even for big trials. There was an apparent effect of placebo interventions on pain (SMD -0.25 (95% CI -0.35 to-0.16)), and phobia (SMD -0.63 (95% CI -1.17 to -0.08)); but also a substantial risk of bias. There was no statistically significant effect of placebo interventions in eight other clinical conditions investigated in three trials or more: nausea, smoking, depression, overweight, asthma, hypertension, insomnia and anxiety, but confidence intervals were wide. There was no evidence that placebo interventions in general have clinically important effects. A possible small effect on continuous patient-reported outcomes, especially pain, could not be clearly distinguished from bias.


Maternal rhabdomyolysis and twin fetal death associated with gestational diabetes insipidus.
Gestational diabetes insipidus is a rare, transient complication of pregnancy typically characterized by polyuria and polydipsia that may lead to mild electrolyte abnormalities. More severe sequelae of gestational diabetes insipidus are uncommon. We present a case of a 25-year-old woman at 23 weeks of gestation in a dichorionic-diamniotic twin pregnancy who developed severe symptomatic gestational diabetes insipidus complicated by rhabdomyolysis and death of both fetuses. Maternal rhabdomyolysis caused by gestational diabetes insipidus is extremely rare. Early recognition and treatment of gestational diabetes insipidus is necessary to prevent maternal and fetal morbidity and mortality.


Dynamin-dependent and dynamin-independent processes contribute to the regulation of single vesicle release kinetics and quantal size.
Accumulating evidence suggests that the kinetics of release from single secretory vesicles can be regulated and that quantal size can be modified during fast kiss-and-run fusion. Multiple pathways for vesicle retrieval have been identified involving clathrin and dynamin. It has been unclear whether dynamin could participate in a fast kiss-and-run process to reclose a transient fusion pore and thereby limit vesicle release. We have disrupted dynamin function in adrenal chromaffin cells by expression of the amphiphysin Src-homology domain 3 (SH3) or by application of guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), and have monitored single vesicle release events, evoked by digitonin and Ca(2+), by using carbon-fiber amperometry. Under both conditions, there was an increase in mean quantal size accompanying an increase in the half-width of amperometric spikes and a slowing of the fall time. These data suggest the existence of a dynamin-dependent process that can terminate vesicle release under basal conditions. Protein kinase C activation changed release kinetics and decreased quantal size by shortening the release period. The effects of phorbol ester treatment were not prevented by expression of the amphiphysin SH3 domain or by GTP gamma S suggesting the existence of alternative dynamin-independent process underlying fast kiss-and-run exocytosis.


Screening programs for renal cell carcinoma: a systematic review by the EAU young academic urologists renal cancer working group.
To systematically review studies focused on screening programs for renal cell carcinoma (RCC) and provide an exhaustive overview on their clinical impact, potential benefits, and harms. A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42021283136) using the MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUality In Prognosis Studies (QUIPS) tool. Overall, nine studies and one clinical trials were included. Eight studies reported results from RCC screening programs involving a total of 159 136 patients and four studies reported screening cost-analysis. The prevalence of RCC ranged between 0.02 and 0.22% and it was associated with the socio-demographic characteristics of the subjects; selection of the target population decreased, overall, the screening cost per diagnosis. Despite an increasing interest in RCC screening programs from patients and clinicians there is a relative lack of studies reporting the efficacy, cost-effectiveness, and the optimal modality for RCC screening. Targeting high-risk individuals and/or combining detection of RCC with other health checks represent pragmatic options to improve the cost-effectiveness and reduce the potential harms of RCC screening.


Ultrasonographic findings of multicentric malignant lymphoma involving the urinary bladder in a dog: Diagnosis and monitoring during chemotherapy.
A 5.5-year-old spayed female cane corso dog was presented for recurrent hematuria and dysuria. Abdominal ultrasound demonstrated severe hypoechoic urinary bladder wall thickening with irregular mucosal surface and polypoid-like lesions protruding into the lumen, abdominal polyadenomegaly, and splenic honeycombing. High-grade lymphoma was diagnosed on urinary bladder wall cytology. Clinical signs and ultrasonographic findings initially improved following a modified CHOP-based chemotherapy protocol, but the multicentric lymphoma then progressed with thoracic spread, leading to the dog's death at 9 wk post-diagnosis. Key clinical message: This case report describes the ultrasonographic features of malignant lymphomatous infiltration of the urinary bladder and emphasizes the importance of including lymphoma in the differential diagnosis for parietal urinary bladder lesions. It also describes the endoscopic findings of such an infiltration that have not yet, to the authors' knowledge, been described or illustrated in the veterinary literature. Finally, this case report underlines the poor prognosis of multicentric lymphoma involving the urinary bladder, with rapid progression of the disease and short survival time despite chemotherapy.


High rates of potentially infectious exposures between immunocompromised patients and their companion animals: an unmet need for education.
A cross-sectional survey of 265 adult patients with haematological malignancy, haemoglobinopathy or human immunodeficiency virus was performed to determine the potential risk of infection from animal exposures. One hundred and thirty-seven (52%) owned an animal; the majority were dogs (74%) and cats (39%), but 14% owned birds and 3% reptiles. Eighty percent engaged in behaviour with their animals that potentially put them at risk of zoonotic infections. The most frequent behaviours were picking up animal faeces 72 (52%), cleaning animal areas 69 (50%) and allowing animals to sleep in the same bed 51 (37%). Twenty-eight percent allowed the animal to lick their face. Of all patients, 80 (30%) had been bitten or scratched by an animal. Only 16% of those who owned pets could recall receiving education regarding safe behaviours around animals. These immunocompromised patients are at risk of infection through exposure to pets. Our study highlights the need for increased education of patients regarding how to remain safe around their pets.


Cholesterol absorption in rat intestine: role of cholesterol esterase and acyl coenzyme A:cholesterol acyltransferase.
Cholesterol esterase of pancreatic juice origin and acyl coenzyme A:cholesterol acyltransferase, both associated with the intestinal mucosa, are implicated in the extensive esterification of exogenous cholesterol during absorption. To assess the role of each enzyme, [4-14C]cholesterol absorption into mesenteric lymph of rats with normal mucosal levels of both esterification enzymes was compared with that of rats with normal acyl coenzyme A:cholesterol acyltransferase activity but deficient cholesterol esterase activity. The cholesterol esterase deficiency was accomplished by either surgical diversion of the pancreatic juice from the intestinal lumen or removal by specific immunoprecipitation of cholesterol esterase from the otherwise complete pancreatic juice. In the rats that were transferase-complete and esterase-deficient, cholesterol absorption into lymph and esterase activity in the mucosa were decreased an average of 83% and 75%, respectively, compared with rats complete with both esterification enzymes. Of the absorbed [4-14C]cholesterol in all rats, 82-90% was esterified and the mucosal levels of cholesterol esterase, even in the esterase-deficient rats, could readily account for this esterification. Because transferase activity was normal in rat intestine in which cholesterol esterase was deficient and cholesterol absorption was inhibited, transferase alone does not support the absorption of exogenous cholesterol in the absence of esterase. These results reconfirm the importance of esterification in the absorption of exogenous cholesterol and demonstrate that cholesterol esterase plays an essential role in the regulation of the absorption process.


High magnitude head impacts experienced during youth football practices.
To reduce the risk of concussion in the 3.5 million youth athletes who participate in organized football leagues in the United States each year, practice structure can be modified to decrease impact frequency and magnitude. The objective of this study is to identify activities that result in high magnitude head impacts in youth football players during practice. The HIT System was used to record the head acceleration magnitude, impact location on the helmet, and time of each impact for each game and practice players participated in. These data were used to quantify the head impact exposure associated with players between the ages of 9 and 11 years. Video footage recorded during each practice and game session was used to identify the activity associated with any impact above 45 g. The incidence rate of high magnitude impacts in various activities were compared by normalizing by the amount of time associated with each activity. It was determined that scrimmages accounted for 0.094 impacts greater than 45 g per minute in practices while contact drills contributed to 0.102 impacts greater than 45 g per minute during practices. The results of this study indicate future youth football practice modifications should focus on both scrimmages and contact drills.


Efficient near-infrared polymer and organic light-emitting diodes based on electrophosphorescence from (tetraphenyltetranaphtho[2,3]porphyrin)platinum(II).
The new metalloporphyrin Pt(tptnp), where tptnp = tetraphenyltetranaphtho[2,3]porphyrin, has been prepared and subjected to photophysical and electrooptical device studies. In degassed toluene solution at room temperature Pt(tptnp) features efficient phosphorescence emission with lambda(max) 883 nm with a quantum efficiency of 0.22. The complex has been used as the active phosphor in polymer and organic light-emitting diodes. Polymer light-emitting diodes based on a spin-coated emissive layer consisting of a blend of Pt(tptnp) doped in poly(9-vinylcarbazole) and 2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole exhibit near-IR emission with lambda(max) 896 nm, with a maximum external quantum efficiency (EQE) of 0.4% and a maximum radiant emittance of 100 muW/cm(2). Organic light-emitting diodes prepared via vapor deposition of all layers and that feature an optimized multilayer hole injection and electron blocking layer heterostructure with an emissive layer consisting of 4,4'-bis(carbazol-9-yl)biphenyl (CBP) doped with Pt(tptnp) exhibit a maximum EQE of 3.8% and a maximum radiant emittance of 1.8 mW/cm(2). The polymer and organic light-emitting diodes characterized in this study exhibit record high efficiency for devices that emit in the near-IR at lambda >800 nm.


Nanoengineered mesenchymal stem cell therapy for pulmonary fibrosis in young and aged mice.
Pulmonary fibrosis (PF) is an age-related interstitial lung disease that results in notable morbidity and mortality. The Food and Drug Administration-approved drugs can decelerate the progression of PF; however, curing aged patients with severe fibrosis is ineffective because of insufficient accumulation of these drugs and wide necrocytosis of type II alveolar epithelial cells (AEC IIs). Here, we constructed a mesenchymal stem cell (MSC)-based nanoengineered platform via the bioconjugation of MSCs and type I collagenase-modified liposomes loaded with nintedanib (MSCs-Lip@NCAF) for treating severe fibrosis. Specifically, MSCs-Lip@NCAF migrated to fibrotic lungs because of the homing characteristic of MSCs and then Lip@NCAF was sensitively released. Subsequently, Lip@NCAF ablated collagen fibers, delivered nintedanib into fibroblasts, and inhibited fibroblast overactivation. MSCs differentiated into AEC IIs to repair alveolar structure and ultimately promote the regeneration of damaged lungs in aged mice. Our findings indicated that MSCs-Lip@NCAF could be used as a promising therapeutic candidate for PF therapy, especially in aged patients.


Expression of E-cadherin in normal oral mucosa, in oral precancerous lesions and in oral carcinomas.
The aim of the present study was to assess the expression of E-cad in oral precancerous lesions and conditions and oral carcinomas in comparison with normal mucosa. Total of 50 samples were selected for the study and were categorized into five groups and 10 samples in each group as Group I-oral leukoplakia (OL), Group II-oral lichen planus (OLP), Group III-oral submucous fibrosis (OSMF), Group IV-oral squamous cell carcinoma (OSCC) and Group V-normal oral mucosa (NOM) as control group. All the samples were assessed for the expression of E-cad by immunohistochemical study. Upon assessing the expression of E-cad in OL, OSMF, OLP and OSCC, as majority of the samples with OSCC (90%), OL (80%), OLP (70%) and OSMF (60%) showed mild to moderate expression of E-cad staining, which was suggestive of reduction in dysplastic cells on comparison to NOM cells. This difference in expression and variation of E-cad upon comparison with normal mucosa was statistically significant (P < 0.001). There is significant (P < 0.001) variation of expression of E-cad with the histopathological dysplasia of the oral precancerous lesions and conditions, and the tumor differentiation of the oral cancers. However, there was no correlation of the degree of loss of expression of E-cad with the degree of dysplasia or the tumor differentiation of oral cancers. We conclude with our study that, there is a variation in the expression of E-cad but its value as a prognostic marker is questionable.


Images of loneliness in Tuareg narratives of travel, dispersion, and return.
This article examines how social, economic, and political upheavals in the Sahara have stimulated re-thinking about loneliness in relation to trauma from mobility, dispersion, and return home in communities of Tamajaq-speaking, Muslim, and semi-nomadic Tuareg in northern Niger and Mali. How do Tuareg, sometimes called Kel Tamajaq after their language, draw on and re-formulate longstanding and new ways of coping with loneliness in regional droughts and wars, which have driven many to alternately disperse from their communities and return to homes that are no longer the same? What is the connection between changing modes of travel, concepts of loneliness, and ways of coping with this experience? In these communities, loneliness is a recurrent theme in personal life histories-in particular, in narratives of both geographic travel and spiritual travel in medico-ritual healing-and is alluded to in poetry, song, and everyday conversation. This article explores the meanings of loneliness and ways of coping with it in this society through analysis of this emotion in symbol, subjective perception, and social experience. The focus is upon representations of loneliness in narratives by travelers who have confronted this emotion, and upon relevant Tamajaq terms often used to express loneliness: namely, essuf (the wild, solitude, and nostalgia); tamazai (approximately, a depression); and tarama (unrequited love), illustrating with cases and examples. More broadly, the article is guided by and builds on insights in psychological anthropology into emotion and affect as well as suffering and subjectivity.


Laboratory evaluation of the TDx assay for detection of cannabinoids in urine from prison inmates.
The TDx (Abbott Laboratories) and the EMIT-Cobas (Syva Corp. & Roche) techniques for cannabinoid assay were evaluated. Authentic urine samples submitted for narcotics screening were analyzed for cannabinoids. All positive findings were confirmed by an HPLC procedure. The results indicated that the EMIT assay detects a few more positive samples, but also yields a higher rate of unconfirmed positive results compared to the TDx. Those additional "true" positives by EMIT had concentrations of the delta 9-THC-11-carboxylic acid below 10 ng/mL.


Systematic review and meta-analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis.
To assess reliability and discriminative validity of cartilage compositional magnetic resonance imaging (MRI) in knee osteoarthritis (OA). The study was carried out per PRISMA recommendations. We searched MEDLINE and EMBASE (1974 - present) for eligible studies. We performed qualitative synthesis of reliability data. Where data from at least two discrimination studies were available, we estimated pooled standardized mean difference (SMD) between subjects with and without OA. Discrimination analyses compared controls and subjects with mild OA (Kellgren-Lawrence (KL) grade 1-2), severe OA (KL grade 3-4) and OA not otherwise specified (NOS) where not possible to stratify. We assessed quality of the evidence using Quality Appraisal of Diagnostic Reliability (QAREL) and Quality Assessment of Diagnostic Accuracy (QUADAS-2) tools. Fifty-eight studies were included in the reliability analysis and 26 studies were included in the discrimination analysis, with data from a total of 2,007 knees. Intra-observer, inter-observer and test-retest reliability of compositional techniques were excellent with most intraclass correlation coefficients >0.8 and coefficients of variation <10%. T1rho and T2 relaxometry were significant discriminators between subjects with mild OA and controls, and between subjects with OA (NOS) and controls (P < 0.001). T1rho showed best discrimination for mild OA (SMD [95% CI] = 0.73 [0.40 to 1.06], P < 0.001) and OA (NOS) (0.60 [0.41 to 0.80], P < 0.001). Quality of evidence was moderate for both parts of the review. Cartilage compositional MRI techniques are reliable and, in the case of T1rho and T2 relaxometry, can discriminate between subjects with OA and controls.


Serial Laboratory Testing for SARS-CoV-2 Infection Among Incarcerated and Detained Persons in a Correctional and Detention Facility - Louisiana, April-May 2020.
Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by asymptomatic and presymptomatic persons poses important challenges to controlling spread of the disease, particularly in congregate settings such as correctional and detention facilities (1). On March 29, 2020, a staff member in a correctional and detention facility in Louisiana developed symptoms† and later had a positive test result for SARS-CoV-2. During April 2-May 7, two additional cases were detected among staff members, and 36 cases were detected among incarcerated and detained persons at the facility; these persons were removed from dormitories and isolated, and the five dormitories that they had resided in before diagnosis were quarantined. On May 7, CDC and the Louisiana Department of Health initiated an investigation to assess the prevalence of SARS-CoV-2 infection among incarcerated and detained persons residing in quarantined dormitories. Goals of this investigation included evaluating COVID-19 symptoms in this setting and assessing the effectiveness of serial testing to identify additional persons with SARS-CoV-2 infection as part of efforts to mitigate transmission. During May 7-21, testing of 98 incarcerated and detained persons residing in the five quarantined dormitories (A-E) identified an additional 71 cases of SARS-CoV-2 infection; 32 (45%) were among persons who reported no symptoms at the time of testing, including three who were presymptomatic. Eighteen cases (25%) were identified in persons who had received negative test results during previous testing rounds. Serial testing of contacts from shared living quarters identified persons with SARS-CoV-2 infection who would not have been detected by symptom screening alone or by testing at a single time point. Prompt identification and isolation of infected persons is important to reduce further transmission in congregate settings such as correctional and detention facilities and the communities to which persons return when released.


Predictors and Clinical Impacts of Aggravated Left Ventricular Diastolic Dysfunction After Off-Pump Coronary Artery Bypass Grafting.
To determine the predictors of aggravated left ventricular diastolic dysfunction (LVDD) in patients undergoing off-pump coronary artery bypass grafting (OPCAB) and to compare late outcomes according to the aggravated LVDD. OPCAB was performed in 1,101 patients (2001-2013). LVDD was classified as normal, mild, moderate or severe. Patients were divided into 2 groups: non-aggravated LVDD (group I) and aggravated LVDD (group II). The primary endpoint was aggravation of LVDD. The secondary endpoint was late mortality and morbidity such as major adverse cardiac and cerebrovascular events (MACCE) related to LVDD aggravation postoperatively. There were 894 patients in group I and 207 in group II. Multivariate analysis revealed that preoperative peripheral artery obstructive disease (PAOD) (P=0.04), renal failure (P<0.01), and A' velocity (P<0.01) anticipated aggravated LVDD. The Cox hazards model revealed that aggravated LVDD was a poor prognostic factor for MACCE (P<0.01) and overall survival (P<0.01). The Kaplan-Meier survival curve showed that aggravated LVDD was related to poor late outcomes (freedom from MACCE, P=0.01; overall survival, P<0.01). Aggravated LVDD significantly affects late clinical outcomes after OPCAB and preoperative PAOD, renal failure, and A' velocity might be predictors. (Circ J 2016; 80: 1937-1945).


The relationship between HbA1c and cardiovascular events in diabetic patients with coronary angioplasty: A cross-sectional study.
Re-establishment of coronary artery blood flow in diabetic patients has always been a controversial issue in the treatment of cardiovascular diseases. Due to the importance of this issue and the increase in mortality due to heart disease, the present study was performed to determine the relationship between HbA1C and cardiovascular events in diabetic patients with coronary angioplasty referred to Imam Khomeini Hospital in Ahvaz. This was a descriptive cross-sectional study in which 114 patients were enrolled in a census study that was followed for 3 to 6 months. Data was collected by a checklist and by the researcher using the patient's medical record. Then it was analyzed by SPSS 22 software and descriptive statistics. There was no significant relationship between age, gender, family history of diabetes, family history of heart disease, duration of diabetes, stroke, myocardial infarction, and heart failure with HbA1c (P > 0.05). However, there was a significant relationship between the type of coronary angioplasty, hypertension, and heart block with HbA1c (P < 0.05). According to the results of this study, there was a significant relationship between the type of coronary angioplasty, hypertension, and heart block with HbA1c; thus HbA1c should be better controlled in diabetic patients who decide to have angioplasty.


Asymmetric proliferation with optically active polyanilines.
Thin optically active polyaniline layers have been shown to function as platforms to induce optical activity in polyanilines (containing achiral dopants) that are formed by subsequent electrodeposition.


Sickness absenteeism among primary health care workers in Qatar before and during the COVID-19 pandemic.
To explore the patterns, trends, nature, and extent of changes in sickness absence among health care workers (HCWs) at the Primary Health Care Corporation (PHCC) in Qatar-during the COVID-19 pandemic compared to previous years and uncover the main associated factors. We conducted a retrospective analysis of all sick leaves' records of PHCC HCWs regardless of their profession from January 2019 till August 2021. A total of 41,132 sick leaves were taken during the studied period. The majority of HCWs who availed sick leaves were between 30-39 years (45.9%), females (65.1%), and expatriates (65.1%). Compared with pre-COVID-19 (Jan 2019-Feb 2020), Wave 1 of COVID-19 had significantly less incidence of sick leaves per day per 1000 HCWs. While wave 2 had significantly higher incidence of sick leaves compared to both pre-COVID-19 and wave 1. The number of sick leaves per person among female HCWs was significantly higher than that of male HCWs. Moreover, the number of sick leaves per person among locals were about two times the number among expatriate HCWs. Physicians and nurses had significantly lower number of sick leave per person compared to other professions. The rates of sick leaves due to suspected or confirmed COVID-19 infection, back/neck pain and gastroenteritis were significantly higher in the second wave compared to the first wave of COVID-19. Overall and cause specific sick leave rates among HCWs varied significantly across different periods of the COVID-19 pandemic. COVID-19 related sick leave rate was higher during the second wave compared to first one. By addressing the root causes of sick leaves, it is possible to reduce the burden on HCWs and ensure their continued ability to provide essential care to those in need.


Current immunotherapy in multiple sclerosis.
The underlying pathophysiology of multiple sclerosis is presumed to be autoimmune in nature. Attempts to find an effective treatment for this common disease of the central nervous system have primarily focused on immune-mediated therapies, both immunosuppressive and immunomodulatory. The wide variety of immunological abnormalities detected in multiple sclerosis and its animal model, experimental allergic encephalomyelitis, has prompted the testing of a diverse array of drugs to be used for treatment. Recent successes in the treatment of relapsing-remitting multiple sclerosis with interferon beta and glatiramer acetate have renewed interest in and raised expectations for the effective control of this neurological disorder. Improved methodology in clinical trials, the development of surrogate markers and the availability of novel therapies bode well for more rapid advances.


The detection of NK cell alloreactivity by flow cytometric CD107a assay.
Natural killer (NK) cell alloreactivity can be exploited in haploidentical (one haplotype mismatched) haematopoietic stem cell transplantation (HSCT) to prevent leukaemia relapse, rejection, and graft-vs-host disease (GVHD) (Blood 94:333-339; Science 295:2097-2100). If NK cell alloreactivity is to be exploited in HSCT, it is important to be able to reliably select donors who have NK alloreactivity towards the patient. The detection of donor NK alloreactivity towards patient target cells has traditionally been evaluated by NK cell cloning and (51)Cr-release cytotoxicity assay. This approach is complex and time consuming with results taking up to 6 weeks. Here, we detail a novel flow cytometric CD107a-based assay capable of detecting NK cell alloreactivity in 14 days.


Factors influencing trends of polychlorinated naphthalenes and other dioxin-like compounds in lake trout (Salvelinus namaycush) from Lake Ontario, North America (1979-2004).
Concentrations of polychlorinated naphthalenes (PCNs) were determined in archived lake trout (Salvelinus namaycush) from Lake Ontario, North America, collected between 1979 and 2004 to evaluate their temporal trends and the factors influencing their trends. Concentrations of PCNs, as well as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and non- and mono-ortho-substituted polychlorinated biphenyls (DL-PCBs), which were measured for comparative purposes, declined by eight-, seven-, and fivefold, respectively, between 1979 and 2004. Apparent elimination rate constants (k2) were calculated as the slopes of the regression lines of concentration versus time for PCN, DL-PCB, and PCDD/F congeners to compare the rate of decrease among congeners within and between compound classes. The k2 values for PCNs that had two pairs or three adjacent carbons unsubstituted with chlorine (congeners that can be biotransformed by vertebrates) were not significantly different from zero, indicating no decline in fish. For PCN congeners having no adjacent carbons unsubstituted with chlorine, the k2 values generally increased with hydrophobicity and degree of chlorination. This pattern differed from that of PCDD/Fs and DL-PCBs and from previous findings for non-DL-PCBs, for which the rate of contaminant decline decreased with hydrophobicity, and the pattern also differed from expectations based on thermodynamics. Differences in the rate of decline of PCN congeners may be caused by changes in source or mixture formulations over time and/or metabolic dechlorination of the less stable, higher-chlorinated PCNs 73, 74, and 75 to lower-chlorinated congeners. Based on suggested dioxin toxic equivalency factors, PCN concentrations in these whole lake trout may be sufficient to trigger consumption restrictions in Ontario, Canada, and our results suggest that PCNs merit incorporation into monitoring and assessment programs.


Bovine sperm hyperactivation is promoted by alkaline-stimulated Ca2+ influx.
Sperm hyperactivated motility is characterized by high flagellar bend amplitude and asymmetrical beating, which are detected by computer-assisted sperm motility analysis as increased curvilinear velocity and lateral head movement. It is required for sperm penetration of the oocyte zona pellucida during fertilization and is induced by an increase in flagellar Ca(2+). Our objective was to determine whether pH plays a role in promoting Ca signaling of hyperactivated motility. The cell-permeant weak base NH(4)Cl increased curvilinear velocity and amplitude of lateral head movement of bovine sperm, indicative of hyperactivation. Fluorometric recordings of sperm loaded with BCECF-AM or fluo3-AM, revealed that NH(4)Cl evoked elevations of intracellular pH and Ca(2+), respectively, with the rise in pH occurring more rapidly than that of Ca(2+). Single-cell image analysis showed increased Ca(2+) levels in the flagellum in response to NH(4)Cl. When extracellular Ca(2+) was lowered with BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) prior to treatment with NH(4)Cl, intracellular pH was increased, but elevation of Ca(2+) and hyperactivation were diminished. This suggests that the rise in intracellular pH precedes an influx of Ca(2+). The Ca(2+) channel blocker Ni(2+) also diminished NH(4)Cl stimulation of hyperactivation, demonstrating that Ca(2+) entry is required for maximal expression of hyperactivation. Ca(2+) ionophore produced an increase in Ca(2+) that was 3-fold greater than that produced by NH(4)Cl; however, it produced a weaker hyperactivation response. These results indicate that a rise in pH increases intracellular Ca(2+)and promotes hyperactivation primarily by stimulating Ca(2+) influx, but also by other mechanisms.


[Prepartal diagnosis of fetal abnormalities from the viewpoint of the obstetrician].
Over a period of 51/2 years 685 amniocenteses were carried out for genetic and obstetric indications at the University Department of Obstetrics and Gynecology Graz. In 39 cases (5,7%) the procedure had to be repeated. Chromosome diagnosis was achieved in altogether 99% of cases. Chromosome aberrations or malformations were found in 25 patients (3,6%). 18 pregnancies (2,6%) ended with a miscarriage or missed abortion up to the 28th week of gestation following amniocentesis. Leakage of amniotic fluid following amniocentesis was recorded in eight women. Seven of these gave birth at term, while one woman had an abortion. No case of maternal injury, bleeding or infection was recorded. In conclusion, when the risk of giving birth to a malformed child is compared with possible complications following amniocentesis there can be no doubt that this procedure is definitely indicated.