Morphology of the hallucial phalanges in extant anthropoids and fossil hominoids.
Pedal phalanges of living anthropoids and several Miocene fossil hominoid taxa were studied to reveal functional adaptations of living anthropoid feet and to infer positional behavior of fossil hominoids. Among the examined living anthropoids, Pan has a very developed (long and robust) hallux. Proconsul and Nacholapithecus, a large hominoid from Nachola, northern Kenya, display a moderately long hallux like Alouatta and Cebus, suggesting the well-developed capability of a hallux-assisted power grip. Allometric analyses revealed that the Miocene hominoids examined (mainly from East Africa) as a whole displayed a different scaling pattern about the width of the proximal articular surface of the hallucial terminal phalanx from that of living anthropoids. Larger-sized hominoids display a wider articular surface than comparable-sized living anthropoids while smaller-sized fossil hominoids do the reverse. Such a difference was less marked for the height of the articular surface. These results may suggest that positional adaptations of Miocene hominoids are not merely resultants of a common body size function that is observed in living anthropods. The wide articular surface of fossil hominoid hallucial terminal phalanges suggests an adaptation for vertical climbing and clinging, in which the hallux is kept perpendicularly to the long axis of the vertical support.


Transsclerally sutured versus ciliary sulcus lenses.
We evaluated retrospectively the results of 39 eyes in which the implantation of a lens in the capsular bag was not possible. Due to the loss of capsule a transsclerally sulcus sutured lens (TSSL) was implanted in 9 eyes. In 30 eyes a ciliary sulcus supported lens (SSL) could be implanted using residual capsule support. Lens implantation in the ciliary sulcus resulted in improved vision in 33/39 eyes (7/9 TSSLs, 26/30 SSLs). Postoperatively slight decentration of the implant lens was observed in 3 eyes, 6 eyes developed glaucoma, 5 eyes developed hyphema after surgery and 2 patients developed retinal detachment in the late postoperative period.


Acylation stabilizes a protease-resistant conformation of protoporphyrinogen oxidase, the molecular target of diphenyl ether-type herbicides.
Protein acylation is an important way in which a number of proteins with a variety of functions are modified. The physiological role of the acylation of cellular proteins is still poorly understood. Covalent binding of fatty acids to nonintegral membrane proteins is thought to produce transient or permanent enhancement of the association of the polypeptide chains with biological membranes. In this paper, we investigate the functional role for the palmitoylation of an atypical membrane-bound protein, yeast protoporphyrinogen oxidase, which is the molecular target of diphenyl ether-type herbicides. Palmitoylation stabilizes an active heat- and protease-resistant conformation of the protein. Palmitoylation of protoporphyrinogen oxidase has been demonstrated to occur in vivo both in yeast cells and in a heterologous bacterial expression system, where it may be inhibited by cerulenin leading to the accumulation of degradation products of the protein. The thiol ester linking palmitoleic acid to the polypeptide chain was shown to be sensitive to hydrolysis by hydroxylamine and also by the widely used serine-protease inhibitor phenylmethylsulfonyl fluoride.


Determination of complex type free, non-conjugated oligosaccharide glucose unit values in tomato xylem sap for early detection of nutrient deficiency.
Although knowledge on glycan biosynthesis and processing is continuously maturing, there are still a limited number of studies that examine biological functions of N-glycan structures in plants, which remain virtually unknown. Here, the statistical correlation between nutrient (nitrogen) deficiency symptoms of crops and changes in 8-aminopyrene-1,3,6-trisulfonic acid (APTS)-labeled complex type free oligosaccharides is reported. While deficiency symptoms are predicted by multispectral images and Kjeldahl digestion, APTS-labeled complex type free oligosaccharides are identified by their glucose unit (GU) values in tomato xylem sap, using capillary electrophoresis with laser induced fluorescence detection (CE-LIF). Given the limited number of structures obtained from plants, archived in the literature, in the future, it is intended to create an open access database of promising indicators, namely, glycan structures that are presumably responsible for the nutrient deficiency caused stress in plants (http://glycoplants.org).


Worsening trends in the management and treatment of back pain.
Back pain treatment is costly and frequently includes overuse of treatments that are unsupported by clinical guidelines. Few studies have evaluated recent national trends in guideline adherence of spine-related care. To characterize the treatment of back pain from January 1, 1999, through December 26, 2010. Using nationally representative data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, we studied outpatient visits with a chief symptom and/or primary diagnosis of back or neck pain, as well as those with secondary symptoms and diagnoses of back or neck pain. We excluded visits with concomitant "red flags," including fever, neurologic symptoms, or cancer. Results were analyzed using logistic regression adjusted for patient and health care professional characteristics and weighted to reflect national estimates. We also present adjusted results stratified by symptom duration and whether the health care professional was the primary care physician (PCP). We assessed imaging, narcotics, and referrals to physicians (guideline discordant indicators). In addition, we evaluated use of nonsteroidal anti-inflammatory drugs or acetaminophen and referrals to physical therapy (guideline concordant indicators). We identified 23,918 visits for spine problems, representing an estimated 440 million visits. Approximately 58% of patients were female. Mean age increased from 49 to 53 years (P< .001) during the study period. Nonsteroidal anti-inflammatory drug or acetaminophen use per visit decreased from 36.9% in 1999-2000 to 24.5% in 2009-2010 (unadjusted P< .001). In contrast, narcotic use increased from 19.3% to 29.1% (P< .001). Although physical therapy referrals remained unchanged at approximately 20%, physician referrals increased from 6.8% to 14.0% (P< .001). The number of radiographs remained stable at approximately 17%, whereas the number of computed tomograms or magnetic resonance images increased from 7.2% to 11.3% during the study period (P< .001). These trends were similar after stratifying by short-term vs long-term presentations, visits to PCPs vs non-PCPs, and adjustment for age, sex, race/ethnicity, PCP status, symptom duration, region, and metropolitan location. Despite numerous published clinical guidelines, management of back pain has relied increasingly on guideline discordant care. Improvements in the management of spine-related disease represent an area of potential cost savings for the health care system with the potential for improving the quality of care.


Composite IS1-tetracycline resistance elements in aerobactin-encoding FIme plasmids from epidemic Salmonella wien.
Class B tetracycline resistance determinants have been identified in two aerobactin-encoding FIme plasmids representative of those isolated from epidemic Salmonella wien. Genetic data, restriction enzyme analysis of recombinant and mutant plasmids, and Southern blot hybridizations indicate that in both plasmids the class B determinant so far found and described only on Tn10-like transposons is part of a different genetic element. This composite insertion sequence element is about 7 kilobases long and has copies of insertion sequence IS1 at the ends.


Acute splenic sequestration in a pregnant woman with homozygous sickle-cell anemia.
Homozygous (SS) sickle-cell anemia complicated by acute splenic sequestration in adults is a rare event, and it has never been reported during pregnancy. A 25-year-old woman with homozygous (SS) sickle-cell disease was hospitalized at 32 weeks' of gestation presenting weakness, abdominal pain, fever and hemoglobin of 2.4 g/dl. Abnormal fetal heart rate was detected by means of cardiotocography, and 5 units of packed red cells were transfused. Cesarean was performed at 37 weeks. Both mother and baby were discharged in a good general condition. This case report demonstrates the importance of immediate blood transfusion for treatment of fetal distress in cases of splenic sequestration during pregnancy. This treatment is essential for avoiding maternal and fetal complications.


Constitutive expression of transforming growth factor alpha does not transform rat thyroid epithelial cells.
To evaluate the role of transforming growth factor alpha (TGF alpha) in transformed rat thyroid epithelial cells, expression and production of TGF alpha were measured in a normal rat thyroid epithelial cell line, FRTL-5, and in the same cells transformed by the Ki-ras oncogene. FRTL-5 cells transformed with Ki-ras exhibit a 5- to 7-fold increase in the levels of TGF alpha-specific mRNA and a 3- to 4-fold enhancement of the amounts of TGF alpha protein in the conditioned medium, as compared with the normal thyroid cells. Although conditioned medium from the Ki-ras transformed FRTL-5 cells or authentic epidermal growth factor or TGF alpha are able to stimulate the anchorage-dependent growth of nontransformed FRTL-5 cells, neither conditioned medium nor the growth factors are able to induce the anchorage-independent growth of these cells in soft agar. FRTL-5 cells were then transfected with an expression vector plasmid containing the human TGF alpha cDNA to directly ascertain if over-expression of this growth factor is able to induce transformation in these cells. The TGF alpha-transfected FRTL-5 clones constitutively produced high amounts of TGF alpha at a level equivalent to or greater than the level found in the conditioned medium from the Ki-ras transformed FRTL-5 clones. Moreover, in contrast to the Ki-ras transformed cells, the TGF alpha transfectants were unable to grow in soft agar, did not form tumors in nude mice, and showed no reduction in the secretion of thyroglobulin. These data demonstrate that unlike Ki-ras, the constitutive expression of biologically active TGF alpha is not entirely sufficient to elicit a transformed phenotype in these cells.


Adverse effects of gestational diabetes-related risk factors on pregnancy outcomes and intervention measures.
This study was designed to investigate the risk factors of gestational diabetes mellitus (GDM), analyze its adverse effects on pregnancy outcomes and propose corresponding interventions. From January 2017 to December 2018, 378 GDM patients (GDM group) awaiting delivery in Weifang People's hospital were selected. At the same time, 200 pregnant women with normal blood glucose (NGT) were randomly selected as the control group. According to general and clinical data, the univariate and multivariate logistic regression analyses were used to screen the risk factors for GDM. The pregnancy outcomes of the two groups were calculated and corresponding intervention measures were proposed to provide a basis for the comprehensive prevention and treatment of gestational diabetes. Multivariate logistic regression analysis showed that age, pre-pregnancy body mass index (BMI), family history of diabetes, 2 h postprandial blood glucose (2hPBG), and glycated hemoglobin (HbA1c) were independent risk factors for GDM (P<0.05). The incidence of dystocia and cesarean section, abnormal amniotic fluid, premature rupture of membranes, and pathological pregnancy in the GDM group were significantly higher than those in the normal control group (P<0.01). The probability of fetal distress, macrosomia, small for date infants, and preterm infants in the GDM group was significantly higher than those in the normal control group (P<0.01). The 2hPBG and HbA1c in the GDM group after the intervention were significantly lower than those before intervention (P<0.05). The age of pregnant women and family history of diabetes play important roles in the presence and progression of GDM. Therefore, pregnant women should pay close attention to the relevant risk factors that trigger GDM, in the screening and prevention of GDM during pregnancy, reduce and prevent the presence of GDM to ensure the safety of mothers and infants.


Fecal bacterial communities of wild-captured and stranded green turtles (Chelonia mydas) on the Great Barrier Reef.
Green turtles (Chelonia mydas) are endangered marine herbivores that break down food particles, primarily sea grasses, through microbial fermentation. However, the microbial community and its role in health and disease is still largely unexplored. In this study, we investigated and compared the fecal bacterial communities of eight wild-captured green turtles to four stranded turtles in the central Great Barrier Reef regions that include Bowen and Townsville. We used high-throughput sequencing analysis targeting the hypervariable V1-V3 regions of the bacterial 16S rRNA gene. At the phylum level, Firmicutes predominated among wild-captured green turtles, followed by Bacteroidetes and Proteobacteria. In contrast, Proteobacteria (Gammaproteobacteria) was the most significantly dominant phylum among all stranded turtles, followed by Bacteroidetes and Firmicutes. In addition, Fusobacteria was also significantly abundant in stranded turtles. No significant differences were found between the wild-captured turtles in Bowen and Townsville. At the family level, the core bacterial community consisted of 25 families that were identified in both the wild-captured and stranded green turtles, while two unique sets of 14 families each were only found in stranded or wild-captured turtles. The predominance of Bacteroides in all groups indicates the importance of these bacteria in turtle gut health. In terms of bacterial diversity and richness, wild-captured green turtles showed a higher bacterial diversity and richness compared with stranded turtles. The marked differences in the bacterial communities between wild-captured and stranded turtles suggest the possible dysbiosis in stranded turtles in addition to potential causal agents.


The performance of South African English first language child speakers on a "low linguistically loaded" central auditory processing test protocol.
The lack of standardized tests for central auditory processing disorders (CAPD) in South Africa (SA) led to the formation of a SA CAPD Taskforce, and the interim development of a "Low Linguistically Loaded" CAPD test protocol using test recordings from the 'Tonal and Speech Materials for Auditory Perceptual Assessment Disc 2.0'. This study compared the performance of 50 SA English first language child speakers (aged 8 to 12 years of age) on this protocol, with the previously published American normative data of Bellis (1996, 2003). Results with respect to predicted pass criteria as calculated by mean-2SD cutoffs, suggested that the SA speakers performed of a lower level than the American speakers by an average of 5.3% per ear for the two pair dichotic digits test, 1.9 dB for the masking level difference test, 8.8% per ear for the frequency pattern test--humming report, 14.5% per ear for the frequency patterns test--verbal report, and 39.7% per ear for the low pass filtered speech test. Consequently, the Bellis (1996, 2003) data was not considered appropriate for immediate use as normative data in SA. Instead, the preliminary data provided in this study was recommended as interim normative data for SA English first language child speakers until larger scale SA normative data can be obtained.


A plea for neutral comparison studies in computational sciences.
In computational science literature including, e.g., bioinformatics, computational statistics or machine learning, most published articles are devoted to the development of "new methods", while comparison studies are generally appreciated by readers but surprisingly given poor consideration by many journals. This paper stresses the importance of neutral comparison studies for the objective evaluation of existing methods and the establishment of standards by drawing parallels with clinical research. The goal of the paper is twofold. Firstly, we present a survey of recent computational papers on supervised classification published in seven high-ranking computational science journals. The aim is to provide an up-to-date picture of current scientific practice with respect to the comparison of methods in both articles presenting new methods and articles focusing on the comparison study itself. Secondly, based on the results of our survey we critically discuss the necessity, impact and limitations of neutral comparison studies in computational sciences. We define three reasonable criteria a comparison study has to fulfill in order to be considered as neutral, and explicate general considerations on the individual components of a "tidy neutral comparison study". R codes for completely replicating our statistical analyses and figures are available from the companion website http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/020_professuren/boulesteix/plea2013.


Design of microchannel free-space optical interconnects based on vertical-cavity surface-emitting laser arrays.
We investigate the design of free-space optical interconnects (FSOIs) based on arrays of vertical-cavity surface-emitting lasers (VCSELs), microlenses, and photodetectors. We explain the effect of the modal structure of a multimode VCSEL beam on the performance of a FSOI with microchannel architecture. A Gaussian-beam diffraction model is used in combination with the experimentally obtained spectrally resolved VCSEL beam profiles to determine the optical channel crosstalk and the signal-to-noise ratio (SNR) in the system. The dependence of the SNR on the feature parameters of a FSOI is investigated. We found that the presence of higher-order modes reduces the SNR and the maximum feasible interconnect distance. We also found that the positioning of a VCSEL array relative to the transmitter microlens has a significant impact on the SNR and the maximum feasible interconnect distance. Our analysis shows that the departure from the traditional confocal system yields several advantages including the extended interconnect distance and/or improved SNR. The results show that FSOIs based on multimode VCSELs can be efficiently utilized in both chip-level and board-level interconnects.


Aortic thrombosis in infancy.
A 33-day-old female was admitted to hospital with the diagnosis of viral bronchiolitis. The physical examination performed after treatment with bronchodilators revealed a grade 2/6 systolic ejection murmur at the left upper sternal edge. The arterial pulses and blood pressure in all extremities were normal. The two-dimensional echocardiogram revealed a mass measuring 3.5 x 3.5 cm at the ductus level consistent with a thrombus; there was flow acceleration at the level of the proximal descending aorta with no significant gradient. All other laboratory tests were normal except for an elevated platelet count. The infant was treated with subcutaneous enoxaparin and oral aspirin for four months and nine months, respectively Progressively the clot became smaller, however still visible at last evaluation at age of 12 months. Her growth and development remained normal. Aorticthrombosis in neonates and young children is uncommon. Until 2000 only 63 cases had been reported in the English literature. Spontaneous aortic thrombosis is rare. A 20-year literature review in 2006 yielded only 12 such cases. The clinical presentation is variable and the prognosis can be life threatening. The prognosis depends on the size and location of the thrombus, the underlying cause, delay in reaching a diagnosis, and the treatment modality.


GAL4/GAL80-dependent nucleosome disruption/deposition on the upstream regions of the yeast GAL1-10 and GAL80 genes.
Metabolic reactivation (incubating spheroplasts with galactose and casamino acids) causes disruption of nucleosomes from the upstream regions of the yeast GAL1, GAL10, and GAL80 genes. The disruption is specific. It depends on the transcription activator Gal4; it only occurs in galactose-reactivated chromatin from galactose-grown cells; it only affects upstream region, gene-proximal nucleosomes. Due to this specificity and because some of the same regions have shown induction-dependent changes by in vivo analyses, we suggest that the nucleosome-disrupted structure produced by reactivation is the authentic chromatin structure for these regions under conditions of galactose-induced GAL1-10 and GAL80 expression. It is necessary to carry out a spheroplast reactivation treatment in order to observe this disrupted structure in nuclear chromatin because nucleosomes are redeposited onto these regions during the preliminary steps of nuclear isolation (cell harvest/spheroplast preparation) probably in response to the nonphysiological conditions associated with these steps. However, during the same isolation procedures in cells lacking Gal80 protein, there is no nucleosome deposition on these regions, and the in vivo disrupted structure remains present in the nuclear chromatin. Therefore, the nucleosome deposition process that operates in wild-type cells is dependent on Gal80 protein, defining another activity of this negative regulator.


Local Order and Dynamics of Nanoconstrained Ethylene-Butylene Chain Segments in SEBS.
Subtle alterations in the mid-block of polystyrene-b-poly (ethylene-co-butylene)-b-polystyrene (SEBS) have a significant impact on the mechanical properties of the resulting microphase separated materials. In samples with high butylene content, the ethylene-co-butylene (EB) phase behaves as a rubber, as seen by differential scanning calorimetry (DSC), time domain (TD) and Magic Angle Spinning (MAS) NMR, X-ray scattering at small (SAXS), and wide (WAXS) angles. In samples where the butylene content is lower-but still sufficient to prevent crystallization in bulk EB-the DSC thermogram presents a broad endothermic transition upon heating from 221 to 300 K. TD NMR, supported by WAXS and dielectric spectroscopy measurements, probed the dynamic phenomena of EB during this transition. The results suggest the existence of a rotator phase for the EB block below room temperature, as a result of nanoconfinement.


Nonadditive protein accumulation patterns in Maize (Zea mays L.) hybrids during embryo development.
Heterosis describes the superior performance of heterozygous F(1)-hybrid plants compared to their homozygous parental inbred lines. In the present study, heterosis was detected for length, weight, and the time point of seminal root primordia initiation in maize (Zea mays L.) embryos of the reciprocal F(1)-hybrids UH005xUH250 and UH250xUH005. A two-dimensional gel electrophoresis (2-DE) proteome survey of the most abundant proteins of the reciprocal hybrids and their parental inbred lines 25 and 35 days after pollination revealed that 141 of 597 detected proteins (24%) exhibited nonadditive accumulation in at least one hybrid. Approximately 44% of all nonadditively accumulated proteins displayed an expression pattern that was not distinguishable from the low parent value. Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) analyses and subsequent functional classification of the 141 proteins revealed that development, protein metabolism, redox-regulation, glycolysis, and amino acid metabolism were the most prominent functional classes among nonadditively accumulated proteins. In 35-day-old embryos of the hybrid UH250xUH005, a significant up-regulation of enzymes related to glucose metabolism which often exceeded the best parent values was observed. A comparison of nonadditive protein accumulation between rice and maize embryo data sets revealed a significant overlap of nonadditively accumulated proteins suggesting conserved organ- or tissue-specific regulatory mechanisms in monocots related to heterosis.


Defining the burden of pneumonia in children preventable by vaccination against Haemophilus influenzae type b.
To determine the burden of pneumonia requiring hospitalization in infants and young children preventable by vaccination against Haemophilus influenzae type b (Hib). Vaccination centers in Santiago, Chile, were randomly selected to administer PRP-T, an Hib conjugate vaccine, combined with diphtheria-tetanus toxoids-pertussis (DTP) vaccine or DTP alone. Infants who received > or =2 doses of DTP or DTP and Hib conjugate vaccine combined. Pneumonia episodes leading to hospitalization accompanied by indicators of likely bacterial infection including radiologic evidence of alveolar consolidation or pleural effusion, an elevated erythrocyte sedimentation rate (> or =40 mm/h) or bronchial breath sounds on auscultation. In participants age 4 to 23 months, PRP-T reduced the incidence of pneumonia associated with alveolar consolidation or pleural effusion by 22% (95% confidence interval, -7 to 43) from 5.0 to 3.9 episodes per 1000 children per year. When the pneumonia case definition included any of the following, alveolar consolidation, pleural effusion, erythrocyte sedimentation rate > or =40 mm/h or bronchial breath sounds, PRP-T provided 26% protection (95% confidence interval, 7 to 44) and prevented 2.5 episodes per 1000 children per year. Hib vaccine provides substantial protection against nonbacteremic pneumonia, particularly those cases with alveolar consolidation, pleural effusion or other signs of likely bacterial infection. Hib vaccination prevented approximately 5 times as many nonbacteremic pneumonia cases in infants as meningitis cases, thus indicating that the largest part of the effect of Hib vaccination might be undetectable by routine culture methods.


Conformation of tropolone ring in antileukemic tropoloisoquinoline alkaloids.
Conformational analysis of antileukemic tropoloisoquinoline alkaloids isolated from Cissampelos pareira was conducted by thermodynamic proton nuclear magnetic resonance (1H NMR) studies. The line-broadening of one of methoxy methyl signals can be explained by the tropolone ring-puckering process. Analysis by dynamical simulated annealing and modified neglect of differential overlap (MNDO) calculations also supported puckering of tropolone ring system.


A finite difference thermal model of a cylindrical microwave heating applicator using locally conformal overlapping grids: part I--theoretical formulation.
In this paper, we present a versatile mathematical formulation of a newly developed 3-D locally conformal Finite Difference (FD) thermal algorithm developed specificallyfor coupled electromagnetic (EM) and heat diffusion simulations utilizing Overlapping Grids (OGFD) in the Cartesian and cylindrical coordinate systems. The motivation for this research arises from an attempt to characterize the dominant thermal transport phenomena typically encountered during the process cycle of a high-power, microwave-assisted material processing system employing a geometrically composite cylindrical multimode heating furnace. The cylindrical FD scheme is only applied to the outer shell of the housing cavity whereas the Cartesian FD scheme is used to advance the temperature elsewhere including top and bottom walls, and most of the inner region of the cavity volume. The temperature dependency of the EM constitutive and thermo-physical parameters of the material being processed is readily accommodated into the OGFD update equations. The time increment, which satisfies the stability constraint of the explicit OGFD time-marching scheme, is derived. In a departure from prior work, the salient features of the proposed algorithm are first, the locally conformal discretization scheme accurately describes the diffusion of heat and second, significant heat-loss mechanisms usually encountered in microwave heating problems at the interfacial boundary temperature nodes have been considered. These include convection and radiation between the surface of the workload and air inside the cavity, heat convection and radiation between the inner cavity walls and interior cavity volume, and free cooling of the outermost cavity walls.


Low Heart Rate Variability Predicts Poor Overall Survival of Lung Cancer Patients With Brain Metastases.
The aim of this prospective study was to evaluate the association between heart rate variability (HRV) and overall survival of lung cancer patients with brain metastases (LCBM). Fifty-six LCBM patients were enrolled in this study. Five-minute electrocardiograms were collected before the time to first brain radiotherapy. HRV was analyzed quantitatively by using the time domain parameters, i.e., the standard deviation of all normal-normal intervals (SDNN) and the root mean square of successive differences (RMSSD). Survival time for LCBM patients was defined as from the date of HRV testing to the date of death or the last follow-up. In the univariate analysis, SDNN ≤ 13 ms (P = 0.003) and RMSSD ≤ 4.8 ms (P = 0.014) significantly predicted poor survival. Multivariate analysis confirmed that RMSSD ≤ 4.8 ms (P = 0.013, hazard ratio = 3.457, 95% confidence interval = 1.303-9.171) was also an independent negative prognostic factor after adjusting for mean heart rate, Karnofsky performance status, and number of brain metastases in LCBM patients. Decreased RMSSD is independently associated with shorter survival time in LCBM patients. HRV might be a novel predictive biomarker for LCBM prognosis.


Cell lines generated from a chronic lymphocytic leukemia mouse model exhibit constitutive Btk and Akt signaling.
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5+ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic expression of SV40 large T antigen. The cell lines exhibit a stable CD5+CD43+IgM+CD19+ CLL phenotype in culture and can be adoptively transferred into Rag1-/- mice. RNA-seq analysis revealed only minor differences between the cell lines and their primary tumors and suggested that NF-κB and mTOR signaling pathways were involved in cell line outgrowth. In vitro survival and proliferation was dependent on constitutive phosphorylation of Bruton's tyrosine kinase (Btk) at Y551/Y223, and Akt(S473). Treatment of the cell lines with small molecule inhibitors specific for Btk (ibrutinib) or PI3K (idelalisib), which is upstream of Akt, resulted in reduced viability, proliferation and fibronectin-dependent cell adhesion. Treatment of cell line-engrafted Rag1-/- mice with ibrutinib was associated with transient lymphocytosis, reduced splenomegaly and increased overall survival. Thus, by generating stable cell lines we established a novel platform for in vitro and in vivo investigation of CLL signal transduction and treatment modalities.


2,6-Dichloro-9-thiabicyclo[3.3.1]nonane: a privileged, bivalent scaffold for the display of nucleophilic components.
The title compound, the condensation product of sulfur dichloride and 1,5-cyclooctadiene, is a reliable acceptor of a wide variety of heteroatom nucleophiles, sometimes in reversible fashion. Optical resolution of the core structure has been achieved and preserved in succeeding transformations. The high reactivity and reliable stereochemical control afforded by this system illustrates the power of neighboring-group participation by the sulfur center.


Effectiveness of Progestogens as Maintenance Tocolysis and Urogenital Cultures: Secondary Analysis of the PROTECT Trial.
Background In a recently published multicenter randomized controlled trial, we demonstrated that progestogens are not effective as maintenance tocolysis. Objective This study was aimed to evaluate if previous finding may be affected by positive urine culture and/or vaginal swab. Study Design We performed a secondary analysis of the PROTECT trial (NCT01178788). Women with singleton pregnancy between 22 and 31 6/7 weeks' gestation, admitted for threatened preterm labor were considered. At admission, we collected urine culture and vaginal swabs. At discharge, women with a cervical length ≤25 mm were randomized to vaginal progesterone or 17α-hydroxyprogesterone caproate or observation group. We used Chi-square statistics, considering 97.5% CI (confidence interval) and p -value less than 0.025 for significance. Results Urine culture and vaginal swabs were collected in 232 out of 235 patients included in the primary analysis. Overall, 31 out of 232 women (13.4%) had positive urine culture and 60 out of 232 (25.9%) had positive vaginal swab. In women with negative urine culture, a higher rate of preterm birth was found in vaginal progesterone group (27/69, 39.7%) respect with controls (14/68, 20.6%; relative risk [RR] = 1.90; 97.5% CI: 1.01-3.57; p = 0.018). Conclusion Among women with negative urine culture, the rate of preterm birth <37 weeks' gestation was significantly increased in those receiving vaginal progesterone, reinforcing our previous findings in symptomatic women.


Epidemiology of female genital Chlamydia trachomatis infections.
The World Health Organization (WHO) has estimated that 92 million new cases of C. trachomatis (Chlamydia trachomatis) infection occur each year. This chapter focuses on the epidemiology of C. trachomatis infection, including the prevalence of infection in high- and low-risk groups, the incidence of infection, and data on secular trends. The evidence on the transmission of infection is reviewed. Risk factors for C. trachomatis infection in women are discussed. The adverse sequelae associated with C. trachomatis infection are described. Areas requiring further research are highlighted.


Expression of the major outer membrane protein of Chlamydia trachomatis in Escherichia coli.
The major outer membrane protein (MOMP) of Chlamydia trachomatis was expressed in Escherichia coli. To assess whether it assembled into a conformationally correct structure at the cell surface, we characterized the recombinant MOMP (rMOMP) by Western immunoblot analysis, indirect immunofluorescence, and immunoprecipitation with monoclonal antibodies (MAbs) that recognize contiguous and conformational MOMP epitopes. Western blot analysis showed that most of the rMOMP comigrated with authentic monomer MOMP, indicating that its signal peptide was recognized and cleaved by E. coli. The rMOMP could not be detected on the cell surface of viable or formalin-killed E. coli organisms by indirect immunofluorescence staining with a MAb specific for a MOMP contiguous epitope. In contrast, the same MAb readily stained rMOMP-expressing E. coli cells that had been permeabilized by methanol fixation. A MAb that recognizes a conformational MOMP epitope and reacted strongly with formalin- or methanol-fixed elementary bodies failed to stain formalin- or methanol-fixed E. coli expressing rMOMP. Moreover, this MAb did not immunoprecipitate rMOMP from expressing E. coli cells even though it precipitated the authentic protein from lysates of C. trachomatis elementary bodies. Therefore we concluded that rMOMP was not localized to the E. coli cell surface and was not recognizable by a conformation-dependent antibody. These results indicate that rMOMP expressed by E. coli is unlikely to serve as an accurate model of MOMP structure and function. They also question the utility of rMOMP as a source of immunogen for eliciting neutralizing antibodies against conformational antigenic sites of the protein.


Prognostic Effect of a Novel Simply Calculated Nutritional Index in Acute Decompensated Heart Failure.
The TCB index (triglycerides × total cholesterol × body weight), a novel simply calculated nutritional index based on serum triglycerides (TGs), serum total cholesterol (TC), and body weight (BW), was recently reported to be a useful prognostic indicator in patients with coronary artery disease. Thus, this study aimed to investigate the relationship between TCBI and long-term mortality in acute decompensated heart failure (ADHF) patients. Patients with a diagnosis of ADHF who were consecutively admitted to the cardiac intensive care unit in our institution from 2007 to 2011 were targeted. TCBI was calculated using the formula TG (mg/dL) × TC (mg/dL) × BW (kg)/1000. Patients were divided into two groups according to the median TCBI value. An association between admission TCBI and mortality was assessed using univariable and multivariable Cox proportional hazard analyses. Overall, 417 eligible patients were enrolled, and 94 (22.5%) patients died during a median follow-up period of 2.2 years. The cumulative survival rate with respect to all-cause, cardiovascular, and cancer-related mortalities was worse in patients with low TCBI than in those with high TCBI. In the multivariable analysis, although TCBI was not associated with cardiovascular and cancer mortalities, the association between TCBI and reduced all-cause mortality (hazard ratio: 0.64, 95% confidence interval: 0.44-0.94, p = 0.024) was observed. We computed net reclassification improvement (NRI) when TCBI or Geriatric Nutritional Risk Index (GNRI) was added on established predictors such as hemoglobin, serum sodium level, and both. TCBI improved discrimination for all-cause mortality (NRI: 0.42, p < 0.001; when added on hemoglobin and serum sodium level). GNRI can improve discrimination for cancer mortality (NRI: 0.96, p = 0.002; when added on hemoglobin and serum sodium level). TCBI, a novel and simply calculated nutritional index, can be useful to stratify patients with ADHF who were at risk for worse long-term overall mortality.


Ethionamide Pharmacokinetics/Pharmacodynamics-derived Dose, the Role of MICs in Clinical Outcome, and the Resistance Arrow of Time in Multidrug-resistant Tuberculosis.
Ethionamide is used to treat multidrug-resistant tuberculosis (MDR-TB). The antimicrobial pharmacokinetics/pharmacodynamics, the contribution of ethionamide to the multidrug regimen, and events that lead to acquired drug resistance (ADR) are unclear. We performed a multidose hollow fiber system model of tuberculosis (HFS-TB) study to identify the 0-24 hour area under the concentration-time curve (AUC0-24) to minimum inhibitory concentration (MIC) ratios that achieved maximal kill and ADR suppression, defined as target exposures. Ethionamide-resistant isolates underwent whole-genome and targeted Sanger sequencing. We utilized Monte Carlo experiments (MCEs) to identify ethionamide doses that would achieve the target exposures in 10000 patients with pulmonary tuberculosis. We also identified predictors of time-to-sputum conversion in Tanzanian patients on ethionamide- and levofloxacin-based regimens using multivariate adaptive regression splines (MARS). An AUC0-24/MIC >56.2 was identified as the target exposure in the HFS-TB. Early efflux pump induction to ethionamide monotherapy led to simultaneous ethambutol and isoniazid ADR, which abrogated microbial kill of an isoniazid-ethambutol-ethionamide regimen. Genome sequencing of isolates that arose during ethionamide monotherapy revealed mutations in both ethA and embA. In MCEs, 20 mg/kg/day achieved the AUC0-24/MIC >56.2 in >95% of patients, provided the Sensititre assay MIC was <2.5 mg/L. In the clinic, MARS revealed that ethionamide Sensititre MIC had linear negative relationships with time-to-sputum conversion until an MIC of 2.5 mg/L, above which patients with MDR-TB failed combination therapy. Ethionamide is an important contributor to MDR-TB treatment regimens, at Sensititre MIC <2.5 mg/L. Suboptimal ethionamide exposures led to efflux pump-mediated ADR.


The Management of Pancreatic Trauma - A Continuous Challenge.
Background: The aim of this analysis was to assess the factors that influence the severity of pancreatic trauma cases, also underlining the importance of early and accurate diagnosis and proper management of each case. Methods: This study is a retrospective analysis of patients that were presented to the Clinical Emergency Hospital of Bucharest, Romania, in several periods of time: 1985-1990 (50 patients); 1990-1999 (102 patients); 2000-2005 (56 patients); 2012-2019 (48 patients). Results: The mean age was around 40 years old, with predominance of male incidence in all the groups and traffic accidents (blunt trauma) as the main cause of injury. Most patients (almost 50% in each group) were operated on within the first 24 hours from hospital presentation. The general mortality rate varied: 42% (1985-1990), 23.5% (1990-1999), 12.7% (2000-2005) and 33% (2012-2015). Pancreatic mortality rate was 6% (1985-1990 and 1990-1999), 3.5% (2000-2005) and 8% (2012-2019). Conclusions: During the last 35 years, the preoperative diagnosis in patients with trauma of the pancreas remained a challenge and the treatment of the pancreatic trauma suffered a very interesting evolution- from the very frequent laparotomy to the nonoperative management and the damage control. These procedures produced a significant decreasing of the negative or nontherapeutic laparotomies. For the effectiveness of treatment, methods must be correlated with the lesion score.


Cognitive functions in patients with panic disorder: a literature review.
To conduct a review of the literature on the possible neuropsychological deficits present in patients with panic disorder. We performed a systematic review and search of the PubMed, ISI and PsycInfo scientific databases, with no time limits, using the following key words: cognitive, function, panic, and disorder. Of the 971 articles found, 25 were selected and 17 were included in this review. The inclusion criterion was at least one neuropsychological assessment task in patients with panic disorder. The number of publications has grown gradually, especially those assessing executive functions, corresponding to the neurobiological model most widely accepted. Of all the functions evaluated, these patients had lower performance in memory tasks and higher performance in affective processing tasks related to the disorder. However, these data require further investigation due to the high rate of comorbidities, the small sample sizes of the included studies and little standardization of instruments used. The results showed a greater occurrence of deficits in memory and enhanced affective processing related to panic disorder.


Medicine on the internet: Jewish perspectives.
The ethical principles of beneficence and non-maleficence are deeply rooted in Judaism. A physician is obligated to heal and is given Divine license to do so. A patient is also obligated to seek healing. Judaism also emphasizes prevention over treatment. Avoidance of danger and thereby the preservation of life and health are biblical mandates. Rules of personal hygiene such as hand washing before eating are also stressed, as are diet, exercise, and general care of the body. Preventive medical services and patient responsibilities are fully in accord with Jewish thought. Specifically with regard to the internet, Judaism views any new technology or scientific advance with favor if it is used for the betterment of mankind, such as the prevention and treatment of illness. The internet is a wonderful tool to accomplish this purpose. It can promote health education to millions of people and thereby help to prevent illness. It can be used to facilitate communication not only between physicians and patients, but between health care providers and large population groups. All these goals are consonant with traditional Jewish thought and practice. However, potential negative consequences from the medical use of the internet must be considered and avoided. Misleading or false medical information should be weeded out. Inappropriate medical commercialism on the internet should be banned. Confidentiality of medical information must be preserved. The limitations of the internet for the practice of medicine (e.g., lack of personal patient-physician contact) should be clearly explained to patients, to help them appreciate those features of the internet which can truly benefit them and society.


Survival is not enough.
Survival is not enough is a yearly international event started in 2007 in Naples, Italy, in the week of the World Kidney Day to discuss the needs of renal patients and the quality of life of a category of patients living a machine-dependent life. Renal patients and their associations, philosophers, economists, nephrologists, and health care managers are enrolled to discuss about the possibility to grant the best cures and care without reducing the quality and the quantity of the services the patients need. Various quests have arisen for (1) a new cadre of managers capable of keeping health accounts in balance without cutting expenditure but by reducing waste of resources, (2) the promotion of prevention as the only measure capable of reducing costs in the long run, and (3) the promotion of clinical and translational research. The changes occurring in the health system should be viewed as a window of opportunity, including the advent of the medical-industrial complex firstly described in 1980, an event originating in the United States of America and now spreading worldwide.


Granulocytic sarcoma of the spine: MRI and clinical review.
Granulocytic sarcoma is a tumor formed by myeloid precursors at an extramedullary site. The purpose of this study was to evaluate the MRI findings and clinical manifestations in 32 cases of granulocytic sarcoma of the spine. Thirty-two patients (21 males, 11 females; mean age, 32 years) with myeloid leukemia and spinal granulocytic sarcoma were included in this study. All of the patients underwent radiotherapy with chemotherapy, and four patients underwent surgical decompression or excisional biopsy. All 32 patients underwent MRI of the spine; 21 patients underwent follow-up MRI. Nine patients had spinal granulocytic sarcoma in the initial manifestation of leukemia. The other 23 diagnoses were made during a remission or relapse period. The lumbosacral and thoracic portions of the spine were commonly involved. Twenty-seven patients had multiple or contiguous multilevel involvement. According to location, spinal granulocytic sarcoma was classified as epidural in the central spinal canal, epidural along the nerve course, thickening of the nerve root itself, or prevertebral. Lesions were seen as isointense on T1-weighted images and had intermediate signal intensity with homogeneous enhancement on T2-weighted images. Nine patients had complete reduction of the tumor volume, and 12 patients had partial reduction. The median survival period was 9 months, and the 1-year survival rate was 41%. Knowledge of the imaging findings of spinal granulocytic sarcoma, which consists of multiple extramedullary masses with diffuse leukemic bone marrow infiltration, can lead to early diagnosis and appropriate treatment to reduce neurologic symptoms.


Scientific rationale for the use of alpha-adrenergic agonists and glucocorticoids in the therapy of pediatric stridor.
Purpose. The most common pharmacological therapies used in the treatment of stridor in children are glucocorticosteroids (GC) and alpha-adrenergic (αAR) agonists. Despite the long-standing reported efficacy of these medications, there is a paucity of data relating to their actual mechanisms of action in the upper airway. Summary. There is compelling scientific evidence supporting the use of αAR-agonists and GCs in pediatric stridor. αAR signaling and GCs regulate the vasomotor tone in the upper airway mucosa. The latter translates into better airflow dynamics, as delineated by human and nonhuman upper airway physiological models. In turn, clinical trials have demonstrated that GCs and the nonselective αAR agonist, epinephrine, improve respiratory distress scores and reduce the need for further medical care in children with stridor. Future research is needed to investigate the role of selective αAR agonists and the potential synergism of GCs and αAR-signaling in the treatment of upper airway obstruction and stridor.


Monitoring the one year postoperative infection rate after primary total hip replacement.
Infection of a total hip replacement is potentially a devastating complication. Statistical process control methods have been generating interest as a means of improving the quality of healthcare, and we report our experience with the implementation of such a method to monitor the one year infection rate after primary total hip replacement. Infection was defined as the growth of the same organism in cultures of at least two aspirates or intra-operative specimens, or growth of one pathogen in a patient with local signs of infection such as erythema, abscess or draining sinus tract. The cumulative summation test (CUSUM test) was used to continuously monitor the one year postoperative infection rate. The target performance was 0.5% and the test was set to detect twice that rate. Over the three year study period, 2006 primary total hip replacements were performed. Infection developed within one year after surgery in eight (0.4%) hips. The CUSUM test generated no alarms during the study period, indicating that there was no evidence that the process was out of control. The one year infection rate after primary total hip replacement was in control. The CUSUM test is a useful method to continuously ensure that performance is maintained at an adequate level.


Mechanistic insights into the amidolysis of a phosphate triester: the antagonistic role of water.
The breakdown of O,O-diethyl-2,4-dinitrophenyl phosphate in formamide (FMD) solutions is assessed using kinetic studies and 31P nuclear magnetic resonance (NMR) analysis. Regiospecific nucleophilic amidolysis via P-O bond cleavage is observed, leading to non-toxic diester and FMD regeneration. In the systems evaluated, water plays an antagonistic role: while it is key for the breakdown of the reaction intermediate, it inhibits the nucleophilic activity of FMD by hydrogen bonding effects.


[Optimizing rheumatoid arthritis treatment with rituximab--individualized patient approach].
Disease activity assessment is a cornerstone of monitoring rheumatoid arthritis (RA) development and guidance for rituximab treatment. Beside clinical signs and symptoms biomarkers (RF and anti-CCP) are important early predictors of response to therapy and they can predict disease development. Autoantibody (RF and anti-CCP) seropositivity has been associated with positive response to rituximab (RTX) in antiTNF-IR patients, DMARD-IR patients and MTX-naive patients. Selecting therapy for TNF-IR patients providing most likely response it should be taken in consideration results form recently published assessments demonstrating for RTX treated patients significant improvement in DAS28 from baseline versus alternative TNF inhibitor treatment. Recently published NICE treatment guideline is recommending upon antiTNF failure RTX treatment (in combination with MTX) instead antiTNF cycling.


A proposed role for the cuticular fatty amides of Liposcelis bostrychophila (Psocoptera: Liposcelidae) in preventing adhesion of entomopathogenic fungi with dry-conidia.
Maximum challenge exposure of Liposcelis bostrychophila to Beauveria bassiana, Paecilomyces fumosoroseus, Aspergillus parasiticus or Metarhizium anisopliae resulted in no more than 16% mortality. We investigated several of L. bostrychophila's cuticular lipids for possible contributions to its tolerance for entomopathogenic fungi. Saturated C14 and C16 fatty acids did not reduce the germination rates of B. bassiana or M. anisopliae conidia. Saturated C6 to C12 fatty acids that have not been identified in L. bostrychophila cuticular extracts significantly reduced germination, but the reduction was mitigated by the presence of stearamide. Cis-6-hexadecenal did not affect germination rates. Mycelial growth of either fungal species did not occur in the presence of caprylic acid, was reduced by the presence of lauric acid, and was not significantly affected by palmitic acid. Liposcelis bostrychophila is the only insect for which fatty acid amides have been identified as cuticular components. Stearamide, its major fatty amide, did not reduce germination of B. bassiana or M. anisopliae conidia or growth of their mycelia. Adhesion of conidia to stearamide preparations did not differ significantly from adhesion to the cuticle of L. bostrychophila. Pretreatment of a beetle known to be fungus-susceptible, larval Oryzaephilus surinamensis, with stearamide significantly decreased adhesion of B. bassiana or M. anisopliae conidia to their cuticles. This evidence indicates that cuticular fatty amides may contribute to L. bostrychophila's tolerance for entomopathogenic fungi by decreasing hydrophobicity and static charge, thereby reducing conidial adhesion.


[Evaluation of Microbial Spoilage in PET Bottled Soft Drinks by Direct Drinking].
In order to evaluate microbial growth in opened PET bottled soft drinks, inoculation tests were carried out using type and reference strains of various microorganisms. Microorganisms were inoculated into a 500 mL PET bottle containing 250 mL of various soft drinks followed by incubation until 1 week at 4, 25, 35℃ without shaking, and 35℃ with shaking. The microbial counts were measured over time and compared with the results of the previous study "Studies on Contaminants in Soft Drink"2)-4). As a result, similar growth patterns were observed in the combination of tomato juice with Lactobacillus fermentum, sports drink with Candida albicans, and mineral water with Klebsiella pneumoniae. However, in green tea, mixed herb tea, orange juice and coffee with milk, the growth of microorganisms generally tended to be weaker than those of the previous studies. It was considered that components in the soft drinks inhibited the growth of the microorganisms. From the above results, the proliferative properties of type and reference strains in soft drinks were clearly different from the spoiled soft drinks isolates. The results in this study indicated that attention must be paid in the safety evaluation.


Effect of folic acid supplementation on homocysteine level in postmenopausal women.
Hyperhomocysteinemia is an independent risk factor for atherosclerotic diseases including Ischaemic heart disease, stroke and peripheral vascular disease. Homocysteine (Hcy) is an intermediate formed during the catabolism of essential sulphur containing amino acid methionine, increased Hcy is associated with endothelial dysfunctions in healthy human. Plasma Hcy is significantly lower in premenopausal women than young men but after menopause basal homocysteinemia increases significantly in women approaching those in men. Several studies showed that hyperhomocysteinemia to be stronger risk factor for CHD (Coronary Heart Disease) in women than men. It seems likely that altered hormonal status and age related low folate intake are responsible for this. The present study was designed to evaluate the effect of folic acid supplements for six months, on Hcy level in postmenopausal women. Hcy was estimated by Flourescence Polarization Immunoassay (FPIA). There was a significant (P < 0.001) decrease in Hcy level after six months of folic acid supplements. Hcy is an independent risk factor for atherosclerotic disease, this study favours the view that after menopause Hcy level increases significantly and a simple non Toxic and relatively inexpensive vitamin (folic acid) intervention might be useful in primary cardiovascular prevention in this high risk group because Hcy is a stronger risk factor for CHD in postmenopausal women than men.


The zebra finch paradox: song is little changed, but number of neurons doubles.
New neurons are added to the high vocal center (HVC) of adult males in seasonally breeding songbirds such as the canary (Serinus canaria) that learns new songs in adulthood, and the song sparrow (Melospiza melodia) that does not. In both cases, the new neurons numerically replace others that have died, resulting in a seasonal fluctuation in HVC volume and neuron number. Peaks in neuronal replacement in both species occur in the fall when breeding is over and song is variable. New neurons are added, too, to the HVC of zebra finches (Taeniopygia guttata) that do not learn new songs in adulthood and whose song remains stereotyped throughout the year. Here, we show that, in contrast to the observations in seasonal songbirds, neurons added to the zebra finch HVC are not part of a replacement process. Rather, they lead to a doubling in the number of neurons that project from HVC to the robust nucleus of the arcopallium (RA). As this happens, HVC volume remains constant and the packing density of its neurons increases. The HVC-RA neurons are part of a descending pathway that carries the pattern of learned song; some HVC-RA neurons are also responsive to song playback. The addition of HVC-RA neurons happens in zebra finches housed singly, but becomes more acute if the birds are housed communally. We speculate that new neurons added to the adult HVC may help with the production or perception of learned song, or both.


Different Characteristics of the Two Glutamate Synthases in the Green Leaves of Lycopersicon esculentum.
The two glutamate synthases, NAD(P)H- and ferredoxin-dependent, from the green leaves of tomato plants (Lycopersicon esculentum L. cv Hellfrucht frühstamm) differed in their chemical properties and catalytic behavior. Gel filtration of NAD(P)H enzyme gave an apparent molecular size of 158 kilodalton, whereas the ferredoxin enzyme molecular size was 141 kilodalton. Arrhenius plots of the activities of the two enzymes showed that the NAD(P)H enzyme had two activation energies; 109.6 and 70.5 kilojoule per mole; the transition temperature was 22 degrees C. The ferredoxin enzyme however, had only one activation energy; 56.1 kilojoule per mole. The respective catalytic activity pH optima for the NAD(P)H- dependent and the ferredoxin dependent enzymes were around 7.3 and 7.8. In experiments to evaluate the effects of modulators aspartate enhanced the NAD(P)H-linked activity, with a K(a) value of 0.25 millimolar, but strongly inhibited that of the ferredoxin-dependent glutamate synthase with a K(i) of 0.1 millimolar. 3-Phosphoserine was another inhibitor of the ferredoxin dependent enzyme with a K(i) value of 4.9 millimolar. 3-Phosphoglyceric acid was a potent inhibitor of the ferredoxin-dependent form, but hardly affected the NAD(P)H-dependent enzyme. The results are discussed and interpreted to propose different specific functions that these activities may have within the leaf tissue cell.


[Age, experience, educational status, and differences in income: the United States and Brazil].
"This paper analyses age and experience profiles of earnings inequality for American and Brazilian males. Decomposition of the inequality profiles using a human capital framework clarifies the determinants of cross-section inequality profiles and demonstrates a number of important differences in the shape of the two countries' profiles and in their underlying components. Changes in the distribution of schooling across cohorts are shown to play a central role in explaining cross-section inequality profiles within each country and in explaining differences in earnings inequality in the United States and Brazil." (SUMMARY IN ENG)


Bacterial sexually transmitted infections and syndromic approach: a study conducted on women at Moroccan University Hospital.
In Morocco, a syndromic approach has been implemented for sexually transmitted infections (STIs) management. However, those infections can be asymptomatic and the use of the syndromic approach to their management can be inappropriate and lead to dissemination of infection. Therefore, it would be important to determine the epidemiology and risk factors of bacterial STIs (Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG)) in a Moroccan population and their association with symptoms to assess the appropriacy of the use of the syndromic approach. Cervical samples were collected from symptomatic and asymptomatic consenting women attending the University Hospital of Fez and were tested by PCR for NG, CT and MG using specific primers. We assessed the infection status and its association with different risk factors and genital STIs-related symptoms. Of 809 tested for CT, NG and MG, 16.6% tested positive for at least one STI. Of the 134 participants who tested positive for at least one bacterial STI, 74.2% had no genital STIs-related symptoms. Moreover, the results showed a significantly high rate of NG and MG infections in asymptomatic women. However, the determined risk factors for NG, MG and CT infections were menopause (p=0.002), oral contraception (p=0.036) and a high number of parities (p=0.048), respectively. This investigation shows a predominance of NG infection and a high prevalence of STIs in asymptomatic patients. These results highlight that the adopted syndromic approach will not be adapted in the management of these STIs. Thus, the implementation of a systematic diagnostic program in order to enhance their management is needed.


Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants.
The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.


Reflections on the integration of virtual GP tutorials to the medical undergraduate curriculum at Glasgow.
Virtual tutorials were introduced into the Year 3 medical undergraduate curriculum at Glasgow in 2020/21. This model of teaching proved highly successful from tutor and student perspective. A hybrid teaching model, comprising virtual tutorial teaching alongside placement time will be implemented this year. Virtual (videoed) GP patient cases are selected for tutorials each week, linked to other curriculum content in Year 3. Pedagogically, this aligns pathological and clinical learning for our students and enables some consistency of taught GP content. Concomitant clinical placement time complements this learning with actual patient cases. Communication and consultation techniques considered in the virtual tutorials with facilitated tutor discussion are practised on GP placement days, encapsulating the essence of experiential learning. Challenging or unusual patient cases can be selected for teaching from the virtual case repertoire. This provides uniform exposure to clinically important aspects of general practice, and simultaneously enables an increased diversity of patient cases for our students. Logistical advantages of virtual tutorial delivery include its appeal to a different demographic of GP tutor, enabling us to diversify and expand our teaching team. Remote tutorial delivery offers a futureproof adjunct to the traditional practice-based GP teaching models.


Anomalous temperature-isotope dependence in proton-coupled electron transfer.
Motivated by the experiments of Hodgkiss et al. [J. Phys. Chem. (submitted)] on electron transfer (ET) through a H-bonding interface, we present a new theoretical model for proton-coupled electron transfer (PCET) in the condensed phase, that does not involve real proton transfer. These experiments, which directly probe the joint T-isotope effects in coupled charge transfer reactions, show anomalous T dependence in k(H)k(D), where k(H) and k(D) are the ET rates through the H-bonding interface with H-bonded protons and deuterons, respectively. We address the anomalous T dependence of the k(H)k(D) in our model by attributing the modulation of the electron tunneling dynamics to bath-induced fluctuations in the proton coordinate, so that the mechanism for coupled charge transfer might be better termed vibrationally assisted ET rather than PCET. We argue that such a mechanism may be relevant to understanding traditional PCET processes, i.e., those in which protons undergo a transfer from donor to acceptor during the course of ET, provided there is an appropriate time scale separating both coupled charge transfers. Likewise, it may also be useful in understanding long-range ET in proteins, where tunneling pathways between redox cofactors often pass through H-bonded amino acid residues, or other systems with sufficiently decoupled proton and electron donating functionalities.


Female cigarette smoking and successful fertility treatment: A Danish cohort study.
Despite smoking being a well-established risk factor for adverse pregnancy and neonatal outcomes, a substantial proportion of women of reproductive age smoke. Previously, meta-analyses have indicated a significantly negative impact of female smoking on outcomes of assisted reproduction, yet most of the included studies have several, essential methodological limitations. We aimed to investigate whether female cigarette smoking may affect the chance of achieving a clinical pregnancy and live birth among women and couples receiving medically assisted reproduction treatment. A cohort study with longitudinally and repeatedly collected exposure information from 1 January 2010 to 31 August 2015, including data on 1708 women and potential partners initiating either intrauterine insemination, in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) or frozen embryo transfer treatment cycles at the public Fertility Clinic, Aarhus University Hospital, Denmark. Smoking was assessed from self-reported questionnaires completed before treatment. Outcomes were a clinical pregnancy and a live birth. Information on these was obtained from the Danish national health registries, allowing complete follow-up. To evaluate associations between female occasional/daily cigarette smoking and successful medically assisted reproduction treatments, a modified Poisson regression with robust standard errors was used. Female occasional/daily cigarette smoking was not associated with the chance of achieving a clinical pregnancy or a live birth in all intrauterine insemination or IVF/ICSI treatment cycles. When compared with nonsmokers, the adjusted relative risk for obtaining a live birth for those reporting smoking was 1.22 (0.70-2.12) among women initiating 1456 intrauterine insemination treatment cycles. Among women initiating 2788 IVF/ICSI treatment cycles, those reporting occasional/daily smoking had a relative risk for obtaining a live birth of 1.15 (0.82-1.60) when compared with nonsmokers. Occasionally/daily cigarette smoking women had similar chance of achieving a clinical pregnancy or a live birth as the nonsmokers when receiving medically assisted reproduction treatments. However, tobacco use before and during pregnancy remains a major cause of reduced fertility as well as maternal, fetal, and infant morbidity and mortality, and should strongly be discouraged.


Pigment-induced glaucoma secondary to bilateral diffuse uveal melanocytic proliferation.
We report the first case of pigment-induced glaucoma in a patient presenting with bilateral diffuse uveal melanocytic proliferation (BDUMP) syndrome. Despite treatment with plasma exchange, the patient developed progression of her lesions and bilateral glaucoma. Surgical treatment with Ahmed valve implant was performed to control her increased intra-ocular pressure. This case demonstrates that BDUMP can be a cause of a refractory pigment-induced glaucoma.


Ondansetron and meperidine prevent postoperative shivering after general anesthesia.
Postoperative shivering is one of the common problems following general anesthesia and may lead to multiple complications. The aim of this study was to examine the preventive effects of Ondansetron and Meperidine on postoperative shivering. This randomized placebo-controlled double blind clinical trial included 90 patients scheduled for elective gynecologic operations, randomly divided to three groups. Ondansetron (4 mg), Meperidine (0.4 mg/kg) and 2 cc normal saline (as a control group) were administered immediately before the induction of anesthesia. Anesthesia induced equivalently for all. Patients were observed in terms of vital signs, side effects and shivering. Postoperative shivering was observed in 13.3% of patients in Ondansetron group and 20% of Meperidine group, significantly lower than the controls (50%). The reduction of core and dermal temperature during the anesthesia and recovery, changes in systolic and diastolic blood pressure and heart rate were similar in all three groups. The incidence of nausea was similar among the three groups of study while vomiting occurred in 6.7% of the Meperidine group and 3.3% of the controls but none in the patients receiving Ondansetron. Ondansetron can effectively reduce post operative shivering.


Anti-Schistosoma IgG responses in Schistosoma haematobium single and concomitant infection with malaria parasites.
Areas prone to schistosomiasis are also at risk of malaria transmission. The interaction between the causal agents of the two diseases could modulate immune responses tailored toward protecting or aggravating morbidity dynamics and impair Schistosoma diagnostic precision. This study aimed at assessing the effect of Plasmodium spp. in concomitant infection with Schistosoma haematobium in modulation of anti-Schistosoma IgG antibodies. The school-based cross-sectional study recruited a total of 322 children screened for S. haematobium and Plasmodium spp. Levels of IgG against S. haematobium-soluble egg antigen (SEA) in single S. haematobium/malaria parasites infection and co-infection of the two parasites in schoolchildren were determined. Data were analyzed using χ(2), Fisher's exact test, and Tukey's multiple comparison test analyses. The prevalence of single infection by S. haematobium, Plasmodium spp., and concurrent infection due to the two pathogens was 27.7, 41.0, and 9.3%, respectively (p < 0.0001). Anti-Schistosoma IgG production during co-infection of the two pathogens (1.950 ± 0.742 AU) was significantly higher than the value recorded for single malaria parasites' infection (1.402 ± 0.670 AU) (p < 0.01) but not in S. haematobium infection (1.591 ± 0.604 AU) (p > 0.05). The anti-Schistosoma IgG production in co-infection status was however dependent on the intensity of Plasmodium spp. with individuals having high intensity of malaria parasites recording lower anti-Schistosoma IgG. This study has implication for diagnosis of schistosomiasis where anti-Schistosoma IgG is used as an indicator of infection. Efforts should be made to control the two infections simultaneously in order not to undermine the efforts targeted toward the control of one.


Undetectable S cone electroretinogram b-wave in complete congenital stationary night blindness.
The short wavelength sensitive (S) cone electroretinograms (ERGs) were examined in two patients with the complete type of congenital stationary night blindness (CSNB). Ganzfeld spectral flashes in the presence of strong white adapting fields were used to elicit the S cone ERGs. The S cone ERG b-wave was not detectable to short wavelength stimuli, while the mixed long (L) and middle (M) wavelength sensitive cone responses appeared normal in waveforms with normal amplitude in both patients. Both patients had normal colour vision on the Farnsworth Panel D-15. These ERG results indicated that the S cone system as well as rod system is more impaired in complete CSNB than the L and M cone system and that normal colour vision may not depend on a normal S cone ERG to full field stimuli.


Early maladaptive schemas in patients with bipolar and unipolar disorder.
The aim of our study is to determine the difference between the bipolar disorder, unipolar disorder and control groups in terms of maladaptive schemes and childhood trauma. Two groups of patients under monitoring with a diagnosis of bipolar or unipolar disorder and one group of healthy controls were enrolled in this study. Each group consisted of 60 subjects. The Young Mania Rating Scale and Beck Depression Inventory were used to confirm that patients were in remission. The Childhood Trauma Questionnaire and Young Schema Questionnaire-Short Form 3 were used to identify childhood traumas and early maladaptive schemas. In bipolar disorder, a positive, low power correlation was observed between the vulnerability to threats schema and emotional, physical and sexual abuse. In the unipolar disorder group, there was a positive, low power correlation between the emotional inhibition, failure, approval seeking, dependence, abandonment and defectiveness schemas and social isolation, and a positive, moderate correlation between social isolation and emotional abuse. Individuals with bipolar disorder suffered greater childhood trauma compared to subjects with unipolar disorder and healthy individuals. Greater maladaptive schema activation were present in individuals with bipolar disorder compared to those with unipolar disorder and healthy individuals.


Cold stress in captive great apes recorded in incremental lines of dental cementum.
Incremental lines in dental cementum of museum specimens of 11 free-ranging great apes were compared to the respective structures in 5 captive specimens of known age-at-death, and with many known life-history parameters. While the dental cementum of the free-ranging apes was regularly structured into alternating dark and light bands, 4 out of 5 captive animals showed marked irregularities in terms of hypomineralized bands which could all be dated to the year 1963. Cementum preservation was insufficient in the fifth specimen and did not permit such a differentiation. All 4 captive apes had been kept in a zoo located in the northern hemisphere, where 1963 was characterized by an extremely cold winter. Since cold stress is a calcium-consuming process, the lack of available calcium in newly forming cementum could be responsible for the observed hypomineralization. The appositional growth characteristics of dental cementum serve as a record for such life-history events.


Automated breast volume scanner (ABVS) in assessing breast cancer size: A comparison with conventional ultrasound and magnetic resonance imaging.
To compare automated breast volume scanner (ABVS), ultrasound (US) and MRI in measuring breast cancer size, and evaluate the agreement between ABVS and US in assessing lesion location and sonographic features. We retrospectively included 98 women with 100 index cancers who had undergone US and ABVS followed by 1.5T MRI. Images were interpreted by a pool of readers reporting lesion size, location and breast imaging reporting and data system (BI-RADS) features. Bland-Altman analysis (with logarithmic data transformation), intraclass correlation coefficient (ICC) and Cohen's kappa statistic were used for statistical analysis. MRI showed the best absolute agreement with histology in measuring cancer size (ICC 0.93), with LOA comparable to those of ABVS (0.63-1.99 vs. 0.52-1.73, respectively). Though ABVS and US had highly concordant measurements (ICC 0.95), ABVS showed better agreement with histology (LOA 0.52-1.73 vs. 0.45-1.86, respectively), corresponding to a higher ICC (0.85 vs. 0.75, respectively). Except for posterior features (k=0.39), the agreement between US and ABVS in attributing site and BI-RADS features ranged from substantial to almost perfect (k=0.68-0.85). ABVS performs better than US and approaches MRI in predicting breast cancer size. ABVS performs comparably to US in sonographic assessment of lesions. • ABVS approaches MRI in predicting breast cancer size. • ABVS is equivalent to US in localising and characterising breast cancer. • ABVS is more accurate than US in assessing breast cancer size. • ABVS has the potential to replace US in breast cancer staging.


Liquid chromatographic determination of prednisolone in tablets and bulk drugs: interlaboratory study.
A normal phase liquid chromatographic (LC) method for the determination of prednisolone in tablets and bulk drugs was studied by 7 analysts. An LC system, consisting of a methanol-water-ethylene dichloride-acetic acid mobile phase and a silica column, was used to analyze bulk drugs, individual tablets, and composite samples. Analysts were supplied with 16 samples, including simulated formulations, composites of commercial tablets, intact tablets, and bulk drug substances. Results agreed with those obtained by the author. The coefficients of variation of the analysts' results ranged from 1.34% for bulk drugs to 2.14% for tablet composites. The LC method is suggested as an alternative to the official AOAC and USP XX blue tetrazolium colorimetric methods.


Shingles vaccine.
Herpes zoster or shingles is a condition with the potential to result in severe debilitation. It affects approximately 10 - 30% of the population. Until recently there were only treatments to shorten the duration and lessen the symptoms of herpes zoster, but no practical or approved method of prevention for susceptible immunocompetent adults. The live attenuated zoster vaccine (Zostavax, Merck & Co., Inc.) is effective in preventing shingles in individuals 60 years of age and older and recommended by the Center for Disease Control's (CDC) Advisory Committee for Immunization Practices (ACIP). Literature related to the live attenuated zoster vaccine is reviewed from its beginnings in the early 1970s through to the present. Background information on herpes zoster and up to date information on the live attenuated zoster vaccine including pharmacology, efficacy and safety are covered. New areas of research in zoster vaccination are also discussed. The live attenuated zoster vaccine is an effective and well-tolerated method of preventing zoster and the potentially debilitating sequelae and is recommended for immunocompetent patients 60 years of age and older. Ongoing clinical trials are investigating new means of effective prevention.


The climate sensitivity of carbon, timber, and species richness covaries with forest age in boreal-temperate North America.
Climate change threatens the provisioning of forest ecosystem services and biodiversity (ESB). The climate sensitivity of ESB may vary with forest development from young to old-growth conditions as structure and composition shift over time and space. This study addresses knowledge gaps hindering implementation of adaptive forest management strategies to sustain ESB. We focused on a number of ESB indicators to (a) analyze associations among carbon storage, timber growth rate, and species richness along a forest development gradient; (b) test the sensitivity of these associations to climatic changes; and (c) identify hotspots of climate sensitivity across the boreal-temperate forests of eastern North America. From pre-existing databases and literature, we compiled a unique dataset of 18,507 forest plots. We used a full Bayesian framework to quantify responses of nine ESB indicators. The Bayesian models were used to assess the sensitivity of these indicators and their associations to projected increases in temperature and precipitation. We found the strongest association among the investigated ESB indicators in old forests (>170 years). These forests simultaneously support high levels of carbon storage, timber growth, and species richness. Older forests also exhibit low climate sensitivity of associations among ESB indicators as compared to younger forests. While regions with a currently low combined ESB performance benefitted from climate change, regions with a high ESB performance were particularly vulnerable to climate change. In particular, climate sensitivity was highest east and southeast of the Great Lakes, signaling potential priority areas for adaptive management. Our findings suggest that strategies aimed at enhancing the representation of older forest conditions at landscape scales will help sustain ESB in a changing world.


Motion facilitates face perception across changes in viewpoint and expression in older adults.
Faces are inherently dynamic stimuli. However, face perception in younger adults appears to be mediated by the ability to extract structural cues from static images and a benefit of motion is inconsistent. In contrast, static face processing is poorer and more image-dependent in older adults. We therefore compared the role of facial motion in younger and older adults to assess whether motion can enhance perception when static cues are insufficient. In our studies, older and younger adults learned faces presented in motion or in a sequence of static images, containing rigid (viewpoint) or nonrigid (expression) changes. Immediately following learning, participants matched a static test image to the learned face which varied by viewpoint (Experiment 1) or expression (Experiment 2) and was either learned or novel. First, we found an age effect with better face matching performance in younger than in older adults. However, we observed face matching performance improved in the older adult group, across changes in viewpoint and expression, when faces were learned in motion relative to static presentation. There was no benefit for facial (nonrigid) motion when the task involved matching inverted faces (Experiment 3), suggesting that the ability to use dynamic face information for the purpose of recognition reflects motion encoding which is specific to upright faces. Our results suggest that ageing may offer a unique insight into how dynamic cues support face processing, which may not be readily observed in younger adults' performance. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


Differential impact of the CYP3A5*1 and CYP3A5*3 alleles on pre-dose concentrations of two tacrolimus formulations.
We investigated the pharmacokinetic and pharmacogenetic implications of conversion from a twice-daily (P-Tac) to a once-daily (A-Tac) tacrolimus (Tac) formulation. We analyzed Tac levels in a cohort of 41 renal transplant patients with a stable graft function over a period of 1 year before and after conversion. After conversion, the patients had, on average, significantly lower Tac trough and dose-normalized trough levels (14%, P=0.0004 and 23%, P=0.001, respectively) despite similar doses. CYP3A5*3/*3 patients (n=27) required significantly lower Tac doses with both the formulations to reach Tac target levels (P-Tac 39%, P=0.011; A-Tac 36%, P=0.003) compared with *1/*3 patients (n=13). Interestingly, after the conversion, mean Tac trough levels and dose-normalized trough level remained almost constant in *1/*3 patients, but decreased significantly in *3/*3 patients (16%, P=0.001 and 25%, P=0.006). This study provides further evidence that the CYP3A5*1/*3 polymorphism significantly impacts Tac pharmacokinetics. Moreover, we show for the first time a pharmacogenetic effect on two different Tac formulations, as Tac trough levels of *3/*3 patients declined significantly after conversion to identical A-Tac doses.


An unusual side effect of interferon alfa 2A: digital clubbing.
Interferon Alfa has been widely used to treat chronic hepatitis C virus infection. In this report, we present a case series of two patients referred to Sarwar Zuberi Liver Centre, Civil Hospital Karachi, who suffered from chronic hepatitis C. After getting detailed clinical examination and baseline work up prior to starting treatment, these patients were offered therapy with usual recommended dose of 3 million units of alpha-interferon subcutaneously thrice weekly. Both these patients developed clubbing of fingers during the course of treatment, one developing it during the 2nd month while the other during the 4th month. It was of grade II in one patient and of grade III in another and was bilateral in both the cases. Clubbing was not presented prior to start of treatment and no other secondary cause of clubbing was found in any of the case. These patients were not on any other drug that is known to interfere with interferon or can be associated with clubbing. No national or international data regarding such unusual side effect is available. Whether this effect is idiosyncratic or dose related and whether it is reversible or not after completion of treatment is yet to be established.


Interleukin-10 suppression of myeloid cell activation--a continuing puzzle.
Efforts to identify the signal transduction pathways used by interleukin-10 (IL-10) have resulted in limited success. The anti-inflammatory effects elicited by IL-10, and the mechanisms by which these are mediated, are still relatively unknown. Understanding the signalling mechanisms behind the suppression of cytokine expression by IL-10 could be of potential therapeutic interest. Although the consensus is that the Janus kinase, Jak1, as well as the signal transducer and activator of transcription STAT3 are central, much controversy exists about the participation and roles of many other signalling pathways targeted by IL-10. The mechanisms of cytokine suppression proposed by various groups have included transcriptional, post-transcriptional and post-translational regulation of IL-10 target genes; nevertheless no unifying model has emerged thus far. Here we would like to highlight novel findings and discuss their implications in the context of current understanding of IL-10 signalling.


Epidermal growth factor receptor targeting in cancer.
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family that is abnormally activated in many epithelial tumors. Several mechanisms lead to the receptor's aberrant activation that is observed in cancer, including receptor overexpression, mutation, ligand-dependent receptor dimerization, and ligand-independent activation. Two classes of anti-EGFR agents are currently approved for the treatment of patients with cancer: cetuximab, a monoclonal antibody directed at the extracellular domain of the receptor, and gefitinib and erlotinib, oral, low-molecular-weight (MW), adenosine triphosphate (ATP)-competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR monoclonal antibodies have demonstrated activity in the therapy of advanced colorectal carcinoma and in a variety of epithelial tumor types, including head and neck cancer and non-small cell lung cancer (NSCLC). The development of low MW, anti-EGFR tyrosine kinase inhibitors (TKIs) has been focused until recently on NSCLC, although responses have been reported for other types of cancer. Erlotinib was the only agent approved based on demonstrating improved survival, which was observed in patients with advanced NSCLC who previously had been treated with chemotherapy. Recent major advances in the EGFR field include the discovery of EGFR somatic mutations in NSCLC that have important implications for biology, treatment, clinical trial design, and methods for mutation detection. Clinical and survival benefits with anti-EGFR agents have been demonstrated in additional tumor types such as head and neck and pancreatic carcinomas. New agents with clinical activity are entering the clinic and new combinatorial approaches with anti-EGFR agents are being explored. Major efforts are, belatedly, attempting to identify molecular markers that can predict patients more likely to respond to anti-EGFR therapy.


Proposed Design of a Real-Time COVID-19 Pandemic Contact Tracing Using Mobile Phone.
As the virus that causes COVID-19 continues to spread from person to persons in communities and rampaging the world, the need for an effective real-time surveillance system becomes paramount. Advance contact tracing and detection of the persons with the virus represents one of the main strategies to prevent transmission. Although COVID-19 surveillance systems such as contact tracing mobile apps have improved the administration and management of virus, there are still challenges such as privacy, cost and ethical issues, the adoption of new technologies, standardized cases, and validly diagnosed case and validity. However, the current mobile apps contact tracing system adopted by different nations has complemented conventional tracing effort in fighting the virus. This proposal is a model for an interactive computer system using mobile phones and the internet for real-time collection and transmission of events related to COVID-19. It will aid the administration and presumptive management of COVID-19 in the world, especially in rural areas. This proposal shows that a sophisticated COVID-19 surveillance system can be build using mobile phones with the right telecommunication technology partner.


Transient absence of CD44 expression and delay in development by anti-CD44 treatment during ontogeny: a surrogate of an inducible knockout?
Because the lack of some adhesion molecules induced by site-directed mutagenesis has been described to be lethal, whereas the lack of others apparently has no effect, we were interested in seeing whether the developing organism might gradually adapt to the absence of adhesion molecules. Therefore, we chose a form of transient interference by i.v. injection of antibody into pregnant rats. As a model, we selected CD44, which has been reported to play a key role during embryogenesis. Rats received either an antibody recognizing an epitope on the CD44 standard isoform (CD44s) or on exon v6 (CD44v6). In the presence of anti-CD44s, delivery was frequently delayed, and intrauterine abortions were often observed. The fetuses were smaller, particularly the anlage of the hair follicle of the whisker, and the formation of alveoli in the lung, of the tubular system of the kidney, and of villi in the gut was delayed. The development of fetuses receiving anti-CD44v6 was hampered until days 16-18 of gestation. Immunodetection revealed a weaker expression of the target molecules at the implantation site and the complete absence of CD44s and CD44v6 expression in fetal tissue until day 12. During the late stages of gestation, the expression pattern of CD44 resembled that of 2-3-day-younger fetuses of untreated rats. Interestingly, degradation of hyaluronate was also delayed, particularly in the kidney. Thus, the diaplacental antibody passage was very efficient and should make it possible to obtain a clearly defined and differentiated concept of the requirements for the CD44 molecule during ontogeny and also for fail-safe mechanisms. Both experiences may be missed in the knockout proper.


The impact of highly active antiretroviral treatment on the blood profiles of patients with acquired immune deficiency syndrome.
This study retrospectively investigated the short- and long-term impact of highly active antiretroviral treatment (HAART) on the blood profiles of patients with acquired immune deficiency syndrome (AIDS), and their relationship with disease progression. CD4(+) T-cell count was measured by flow cytometry, plasma viral load of human immunodeficiency virus (HIV) RNA was detected by reverse transcription-polymerase chain reaction, and blood profile was determined by an automated analyser. CD4(+) T-cell count, total lymphocyte count (TLC) and haemoglobin concentration improved gradually in patients with AIDS after the initiation of HAART. Long-term effective HAART significantly increased CD4(+) T-cell counts TLC and haemoglobin concentrations, and reduced viral load to undetectable levels. An increase in haemoglobin was positively correlated with an increase in CD4(+) T-cells. These findings suggest that TLC is a valuable tool for determining the initiation of HAART, and that the haemoglobin concentration could be an additional indicator for long-term monitoring of HAART in resource-limited settings.


Clinical impact of high serum hepatocyte growth factor in advanced non-small cell lung cancer.
Activation of c-MET through hepatocyte growth factor (HGF) increases tumorigenesis, induces resistance, and is associated with poor prognosis in various solid tumors. However, the clinical value of serum HGF (sHGF) in patients with advanced non-small cell lung cancer (NSCLC), especially those receiving cytotoxic chemotherapy, remains unknown. Here, we show that sHGF may be useful to predict tumor response and progression-free survival (PFS) in patients with advanced NSCLC. A total of 81 patients with NSCLC were investigated. sHGF levels were evaluated using ELISA at 4 time-points: at pre-treatment, at response-evaluation (1-2 months after treatment initiation), at the best tumor response, and at disease progression. As a control biomarker, CEA was also evaluated in lung adenocarcinoma. Positive-sHGF at response-evaluation predicted poor PFS compared with Negative-sHGF in both first-line (median, 153.5 vs. 288.0; P < 0.05) and second-line treatment (87.0 vs. 219.5; P = 0.01). In 55 patients that received cytotoxic chemotherapy, multiple Cox proportional hazards models showed significant independent associations between poor PFS and Positive-sHGF at response-evaluation (hazard ratio, 4.24; 95% CI, 2.05 to 9.46; P < 0.01). Lung adenocarcinoma subgroup analysis showed that in patients receiving second cytotoxic chemotherapy, there were no significant differences in PFS between patients with low-CEA compared with those with high-CEA, but Positive-sHGF at pre-treatment or at response-evaluation predicted poor PFS (35.0 vs. 132.0; P < 0.01, 50.0 vs. 215.0; P < 0.01, respectively). These findings give a rationale for future research investigating the merit of sHGF as a potential clinical biomarker to evaluate HGF/c-MET activity, which would be useful to indicate administration of c-MET inhibitors.


The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles.
To understand the chronic spleen injury induced by intragastric administrations with 2.5, 5, and 10 mg kg(-1) body weight titanium dioxide nanoparticles (TiO(2) NPs) for 90 consecutive days, histopathological and ultrastructure changes, hematological parameters, lymphocyte subsets, the inflammatory, and apoptotic cytokines in the mouse spleen were investigated. Our findings indicate that TiO(2) NPs exposure results in the significant increase in the spleen indices, histopathological changes, and splenocyte apoptosis in spleen. Especially, in these TiO(2) NPs-treated mice, immunoglobulin, blood cells, platelets, hemoglobin, lymphocyte subsets (such as CD3, CD4, CD8, B cell, natural killer cell) of mice were significantly decreased. Furthermore, TiO(2) NPs exposure can significantly increase the levels of nucleic factor-κB, tumor necrosis factor-α, macrophage migration inhibitory factor, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1β, cross-reaction protein, transforming growth factor-β, interferon-γ, Bax, and CYP1A1 expression, whereas decrease the levels of Bcl-2 and heat shock protein 70 expression. These findings suggest that long-term exposure to low dose TiO(2) NPs may result in spleen injury and reduction of immune capacity, TiO(2) NP-induced injury in spleen may result from alteration of inflammatory and apoptotic cytokines expression, and workers and consumers should take great caution when handling nanomaterials.


Radiographic patterns of orbital involvement in IgG4-related disease.
Immunoglobin G4 (IgG4)-related disease is a systemic condition characterized by lymphoplasmacytic infiltrates that can involve the orbit. The purpose of this study was to identify the various patterns of orbital IgG4-related disease on imaging. Retrospective review of radiologic examinations including CT, MRI, and positron emission tomography was performed in patients with proven cases of IgG4-related disease. A total of 9 patients with orbital IgG4-related disease were identified, including 9 with CT, 4 with MRI, and 4 with 18-fluorodeoxyglucose positron emission tomography. Patterns of involvement included lacrimal gland enlargement, lacrimal sac involvement, extraocular muscle thickening, preseptal involvement, orbital fat involvement, and cranial nerve involvement, many of which occurred simultaneously. Associated demineralization of the orbital wall was evident on CT in 2 cases. On T2-weighted MRI, the lesions appeared as hypointense in 2 cases, heterogeneously hypointense to isointense in 1 case, and hyperintense in 1 case. Diffuse enhancement was present in all 3 cases in which postcontrast T1-weighted sequences were available. The lesions were hypermetabolic on positron emission tomography in 3 of 4 cases. There was definite extraorbital involvement by IgG4-related disease in 3 of the 9 patients and suspected involvement in another 3 of the 9 patients. IgG4-related disease displays a wide variety of imaging manifestations in the orbit. Extraorbital disease is often present and can help suggest the diagnosis.


Respiratory diseases: meeting the challenges of screening, prevention, and treatment.
Respiratory conditions, both acute and chronic, continue to have a significant impact on worldwide health because of their high prevalence, the high disease burden they place on individual health, and their enormous cost to the health care system. There are also unmeasured indirect economic costs due to loss of productivity. Despite advances in our understanding of the complex pathophysiology of respiratory diseases, as well as the availability of relatively straightforward primary prevention measures, the prevalence of chronic respiratory diseases continues to rise. In addition, periodic outbreaks of acute infectious respiratory conditions result in significant cost and even mortality, and the incidence of these conditions fluctuates widely from year to year. Although we have seen recent developments in medical therapies for respiratory diseases, and there are established and well-publicized disease management guidelines, morbidity and mortality remain high. One intervention that has lagged behind has been smoking prevention and cessation, which is the mainstay of prevention for chronic obstructive pulmonary disease and lung cancer. The persistence of these conditions underscores vulnerabilities within our national and regional health care systems. Several of the articles in this issue of the NCMJ describe innovative programs to address these challenges.