A Review of Regimens Combining Pemetrexed With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in the Treatment of Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Pemetrexed is a standard first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for advanced nonsquamous NSCLC with activating EGFR mutations. Pemetrexed and EGFR TKIs have different mechanisms of action and minimally overlapping toxicity profiles; therefore, it is hypothesized that their combination might result in acceptable toxicity, provided that the synergistic antitumor activity observed in preclinical studies is achieved. This review summarizes clinical trials of pemetrexed in combination with an EGFR TKI for the treatment of advanced nonsquamous NSCLC in the first- and second-line settings, using intercalated, sequential, and concurrent treatment strategies. As would be expected, such strategies were most efficacious in patients with the activating EGFR mutations associated with response to an EGFR TKI. In the studies that compared a pemetrexed-EGFR TKI combination with pemetrexed alone or the EGFR TKI alone, the pemetrexed-EGFR TKI combination was more efficacious than the single-agent regimens. The pemetrexed-EGFR TKI combinations were generally associated with a higher incidence of grade 3/4 treatment-related adverse events than the single-agent regimens; however, such toxicities were clinically manageable. Future studies of pemetrexed-EGFR TKI combinations should focus on optimizing treatment strategies in patients with activating EGFR mutations.


Weight variation before and after surgery in Parkinson's disease: a noradrenergic modulation?
Changes in the nutritional profile of patients with Parkinson's disease have been reported before and after deep brain stimulation surgery. The major determinants of the weight variation in Parkinson's disease are not yet understood, and the mechanism seems complex. Based on the influence of the sympathetic nervous system in metabolic syndrome obesity, the intent of the present review is to consider the role of noradrenergic modulation on weight variations in Parkinson's disease. In this review the authors raise the following hypothesis: weight variation in Parkinson's disease before and after deep brain stimulation of the subthalamic nucleus could be influenced by noradrenergic interaction between the locus coeruleus, subthalamic nucleus, and hypothalamic nucleus.


Growth of the chick embryo in vitro.
An improved technique is described for in vitro culture of the chick embryo from three days through 21 days of total incubation (three days in shell plus 18 days in culture). Mean survival time for cultured embryos is 18 days of total incubation, and mean morphological stage is Hamburger-Hamilton stage 41 (15 days). Mean measurements of wet weight, dry weight, and right third toe length for stage 45 (partial or complete abdominal yolk sac retraction, 19-20 days) cultured embryos are comparable with corresponding means for stage 42-43 (16-17 days) embryos from control intact eggs. Possible causes of growth retardation in vitro are briefly discussed.


Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restriction.
Base-line urinary potassium secretion in the distal nephron is mediated by small conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp technique applied to split-open cortical collecting ducts (CCDs) isolated from rats fed a normal potassium (NK) or low potassium (LK) diet to test the hypothesis that AngII directly inhibits ROMK channel activity. We found that AngII inhibited ROMK channel activity in LK but not NK rats in a dose-dependent manner. The AngII-induced reduction in channel activity was mediated by AT1 receptor (AT1R) binding, because pretreatment of CCDs with losartan but not PD123319 AT1 and AT2 receptor antagonists, respectively, blocked the response. Pretreatment of CCDs with U73122 and calphostin C, inhibitors of phospholipase C (PLC) and protein kinase C (PKC), respectively, abolished the AngII-induced decrease in ROMK channel activity, confirming a role of the PLC-PKC pathway in this response. Studies by others suggest that AngII stimulates an Src family protein-tyrosine kinase (PTK) via PKC-NADPH oxidase. PTK has been shown to regulate the ROMK channel. Inhibition of NADPH oxidase with diphenyliodonium abolished the inhibitory effect of AngII or the PKC activator phorbol 12-myristate 13-acetate on ROMK channels. Suppression of PTK by herbimycin A significantly attenuated the inhibitory effect of AngII on ROMK channel activity. We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase-, and PTK-dependent pathways under conditions of dietary potassium restriction.


Interfacial behavior of confined mesogens at smectic-C*-water boundary.
In this paper, we have investigated the behavior of mesogens at smectic-C*-water interface confined in a liquid crystal (LC) cell with interfacial geometry. Polarized optical microscopy was used to probe the appearance of various smectic-C* domain patterns at water interface owing to the reorientation of mesogens. The undulated stripe domains observed at the air interface of smectic-C* meniscus vanished as the water entered into the smectic layers and focal conical domain patterns appeared at smectic-C*-water boundary. A spatially variable electro-optical switching of LC molecules was also observed outside the electrode area of the interfacial cell. The electrode region at the interface, as well as on the water side, was damaged upon application of an electric field of magnitude more than 150 kV/m. The change in dielectric parameters of mesogens was extensively studied at interface after evaporating the water. These studies give fundamental insights into smectic-C*-water interface and also will be helpful in fabricating better LC devices for electro-optical and sensing applications.


Examining health problems and intensity of need for care in family-focused community and public health nursing.
The purpose of this study was to advance evidence-based family-focused community and public health nursing (C/PHN) practice by examining 2 important indicators of health need, family health problem labels, and intensity of need for care, and their relationship to each other. The Omaha System (OS; Martin & Scheet, 1992) was the framework used to classify the most common family health problems. Intensity of need for care was determined using the Community Health Intensity Rating Scale (CHIRS; Hays, Sather, & Peters, 1998). Secondary analysis of C/PHN clinical data was done using a descriptive correlational design (n = 205). An investigator scored the CHIRS and assigned OS family problems based on clinical record data. The mean number of family health problems per person was 4.40 (+/- 2.06). The mean CHIRS total score was 33.9 (+/- 6.34). The total number of OS problems was significantly correlated with CHIRS total scores (r = .586, p < .001). Family problem labels and intensity of need for care both provide essential information for health need determination in C/PHN practice.


Polycyclic aromatic hydrocarbon removal from water by natural fiber sorption.
The use of two natural sorbents, kapok and cattail fibers, were investigated for polycyclic aromatic hydrocarbon (PAH) removal from water. Naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, and fluoranthene were the PAHs studied. For comparative purposes, a commercial polyester fiber sorbent was included in the investigation. The PAH sorption and retention capabilities of the three fibers were determined through batch and continuous-flow experiments under non-competitive and competitive conditions. In the batch experiments, cattail fiber was the most effective sorbent. Kapok fiber provided the lowest PAH retention, while cattail fiber had slightly less PAH retention than polyester fiber. When two PAHs were present in the same system, a competitive effect on the much less hydrophobic PAH was observed. Similar results were obtained in the column experiments, except that polyester fiber performed much poorer on naphthalene. Cattail fiber is a promising sorbent for treating PAH-contaminated water, such as urban runoff.


[Effect of fragmented sleep on postoperative cognitive function and central neuroinflammation].
Objective: To investigate the effect of sleep fragmentation on perioperative neurocognitive disorders (PND) and central neuroinflammation by simulating sleep patterns of postoperative patients with sleep fragmentation in aged mice. Methods: Thirty-two elderly ICR mice were randomly divided into four groups (n=8): normal group (C), surgery group (S), fragmented sleep group (F), and surgery+fragmented sleep group (D). Fragmented sleep was conducted after internal fixation of tibia fractures, cognitive function was evaluated by novel object recognition (NOR) and fear conditioning (FC) test, and changes in expression of inflammatory cytokines in hippocampus were detected by ELISA. Results: NOR test: the recognition index (RI) of mice in group C, group S, group F and group D was 0.69±0.07, 0.48±0.07, 0.54±0.10 and 0.50±0.12, respectively. The RI of mice in group S, group F and group D was significantly lower than that in group C (t=4.885, 3.521 and 4.433, all P<0.01). There was no significant difference in RI between group S and group D (t=0.967 1, P>0.05). Contextual FC test: the freezing time of mice in group C, group S, group F and group D was(21.34±6.48), (13.83±4.26), (11.50±6.25) and (6.17±4.77) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=2.722, 3.566, 5.496, P<0.05 or P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.774, P<0.05). Cue FC test: the freezing time of mice in group C, group S, group F and group D was (74.36±17.09), (43.91±9.71), (46.34±13.43) and (24.90±14.21) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=4.393, 4.043 and 7.136, all P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.743, P<0.05). The levels of TNF-α, IL-6 and IL-1β in hippocampus of mice in group S, F and D were significantly higher than those in group C, while the levels of TNF-α and IL-6 in hippocampus of mice in group D were significantly higher than those in group S, with statistically significant differences (P<0.05 or P<0.01). Conclusion: Postoperative fragmented sleep aggravates postoperative cognitive impairment and increases the hippocampal neuroinflammation in aged mice.


Experimental infection of elaphid snakes with Cryptosporidium serpentis (Apicomplexa: Cryptosporidiidae).
The shedding pattern of fecal Cryptosporidium serpentis oocysts, histopathologic changes in the gastric region, and the effect of spiramycin treatment were investigated in 6 experimentally infected, captive black rat (Elaphe obsoleta obsoleta), 4 yellow rat (Elaphe obsoleta quadrivittata), and 2 corn snakes (Elaphe guttata guttata). Feces were monitored for up to 2 years postinfection (PI). No significant (P > 0.07) differences were observed between expected and observed numbers of PI oocyst-positive feces. Two of 5 control animals acquired natural infections of C. serpentis over the period of study. No morphological differences were observed between oocysts from experimental and natural infections. Clinical signs included postprandial regurgitation in 5 of 13 (38%) snakes, not coinciding with the shedding of fecal oocysts. Midbody swelling and self-cure were not observed. Spiramycin treatment of 4 of 12 experimentally infected animals resulted in negative fecal examinations in 2 snakes and reduced the percentage of oocyst-positive feces in 2 other snakes from 75.5% to 24.5% and from 83.9% to 33.6%. Biopsies and necropsies revealed stages of Cryptosporidium in the gastric mucosa of all spiramycin-treated animals. The gastric mucosa was thickened and edematous, with focal necrosis, mucosal petechiae, and brush hemorrhages. Fibroplasia of lamina propria associated with chronic mucosal inflammation were common. Examination of direct fecal smears was found not to be a reliable technique for diagnosis of cryptosporidial infections in snakes.


Neural network execution using nicked DNA and microfluidics.
DNA has been discussed as a potential medium for data storage. Potentially it could be denser, could consume less energy, and could be more durable than conventional storage media such as hard drives, solid-state storage, and optical media. However, performing computations on the data stored in DNA is a largely unexplored challenge. This paper proposes an integrated circuit (IC) based on microfluidics that can perform complex operations such as artificial neural network (ANN) computation on data stored in DNA. We envision such a system to be suitable for highly dense, throughput-demanding bio-compatible applications such as an intelligent Organ-on-Chip or other biomedical applications that may not be latency-critical. It computes entirely in the molecular domain without converting data to electrical form, making it a form of in-memory computing on DNA. The computation is achieved by topologically modifying DNA strands through the use of enzymes called nickases. A novel scheme is proposed for representing data stochastically through the concentration of the DNA molecules that are nicked at specific sites. The paper provides details of the biochemical design, as well as the design, layout, and operation of the microfluidics device. Benchmarks are reported on the performance of neural network computation.


Intraoperative arterial oxygenation in obese patients.
Although obese patients have been shown to represent a particularly high risk group with respect to hypoxemia both pre and postoperatively, no data exist to delineate the intraoperative arterial oxygenation pattern of these patients. Furthermore, no one has studied the effects of a change in operative position or a subdiaphragmatic laparotomy pack on arterial oxygenation (PaO2). Sixty-four adults undergoing jejunoileal bypass for morbid exogenous obesity, with a mean weight of 142.0 +/- 31.4 kg and a mean age of 33.3 +/- 10.4 years, were studied. Twenty-five patients (Group I) were maintained in the supine position throughout the operative procedure, while the remaining 39 patients (Group II) were changed to a 15 degrees head down position 15 minutes after a control blood sample was taken. Four additional markedly obese patients were studied to determine the effect of an abdominal pack of PaO2 values. The following findings were demonstrated: 1) 40% oxygen did not uniformly produce adequate arterial oxygenation for intra-abdominal surgery in otherwise healthy obese patients; 2) placement of a subdiaphragmatic abdominal laparotomy pack without a change in operative position resulted in a consistent fall in PaO2 in each patient to less than 65 mm Hg even though 40% oxygen was being administered; and 3) a change from supine to a 15 degrees head down operative position resulted in a significant (P less than 0.001) reduction in mean PaO2 (73.0 +/- 26.3 mm Hg). Seventy-seven per cent of these patients demonstrated PaO2 values of less than 80 mm Hg on 40% oxygen. Because of these findings, serious consideration should be given to the routine use of the Trendelenberg position intraoperatively in obese patients. However, if one elects this posture, prudence would dictate careful monitoring and maintenance of arterial oxygenation. Certainly, in obese patients, the intraoperative combination of the head down position and a subdiaphragmatic laparotomy pack should be avoided. In addition, since our data were collected in obese but otherwise healthy, young patients free of cardiorespiratory disease, special attention should be directed at the continuous measurement of arterial oxygenation in the older obese patient with either intrinsic dysfunction of vital organs (heart, lung, liver, kidney) or surgical disorders (peritonitis, sepsis).


Cyclosporine 0.05% ophthalmic emulsion for the treatment of radiation-associated dry eye in children.
Dry eye disease is a well-known late complication of radiation therapy and is often difficult to treat. We evaluated the usefulness of cyclosporine 0.05% ophthalmic emulsion for the treatment of radiation-associated dry eye in children. Eleven children received cyclosporine 0.05% emulsion twice daily after failure of conventional therapy. After 6 months, dry eye manifestations improved in three children (27.3%). The remaining eight children showed no improvement with cyclosporine 0.05% ophthalmic emulsion. These results suggest that twice-daily cyclosporine 0.05% ophthalmic emulsion has limited use in children with refractory radiation-associated chronic dry eye.


Risk Factors Predicting Complications of Transvenous Lead Extraction.
Transvenous lead extraction (TLE) is the gold standard in the management of patients with cardiac implantable electronic devices (CIED)-related complications. Knowledge of TLE risk factors is very important. Clinical data from 1915 patients undergoing TLE at the Reference Center between 2006 and 2015 were analyzed. The effects of clinical and procedure-related factors on the development of major (MJC) and minor (MIC) complications and survival after TLE were evaluated. MJC were caused mainly by lead implant duration, presence of abandoned leads, multiple procedures preceding TLE, and any technical problem during TLE. Of clinical factors female gender and anemia increased the risk of MJC. MIC were reported in patients with the first implantation of CIED under the age of 30 and after sternotomy analysis of 30-day survival after procedure demonstrated a significant effect of clinical factors and lead dwell times, previous unsuccessful TLE, and MIC. Efficacy and safety of TLE depend mainly on procedure-related factors. This knowledge is essential for preventing MJC and MIC. Mortality at 30 days following TLE is mainly associated with the clinical factors; however, there was also a significant effect of lead dwell time and periprocedural complications on the short-term prognosis of patients undergoing TLE.


Modulation of a photoswitchable dual-color quantum dot containing a photochromic FRET acceptor and an internal standard.
Photoswitchable semiconductor nanoparticles, quantum dots (QDs), couple the advantages of conventional QDs with the ability to reversibly modulate the QD emission, thereby improving signal detection by rejection of background signals. Using a simple coating methodology with polymers incorporating a diheteroarylethene photochromic FRET acceptor as well as a spectrally distinct organic fluorophore, photoswitchable QDs were prepared that are small, biocompatible, and feature ratiometric dual emission. With programmed irradiation, the fluorescence intensity ratio can be modified by up to ∼100%.


Ultrasonography of hepatic hydatid cysts: new diagnostic signs.
Eighty-five cases of hepatic hydatid cysts were examined by ultrasonography. On the basis of sonographic patterns (as well as clinical symptomatology and surgical, bacteriologic, and pathologic findings), four groups of cysts were identified: uninfected, organizing, suppurative, and degenerated. A specific sign is defined to differentiate hydatid cysts from cystic lesions of other types. Organizing cysts are defined and ways to differentiate them from infected cysts sonographically are discussed. An analysis was made of the echographically detected material between the daughter cysts previously referred to as "matrix." Clues are given to differentiate infected cysts from liver abscesses. A classification correlating the pathology with the life cycle of the parasite in the human body is proposed.


Point-of-Care Ultrasound Attitudes, Barriers, and Current Use Among Family Medicine Residents and Practicing Physicians.
Point-of-care ultrasound (POCUS) has high interest among learners and educators, but many barriers inhibit training and clinical use. Interest and barriers may differ between educators, trainees, and practicing physicians. This study investigates interest in POCUS, confidence in POCUS skills, and barriers to POCUS use for residents, academic family physicians, and community providers. Online surveys sent to current residents, faculty, and graduates of an academic family medicine residency compared current use, comfort, training, perceived importance, barriers, and interest in future use of POCUS. Most participants (95.6%) agreed that POCUS was somewhat or extremely important to family medicine. Most participants also reported interest in all POCUS indications, other than obstetrics. Very few (5.4%) reported being extremely comfortable using POCUS. Most residents were somewhat comfortable, whereas most faculty and graduates were not at all comfortable. A majority in each group reported inexperience with equipment and interpreting images as a barrier. One-third of faculty and graduates reported "not billable" as a barrier. Statistically significant differences were found between groups' reports of prior training, current use, and interest in POCUS for obstetrics. Family medicine residents, faculty, and community physicians reported high perceived importance of and interest in nonobstetric POCUS, but low comfort level in performing POCUS. Resident and faculty barriers may vary according to practice environment and differing time constraints. Senior faculty may have less POCUS training and comfort using POCUS than residents, highlighting the importance of continuing faculty education.


Mutational analysis of the transcription factor IIIB-DNA target of Ty3 retroelement integration.
The Ty3 retrovirus-like element inserts preferentially at the transcription initiation sites of genes transcribed by RNA polymerase III. The requirements for transcription factor (TF) IIIC and TFIIIB in Ty3 integration into the two initiation sites of the U6 gene carried on pU6LboxB were previously examined. Ty3 integrates at low but detectable frequencies in the presence of TFIIIB subunits Brf1 and TATA-binding protein. Integration increases in the presence of the third subunit, Bdp1. TFIIIC is not essential, but the presence of TFIIIC specifies an orientation of TFIIIB for transcriptional initiation and directs integration to the U6 gene-proximal initiation site. In the current study, recombinant wild type TATA-binding protein, wild type and mutant Brf1, and Bdp1 proteins and highly purified TFIIIC were used to investigate the roles of specific protein domains in Ty3 integration. The amino-terminal half of Brf1, which contains a TFIIB-like repeat, contributed more strongly than the carboxyl-terminal half of Brf1 to Ty3 targeting. Each half of Bdp1 split at amino acid 352 enhanced integration. In the presence of TFIIIB and TFIIIC, the pattern of integration extended downstream by several base pairs compared with the pattern observed in vitro in the absence of TFIIIC and in vivo, suggesting that TFIIIC may not be present on genes targeted by Ty3 in vivo. Mutations in Bdp1 that affect its interaction with TFIIIC resulted in TFIIIC-independent patterns of Ty3 integration. Brf1 zinc ribbon and Bdp1 internal deletion mutants that are competent for polymerase III recruitment but defective in promoter opening were competent for Ty3 integration irrespective of the state of DNA supercoiling. These results extend the similarities between the TFIIIB domains required for transcription and Ty3 integration and also reveal requirements that are specific to transcription.


Enzymatic catalysis in microemulsions: enzyme reuse and product recovery.
A technique for enzyme reuse and product recovery from enzymatic catalysis in microemulsions is demonstrated. The enzymatic reaction is performed in a homogeneous isotropic microemulsion; AOT (sodium bis-(2-ethyl- hexyl)sulfosuccinate)/isooctane/buffer or C(12)E(5)(penta ethylene glycol dodecyl ether)/heptane/buffer. By small temperature changes the systems are shifted to two phase regions, where an oil-rich phase, containing the product, coexists with a water-rich phase containing surfactant and enzyme. The oil-rich phase may be replaced by an oil solution containing new substrate. Thus, the reaction may be continued and the enzyme reused. This procedure was repeated nine times in the present study. Data on phase behavior in presence and in absence of protein, partitioning of the components and a radioactive-labelled protein between the phases, and the repeated use of horse liver alcohol dehydrogenase (HLADH) in the microemulsions are presented.


Polyamine-substituted gadolinium chelates: a new class of intracellular contrast agents for magnetic resonance imaging of tumors.
A new class of intracellular contrast agents (CA) for magnetic resonance imaging has been developed, based on Gd(DTPA) with two positively charged amide-linked substituents. Uptake of Gd(DTPA) into cultured tumor cell lines (B16 mouse melanoma, MH3924A Morris hepatoma) was below the detection limit while CA with the melanin-binding pharmacophore 2-(diethylamino)ethylamine reached intracellular concentrations of ca. 0.03 fmol/cell (ca. 20 microM) for melanoma and 0.02 fmol/cell for hepatoma (24 h at 10 microM CA). With the polyamine substituents bis(2-aminoethyl)amine or spermidine, CA uptake increased up to 3-fold for melanoma (0.083 fmol/cell) and 9-fold for hepatoma (0.18 fmol/cell). Uptake of polyamine-substituted CA was reduced by the polyamine transport inhibitor benzyl viologen. Molar relaxivities for three Gd-DTPA-polyamine complexes were in the range 5.6-6.9 for the free complex in solution and 7.7-23.5 s-1 mM-1 for Morris hepatoma cell pellets. T1-weighted magnetic resonance imaging at 2.35 T of rats with MH3924A tumors showed contrast enhancement in tumor at 1 and 24 h postinjection of polyamine-substituted CA.


Recent advances of exosomes in immune modulation and autoimmune diseases.
Exosomes are small membrane-bound vesicles (30-100 nm) that are secreted by different types of cells and they have been well documented to resemble saucers or flattened spheres under the electron microscope. Recently, evidence indicates that exosomes play important roles in the immune modulation and are associated with the immune pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA), Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). In this review, we will summarize current research advances of exosomes in immunoregulation, pathogenesis, diagnosis and therapeutics of autoimmune diseases.


Dystonia as a prominent presenting feature in developmental and epileptic encephalopathies: A case series.
Although there has been increasing recognition of the occurrence of non-epileptic involuntary movements in developmental and epileptic encephalopathies (DEEs), the spectrum of dystonic presentations associated with these conditions remains poorly described. We sought to expand the catalogue of dystonia-predominant phenotypes in monogenic DEEs, building on the recently introduced concept of an epilepsy-movement disorder spectrum. Cases were identified from a whole-exome-sequenced cohort of 45 pediatric index patients with complex dystonia (67% sequenced as parent-child trios). Review of molecular findings in DEE-associated genes was performed. For five individuals with identified DEE-causing variants, detailed information about presenting phenotypic features and the natural history of disease was obtained. De-novo pathogenic and likely pathogenic missense variants in GABRA1, GABBR2, GNAO1, and FOXG1 gave rise to infantile-onset persistent and paroxysmal dystonic manifestations, beginning in the limb or truncal musculature and progressing gradually to a generalized state. Coexisting, less prominent movement-disorder symptoms were observed and included myoclonic, ballistic, and stereotypic abnormal movements as well as choreoathetosis. Dystonia dominated over epileptic neurodevelopmental comorbidities in all four subjects and represented the primary indication for molecular genetic analysis. We also report the unusual case of an adult female patient with dystonia, tremor, and mild learning disability who was found to harbor a pathogenic frameshift variant in MECP2. Dystonia can be a leading clinical manifestation in different DEEs. A monogenic basis of disease should be considered on the association of dystonia and developmental delay-epilepsy presentations, justifying a molecular screening for variants in DEE-associated genes.


Direct Detection and Discrimination of Carbapenemases of Acinetobacter baumannii from Uncultured Tracheal Aspirates.
Carbapenemases play important roles in conferring resistance to beta-lactam antibiotics, including the carbapenems. Detection of carbapenemase activity helps to understand the possible mechanism(s) of carbapenem resistance. Identification of carbapenemases is currently being done by various phenotypic methods and molecular methods. However, innovative biochemical and spectrophotometric methods are desirable as they will be easy to perform, affordable, and rapid. A novel chromogenic method called Carba NP test was introduced recently to screen for carbapenemases in clinical isolates of gram-negative pathogens. We adopted this assay (1) to detect the total carbapenemase activity, (2) to discriminate Class A, B, and D carbapenemases with inhibitors, (3) to compare with carbapenemase genotype, and (4) for direct differential diagnosis of carbapenemases in uncultured clinical sample such as tracheal aspirate. The study included 132 purulent tracheal aspirates. All samples were processed and screened by a protocol optimized in our laboratory, which showed good sensitivity and correlation with genotyping and conventional phenotyping. Our protocol not only offers the fastest way to identify the pathogen but also its carbapenemase profile, directly from uncultured clinical samples in less than 4 hr. Our protocol is currently being validated on other types of clinical specimens in our laboratory.


Psychological and social factors associated with histories of risk for human immunodeficiency virus infection among African-American inner-city women.
Minority women constitute the fastest-growing segment of the American epidemic of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The present study examined the psychological and social factors related to HIV risk among 153 African-American inner-city women who completed measures of HIV risk history, sexual and substance use behaviors, perceived risk for HIV infection, self-efficacy to reduce risk (belief that one can effectively perform specific behaviors), and perceived social norms supporting risk reduction. Fifty-five percent of the women (n = 84) reported at least one factor that had placed them at known risk for HIV infection. Results of a stepwise regression analysis showed that HIV risk history was associated with self-perceived risk for HIV infection and self-efficacy to perform risk-reducing actions. Social norms for safer sex did not contribute significantly to the explained variance. Women at risk were more likely to have been forced or coerced into unwanted sex and were less likely to have been familiar with their most recent sex partner. These result suggest that HIV risk-reduction interventions targeting inner-city women should focus on skills training approaches to build self-efficacy and empower women to adopt risk-reducing practices.


Asymmetric synthesis of metallocenes through enantioselective addition of organolithium reagents to 6-(dimethylamino)fulvene.
Enantioselective addition of aryllithiums 2a-d (Ar = Ph (a), 2-MeC(6)H(4) (b), 2-MeOC(6)H(4) (c), 1-naphthyl (d)) to 6-(dimethylamino)fulvene (1) in the presence of (-)-sparteine in toluene at -78 degrees C generated chiral cyclopentadienyllithiums (4) substituted with an N,N-dimethylamino(aryl)methyl group, where the enantioselectivities are 51, 91, 90, and 83% for 4a, 4b, 4c, and 4d, respectively. Treatment of the chiral cyclopentadienides 4 with FeCl(2) or Fe(acac)(2) gave ferrocenes, which contain an N,N-dimethylamino(aryl)methyl side chain on both of the cyclopentadienyl rings. The enantiomeric purity of the chiral ferrocenes 7 thus obtained is 99% ee or higher for those containing a 2-MeC(6)H(4) (7b) or a 2-MeOC(6)H(4) (7c) group.


Microarray analysis reveals key genes and pathways in Tetralogy of Fallot.
The aim of the present study was to identify key genes that may be involved in the pathogenesis of Tetralogy of Fallot (TOF) using bioinformatics methods. The GSE26125 microarray dataset, which includes cardiovascular tissue samples derived from 16 children with TOF and five healthy age‑matched control infants, was downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed between TOF and control samples to identify differentially expressed genes (DEGs) using Student's t‑test, and the R/limma package, with a log2 fold‑change of >2 and a false discovery rate of <0.01 set as thresholds. The biological functions of DEGs were analyzed using the ToppGene database. The ReactomeFIViz application was used to construct functional interaction (FI) networks, and the genes in each module were subjected to pathway enrichment analysis. The iRegulon plugin was used to identify transcription factors predicted to regulate the DEGs in the FI network, and the gene‑transcription factor pairs were then visualized using Cytoscape software. A total of 878 DEGs were identified, including 848 upregulated genes and 30 downregulated genes. The gene FI network contained seven function modules, which were all comprised of upregulated genes. Genes enriched in Module 1 were enriched in the following three neurological disorder‑associated signaling pathways: Parkinson's disease, Alzheimer's disease and Huntington's disease. Genes in Modules 0, 3 and 5 were dominantly enriched in pathways associated with ribosomes and protein translation. The Xbox binding protein 1 transcription factor was demonstrated to be involved in the regulation of genes encoding the subunits of cytoplasmic and mitochondrial ribosomes, as well as genes involved in neurodegenerative disorders. Therefore, dysfunction of genes involved in signaling pathways associated with neurodegenerative disorders, ribosome function and protein translation may contribute to the pathogenesis of TOF.


A randomized trial of lifestyle intervention in primary healthcare for the modification of cardiovascular risk factors.
To evaluate the effects of a lifestyle intervention programme in primary healthcare, targeted to patients with moderate to high risk of cardiovascular disease in terms of cardiovascular risk factors, physical activity, and quality of life. Randomized controlled trial with one-year follow-up, carried out in a primary healthcare centre in Northern Sweden. A total of 151 middle-aged men and women, with hypertension, dyslipidemia, type 2 diabetes, or obesity were enrolled. The subjects were randomized to either the intervention (n = 75) or the control group (n = 76). A total of 123 subjects completed the one-year follow-up. Exercise: supervised endurance and circuit training in groups three times a week for three months. Diet: five group sessions of diet counselling with a dietitian. Follow- up meetings with a physiotherapist were conducted monthly thereafter. Primary outcomes were changes in anthropometry, maximal oxygen uptake, health-related quality of life, and self-reported physical activity. The secondary outcomes were changes in blood pressure and metabolic variables. After one year the intervention group significantly increased maximal oxygen uptake, physical activity, and quality of life and significantly decreased body weight, waist and hip circumference, body mass index, waist-hip ratio, systolic and diastolic blood pressure, triglycerides, and glycosylated haemoglobin. There were significant differences between groups, mean changes (and their 95% confidence intervals, CI) in waist circumference -1.9 cm (-2.80 to -0.90; p<0.001), in waist-hip ratio -0.01 (-.02 to -0.004; p<0.01) and in diastolic blood pressure -2.3 mmHg (-4.04 to -0.51; p<0.05). A prevention programme in primary healthcare with a focus on physical activity and diet counselling followed by structured follow-up meetings can favourably influence several risk factors for cardiovascular diseases and quality of life in high-risk subjects for at least one year.


Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair.
Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage.


Arctic freshwater impact on the Atlantic Meridional Overturning Circulation: status and prospects.
Arguably, the most conspicuous evidence for anthropogenic climate change lies in the Arctic Ocean. For example, the summer-time Arctic sea ice extent has declined over the last 40 years and the Arctic Ocean freshwater storage has increased over the last 30 years. Coupled climate models project that this extra freshwater will pass Greenland to enter the sub-polar North Atlantic Ocean (SPNA) in the coming decades. Coupled climate models also project that the Atlantic Meridional Overturning Circulation (AMOC) will weaken in the twenty-first century, associated with SPNA buoyancy increases. Yet, it remains unclear when the Arctic anthropogenic freshening signal will be detected in the SPNA, or what form the signal will take. Therefore, this article reviews and synthesizes the state of knowledge on Arctic Ocean and SPNA salinity variations and their causes. This article focuses on the export processes in data-constrained ocean circulation model hindcasts. One challenge is to quantify and understand the relative importance of different competing processes. This article also discusses the prospects to detect the emergence of Arctic anthropogenic freshening and the likely impacts on the AMOC. For this issue, the challenge is to distinguish anthropogenic signals from natural variability. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.


1-Acetyl-3'-(4-bromophenyl)-3'-chlorospiro[3H-indole-3,2'-oxetan]-2(1H)-one.
In the title compound, C(18)H(13)BrClNO(3), the heterocyclic ring of the indole is distorted from planarity towards an envelope conformation. The orientations of the indole, oxetane, chloro and bromophenyl substituents are conditioned by the sp(3) states of the spiro-junction and the Cl-attached C atoms.


[Orbital neurinoma presenting orbital apex syndrome].
A 75-year-old man presented a twelve-day history of double vision and retro-ocular pain with rapid deterioration of visual acuity. Neurological examination on admission demonstrated right oculomotor palsy and abducence palsy, visual loss in the right eye, and hypesthesia and pain in the right supraorbital nerve. CT scan and MRI disclosed a mass in the right orbital apex. An emergency operation via a frontotemporal extradural approach was performed to decompress the optic nerve. The anterior clinoid process and minor wing of the sphenoid were drilled to expose the optic canal and superior orbital fissure. When the periorbita just beside the optic sheath was opened, a grayish colored mass was observed beneath the superior rectus muscle. The mass was dissected from the surrounding intraorbital tissue and was removed completely. The postoperative course was uneventful. The patient experienced complete disappearance of the ocular pain and complete restoration of his visual acuity. Orbital neurinoma is a benign tumor accounting for between 2.1 and 6.8% of all orbital tumors in the large series. The salient clinical symptom is exophthalmos followed by mass palpability. However, an orbital neurinoma presenting orbital apex syndrome is quite rare. In the case with orbital apex syndrome, it is sometimes impossible to recover visual acuity even though the optic nerve decompression is promptly performed. In such a case, only an emergency approach to the lesion can rescue the visual acuity.


Endothelial cell-associated platelet-activating factor primes neutrophils for enhanced superoxide production and arachidonic acid release during adhesion to but not transmigration across IL-1 beta-treated endothelial monolayers.
The role of platelet-activating factor (PAF) in stimulating neutrophils during interaction with HUVEC has been investigated using the specific PAF receptor antagonists WEB 2086 and YM 264. PAF antagonists at concentrations up to 40 microM had little effect on the adhesion of neutrophils to control or IL-1 beta-stimulated HUVEC monolayers. However, polarization of neutrophils on adhesion to IL-1-treated HUVEC was markedly diminished in the presence of PAF antagonists. In addition, the PAF antagonists WEB 2086 and YM 264 strongly inhibited the migration of neutrophils across IL-1-treated endothelial monolayers. Priming of neutrophil respiratory burst and arachidonic acid release caused by contact with IL-1-treated endothelial cells was also inhibited by PAF antagonists. However, priming as a consequence of transmigration was not inhibited by either WEB 2086 or YM 264. These results suggest that HUVEC-associated PAF plays a central role in the polarization and subsequent transmigration of neutrophils during interaction with HUVEC monolayers. Moreover, the results further suggest that PAF is responsible for priming neutrophils during contact with HUVECs. However, after transmigration, factors other than PAF are responsible for the priming of neutrophil function.


A double-blind trial of methocarbamol versus placebo in painful muscle spasm.
A double-blind trial of methocarbamol versus placebo was carried out in 59 matched pairs of patients suffering from painful muscle spasm. Methocarbamol (1500 mg. q.d.s.) was found to be effective in approximately 60% of patients compared with 30% of patients receiving placebo (p less than 0.01). Side-effects were of almost equal incidence in the two groups.


Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer.
Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival. In this study, we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio (NLR) in predicting the survival of patients with non-small cell lung cancer (NSCLC). We retrospectively enrolled 589 patients with NSCLC who underwent surgery. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the combination of fibrinogen and NLR (F-NLR). The cut-off values for fibrinogen, NLR, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30, respectively. Patients with both a high NLR (≥ 2.30) and hyperfibrinogenemia (≥ 3.48 g/L) were given a score of 2, whereas those with one or neither were scored as 1 or 0, respectively. Our results showed that F-NLR was an independent prognostic indicator for disease-free survival (DFS) [hazard ratio (HR), 1.466; 95% confidence interval (CI), 1.243-1.730; P < 0.001] and overall survival (OS) (HR, 1.512; 95% CI, 1.283-1.783; P < 0.001). The five-year OS rates were 66.1%, 53.5%, and 33.3% for the F-NLR = 0, F-NLR = 1, and F-NLR = 2, respectively ( P < 0.001). Correspondingly, their five-year DFS rates were 62.2%, 50.3%, and 30.4%, respectively ( P < 0.001). In the subgroup analyses of the pathological stages, the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers. Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.


PDE-5 Inhibitor Therapy for Erectile Dysfunction Secondary to Nerve-Sparing Radical Retropubic Prostatectomy.
The majority of patients receiving therapy for erectile dysfunction (ED) following post-radical retropubic prostatectomy (RRP) are treated with phosphodiesterase (PDE)-5 inhibitors, which seem to have variable efficacy in this population. So far, the only head-to-head trials with PDE-5 inhibitors have been in general ED patients and not in post-RRP patients. Both vardenafil and tadalafil failed to meet statistical noninferiority to sildenafil in head-to-head trials. To date, only sildenafil has demonstrated efficacy in the prevention of post-nerve-sparing RRP ED. The selection of a PDE-5 inhibitor requires consideration of the patient's sexual activity pattern as well as the drug's efficacy and its ability to meet the patient's expectations. In this regard, sildenafil continues to account for almost 70% of PDE-5 inhibitor prescriptions in the United States.


Determinant of Osteoporosis Preventive Behaviors among Perimenopausal Women: A Cross-Sectional Study to Explore the Role of Knowledge and Health Beliefs.
Osteoporosis is a silent chronic disease, and many people did not discover it until they were diagnosed with a fracture. Therefore, regular scanning and appropriate Osteoporosis Preventive Behaviors (OPB) are the management cornerstone. OPB is strongly affected by personal knowledge and health beliefs. This study explores the role of knowledge and health beliefs as determinants of OPB among perimenopausal women. This cross-sectional study was performed on 1075 perimenopausal women in Najran City, Saudi Arabia, from January 2023 to March 2023. The data collection instrument is a self-reported questionnaire consisting of basic data, the OPB scale, an osteoporosis knowledge assessment tool, and the osteoporosis health belief scale. The current study results showed that approximately one-quarter (27.8%) of the study participants had high OPB with an overall mean of 20.83 ± 5.08 grade. The group practicing high OPB demonstrated a higher knowledge mean (11.37 ± 2.99) than the low OPB group (9.93 ± 3.51). In addition, all health beliefs constructs significantly differed among the low and high OPB groups (p ˂ 0.05). The participant's age, occupational status, educational level, attendance of training courses, and history of bone fractures were significantly associated with high OPB. Osteoporosis knowledge, perceived susceptibility, perceived seriousness, exercises' perceived benefits, and health motivations are positive predictors of high OPB (p ˂ 0.05). The study concluded that osteoporosis-related knowledge and health beliefs-especially perceived susceptibility, perceived seriousness, exercises' perceived benefits, and health motivations-are positive predictors of high OPB. The health belief model can be an effective tool used to determine high-risk groups who practice low OPB and build need-based educational interventions.


Clinically suspected pulmonary embolism: utility of spiral CT.
To prospectively determine the utility of contrast material-enhanced spiral computed tomography (CT) in the examination of patients clinically suspected of having pulmonary embolism (PE). One hundred ten patients clinically suspected of having PE were examined with contrast-enhanced spinal CT and at least one other imaging modality: ventilation-perfusion scintigraphy, Doppler ultrasonography of deep leg veins, or pulmonary angiography. Chart review or telephone contact with the referring clinician was used to evaluate the contribution of spiral CT to the final clinical diagnosis. Spiral CT helped correctly identify 23 of 25 patients with PE (sensitivity, 92%). In 57 (67%) of the 85 patients without PE, spiral CT provided additional information that suggested or confirmed the alternate clinical diagnosis: pneumonia (n = 14), cardiovascular disease (n = 10), pulmonary fibrosis (n = 7), trauma (n = 6), malignancy (n = 5), pleural disease (n = 4), postoperative changes (n = 4), and other (n = 7). In the remaining 28 patients, spiral CT scans were normal (n = 12), failed to produce findings supportive of the final clinical diagnosis (n = 13), or were false-positive for PE (n = 3; specificity, 96%). Spiral CT has good sensitivity and specificity for the diagnosis of PE. In the majority of patients who do not have PE, it also provides important ancillary information for the final diagnosis.


Quantification of Empty, Partially Filled and Full Adeno-Associated Virus Vectors Using Mass Photometry.
Adeno-associated viruses (AAV) are one of the most commonly used vehicles in gene therapies for the treatment of rare diseases. During the AAV manufacturing process, particles with little or no genetic material are co-produced alongside the desired AAV capsid containing the transgene of interest. Because of the potential adverse health effects of these byproducts, they are considered impurities and need to be monitored carefully. To date, analytical ultracentrifugation (AUC), transmission electron microscopy (TEM) and charge-detection mass spectrometry (CDMS) are used to quantify these subspecies. However, they are associated with long turnaround times, low sample throughput and complex data analysis. Mass photometry (MP) is a fast and label-free orthogonal technique which is applicable to multiple serotypes without the adaption of method parameters. Furthermore, it can be operated with capsid titers as low as 8 × 1010 cp mL-1 with a CV < 5% using just 10 µL total sample volume. Here we demonstrate that mass photometry can be used as an orthogonal method to AUC to accurately quantify the proportions of empty, partially filled, full and overfull particles in AAV samples, especially in cases where ion-exchange chromatography yields no separation of the populations. In addition, it can be used to confirm the molar mass of the packaged genomic material in filled AAV particles.


Validity of Rorschach inanimate movement and diffuse shading responses as measures of frustration and anxiety.
The purpose of this study was to validate Rorschach inanimate movement and diffuse shading responses as measured of frustration and anxiety. 48 subjects were assigned into four cells of no treatment, frustration condition, anxiety condition, and a combination of both the frustration and anxiety conditions in a 2 x 2 (anxiety by frustration) design. Two-way analyses of variance of the influence of anxiety and frustration on inanimate movement responses and shading responses gave no significant main effects or interactions. Also, no significant relationships were found between state anxiety scores and inanimate movement or shading responses.


Direct observation of the growth process of MgO nanoflowers by a simple chemical route.
Novel flowerlike nanostructures consisting of MgO nanofibers were successfully synthesized by a simple chemical route with H(2)O at 950 degrees C in an Ar atmosphere. Various durations of heating gave different growth stages that led to varied product morphologies. The synthesized products were systematically studied by X-ray powder diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray analysis. The results show that the nucleation and growth process of the nanoflowers seems to be a vapor-solid mechanism, and that the total heating time during the reaction process is a critical factor for the development of MgO nanoflowers. Initially, Mg particles formed on the Si substrate, followed by the formation of MgO clusters as nucleation centers on the magnesium melt surface and the nucleation of short MgO nanofibers, then growth of the MgO nanofibers occurred, and finally MgO nanoflowers were formed. Besides nanoflowers, novel hierarchical MgO nanostructures were also observed. These nanostructures may be used as three-dimensional composite materials and as supports for other materials.


Cytokines in acute and chronic inflammation.
Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. Inflammatory cytokines can be divided into two groups: those involved in acute inflammation and those responsible for chronic inflammation. This review describes the role played in acute inflammation by IL-1, TNF-alpha, IL-6, IL-11, IL-8 and other chemokines, G-CSF, and GM-CSF. It also describes the involvement of cytokines in chronic inflammation. This latter group can be subdivided into cytokines mediating humoral responses such as IL-4, IL-5, IL-6, IL-7, and IL-13, and those mediating cellular responses such as IL-1, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons, transforming growth factor-beta, and tumor necrosis factor alpha and beta. Some cytokines, such as IL-1, significantly contribute to both acute and chronic inflammation. This review also summarizes features of the cell-surface receptors that mediate the inflammatory effects of the described cytokines.


Growth of Salmonella enterica in model mixed cultures during a two-step enrichment.
Growth of Salmonella enterica was studied in model mixed cultures with Citrobacter freundii or Escherichia coli in buffered peptone water (BPW) and in Rappaport-Vassiliadis medium with soya (RVS) with modified concentrations of MgCl2 and malachite green, and at modified incubation temperatures. Selected S. enterica strains were inoculated in BPW (10(0) cfu/ml) together with selected strains of Citrobacter freundii (up to 10(8) cfu/ml) or selected strains of Escherichia coli (up to 10(8) cfu/ml), incubated overnight and then subcultured (1: 100) in RVS variants. Growth of individual bacterial species was followed by the quantitative real-time polymerase chain reaction (PCR). Optimal culture conditions during the second selective step were: MgCl2.6 H2O concentration of 29 g/l, malachite green concentration of 36 mg/1l, and the incubation temperature of 41.5 degrees C. Citr. freundii was found to be a potent competitor and E. coli was a weaker competitor. At optimal culture conditions, competition was reduced and the density of S. enterica cultures reached the level of 10(4) cfu/ml after not later than 2 h of selective enrichment. The results obtained provide a basis for the development of a short two-step enrichment to be used in rapid real-time PCR-based methods for the detection of S. enterica in food and other matrices.


In vivo alternative testing with zebrafish in ecotoxicology.
Although rodents have previously been used in ecotoxicological studies, they are expensive, time-consuming, and are limited by strict legal restrictions. The present study used a zebrafish (Danio rerio) model and generated data that was useful for extrapolating toxicant effects in this system to that of humans. Here we treated embryos of the naive-type as well as a transiently transfected zebrafish liver cell line carrying a plasmid (phAhREEGFP), for comparing toxicity levels with the well-known aryl hydrocarbon receptor (AhR)-binding toxicants: 3,3',4,4',5-pentachlorobiphenyl (PCB126), 2,3,7,8-tetrachlorodibenzo-p-dioxin, and 3-methylcholanthrene. These toxicants induced a concentration-dependent increase in morphological disruption, indicating toxicity at early life-stages. The transient transgenic zebrafish liver cell line was sensitive enough to these toxicants to express the CYP1A1 regulated enhanced green fluorescent protein. The findings of this study demonstrated that the zebrafish in vivo model might allow for extremely rapid and reproducible toxicological profiling of early life-stage embryo development. We have also shown that the transient transgenic zebrafish liver cell line can be used for research on AhR mechanism studies.


Intrinsic vs environment driven equilibrium folding transitions in GTPase effector domain of dynamin: NMR insights.
Relative importance of the intrinsic properties of the polypeptide chain vis-a-vis the environmental influences, in driving the folding of a protein, has been a subject of extensive debate and investigation. Folding/misfolding lead to self association in many systems, which have biological functional significance. We compare here, the NMR derived equilibrium folding transitions driven under different environmental conditions in the GTPase Effector Domain of dynamin, which self-associates into megadalton size species. We conclude that though hierarchy of folding and association of GED is substantially influenced by the solvents, these properties, to a good extent are also driven by intrinsic properties of the polypeptide chain, and the regions that form secondary structures, the types of secondary structures formed in those regions, and finally the regions that participate in the self-association are the same, indicating near neighbor interactions would have a telling effect on the final outcome of the folding process. These observations would open a new reliable frontier for elucidating the multiple folding trajectories and consequent self-association, by simulations in vacuum, for this protein.


Are women with more of 'social capital' more empowered? A cross-sectional analysis from rural Wardha, Central India.
Despite international commitment and government policies and programmes, a vast majority of women of rural India are socially and economically deprived in the patriarchal sociocultural framework. Strategies to improve women empowerment need context-specific field-based evidence. This study was undertaken to address the research question: "Are women with a higher level of social capital more empowered than their counterparts?" A community-based cross-sectional analytical study was carried out in the Wardha district of Maharashtra, where a two-stage cluster random sampling technique was used to select the 300 study subjects. The outcome variable, women empowerment was assessed using four domains: mobility, inter-spouse communication, household decision-making and asset ownership. The independent variables included social capital along with potential sociodemographic confounders. Multivariate linear regression was applied using the backward stepwise method. The participants had better women empowerment percentage score in the "Household decision-making" domain compared to the other domains. The women empowerment score was found to be significantly higher in the participants with increasing age, higher education, those involved in business/service, above poverty line (ABL), nuclear family, married, and those having at least one living child. In the adjusted analysis, the social capital was found to be a significant determinant of women empowerment, along with age, education, religion, marital status and family type. The improvement of social capital in the form of community-based development projects through Self-Help Groups (SHG) and microfinance programmes need to be encouraged by the Government and NGOs, as this strategy has the potential to improve women empowerment through community-driven development.


Relation between some haematological abnormalities, degree of immunosuppression and viral load in treatment-naïve HIV-infected patients.
This cross-sectional study at a teaching hospital in north-eastern Nigeria estimated the prevalence of anaemia, leukopenia and thrombocytopenia in treatment-naïve HIV-infected patients (177 males and 316 females), and the associations with virological and immunological markers. The overall prevalences of anaemia, leukopenia and thrombocytopenia were 49.5%, 5.5% and 4.5% respectively. The prevalence of anaemia was significantly higher in males than females (61.6% versus 42.7%), while the rates of leukopenia (5.1% versus 5.7%) and thrombocytopenia (5.7% versus 3.8%) were similar. Almost two-thirds of the HIV treatment-naïve studied patients, 293/493 (59.4%), had cytopenia and would require antiretroviral drugs. AIDS was diagnosed by clinical or immunological criteria in 70% of patients. The degree of cytopenia was directly related to the degree of immunosuppression and clinical AIDS status. No relationship was observed between cytopenia and viral load.


Phlebotomy treatment for elimination of perfluoroalkyl acids in a highly exposed family: a retrospective case-series.
Perfluoroalkyl acids (PFAAs) are a family of commonly used synthetic chemicals that have become widespread environmental contaminants. In human serum, perfluorohexane sulfonate (PFHxS), perflurooctane sulfonate (PFOS), and perfluorooctanoate (PFOA) are most frequently detected, in part owing to their long elimination half-lives of between 3.8 yrs (PFOA) and 8.5 yrs (PFHxS). These PFAAs also cross the placenta and have been associated with developmental toxicity, and some are considered likely human carcinogens. Interventions to eliminate PFAAs in highly contaminated individuals would reduce future health risks, but minimal research has been conducted on methods to facilitate accelerated human clearance of these persistent substances. Six patients with elevated serum concentrations from a single family were treated by intermittent phlebotomy over a 4-5 year period at intervals similar to, or less frequent than what is done for routine blood donation at Canadian Blood Services. The apparent elimination half-life (HLapp) for PFHxS, PFOS, and PFOA in this treated population was calculated in each patient and compared to the intrinsic elimination half-lives (HLin) from a literature reference population of untreated fluorochemical manufacturing plant retirees (n = 26, age >55 yrs). For all three PFAAs monitored during phlebotomy, HLapp in each of the family members (except the mother, who had a low rate of venesection) was significantly shorter than the geometric mean HL measured in the reference population, and in some cases were even shorter compared to the fastest eliminator in the reference population. This study suggests significantly accelerated PFAA clearance with regular phlebotomy treatment, but the small sample size and the lack of controls in this clinical intervention precludes drawing firm conclusions. Given the minimal risks of intermittent phlebotomy, this may be an effective and safe clinical intervention to diminish the body burden of PFAAs in highly exposed people.


Multi-Behavior Graph Neural Networks for Recommender System.
Recommender systems have been demonstrated to be effective to meet user's personalized interests for many online services (e.g., E-commerce and online advertising platforms). Recent years have witnessed the emerging success of many deep-learning-based recommendation models for augmenting collaborative filtering (CF) architectures with various neural network architectures, such as multilayer perceptron and autoencoder. However, the majority of them model the user-item relationship with single type of interaction, while overlooking the diversity of user behaviors on interacting with items, which can be click, add-to-cart, tag-as-favorite, and purchase. Such various types of interaction behaviors have great potential in providing rich information for understanding the user preferences. In this article, we pay special attention on user-item relationships with the exploration of multityped user behaviors. Technically, we contribute a new multi-behavior graph neural network (), which specially accounts for diverse interaction patterns and the underlying cross-type behavior interdependencies. In the framework, we develop a graph-structured learning framework to perform expressive modeling of high-order connectivity in behavior-aware user-item interaction graph. After that, a mutual relationship encoder is proposed to adaptively uncover complex relational structures and make aggregations across layer-specific behavior representations. Through comprehensive evaluation on real-world datasets, the advantages of our method have been validated under different experimental settings. Further analysis verifies the positive effects of incorporating the multi-behavioral context into the recommendation paradigm. In addition, the conducted case studies offer insights into the interpretability of user multi-behavior representations. We release our model implementation at https://github.com/akaxlh/MBRec.


Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis.
The presence of autoantibodies in the serum of 110 patients with primary biliary cirrhosis (PBC), 50 with HBsAg negative chronic active hepatitis (HBsAg- CAH) and 30 with HBsAg positive chronic active hepatitis (HBsAg+ CAH) was assessed using two methods: indirect immunofluorescence on cells grown in tissue culture (HEp-2 cell line) or standard mouse tissue sections, and counter immunoelectrophoresis (CIE) with soluble tissue extracts. Anti-nuclear antibodies (ANA) were found in 38% of sera from patients with PBC using HEp-2 cells compared with 10% using mouse tissue. A variety of staining patterns were detected including a pattern of multiple nuclear dots. In contrast, ANA was detected in 70% of sera from patients with HBsAg- CAH and 27% with HBsAg+ CAH. Using CIE four distinct antibody antigen systems were detected: Ro (SS-A), La (SS-B) and two new systems, designated XH and XR, reacting with extracts of human spleen and rabbit thymus, respectively. Correlation of the presence of antibody with clinical conditions confirmed the close association between anti-centromere antibody and sclerodactyly in patients with PBC and indicated an association between 'multiple nuclear dot' staining and the sicca syndrome in PBC. No association was found between the presence of either Ro or La antibody and the sicca syndrome in patients with PBC.


Time Prediction Models for Echinococcosis Based on Gray System Theory and Epidemic Dynamics.
Echinococcosis, which can seriously harm human health and animal husbandry production, has become an endemic in the Xinjiang Uygur Autonomous Region of China. In order to explore an effective human Echinococcosis forecasting model in Xinjiang, three grey models, namely, the traditional grey GM(1,1) model, the Grey-Periodic Extensional Combinatorial Model (PECGM(1,1)), and the Modified Grey Model using Fourier Series (FGM(1,1)), in addition to a multiplicative seasonal ARIMA(1,0,1)(1,1,0)₄ model, are applied in this study for short-term predictions. The accuracy of the different grey models is also investigated. The simulation results show that the FGM(1,1) model has a higher performance ability, not only for model fitting, but also for forecasting. Furthermore, considering the stability and the modeling precision in the long run, a dynamic epidemic prediction model based on the transmission mechanism of Echinococcosis is also established for long-term predictions. Results demonstrate that the dynamic epidemic prediction model is capable of identifying the future tendency. The number of human Echinococcosis cases will increase steadily over the next 25 years, reaching a peak of about 1250 cases, before eventually witnessing a slow decline, until it finally ends.


Pyoderma gangrenosum with an underlying ulcerative colitis associated with bone tuberculosis.
Pyoderma gangrenosum is a rare noninfective neutrophilic dermatosis, characterized by progressive painful ulceration. It is frequently associated with systemic disorders like inflammatory bowel disease, rheumatoid arthritis and myeloproliferative diseases. However, its association with infectious diseases in particular with tuberculosis is extremely rare. Diagnosis is based on the history of an underlying disease, a typical clinical presentation, histopathology and exclusion of other diseases leading to ulcerations of similar appearance. Immunosuppression with corticosteroids remains the mainstay of treatment. We report a case of a 49-year-old male with long-standing ulcerative colitis, associated with tuberculosis of hip, who presented with nonhealing ulcers over the lower extremity.


Acetylation changes at lysine 5 of histone H4 associated with lytic gene promoters during reactivation of Kaposi's sarcoma-associated herpesvirus.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a pathogenic agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease in humans. Similarly to other gammaherpesviruses such as Epstein-Barr virus (EBV) and herpesvirus saimiri (HVS), KSHV displays two alternative life cycles, latent and lytic one. The transactivation from latency to the lytic phase is the result of transcriptional changes in the KSHV genome caused by the replication and transcriptional activator (RTA). During KSHV reactivation, epigenetic modifications of histone protein on the viral genome occur, which regulate the transcriptional activation of a number of lytic genes. The reactivation of EBV from latency to lytic cycle, induced by an immediate-early Zta protein, was shown to be accompanied by acetylation of specific lysines in histone H4. Accordingly, we hypothesized that the RTA-induced transactivation of KSHV could also be accompanied by histone acetylation. To validate this hypothesis, we assayed alterations of acetyl-histone H4-lysine 5 (acH4K5) during the RTA-mediated KSHV reactivation. While the modified histone protein in a total cell lysate was not distinguished between control and RTA-expressed cells, upregulated acH4K5 was detected on several lytic gene promoter regions during KSHV reactivation. Our results clearly indicate that this epigenetic change is related to transcription of genes expressed in the lytic cycle of KSHV.


Lower dose of hypertonic saline dextran reduces the risk of lethal rebleeding in uncontrolled hemorrhage.
To challenge whether the recommended dose of 4 mL/kg of 7.5% sodium chloride in 6% Dextran (HSD) is optimal for fluid resuscitation in uncontrolled hemorrhage, 30 anesthetized pigs were randomized to receive a 5-min intravenous infusion of either 1, 2, or 4 mL/kg of HSD beginning 10 min after inducing a 5-mm laceration in the infrarenal aorta. In addition to conventional hemodynamic monitoring, the blood loss was calculated as the difference in blood flow rates between flow probes placed proximal and distal to the injury. The results show that the bleeding stopped between 3 and 4 min after the injury and amounted to 338+/-92 mL (mean +/- SEM), which corresponds to 28.5%+/-6.6% of the estimated blood volume. After treatment with HSD was started, six rebleeding events occurred in the 1-mL group, 11 in the 2-mL group, and 16 in the 4-mL group. The amount of blood lost due to rebleeding increased significantly with the dose of HSD and was also associated with a fatal outcome. The total blood loss was 408 mL in the survivors and 630 mL in the nonsurvivors (median, P < 0.007). The mortality in the three groups was 20%, 50%, and 50%, respectively. In conclusion, infusing 4 mL/kg of HSD after uncontrolled aortic hemorrhage promoted rebleeding and increased the mortality, while a dose of 1 mL/kg appeared to be more suitable.


Epigenetic insights into multiple sclerosis disease progression.
Multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system, is today a leading cause of unpredictable lifelong disability in young adults. The treatment of patients in progressive stages remains highly challenging, alluding to our limited understanding of the underlying pathological processes. In this review, we provide insights into the mechanisms underpinning MS progression from a perspective of epigenetics, that refers to stable and mitotically heritable, yet reversible, changes in the genome activity and gene expression. We first recapitulate findings from epigenetic studies examining the brain tissue of progressive MS patients, which support a contribution of DNA and histone modifications in impaired oligodendrocyte differentiation, defective myelination/remyelination and sustained neuro-axonal vulnerability. We next explore possibilities for identifying factors affecting progression using easily accessible tissues such as blood by comparing epigenetic signatures in peripheral immune cells and brain tissue. Despite minor overlap at individual methylation sites, nearly 30% of altered genes reported in peripheral immune cells of progressive MS patients were found in brain tissue, jointly converging on alterations of neuronal functions. We further speculate about the mechanisms underlying shared epigenetic patterns between blood and brain, which likely imply the influence of internal (genetic control) and/or external (e.g. smoking and ageing) factors imprinting a common signature in both compartments. Overall, we propose that epigenetics might shed light on clinically relevant mechanisms involved in disease progression and open new avenues for the treatment of progressive MS patients in the future.


Home sweet home: the tumor microenvironment as a haven for regulatory T cells.
CD4(+)Foxp3(+) regulatory T cells (Tregs) have a fundamental role in maintaining immune balance by preventing autoreactivity and immune-mediated pathology. However this role of Tregs extends to suppression of anti-tumor immune responses and remains a major obstacle in the development of anti-cancer vaccines and immunotherapies. This feature of Treg activity is exacerbated by the discovery that Treg frequencies are not only elevated in the blood of cancer patients, but are also significantly enriched within tumors in comparison to other sites. These observations have sparked off the quest to understand the processes through which Tregs become elevated in cancer-bearing hosts and to identify the specific mechanisms leading to their accumulation within the tumor microenvironment. This manuscript reviews the evidence for specific mechanisms of intra-tumoral Treg enrichment and will discuss how this information may be utilized for the purpose of manipulating the balance of tumor-infiltrating T cells in favor of anti-tumor effector cells.


Recurrent Hodgkin's Disease Presenting as a Clinically Isolated Cavernous Sinus Syndrome.
Hodgkin's disease involving the central nervous system is uncommon and is usually seen in patients with uncontrolled systemic disease or those who have had multiple episodes of recurrent disease. Common symptoms of intracranial Hodgkin's disease are motor and/or sensory deficits, headache, papilloedema, coma, and seizures. The rarity of Hodgkin's disease presenting with intracranial involvement is marked, but patients presenting with cavernous sinus syndrome is even rarer. Despite its rarity, the presence of a cavernous sinus syndrome in a patient with a known history of Hodgkin's disease warrants full utilization of modern diagnostic techniques in terms of investigation. Case Presentation. A 34-year-old woman, known with previous Hodgkin's lymphoma and now in remission for the past 7 years, presented with signs and symptoms suggestive of a left cavernous sinus syndrome. She was otherwise systemically well with no other complaints. Extensive investigations revealed no obvious cause for the cavernous sinus syndrome. A CT chest revealed subclinical axillary lymphadenopathy, which on excisional biopsy confirmed recurrent Hodgkin's disease. The patient's sole clinical presentation of her recurrent disease was the cavernous sinus syndrome, with no other clinically obvious systemic signs or symptoms to suggest a relapse. This was treated with steroids, and clinical improvement was noted; she was referred to oncology for extensive chemotherapy. Whilst there is a paucity of literature around this topic, it must be remembered by the clinician that cavernous sinus syndrome may be the sole clinical presentation of recurrent Hodgkin's disease. Even though it is reported that lymphomatous involvement in the brain usually occurs late in the disease process, this case is evidence that cavernous sinus syndrome may precede other systemic signs and symptoms. Recognising this possibility will ensure a rigorous search for Hodgkin's disease, an early and effective diagnosis, and a better prognosis in affected patients.


Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism.
Postprandial hypertriglyceridemia and low plasma HDL levels, which are principal features of the metabolic syndrome, are displayed by transgenic mice expressing human apolipoprotein A-II (hapoA-II). In these mice, hypertriglyceridemia results from the inhibition of lipoprotein lipase and hepatic lipase activities by hapoA-II carried on VLDL. This study aimed to determine whether the association of hapoA-II with triglyceride-rich lipoproteins (TRLs) is sufficient to impair their catabolism. To measure plasma TRL residence time, intestinal TRL production was induced by a radioactive oral lipid bolus. Radioactive and total triglyceride (TG) were rapidly cleared in control mice but accumulated in plasma of transgenic mice, in relation to hapoA-II concentration. Similar plasma TG accumulations were measured in transgenic mice with or without endogenous apoA-II expression. HapoA-II (synthesized in liver) was detected in chylomicrons (produced by intestine). The association of hapoA-II with TRL in plasma was further confirmed by the absence of hapoA-II in chylomicrons and VLDL of transgenic mice injected with Triton WR 1339, which prevents apolipoprotein exchanges. We show that the association of hapoA-II with TRL occurs in the circulation and induces postprandial hypertriglyceridemia.


[The role of cytokines in bacterial meningitis].
Bacterial meningitis is the serious infection of the central nervous system (CNS), and stimulated by bacteria inflammatory host response has crucial role in its pathogenesis. The most important elements of this response are cytokines, especially tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10), which have antiinflammatory activity. Production of cytokines in the CNS triggers a cascade of inflammatory mediators. Better understanding of mechanisms which take place during the course of the bacterial meningitis can be useful in differential diagnosis, prognosis and treatment of this disease. Investigations on the role of cytokines in the bacterial meningitis, have great therapeutic implications, and can result in introduction to the treatment antiinflammatory drugs, which can help to reduce mortality rate and number of complications.


Switching to fast growth: the insulin-like growth factor (IGF) system in skeletal muscle of Atlantic salmon.
In this study we describe the complete coding sequence for insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), insulin-like growth factor binding protein (IGFBP) 1, 2, 4, 5 and 6 and IGFBP-related protein 1 (IGFBP-rP1) of Atlantic salmon (Salmo salar L.). We also report the characterisation of two gene paralogues of IGFBP-2 and IGFBP-5. Following 22 days restricted feeding (0 d) to achieve zero growth, fish were fed to satiation and sampled at 3, 5, 7, 14, 30 and 60 days. Expression profiles for genes involved in the IGF signalling pathway in fast myotomal muscle were determined using real-time quantitative RT-PCR. The transition from zero to fast growth is characterised by constitutive upregulation of IGF-I and IGFBP-4, a transient increase in IGFBP-5.2, and downregulation of IGFBP-2.1, IGF-II, IGF2R (IGF-II receptor) and IGFR1a (IGF-I receptor a). Expression of IGFBP-2.2, IGFBP-5.1, IGFBP-6, IGFBP-rP1 and IGFR1b showed little or no response to feeding. Expression of the myogenic marker genes myogenin, MHC and MLC2 were higher with feed restriction, and decreased as an early response to feeding, before increasing to a peak at 14 days, corresponding with a peak in IGF-I expression. IGFBP-4, which contains a putative connective tissue localisation signal, was the only IGFBP constitutively upregulated following feeding, and was positively correlated with IGF-I expression. Together, these data show that switching to fast growth in Atlantic salmon skeletal muscle involves the local upregulation of IGF-I, IGFBP-5.2 and IGFBP-4, with downregulation of IGFBP-2.1.


Group A streptococcal RofA-type global regulators exhibit a strain-specific genomic presence and regulation pattern.
RofA-like protein (RALP) type regulators have been shown to exist in different forms in group A streptococci (GAS) and to regulate the expression of important bacterial adhesins. This study shows that the vast majority of strains from different GAS M serotypes carried a rofA virulence regulator gene in their genome and that this gene could be detected in combination with other RALP genes and RALP-dependent adhesin genes in a strain-specific manner. The gene encoding the Nra regulator was predominantly found in opacity factor (OF)-negative serotypes. When analysing a rofA mutant in a serotype M2 strain, the strain specificity was also found in the positive and negative regulatory functions of RALP genes as well as in the type and number of virulence genes and functions controlled by the RALP genes. Of 17 virulence-associated genes tested, only one, the putative streptolysin S gene, was observed to be derepressed in RALP mutants of three different GAS serotype strains. This strain-specific variability of RALP regulon sizes is associated with different patterns of host cell attachment and internalization. In addition, RofA2 was shown to control expression of the ribosomal protein gene rpsL. As a consequence, it was demonstrated for the first time in streptococci that aminoglycoside resistance mediated by rpsL expression is apparently controlled by a virulence gene regulator.


Congenital Thymic Cyst: Antenatal Diagnosis and Postnatal Management.
Thymic cyst is regarded as a rare anomaly, accounting for about 3% of all anterior mediastinal masses. It can be either congenital or acquired. Congenital thymic cysts are usually asymptomatic, with about 50% found incidentally in childhood or adolescence. We report a case of 1-month 23-day-old male baby who was antenatally diagnosed at 32 weeks' gestation. Spontaneous resolution did not take place in the antenatal or neonatal period; instead, there was an increase in size on follow-up imaging. The baby was successfully managed by surgical excision.


Bioremoval of heavy metals from industrial effluent by fixed-bed column of red macroalgae.
Three different species of nonliving red algal biomass Laurancia obtusa, Geldiella acerosa and Hypnea sp. were used to build three types of fixed-bed column for the removal of toxic heavy metal ions such as Cu(2+), Zn(2+), Mn(2+) and Ni(2+) from industrial effluent. In general, the highest efficiency of metal ion bioremoval was recorded for algal column of L. obtusa followed by G. acerosa and the lowest one was recorded for Hypnea sp., with mean removal values of 94%, 85% and 71%, respectively. The obtained results showed that biological treatments of industrial effluents with these algal columns, using standard algal biotest, Pseudokirchneriella subcapitata, were capable of reducing effluent toxicities from 75% to 15%, respectively. Red algal column may be considered as an inexpensive and efficient alternative treatment for conventional removal technology, for sequestering heavy metal ions from industrial effluents.


Absorption, distribution and excretion of GT31-104, a novel bile acid sequestrant, in rats and dogs after acute and subchronic administration.
The absorption, distribution, and excretion of GT31-104, a novel bile acid sequestrant, was studied in rats and dogs after both acute and subchronic oral administration. The polyallylamine backbone of GT31-104 was labeled with tritium and one of the alkyl side chains was labeled with 14C. The mean blood and plasma concentration of [3H, 14C]GT31-104 in rats, in both treatment regimens, was negligible at all time points, with the highest amount observed being 0.69 microgram eq/g blood; in dogs the mean blood and plasma concentration of [3H, 14C]GT31-104 was below the limit of quantitation (< 0.001% total dose) at all time points. In both rats and dogs, the mean total urinary excretion of [3H, 14C]GT31-104 was approximately 0.06% of the total dose. The fecal excretion data indicates that both 3H- and 14C-derived radioactivity was excreted entirely in the feces. Mean total radioactivity excreted in the feces ranged from approximately 95 to 105% in the rats and 92 to 102% in the dogs. Across the different treatment regimens, in both species, tissue concentrations were negligible (< 0.01% total dose) and no differences in tissue profile were noted, indicating that there was no effect of pretreatment on [3H, 14C]GT31-104 absorption. GT31-104 was extracted with water, and the water-soluble portion contained radioactivity that would correlate to approximately 0.19% of the 3H dose and 0.41% of the 14C dose; this portion probably accounted for the negligible radioactivity observed systemically. Analysis of gastrointestinal (GI) tract tissues with contents indicated that GT31-104 is rapidly cleared from the GI tract. These data indicate that GT31-104 is not absorbed from the GI tract in rats and dogs.


A local Vapnik-Chervonenkis complexity.
We define in this work a new localized version of a Vapnik-Chervonenkis (VC) complexity, namely the Local VC-Entropy, and, building on this new complexity, we derive a new generalization bound for binary classifiers. The Local VC-Entropy-based bound improves on the original Vapnik's results because it is able to discard those functions that, most likely, will not be selected during the learning phase. The result is achieved by applying the localization principle to the original global complexity measure, in the same spirit of the Local Rademacher Complexity. By exploiting and improving a recently developed geometrical framework, we show that it is also possible to relate the Local VC-Entropy to the Local Rademacher Complexity by finding an admissible range for one given the other. In addition, the Local VC-Entropy allows one to reduce the computational requirements that arise when dealing with the Local Rademacher Complexity in binary classification problems.


The significance of personality factors for various dimensions of life quality among older people.
Quality of life has various dimensions with multiple meanings for people. One vital issue is whether a person's subjective experienced quality of life correlates with his or her personality. Several studies show a correlation between personality and quality of life, life satisfaction or well-being. The aim of this study was to examine the relationship between personality and life quality, in particular the way in which multi-dimensional conceptualization of personality relates to a multi-dimensional definition of life quality. Seventy-eight elderly individuals completed a quality of life questionnaire, the Lund Gerontology Centre's Life Quality Questionnaire (LGC), and a personality questionnaire, the Gordon Personal Profile Inventory (GP:A). Discriminant analysis showed that various personality characteristics relate to different aspects of life quality. Vigour alone predicted current quality of life, while emotional stability was related to psychological well-being and satisfaction with significant relationships. Ascendancy and ability to maintain personal relations were related to an optimistic outlook on life and absence of psychosomatic symptoms. Original thinking and sociability related to increased psychosomatic symptoms and sociability also correlated negatively with satisfaction with significant relationships. The results support the idea that various personality characteristics are related to various life quality dimensions in the investigated group, increasing the understanding of unique experience of life quality for each individual.


Organic vs functional obstruction of the fallopian tubes: differentiation with prostaglandin antagonist- and beta 2-agonist-mediated hysterosalpingography and selective ostial salpingography.
In order to determine the prevalence and cause of functional vs organic obstruction of the fallopian tubes, hysterosalpingography was repeated after pharmacologic manipulation with a prostaglandin antagonist (aspirin) and/or a beta 2-agonist (terbutaline) in 100 patients in whom the fallopian tubes did not fill with contrast medium on the initial hysterosalpingogram. Selective ostial salpingography was performed in those in whom the fallopian tubes did not fill on the second hysterosalpingogram. Patients referred from three infertility clinics were included in the study if they could be rescheduled for a second hysterosalpingogram after at least 1 week of preparation with aspirin. Hysterosalpingograms obtained after administration of aspirin showed normal filling in 21 of 100 patients with initially obstructed tubes; the tubes filled in four more patients after administration of terbutaline. Selective ostial salpingography opacified the tubes in another 36 patients in whom the tubes had so far failed to fill. On the basis of the radiographic appearance and sometimes laparoscopic observation, initial nonfilling was attributed to spasma and debris in 49 patients, submucosal fibroids in six, synechiae in three, salpingitis isthmica nodosa in two, and septated uterus in one. Hysterosalpingography, after pharmacologic manipulation with aspirin and/or selective ostial salpingography, revealed false-positive and functional tube obstructions in 61 of 100 patients. Moreover, the radiologic appearance improved categorization of organic obstructions.


Perforin protects against autoimmunity in lupus-prone mice.
The roles of cytolytic regulatory mechanisms in the immune system of lupus-prone mice were examined in perforin-deficient animals bearing functional or defective (lpr) Fas Ag (CD95). Perforin-deficient Fas+ animals developed accelerated autoimmunity, characterized by increased hypergammaglobulinemia, autoantibody production, and immune deposit-related end-organ disease compared with perforin-intact counterparts. In comparison, perforin-deficient lpr animals had accelerated mortality compared with perforin-intact lpr mice, associated with the abnormal accumulation of CD3+CD4-CD8- alphabeta T cells in conjunction with unaltered hypergammaglobulinemia, autoantibody production, and immune complex renal disease. These results indicate that cytolytic lymphoid regulation plays critical roles in the immune homeostasis of lupus-prone animals, and identify perforin-mediated cytotoxicity as a specific mechanism in the regulation of systemic autoimmunity.


Association of sFlt-1 and C-reactive protein with outcomes in severe preeclampsia: A cohort study.
To determine the association between soluble FMS-like tyrosine kinase-1 (sFlt-1) and high-sensitivity C-reactive protein (hs-CRP) with maternal and perinatal outcomes in patients with preeclampsia (PE) with severe features.A cohort study was conducted on 100 patients, 60 with PE with severe features, and 40 healthy women in the third trimester of pregnancy. Admission serum levels of sFlt-1 and hs-CRP and clinical and epidemiological parameters were evaluated to quantify the predictive ability of adverse maternal and perinatal outcomes using hierarchical multiple regression and receiver operating characteristic curves.Compared to controls, patients with PE and severe features had significantly higher levels of sFlt-1 but not hs-CRP. sFlt-1 and hs-CRP proved to be reasonable parameters for the prediction of composite adverse maternal outcomes. However, we found no correlation between these 2 biomarkers. PE integrated estimate of risk scores were correlated only with sFlt-1 levels. Regarding fetal outcomes, unlike hs-CRP, sFlt-1 was strongly associated with birth weight and Apgar score < 7 at 5 minutes. Following multivariate analysis, maternal age, previous hypertension, sFlt-1, and hs-CRP levels remained independently associated with composite adverse maternal outcomes.sFlt-1 levels were elevated in patients with PE and severe features. Both sFlt-1 and hs-CRP may predict composite adverse maternal outcomes but do not correlate with each other and differ in perinatal morbidity patterns. These data support the hypothesis that the varied outcomes in PE may result from different pathogenic pathways.


Contemporary experimental models of traumatic brain injury.
This review article aims to bring investigators' attention to experimental models of traumatic brain injury, widely employed in research in western countries and almost unknown in Eastern Europe. We describe the most successful animal models that cause neurotrauma by applying mechanical energy to the head, skull or dura. It attempts to provide a short compendium of the main characteristics of each of these experimental models of TBI in respect to main human neurotrauma features, histological findings and behavioral impairment in neurologic motor and cognitive function.


In vitro psoriasis models with focus on reconstructed skin models as promising tools in psoriasis research.
Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis skin or the disease pathology. This work provides a complete overview of the different available in vitro psoriasis models and suggests improvements for future models. Moreover, a focus was given to psoriatic skin equivalent models, as they offer several advantages over the other models, including commercial availability and validity. The potential and reported applicability of these models in psoriasis pre-clinical research is extensively discussed. As such, this work offers a guide to researchers in their choice of pre-clinical psoriasis model depending on their type of research question.


Inhibitory effects of a gonadotropin-releasing hormone agonist on the luteal synthesis of progesterone, estradiol receptors, and prolactin surges during early pregnancy.
Our recent studies demonstrated that the continuous administration of a GnRH agonist (GnRH-Ag; WY 40972) induces abortion in rats by suppressing plasma progesterone (P) levels within 24 h. This fall in P levels is not accompanied by a fall in ovarian venous plasma testosterone (T) or estradiol (E) levels. In this study an attempt was made 1) to determine whether the suppression of P by GnRH-Ag is due to decreased estrogen present in the corpora lutea (CL) and/or a decrease in luteal receptors of E, and 2) to investigate the effects of GnRH-Ag on the nocturnal surges of PRL. Rats were treated continuously on days 7-11 of pregnancy with 5 micrograms/day GnRH-Ag using an osmotic minipump. Ovarian blood samples were obtained on day 8; at autopsy CL were harvested and incubated with medium 199 for 4 h at 37 C under an atmosphere of 95% oxygen-5% carbon-dioxide. Additional rats were killed on day 8 or 10; CL were isolated from the ovary and pooled within the group for the measurement of nuclear and cytosolic E receptors. In other experiments, on days 8, 9, 10, and 11 of pregnancy, blood samples (0.3 ml) were collected via an indwelling intraatrial Silastic cannula at 0330, 0500, or 0600 h for the measurement of PRL and P. While the net synthesis of P by CL in the GnRH-Ag-treated rats decreased to 48 +/- 12 from 224 +/- 47 ng/CL in controls, T and E levels were not different from their respective control values. Steroid levels in ovarian venous plasma reflected a similar response. Nuclear E receptors levels were 82 and 80 in controls and 39 and 41 fmol/mg DNA in the treated group on days 8 and 10, respectively. Nocturnal surges of PRL in plasma were detected at 0330 h in controls as well as in treated rats. However, plasma PRL levels at 0330 h were 101 +/- 24, 120 +/- 22, 196 +/- 40, and 103 +/- 13 ng/ml in controls and 44 +/- 8, 50 +/- 10, 29 +/- 13, and 20 +/- 9 in the GnRH-Ag-treated group on days 8, 9, 10, and 11, respectively. These results suggest that GnRH-Ag has no effect on the ability of the luteal synthesis of T and E and that the antipregnancy effect of GnRH-Ag may be at the level of the CL due to the direct inhibitory effect of GnRH-Ag on the luteal synthesis of P, which, in turn, results in decreased nocturnal surges of PRL and a fall in E receptors in the CL. Alternatively, GnRH-Ag treatment could suppress ovarian or luteal receptors for PRL, which, in turn, lower luteal E receptors, leading to a fall in luteal synthesis and release of P.