Evaluation of ocular arterial changes in glaucoma with color Doppler ultrasonography.
The purpose of this study was to evaluate hemodynamic changes of the retrobulbar vasculature caused by different intraocular pressures with color Doppler ultrasonography. Fifty normal eyes in 25 patients, 13 patients with normal tension glaucoma, and 19 patients with acute glaucoma and increased intraocular pressure (greater than 30 mm Hg) were enrolled in this study. In 15 of 19 patients with acute glaucoma patients, follow-up color Doppler ultrasonography was also undertaken after laser peripheral iridectomy when the intraocular pressure had returned to normal. The peak systolic velocity, end diastolic velocity, resistive index, time average maximum velocity, and pulsatility index were compared in different vessels, including the central retinal artery, lateral posterior ciliary artery, medial posterior ciliary artery, and ophthalmic artery in each orbit. The peak systolic velocity, end diastolic velocity, and time average maximum velocity of the central retinal artery were significantly lower (P<0.01) in acute glaucoma patients than in the control group. The resistive index and pulsatility index of the central retinal artery were significantly higher (P<0.01) in acute glaucoma patients than in the control group. The end diastolic velocity of the lateral and medial posterior ciliary arteries was significantly lower in patients with acute glaucoma than in the control group, and the resistive index and pulsatility index of both of these arteries were significantly higher (P<0.001) in patients with acute glaucoma than in the control group. However, no statistical significantly differences were found in the peak systolic velocity or time average maximum velocity in either of the posterior ciliary arteries; similarly, no statistically significant differences were noted in any of the parameters in the ophthalmic artery between the control group and the group with acute glaucoma. The pulsatility index of the central retinal artery and of the lateral and medial posterior ciliary arteries was significantly lower (P<0.01) in acute glaucoma patients after laser therapy than in acute glaucoma patients before laser therapy. The resistive index of both posterior ciliary arteries was also significantly lower (P<0.004) in acute glaucoma patients after laser therapy than before laser therapy. All parameters for all vessels examined among the normal subjects, the patients with normal tension glaucoma, and the patients with acute glaucoma after laser therapy when the intraocular pressure had returned to normal showed no statistically significant differences. Color Doppler ultrasonography is a good modality for both imaging and studying the hemodynamics of the perioptic nerve vessels.


Infections of Wolbachia may destabilize mosquito population dynamics.
Recent efforts in controlling mosquito-borne diseases focus on biocontrol strategies that incapacitate pathogens inside mosquitoes by altering the mosquito's microbiome. A case in point is the introduction of Wolbachia into natural mosquito populations in order to eliminate Dengue virus. However, whether this strategy can successfully control vector-borne diseases is debated; particularly, how artificial infection affects population dynamics of hosts remains unclear. Here, we show that natural Wolbachia infections are associated with unstable mosquito population dynamics by contrasting Wolbachia-infected versus uninfected cage populations of the Asian tiger mosquito (Aedes albopictus). By analyzing weekly data of adult mosquito abundances, we found that the variability of the infected populations is significantly higher than that of the uninfected. The elevated population variability is explained by increased instability in dynamics, as quantified by system nonlinearity (i.e., state-dependence). In addition, predictability of infected populations is substantially lower. A mathematical model analysis suggests that Wolbachia may alter mosquito population dynamics by modifying larval competition of hosts. These results encourage examination for effects of artificial Wolbachia establishment on mosquito populations, because an enhancement of population variability with reduced predictability could pose challenges in management. Our findings have implications for application of microbiome alterations in biocontrol programs.


State Preemption of Municipal Laws and Policies that Protect Immigrant Communities: Impact on Latine Health and Well-Being in North Carolina.
Some U.S. municipalities have proclaimed themselves "sanctuary cities" and/or adopted laws and policies limiting local involvement in enforcement of federal immigration policies. Several states, however, have adopted laws that preempt municipal laws and policies designed to protect immigrants. We explored the consequences of House Bill (H.B.) 318, one such preemption law in North Carolina (NC), on the health and well-being of Latine immigrants. We conducted focus groups with Latine immigrants (n=49) and in-depth interviews with representatives from health, social service, and immigrant-serving organizations and local government (including law enforcement) (n=21) in NC municipalities that, before HB 318, adopted laws and policies supporting immigrants. Data were analyzed using constant comparison. Twelve themes emerged, including the positive impacts of municipal sanctuary laws and policies are limited by preemption and other state and federal actions; laws and policies like HB 318 are confusing, have a chilling effect on health services use, and make life harder overall for Latine communities; intensified federal immigration enforcement has increased fear among Latine communities; Trump administration policies worsened anti-immigrant climates; and use of community identification cards and greater information dissemination and inter-organization coordination can lessen the consequences of preemption and other restrictive laws and policies. State preemption of protective municipal laws and policies negatively and profoundly affects immigrant health and well-being. However, creative strategies have been implemented to respond to preemption. These findings provide critical data for decision-makers and community leaders regarding the detrimental impacts of preemption laws and mitigation of these impacts.


Pharmacokinetic/Pharmacodynamics-Optimized Antimicrobial Therapy in Patients with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia.
Hospital-acquired pneumonia and ventilator-associated pneumonia continue to cause significant morbidity and mortality. With increasing rates of antimicrobial resistance, the importance of optimizing antibiotic treatment is key to maximize treatment outcomes. This is especially important in critically ill patients in intensive care units, in whom the infection is usually caused by less susceptible organisms. In addition, the marked physiological changes that can occur in these patients can cause serious changes in antibiotic pharmacokinetics which in turn alter the attainment of therapeutic drug exposures. This article reviews the various aspects of the pharmacokinetic changes that can occur in the critically ill patients, the barriers to achieving therapeutic drug exposures in pneumonia for systemically delivered antibiotics, the optimization for commonly used antibiotics in hospital- and ventilator-associated pneumonia, the agents that should be avoided in the treatment regimen, as well as the use of adjunctive therapy in the form of nebulized antibiotics.


Interleukin 1 stimulates endothelial cell tissue factor production and expression by a prostaglandin-independent mechanism.
Activation of coagulation occurs at inflammatory sites following the ingress of mononuclear cells, and may result from alterations in the vessel wall. Since the monokine, interleukin 1, initiates diverse responses to inflammation, its ability to enhance vascular procoagulant activity was studied. Interleukin 1-treated cultured human endothelial cells acquired elevated levels of the procoagulant, tissue factor. This required de novo protein synthesis, was maximal at 2 h after exposure to interleukin 1, and resulted in persistently elevated cellular procoagulant activity. Tissue factor was later expressed (6-24 h) on the surface of uninjured endothelial cells. Endothelial cell procoagulant production and expression in response to interleukin 1 could be dissociated from endogenous prostaglandin metabolism, being insensitive to hydrocortisone, indomethacin, eicosatetrayionic acid and exogenous arachidonic acid. In addition, no increase in prostaglandin synthesis occurred during the interval in which tissue factor was synthesized. We therefore conclude that interleukin 1 stimulates endothelial synthesis and surface expression of tissue factor by a prostaglandin-independent mechanism.


The influence of tightening sequence and method on screw preload in implant superstructures.
This study evaluated the effect of six screw-tightening sequences and two tightening methods on the screw preload in implant-supported superstructures. The preload was measured using strain gauges following the screw tightening of a metal framework connected to four implants. The experiment included six sequences ([1] 1-2-3-4, [2] 4-2-3-1, [3] 4-3-1-2, [4] 1-4-2-3, [5] 2-3-4-1, and [6] 3-2-4-1), two methods (onestep, three-step), and five replications. Significant differences were found between tightening sequences and methods. In the three-step method, a higher total preload was found in sequences 2 (312 ± 85 N), 3 (246 ± 54 N), and 4 (310 ± 96 N). In the one-step method, a higher total preload was found in sequences 1 (286 ± 94 N), 5 (764 ± 142 N), and 6 (350 ± 69 N). It is concluded that the highest total screw preload was achieved when anterior implants of the superstructure were first tightened in one step, followed by posterior implants.


Tumor-derived factors impaired motility and immune functions of dendritic cells through derangement of biophysical characteristics and reorganization of cytoskeleton.
The generation and progress of tumors are accompanied with a marked suppression of human immune system. To explore the mechanisms by which tumors escape from immune recognition, we studied the influences of tumor microenvironment on differentiation of dendritic cells (DCs), which play an important role in tumor immunology, by biophysical and immunological methods. It was found that the cytokines derived from tumors caused an increase in osmotic fragility and a decrease in membrane fluidity of DCs, disordering and elevated expression levels of cytoskeleton, and changes of the gene transcriptional levels and energy status of the cells. Moreover, IL-12 production and the expression levels of some surface-marker molecules were also suppressed. These changes led to impaired capabilities of antigen uptake, cell motility and naïve T cell activation; the abnormal biophysical characteristics of DCs may be one aspect of the immune escape mechanism of tumor. These results provide insights into the importance of the reconstruction of tumor microenvironment for immunotherapy based on the anti-cancer activities of DCs.


Tradition- and science-based quality control of Chinese medicines--introducing the Phyto-True system.
The current QC practice of quantifying presumed active chemicals or arbitrarily selected chemical markers is of doubtful value in assessing multicomponent complex traditional Chinese medicines (CMs) and often leads to an inconsistent or irreproducible research and clinical outcome. Consequently, the first and most important step in the QC of CMs (or other botanical medicines) whose exact active chemical components are unknown is to use analytical techniques that can comprehensively define the totality of the components/attributes making up their identity and quality. One of the most versatile techniques is HPTLC. Using HPTLC, along with other simple techniques such as FTIR spectroscopy and UV-Vis spectroscopy combined with complementary gene expression profiling, we have been able to correctly identify CM materials, detect adulterants, and differentiate closely related materials and botanical species. Our research has resulted in the introduction of the concept and specimens of Phyto-True Reference Material (PTRM), aka Representative Botanical Reference/Research Material (RBRM), now commercially available, and a novel patent-pending technology (Phyto-True system) that can serve as a starting point for the meaningful QC of traditional CMs so far not possible for these complex materials. Examples will be highlighted to demonstrate this new concept.


Colocalisation of acetylated microtubules, glial filaments, and mitochondria in astrocytes in vitro.
We have recently shown that acetylated alpha-tubulin containing microtubules (acetyl-MTs; labeled by antibody 6-11B-1) constitute a cold-stable subset of the microtubule network of nonneuronal cells in rat primary forebrain cultures [Cambray-Deakin and Burgoyne: Cell Motil. 8(3):284-291, 1987b]. In contrast, tyrosinated alpha-tubulin containing MTs (tyr-MTs; labeled by antibody YL1/2) are cold-labile. Here we have examined the distribution of acetyl-MTs and tyr-MTs in cultures of newborn rat forebrain astrocytes and simultaneously investigated the distribution of mitochondria and glial filaments. In double-label immunofluorescence experiments a marked colocalisation of acetyl-MTs and glial filament bundles was observed. Tyr-MTs did not show a similar colocalisation with glial filament bundles. Furthermore, the distribution of mitochondria closely followed that of the acetyl-MT and glial filament bundles. When cells were exposed to short-term (30-min) treatments with MT-disrupting agents such as colchicine and nocodazole, the tyr-MT network was removed but the distributions of acetyl-MTs, glial filaments, and mitochondria were unchanged. Increased exposure to colchicine (9-16 hr) caused a progressive disruption of the acetyl-MTs and the collapse of glial filaments and mitochondria to the perinuclear region. These results suggest that acetyl-MTs and glial filaments but not tyr-MTs may be involved in the intracellular transport of organelles and/or in the control of their cytoplasmic distribution.


Comparison of physical activity in male and female children: does maturation matter?
To investigate whether observed differences in physical activity levels in boys and girls are confounded by biological age differences particularly during the circumpubertal years. The physical activity questionnaire for children (PAQ-C) was administered biannually or triannually to 138 (70 boys; 68 girls) Canadian children for seven consecutive years from 1991 to 1997. Participants were 9-18 yr of age. Anthropometric measurements were taken biannually and age at peak height velocity (PHV) determined. Biological age was defined as years from PHV. The data were analyzed using t-tests and random effects models. Level of physical activity decreased with increasing chronological age in both sexes. When aligned on chronological age bands, boys had statistically significantly higher PAQ-C summary scores than girls from 10 through 16 yr of age (P < 0.05). However, when aligned on biological age, sex differences were not apparent, except at 3 yr before PHV. Random effects models of individual growth patterns confirmed these findings. Physical activity decreased with increasing chronological age in boys and girls. There were no sex differences in the longitudinal pattern of physical activity when the confounding effects of biological age were controlled except at 3 yr before PHV.


Cochleosaccular (Scheibe) dysplasia in dogs: A temporal bone study.
The objective of this study was to evaluate any otopathologic changes in temporal bone specimens from dogs with deafness related to cochleosaccular (Scheibe) dysplasia (CSD). We used the canine temporal bone collections of the Otopathology Laboratory at the University of Minnesota and of the Massachusetts Eye and Ear Infirmary at Harvard University in Boston. Our morphometric analysis included measuring the areas of the stria vascularis and the spiral ligament and counting the number of spiral ganglion cells. In addition, we noted the presence of the organ of Corti and cochlear hair cells, assessed the location of Reissner's membrane and the saccular membrane, and counted the number of both Type I and Type II vestibular hair cells in the macule of the saccule and vestibular ganglion cells. In the group of specimens from dogs with cochleosaccular dysplasia, we observed generalized degeneration in the cochlea and a significantly decreased number of Type I and Type II vestibular hair cells and vestibular ganglion cells. As hereditary deafness is presently untreatable with known therapeutic methods, dogs with cochleosaccular dysplasia should not be considered for breeding. Future therapeutic approaches, such as stem cell therapies, should be designed to target all the elements of the cochlea in addition to the saccule as it was found that both are affected in dogs with CSD.


PDE-5 inhibition impedes TSP-1 expression, TGF-beta activation and matrix accumulation in experimental glomerulonephritis.
Matrix expansion and mesangial proliferation are hallmarks of mesangial proliferative glomerulonephritis. Specific inhibition of PDE-5, an enzyme catalyzing the intracellular degradation of cyclic GMP, can be achieved by the inhibitor vardenafil. In this study, we investigated the effects of PDE-5 inhibition in the anti-Thy1 model in the rat in vivo. After disease induction, rats received 10 mg/kg bw vardenafil twice a day via gavage. On Days 2 and 6, renal biopsies, as well as glomerular isolates, urine and blood samples were taken to compare vardenafil- and placebo-treated groups during the course of disease. Small amounts of PDE-5 were detected in healthy kidneys, but induced in a typical mesangial pattern during disease (by IHC and WB). Specific PDE-5 inhibition resulted in increased glomerular levels of cGMP. Treated animals demonstrated inhibition of MC proliferation and matrix accumulation while renal function and influx of inflammatory cells were not affected. Due to PDE-5 inhibition, the endogenous TGF-beta-activating protein TSP-1 and the TGF-beta-signalling protein p-smad-2/3 were decreased suggesting this as an antifibrotic mechanism of action of vardenafil in this model. Considering the availability and safety profile of vardenafil, the beneficial antiproliferative and antifibrotic effect in experimental glomerulonephritis may potentially be applicable to the treatment of mesangial proliferative glomerulonephritis in man.


Effects of phospholipid and polyethylene glycol monostearate (100) on the in vitro and in vivo physico-chemical characterization of poly(n-butyl cyanoacrylate) nanoparticles.
In this study, poly(n-butyl cyanoacrylate) nanoparticles (PBCA-NPs) modified with various amounts of soybean phospholipid (PC) and polyethylene glycol monostearate (S100) were prepared in order to investigate the effects of PC and S100 on the nanoparticles' physico-chemical properties, cytological properties and in vivo gastrointestinal absorption. Coumarin-6 (C6) was used as a fluorescent probe; C6-loaded PBCA-NPs modified with both PC and S100 (C6-PS-PBCA-NPs) were prepared using miniemulsion polymerization, and C6-loaded PBCA-NPs modified with either S100 (C6-S-PBCA-NPs) or PC (C6-P-PBCA-NPs) were used as references. All of the different NPs were shown to be stably dispersed and to have a small particle size. A cytotoxicity study indicated that all of the blank PBCA-NPs were safe and nontoxic. The uptake of NPs by Caco-2 cells was shown to be increased when the amount of PC was increased from 0% to 1.25% and the amount of S100 was increased from 0% to 0.725%. The use of a ligated intestinal loop model demonstrated that C6-PS-PBCA-NPs could rapidly penetrate a highly viscoelastic mucous layer, leading to an improvement in the absorption efficiency. During a pharmacokinetic study, C6-PS-PBCA-NPs improved the absorption of C6, as indicated by their higher Cmax and AUC0-t values compared with those of C6-S-PBCA-NPs or C6-P-PBCA-NPs. Overall, the results of this study indicate that PBCA-NPs modified with PC and S100 can enhance the absorption of orally administered drugs.


Water-Centered Interpretation of Intrinsic pPII Propensities of Amino Acid Residues: In Vitro-Driven Molecular Dynamics Study.
Amino acid residues of unfolded peptides in water sample only a few basins in the Ramachandran plot, including prominent polyproline II-like (pPII) conformations. Dynamics of guest residues, X, in GXG peptides in water were recently reported to be dominated by pPII and β-strand-like (β) conformations, resulting in an enthalpy-entropy compensation at ∼300 K. Using molecular dynamics (MD) in explicit solvent, we here examine pPII and β conformational ensembles of 15 guest residues in GXG peptides, quantify local orientation of water around their side chains through novel water orientation plots, and study their hydration and hydrogen bonding properties. We show that pPII and β ensembles are characterized by distinct water orientations: pPII ensembles are associated with an increased population of water oriented in parallel to the side chain surface whereas β ensembles exhibit more heterogeneous water orientations. The backbone hydration is significantly higher in pPII than in β ensembles. Importantly, pPII to β hydration differences and the solvent accessible surface area of Cβ hydrogens both correlate with experimental pPII propensities. We propose that pPII conformations are stabilized by a local, hydrogen-bonded clathrate-like water structure and that residue-specific intrinsic pPII propensities reflect distinct abilities of side chains to template this water structure.


Structured physician order entry for trauma CT: value in improving clinical information transfer and billing efficiency.
The purpose of this study was to measure the effects of use of a structured physician order entry system for trauma CT on the communication of clinical information and on coding practices and reimbursement efficiency. This study was conducted between April 1, 2011, and January 14, 2013, at a level I trauma center with 59,000 annual emergency department visits. On March 29, 2012, a structured order entry system was implemented for head through pelvis trauma CT, so-called pan-scan CT. This study compared the following factors before and after implementation: communication of clinical signs and symptoms and mechanism of injury, primary International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code category, success of reimbursement, and time required for successful reimbursement for the examination. Chi-square statistics were used to compare all categoric variables before and after the intervention, and the Wilcoxon rank sum test was used to compare billing cycle times. A total of 457 patients underwent pan-scan CT in 2734 distinct examinations. After the intervention, there was a 62% absolute increase in requisitions containing clinical signs or symptoms (from 0.4% to 63%, p<0.0001) and a 99% absolute increase in requisitions providing mechanism of injury (from 0.4% to 99%, p<0.0001). There was a 19% absolute increase in primary ICD-9-CM codes representing clinical signs or symptoms (from 2.9% to 21.8%, p<0.0001), and a 7% absolute increase in reimbursement success for examinations submitted to insurance carriers (from 83.0% to 89.7%, p<0.0001). For reimbursed studies, there was a 14.7-day reduction in mean billing cycle time (from 68.4 days to 53.7 days, p=0.008). Implementation of structured physician order entry for trauma CT was associated with significant improvement in the communication of clinical history to radiologists. The improvement was also associated with changes in coding practices, greater billing efficiency, and an increase in reimbursement success.


Genotyping assay for differentiation of wild-type and vaccine viruses in subjects immunized with live attenuated influenza vaccine.
Live attenuated influenza vaccines (LAIVs) are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW) specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.


Trisomy 9p syndrome in two brothers: with new clinical findings and review of the literature.
We report an eleven years old boy and his fourteen years old brother who both have trisomy 9p syndrome. Their cytogenetic analysis using GTL-banding showed 46,XY,der(22)add(22)(p11) karyotype. Cytogenetic analysis of their mother and sister revealed a karyogram designated as 46,XX,t(9;22) (9pter-->9p12::22p11-->22qter). With the help of FISH technique, the derivative chromosome in the proband was further confirmed to be a translocation chromosome 22 carrying the aforementioned segments from chromosome 9 which originated from a segregation event of a mother's balanced translocation. Regarding clinical aspects of our cases, both showed similar findings of 9p trisomy syndrome but low frontal hairline, circular placement of the hair around the face and scarce, inverted eyebrows, findings not previously mentioned in the literature. We conclude that these new clinical findings could be used in the clinical diagnosis of the 9p trisomy syndrome along with the other well-documented symptoms.


Clinical-grade myeloma Ag pre-loaded DC vaccines retain potency after cryopreservation.
The use of myeloma Ag-loaded mature DC vaccines, cryopreserved in single-use aliquots, is an attractive immunotherapeutic strategy. In this study we investigated the retention of phenotype, viability and potency of DC vaccines after freezing and thawing. Plastic-adherent monocytes, derived from a steady-state leukapheresis, were cultured in serum-free media containing GM-CSF and IL-4. DC were loaded on day 6 with myeloma lysate (ML) or idiotype (Id) Ag and keyhole limpet hemocyanin (KLH), induced to mature on day 7 with CD40-ligand and cryopreserved on day 9. Seventeen clinical-scale cultures were evaluated for DC yield, recovery and immunophenotype after potency was validated with allogeneic mixed lymphocyte culture and Ag presentation assays. We produced 88 individual vaccines from 17 clinical-scale cultures. Median DC yield at harvest was 131 x 10(6) (range 37-375 x 10(6)) and median recovery of viable DC after thawing was 69% (range 11-100%). We confirmed viability (7AAD-), phenotype (CD14-, CD83+/CD40+, CD83+/CD80+, CD83+/CD86+, CD83+/CD54+, HLA-DR++) and the ability of the DC to present Ag and stimulate allogeneic T cells post-thawing. We have validated a serum-free culture system for the production of DC. Cryopreservation did not interfere with DC activity, allowed time for rigorous quality control (QC) and flexible scheduling of intranodal vaccination, and reduced the time to prepare multiple vaccines.


Sp1 control of gene expression in myeloid cells.
Gene transcription plays a critical role in the differentiation of myeloid cells. However, there is no single, master regulator of all myeloid genes. Rather, myeloid gene transcription is regulated by the combinatorial effects of a limited number of key transcription factors. Sp1 is a powerful activator of gene transcription in many cell types. Although it is wildly expressed, Sp1 binds and activates the promoters of a large number of important myeloid genes. This presents the paradox of how a widely expressed transcription factor can regulate lineage-specific gene transcription. This review discusses the structure, function, and expression patterns of Sp1 and its related Sp family members. Illustrative examples of the tissue-specific regulation of myeloid target genes are presented. The roles of post-translational modifications of Sp1, alterations in target gene chromatin structure, and important cooperating transcription factors are discussed. Thus, Sp1 serves as a model of how a widely expressed transcription factor regulates the expression of tissue-specific genes.


French general practitioners' attitudes toward therapeutic advances in HIV care: results of a national survey.
We aimed to assess attitudes to French primary care providers towards recent advances in HIV care. Telephone surveys in a random sample of French general practitioners (GPs) were carried out in April 1996 (response rate=70.3%; n=1186). Only 40.5% of the sample had participated in the regular medical follow-up of HIV-infected patients during the previous year. Among these 480 respondents, only a few (13.3%) declared that they would take care of an asymptomatic patient with a high (>500 cells/mm3) CD4 count as the unique provider. A majority (66.2%) had referred at least one HIV-infected patient to a hospital specialist in the previous year. A total of 31.4% declared that they considered it appropriate for an antiretroviral treatment to be initiated to an asymptomatic patient with 300 CD4 cells/mm3, and only 23.5% were already in favour of combination therapies rather than zidovudine monotherapy as treatment of choice. GPs with the most experience with HIV care tended to be the most reluctant to modify their attitude in favour of earlier initiation of antiretroviral therapies and of the switch from monotherapy to combination therapies. The survey suggests there is a gap between attitudes of GPs and those of AIDS specialists toward preliminary reports of therapeutic advances in HIV care. Whether or not such a gap may create problems for an appropriate diffusion of new antiretroviral therapies should be carefully monitored, in the context of current reforms emphasizing the key role of primary providers in most health-care systems.


The use of effective treatments: the case of an adolescent girl with anorexia nervosa in the context of a conversion disorder.
The use of empirically supported treatment (EST) has been shown to enhance treatment outcome. The purpose of this case study was to suggest that ESTs further encourage effective reconceptualisation and the ongoing delivery of effective treatment, especially in the case of complex or atypical presentations or response to treatment. This report describes the case of an adolescent girl who underwent Maudsley family-based treatment for anorexia nervosa (AN) for a period of 12 months. Atypical response lead to an understanding of her presentation as representing a primary conversion disorder, within which AN symptoms were conceptualised as another somatic conversion of emotional distress. The report details her clinical presentation and management over the course of her illness. The case offers an important opportunity to explore the central role of the use of ESTs in guiding effective treatment delivery.


Body fat distribution and lipids profile of elderly in southern Jakarta.
A cross-sectional study on 222 elderly subjects was carried out at Health Centers in 10 subdistricts in south Jakarta, Indonesia. The anthropometric data (body mass index (BMI), body fat distribution), fasting blood glucose, serum total cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides were assessed. There was a positive correlation between body fat distribution and serum lipid concentration (total cholesterol, LDL cholesterol and triglycerides). Body fat distribution appears to be a stronger determinant of serum lipids than BMI.


Sensitization of unmyelinated sensory fibers of the joint nerve to mechanical stimuli by interleukin-6 in the rat: an inflammatory mechanism of joint pain.
Pain during mechanical stimulation of the joint and spontaneous pain are major symptoms of arthritis. An important neuronal process of mechanical hypersensitivity of the joint is the sensitization of thin myelinated Adelta fibers and unmyelinated C fibers innervating the joint. Because interleukin-6 (IL-6) is a major inflammatory mediator, we investigated whether this cytokine has the potential to sensitize joint afferents to mechanical stimuli. In electrophysiologic experiments conducted on anesthetized rats, action potentials were recorded from afferent fibers supplying the knee joint. Responses to innocuous and noxious rotation of the tibia against the femur in the knee joint were monitored before and 1-2 hours after injection of test compounds into the joint cavity. Injection of IL-6 and coinjection of IL-6 plus soluble IL-6 receptor (sIL-6R) caused a gradual increase in the responses of C fibers to innocuous and noxious rotation within 1 hour. The increase in responses to IL-6 and IL-6 plus sIL-6R was prevented by coadministration of soluble glycoprotein 130 (sgp130), but sgp130 did not reverse established mechanical hyperexcitability. Responses of Adelta fibers were not altered by the compounds. While injection of sIL-6R alone into the normal knee joint did not influence responses to mechanical stimulation, injection of sIL-6R into the acutely inflamed knee joint caused an increase in responses. IL-6 has the potential to sensitize C fibers in the joint to mechanical stimulation. Thus, IL-6 contributes to mechanical hypersensitivity, most likely due to an action of IL-6 on nerve fibers themselves.


The economic impact of sight loss and blindness in the UK adult population.
To quantify the economic impact of sight loss and blindness in the United Kingdom (UK) population, including direct and indirect costs, and its burden on health. Prevalence data on sight loss and blindness by condition, Census demographic data, data on indirect costs, and healthcare cost databases were used. Blindness was defined as best corrected visual acuity (BCVA) of < 6/60, and sight loss as BCVA < 6/12 to 6/60, in the better-seeing eye. Sight loss and blindness from age-related macular degeneration (AMD), cataract, diabetic retinopathy, glaucoma and under-corrected refractive error are estimated to affect 1.93 (1.58 to 2.31) million people in the UK. Direct health care system costs were £3.0 billion, with inpatient and day care costs comprising £735 million (24.6%) and outpatient costs comprising £771 million (25.8%). Indirect costs amounted to £5.65 (5.12 to 6.22) billion. The value of the loss of healthy life associated with sight loss and blindness was estimated to be £19.5 (15.9 to 23.3) billion or £7.2 (5.9 to 8.6) billion, depending on the set of disability weights used. For comparison with other published results using 2004 disability weights and the 2008 estimates, the total economic cost of sight loss and blindness was estimated to be £28.1 (24.0 to 32.5) billion in 2013. Using 2010 disability weights, the estimated economic cost of sight loss and blindness was estimated to be £15.8 (13.5 to 18.3) billion in 2013. The large prevalence of sight loss and blindness in the UK population imposes significant costs on public funds, private expenditure, and health. Prevalence estimates relied on dated epidemiological studies and may not capture recent advances in treatment, highlighting the need for population-based studies that track the prevalence of sight-impairing eye conditions and treatment effects over time.


Impact of influenza on young children and the shaping of United States influenza vaccine policy.
In 2002 the Advisory Committee on Immunization Practices (ACIP) began encouraging annual influenza vaccination of children 6 to 23 months of age, when feasible. Literature and issues related to annual influenza vaccination of young children were reviewed. The ACIP first encouraged influenza vaccination of children 6 to 23 months of age in 2002 because recent studies showed that influenza-related hospital admissions were substantially higher among healthy children <2 years than among healthy older children or young adults. However, the ACIP deferred a full recommendation for several reasons, including limited safety and efficacy data on trivalent inactivated influenza virus in the 6- to 23-month age group, the need for more education of parents and physicians and concerns over the stability and adequacy of the vaccine supply. The risk of hospital admission from influenza-related causes is high in young children and similar to the risk in the elderly and other high risk groups for whom annual influenza vaccination is already recommended. Data from additional studies, especially those on vaccine safety and efficacy, will be important for proceeding to a full recommendation for annual influenza vaccination of children 6 to 23 months.


Body heating induced by sub-resonant (350 MHz) microwave irradiation: cardiovascular and respiratory responses in anesthetized rats.
These experiments were designed to investigate the effects of sub-resonant microwave (MW) exposure (350 MHz, E orientation, average power density 38 mW/cm2, average whole-body specific absorption rate 13.2 W/kg) on selected physiological parameters. The increase in peripheral body temperature during 350 MHz exposure was greater than that in earlier experiments performed at 700 MHz (resonance). Heart rate and mean arterial blood pressure were significantly elevated during a 1 degree C increase in colonic temperature due to 350 MHz exposure; respiratory rate showed no significant change. The results are consistent with other investigators' reports comparing sub-resonance exposures with those at resonance and above.


Protective Effects of Hydrogen Sulfide Against Cigarette Smoke Exposure-Induced Placental Oxidative Damage by Alleviating Redox Imbalance via Nrf2 Pathway in Rats.
Cigarette smoke exposure (CSE) during pregnancy is a well-recognized health hazard that causes placental damage. Hydrogen sulfide (H2S) has been reported to protect multiple organs from injury. However, the protective effects of H2S have not been tested in the placenta. This study aimed to explore the potential of H2S in protecting placenta against oxidative injury induced by CSE during pregnancy and the possible underlying mechanisms. Pregnant SD rats were randomly divided into 4 groups: NaCl, NaHS (a donor of H2S), CSE and CSE+NaHS. Placental oxidative damage was detected by 8-hydroxy-2-deoxyguanosine (8-OHdG) stain and malondialdehyde (MDA) assay. Placental redox status was assessed by measuring reactive oxygen species (ROS), total antioxidant capacity (T-AOC) and glutathione (GSH) levels, as well as copper/zinc SOD (SOD1), manganese SOD (SOD2), catalase (CAT) and glutathione peroxidase (GPx) activities and expressions. Meanwhile, nuclear factor erythroid 2-related factor 2 (Nrf2) was analyzed by immunohistochemistry, real-time PCR and Western blot. We found that NaHS markedly reduced the elevated levels of 8-OHdG and MDA induced by CSE. Further, NaHS treatment effectively mitigated CSE-induced placental redox imbalance by inhibiting ROS production, restoring T-AOC level, increasing GSH/GSSG ratio, and augmenting SOD1 SOD2, CAT and GPx activities and expressions. More notably, NaHS administration also reversed the aberrant decrease of Nrf2 due to CSE in rat placentas. Our data demonstrate that H2S can protect against CSE-induced placental oxidative damage probably by alleviating redox imbalance via Nrf2 pathway.


Distribution and predictors of carotid intima-media thickness in young adults.
The authors' aim was to determine reference values and predictors for carotid intima-media thickness (CIMT) in the Bogalusa Heart Study. Carotid ultrasound images from 1203 young adults (mean age 36 years; 30% black, 43% male) were reviewed. Age-, sex-, and race-specific CIMT percentiles were estimated using multivariable regression. Nomograms of CIMT quartiles for persons aged 25 to 40 years are provided in 5-year increments. CIMT was thickest in the carotid bulb and increased linearly with age, most rapidly in the bulb. With age, composite CIMT increased most slowly in white women and more rapidly in white men and black women. Systolic blood pressure (P<.001) was the strongest predictor of composite CIMT. Male sex, total to high-density lipoprotein cholesterol ratio, and age independently predicted CIMT in all segments. This report may be used to help plan epidemiologic investigations and clinical trials investigating atherosclerosis and its changes with interventions.


[Tuberculosis in patients with human immunodeficiency virus infection].
Six men (mean age: 36.3 +/- 29 years) infected with the human immunodeficiency virus (HIV), four Japanese and two from Myammar, were admitted to our hospital for treatment of tuberculosis. In five, HIV positivity on serologic testing was first found when tuberculosis was diagnosed. The mean CD4 cell count was 37.3 +/- 29.6/microliters. Results of tuberculin skin tests were negative in 5 patients. One patient had pulmonary tuberculosis and 5 had miliary tuberculosis. Hilar and mediastinal lymphadenopathy was found on chest X-ray films in 4 patients and superficial lymphadenopathy was found in all patients. All patients had positive mycobacterial cultures of sputum and 2 patients had positive tests for acid-fast bacilli on smears of lymph-node aspirates. In one patient with tuberculosis meningitis, a culture of cerebrospinal fluid for acid-fast bacilli was positive. Epithelioid cell granulomas were found in samples of lung, liver, and bone marrow from 4 patients. Mycobacterium tuberculosis was isolated from all patients, and was not resistant to isoniazid, rifampicin, ethambutol, or streptomycin. Therefore all patients responded well to treatment of tuberculosis.


Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor.
Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.


An indigenously designed apparatus for measuring orthodontic force.
An indigenous apparatus is designed to measure the orthodontic force delivered from elastomeric chains and compare this force with values obtained from the Instron universal testing machine. An indigenously designed apparatus is developed to evaluate forces delivered by various orthodontic auxiliaries. The apparatus consists of a flat steel platform, movable arm, and a mounted screw gauge arm. Orthodontic brackets can be attached to these arms. An electric circuit is connected, to the movable arm, which will estimate the forces exerted between brackets with elastomeric chain. The circuit is connected to the signal conditioner which will display the reading. Elastomeric chain with four links is attached to the arms. The movable arm is adjusted to create orthodontic forces and calibrated on the digital displayer. Twenty Elastomeric chains are used and forces are calibrated with the indigenously designed apparatus. The values of the force is compared with the forces calibrated with Instron universal testing machine to compare the efficacy of the indigenous apparatus. The force values obtained from activation of elastomeric chain segments, in the Instron universal testing machine and the indigenous apparatus were in the range of 100 to 150 grams, initially at 1mm activation then, took a steep rise to 300 to 350 grams at 5mm activation and then, had a gradual increase for the remaining 5mm activation, reaching 400 to 450 grams. The Indigenous apparatus can be considered efficient in measuring tensile force generated by orthodontic auxiliaries.


Circular RNA HIPK3 is a Prognostic and Clinicopathological Predictor in Malignant Tumor Patients.
Objectives: Circular RNA Homeodomain Interacting Protein Kinase 3 (circHIPK3) is one of the most researched circRNAs in recent 5 years. Many individual studies confirmed that aberrantly expression of circHIPK3 held prognostic value in various tumors. Thus, the aim of this meta-analysis is to assess its prognostic potentials and functions in malignant tumors. Materials and methods: Multiple databases were carefully searched for articles published about circHIPK3 over the past 10 years. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to demonstrate prognostic value of circHIPK3 using Stata 15.0 software. Results: 8 studies including 1175 patients were ultimately enrolled in this meta-analysis. Pooled results showed that abnormal expression of circHIPK3 was significantly correlated with unfavorable OS (pooled HR=2.12, 95% CI: 1.69-2.66) and DFS/PFS (HR=2.28, 95% CI: 1.67-3.10) in cancer patients. Additionally, abnormal expression of circHIPK3 was also related to the distal metastasis of the tumors (OR: 3.27, 95%CI: 2.16-4.97, p<0.001). Conclusions: Abnormal expression of circHIPK3, no matter high or low expression, was associated with poor clinical outcomes in multiple cancer types. More comprehensive studies were required to verify and strengthen the clinical value of circHIPK3 in human malignant diseases.


The impact of acute high-risk abdominal surgery on quality of life in elderly patients.
Undergoing acute high-risk abdominal (AHA) surgery is associated with reduced survival and a great risk of an adverse outcome, especially in the elderly. The primary aim of this study was to investigate the residential status and quality of life in elderly patients undergoing AHA surgery. From 1 November 2014 to 30 April 2015, consecutive patients (≥ 75 years) undergoing AHA surgery were included for follow-up after six months. The patients included answered a health-related quality-of-life questionnaire and a supplemental questionnaire regarding residential status. The results were compared with an age-matched national control group. A total of 52 patients matched the inclusion crit-eria. Mortality at six months after surgery was 46%. Out of the 28 survivors, 22 participated in the study. Quality of life was estimated as good in 77% of the survivors and they were willing to undergo surgery again, if necessary. All study participants were admitted from their own home, and 95% had no change in residential status after six months. The self-reported quality of life in elderly survivors six months after AHA surgery was surprisingly good in a small study where all findings should be interpreted with precaution. The majority had no change in residential status. Our study may provide useful information for surgeons advising elderly patients and their families about realistic outcomes following AHA surgery. none. The study was approved by the Danish Data Protection Agency and registered with clinicaltrials.gov.


Initiation of selective proteolysis by metabolic interconversion.
After the addition of glucose to acetate- or ethanol-grown yeast cells a small group of selected enzymes is rapidly inactivated. This phenomenon has been called "catabolite inactivation". Among other enzymes participating in gluconeogenesis, fructose-1,6-bisphosphatase is inactivated during this catabolite inactivation process. It was shown by FUNAYAMA et al. (Eur. J. Biochem. 109, 61-66 (1980)) that the mechanism of inactivation is proteolysis. In the present paper evidence is presented that after addition of glucose a covalent conversion of the enzyme protein by phosphorylation of a serine-residue initiates its subsequent proteolysis. It is suggested that the covalent modification triggered by glucose and/or products of its catabolism renders the enzyme susceptible to proteinases and thereby initiates proteolysis of a selected enzyme without the necessity of a specific proteinase present.


[Lipoma of the spermatic cord. Description of a case and review of the literature].
The authors analyse a case of fibrolipoma of the spermatic cord. It is the most common entity in the non testicular tumors. Ultrasound imaging has proven his utility. Lipoma is homogeneous, a little hyperechoic compared with the next testicle. But surgically exploration of all solid tumors of the cord is appropriated.


A self-powered vibration sensor for downhole drilling tools based on hybrid electromagnetic-triboelectric nanogenerator.
The vibration of downhole drilling tools is important to the drilling process, which needs to be measured in real time. Here, a self-powered vibration sensor for downhole drilling tools based on a hybrid electromagnetic-triboelectric nanogenerator is proposed in this research. The sensor has high reliability because the triboelectric nanogenerator (TENG) and the electromagnetic generator (EMG) parts of the sensor can be used as vibration sensors alone, and it may also supply power to other micro-power measurements while drilling instruments when the TENG and the EMG are used in parallel to increase the output power. Test results show that for the TENG part, the maximum output voltage, current, and power are 14 V, 5.2 µA, and 3.2 µW, respectively, with a 1 MΩ resistance in series, and for the EMG part, they are 1.22 V, 33 µA, and 21.8 mW, respectively, with a 10 Ω resistance in series. Further tests show that the measurement range of both the TENG and EMG is 0-11 Hz, the measurement error of both is less than ±5%, and both can work normally in the temperature range of less than 250 °C. In addition, this research also builds a wireless vibration data transmission system based on the sensor, which shows the potential for use in the wireless sensing field.


Comparative functional characterization of the CSR-1 22G-RNA pathway in Caenorhabditis nematodes.
As a champion of small RNA research for two decades, Caenorhabditis elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation and germline gene expression via 22G-small RNAs. Despite CSR-1 being preserved among diverse nematodes, the conservation and divergence in function of the targets of small RNA pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. elegans and Caenorhabditis briggsae to characterize the CSR-1 pathway, its targets and their evolution. C. briggsae CSR-1-associated small RNAs that we identified by immunoprecipitation-small RNA sequencing overlap with 22G-RNAs depleted in cbr-csr-1 RNAi-treated worms. By comparing 22G-RNAs and target genes between species, we defined a set of CSR-1 target genes with conserved germline expression, enrichment in operons and more slowly evolving coding sequences than other genes, along with a small group of evolutionarily labile targets. We demonstrate that the association of CSR-1 with chromatin is preserved, and show that depletion of cbr-csr-1 leads to chromosome segregation defects and embryonic lethality. This first comparative characterization of a small RNA pathway in Caenorhabditis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regulation across multiple animal species.


Self-nonself recognition by T and B lymphocytes and their roles in autoimmune phenomena.
Evidence is presented which supports the suggestion that whether a given antigen is vulnerable to an autoimmune attack is dependent upon the specific immune status of B cells and T cells to that antigen which, in turn, is dictated by the concentration of self antigen in their microenvironment. That B cells require much higher concentrations of self antigens than do T cells for the maintenance of tolerance is supported by data presented using an experimental model of acquired tolerance to serum proteins. Depending on the immune status of T cells and B cells to self antigen, the following three models are suggested for the early events leading to autoimmunity: 1) polyclonal activation of competent B cells, 2) direct activation of competent T cells, and 3) bypass of specifically tolerant T cells and activation of competent B cells. The role of a regulatory network involving the suppressor cell circuit in the induction and regulation of autoimmunity is discussed.


Unsupervised 3D ring template searching as an ideas generator for scaffold hopping: use of the LAMDA, RigFit, and field-based similarity search (FBSS) methods.
Crystal structures taken from the Cambridge Structural Database were used to build a ring scaffold database containing 19 050 3D structures, with each such scaffold then being used to generate a centroid connecting path (CCP) representation. The CCP is a novel object that connects ring centroids, ring linker atoms, and other important points on the connection path between ring centroids. Unsupervised searching in the scaffold and CCP data sets was carried out using the atom-based LAMDA and RigFit search methods and the field-based similarity search method. The performance of these methods was tested with three different ring scaffold queries. These searches demonstrated that unsupervised 3D scaffold searching methods can find not only the types of ring systems that might be retrieved in carefully defined pharmacophore searches (supervised approach) but also additional, structurally diverse ring systems that could form the starting point for lead discovery programs or other scaffold-hopping applications. Not only are the methods effective but some are sufficiently rapid to permit scaffold searching in large chemical databases on a routine basis.


Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation.
A biologically based model is developed to predict radiation-induced normal tissue complication probability (NTCP) in inhomogeneously irradiated organs such as the lung or the kidney. The organ is assumed to be composed of independent functional subunits (FSUs) organized with a parallel architecture and it is assumed that the complication is produced only if a sufficiently large number of FSUs (the "functional reserve") are destroyed. A general expression for NTCP is derived, as well as simple expressions for the mean and standard deviation of the radiation damage to the FSUs. It is demonstrated that these results for inhomogeneous irradiation reproduce those of the serial and tumor control models when the functional reserve consists of one or all of the FSUs, respectively. When the number of FSUs is large, the dose response for organs with identical characteristics is very steep. Since clinical dose-response curves may arise from populations with varying functional reserves and radiosensitivities, we derive expressions for the NTCP for inhomogeneously irradiated organs that incorporate such variations.


[Problems of lung function testing in the laboratory].
Spirometry is indispensable for the screening test of general respiratory function, and measurements of lung volume and diffusing capacity play an important role in the assessment of disease severity, functional disability, disease activity and response to treatment. Pulmonary function testing requires cooperation between the subjects and the examiner, and the results obtained depend on technical as well as personal factors. In order to diminish the variability of results and improve measurement accuracy, the Japan Respiratory Society published the first guidelines on the standardization of spirometry and diffusing capacity for both technical and clinical staff in 2004. It is therefore essential to distribute the guidelines to both laboratory personnel and general physicians. Furthermore, training workshops are mandatory to improve their understanding of the basics of lung function testing. Recently, there has been increasing interest in noninvasive methods of lung function testing without requiring the patient's cooperation during spontaneous breathing. Three alternative techniques, i.e. the negative expiratory pressure (NEP) method to detect expiratory flow limitation, impulse oscillation system (IOS) to measure respiratory system resistance (Rrs) and reactance (Xrs), and interruption resistance (Rint) to measure respiratory resistance have been introduced. Further study is required to determine the advantage of these methods.


Inpatient care in rural hospitals at the beginning of the 21st century.
National data documenting the role that rural hospitals play in providing inpatient care to patients both younger than 65 and 65 years and older has previously been unavailable. To present descriptive nationally representative data on the numbers and types of inpatients, and the care they received, in rural hospitals. This study includes inpatient data from the 2001 National Hospital Discharge Survey, a nationally representative survey of short-stay, nonfederal hospitals in the United States. Inpatients in rural hospitals were compared to those in urban hospitals in terms of demographic and clinical characteristics and patterns of utilization. Among the variables examined were age, number and type of diagnoses, avoidable hospitalizations, comorbidity, procedures received, source of payment, average length of stay, and discharge disposition. Seventeen percent (5.7 million) of hospitalizations were in rural hospitals in 2001 and a similar percent of the US population lived in rural areas. Rural hospitals provided 23 million days of inpatient care and 4.7 million inpatient procedures. Despite the emphasis placed on Medicare's role in supporting rural hospitals, half of rural hospital inpatients were younger than 65 years. Rural hospital inpatients had shorter average stays and received fewer procedures on average. Seven percent of rural hospital inpatients were transferred to other short-stay hospitals. National data on the broad scope of patients served and inpatient services provided by rural hospitals illustrate one important role these hospitals play in serving rural communities.


Cysteine-rich low molecular weight antimicrobial peptides from Brevibacillus and related genera for biotechnological applications.
The production of natural antimicrobial peptides (AMPs) is an innate immunity trait of all life forms including eukaryotes and prokaryotes. While these AMPs are usually called as defensins in eukaryotes, they are known as bacteriocins in prokaryotes. Bacteriocins are more diverse AMPs considering their varied composition and posttranslational modifications. Accordingly, this review is focused on cysteine-rich AMPs resembling eukaryotic defensins such as laterosporulin from Brevibacillus spp. and associated peptides secreted by the members of related genera. In fact, structural studies of laterosporulin showed the pattern typically observed in human defensins and therefore, should be considered as bacterial defensin. Although the biosynthesis mechanism of bacterial defensins displayed high similarities, variations in amino acid composition and structure provided the molecular basis for a better understanding of their properties. They are reported to inhibit Gram-positive, Gram-negative, non-multiplying and human pathogenic bacteria. The extreme stability is due to the presence of intra-molecular disulfide bonds in prokaryotic defensins and reveals their potential clinical and food preservation applications. Notably, they are also reported to have potential anticancer properties. Therefore, this review is focused on multitude of diverse applications of bacterial defensins, exploring the possible correlations between their structural, functional and possible biotechnological applications.


Provider Integrated Medicare Advantage Plans Are Associated With Differences In Patterns Of Inpatient Care.
Health systems have increasingly developed integrated Medicare Advantage (MA) plans to align financial incentives and improve coordination of care and services across payer and provider. However, little is known about integrated MA plans' effects on patient outcomes and care processes. We used 2015 MA hospitalization data to assess whether these new models are associated with differences in the processes that take place during hospitalizations and to differences in patient outcomes. We found that enrollees who received care in a fully integrated context were less likely to disenroll from Medicare Advantage or switch MA plans and had marginally lower adjusted mortality rates, compared to enrollees hospitalized in less integrated settings-with no differences in readmissions between the two groups. The fully integrated enrollees also acquired more diagnoses but were less often admitted to the ICU compared to other patients admitted to the same hospitals. As the number of these arrangements continues to grow, the potential advantages of coordination may need to be balanced against the increased cost to Medicare associated with apparently more diagnostic complexity.


TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells.
Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines. To identify the molecules and signaling pathways with which TUSC3 might interact, we completed immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays. We demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT progress by upregulating claudin-1 expression. Overall, our observations suggest that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal transition in non-small-cell lung cancer cells; we also identified claudin-1 as a target of TUSC3.


Rapid engraftment without significant graft-versus-host disease after allogeneic transplantation of CD34+ selected cells from peripheral blood.
We have prospectively evaluated the feasibility and results of the biotin-avidin immunoadsorption method (Ceprate SC system) for a phase I/II study of T-cell depletion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cells (PBPC) for allogeneic transplantation. Twenty consecutive patients, median age, 40 years (21 to 54) and diagnoses of chronic myeloid leukemia in chronic phase (n = 5), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2), chronic myelomonocytic leukemia (n = 1), refractory anemia with excess of blasts in transformation (n = 3), histiocytosis X (n = 1), and chronic lymphocytic leukemia (n = 1), were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (13 Gy; 4 fractions). HLA identical sibling donors received G-CSF at 10 microg/kg/d subcutaneously (SC); on days 5 and 6 (19 cases) and days 5 to 8 (1 case) donors underwent 10 L leukapheresis. PBPC were purified by positive selection of CD34+ cells using immunoadsorption biotin-avidin method (Ceprate SC) and were infused in the patients as the sole source of progenitor cells. No growth factors were administered posttransplant. The median recovery of CD34+ cells after the procedure was of 65%. The median number of CD34+ cells infused in the patients was 2.9 (range, 1.5 to 8.6) x 10(6)/kg. The median number of CD3+ cells administered was 0.42 x 10(6)/kg (range, 0.1 to 2). All patients engrafted. Neutrophil counts >500 and >1,000/microL were achieved at a median of 14 days (range, 10 to 18) and 15 days (range, 11 to 27), respectively. Likewise, platelet counts >20,000 and >50,000/microL were observed at a median of 10 days (range, 6 to 23) and 17 days (range, 12 to 130), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine plus methylprednisolone. No patient developed either grade II to IV acute or extensive chronic GVHD. After a median follow-up of 7.5 months (range, 2 to 22) three patients have relapsed, and one of them is again in hematologic and cytogenetic remission after infusion of the donor lymphocytes. Two patients died in remission: one on day +109 of pulmonary aspergillosis and the other on day +251 of metastasic relapse of a previous breast cancer. Sixteen of the 20 patients are alive in remission after a median follow-up of 7.5 months (range, 2 to 22). In conclusion, despite the small number of patients and limited follow-up, it appears that this method allows a high CD34+ cell recovery from G-CSF mobilized PBPC and is associated with rapid engraftment without significant GVHD, and with low transplant related mortality.


Experimental periodontitis induces gene expression of proinflammatory cytokines in liver and white adipose tissues in obesity.
Recent studies indicated that periodontitis induces systemic low-grade inflammation. The increase in systemic low-grade inflammation induced by periodontitis may alter the effects of obesity on the production of inflammatory molecules, including C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-alpha), in the liver and white adipose tissue (WAT). The purpose of the present study is to investigate the effects of periodontitis on the expression of proinflammatory cytokines in the liver and WAT in obese Zucker rats. Obese Zucker rats and their lean litter mates were divided into four groups of six rats each: lean Zucker rats without periodontitis (control group), lean Zucker rats with periodontitis (periodontitis group), obese Zucker rats without periodontitis (obesity group), and obese Zucker rats with periodontitis (combination group). Periodontitis was ligature induced for 4 weeks in the periodontitis and combination groups, whereas the other groups were left unligated. At 4 weeks, the gene expression for CRP, IL-6, and TNF-alpha in the liver and CRP and IL-6 in the WAT of combination groups was significantly higher than in each of the three groups. Serum TNF-alpha in the periodontitis and obesity groups was significantly higher than in the control group. Serum CRP and TNF-alpha in the combination group was significantly higher than in each of the three groups. Systemic low-grade inflammation after experimental periodontitis was associated with increased gene expression for hepatic levels of TNF-alpha and CRP and adipose tissue levels of IL-6 and CRP in the obese-rat model.


Who needs preoperative routine chest computed tomography for prevention of stroke in cardiac surgery?
Although chest computed tomography (CT) is useful for identifying ascending aortic calcification before surgery, the efficacy of routine preoperative CT in cardiac surgery is unknown. We sought to clarify the role of routine preoperative chest CT for the determination of ascending aortic calcification before cardiac surgery to aid in the prevention of stroke. Three hundred consecutive patients who underwent elective cardiac operations excluding thoracic aortic surgery had preoperative non-contrast CT. Thirteen patients (4.3%) had severe calcification in the ascending aorta which required alteration of the cannulation site. Univariate analysis showed preoperative renal dysfunction, dialysis and aortic stenosis as predictors for ascending aortic calcification, but not history of stroke, peripheral vascular disease, and age. In multivariate analysis, aortic stenosis was found as the only predictor. The prevalence of severe ascending aortic calcification was 11.9% (10/84) in patients with aortic stenosis. Stroke occurred in two (0.67%) of the patients in the entire group but none in the 13 patients with surgical modification. For patients with aortic stenosis or hemodialysis, a low postoperative stroke rate can be achieved in elective cardiac surgery by use of routine preoperative chest CT to identify patients with ascending aortic calcification who require modification of the surgical technique.


Biological basis of radiation protection needs rejuvenation.
Human beings encounter radiation in many different situations - from proximity to radioactive waste sites to participation in medical procedures using X-rays etc. Limits for radiation exposures are legally regulated; however, current radiation protection policy does not explicitly acknowledge that biological, cellular and molecular effects of low doses and low dose rates of radiation differ from effects induced by medium and high dose radiation exposures. Recent technical developments in biology and medicine, from single cell techniques to big data computational research, have enabled new approaches for study of biology of low doses of radiation. Results of the work done so far support the idea that low doses of radiation have effects that differ from those associated with high dose exposures; this work, however, is far from sufficient for the development of a new theoretical framework needed for the understanding of low dose radiation exposures. Mechanistic understanding of radiation effects at low doses is necessary in order to develop better radiation protection policy.


Fatal Intracerebral Hemorrhage in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL): A Case Report.
The main clinical manifestations of Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are migraine with aura, ischemic strokes, and progressive cognitive decline. Intracerebral hemorrhage (ICH) has been described in CADASIL, but is not widely recognized. Here we report a case with CADASIL that presented with fatal ICH. A 57-year-old right-handed man of Pakistani descent with history of genetically confirmed CADASIL, hypertension, and mood disorder presented to the emergency department via Emergency Medical Services (EMSs) after he was found down. Initial neurological examination showed a Glasgow Coma Scale (GCS) of 7 (E2, V1, M4), left gaze deviation, pinpoint pupils, and left hemiplegia. His medications included antihypertensive agents and aspirin. He was intubated in the emergency department due to inability to protect his airway. Computed tomographic scan of the head revealed acute hemorrhage in the right pons (ICH score 2) with extension into the right cerebral peduncle, as well as enlargement of the third and lateral ventricles suggesting early obstructive hydrocephalus that required an external ventricular drain placement. He had no improvement of his clinical status, and eventually extubation and comfort care were pursued. He died 6 days after presentation. CADASIL vasculopathy, cerebral microbleeds, hypertension, and antithrombotic agents are factors that could be related to ICH in patients with CADASIL. This case highlights the importance of adequate blood pressure control, magnetic resonance imaging assessment of cerebral microbleed, and careful discussion of the risk and benefits of antiplatelet agents when evaluating and treating patients with CADASIL.


A new phenanthrene derivative and two diarylheptanoids from the roots of Brassica rapa ssp. campestris inhibit the growth of cancer cell lines and LDL-oxidation.
Brassica rapa ssp. campestris (Brassicaceae) is a conical, deep purple, edible root vegetable commonly known as a turnip. We initiated phytochemical and pharmacological studies to search for biological active compounds from the roots of B. rapa ssp. campestris. We isolated a novel phenanthrene derivative, 6-methoxy-1-[10-methoxy-7-(3-methylbut-2-enyl)phenanthren-3-yl]undecane-2,4-dione, named brassicaphenanthrene A (3) along with two known diarylheptanoid compounds, 6-paradol (1) and trans-6-shogaol (2), through the repeated silica gel (SiO2), octadecyl silica gel, and Sephadex LH-20 column chromatography. The chemical structures of the compounds were determined by spectroscopic data analyses including nuclear magnetic resonance, mass spectrometry, ultraviolet spectroscopy, and infra-red spectroscopy. All compounds exhibited high inhibitory activity against the growth of human cancer lines, HCT-116, MCF-7, and HeLa, with IC50 values ranging from 15.0 to 35.0 μM and against LDL-oxidation with IC50 values ranging from 2.9 to 7.1 μM.


The relevance of pre-motor symptoms in Parkinson's disease.
Parkinson's disease (PD) has a wide range of non-motor symptoms including; constipation, sleep disturbance, deficits in vision and olfaction, mood disorders and cardiac autonomic dysfunction. Several of these non-motor symptoms can manifest prior to the onset of motor symptoms. Recognizing these pre-motor symptoms may enable early diagnosis of PD. Currently, no single pre-motor symptom is able to predict the development of PD with 100% sensitivity or specificity. Ongoing studies in several independent at-risk cohorts should reveal the potential of combinations of pre-motor symptoms and multi-stage screening strategies to identify individuals at increased risk of PD. PD progression may be governed by a prion-like spread of a-syn throughout the nervous system. Identifying individuals at the earliest stage will likely be critical to preventing the pathological progression of PD, highlighting the relevance of pre-motor symptoms in the future treatment of the disease.


Unusual presentations of actinomycosis: a case series and literature review.
To review unusual actinomycosis cases that appeared as a diagnostic and therapeutic challenge at our institution and to present a literature review on the usual clinical presentations. This retrospective review included all patients hospitalized for actinomycosis in a 10-year period at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević", Zagreb, Croatia. A total of 15 patients were hospitalized during the observed period, 9 (60%) females and 6 (40%) males. The localizations of actinomycosis were: pelvis (5), lungs (3), blood stream (2), colon (1), penis (1), stomach (1), skin (1), cervicofacial region (1). We present four unusual cases: subcutaneous actinomycotic abscess, actinomycosis of the stomach with underlying non-Hodgkin lymphoma, sepsis due to Actinomyces neslundii originated from chronic asymptomatic periapical tooth abscesses and actinomycosis of the distal part of the penile shaft. Actinomycosis was a very rare clinical problem in our clinical practice (0.032% of all hospitalizations and 0.0034% of all outpatients) but among those cases classical clinical presentations were also very rare.


Ovarian activin receptor subtype and follistatin gene expression in rats: reciprocal regulation by gonadotropins.
The production of activin, follistatin (FS), and inhibin, proteins present in the ovary and involved in mammalian reproduction, is regulated by gonadotropins and estradiol. We report here gonadotropin regulation of ovarian activin receptor (ActR) subtype and FS mRNAs. Expression of ActRI, ActRIIA, ActRIIB, and FS mRNA was measured on the afternoon of proestrus (1800 h) and the morning of estrus (0800 h). ActRI and ActIIA subtype mRNA concentrations fell by approximately 50% (p < 0.05) following the proestrous gonadotropin surge (ActRIIB mRNA was undetectable), while FS mRNA was unchanged. To define the contribution of gonadotropins, hypophysectomized (HYPOX) female rats were given recombinant human (rh) FSH and hCG, which decreased both ActR mRNAs (by approximately 70% and aproximately 50% for ActRI and IIA, respectively) and increased FS mRNA by 2-fold. As gonadotropins could act via estradiol (E2), HYPOX rats were given E2; ActRI was decreased, but ActRIIA mRNA was increased. The actions of gonadotropins were preferential, as the combination of rhFSH and hCG with E2 reduced ActRIIA mRNA. FS mRNA was increased to a similar degree by E2 and/or gonadotropins. These data suggest that gonadotropins regulate ActR and FS gene expression via multiple mechanisms. Both a direct action on ActRIIA (inhibition) and an indirect action through E2 on ActRI (inhibition) and FS (stimulation) suggest potential physiologic mechanisms for the reciprocal regulation of ActR subtype and FS mRNAs.


Cooperativity in supported metal single atom catalysis.
The discussion concerning cooperativity in supported single-atom (SA) catalysis is often limited to the metal-support interaction, which is certainly important, but which is not the only lever for modifying the catalytic performance. Indeed, if the interaction between the SA and the support, which can be seen as a solid ligand presenting its own specificities that fix the first coordination sphere of the metal, plays a central role as in homogeneous catalysis, other factors can strongly contribute to modification of the activity, selectivity and stability of SAs. Therefore, in this mini-review, we briefly summarize the importance of the support (oxide, carbon or a second metal) in SA photo- electro- and thermal-catalysis (support-assisted operation), and concentrate on other types of cooperativities that in some cases enable previously impossible reaction pathways on supported metal SAs. This includes topics that are not specific to SA catalysis, such as metal-ligand or heterobimetallic cooperativity, and cooperativity which is SA-specific such as nanoparticle-SA or mixed-valence SA cooperativity.


Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum.
The life cycle of the parasite Plasmodium falciparum, responsible for the most deadly form of human malaria, requires specialized protein expression for survival in the mammalian host and insect vector. To identify components of processes controlling gene expression during its life cycle, the malarial genome--along with seven crown eukaryote group genomes--was queried with a reference set of transcription-associated proteins (TAPs). Following clustering on the basis of sequence similarity of the TAPs with their homologs, and together with hidden Markov model profile searches, 156 P. falciparum TAPs were identified. This represents about a third of the number of TAPs usually found in the genome of a free-living eukaryote. Furthermore, the P. falciparum genome appears to contain a low number of sequences, which are highly conserved and abundant within the kingdoms of free-living eukaryotes, that contribute to gene-specific transcriptional regulation. However, in comparison with these other eukaryotic genomes, the CCCH-type zinc finger (common in proteins modulating mRNA decay and translation rates) was found to be the most abundant in the P. falciparum genome. This observation, together with the paucity of malarial transcriptional regulators identified, suggests Plasmodium protein levels are primarily determined by posttranscriptional mechanisms.


A PowerPack of SuperScientists: An innovative concept by African scientists to address gender bias and inequity in science.
Underrepresentation of women in scientific leadership is a global problem. To understand and counter narratives that limit gender equity in African science, we conducted a public engagement campaign. Scientists representing six sub-Saharan African countries and multiple career stages used superhero imagery to create a diverse and unified team advocating for gender equity in science. In contrast to many traditional scientific environments and global campaigns, this "PowerPack of SuperScientists" was led by early-career Black female scientists whose perspectives are often under-represented in discussions about gender equity in science. The superhero imagery served as a powerful and fun antidote to imposter syndrome and helped to subvert traditional power structures based on age, race and sex. In an interactive social media campaign, the PowerPack developed insights into three themes: a) cultural stereotypes that limit women's scientific careers, b) the perception of a "conflict" between family and career responsibilities for women scientists, and c) solutions that can be adopted by key stakeholders to promote gender equity in African science. The PowerPack proposed solutions that could be undertaken by women working individually or collectively and interventions that require allyship from men, commitment from scientific institutions, and wider societal change. Further work is required to fully engage African scientists from even more diverse and disadvantaged backgrounds and institutions in these solutions and to enhance commitment by different stakeholders to achieving gender equity in science. Our experience suggests that creative tools should be used to subvert power dynamics and bring fresh perspectives and urgency to this topic.


Survival in progressive supranuclear palsy and frontotemporal dementia.
To compare survival and to identify prognostic predictors for progressive supranuclear palsy and frontotemporal dementia. Progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD) are related disorders. Homozygosity for H1 haplotype is associated with PSP, whereas several MAPT mutations have been identified in FTLD-tau. Survival duration probably reflects underlying pathophysiology or disease. Patients with PSP and FTD were recruited by nationwide referral. Survival of 354 FTD patients was compared with that of 197 PSP patients. Cox regression analysis was performed to identify prognostic predictors. FTLD-tau was defined as Pick disease and FTDP-17 with MAPT mutations. Semiquantitative evaluation of tau-positive pathology was performed on all pathologically proven cases. The median survival of PSP patients (8.0 years; 95% CI 7.3 to 8.7) was significantly shorter than that of FTD patients (9.9 years; 95% CI 9.2 to 10.6). Corrected for demographic differences, PSP patients were still significantly more at risk of dying than FTD patients. In PSP, male gender, older onset-age and higher PSP Rating Scale score were identified as independent predictors for shorter survival, whereas in FTD a positive family history and an older onset-age were associated with a poor prognosis. The difference in hazard rate was even more pronounced when comparing pathologically proven cases of PSP with FTLD-tau. Survival of PSP patients is shorter than that of FTD patients, and probably reflects a more aggressive disease process in PSP. Independent predictors of shorter survival in PSP were male gender, older onset-age and higher PSP rating scale score, whereas in FTD a positive family history and higher onset-age were predictors for worse prognosis.


[An algorithm for reconstruction of soft tissue defects of the distal lower leg, ankle and heel].
The purpose of the study was to establish an algorithm for the reconstruction of soft tissue defects of the distal lower leg, ankle and heel. 81 patients presenting with soft tissue defects in these regions underwent flap coverage. The average age was 44.1 years. Small defects (up to 4 x 4 cm) were covered by local flaps. The neurovascular sural flap was the predominant flap procedure for medium size defects (up to 10 x 15 cm). Free flaps were used for larger defects or in cases of stenosis or occlusion of the peroneal artery. Femoro-crural bypasses were performed in three cases to improve peripheral arterial perfusion. The reconstructive goals were achieved in 95% of the cases by performing reconstruction according to the established algorithm. Minor complications occurred in 29.6% of the cases. The results appear to be very good considering a patient population with complex and predominantly contaminated wounds. A preoperative angiography represents an important part of the algorithm for flap reconstruction to detect abnormal arterial vascular conditions and thus to plan vascular reconstruction prior to or simultaneously with free flap coverage. Additionally, a non-patency of the peroneal artery represents a contraindication for sural flaps.


Aroclor 1254 causes atrophy of exocrine pancreas in mice and the mechanism involved.
Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been linked to pancreatic disease. However, their role in affecting the exocrine function of pancreas and the underlying mechanism remains elusive. In the present study, male C57 mice were treated with Aroclor 1254, a commercially available PCBs mixture, at a dosage of 0.5, 5, 50, or 500 μg kg(-1) every 3 days by oral gavage. Decrease in pancreas/soma index and acinar atrophy were observed in the mice after exposure for 50 days. Aroclor 1254 exposure significantly decreased the PCNA-positive cells in the pancreatic acini in a dose-dependent manner. In addition, western blot analysis showed that PCNA expression was decreased in pancreas in the presence of Aroclor 1254, which suggests that Aroclor 1254 suppresses cell proliferation. TUNEL-positive apoptotic cells as well as the expression of Bcl2, BclXL, BAX, and Bad of exocrine pancreas did not show significant changes in the treated mice, indicating that Aroclor 1254 has no effect on apoptosis. We also found that phosphorylation of ERK1/2, P90RSK1 and Bad was increased in the treated groups; this compensatory activation of phosphorylation in ERK1/2-P90RSK1-Bad signaling cascade could protect cell from apoptosis to maintain the cell numbers and function of exocrine pancreas. Moreover, we found that the expression of Kras and TNFα was increased in the pancreas, indicating that Aroclor 1254 exposure could result in increased risk of inflammation and carcinoma. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 671-678, 2016.


Fusion of an oligopeptide to the N terminus of an alkaline α-amylase from Alkalimonas amylolytica simultaneously improves the enzyme's catalytic efficiency, thermal stability, and resistance to oxidation.
In this study, we constructed and expressed six fusion proteins composed of oligopeptides attached to the N terminus of the alkaline α-amylase (AmyK) from Alkalimonas amylolytica. The oligopeptides had various effects on the functional and structural characteristics of AmyK. AmyK-p1, the fusion protein containing peptide 1 (AEAEAKAKAEAEAKAK), exhibited improved specific activity, catalytic efficiency, alkaline stability, thermal stability, and oxidative stability compared with AmyK. Compared with AmyK, the specific activity and catalytic constant (kcat) of AmyK-p1 were increased by 4.1-fold and 3.5-fold, respectively. The following properties were also improved in AmyK-p1 compared with AmyK: kcat/Km increased from 1.8 liter/(g·min) to 9.7 liter/(g·min), stable pH range was extended from 7.0 to 11.0 to 7.0 to 12.0, optimal temperature increased from 50°C to 55°C, and the half-life at 60°C increased by ∼2-fold. Moreover, AmyK-p1 showed improved resistance to oxidation and retained 54% of its activity after incubation with H2O2, compared with 20% activity retained by AmyK. Finally, AmyK-p1 was more compatible than AmyK with the commercial solid detergents tested. The mechanisms responsible for these changes were analyzed by comparing the three-dimensional (3-D) structural models of AmyK and AmyK-p1. The significantly enhanced catalytic efficiency and stability of AmyK-p1 suggests its potential as a detergent ingredient. In addition, the oligopeptide fusion strategy described here may be useful for improving the catalytic efficiency and stability of other industrial enzymes.


Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats.
Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17β-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects. ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.


Lysophospholipids in development: Miles apart and edging in.
Sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are endogenous bioactive lipids that participate in the regulation of mammalian cell proliferation, apoptosis, migration, and angiogenesis. These processes are each critical for successful embryogenesis, raising the possibility that lysophospholipid signaling may contribute to normal animal development. In fact, recent studies in developmental model systems have established that S1P and LPA are necessary for diverse developmental programs including those required for morphogenesis of vertebrate reproductive, cardiovascular and central and peripheral nervous systems (PNS), as well as the establishment of maternal-fetal circulation and the immune system. Genetic, morphological, and biochemical characterization of developmental model systems offer powerful approaches to elucidating the molecular mechanisms of lysophospholipid signaling and its contributions to animal development and postnatal physiology. In this review, the routes of S1P and LPA metabolism and our current understanding of lysophospholipid-mediated signal transduction in mammalian cells will be summarized. The evidence implicating lysophospholipid signaling in the development of specific vertebrate systems will then be reviewed, with an emphasis on signals mediated through G protein-coupled receptors of the Edg family. Lastly, recent insights derived from the study of simple metazoan models and implications regarding lysophospholipid signaling in organisms in which Edg receptors are not conserved will be explored.


The possible use of telemedicine in developing countries.
Telemedicine may be a useful technique for delivering health care in the developing world. However, there is little practical experience to draw on and real concerns that if additional resources were to become available telemedicine might not be the most appropriate use for them. The logical steps to determine the place of telemedicine in the developing world therefore appear to be: (1) to identify potential telemedicine projects-the Telecommunication Development Bureau of the International Telecommunication Union is trying to do this and has recently sponsored missions to various countries in Africa and Asia; (2) to carry out properly controlled pilot projects in order to demonstrate technical feasibility and to quantify the benefits to the healthcare system; (3) to calculate the costs of large-scale deployment. Assuming that telemedicine is shown to be beneficial, it is only at this final stage that a rational decision can be made about whether telemedicine would be an appropriate use of additional resources in a developing country, as opposed to alternative uses of those resources to solve other important problems of health care.


Twenty-year experience of atrial fibrillation ablation: a single-centre cohort study.
While several studies in the literature have reported results of catheter ablation of AF, few is known regarding outcome for more than 10 years. The complete population of patients who underwent AF ablation in the years 2002-2021 in the department of cardiology of the hospital of Reggio Emilia has been analysed. The last follow-up was made in the second half of 2022. During this period the technique of ablation remained relatively unchanged as well the physicians performing ablation. Primary endpoint was the recurrence of symptomatic AF, defined as AF that caused symptoms that were defined by the patient as able to alter their quality of life. 669 patients underwent catheter ablation and 618 were followed until 2022. Median age of the patients was 58 ± 9 years and 521 (78%) were male. There were 407 (61%) of patients with paroxysmal AF, 167 (25%) with persistent AF and 95 (14%) with long-lasting AF. A total of 838 procedures were performed, with a mean of 1.25 per patient. 163 (26%) patients had 2 procedures and 6 had 3 ablations. Periprocedural complications occurred in 4.8% of procedures. Follow-up data were available for 618 patients (92.4%). The median follow-up duration was 6.6 years (IQR 3.2-10.8). The estimated recurrence rate of symptomatic AF was 26% at 10 years, 54% at 15 years and 82% at 20 years. The recurrence rate was similar in patients who had performed one procedure and in those who had performed 2 or 3 procedures. Progression to permanent AF occurred in 112 patients (18%). The major events that occurred during the follow-up consisted of total mortality in 4.5%, heart failure in 3.1% and TIA/stroke in 2.4%. Symptomatic AF tends to recur during long-term follow-up despite one or more procedures. Catheter ablation seems able to reduce the rate of symptomatic recurrences and to delay the time of their occurrence. These findings are consistent with the knowledge that an age-dependent progressive structural atriomiopathy is the basis for the development of AF.


Prelinguistic predictors of language outcome at 3 years of age.
The purpose of this study was to examine the predictive validity of a collection of prelinguistic skills measured longitudinally in the 2nd year of life to language outcome in the 3rd year in children with typical language development. A collection of prelinguistic skills was assessed in 160 children early (M = 14.31 months; SD = 1.36) and late (M = 19.76 months; SD = 1.16) in their 2nd year by using the Communication and Symbolic Behavior Scales Developmental Profile Behavior Sample (A. Wetherby & B. Prizant, 2002). The relation between the prelinguistic skills and the receptive and expressive language near the 3rd birthday was examined. Significant correlations were observed between many prelinguistic skills and language outcome. Regression analyses indicated that comprehension both early and late contributed unique variance to receptive and expressive language outcome. In addition, early in the 2nd year, inventory of conventional gestures contributed uniquely to receptive language outcome, and acts for joint attention contributed uniquely to expressive outcome. Late in the 2nd year, inventory of consonants contributed uniquely to expressive outcome. The findings demonstrate continuity between prelinguistic and linguistic skills and how individual differences in a number of prelinguistic skills contribute collectively and uniquely to language outcome in typically developing children.


Rational Design of Two-dimensional Anode Materials: B2S as a Strained Graphene.
Alkali metal atom adsorption energy is an important descriptor for anode material design. In this study, an energy decomposition model is developed to provide valuable insights in understanding how the adsorption behavior can be tuned. As an example, Li adsorption on graphene enhanced by a tensile strain is analyzed based on this model. Such an analysis then motivates us to find a system with similar electronic structure but larger lattice parameter compared to graphene as an anode material. Our first-principles calculations indicate that B2S, as an isoelectronic system of graphene, is a good candidate. Its capacity is as high as 1498 mA h g-1 for both Li and Na ion batteries. Li and Na diffusion barriers on B2S are 0.45 and 0.23 eV, respectively. This study opens a new avenue for adsorption-behavior-guided two-dimensional material design.