Impaired slow inactivation due to a polymorphism and substitutions of Ser-906 in the II-III loop of the human Nav1.4 channel.
The loop connecting domains II and III of the sodium channel alpha-subunit is not known to have a major effect on channel gating. Recently mutations in the II-III loop of various sodium channel isoforms have been reported to cause channelopathies suggesting the functional importance of this region. In the II-III loop of the skeletal muscle isoform Na(v)1.4, we found a Ser-to-Thr substitution at position 906 in 5% of patients with dyskalemic periodic paralysis but also in 4% of healthy human individuals. To investigate whether this position is important for channel gating, we characterized the following amino acids at 906 by whole-cell patch-clamp experiments: Gln, Ser, Thr, Cys, Pro, Val, ordered according to their hydrophobicity. All substitutions mainly affected slow inactivation. For example, Gln caused a +13-mV right-shift of the steady-state slow inactivation curve, and entry into slow inactivation was 6 times slower compared with Ser, leading to a destabilization of the slow inactivated state; in contrast, Val, at the other end of the hydrophobicity spectrum, shifted the steady-state slow inactivation curve by -6 mV and slowed the recovery from the slow inactivated state threefold compared with Ser, resulting in an enhancement of slow inactivation. Recovery from the slow inactivated state was also slowed by Pro, Cys and Thr. Our results suggest that (1) a benign polymorphism affects channel function, (2) the II-III loop is important for slow inactivation, and (3) the effects on slow inactivation may depend on the hydrophobicity of the residue at position 906.


unpaired (upd)-3 expression and other immune-related functions are stimulated by interleukin-8 in Drosophila melanogaster SL2 cell line.
Invertebrate innate immunity relies on both cellular and humoral components. Among humoral factors, there is less information on soluble molecules able to act as signals during the immune response (i.e. cytokines). In Drosophila melanogaster, the cytokine Unpaired (Upd)-3, is known to activate the JAK/STAT pathway, but it is still not clear which molecules and pathways are responsible for its induction and secretion. It has been proposed that highly chemotactic factors may increase the expression of upd-3. In this respect, we have studied the effects of the chemotactic human recombinant (hr) interleukin (IL)-8 on the immune functions of Drosophila SL2 macrophage-like cells. The hrIL-8 increases the percentage of phagocytic cells with a specific timing and enhances the expression of the cytokine, upd-3, as well as that of the putative cytokine Drosophila helical factor (dhf). The antimicrobial peptides defensin, cecropin A1 and diptericin, are all influenced in their expression by the human chemokine, while hrIL-8 leaves unaffected the expression of drosomycin, i.e. the antimicrobial peptide more strictly connected with the Toll pathway. Similar effects to those registered for hrIL-8 are also provoked by a specific activator of the Imd pathway, i.e. the Escherichia coli peptidoglycan. RNAi experiments demonstrated that the silencing of the Imd pathway-associated kinase dTAK1, leaves unaffected the induction of upd-3, while it completely abolishes the effects of hrIL-8-on the expression of dhf. Our data suggest that the Imd pathway is not fundamental in regulating the levels of upd-3, whereas it controls the expression of the putative cytokine dhf.


Effect of eggshell membrane as porogen on the physicochemical structure and protease immobilization of chitosan-based macroparticles.
Chitosan-based macroparticle is a common carrier for enzyme immobilization applied in food industry. Driven by the requirement of large carrier pores for the biomacromolecular substrates such as protein, the eggshell membrane powder (ESMP) was employed as multifunctional porogen to improve the physicochemical structure of chitosan-based macroparticles. The prepared macroparticles were characterized by SEM, XRD, FTIR, Raman spectroscopy, nitrogen adsorption-desorption isotherms, and thermogravimetric analysis. The results showed that an increase of ESMP percentage could improve the porosity of macro holes in macroparticles, and it also enlarged the size of mesopores. Moreover, the ESMP significantly increased (P < 0.05) the amount of papain immobilization, whereas the specific activity of immobilized papain achieved a maximum value of 871.95 U/mg at CSESM2 and then declined with the increase of ESMP. Therefore, the inclusion of 20 % ESMP in chitosan-based macroparticles gave the highest activity of its immobilized protease.


Comparison of contact angle measurement and microbial adhesion to solvents for assaying electron donor-electron acceptor (acid-base) properties of bacterial surface.
The electron donor-electron acceptor (acid-base properties) of cell surfaces of a series of bacteria were determined by two methods, namely, Microbial Adhesion to Solvents (MATS) and Contact Angle Measurements (CAM) combined with equation of Van Oss. The efficiency of these two methods was then compared. Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ILP 142B, Staphylococcus aureus ATCC 25923 and four Escherichia coli strains including HB101, AL52, O128B12 and ATCC 25922, acid-base properties were examined under the two different conditions mentioned above. The results showed that the correlation between acid-base properties determined by MATS and CAM was very weak. We have also found that when the microbial cell surface was electron donor by CAM method, similar result was found by MATS, but the reverse was not always true. In contrast, a good correlation between the two methods was obtained when the four E. coli strains were examined.


Evaluating drug distribution and release in ophthalmic emulsions: Impact of release conditions.
The purpose of this study is to investigate the process of drug distribution and mechanism of drug release of ophthalmic emulsions in the context of factors associated with the drug release. Cyclosporine and difluprednate emulsions were chosen as model systems. A kinetic method was used to quantitatively evaluate the drug distribution within a simplified biphasic (emulsion) system. The impacts of release associated factors were investigated, including the amount of sodium dodecyl sulfate (SDS), ethanol, and ionic strength in the release medium as well as the temperature. SDS and ethanol were found to significantly enhance both rate and extent of drug diffusion from oil to aqueous phase for both cyclosporine and difluprednate emulsions. The ionic strength was found to decrease the rate and extent of cyclosporine transfer from oil to aqueous phase but had little impact on the transfer of difluprednate between phases. Diffusion of cyclosporine to aqueous phase exhibited a decreasing trend with increasing temperature due to its atypical temperature dependent solubility in water. Based on our previous method to investigate the impact of formulation variables on drug diffusion and the findings in the current study, a biphasic release model for emulsions is proposed and discussed. Lastly, the underlying relationship of three key quality attributes (i.e., globule size distribution, drug distribution, and release characteristics) and their effect on product quality and performance were discussed. This study provides a fundamental insight into the drug distribution and release in complex emulsion systems. It also elucidates the critical variables for the development of in vitro release method to support regulatory assessment of ophthalmic emulsions and formulation development.


Custody of cocaine-exposed newborns: determinants of discharge decisions.
Maternal cocaine use is a leading grounds for newborn foster placement. This study was initiated to investigate the factors that predict custody status of infants born to substance-abusing women. A retrospective cohort design was used to study the correlates of discharge custody decisions for 99 consecutive infants testing positive for cocaine in a public hospital. The population was 49% Black, 40% Hispanic, and 11% other or unknown. Custody at discharge was to mothers (38%), other family members (25%), or agency foster care (36%). Placement outside the family was greater when mothers had prior child welfare records, in Blacks vs others, with no prenatal care, and when mothers were younger at their first delivery or older at the index birth. Denial of custody to the mother was higher with prior child welfare involvement, in Blacks, and when the mother did not live in her own home. Both models also controlled for parity, child sex, and birthweight. Earlier involvement with child welfare authorities, race, and other factors predict continued separation of mothers and children at newborn discharge, suggesting the need to reexamine current policies and practices.


The mouse formin (Fmn) gene: abundant circular RNA transcripts and gene-targeted deletion analysis.
Mutations in the mouse formin (Fmn) gene result in limb deformities and incompletely penetrant renal aplasia. A molecular genetic approach was taken to characterize novel circular RNAs from the Fmn gene and to understand the developmental effects of gene-targeted mutations. RT-PCR and ribonuclease protection analyses were done to characterize the circular RNA transcripts arising from the Fmn gene. Two lines of mice with gene-targeted deletions of specific Fmn exons, namely exon 4 or exon 5, were generated and analyzed. In our analysis of formin cDNAs, we discovered a class of transcripts in which the exon order is reversed such that downstream exons are joined to the acceptor end of a specific exon that lies 5' to them in the genome. RT-PCR and ribonuclease protection analyses indicate that these transcripts are circular and are the major transcripts arising from this locus in adult brain and kidney. To gain insight into the biological function of these transcripts, we have systematically deleted the relevant exons using gene-targeted homologous recombination. The resulting mice fail to produce circular transcripts, but appear to produce normal amounts of the linear RNA isoforms from this locus. While these deficient mice have normal limbs, they display variably penetrant renal aplasia characteristic of other mutant formin alleles. Our results demonstrate novel circular transcripts arising from the Fmn gene. Moreover, their high levels of expression suggest that they are not products of aberrant splicing events, but instead, may play important biological roles. Mice with gene-targeted deletions of Fmn exons 4 or 5 lack these circular transcripts and have an incompletely penetrant renal agenesis phenotype. While the biologic function of circular Fmn RNA transcripts is not entirely known, our work suggests their possible involvement in kidney development.


Factors associated with condom use in women from an urban area in southern Brazil.
This study investigated the prevalence of factors associated with condom use during last sexual intercourse in 15-49-year-old women in a probabilistic sample from the urban area of Pelotas, southern Brazil. A questionnaire administered by an interviewer, investigating socioeconomic characteristics and habits, and another (self-administered) questionnaire on sexual behavior-related variables were used. Poisson regression, following a hierarchical model, was used for data analysis. 1,543 women were included, and losses and refusals amounted to 3.5%. Prevalence of condom use in last sexual intercourse was 28.0%. Condom use was positively associated with younger age, greater schooling, non-white color, single marital status, and greater number of sex partners in the previous three months. This suggests that the group most vulnerable to STDs/AIDS due to lack of condom use is white, adult women, in stable unions, with fewer sexual partners.


Targeting glycan sulfation in a CD11c+ myeloid population inhibits early KRAS-mutant lung neoplasia.
Early lung carcinoma development may be modulated by innate host cellular mechanisms that promote tumor growth and invasion. We recently identified how a loss-of-function mutation in the glycan sulfating enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1; involved in heparan sulfate biosynthesis) targeted to antigen presenting cells (APCs) may augment acquired anti-tumor T cell immune mechanisms. Crossing this mutation (Ndst1f/f CD11cCre+) onto a model of inducible spontaneous Kras mutant lung cancer [CCSP-rtTA; (tetO7) CMV-Kras-G12D] allowed us to examine how the APC mutation affects the formation and growth of early lung carcinoma. We examined early bronchocentric adenoma formation in the model, and the frequency of such events was significantly reduced on the mutant background. This was associated with significant reductions in tumor associated FOXP3+ cellular infiltration and CD163+ M2-type macrophage infiltration. The findings evolved prior to effector CD8+ T cell infiltration into tumors. The impact of this unique glycan under-sulfating mutation on inhibiting early Kras G12D mutant bronchocentric adenoma formation along with a cellular phenotype of inhibited tumor infiltration by cells involved in suppressive T-regulatory cell signaling (FOXP3+ cells) or tumor-permissive M2 macrophage functions (CD163+ cells) provides insight on how glycan targeting may modulate innate cellular mechanisms during early lung tumor development. The findings may also impact the future design of host-centered immunologic anti-tumor therapeutic strategies.


Molecular insights into biochar-mediated plant growth promotion and systemic resistance in tomato against Fusarium crown and root rot disease.
Molecular mechanisms associated with biochar-elicited suppression of soilborne plant diseases and improved plant performance are not well understood. A stem base inoculation approach was used to explore the ability of biochar to induce systemic resistance in tomato plants against crown rot caused by a soilborne pathogen, Fusarium oxysporum f. sp. radicis lycopersici. RNA-seq transcriptome profiling of tomato, and experiments with jasmonic and salycilic acid deficient tomato mutants, were performed to elucidate the in planta molecular mechanisms involved in induced resistance. Biochar (produced from greenhouse plant wastes) was found to mediate systemic resistance against Fusarium crown rot and to simultaneously improve tomato plant growth and physiological parameters by up to 63%. Transcriptomic analysis (RNA-seq) of tomato demonstrated that biochar had a priming effect on gene expression and upregulated the pathways and genes associated with plant defense and growth such as jasmonic acid, brassinosteroids, cytokinins, auxin and synthesis of flavonoid, phenylpropanoids and cell wall. In contrast, biosynthesis and signaling of the salicylic acid pathway was downregulated. Upregulation of genes and pathways involved in plant defense and plant growth may partially explain the significant disease suppression and improvement in plant performance observed in the presence of biochar.


Alpha-fetoprotein half-life as a predictor of residual testicular tumor. Effect of the analytic strategy on test sensitivity and specificity.
Alpha-fetoprotein (AFP) serum values after orchiectomy for testicular cancer can be used to predict the residual disease status. However, the optimal strategy for postorchiectomy marker analysis has not been studied. This article evaluated different analytic methods in an effort to identify the approach that provided the greatest sensitivity and specificity for occult residual disease. Statistical information on the AFP half-life (t1/2) derived from a clinical data set of 24 patients with AFP-secreting clinical Stage A testicular cancer and pathologically defined nodal status was incorporated into a mathematic model of postorchiectomy marker values as a function of residual tumor volume and time. The model was used to test the effect of various analytic strategies on detecting the residual tumor. The clinical data set then was analyzed to measure the effect of different analytic methods on the predictive value of the AFP t1/2. In the model, the AFP t1/2 calculated from a single set of serum measurements obtained from the initial serum t1/2 was a poor predictor of disease status in patients with up to 40% residual tumor volume. Determined by the sequential addition of serum values obtained at normal t1/2 intervals, the AFP t1/2 improved in sensitivity but required up to seven serial values (35 days) to detect an abnormal t1/2 in patients with 10% residual tumor. By contrast, changes in the most recent interval t1/2 relative to the initial calculated t1/2 predicted the disease status in patients with 10% residual tumor after four t1/2 (20 days) and in patients with 1% residual volume after 35 days. The use of this last strategy in the clinical data set improved both the sensitivity and specificity of the AFP t1/2 in predicting residual tumor relative to the other methods.


Clinical Relevance of Parafoveal Intercapillary Spaces and Foveal Avascular Zone in Diabetic Retinopathy Without Macular Edema.
To investigate the clinical significance of intercapillary spaces on swept source optical coherence tomography angiography images in diabetic retinopathy. We retrospectively reviewed 110 eyes of 110 patients suffering from diabetic retinopathy without macular edema for whom 3 × 3 mm swept source optical coherence tomography angiography images centered on the fovea were obtained. Automatic image processing of the superficial slab images allowed us to define the areas encircled by retinal vessels as intercapillary spaces within the central 2-mm circle. We evaluated how the quantitative parameters of intercapillary spaces are associated with logMAR and feasible to diagnose diabetic macular ischemia. Total counts (ρ = -0.419; P < 0.001) rather than morphologic parameters of the intercapillary spaces showed a significant correlation with logMAR. There were individual levels of correlations between logMAR and counts of intercapillary spaces in individual sectors. In particular, the summed numbers of the spaces in three highly significant sectors were more significantly associated with logMAR (ρ = -0.515; P < 0.001). Multivariate analyses confirmed that the number of the intercapillary spaces (β = -0.266; P = 0.016) and foveal avascular zone area (β = 0.227; P = 0.042) were related to logMAR. The clustering using the foveal avascular zone area and the number of intercapillary spaces revealed two major clusters; one had fewer intercapillary spaces (P < 0.001) and poorer logMAR (P < 0.001) than the other, with a wide range of the foveal avascular zone area. Decreased intercapillary spaces contribute to visual impairment in diabetic retinopathy and suggest one possible criterion of objective diagnosis of diabetic macular ischemia.


Dual excitatory inputs to caudate spiny neurons from substantia nigra stimulation.
In the present set of experiments of two component excitatory postsynaptic potential (EPSP) (fast and slow) was recorded from caudate (Cd) neurons after substantia nigra (SN) stimulation in the alpha-chloralose anesthetized cat. Several unique properties of the fast response are demonstrated and used to determine certain functional properties of Cd neurons. The following conclusions have been drawn from these experiments. (1) A dual excitatory innervation pattern (fast and slow) exists to the Cd from SN stimulation. (2) The fast system is independent of the Cd efferent system. (3) Neurons receiving this dual input are spine laden neurons. (4) Dendritic inhibition is operating on these neurons and often has little or no direct influence on the observed soma membrane potential. The dendritic inhibition reduced test EPSP amplitude for several hundred milliseconds for all Cd afferents except for the fast SN input. Such a decoupling of the fast input from the inhibition may play an important role in Cd signal processing.


Turning cork by-products into smart and green materials for solid-phase extraction - gas chromatography tandem mass spectrometry analysis of fungicides in water.
During stoppers production, large amounts of cork by-products (CBPs) are generated, being used as low-value material. This project aims to turn CBPs into smart, natural and sustainable materials (sorbent) for solid-phase extraction (SPE) of pesticides from water. The study describes the use of CBPs for the extraction of 17 fungicides (metalaxyl, cyprodinil, tolylfluanid, procymidone, folpet, fludioxonil, myclobutanil, kresoxim methyl, iprovalicarb, benalaxyl, trifloxystrobin, fenhexamid, tebuconazole, iprodione, pyraclostrobin, azoxystrobin and dimethomorph) followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. The most critical parameters affecting SPE were optimized by experimental design methodology. Under the optimal conditions, the method was successfully validated in terms of linearity, repeatability, and intermediate precision. Fungicide recovery was assessed in different real water samples including river, fountain, rainwater and spring water at 3 concentration levels (0.1, 0.5 and 10 µg L-1). Recoveries ranged between 70-118% with RSD values lower than 20%, and matrix effects were not observed. Finally, the method was applied to samples from irrigation, rain, and river water, all collected in vineyards areas, revealing the presence of 10 of the 17 fungicides, at concentration up to hundreds of µg L-1. The use of CBPs seems to be a promising low-cost and ecofriendly alternative to be employed as sorbent in SPE techniques to extract fungicides from the aquatic environment.


Extracellular alpha-synuclein induces calpain-dependent overactivation of cyclin-dependent kinase 5 in vitro.
Extracellular alpha-synuclein (ASN) could be involved in the pathomechanism of Parkinson's disease (PD) via disturbances of calcium homeostasis, activation of nitric oxide synthase and oxidative/nitrosative stress. In this study we analyzed the role of cyclin-dependent kinase 5 (Cdk5) in the molecular mechanism(s) of ASN toxicity. We found that exposure of PC12 cells to ASN increases Cdk5 activity via calpain-dependent p25 formation and by enhancement of Cdk5 phosphorylation at Tyr15. Cdk5 and calpain inhibitors prevented ASN-evoked cell death. Our findings, indicating the participation of Cdk5 in ASN toxicity, provide new insight into how extracellular ASN may trigger dopaminergic cell dysfunction in PD.


Modeling the spatial distribution of Chagas disease vectors using environmental variables and people´s knowledge.
Chagas disease is caused by the protozoan Trypanosoma cruzi, which is transmitted to mammal hosts by triatomine insect vectors. The goal of this study was to model the spatial distribution of triatomine species in an endemic area. Vector's locations were obtained with a rural householders' survey. This information was combined with environmental data obtained from remote sensors, land use maps and topographic SRTM data, using the machine learning algorithm Random Forests to model species distribution. We analysed the combination of variables on three scales: 10 km, 5 km and 2.5 km cell size grids. The best estimation, explaining 46.2% of the triatomines spatial distribution, was obtained for 5 km of spatial resolution. Presence probability distribution increases from central Chile towards the north, tending to cover the central-coastal region and avoiding areas of the Andes range. The methodology presented here was useful to model the distribution of triatomines in an endemic area; it is best explained using 5 km of spatial resolution, and their presence increases in the northern part of the study area. This study's methodology can be replicated in other countries with Chagas disease or other vectorial transmitted diseases, and be used to locate high risk areas and to optimize resource allocation, for prevention and control of vectorial diseases.


Serum immunoglobulin G subclasses in patients during acute hepatitis A.
IgG subclasses were measured in sera of 47 patients with acute hepatitis A during the course of the disease. IgG1 and IgG3 serum levels were found to be elevated, whereas IgG2 and IgG4 subclass concentrations did not differ from that found in healthy control individuals. These findings indicate that, similar to the specific antiviral antibody, the polyclonal increase of serum concentrations of IgG in acute hepatitis A is not equally distributed to all IgG subclasses but is restricted to IgG1 and IgG3.


Hemostimulating effects of erythropoietin immobilized by the nanotechnology method of electron-beam synthesis.
The hemostimulating effect of erythropoietin immobilized by the nanotechnology method of electron-beam synthesis was studied on the model of carboplatin-induced myelosuppression. Subcutaneous injection or oral administration of immobilized erythropoietin was followed by stimulation of erythropoiesis. The effect was most pronounced after parenteral treatment with this agent. The increase in proliferative activity and maturation of erythroid precursor cells serve as a factor determining acceleration of reparative processes in the hemopoietic tissue.


Correction: People making deontological judgments in the Trapdoor dilemma are perceived to be more prosocial in economic games than they actually are.
[This corrects the article DOI: 10.1371/journal.pone.0205066.].


Management of psychiatric symptoms in medically ill patients in the homecare setting.
Nurses with critical care knowledge and experience increasingly provide technologically advanced care to patients at home who often present comorbid psychiatric symptoms. Failure to accurately recognize and provide appropriate intervention can be devastating for patients because these symptoms can exacerbate the medical condition and may lead to mortality. The Biopsychosocial Model and the Transactional Model of Stress were presented as guides for nursing practice. Practice is directed at 1) understanding the patient's perception of events, 2) involving the caregiver(s) in the patient's recovery, and 3) enhancing the individual's adaptive coping efforts and resources. The article attempts to guide nurses in making decisions on when to consult and collaborate with an APPN to achieve desired patient outcomes.


A sequential procedure for a phase II efficacy trial in hypercholesterolemia.
The design of a phase II placebo-controlled efficacy trial to evaluate a new treatment for hypercholesterolemia using a sequential procedure is presented. The sequential procedure used is the triangular test which offers flexibility of monitoring and allows early stopping even when the null hypothesis is "accepted." The primary response is reduction in total serum cholesterol level, which is assumed to be normally distributed with unknown variance. The treatment difference is parameterized in terms of the standardized difference between the means. The accuracy of the error rates of the triangular test using this parameterization is compared with the test based on the difference between the means.


Secondary metabolites from a Gloeophyllum species.
Six new sesquiterpenoids, four rearranged illudalanes, one rearranged protoilludane and one sterpurane, were isolated from fermentations of Gloeophyllum sp. 97022. Their structures were elucidated by spectroscopy. Gloeophyllol B and C show weak antifungal activity, while 1-hydroxy-3-sterpurene shows weak antifungal, antibacterial and cytotoxic activities.


Cardiovascular effects of injections of vasopressin into the nucleus tractus solitarius in conscious rats.
The effects of injections of arginine vasopressin (AVP) into the nucleus tractus solitarius (NTS) on mean arterial pressure (MAP), heart rate (HR) and plasma concentrations of noradrenaline and adrenaline were investigated in conscious, unrestrained rats. Injection of 2 ng AVP into the NTS significantly increased MAP but not plasma catecholamine concentrations, while injection of 10 ng AVP significantly increased MAP and plasma noradrenaline and adrenaline levels. Neither dose of AVP produced any change in HR. The vehicle did not affect MAP, HR or plasma catecholamine levels. Injection of a specific pressor antagonist of AVP, d(CH2)5Tyr-(Me)AVP (10 ng), did not change MAP, HR or plasma noradrenaline or adrenaline levels. These results suggest that the NTS is a central site of the pressor action of AVP. However, since the injection of the AVP antagonist did not reduce MAP or plasma noradrenaline or adrenaline levels, it suggests that AVP does not act tonically at the NTS to influence sympathoadrenal outflow.


Delayed Rapid Response Team Activation Is Associated With Increased Hospital Mortality, Morbidity, and Length of Stay in a Tertiary Care Institution.
To identify whether delays in rapid response team activation contributed to worse patient outcomes (mortality and morbidity). Retrospective observational cohort study including all rapid response team activations in 2012. Tertiary academic medical center. All those 18 years old or older who had a rapid response team call activated. Vital sign data were abstracted from individual patient electronic medical records for the 24 hours before the rapid response team activation took place. Patients were considered to have a delayed rapid response team activation if more than 1 hour passed between the first appearance in the record of an abnormal vital sign meeting rapid response team criteria and the activation of an rapid response team. None. A total of 1,725 patients were included in the analysis. Data were compared between those who had a delayed rapid response team activation and those who did not. Fifty seven percent patients met the definition of delayed rapid response team activation. Patients in high-frequency physiologic monitored environments were more likely to experience delay than their floor counterparts. In the no-delay group, the most common reasons for rapid response team activation were tachycardia/bradycardia at 29% (217/748), respiratory distress/low SpO2 at 28% (213/748), and altered level of consciousness at 23% (170/748) compared with respiratory distress/low SpO2 at 43% (423/977), tachycardia/bradycardia at 33% (327/977), and hypotension at 27% (261/977) in the delayed group. The group with no delay had a higher proportion of rapid response team calls between 8:00 and 16:00, whereas those with delay had a higher proportion of calls between midnight and 08:00. The delayed group had higher hospital mortality (15% vs 8%; adjusted odds ratio, 1.6; p = 0.005); 30-day mortality (20% vs 13%; adjusted odds ratio, 1.4; p = 0.02); and hospital length of stay (7 vs 6 d; relative prolongation, 1.10; p = 0.02) compared with the no-delay group. Delays in rapid response team activation occur frequently and are independently associated with worse patient mortality and morbidity outcomes.


Determinants of late presentation to HIV/AIDS care in Southern Tigray Zone, Northern Ethiopia: an institution based case-control study.
Late diagnosis and presentation to human immune deficiency virus (HIV)/acquired immune deficiency syndrome care reduce the benefits of antiretroviral therapy and increase the risk of HIV transmission. This study was conducted to identify determinants of late presentation to HIV care among people living with HIV in Southern Tigray, Northern Ethiopia. An institution based un-matched case-control (1:2 ratios) supported with qualitative data was conducted in Southern Tigray Zone from March 1 to April 30, 2014. Individuals with HIV enrolled from six randomly selected health facilities were included in the study. Cases were people living with HIV who had cluster of differentiation four count <350 cells/μl or World Health Organization stages 3 or 4. A total of 442 study participants were included by systematic sampling techniques. Bivariable and multivariable binary logistic regression model was used to identify associated factors. Odds ratio with 95 % CI was computed to assess the strength of the associations. Age categories, 25-29 years [AOR 3, 95 % CI (1.2-8.1)] and 35-39 years [AOR 4.1, 95 % CI (1.4-12.5)], having two [AOR 6, 95 % CI (1.3-28)] and more [AOR 5.2, 95 % CI (1.1-24.8)] lifetime sexual partners, poor social support [AOR 2.3, 95 % CI (1.26-4.30)], second (next to lowest) wealth quintile [AOR 3.3, 95 % CI 91.3-8.5)], fear of stigma [AOR 4.4, 95 % CI (2.2-8.3)], fear of losing job [AOR 6.8, 95 % CI (1.8-24.5)], and reported severe illness [AOR 4.3, 95 % CI (2.26-8)] were identified to be the risk factors for late presentation. Low socio-economic status and social support, fear of stigma were potential risk factors for late presentation. Efforts towards promoting early care seeking should target on these factors in the study area and other similar settings.


Targeting duplex DNA with DNA-PNA chimeras? Physico-chemical characterization of a triplex DNA-PNA/DNA/DNA.
Targeting double-stranded DNA with homopyrimidine PNAs results in strand displacement complexes PNA/DNA/PNA rather than PNA/DNA/DNA triplex structures. Not much is known about the binding properties of DNA-PNA chimeras. A 16-mer 5'-DNA-3'-p-(N)PNA(C) has been investigated for its ability to hybridize a complementary duplex DNA by DSC, CD, and molecular modeling studies. The obtained results showed the formation of a triplex structure having similar, if not slightly higher, stability compared to the same all-DNA complex.


The influence of PBAT content in the nanocapsules preparation and its effect in essential oils release.
Nanoencapsulation provides new alternatives for the food industry, enabling a controlled and slow release of active antimicrobial agents, such as essential oils (EO). Poly (butylene adipate-co-terephthalate) (PBAT) nanocapsules loaded with linalool EO were prepared using an extrusion method with 1, 3, and 5% w/v (PBAT to chloroform). Nanocapsules' sizes ranged from 100 to 250 nm and were spherical. The release profile was studied using an ethanoic medium over 24 h, and according to the Korsmeyer-Peppas model, a Fick diffusion mechanism was involved. FT-IR and thermogravimetric analyses confirmed EO encapsulation with an encapsulation efficiency of 55%, 71%, and 74% for 1, 3, and 5%, respectively. The results indicated that encapsulation depended on organic phase concentration, with higher PBAT contents achieving better results. The resulting nanocapsules had antimicrobial activity against E. coli, which could be extended to develop active packaging systems.


Left bundle branch pacing on mechanical synchrony and myocardial work in bradycardia patients.
Left bundle branch pacing (LBBP) has emerged as a novel physiological pacing method to produce narrower QRS duration, but whether it could restore mechanical synchrony and improve myocardial work still lacks sufficient evidence. Therefore, the goal of this study was to evaluate mechanical synchrony and myocardial work in LBBP. We collected 20 patients with LBBP due to symptomatic bradycardia and another 29 age-matched patients with right ventricular pacing (RVP). For LBBP patients, cardiac electro-mechanical synchrony and myocardial work were measured at baseline and 7 days after implantation and compared with the RVP patients. In the LBBP group, paced QRS duration and mechanical synchrony were not significantly different from baseline(all P > 0.05), but significantly smaller than that in the RVP group (all P<0.05). Meanwhile, global longitudinal strain (GLS) in LBBP was greater than that in the RVP group (17.7 ± 3.5% vs. 14.8 ± 3.1%, P < 0.05). Global myocardial work index and global constructive work were also better than that in the RVP group(all P<0.05). Global work efficiency was 91.9 ± 3.1%, which was greater when compared with RVP (P < 0.05). LBBP provides better cardiac electro-mechanical synchrony and more effective myocardial work than that in RVP, thus improving global heart function.


Proteomic analysis of anti-aging effects of Dendrobium nobile Lindl. alkaloids in aging-accelerated SAMP8 mice.
Senescence-accelerated mouse prone 8 (SAMP8) mice exhibit cognitive defects and neuron loss with aging, and were used to study anti-aging effects of Dendrobium nobile alkaloids (DNLA). DNLA (20 and 40 mg/kg) were orally administered to SAMP8 mice from 6 to 10 months of age. At 10-month of age, behavioral tests via Y-maze and Open-field and neuron damage via Nissl staining were evaluated. Protein was extracted and subjected to phosphorylated proteomic analysis followed by bioinformatic analysis. The cognitive deficits and neuron loss in hippocampus and cortex of aged SAMP8 mice were improved by DNLA. Hippocampal proteomic analysis revealed 196 differentially expressed protein/genes in SAMP8 compared to age-matched senescence-accelerated resistant SAMR1 mice. Gene Oncology enriched the tubulin binding, microtubule binding, and other activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed endocytosis, mRNA surveillance, tight junction, protein processing in endoplasmic reticulum, aldosterone synthesis and secretion, and glucagon signaling pathway changes. Upregulated protein/genes in the hippocampus of SAMP8 mice, such as Lmtk3, Usp10, Dzip1, Csnk2b, and Rtn1, were attenuated by DNLA; whereas downregulated protein/genes, such as Kctd16, Psd3, Bsn, Atxn2l, and Kif1a, were rescued by DNLA. The aberrant protein/gene expressions of SAMP8 mice were correlated with transcriptome changes of Alzheimer's disease in the Gene Expression Omnibus (GEO) database, and the scores were attenuated by DNLA. Thus, DNLA improved cognitive dysfunction and ameliorated neuronal injury in aged SAMP8 mice, and attenuated aberrant protein/gene expressions.


Serum folate deficiency and associated factors among pregnant women in Haramaya District, Eastern Ethiopia: a community-based study.
We aimed to estimate the prevalence of folate deficiency and contributing factors among pregnant women. A community-based, cross-sectional study. Haramaya District, Eastern Ethiopia. Four hundred and forty-six pregnant women participated in the study. The prevalence of folate deficiency and risk factors. Overall, the prevalence of folate deficiency was 49.3% (95% CI 44.6% to 54.1%). Pregnant women with iron deficiency anaemia were 2.94 times more likely to develop folate deficiency (adjusted OR (AOR)=2.9, 95% CI 1.9 to 4.7). Respondents with good knowledge of folate-rich foods (AOR=0.3, 95% CI 0.1 to 0.7) and those who took iron and folic acid supplementation (AOR=0.6, 95% CI 0.4 to 0.9) during their pregnancy were less likely to develop folate deficiency. In this study, a considerable proportion of pregnant women had folate deficiency during their pregnancy. Therefore, it is critical that nutritional treatment, education and counselling be strengthened to facilitate iron and folic acid supplementation during pregnancy.


The epigenetic silencing of microRNA-433 facilitates the malignant phenotypes of non-small cell lung cancer by targeting CREB1.
MicroRNAs (miRNAs) play a big role in the regulation of non-small cell lung cancer (NSCLC) development. The objective of this study is to determine how DNA methylation regulates miR-433 in NSCLC. The degree of DNA methylation was determined, and the relevance of miR-433 and the features of NSCLC patients were assessed. The MiR-433 and CREB1 expressions were tested, and the biological characteristics of the NSCLC cells were determined. Subcutaneous tumorigenesis in nude mice and luciferase activity assays were performed. MiR-433 was downregulated, and CREB1 was upregulated in the NSCLC tissues, and the methylating rate of the C-phosphate-G (CpG) island in the miR-433 promoter region was enhanced. MiR-433 was also downregulated, and CREB1 was upregulated in the NSCLC cells and there was a low degree of promoter methylation of miR-433 in the NSCLC cells after demethylation. Upregulated miR-433 or downregulated CREB1 repressed the cell vitality and colony formation abilities and increased the amount of apoptotic A549 cells. Moreover, upregulated miR-433 also decelerated tumor growth. Conversely, the H460 cells and xenografts with reduced miR-433 or overexpressed CREB1 had contrary results. CREB1 was found to be targeted by miR-433, as verified by a luciferase activity assay. We found that DNA methylation can downregulate miR-433 in NSCLC, which promotes the malignant behaviors of NSCLC cells.


[Differential radiation susceptibility of endogenous precursor cells forming "early" and "late" hematopoietic foci in the spleen of mice].
No colonies were found in the spleen at "early" times (7-8 days) after irradiation of mice with doses of 8-9 Gy, while at "later" times (after 15 days) a confluent growth of the colonies was observed. The endogenous splenic foci of haemopoiesis of the "late" type were characterized by the preferable growth of granulocytic colonies.


Diabetes in the post-GWAS era.
Large sample sizes, high-resolution arrays and comprehensive imputation are pushing genetic fine-mapping of complex trait loci to its limits without, in most cases, pinpointing a unique variant-gene combination. Superimposing these results on sophisticated maps of functional chromatin elements promises to break this logjam, as a new study of type 2 diabetes compellingly demonstrates.


Mortality and morbidity after resection for adenocarcinoma of the gastroesophageal junction: predictive factors.
Resection for adenocarcinoma of the gastroesophageal junction (AGEJ) is associated with severe mortality and morbidity. This retrospective study aimed to evaluate mortality and morbidity after resection for AGEJ and to determine their predictive factors. Data from 1,192 patients (mean age 65 +/- 11 years) who underwent resection for AGEJ by members of French Association of Surgery from 1985 to 2000 were collected. A stepwise logistic regression model was built to identify by multivariate analysis the variables independently associated with mortality, morbidity, anastomotic leakage, and major pulmonary complications. Distribution of Siewert's type was: I = 480 (40%), II = 500 (42%), and III = 212 (18%). Most type I and II tumors were treated by esophagectomy and proximal gastrectomy (93% and 58%, respectively), using an approach including a thoracotomy (82% and 64%, respectively); type III tumors were treated mainly by total gastrectomy and distal esophagectomy (83%), through an exclusive transabdominal approach (69%). Seventy-six (6%) patients died postoperatively. Only American Society of Anesthesiologists (ASA) scores III and IV (p < 0.001) and period of study (p = 0.025) were predictive of mortality. Predictive factors of overall morbidity (overall rate = 35%) were high ASA score (p < 0.001), age more than 60 years (p = 0.020), male gender (p = 0.039), and cervical anastomosis (p = 0.001). Factors predictive of anastomotic leakage (overall rate = 9%) were high ASA score (p = 0.006) and manual anastomosis (p = 0.010). Factors predictive of major pulmonary complications (overall rate = 23%) were high ASA score (p = 0.015), age more than 60 years (p < 0.001), anastomotic leakage (p < 0.001), and abdominal complications (p = 0.003). ASA score is a reliable predictive factor of operative mortality and morbidity after resection of AGEJ.


Electric field and grain size dependence of Meyer-Neldel energy in C(60) films.
Meyer-Neldel rule for charge carrier mobility measured in C(60)-based organic field-effect transistors (OFETs) at different applied source drain voltages and at different morphologies of semiconducting fullerene films was systematically studied. A decrease in the Meyer-Neldel energy E(MN) from 36 meV to 32 meV was observed with changing electric field in the channel. Concomitantly a decrease from 34 meV to 21 meV was observed too by increasing the grain size and the crystallinity of the active C(60) layer in the device. These empiric findings are in agreement with the hopping-transport model for the temperature dependent charge carrier mobility in organic semiconductors with a Gaussian density of states (DOS). Experimental results along with theoretical descriptions are presented.


Understanding VPAC receptor family peptide binding and selectivity.
The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite recent structural data, a comprehensive understanding of peptide binding and selectivity among different subfamily receptors is lacking. Here, we determine structures of active, Gs-coupled, VIP-VPAC1R, PACAP27-VPAC1R, and PACAP27-PAC1R complexes. Cryo-EM structural analyses and molecular dynamics simulations (MDSs) reveal fewer stable interactions between VPAC1R and VIP than for PACAP27, more extensive dynamics of VIP interaction with extracellular loop 3, and receptor-dependent differences in interactions of conserved N-terminal peptide residues with the receptor core. MD of VIP modelled into PAC1R predicts more transient VIP-PAC1R interactions in the receptor core, compared to VIP-VPAC1R, which may underlie the selectivity of VIP for VPAC1R over PAC1R. Collectively, our work improves molecular understanding of peptide engagement with the PAC1R and VPAC1R that may benefit the development of novel selective agonists.


CAP amplitude after impulse noise exposure in guinea pigs.
In this study, 21 guinea pigs were submitted to a single high energy impulse noise (gun shot with blank projectiles). The auditory function was evaluated over a 7-day recovery period by recording the compound action potential (CAP) from the round window. The threshold shift and input/output function (CAP amplitude and delay function of the stimulus intensity) were studied at different frequencies. CAP amplitude fell after the noise trauma, especially at the lower sound level, resulting in a threshold shift. Latency was significantly increased. During recovery, whereas latency returned to its initial value, CAP amplitude gradually increased and, in half the animals, exceeded the control value for the higher levels of stimulus. This could have been because of progressive disinhibition or recruitment, and may correspond clinically to hyperacusis. These results are discussed referring to those obtained by other authors using other methods.


High intravascular tissue factor expression in dogs with idiopathic immune-mediated haemolytic anaemia.
A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the contribution of whole blood tissue factor (TF) and IL-8 gene expressions. Gene expressions in dogs with IMHA were compared to healthy dogs, dogs with DIC, dogs with sepsis, and in two groups of dogs that underwent intensive care treatment but had no evidence for either DIC or sepsis. The whole blood TF and IL-8 expressions were up regulated in all non-IMHA groups. Similarly, the TF expression in IMHA dogs was high, but the intravascular IL-8 expression was not increased. The dogs with IMHA had a pronounced inflammatory response that included a high WBC, left shift and monocytosis in comparison to the other disease groups. Coagulation factor activities in IMHA dogs were decreased fitting consumptive coagulopathy and the acute phase proteins FVIII and fibrinogen were increased. The platelet parameters suggested platelet activation and high platelet turnover in IMHA dogs. The model that best explained mortality contained monocytosis, increased activated partial thromboplastin time and elevated creatinine. Whole blood TF gene expression is up regulated and may contribute to consumptive coagulopathy in dogs with IMHA. Increased TF expression by activated platelets is an alternative explanation and should be investigated.


Plasminogen activator activity of normal and retinoic acid-treated post-implantation embryos.
Urokinase-type plasminogen activator (uPA) has been implicated in cellular migration accompanying different biological phenomena including organogenesis. An increase in uPA activity was observed in mouse post-implantation embryos during the early organogenesis period. Since we have previously shown that all-trans retinoic acid (RA) prevented the induction of uPA in mouse peritoneal macrophages, we have now assessed whether teratogenic doses of this agent could also interfere with uPA activity in mouse embryo in vitro and in vivo. Post-implantation embryos (8.5 days) were incubated for up to 24 hr with micromolar concentration of RA resulting in the occurrence of malformations. No significant difference in uPA activity was found between control and treated embryos. Likewise, uPA activity was not altered in embryos explanted on day 9.5 from dams treated 24 hr before with a teratogenic dose of RA. This study indicates that the teratogenic activity of RA is not caused by an inhibition of the induction of uPA in embryos.


[Hydrogen peroxide (H2O2) and methyl-beta-cyclodextrin (MPCD) down regulate caveolin expression in human lens epithelial cells (HLECs)].
Oxidative stimulation induced by hydrogen peroxide (H2O2) on human epithelial cells (HLECs) was performed to observe the effects on cell viability, caveolin expression, and cholesterol depletion in HLECs caused by methyl-beta-cyclodextrin (MbetaCD) was also studied. SRA01/04 HLECs were exposed to H2O2 or MbetaCD of various concentrations and durations. We used a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to measure the effect of H2O2 on the viability of SRA01/04 HLECs. The distributions of caveolins after oxidative stimulation were probed by fluorescence microscopy and laser scanning confocal microscopy. Immunoblotting was performed to analyze alterations of caveolins expression. We observed that the viability of SRA01/04 HLECs under 0.1 mM H2O2 for 10 min or longer was significantly reduced (*p < 0.05, F = 11.63). Laser scanning microscopy showed immunofluorescent caveolins in SRA01/04 HLECs under 0.1 mM H2O2 for 10 min or longer, caveolins were largely confined to intracellular domains. Western blots showed both membrane and total caveolin protein (22 kDa) levels in SRA01/04 HLECs treated with 0.1, 0.2, 0.5 or 1.0 mM H2O2 for 30 min were significantly reduced, compared with the untreated (*p < 0.05, F = 6.149, or *p < 0.05, F = 14.489 respectively). In addition, the membrane and total caveolin protein level after treated with 0.1 mM (*p < 0.05, F = 6.843, or *p < 0.05, F = 7.944 respectively) H2O2 for different durations also down regulated. Fluorescence microscopy also showed that phosphorylated caveolin-1 was distributed near the focal adhesions of the cells. This study concludes that the responses of HLECs to oxidative stress may include down regulation of caveolin and phosphorylation of caveolin-1 on Tyr14, and that MbetaCD also down regulates caveolin while depleting cholesterol in HLECs.


Application of machine learning to determine top predictors of noncalcified coronary burden in psoriasis: An observational cohort study.
Psoriasis is associated with elevated risk of heart attack and increased accumulation of subclinical noncalcified coronary burden by coronary computed tomography angiography (CCTA). Machine learning algorithms have been shown to effectively analyze well-characterized data sets. In this study, we used machine learning algorithms to determine the top predictors of noncalcified coronary burden by CCTA in psoriasis. The analysis included 263 consecutive patients with 63 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative. The random forest algorithm was used to determine the top predictors of noncalcified coronary burden by CCTA. We evaluated our results using linear regression models. Using the random forest algorithm, we found that the top 10 predictors of noncalcified coronary burden were body mass index, visceral adiposity, total adiposity, apolipoprotein A1, high-density lipoprotein, erythrocyte sedimentation rate, subcutaneous adiposity, small low-density lipoprotein particle, cholesterol efflux capacity and the absolute granulocyte count. Linear regression of noncalcified coronary burden yielded results consistent with our machine learning output. We were unable to provide external validation and did not study cardiovascular events. Machine learning methods identified the top predictors of noncalcified coronary burden in psoriasis. These factors were related to obesity, dyslipidemia, and inflammation, showing that these are important targets when treating comorbidities in psoriasis.


Incomplete penetrance and variable expressivity in monogenic diabetes; a challenge but also an opportunity.
Monogenic Forms of Diabetes (MFD) account for about 3% of all diabetes, and their accurate diagnosis often results in life-changing therapeutic reassignment for the patients. Like other Mendelian diseases, reduced penetrance and variable expressivity are often seen in several different types of MFD, where symptoms develop only in a portion of the persons who carry the pathogenic variant or vary widely in symptom severity and age of onset. This complicates diagnosis and disease management in MFD. In addition to its clinical importance, knowledge of genetic modifiers that confer penetrance and expressivity variability opens possibilities to identify protective genetic variants which may help probe the mechanisms of more common forms of diabetes and shed light in new therapeutic strategies. In this review, we will mainly address penetrance and expressivity variation in different types of MFD, factors that confer such variations and opportunities that come with such knowledge. Related literature was searched in PubMed, Medline and Embase. Papers with publication year from 1974 to 2023 are included. Data are either sourced from literatures or from OMIM, Clinvar and 1000 genome browser.


Immune system of swine: dissection of mononuclear leucocyte subpopulations by means of two-colour cytofluorometric analysis.
Expression of the differentiation antigen 8/1, a porcine leucocyte marker for which no counterpart is known as yet in other species, was tested in relation to the expression of surface Ig and the monocyte marker 74-22-15. B lymphocytes and T lymphocytes can be typified by the exclusive expression of surface Ig and 8/1, respectively, while all monocytes defined by the expression of the 74-22-15 antigen co-express 8/1 with the highest staining density observed for this marker. 8/1+ T lymphocyte subsets defined by the expression of CD4 and CD8 cell surface antigens differed in the expression of 8/1 with the staining density being high in CD4+ T lymphocytes, intermediate in CD8+ as well as in CD4+CD8+ T lymphocytes, and low in the CD4-CD8- subset. Practically all mononuclear leucocytes present in peripheral blood are included in the subpopulations defined by this kit of reagents, and thus it can be predicted that if mononuclear leucocytes which do not belong to any of these subpopulations exist at all, these must be rare and will not be accessible to an analysis without enrichment.


Quercetin, Engelitin and Caffeic Acid of Smilax china L. Polyphenols, Stimulate 3T3-L1 Adipocytes to Brown-like Adipocytes Via β3-AR/AMPK Signaling Pathway.
The aim of the present study was to investigate the browning effects mechanism of Smilax china L. polyphenols (SCLP) and its monomer. In this study, polyphenols (SCLP, engeletin, quercetin and caffeic acid) markedly suppressed lipid accumulation. Polyphenols significantly up-graded the expression of protein kinase A (PKA), adipose triglyceride lipase (ATGL), peroxisome proliferators-activated receptors alpha (PPARα), carnitine palmitoyl transferase (CPT) and acyl-CoA oxidase (ACO) to promote lipolysis and β-oxidation. Moreover, polyphenols greatly enhanced mitochondrial biogenesis in adipocytes, as demonstrated by the expression of Nrf1 and Tfam were up-regulated. Furthermore, polyphenols treatment greatly up-regulated the browning program in adipocytes by increased brown-specific genes and proteins uncoupling protein 1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and PR domain containing 16 (PRDM16), as well as beige-specific genes (Tmem26, Tbx1, CD137, Cited1), especially engeletin. Further research found that the brown-specific markers were decreased by antagonist treatment of AMPK or β3-AR, but polyphenols treatment reversed the effect of antagonists and improved the expression of UCP-1, PRDM16 and PGC-1α. In conclusion, these results indicated that polyphenols stimulate browning in adipocytes via activation of the β3-AR/AMPK signaling pathway, and SCLP and its monomer may be worth investigating to prevent obesity.


Short-chain fatty acid topical treatment in distal ulcerative colitis.
Some evidence indicates that short-chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis. In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study. Fourteen patients on SCFA improved (overall score 11.3 +/- 2.0 vs. 7.4 +/- 3.5) as compared to five in the placebo group (overall score 10.0 +/- 1.9 vs. 8.9 +/- 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pretrial differences between the two groups. The present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.


Squamous/adenosquamous carcinoma of the gallbladder: Analysis of 34 cases and comparison of clinicopathologic features and surgical outcomes with adenocarcinoma.
To explore clinicopathological features and effects of surgical treatment of squamous/adenosquamous carcinoma of the gallbladder. We enrolled 411 patients who were surgically treated for gallbladder cancer in our hospital, including 10 with squamous cell carcinoma (SCC), 24 with adenosquamous carcinoma (ASC), and 377 with adenocarcinoma (AC). The ASC-SCC group was compared with the AC group for clinicopathological features and surgical outcomes. The patients' average age was 61.4 years. Abdominal pain was the most common presenting symptom, and 67.6% of patients had gallstones. All patients had advanced-stage (T3/T4) carcinomas. The ASC-SCC group had significantly higher percentages of T4 disease (61.8%) and N1 nodal involvement (58.8%) than did the AC group (T4 disease: 34.0%, P = 0.001; N1 involvement: 39.0%, P = 0.02). Patients in the ASC-SCC group who underwent R0 resections had significantly better 1-year survival (30%) than those who underwent R1 or R2 resections (0%; P = 0.025), but lower 1-year survival rates than similar-staged patients in the AC group (69.3%; P = 0.016). Patients with gallbladder ASC-SCC were similar to those with AC in clinical characteristics, but tended to have more infiltration of multiple adjacent organs and lymphatic metastasis. Curative resection could give these patients better outcomes.


Experimental and theoretical study on the driving force and glass flow by laser-induced metal sphere migration in glass.
Light is able to remotely move matter. Among various driving forces, laser-induced metal sphere migration in glass has been reported. The temperature on the laser-illuminated side of the sphere was higher than that on the non-illuminated side. This temperature gradient caused non-uniformity in the interfacial tension between the glass and the melted metal as the tension decreased with increasing temperature. In the present study, we investigated laser-induced metal sphere migration in different glasses using thermal flow calculations, considering the temperature dependence of the material parameters. In addition, the velocity of the glass flow generated by the metal sphere migration was measured and compared with thermal flow calculations. The migration velocity of the stainless steel sphere increased with increasing laser power density; the maximum velocity was 104 μm/s in borosilicate glass and 47 μm/s in silica glass. The sphere was heated to more than 2000 K. The temperature gradient of the interfacial tension between the stainless steel sphere and the glass was calculated to be -2.29 × 10-5 N/m/K for borosilicate glass and -2.06 × 10-5 N/m/K for silica glass. Glass flowed in the region 15-30 μm from the surface of the sphere, and the 80-μm sphere migrated in a narrow softened channel.


Recurrent pneumonia in a child with Jacobsen syndrome and common variable immune deficiency.
Recurrent severe respiratory infections in Jacobsen syndrome (JS) are unusual and should prompt evaluation of the immune system. A variety of immune defects have been reported in JS and intravenous immune globulin (IVIG) treatment reduces severe infections.


Tumor heterogeneity and its implication for drug delivery.
Evidence continues to accumulate that patient tumors contain heterogeneous cell populations, each of which may contribute differently in extent and mechanism to the progression of malignancy. However, the field of tumor drug delivery research, while continually presenting new and innovative approaches, in many ways continues to operate on the premise that essentially all tumor cells are identical. In some in vivo models, xenograft tumors using cell lines may actually be comparatively homogeneous, and thus result in overly encouraging results when a particular drug or delivery system is reported to successfully treat tumors in mice. It is well known, however, that many drugs that show success in preclinical studies will fail in clinical trials. Tumor heterogeneity is possibly one of the most significant factors that most treatment methods fail to address sufficiently. While a particular drug may exhibit initial success, the eventual relapse of tumor growth is due in many cases to subpopulations of cells that are either not affected by the drug mechanism, possess or acquire a greater drug resistance, or have a localized condition in their microenvironment that enables them to evade or withstand the drug. These various subpopulations may include cancer stem cells, mutated clonal variants, and tumor-associated stromal cells, as well as cells experiencing a spatially different condition such as hypoxia within a diffusion-limited tumor region. This review briefly discusses some of the many aspects of tumor heterogeneity and their potential implications for future drug design and delivery methods.


Fatal Mycobacterium tuberculosis infection in a lung transplant recipient.
Lung transplant recipients are at increased risk for Mycobacterium tuberculosis infection secondary to the intense immunosuppressive regimen after transplantation. We report a case of fatal M tuberculosis infection that presented as a pericardial abscess in a lung transplant recipient and review the literature.


Cell radiolabeling with acoustophoresis cell washing.
Labeling immune cells with zirconium-89 (89Zr)-oxine has become a viable method to track cells in vivo by PET in various pre-clinical animal models and in clinical applications. Currently, 89Zr-oxine cell labeling is performed manually, which requires a highly trained specialist and is prone to human error. As the first phase in developing a fully automated radiolabeling system to address this problem, we assess the use of acoustophoresis cell washing to replace the centrifugal cell washing used in the current 89Zr-oxine cell radiolabeling procedure. To accomplish this, a cell radiolabeling procedure was developed in which two steps requiring a centrifuge to wash cells were replaced using acoustophoresis cell washing methods. The process was tested using murine EL4 lymphoma and T cells. The centrifuge cell labeling procedure was used as a control to compare the acoustophoresis cell washing procedure. The acoustophoresis method produced radiolabeled cells with similar properties to the centrifugal method when comparing labeling efficiency, labeled specific activity, efficacy of removing unbound 89Zr-oxine from the suspension, cell viability measured using annexin V/propidium iodide staining and activation function. This suggests that acoustophoresis cell washing can be used in the design of an automated benchtop, good manufacture practice-qualified acoustophoresis cell radiolabeling device.


A survey of pressure ulcer education within pre-registration radiography courses.
The prevention of pressure ulcers and the management of people with pressure ulcers is multi-disciplinary, though in many places it is considered a nursing problem. Radiography environments are a potential cause of pressure ulcers. This paper describes the results of a survey of pre-registration radiography education institutions regarding the education provision on the prevention of pressure ulcers within radiography environments. The survey comprised two parts--a desk top review of course prospectuses and a postal questionnaire. Course prospectuses for 23 of the 24 institutions were examined for specific mention of prevention and management of pressure ulcers but none was found. All 24 institutions in the United Kingdom were invited to respond to a questionnaire survey, and 14 replied (58% response rate). Responses covered both diagnostic and therapeutic radiography programmes. Nine institutions specifically identify teaching on pressure ulcers, with the majority of education appearing in year 1 of the course, with some courses providing further material later in the programme. The survey confirms anecdotal evidence reported in a previous study that radiographers have little training in the prevention and management of patients at risk of developing pressure ulcers during radiographic procedures. Thirteen out of 14 institutions stated that no final year student project had considered the prevention and management of pressure ulcers in radiography environments.


Efficacy and safety of botulinum toxin for treating motor dysfunction in patients with Parkinson's disease: a systematic review and meta-analysis.
To evaluate the efficacy and safety of botulinum toxin (BTX) for motor dysfunction in Parkinson's disease (PD). Systematic review and meta-analysis. Searches of PubMed, EMBASE and the Cochrane Library, from database inception to 20 October 2022. Studies reported in English with adult PD patients treated with BTX. Primary outcomes were United Parkinson's Disease Rate Scale Section (UPDRS) III (or its items) and Visual Analogue Scale (VAS). Secondary outcomes were UPDRS-II (or its items), Freezing of Gait Questionnaire (FOG-Q), Timed Up and Go test (TUG) and treatment-related adverse events (TRAEs). Mean difference (MD) or standardised MD (SMD) before and after treatment with 95% CIs were used for continuous variables and risk ratios (RRs) with 95% CIs was used for TRAEs. Six randomised controlled trials (RCTs) and six non-RCTs (case series) were included (ntotal=224 participants, nRCT=165). No significant difference was found in pooled results of UPDRS-III (available in four RCTs and two non-RCTs, SMD=-0.19, 95% CI -0.98 to 0.60), UPDRS-II (four RCTs and one non-RCT, SMD=-0.55, 95% CI -1.22 to 0.13), FOG-Q (one RCT and one non-RCT, SMD=0.53, 95% CI -1.93 to 2.98) or the risk of TRAEs (five RCTs, RR 0.87, 95% CI 0.37 to 2.01). Significant decreases were found in pooled VAS score (three RCTs and five non-RCTs, MD=-2.14, 95% CI -3.05 to -1.23) and TUG (MD=-2.06, 95% CI -2.91 to -1.20) after BTX treatment. BTX may not be associated with motor symptoms alleviation, although it benefits pain alleviation and functional mobility improvement.


The interplay of parental support, parental pressure and test anxiety--Gender differences in adolescents.
This study examined gender-specific relationships between adolescents' perceptions of school-related support/pressure from their parents and test anxiety. A sample of German students (N = 845; Mage = 15.32; SD = .49) completed questionnaires that measured their perceived parental support/pressure (for mother and father separately) as well as the four main components of test anxiety (worry, interference, lack of confidence, and emotionality). Gender-specific relations were identified using multigroup structural equation modeling: For girls, perceived maternal pressure was positively associated with emotionality and interference; for boys, perceived father pressure and father support were positively associated with interference and worry, respectively. For both genders, perceived mother pressure and support were related to lack of confidence. Our findings suggest that adolescents' perceptions of maternal attitudes are associated with students' self-confidence irrespective of the child's gender, whereas the remaining facets of test anxiety follow same-sex trajectories between perceived parental attitudes and adolescents' test anxiety.


Redox and Epigenetics in Human Pluripotent Stem Cells Differentiation.
Significance: Since their discovery, induced pluripotent stem cells (iPSCs) had generated considerable interest in the scientific community for their great potential in regenerative medicine, disease modeling, and cell-based therapeutic approach, due to their unique characteristics of self-renewal and pluripotency. Recent Advances: Technological advances in iPSC genome-wide epigenetic profiling led to the elucidation of the epigenetic control of cellular identity during nuclear reprogramming. Moreover, iPSC physiology and metabolism are tightly regulated by oxidation-reduction events that mainly occur during the respiratory chain. In theory, iPSC-derived differentiated cells would be ideal for stem cell transplantation as autologous cells from donors, as the risks of rejection are minimal. Critical Issues: However, iPSCs experience high oxidative stress that, in turn, confers a high risk of increased genomic instability, which is most often linked to DNA repair deficiencies. Genomic instability has to be assessed before iPSCs can be used in therapeutic designs. Future Directions: This review will particularly focus on the links between redox balance and epigenetic modifications-in particular based on the histone variant macroH2A1-that determine DNA damage response in iPSCs and derived differentiated cells, and that might be exploited to decrease the teratogenic potential on iPSC transplantation. Antioxid. Redox Signal. 34, 335-349.


Immune Dysregulation in Treatment-Resistant Depression: Precision Approaches to Treatment Selection and Development of Novel Treatments.
Owing to the link between immune dysfunction and treatment-resistant depression (TRD) and the overwhelming evidence that the immune dysregulation and major depressive disorder (MDD) are associated with each other, using immune profiles to identify the biological distinct subgroup may be the step forward to understanding MDD and TRD. This report aims to briefly review the role of inflammation in the pathophysiology of depression (and TRD in particular), the role of immune dysfunction to guide precision medicine, tools used to understand immune function, and novel statistical techniques.


Electrocardiographic activity before onset of postoperative atrial fibrillation in cardiac surgery patients.
Electrocardiographic (ECG) characteristics were analyzed in postoperative cardiac surgery patients in an attempt to predict development of new-onset postoperative atrial fibrillation (AF). Nineteen ECG characteristics were analyzed using computer-based algorithms. The parameters were retrospectively analyzed from ECG signals recorded in postoperative cardiac surgery patients while they were in the cardiovascular intensive care unit (CVICU) at our institution. ECG data from 99 patients (of whom 43 developed postoperative AF) were analyzed. A bootstrap variable selection procedure was applied to select the most important ECG parameters, and a multivariable logistic regression model was developed to classify patients who did and did not develop AF. Premature atrial activity (PAC) was greater in AF patients (P < 0.01). Certain heart rate variability (HRV) and turbulence parameters also differed in patients who did and did not develop AF. In contrast, P-wave morphology was similar in patients with and without AF. Receiver operating curve (ROC) analysis applied to the model produced a C-statistic of 0.904. The model thus correctly classified AF patients with more than a 90% sensitivity and a 70% specificity. Among the 19 ECG parameters analyzed, PAC activity, frequency-domain HRV, and heart rate turbulence parameters were the best discriminators for postoperative AF.


Measurements of metabolites during cAMP oscillations of Dictyostelium discoideum.
During aggregation the cellular slime mold Dictyostelium discoideum synthesizes and releases pulses of cAMP about every five minutes. Current models proposed to explain this phenomenon postulate that oscillating levels of some key intracellular metabolite control the oscillatory synthesis of cAMP. We have assayed the levels of likely candidates for this metabolite during a cAMP oscillation, but have found them to remain constant. Compounds measured include ATP, GTP, glucose-1-phosphate, glucose-6-phosphate, isocitrate, alpha-ketoglutarate, amino acids, and other aminated metabolites. On the basis of this negative data, as well as results described elsewhere (Geller and Brenner, '78), we question whether the proposed models are correct, and discuss several alternatives.


Surgical repair of a pseudoaneurysm derived from a nine-year-old saphenous vein graft after coronary artery bypass.
A 57-year-old male presented intermittent pain between the left shoulder and neck. He had undergone coronary artery bypass twice and all grafts had been confirmed to be angiographically intact at three and a half years prior. Coronary angiography revealed that a pseudoaneurysm derived from around the proximal ascending aortic anastomosis of the saphenous vein graft that connected to the left anterior descending branch and #4-atrioventricular branch sequentially. The pseudoaneurysm compressed the saphenous vein graft itself. He underwent repair of the pseudoaneurysm through median sternotomy after left subclavian artery-saphenous vein graft bypass utilizing a free left radial artery without cardiopulmonary bypass through left anterolateral thoracotomy. A 7 mm length longitudinal tear in the saphenous vein graft near the proximal anastomosis had caused the pseudoaneurysm. This tear had likely been caused by perforation by a catheter during coronary arteriography three and a half years ago.


Influence of Withania somnifera on obsessive compulsive disorder in mice.
To study the influence of methanolic and aqueous extract of Withania somnifera (W. somnifera) root on the marble-burying behavior of mice a well-accepted model of obsessive compulsive behavior. Mice were divided in different groups (n = 6). Fluoxetine (5, 10, 15 mg/kg), (10, 25, 50, 100 mg/kg) and methanolic extract W. somnifera (MEWS) (10, 25, 50, 100 mg/kg) were administered i.p. 30 min. prior to the assessment of marble burying behavior and locomotor activity. The control group received vehicle of the extract. Administration of aqueous extracts W. somnifera (AEWS) and MEWS (50 mg/kg) successively decreased the marble burying behavior activity without affecting motor activity. This effect of AEWS and MEWS was comparable to standard fluoxetine, ritanserin and parachlorophenylalanine. W. somnifera extract is effective in treating obsessive compulsive disorder.


Extraosseous aneurysmal cyst in hand: a case report.
The presence of primary aneurysmal cyst in soft tissues is a extremely rare and its presence in the soft tissues of hand has never been reported in literature before. We report the first ever case of extraosseous aneurysmal cyst in hand. A twelve years old girl presented with a swelling in the thenar region on palmer aspect of right hand growing slowly since three months. On X ray, CT scan and excision biopsy the lesion was found to be separate from bone and located in the soft tissue. Its diagnosis was confirmed on histopatholgical examination. Previously few authors have reported extraosseous aneurysmal cyst in the soft tissues of shoulder, hip and pelvic girdle but nobody has reported its presence in the soft tissues of hand.


Computer-analyzed dietary intake printouts: guidelines for their design and student comprehension.
The purpose of this study was to determine the ability of individuals to comprehend and interpret information on nutrient analysis computer program printouts and to assess their understanding of certain concepts closely related to such printouts, specifically the Recommended Dietary Allowances (RDAs) and vitamin and mineral supplementation. The study sample comprised 553 college students who were randomly assigned to one of seven groups. Each group received a nutrient analysis computer printout that varied in terms of type, amount, and format of information supplied. Printouts with varying characteristics were used in order to identify those elements that contributed to the greatest and most correct understanding and interpretation. A 30-item objective knowledge test was used to assess understanding and ability to interpret information on the printouts. Research results indicate that most individuals had misconceptions concerning the RDAs and vitamin and mineral supplementation. Recommendations were made for improving the information provided on printouts regarding these two topics. Subjects had little difficulty in reading the printout correctly. However, groups whose printouts included only nutrient data generally had more difficulty using the information to draw appropriate conclusions and identify ways to improve dietary intake than did individuals whose printouts included short messages listing sources and functions of nutrients. Data presented in graphic format were more easily understood than data in spreadsheet form. Eight design recommendations intended to assist nutritionists and software designers in selecting and/or creating printouts were made on the basis of the results of this study.


Linear extragenital lichen sclerosus with underlying bony atrophy.
We describe a 21-year-old male patient with linear extragenital lichen sclerosus. The lesions are confined to the left side of his body and consist of 3 long bands running along the left leg and several patchy and linear lesions on the left side of his trunk. An associated finding is a smaller diameter of the distal part of his left lower leg caused by bony atrophy of the underlying portion the tibia. This is the fifth reported case of linear lichen sclerosus.


Early response of wheat antioxidant system with special reference to Fusarium head blight stress.
Fusarium head blight (FHB) is a destructive fungal disease of wheat (Triticum aestivum L.) that causes significant grain yield losses and end-use quality reduction associated with contamination by the mycotoxin deoxynivalenol (DON). Three winter wheat varieties ('Vulkan', 'Kraljica' and 'Golubica') were screened for FHB resistance using artificial inoculation technique under field conditions. The aim of this study was to examine a relationship between FHB resistance and the effectiveness of enzyme antioxidant system of wheat varieties under different sampling times (3, 15, 24, 48, 96, 120 and 336 hai). In the time-course experiments FHB-resistant variety 'Vulkan' showed rapid induction of ascorbate peroxidase (APX) and polyphenol oxidase (PPO) activity in the early stages after infection (3 hai) and it seems that in 'Vulkan' FHB-resistance is associated with antioxidative enzymes activity. Moderately FHB resistant variety 'Kraljica' showed the higher guaiacol peroxidase (POD) activity and higher H2O2 content after 24 hai, increased malondialdehyde (MDA) content at the beginning of infection (3, 15 hai) while induction of catalase (CAT), APX and PPO was delayed. FHB-susceptible variety 'Golubica' involved antioxidant enzymes in defense response much later. Based on our results the activity of antioxidant enzymes (APX and PPO) was more pronounced in 'Vulkan' than in FHB-medium resistant variety 'Kraljica' and FHB-susceptible 'Golubica'. The differences in antioxidant response of wheat varieties under Fusarium infestation could be the result of genetic properties.


Multimodal cocktail analgesic injection in PIVD with lower limb radiculopathy - A mixed design cohart study.
The role of Sodium Channel Blocker and steroid is well established for pain relief in neuropathic pain by reducing inflamation and desensitization of nerve roots. Our study aims at analyzing the effectiveness of multimodal cocktail injections for redicular pain relief & functional outcome in patients with intervertebral disc herniation. This was a Mixed design (prospective & retrospective) cohort study; we included 113 patients between the age group of 18-70 years, diagnosed with Prolapse of intervertebral disc (PIVD) with lower limb radiculopathy with MRI finding L4-L5/L5-S1 vertebral disc involvement. Patients were injected with total 15 ml of cocktail injection in 3 divided doses at 3 identified sites in affected lower limb. . Patient was examined & evaluated clinically for VAS pain score, SLRT, Sensory, Motor Examination on day 2, day 7, day 15 & after 1 month. We found that the mean pre-VAS score was 7.83 followed by the mean VAS score on post 2 days was 1.05, post 7 days was 3.47, post 15 days was 3.9 and post 30 days was 3.81. There was a statistically significant difference in the mean VAS score (p-value<0.0001). After one month majority of patients (54.62%) had comfortable painless walk and comfortable walking distance increased up to 1 km in 45.37% of them. Use of cocktail multimodal injections for radiculopathy pain suggests that this non-operative,OPD based technique could be reasonable, efficient, and safe.


Marginal structural models for the estimation of the risk of Diabetes Mellitus in the presence of elevated depressive symptoms and antidepressant medication use in the Women's Health Initiative observational and clinical trial cohorts.
We evaluate the combined effect of the presence of elevated depressive symptoms and antidepressant medication use with respect to risk of type 2 diabetes among approximately 120,000 women enrolled in the Women's Health Initiative (WHI), and compare several different statistical models appropriate for causal inference in non-randomized settings. Data were analyzed for 52,326 women in the Women's Health Initiative Clinical Trials (CT) Cohort and 68,169 women in the Observational Study (OS) Cohort after exclusions. We included follow-up to 2005, resulting in a median duration of 7.6 years of follow up after enrollment. Results from three multivariable Cox models were compared to those from marginal structural models that included time varying measures of antidepressant medication use, presence of elevated depressive symptoms and BMI, while adjusting for potential confounders including age, ethnicity, education, minutes of recreational physical activity per week, total energy intake, hormone therapy use, family history of diabetes and smoking status. Our results are consistent with previous studies examining the relationship of antidepressant medication use and risk of type 2 diabetes. All models showed a significant increase in diabetes risk for those taking antidepressants. The Cox Proportional Hazards models using baseline covariates showed the lowest increase in risk , with hazard ratios of 1.19 (95 % CI 1.06 - 1.35) and 1.14 (95 % CI 1.01 - 1.30) in the OS and CT, respectively. Hazard ratios from marginal structural models comparing antidepressant users to non-users were 1.35 (95 % CI 1.21 - 1.51) and 1.27 (95 % CI 1.13 - 1.43) in the WHI OS and CT, respectively - however, differences among estimates from traditional Cox models and marginal structural models were not statistically significant in both cohorts. One explanation suggests that time-dependent confounding was not a substantial factor in these data, however other explanations exist. Unadjusted Cox Proportional Hazards models showed that women with elevated depressive symptoms had a significant increase in diabetes risk that remained after adjustment for confounders. However, this association missed the threshold for statistical significance in propensity score adjusted and marginal structural models. Results from the multiple approaches provide further evidence of an increase in risk of type 2 diabetes for those on antidepressants.


Selective potentiating effect of beta-p-chlorophenylglutamate on responses induced by certain sulphur-containing excitatory amino acids and quisqualate.
In dorsal horn neurones of the cat spinal cord iontophoretically administered (+/-)-beta-p-chlorophenylglutamate (chlorpheg) markedly enhanced the excitatory responses induced by L-homocysteate, L-homocysteine sulphinate, S-sulpho L-cysteine, L-cysteate and quisqualate, while responses to NMDA, kainate, L-glutamate, L-aspartate and L-cysteine sulphinate were generally unaffected. Preliminary data obtained on frog spinal cord in vitro supports the possibility that such selective potentiation may be due to differential inhibition by chlorpheg of amino acid uptake. No potentiating effects of chlorpheg were observed on spinal synaptic excitation.


Familiarity Trends of Successful Urology Residency Match Applicants.
We sought to determine if training program "familiarity" played a role in the successful match of urological surgery residents. We analyzed information from successful urology match participants in the United States between 2015 and 2020. Data were collected from the Association of American Medical Colleges applications, UrologyMatch.com and SurveyMonkey®. Information recorded included each candidate's name, hometown, undergraduate institution, graduate or research program (if applicable), medical school, location of visiting subinternships in urological surgery and urology residency training program. Overall, 1,080 of 1,451 successful urology match candidates (74.4%) met 1 or more "familiarity" criteria. Specifically, 329 (22.7%) and 508 (35.0%) students successfully matched into their home and visiting urology training programs, respectively. Of the remaining applicants 153 (10.5%) and 90 (6.2%) matched into training programs <150 miles from their hometowns and within institutions of previous academic pursuits, respectively. South Central section programs were most likely to match students into their home programs (p=0.010). Visiting students were most and least likely to match at programs from Western (p=0.044) and Northeastern (p=0.001) sections, respectively. The New York section matched more candidates from hometowns within 150 miles compared to other sections of the American Urological Association (p=0.0003). Student and program "familiarity" may play a role in residency match success. Our study demonstrated nearly 75% of urology applicants matched into either their home institutions, visiting subinternship programs, sites of previous undergraduate/graduate studies or training programs <150 miles from their hometowns.


The role of endogenous opioid peptides in the antinociceptive effect of 15-deoxy(Δ12,14)-prostaglandin J2 in the temporomandibular joint.
We have previously demonstrated that peripheral administration of 15d-PGJ2 in the Temporomandibular joint (TMJ) of rats can prevent nociceptor sensitization, mediated by peroxisome proliferator activated receptor-γ (PPAR-γ), and κ- and δ- opioid receptors. However, the mechanism that underlies the signaling of PPAR-γ (upon activation by 15d-PGJ2) to induce antinociception, and how the opioid receptors are activated via 15d-PGJ2 are not fully understood. This study demonstrates that peripheral antinociceptive effect of 15d-PGJ2 is mediated by PPAR-γ expressed in the inflammatory cells of TMJ tissues. Once activated by 15d-PGJ2, PPAR-γ induces the release of β-endorphin and dynorphin, which activates κ- and δ-opioid receptors in primary sensory neurons to induce the antinociceptive effect.


[Determination of the necessary time for prevention of thromboembolism using heparin/dihydroergotamine during implantation of partial hip joint endoprostheses].
The paper presents investigation of efficiency of thromboembolic prophylaxis heparin/dihydroergotamine in patients with femur cervix fracture undergoing standard operational treatment with insertion of partial femur endoprosthesis. Various thrombo-prophylaxis durations have been considered, after the patients have been divided into a control group (without thrombo-prophylaxis) and the group of patients which were subjected to thrombo-prophylaxis for period of up to one week and two, three and four weeks. The investigations have encompassed a rather large group of 162 patients operatively treated within a 12 year period (1974-85) at Orthopaedic Clinic in Biograd o/s. Based on the analysis of general characteristics of standard cases, where thrombo-prophylaxis duration has been examined by statistical methods applied to observed material, and on the basis of comparison with previously published experiences, optimum duration of thromboembolic prophylaxis is proposed.


Demographic and clinical characteristics of human bocavirus-1 infection in patients with acute respiratory tract infections during the COVID-19 pandemic in the Central Province of Sri Lanka.
Human bocavirus-1 (hBoV-1) was first detected in respiratory specimens in 2005. Due to high co-infection rates and prolonged shedding of the virus, the pathogenic role of hBoV-1 as a primary causative agent of respiratory infections is still under discussion. This study aimed to determine the prevalence of hBoV-1 infection in patients with acute respiratory tract infections (ARTIs) during the COVID-19 pandemic in the Central Province of Sri Lanka. A total of 1021 patients (Age 12 days to ≤ 85 years) with ARTI symptoms including fever, cough, cold, sore throat and shortness of breath within first 7 days of the illness were included. The study was carried out at the National Hospital, Kandy, Sri Lanka from January 2021 to October 2022. Respiratory specimens were tested to detect 23 pathogens including hBoV-1 using a real time PCR. Prevalence of hBoV-1 co-infections with other respiratory pathogens and distribution of hBoV-1 infection among different age groups were determined. Moreover, clinical and demographic characteristics of hBoV-1 mono-infection associated ARTI were compared with that of the hBoV-1 co-infections. Respiratory infections were detected in 51.5% (526/1021) of the patients and of these 82.5% were mono- and 17.1% were co-infections. hBoV-1 was detected in 66 patients and this was the most prevalent respiratory virus associated with 40% co-infections. Of the 66 hBoV-1 positive patients, 36 had co-infections and of these 33 had dual and 3 had triple infections. Most of the hBoV-1 co-infections were identified in children aged 2-<5 years. hBoV-1 co-infections were most frequently detected with respiratory syncytial virus (RSV) and Rhino/ Entero viruses (Rh/EnV). No differences were observed in age, gender and clinical presentations in those with hBoV-1 mono- compared to co-infections. Intensive care admissions were less among hBoV-1 mono-infected than hBoV-1 co-infected patients. This study shows a prevalence of 12.5% for hBoV-1 infections in patients with ARTI. RSV and Rh/EnV were the most common co-infecting pathogens with hBoV-1. Clinical features of hBoV-1 mono-infections were not different to that of the hBoV-1 co-infections. Interactions between hBoV-1 and other respiratory pathogens need investigation to identify the role of hBoV-1 in clinical severity of co-infections.


Autofluorescence prediction model for fluorescence unmixing and age determination.
Flow cytometry is a powerful tool for identifying and quantifying various cell markers, such as viability, vitality, and individual cell age, at single-cell stages. However, cell autofluorescence and marker fluorophore signals overlap at low fluorescence intensities. Thus, these signals must be unmixed before determining the age fraction. A comparison was made between principal component regression (PCR) and random forest (RF) to predict autofluorescence signals of Saccharomyces pastorianus var. carlsbergensis in a flow cytometer. RF provided better prediction results than the PCR and was therefore determined to be better suited for unmixing signals. In the subsequent application for unmixing the autofluorescence signal from the marker fluorophore signal, the Gaussian mixture analysis based on RF was in better agreement with the microscopy-determined replicative age distribution than the PCR-based method. The proposed approach of single-laser spectral unmixing and subsequent Gaussian mixture analysis showed that the microscopy data was consistent with the unmixed fluorescence spectra. The demonstrated approach enables fast and reliable unmixing of flow cytometric spectral data using a single-laser spectral unmixing method. This analysis method enables age determination of cells in industrial processes. This age determination allows for quantifying the yeast cell's age fractions, providing a detailed view of age-related changes. Additionally, the bud scar labeling technique can be used to determine age-related changes in Pichia pastoris yeast for biotechnological applications or recombinant protein expression.


Mutations of microsatellite autosomal loci in paternity investigations of the Southern Poland population.
In this study, germline mutations were analyzed for 26,040 parent-child allelic transfers among subjects referred to paternity testing and originating from the Slavonic population of the Southern Poland. Mutation rates were estimated for 15 autosomal microsatellite loci: D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA. There were 35 mutation events observed at 11 from 15 analyzed loci. No mutations were found at TH01, D2S1338, D19S433 and TPOX loci. The mutation rate estimate was 0.0019 [0.0012-0.0028 95% CI] for paternal and 0.0004 [0.0002-0.0009] for maternal meiosis, while 25% mutations remained unassigned. The locus-specific mutation rate ranged from 0.0000 [0.0000-0.0014] to 0.0046 [0.0022-0.0087]. Mutations observed in male germlines were more frequent than in female germlines.


Mechanisms of transmembrane signalling in human T cell activation.
Several monoclonal antibodies directed against a number of T cell surface molecules are used to elucidate the role of these molecules (cell surface molecules) in T cell activation. The activation of T cells via these molecules are both antigen-dependent (CD3/TcR complex) and antigen-independent. Irrespective of their antigen dependency, these monoclonal antibodies activate T cells by a classical signal transduction pathway, in which the binding of monoclonal antibodies to their cell surface receptors leads to activation of phospholipase C resulting in the depolarization of plasma membrane, hydrolysis of IP2 and IP3 and DAG, the 'second messengers'. IP3 leads to mobilization of intracellular calcium to contribute to an increase in [Ca++]i, whereas DAG causes activation and translocation of PKC and an increasing apparent affinity for Ca++. The role of IP4 in the mobilization of intracellular calcium is emerging. In addition, influx of extracellular calcium also contributes to increase in [Ca++]i. The increase in [Ca++]i following activation via some T cell surface antigen is predominantly due to intracellular mobilization of Ca++ (e.g. CD3/TcR complex), whereas activation via other T cell surface antigen, the increase in [Ca++]i is almost entirely due to an influx of extracellular calcium (e.g. CD5 antigen). All these molecules activate autocrine system of T cell growth, namely IL-2 production, IL-2 receptor expression and T cell proliferation.


Imaging of colon carcinoma with 111-indium-labeled anti-CEA monoclonal antibodies (Indacea) prior to surgery.
Patients with primary and/or metastatic colorectal cancer who had been scheduled for operative intervention were injected intravenously with 200 micrograms of a high-affinity anti-carcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111-indium (Indacea). Patients were imaged by gamma camera at 24 and 48 hours. Primary tumors were identified in 3/10 cases and were not visualized in 3/10 cases. Four scans were considered equivocal. Hepatic metastases were identified as image defects in 5/13 cases and were not visualized in 8/13 cases. All tumors contained CEA by immunoperoxidase staining. In all cases, the primary tumor uptake (5.44 +/- 1.07% ID/kg) was much higher than the uptake of the adjacent fat (0.18 +/- 0.04% ID/kg). There was a direct correlation between tumor CEA content, tumor radioactivity, and the imaging of primary tumor by Indacea. High liver uptake (30.3 +/- 3.0% ID/kg), seen when scanning all patients, was the main limitation of imaging and led to photopenic visualization of hepatic metastases. These results suggest that selection of patients with colorectal carcinoma on the basis of tumor CEA content will lead to improved rates of tumor imaging by Indacea in post-surgical scanning.


Preparation of cationic cotton through reaction with different polyelectrolytes.
Cationization of cotton fabrics was performed by exhaustion procedure utilizing four different reagents provided with quaternary ammonium groups: poly diallyldimethylammonium chloride (PDDACl), poly acrylamide-co-diallyldimethylammonium chloride (PAcD), poly[bis(2-chloroethyl) ether-alt-1,3-bis[3-(dimethylamino)propyl]urea] quaternized (P42) and 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHPTAC). Pretreated samples were dyed using Reactive Red 195 dye. The cationic fabrics were analyzed by colorimetric and fastness properties, zeta potential, SEM, FTIR and an estimate of the bactericidal effect. Cationic cotton treated with PDDACl and CHPTAC showed a higher affinity for the reactive dye, with color strength (K/S) values varying from 41 to 48, against 32 for conventional dyeing. P42 presented competitive results with K/S of 27-28. The cationic dyeing considerably reduced the amount of effluent, especially for the CHPTAC samples, which requires a single washing bath for complete removal of unfixed dye. The PDDACl and P42 samples presented bactericidal activity. The online version contains supplementary material available at 10.1007/s10570-021-04260-4.