The Schistosoma mansoni protein Sm16/SmSLP/SmSPO-1 is a membrane-binding protein that lacks the proposed microtubule-regulatory activity.
Sm16/SmSLP/SPO-1 (Sm16) has been identified as a developmentally regulated protein that is released from specific glands of the Schistosoma mansoni parasite during skin penetration. Sm16 has been ascribed both anti-inflammatory activities and a functional similarity with the conserved cytosolic tubulin-binding protein stathmin/Op18. Here we used a cell line to confirm signal peptide-dependent secretion and to define the secreted form of Sm16 for production in E. coli. We present evidence from both in vitro experiments and studies on transfected human cells that refute any functional similarity with stathmin/Op18. Instead of an Op18-like activity, we found that targeting of Sm16 to the cytosol of human cells, which was achieved by ectopic expression of Sm16 lacking the signal peptide, results in a caspase-dependent apoptotic response. Interestingly, by analysis of recombinant preparations we found that the secreted form of Sm16 is a lipid bilayer-binding protein that efficiently binds to the surface of diverse cell types by a polyanion-independent mechanism, which results in uptake by endocytosis. While the significance of the pro-apoptotic activity exerted by cytosolic Sm16 remains unclear, the present findings on cell-surface-binding properties of Sm16 seems likely to be of functional relevance during skin penetration of the parasite.


A novel role of the chromokinesin Kif4A in DNA damage response.
Chromokinesins are microtubule-motor molecules that possess chromatin binding activity and are important for mitotic and meiotic regulation. The chromokinesin-member Kif4A is unique in that it localizes to nucleus during interphase of the cell cycle. Kif4 deletion by gene targeting in mouse embryonic cells was known to associate with DNA damage response. However, its precise role in DNA damage or repair pathway is not clear. Here we report that Kif4A associates with BRCA2 in a biochemical identification and that the interaction is mediated by the Kif4A C-terminal cargo-binding domain and BRCA2 C-terminal conserved region. Upon nucleus-specific laser micro-irradiation, Kif4A was rapidly recruited to sites of DNA damage. Significantly, the depletion of Kif4A from cells by shRNA impaired the ionizing-radiation induced foci (IRIF) formation of Rad51, both quantitatively and qualitatively. In contrast, the IRIF of gamma-H2AX or NBS1 was largely intact. Moreover, Kif4A knockdown rendered cells hypersensitive to ionizing radiation in a colonogenic survival assay. We further demonstrated that Kif4A deficiency led to significantly decreased homologous recombination in an I-SceI endonuclease induced in vivo recombination assay. Together, our results suggest a novel role for a chromokinesin family member in the DNA damage response by modulating the BRCA2/Rad51 pathway.


Interfacial ordering of thermotropic liquid crystals triggered by the secondary structures of oligopeptides.
We report that assemblies formed by eight oligopeptides at phospholipid-decorated interfaces of thermotropic liquid crystals (LCs) trigger changes in ordering of the LCs that are dependent on the secondary structures of the oligopeptides (as characterized in situ using infrared-visible sum-frequency spectroscopy).


Gonadotrophin stimulation of donor females decreases post-implantation viability of cultured one-cell hamster embryos.
Hamster one-cell embryos were collected from two groups of donors: females that were super-stimulated with pregnant mare's serum gonadotrophin (PMSG) and females that were not. Embryos were cultured for 72 h and scored for development. Morulae and blastocysts from the PMSG- and non-stimulated females were transferred into contralateral uterine horns of non-stimulated recipient females, so that experimental embryos (from PMSG-stimulated females) and control embryos (from non-stimulated females) were paired within a single recipient. Right and left uterine horns of recipient females were examined 11 days later for the number of implantation sites and fetuses. After 72 h of culture, development to morulae and blastocysts was not significantly different for embryos from PMSG- and non-stimulated females. However, embryos from PMSG-stimulated females compared to controls had significantly reduced mean cell numbers (18 versus 21; P=0.003) and a two-fold decrease in viability post-transfer (20 versus 45%; P=0.02). These findings indicate that gonadotrophin stimulation compromises subsequent developmental competence either during oocyte maturation or in the very early embryo, but it is unclear whether reduced viability is a direct effect or is an indirect consequence of PMSG stimulation.


Associations of polymorphisms in the apolipoprotein APOA1-C3-A5 gene cluster with acute coronary syndrome.
Acute coronary syndromes (ACSs) are clinically cardiovascular events associated with dyslipidemia in common. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A5 gene cluster are associated with diabetes and familial combined hyperlipidaemia (FCH). Little is known about whether the polymorphisms in these genes affect lipid homeostasis in patients with ACSs. The present paper aimed to examine these associations with 4 SNPs in the APOA1 -75G > A, the APOC3 -455T > C, and APOA5 -1131T > C, c.553G > T variant to ACSs in Chinese Han. Chinese Han of 229 patients with ACSs and 254 unrelated controls were analyzed. Four SNPs in APOA1/C3/A5 cluster were genotyped and lipid was determined. Our data show that minor allelic frequencies of APOC3 -455T > C, APOA5 -1131T > C, and c.553G > T polymorphisms in patients with ACSs were significantly higher than control group (P < 0.05). Furthermore, the 3 polymorphic sites were strongly of linkage disequilibrium, and minor alleles of 3 SNP sites had higher TG level than wild alleles (P < 0.05), APOC3 -455C and APOA5 c.553T allele carriers also had lower level of HDL-C. The minor alleles of APOC3 -455T > C, APOA5 -1131T > C, and c.553G > T polymorphisms are closely associated with ACSs.


The number of discernible colors in natural scenes.
The number of colors discernible by normal trichromats has been estimated for the idealized object-color solid. How well these estimates apply to natural scenes is an open question, as it is unknown how much their colors approach the theoretical limits. The aim of this work was to estimate the number of discernible colors based on a database of hyperspectral images of 50 natural scenes. The color volume of each scene was computed in the CIELAB color space and was analyzed using the CIEDE2000 color-difference formula. It was found that the color volume of the set of natural scenes was about 30% of the theoretical maximum for the full object-color solid, and it corresponded to a number of about 2.3 million discernible colors. Moreover, when the lightness dimension was ignored, only about 26,000 (1%) could be perceived as different colors. These results suggest that natural stimuli may be more constrained than expected from the analysis of the theoretical limits.


Efficacy and Safety of Clazosentan After Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis.
Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH. Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment. Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76). Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.


Enhancement of short coherence digital holographic microscopy by optical clearing.
In this work, we used a short coherence digital holographic microscopy system to demonstrate cross-talk noise suppression and imaging performance enhancement by optical clearing. Performance of the system on both phantom and in vitro porcine skin tissues before and after the treatment of 70% v./v. glycerol-saline solution was investigated. Our results showed that optical clearing effectively inhibits the cross-talk noise and improves the image quality in the deep of the in vitro porcine skin tissues. The imaging depth was increased by about 30% after topical application of the glycerol-saline solution for 30 min.


Logical empiricists on race.
The logical empiricists expressed a consistent attitude to racial categorisation in both the ethical and scientific spheres. Their attitude may be captured in the following slogan: human racial taxonomy is an empirically meaningful mode of classifying persons that we should refrain from deploying. I offer an interpretation of their position that would render coherent their remarks on race with positions they adopted on the scientific status of taxonomy in general, together with their potential moral or political motivations for adopting that position.


A CASE OF ADENOCARCINOMA OF THE EPIDIDYMIS WITH HYDROCELE.
A 72-year-old man presented with left scrotal swelling. The patient was diagnosed with left testicular hydrocele and underwent the hydrocele aspiration. However, it recurred within a short period. Magnetic resonance imaging (MRI) revealed a tumor in the epididymis and the patient then underwent left high orchiectomy. The histopathological examination revealed an adenocarcinoma of the epididymis. Ten months after the surgery, the patient has been free of disease.


[IMMUNE RESPONSE IN CHRONIC BRONCHIOLITIS OBLITERANS IN CHILDREN].
The qaim of the research was to evaluate a condition of cellular and humoral immunity in 139 children with bronchiolitis obliterans in age from 2 years to 14 years of life. There was a minor immunosuppression during exacerbation followed by normalization in remission. There was a slight decrease in the level of IgA, an increased concentration of İgM and high value of the circulating immune complexes during the exacerbation with normalization as acute inflammation subsided. An analysis of interleukin dynamics revealed a significant increase in the concentration of pro- and anti-inflammatory cytokines in the acute stage of the disease with a tendency to normalization in remission. Thus, there is no place marked immunosuppression. Analyzed changes are adequate and are a response to viral and bacterial infection.


Scoping the role and education needs of practice nurses in London.
Aims To identify education priorities for practice nursing across eight London Clinical Commissioning Groups (CCGs); to identify the education, training, development and support needs of practice nurses in undertaking current and future roles. The education needs of practice nurses have long been recognised but their employment status means that accessing education requires the support of their GP employer. This study scopes the educational requirements of the practice nurse workforce and working with educational providers and commissioners describes a coherent educational pathway for practice nurses. A survey of practice nurses to scope their educational attainment needs was undertaken. Focus groups were carried out which identified the education, training, development and support needs of practice nurses to fulfil current and future roles. Findings A total of 272 respondents completed the survey. Practice nurses took part in three focus groups (n=34) and one workshop (n=39). Findings from this research indicate a practice nurse workforce which lacked career progression, role autonomy or a coherent educational framework. Practice nurses recognised the strength of their role in building relationship-centred care with patients over an extended period of time. They valued this aspect of their role and would welcome opportunities to develop this to benefit patients. This paper demonstrates an appetite for more advanced education among practice nurses, a leadership role by the CCGs in working across the whole system to address the education needs of practice nurses, and a willingness on the part of National Health Service education commissioners to commission education which meets the education needs of the practice nurse workforce. Evidence is still required, however, to inform the scope of the practice nurse role within an integrated system of care and to identify the impact of practice nursing on improving health outcomes and care of local populations.


Discerning the Primary Carcinoma in Malignant Peritoneal and Pleural Effusions Using Imaging Mass Spectrometry-A Feasibility Study.
Malignant effusions challenge diagnostic accuracy due to cytomorphologic overlaps between various malignant primaries. Workup of this material to establish a correct diagnosis is time consuming and limited by the sparsity of material. In order to circumvent these drawbacks, the use of MALDI imaging MS (IMS) as a diagnostic platform has been explored. Cytology cell blocks from malignant effusions (serous ovarian carcinoma and several non-ovarian carcinomas including gastric adenocarcinoma) containing at least 30% neoplastic cells are selected for generation of cytology microarrays (CMA). CMA sections are transferred to conductive glass slides, subjected to on-tissue tryptic digestion, and matrix application for MALDI-IMS analysis. Supervised classification analysis identifies serous ovarian carcinomas as the source of malignant effusions with a sensitivity of 85.7% when compared to samples from all other included primary sites. When compared to gastric adenocarcinoma, serous ovarian carcinoma samples can be delineated with a sensitivity of 97.3%. These preliminary results highlight that MALDI-IMS allows subtyping of malignant effusions to identify the precise origin of neoplastic cells. While achieving similar results compared to classical approaches such as immunocytology, more material is conserved that will be available for further tests.


Increased risk for thionamide-induced agranulocytosis in elderly patients: a case presentation and literature review.
Thionamides, such as methimazole and propylthiouracil, are used for the management of hyperthyroidism. Agranulocytosis is a rare adverse effect of thionamides and elderly patients are especially vulnerable. Here we discuss a case of an 80-year-old woman who developed agranulocytosis and pneumonia approximately 4 weeks after starting low dose methimazole therapy. Despite aggressive treatment with broad-spectrum antibiotics and granulocyte colony stimulating factor, she developed multiorgan failure and died. Our goals are to identify risk factors common to elderly patients and hopefully improve outcomes in this population when prescribed thionamides.


Gamma-glutamyl transpeptidase in leprosy.
Activity of the enzyme-gamma-glutamyl transpeptidase (GGTP) was measured in sera of 20 patients each of paucibacillary and multibacillary leprosy and 20 healthy controls. None of the subjects had any systemic or hepatic disease and none had taken any hepatotoxic or antileprotic drugs in the past 3 months. Mean values in the paucibacillary group (38.62 +/- 1.99 U/L) and in the multibacillary group (59.04 +/- 3.13 U/L) were significantly higher compared to that in controls (32.04 +/- 0.66 U/L). Mean value in the multibacillary group was also significantly higher compared to that in the paucibacillary group.


ICAM-1 has a critical role in the regulation of metastatic melanoma tumor susceptibility to CTL lysis by interfering with PI3K/AKT pathway.
Human primary melanoma cells (T1) were found to be more susceptible to lysis by a Melan-A/MART-1-specific CTL clone (LT12) than their metastatic derivative (G1). We show that this differential susceptibility does not involve antigen presentation by target cells, synapse formation between the metastatic target and CTL clone, or subsequent granzyme B (GrB) polarization. Although PI-9, an inhibitor of GrB, was found to be overexpressed in metastatic G1 cells, knockdown of the PI-9 gene did not result in the attenuation of G1 resistance to CTL-induced killing. Interestingly, we show that whereas T1 cells express high levels of intercellular adhesion molecule-1 (ICAM-1), a dramatically reduced expression was noted on G1 cells. We also showed that sorted ICAM-1+ G1 cells were highly sensitive to CTL-induced lysis compared with ICAM-1- G1 cells. Furthermore, incubation of metastatic G1 cells with IFN-gamma resulted in the induction of ICAM-1 and the potentiation of their susceptibility to lysis by LT12. More importantly, we found that the level of ICAM-1 expression by melanoma cells correlated with decreased PTEN activity. ICAM-1 knockdown in T1 cells resulted in increased phosphorylation of PTEN and the subsequent activation of AKT. We have additionally shown that inhibition of the phosphatidylinositol (3,4,5)-triphosphate kinase (PI3K)/AKT pathway by the specific inhibitor wortmannin induced a significant potentiation of susceptibility of G1 and ICAM-1 small interfering RNA-treated T1 cells to CTL-induced lysis. The present study shows that a shift in ICAM-1 expression, which was associated with an activation of the PI3K/AKT pathway, can be used by metastatic melanoma cells to escape CTL-mediated killing.


Informed consent in clinical research: policies and practices in Singapore.
The policies and practices for obtaining informed consent from research subjects in clinical research play a vital role in determining a nation's success as a center for clinical research. The difficulty lies in the fact that while on the one hand, informed consent is a necessary pre-condition for ethical clinical research, a scrupulous observance of the guidelines for informed consent could, on the other hand, cripple medical research. Crippling of ethical medical research can be adverse to public interest, and consequently, unethical. Hence, a fine balance must be struck in the application of the guidelines for obtaining informed consent. This, in turn, would depend on the constitution and skill of research ethics committees who are appointed to consider and approve clinical research proposals. The discussion below addresses the above difficulty with recommendations that could further enhance Singapore's image as a regional clinical trial hub.


Sleep and the menstrual cycle.
To evaluate changes in sleep across the phases of the menstrual cycle, sleep-wake diaries were completed by 32 healthy women twice daily for 2 menstrual cycles. There was a significant increase in sleep onset latency and a significant decrease in sleep efficiency and sleep quality during the luteal phase. This increase in sleep disturbance was observed in the entire sample and was not related to the severity of other premenstrual symptoms. However, women having increased severity of other premenstrual symptoms reported greater luteal increase in daytime sleepiness. Thus, although menstruating women are likely to show increased sleep disturbance during the luteal phase, those with other, more severe premenstrual symptoms are more likely to experience a luteal increase in daytime sleepiness.


RCPedia: a database of retrocopied genes.
Retrocopies are copies of mature RNAs that are usually devoid of regulatory sequences and introns. They have routinely been classified as processed pseudo-genes with little or no biological relevance. However, recent findings have revealed functional roles for retrocopies, as well as their high frequency in some organisms, such as primates. Despite their increasing importance, there is no user-friendly and publicly available resource for the study of retrocopies. Here, we present RCPedia, an integrative and user-friendly database designed for the study of retrocopied genes. RCPedia contains a complete catalogue of the retrocopies that are known to be present in human and five other primate genomes, their genomic context, inter-species conservation and gene expression data. RCPedia also offers a streamlined data representation and an efficient query system. RCPedia is available at http://www.bioinfo.mochsl.org.br/rcpedia.


Effects of pituitary adenylate cyclase activating polypeptide on small intestinal INT 407 cells.
Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide having a widespread distribution both in the nervous system and peripheral organs including the gastrointestinal tract. It has been shown to exert actions on intestinal functions, mainly affecting glandular secretion and motility. PACAP has several different effects on cell survival depending on the cell type and the applied stimulus. Its influences on small intestinal epithelial cells are not yet elucidated, therefore the aim of the present study was to investigate the effects of PACAP on intestinal epithelial cells having high turnover (INT 407) against different harmful stimuli, such as oxidative stress, in vitro hypoxia and gamma radiation. We tested the effect of PACAP on proliferation and cell survival using MTT assay. Moreover, various cancer-related factors were evaluated by oncology array. PACAP did not influence the proliferation rate of INT 407 cells. Its cell survival-enhancing effect could be detected against oxidative stress, but not against in vitro hypoxia or gamma irradiation. Clonogenic survival assay was performed to analyze the effect of PACAP on clonogenic potential of cells exposed to gamma radiation. Surprisingly, PACAP enhanced the clone-forming ability decrease induced by irradiation. Western blot analysis of ERK1/2 phosphorylation was performed in order to obtain further information on the molecular background. Our data showed phospho-ERK1/2 suppression of PACAP in irradiated cells. Furthermore, the role of endogenous PACAP against oxidative stress was also investigated performing ADCYAP1 small interfering RNA transfection. We found significant difference in the cell vulnerability between cells undergoing silencing and cells without transfection suggesting the protective role of the endogenously present PACAP against oxidative stress in INT 407 cells. In summary, PACAP seems to be able to exert contradictory effects in INT 407 cells depending on the applied stressor, suggesting its regulatory role in the cellular household.


A conceptual framework of bonding.
Nurses involved in maternal-infant child care should objectively analyze any tools that purport to measure attachment and/or bonding. Has the author adequately defined the terms? Are directions given for making concepts operational for the practicing nurse? What are the foundations for placing values on parental behaviors? Do deviant parental behaviors reflect poor attachment or bonding, or are such behaviors merely indicative of limited parental opportunities for acquaintance? The presentation of of any conceptual framework should not be considered complete without empirical testing. Such testing and peer critique of a framework are essential fro any theory of bonding to evolve. With further research into the parental-child relationship, nurses can learn to provide adequate care for facilitating the bonding process in families.


Severe vitamin D deficiency affects the expression of autophagy related genes in PBMCs and T-cell subsets in active systemic lupus erythematosus.
We aimed to investigate whether vitamin D levels affect the expression of autophagy related genes (Atgs) and the counts of T-cell subsets in active systemic lupus erythematosus (SLE), as well as to assess the association between Atgs and T-cell subsets. Serum levels of 25(OH)D3, Atgs and T-cell subsets were measured in 50 patients with active SLE. Serum 25(OH)D3 levels <10 ng/ml and 10-30 ng/ml were defined as severe vitamin D deficiency and vitamin D insufficiency, respectively. Comparisons were made between values of severe vitamin D deficiency and vitamin D insufficiency patients, and the correlations between Atgs in PBMCs and T-cell subsets were carried out. mTOR mRNA levels were higher (P=0.036) and LC3 mRNA levels were lower (P<0.001) in severe vitamin D deficiency group compared to vitamin D insufficiency group. The counts of CD4+ T cells and the CD4/CD8 ratio were significantly higher in severe vitamin D deficiency group compared to vitamin D insufficiency group (P=0.001, P<0.001,respectively). LC3 mRNA levels correlated negatively with CD4+ T cells counts (r=-0.302, P=0.033), while correlated positively with CD8+ T cells counts (r=0.299, P=0.035). Serum 25(OH)D3 levels correlated negatively with the counts of CD4+ T cells (r=-0.423, P=0.002) and correlated positively with the counts of CD8+ T cells (r=0.318, P=0.024). Our results suggested that severe vitamin D deficiency affected the expression of Atgs in PBMCs and T-cell subsets in active SLE, indicating that vitamin D may affect T-cell subsets via regulating autophagy.


Ocular response analyzer versus Goldmann applanation tonometry for intraocular pressure measurements.
To establish correlations between intraocular pressure (IOP) measurements obtained with the ocular response analyzer (ORA) and the Goldmann applanation tonometer (GAT). The effects of central corneal thickness on the measures obtained were also examined. This was a cross-sectional study. IOP was determined in 48 eyes of 48 patients with glaucoma In all patients, central corneal thickness (CCT) was measured by ultrasound pachymetry. ORA readings were consistently higher than GAT measurements (Goldmann-correlated IOP - IOP GAT mean difference, 7.2 +/- 3.5 mm Hg; corneal-compensated IOP - IOP GAT mean difference, 8.3 +/- 4.0 mm Hg) However, differences were not constant and increased with increasing IOP GAT readings, both with respect to Goldmann-correlated IOP (slope = 0.623, P < 0.0001) and corneal-compensated IOP (slope = 0.538, P < 0.0001). Both pressure measurements provided by the ORA showed significant correlation with CCT (CCT versus Goldmann-correlated IOP: r = 0.460, P = 0.001; CCT versus corneal-compensated IOP: r = 0.442, P = 0.001). No significant effects of corneal curvature or refraction on any of the pressures were observed. The ORA significantly overestimates IOP compared with the GAT. Differences between both sets of measures increase as the GAT-determined IOP increases. ORA readings seem to be affected by central corneal thickness.


Yolk-shell nanostructured Fe3O4@NiSiO3 for selective affinity and magnetic separation of His-tagged proteins.
Recent developments of nanotechnology encourage novel materials for facile separations and purifications of recombinant proteins, which are of great importance in disease diagnoses and treatments. We find that Fe3O4@NiSiO3 with yolk-shell nanostructure can be used to specifically purify histidine-tagged (His-tagged) proteins from mixtures of lysed cells with a recyclable process. Each individual nanoparticle composes by a mesoporous nickel silicate shell and a magnetic Fe3O4 core in the hollow inner, which is featured by its great loading efficiency and rapid response toward magnetic fields. The abundant Ni(2+) cations on the shell provide docking sites for selective coordination of histidine and the reversible release is induced by excess imidazole solution. Because of the Fe3O4 cores, the separation, concentration, and recycling of the nanocomposites become feasible under the controls of magnets. These characteristics would be highly beneficial in nanoparticle-based biomedical applications for targeted-drug delivery and biosensors.


Characterization of an isodicentric Y-chromosome for the long arm in a newborn with mixed gonadal dysgenesis.
A newborn infant was referred for evaluation because of ambiguous genitalia. Examination of the genitalia revealed a hypospadiac phallus measuring 1.5 cm in length with chordee. Subtle phenotypic features consistent with Turner syndrome were present including hypertelorism, anti-mongoloid slant to the eyes, mild widening of the neck, but no definitive webbing, shield like chest and positive cubitus valgus. A pelvic and renal sonogram confirmed the presence of a uterus and normal-appearing kidneys. There was incomplete fusion of the scrotum. No gonads were palpable within the scrotal sac. The patient was assigned a female gender on the basis of the presence of a uterus, the phenotypic appearance of the genitalia and the malignant potential of the gonads. The cytogenetic findings with QFQ-banding revealed an abnormal karyotype, i.e., mos 46,X,idic(Y) (p11.2)[77]/45,X[29]/46,X,idic(Y) (p11?) [2]/ 47,XY,idic(Y)(p11.2)[2]/47,X,idic(Y)(p11.2), + idic(Y)(p11.2)[1]/46,XY[1]. The presence of an abnormal isodicentric Y-chromosome was evaluated by FISH-technique to ensure a finer characterization than routine methods. The genotype-phenotype correlation could not be established since mosaicisms of highly variable nature can exhibit an unpredictable outcome.


Survey of academic pediatric hospitalist programs in the US: organizational, administrative, and financial factors.
Many pediatric academic centers have hospital medicine programs. Anecdotal data suggest that variability exists in program structure. To provide a description of the organizational, administrative, and financial structures of academic pediatric hospital medicine (PHM). This online survey focused on the organizational, administrative, and financial aspects of academic PHM programs, which were defined as hospitalist programs at US institutions associated with accredited pediatric residency program (n = 246) and identified using the Accreditation Council for Graduate Medical Education (ACGME) Fellowship and Residency Electronic Interactive Database. PHM directors and/or residency directors were targeted by both mail and the American Academy of Pediatrics Section on Hospital Medicine LISTSERV. The overall response rate was 48.8% (120/246). 81.7% (98/120) of hospitals reported having an academic PHM program, and 9.1% (2/22) of hospitals without a program reported plans to start a program in the next 3 years. Over a quarter of programs provide coverage at multiple sites. Variability was identified in many program factors, including hospitalist workload and in-house coverage provided. Respondents reported planning increased in-house hospitalist coverage coinciding with the 2011 ACGME work-hour restrictions. Few programs reported having revenues greater than expenses (26% single site, 4% multiple site). PHM programs exist in the majority of academic centers, and there appears to be variability in many program factors. This study provides the most comprehensive data on academic PHM programs and can be used for benchmarking as well as program development.


Pleural tuberculosis in patients infected with HIV in Addis Ababa.
To determine the prevalence of HIV-1 infection in patients with pleural tuberculosis and compare the clinical and radiological characteristics, effects and side effects of drugs, compliance to treatment and outcome by HIV status. A hospital based, prospective study. 90 adult patients with pleural tuberculosis. 120 surgical patients admitted for non-HIV related conditions served as controls. Black Lion Hospital, a tertiary care referral hospital in Addis Ababa, Ethiopia. 22% of the patients with pleural tuberculosis versus 6.7% for the controls (p < 0.01) were seropositive for HIV-1. Amongst patients with pleural tuberculosis, HIV seropositive patients were more likely to be male, and had longer duration of illness prior to coming to hospital (p < 0.05). They had more disseminated disease (p < 0.01), bilateral pleural effusion (p < 0.05), adverse reaction to anti-tuberculosis drugs (p < 0.05) and increased mortality (p < 0.05). Hepatitis was the most common side effect observed. There was no difference in size of the effusion, clinical improvement, radiographic resolution or defaulter rate. HIV associated pleural tuberculosis commonly occurs with other forms of extra pulmonary tuberculosis and responds well to treatment. Hepatitis is a frequent side effect and entails poor prognosis. We therefore recommend careful documentation of a previous history of liver disease and baseline investigation of liver function tests before initiation of treatment. The finding of bilateral pleural effusion may indicate the presence of underlying HIV infection.


A structure-function based approach to floc hierarchy and evidence for the non-fractal nature of natural sediment flocs.
Natural sediment flocs are fragile, highly irregular, loosely bound aggregates comprising minerogenic and organic material. They contribute a major component of suspended sediment load and are critical for the fate and flux of sediment, carbon and pollutants in aquatic environments. Understanding their behaviour is essential to the sustainable management of waterways, fisheries and marine industries. For several decades, modelling approaches have utilised fractal mathematics and observations of two dimensional (2D) floc size distributions to infer levels of aggregation and predict their behaviour. Whilst this is a computationally simple solution, it is highly unlikely to reflect the complexity of natural sediment flocs and current models predicting fine sediment hydrodynamics are not efficient. Here, we show how new observations of fragile floc structures in three dimensions (3D) demonstrate unequivocally that natural flocs are non-fractal. We propose that floc hierarchy is based on observations of 3D structure and function rather than 2D size distribution. In contrast to fractal theory, our data indicate that flocs possess characteristics of emergent systems including non-linearity and scale-dependent feedbacks. These concepts and new data to quantify floc structures offer the opportunity to explore new emergence-based floc frameworks which better represent natural floc behaviour and could advance our predictive capacity.


Few highly abundant operational taxonomic units dominate within rumen methanogenic archaeal species in New Zealand sheep and cattle.
Sequencing and analyses of 16S rRNA gene amplicons were performed to estimate the composition of the rumen methanogen community in 252 samples from eight cohorts of sheep and cattle, separated into 16 different sample groups by diet, and to determine which methanogens are most prominent in the rumens of farmed New Zealand ruminants. Methanobacteriales (relative abundance ± standard deviation, 89.6% ± 9.8%) and Methanomassiliicoccales (10.4% ± 9.8%) were the two major orders and contributed 99.98% (±0.1%) to the rumen methanogen communities in the samples. Sequences from Methanobacteriales were almost entirely from only four different species (or clades of very closely related species). Each was detectable in at least 89% of the samples. These four species or clades were the Methanobrevibacter gottschalkii clade and Methanobrevibacter ruminantium clade with a mean abundance of 42.4% (±19.5% standard deviation) and 32.9% (±18.8%), respectively, and Methanosphaera sp. ISO3-F5 (8.2% ± 6.7%) and Methanosphaera sp. group5 (5.6% ± 5.7%). These four species or clades appeared to be primarily represented by only one or, in one case, two dominant sequence types per species or clade when the sequences were grouped into operational taxonomic units (OTUs) at 99% sequence identity. The mean relative abundance of Methanomassiliicoccales in the samples was relatively low but exceeded 40% in some of the treatment groups. Animal feed affected the apparent methanogen community structure of both orders, as evident from differences in relative abundances of the major OTUs in animals under different feeding regimens.


Diagnosis and management of brain tumours at Jos University Teaching Hospital, Nigeria.
To report on the incidence of brain tumours in Jos Plateau of Nigeria and to highlight areas of interest regarding diagnosis, management and outcome. A retrospective study. Jos University Teaching Hospital (JUTH), Jos, Nigeria. Thirty patients with brain tumours. Specific management of primary lesions was carried out in cases of metastatic brain tumours. Steroids were administered in one case of cerebellar oligodendroma. Craniotomy and excision was achieved in two cases of meningioma and two of sarcoma. Palliative excision was employed in another two cases of meningioma. Two cases each of pituitary adenomas were managed by craniotomy and excision and trans-nasal transsphenoidal excision. Brain tumours ranked third in frequency relative to other tumours. The relative frequency of different histological types in percentages were: metastatic (30%), anterior pituitary (21%), meningeal (18%), neuroepithelial (15%) and nerve-sheath (6%). The mean age of presentation was 33 years. The three commonest clinical features in percentages included headaches (43%), cranial masses (39%) and visual defects (26%). Eighty three per cent of the total number of patients died within three weeks to one year irrespective of management modality employed. Two patients who had transnasal excision of pituitary tumours abroad are, however, well and alive at one and two years post-operation respectively. In this study, roentgenograms of the skull had a diagnostic value of 76% for tumours of meningeal origin and pituitary adenomas. CT scan is the mainstay for diagnosis of brain tumours. The outcome was poor with a mortality of 83%.


Clinical applications of therapeutic phlebotomy.
Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program.


Lipopolysaccharide-responsive beige-like anchor acts as a cAMP-dependent protein kinase anchoring protein in B cells.
Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) protein was initially described as a monogenetic cause for common variable immune deficiency, a syndrome characterized by low levels of B cells, defects in memory B cell differentiation and hypogammaglobulinaemia. LRBA was identified as an LPS up-regulated gene in B cells, macrophages and T cells. LRBA weighs 320 kDa and has 2863 amino acids. Its sequence contains multiple domains, suggesting that LRBA can act as a scaffolding protein. It contains two putative binding sites for cAMP-dependent kinase (PKA) regulatory subunits, suggesting this protein can act as A-kinase anchor protein (AKAP); however, physical interactions involving LRBA and PKA have not been demonstrated to date, and functional roles for such interactions are unexplored. In this work, we investigated physical interactions involving LRBA with regulatory subunits of PKA in human B cell lines and primary human B cells. PKA is a holoenzyme composed of two regulatory subunits, which can be RIα, RIβ, RIIα or RIIβ, and two catalytic subunits, Cα or Cβ. We co-immunoprecipitated LRBA using Ramos B cell lymphoma cells and observed that LRBA interacts with RIIβ. Interestingly, St-Ht31, an inhibitory peptide that disrupts AKAP interactions with regulatory subunits, reduced the amount of interacting protein. Furthermore, in primary human B cells, LRBA was induced after CD40L and IL-4 stimulation, and under such activation, we found that LRBA interacts with RIIα and RIIβ, suggesting that LRBA acts as an AKAP and binds RII subunits. Interestingly, we also identified that LRBA interacts with activation-induced cytidine deaminase in primary B cells, suggesting that it is involved in B cell function.


Dynamic Assembly of Small Parts in Vortex-Vortex Traps Established within a Rotating Fluid.
Stable, purely fluidic particle traps established by vortex flows induced within a rotating fluid are described. The traps can manipulate various types of small parts, dynamically assembling them into high-symmetry clusters, cages, interlocked architectures, jammed colloidal monoliths, or colloidal formations on gas bubbles. The strength and the shape of the trapping region can be controlled by the strengths of one or both vortices and/or by the system's global angular velocity. The system exhibits a range of interesting dynamical behaviors including a Hopf-bifurcation transition between equilibrium-point trapping and the so-called limit cycle in which the particles are confined to circular orbits. Theoretical considerations indicate that these vortex-vortex traps can be further miniaturized to manipulate objects with sizes down to ≈10 µm.


Administration of the metabotropic glutamate receptor subtype 5 allosteric modulator GET 73 with alcohol: A translational study in rats and humans.
Preclinical work suggests that GET 73 (N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide), a novel metabotropic glutamate receptor subtype 5 negative allosteric modulator, may represent a novel pharmacological treatment for alcohol use disorder. Two independent experiments evaluated the effect of acutely administered GET 73 (0, 30, and 100 mg/kg, intragastrically) on alcohol-induced hypolocomotion ( n=72) and sedation/hypnosis ( n=36) in rats. In healthy male volunteers ( n=14), an open-label, randomised, crossover study was conducted to compare adverse events and pharmacokinetic parameters, in two experiments in which 300 mg GET 73 was administered, with and without alcohol, once and thrice. In rats, when administered with alcohol-vehicle, 100 mg/kg, but not 30 mg/kg, GET 73 reduced spontaneous locomotor activity. When administered with alcohol, no dose of GET 73 altered either alcohol-induced hypolocomotion or sedation/hypnosis. In humans, both single and thrice 300 mg GET 73 administration were well tolerated, in the presence and absence of alcohol, with no differences in adverse events. There were no significant differences in relative bioavailability between administering 300 mg GET 73 in the presence or absence of alcohol.


Primary care and behavioral health practice size: the challenge for health care reform.
We investigated the size profile of US primary care and behavioral health physician practices since size may impact the ability to institute care management processes (CMPs) that can enhance care quality. We utilized 2009 claims data from a nationwide commercial insurer to estimate practice size by linking providers by tax identification number. We determined the proportion of primary care physicians, psychiatrists, and behavioral health providers practicing in venues of >20 providers per practice (the lower bound for current CMP practice surveys). Among primary care physicians (n=350,350), only 2.1% of practices consisted of >20 providers. Among behavioral health practitioners (n=146,992) and psychiatrists (n=44,449), 1.3% and 1.0% of practices, respectively, had >20 providers. Sensitivity analysis excluding single-physician practices as "secondary" confirmed findings, with primary care and psychiatrist practices of >20 providers comprising, respectively, only 19.4% and 8.8% of practices (difference: P<0.0001). In secondary analyses, bipolar disorder was used as a tracer condition to estimate practice census for a high-complexity, high-cost behavioral health condition; only 1.3-18 patients per practice had claims for this condition. The tax identification number method for estimating practice size has strengths and limitations that complement those of survey methods. The proportion of practices below the lower bound of prior CMP studies is substantial, and care models and policies will need to address the needs of such practices and their patients. Achieving a critical mass of patients for disorder-specific CMPs will require coordination across multiple small practices.


Integrating generational perspectives in nursing.
Although nurses from four different generations work closely together, tension may occur as the different generational perspectives result in misinterpretation and misunderstanding. Learning to create integrated and collegial relationships with people from different generations is a critical skill for nurses who work in multigenerational teams. This article will begin with a review of the historical perspective of the four generational cohorts currently in the workplace. This review will set a foundation for understanding each generation's unique set of work and personal values. Then the article will discuss various sources of multigenerational misunderstandings and conclude with a discussion of approaches to strengthen intergenerational work teams. The article will emphasize that learning to appreciate the diverse points of view, leverage the strengths, and value the differences in colleagues from various generations can enable individuals to form creative, adaptable, and cohesive work groups.


[Fluoride content in rural drinking water in Shaanxi Province during 2008-2018].
To understand the fluoride index of drinking water quality and its trend in rural areas of Shaanxi Province since 2008, to evaluate the effect of water improvement on reducing fluoride. In 2008-2018, rural drinking water monitoring points were set up in the jurisdiction of the agriculture-related counties( districts) in Shaanxi Province. Water samples were collected in the April-June dry seasons and July-September wet seasons, and tested according to the Standard Test Method for Drinking Water( GB/T 5750-2006). Collected and sorted water quality monitoring information through the National Drinking Water Quality Monitoring Information System, according to the Sanitary Standards for Drinking Water( GB 5749-2006), the comparison between groups and linear trend analysis were carried out according to different annual, water period, water source type, water supply mode and region. From 2008 to 2018, the overall compliance rate of fluoride in rural drinking water in Shaanxi Province was 93. 37%, the concentration of fluoride in water was in the range of0. 001-9. 880 mg/L, the median was 0. 370 mg/L, and the cumulative coverage of water quality fluoride exceeded the standard project was 3. 669 million. The difference of fluoride compliance rate in different years was statistically significant( χ~2= 120. 962, P<0. 001), and the fluoride compliance rate increased with the increase of the year( χ~2= 9. 241, P =0. 002), the fluoride compliance rate of surface water was higher than that of groundwater( χ~2= 1188. 563, P < 0. 001), there was a statistically significant difference in the compliance rate of fluoride in different water treatment processes in centralized water supply projects( χ~2= 2931. 231, P < 0. 001), the highest rate of fluoride in conventional treatment was 96. 63%( P < 0. 001), and the lowest disinfection rate was 84. 78%( P <0. 001). The distribution of drinking water sources in rural areas of Guanzhong and Northern Shaanxi was mainly groundwater, accounting for 88. 12% and 92. 25%, respectively, while Southern Shaanxi was dominated by surface water, accounting for69. 99%. There were significant differences in the fluoride compliance rates in Guanzhong region, Northern Shaanxi and Southern Shaanxi( χ~2= 1919. 335, P < 0. 001). Among them, the highest in Southern Shaanxi was 99. 84%( P < 0. 001), and the lowest in Northern Shaanxi was 89. 33%( P < 0. 001)( χ~2 SouthernShaanxi, Guanzhong= 1755. 724, χ~2 Southern Shaanxi, Northern Shaanxi= 2033. 8, χ~2 Northern Shaanxi, Guanzhong= 27. 535, P < 0. 001). The overall compliance rate of fluoride in water-reducing projects was 73. 80%, which cannot prove the trend of the overall compliance rate of fluoride in water-reducing projects with the year( χ~2= 3. 168, P = 0. 075). While achieving high result in the prevention and control of high fluorine water in Shaanxi Province, it is necessary to continue to implement effective measures to reduce fluorine content in rural drinking water, and to ensure the safety of drinking water from the aspects of water supply and treatment technology.


Homology modelling of human CYP2 family enzymes based on the CYP2C5 crystal structure.
1. The construction of molecular models for human cytochromes P450 from the CYP2 family are reported, utilizing the recently available crystal structure of CYP2C5, which is also a mammalian (rabbit) form of the enzyme. 2. In particular, selective substrate interactions with CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 are described in the context of favourable contacts with active site amino acid residues that appear to orientate each substrate for metabolism at the experimentally observed position. 3. The results are consistent with reported findings from site-directed mutagenesis experiments with the CYP2 family, and with published information on substrate metabolism.


Retardation of organic contaminants in natural fractures in chalk.
Transport of a conservative compound and two sorbing compounds through fractured chalk was studied using flow-through columns consisting of chalk cores with a single subvertical fracture. Two types of chalk matrix were compared, an oxidized white chalk with low organic carbon content (0.2%), and a gray chalk with a higher organic carbon content (1.3%). Initial rapid breakthrough followed by a delayed approach to a relative concentration of unity for the conservative compound (2,6-difluorobenzoic acid [DFBA]) was clear evidence for diffusion into the porous chalk matrix. Matrix diffusion of DFBA was apparently much greater in the gray chalk columns than in the white chalk columns. Breakthrough curves (BTCs) of the sorbing compounds (2,4,6-tribromophenol [TBP] and ametryn [AME]) were retarded in all cases as compared to the conservative compound. Sorption retardation was far greater in the gray chalk as compared with the white chalk, in good agreement with results from batch sorption experiments. BTCs for the conservative compound were relatively nonhysteretic for both white and gray chalk columns. In contrast, BTCs for the sorbing compounds were hysteretic in all cases, demonstrating that sorption was not at equilibrium before desorption began. These experiments suggest that on a field scale, transport of contaminants through fractures in chalk and other fractured porous media will be attenuated by diffusion and sorption into the matrix.


ICD-10: cracking the code.
Healthcare organizations should address physician clinical documentation improvement now, before the Oct. 1, 2014, implementation deadline for ICD-10, if they are to mitigate risk related to ICD-10 and optimize operational processes. Improving documentation now will have an immediate effect on revenue and will minimize the potential for losses related to denied claims after ICD-10 goes into effect. Training of physicians should not be just a "once-and-done" process. Organizations should plan now for training to continue even after the implementation deadline.


The normal chain length distribution of the O antigen is required for the interaction of Shigella flexneri 2a with polarized Caco-2 cells.
Shigella flexneri causes bacillary dysentery in humans. Essential to the establishment of the disease is the invasion of the colonic epithelial cells. Here we investigated the role of the lipopolysaccharide (LPS) O antigen in the ability of S. flexneri to adhere to and invade polarized Caco-2 cells. The S. flexneri 2a O antigen has two preferred chain lengths: a short O antigen (S-OAg) regulated by the WzzB protein and a very long O antigen (VL-OAg) regulated by Wzz pHS2. Mutants with defined deletions of the genes required for O-antigen assembly and polymerization were constructed and assayed for their abilities to adhere to and enter cultured epithelial cells. The results show that both VL- and S-OAg are required for invasion through the basolateral cell membrane. In contrast, the absence of O antigen does not impair adhesion. Purified LPS does not act as a competitor for the invasion of Caco-2 cells by the wild-type strain, suggesting that LPS is not directly involved in the internalization process by epithelial cells.


Compliance with peak expiratory flow monitoring in home management of asthma.
The recent consensus reports on asthma management emphasize the importance of using peak flowmeters to accurately assess the degree of airflow obstruction. However, the optimal way to use those devices has not yet been determined. To assess compliance with peak expiratory flow (PEF) measurements in the long-term management of asthma, and identify the characteristics of patients with poor compliance. Asthma clinics from three tertiary-care hospitals. A descriptive and prospective study of 1-year duration. Twenty-six patients with moderate to severe asthma taking part in an asthma education program. Patients were asked to measure morning and evening PEF using an electronic peak flowmeter with a 3-month memory; they were unaware that PEF values were being recorded by this device. Compliance with PEF measurements was relatively good during the first month (63% of the measurements done) but even with regular reinforcement, fell to 50% at 6 months and to 33% at 12 months. Right from the beginning, 8 of 26 subjects (30%) never or almost never (<5% of the readings done) measured PEF, with seven of these subjects writing fabricated results in their diaries most of the time. At 12 months, 60% of the subjects were measuring PEF <25% of the time, and most of them continued writing fabricated PEF values in their diaries. None of the subjects' characteristics helped us to identify those who had poor compliance with these measurements. While short-term compliance with PEF measurements is fairly good, most patients with moderate to severe asthma are not interested in measuring PEF twice daily over a prolonged period. In the current management of asthma, PEF measurement devices can be suggested to those showing a strong personal interest in using them, but should be limited to short periods of time. Furthermore, this study outlines the usefulness of electronic peak flowmeters when doing clinical research where PEF improvement is an important outcome.


Diurnal variation of macular oedema in CRVO: prospective study.
Patients with central retinal vein occlusion (CRVO) may experience reduced vision in the morning. This may be due to increased cystoid macular oedema (CMO), which can be measured on optical coherence tomography (OCT). A prospective study was performed on ten patients. Retinal thickness measurements were made with the Topcon 3D OCT-1000: at 9 A.M., 11 A.M., 1 P.M., 3 P.M., 5 P.M. In addition, at 9 A.M. and 5 P.M. visual acuity was recorded using ETDRS LogMAR. There were seven males and three females with average age of 59.4 years (range 40-80 years). The average duration of symptoms was 5.4 months (range 3-9 months). In eyes with CRVO, median central macular thickness (CMT) significantly reduced from 571 microm at 9 A.M. to 475 microm at 5 P.M. (p < 0.05). Comparison of CMT at 9 A.M. to each of the subsequent time intervals found that there was a significant reduction in the central macula thickness late in the day (p < 0.05). There was no statistical difference in the visual acuity and change in macular thickness did not correlate with change in visual acuity in eyes affected by CRVO. Patients with CRVO demonstrate increase in CMO in morning compared with late morning and afternoon. Possible causes are diurnal variation in blood pressure, retinal metabolism and erect posture. Interventions designed to influence these factors could be used to try to reduce CMO severity.


LC-MS-based serum metabolomics analysis for the screening and monitoring of colorectal cancer.
Colorectal Cancer (CRC) is a prevalent digestive system tumour with significant mortality and recurrence rates. Serum metabolomics, with its high sensitivity and high throughput, has shown potential as a tool to discover biomarkers for clinical screening and monitoring of the CRC patients. Serum metabolites of 61 sex and age-matched healthy controls and 62 CRC patients (before and after surgical intervention) were analyzed using a ultra-performance liquid chromatography-high resolution mass spectrometer (UPLC-MS). Statistical methods and pathway enrichment analysis were used to identify potential biomarkers and altered metabolic pathways. Our analysis revealed a clear distinction in the serum metabolic profile between CRC patients and healthy controls (HCs). Pathway analysis indicated a significant association with arginine biosynthesis, pyrimidine metabolism, pantothenate, and CoA biosynthesis. Univariate and multivariate statistical analysis showed that 9 metabolites had significant diagnostic value for CRC, among them, Guanosine with Area Under the Curve (AUC) values of 0.951 for the training group and0.998 for the validation group. Furthermore, analysis of four specific metabolites (N-Phenylacetylasparticacid, Tyrosyl-Gamma-glutamate, Tyr-Ser and Sphingosine) in serum samples of CRC patients before and after surgery indicated a return to healthy levels after an intervention. Our results suggest that serum metabolomics may be a valuable tool for the screening and monitoring of CRC patients.


Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway.
Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection. B cells from mice acutely infected with gammaherpesvirus 68 are defective in BCR- and CXCR4-mediated activation of the PI3K pathway, and this, we show, is associated with increased PTEN expression. This viral infection-induced PTEN overexpression appears responsible for the suppression of antibody responses observed in infected mice because PTEN deficiency or expression of a constitutively active PI3K rescued function of B cells in infected mice. Conversely, induced overexpression of PTEN in B cells in uninfected mice led to suppression of antibody responses. Finally, we demonstrate that PTEN up-regulation is a common mechanism by which infection induces suppression of antibody responses. Collectively, these findings identify a novel role for PTEN during infection and identify regulation of the PI3K pathway, a mechanism previously shown to silence autoreactive B cells, as a key physiological target to control antibody responses.


Compliance problems with hormone replacement therapy.
Because menopause and its consequences constitute an endocrinopathy, long-term administration of HRT is often necessary to achieve optimal results. Compliance is therefore an important consideration in the clinical use of HRT. A number of factors appear to influence physicians in their prescribing of HRT, including estimates of benefits and risks that may not be supported by scientific data. In addition, some physicians appear to use patterns of administration of HRT that may diminish the chance of appropriate patient compliance, or of maximizing benefits while minimizing risks. Patients may elect to avoid HRT or stop HRT prematurely because of incorrect impressions about the benefits and risks, or because of bothersome side effects. Although the side effects are more prevent some appropriate candidates from using HRT. Fortunately, a range of possible options is available for prescribing HRT, and modifications may be used for patients who are experiencing problems. In order for patients to receive maximum benefit from HRT, clinicians must be willing to educate and reassure patients, and to adjust therapy when problems occur.


The Role of BIA Analysis in Osteoporosis Risk Development: Hierarchical Clustering Approach.
Osteoporosis is a common musculoskeletal disorder among the elderly and a chronic condition which, like many other chronic conditions, requires long-term clinical management. It is caused by many factors, including lifestyle and obesity. Bioelectrical impedance analysis (BIA) is a method to estimate body composition based on a weak electric current flow through the body. The measured voltage is used to calculate body bioelectrical impedance, divided into resistance and reactance, which can be used to estimate body parameters such as total body water (TBW), fat-free mass (FFM), fat mass (FM), and muscle mass (MM). This study aims to find the tendency of osteoporosis in obese subjects, presenting a method based on hierarchical clustering, which, using BIA parameters, can group patients who show homogeneous characteristics. Grouping similar patients into clusters can be helpful in the field of medicine to identify disorders, pathologies, or more generally, characteristics of significant importance. Another added value of the clustering process is the possibility to define cluster prototypes, i.e., imaginary patients who represent models of "states", which can be used together with clustering results to identify subjects with similar characteristics in a classification context. The results show that hierarchical clustering is a method that can be used to provide the detection of states and, consequently, supply a more personalized medicine approach. In addition, this method allowed us to elect BIA as a potential prognostic and diagnostic instrument in osteoporosis risk development.


Identification of ISMyo2, a novel insertion sequence element of IS21 family and its diagnostic potential for detection of Mycobacterium yongonense.
Mycobacterium yongonense, as a novel member of the M. avium complex (MAC), was recently reported to be isolated from human specimens in South Korea and Italy. Due to its close relatedness to other MAC members, particularly M. intracellulare in taxonomic aspects, the development of a novel diagnostic method for its specific detection is necessary for clinical or epidemiologic purposes. Using the Mycobacterium yongonense genome information, we have identified a novel IS-element, ISMyo2. Targeting the ISMyo2 sequence, we developed a real-time PCR method and applied the technique to Mycobacterial genomic DNA. To identify proper nucleic acid targets for the diagnosis, comparisons of all insertion sequence (IS) elements of 3 M. intracellulare and 3 M. yongonense strains, whose complete genome sequences we reported recently, led to the selection of a novel target gene, the M. yongonense-specific IS element, ISMyo2 (2,387 bp), belonging to the IS21 family. Next, we developed a real-time PCR method using SYBR green I for M. yongonense-specific detection targeting ISMyo2, producing a 338-bp amplicon. When this assay was applied to 28 Mycobacterium reference strains and 63 MAC clinical isolates, it produced amplicons in only the 6 M. yongonense strains, showing a sensitivity of 100 fg of genomic DNA, suggesting its feasibility as a diagnostic method for M. yongonense strains. We identified a novel ISMyo2 IS element belonging to the IS21 family specific to M. yongonense strains via genome analysis, and a real-time PCR method based on its sequences was developed.


[Ionic binding of 3H-gentamicin and short-term bactericidal activity of gentamicin against Pseudomonas aeruginosa isolates differing in lipopolysaccharide structure].
The clinical isolates of Pseudomonas aeruginosa can be roughly classified into long- and short-lipopolysaccharide (LPS) strains and LPS-deficient strains, based on the silver-stained patterns of their LPSs after SDS-PAGE. The ionic binding of 3H-gentamicin, a polycationic antibiotic, to the negatively charged sites on the surface structures of P. aeruginosa strains, often differing in LPS structure, was the highest in the long-LPS strains followed in descending order by the short-LPS strains and LPS-deficient strains. It was presumed that a clinical isolate of P. aeruginosa No. 45 is lacking in the O-polysaccharide chains and some structures of the core-regions consisting of its LPS-structure after SDS-PAGE. On the other hand, the binding of 3H-gentamicin to this strain was quite. high, i.e., similar to that to of the long-LPS strains. To clarify this finding, P. aeruginosa PAC1R and its LPS-deficient mutants were used as reference strains because the chemical structures of their LPSs containing the repeated units of O-polysaccharides and the neutral sugar contents in the core-regions were previously confirmed. The PAC605 strain of the LPS-mutants of the PAC series, was completely lacking in the repeated units of O-polysaccharide and also lacking in some neutral sugar residues of the core-oligosaccharide region. However, this strain was highly bound to 3H-gentamicin, suggesting that the negatively charged sites on the deep core-oligosaccharide region and/or on lipid A participated in the binding of 3H-gentamicin. This manner of binding may be also applied to P. aeruginosa No. 45. When P. aeruginosa PAC1R, PAC605 and No. 45 strains were each exposed to gentamicin (20 micrograms/ml) for 10 minutes, the viable cell counts of PAC1R decreased to about 70% of the initial count, whereas the viable cell counts of PAC605 and No. 45 strains decreased to 3.6 and 11.0% respectively, indicating the vulnerability of both types of the strains to be enhanced by the bactericidal action of gentamicin with short-term incubation.


Laparoscopic bariatric surgery can be performed safely in secondary health care centres with a dedicated service corridor to an affiliated tertiary health care centre.
Canada needs to increase capacity for bariatric surgery to reduce the wait for this cost-effective, life-saving surgery. The aim of this study was to test whether laparoscopic bariatric surgery, including gastric bypass, can be delivered safely in secondary health care centres (SHCCs). In this prospective cohort study, patients received bariatric surgery at an SHCC that had no intensive care unit but had a dedicated operating room and ward teams and a patient-monitoring environment. Patients with life-threatening complications were transferred to an affiliated tertiary health care centre (THCC) via a dedicated "service corridor." In all, 830 patients were treated: 676 at the SHCC and 154 at the THCC. Gastric bypass was performed in 85.4%, gastric band in 11.1% and gastric sleeve in 3.5%. The body mass index (BMI) was significantly higher in the THCC than the SHCC group (mean 54.4 [standard deviation (SD) 9.7] v. 47.5 [SD 7.4]). Obesity-associated diseases were similar between the groups. Major complications occurred in 2.6% of SHCC patients and 1.7% of THCC patients. Seven patients (1%) required direct transfer to the THCC, and all were treated successfully. There were 2 deaths (1.3%) in the THCC and none in the SHCC groups (combined mortality 0.2%). Weight loss was equivalent up to the fourth year of the study. With proper patient selection, a dedicated health care team and a service corridor to an affiliated THCC, laparoscopic bariatric surgery, including gastric bypass can be performed safely in SHCCs. Further study is needed to determine whether the model can be applied across Canada.


Attributable Risk to Assess the Health Impact of Air Pollution: Advances, Controversies, State of the Art and Future Needs.
Despite the increased attention given to the health impact assessment of air pollution and to the strategies to control it in both scientific literature and concrete interventions, the results of the implementations, especially those involving traffic, have not always been satisfactory and there is still disagreement about the most appropriate interventions and the methods to assess their effectiveness. This state-of-the-art article reviews the recent interpretation of the concepts that concern the impact assessment, and compares old and new measurements of attributable risk and attributable fraction. It also summarizes the ongoing discussion about the designs and methods for assessing the air pollution impact with particular attention to improvements due to spatio-temporal analysis and other new approaches, such as studying short term effects in cohorts, and the still discussed methods of predicting the values of attributable risk (AR). Finally, the study presents the more recent analytic perspectives and the methods for directly assessing the effects of not yet implemented interventions on air quality and health, in accordance with the suggestion in the strategic plan 2020-2025 from the Health Effect Institute.


Methods of Biotyping of Streptococcus mutans Species with the Routine Test as a Prognostic Value in Early Childhood Caries.
In order to investigate the suitability of Streptococcus mutans species biotyping by measuring the activity of selected enzymes from a commercial test, criteria were established for biotyping clinical strains from children with dental caries. In addition, the relationships between the selected biotypes, sensitivity to commonly used antibiotics, and early childhood caries were determined. A total of 142 S. mutans isolates from dental plaque of children with caries were divided into different biotypes. Patients were divided into two groups: noncavitated (1-2 in ICDAS) and cavitated (5-6 in ICDAS) lesions. Biotyping criteria were determined based on both the arbitrary method and the clusterization method. The susceptibility of the strains to amoxicillin, cefazolin, erythromycin, and teicoplanin was studied by diluting a solid medium. Biotype I was the most common. Mean MIC values showed that the strains belonging to biotypes II and IV were the most sensitive to amoxicillin. For predetermined biotypes, observed differences were dependent on the severity of dental caries. The proposed method of S. mutans strains biotyping is relatively quick and simple to use, provided the application of suitable biotyping criteria, and may contribute to the effective prevention of dental caries induced by S. mutans.


Mesenteric venous thrombosis: a rare complication of small bowel neuroendocrine tumor presenting with gangrenous appendicitis.
A 61-year-old woman presented to the hospital with a clinical picture consistent with acute appendicitis. During surgery, the appendix was found to be gangrenous and involved the appendiceal base, so an ileocecectomy was performed. Pathology revealed an incidental neuroendocrine tumor of the terminal ileum involving five of nine lymph nodes. The patient later developed mesenteric venous thrombosis but was diagnosed and treated promptly, and she is now doing well. There have been previous reports of small bowel neuroendocrine tumor resulting in bowel ischemia, usually due to fibrosis which can result in obstruction of the mesenteric vessels. However, this is the first known report of a small bowel neuroendocrine tumor presenting with appendicitis, which most likely was from an ischemic etiology. This case also demonstrates the importance of a high index of suspicion for mesenteric ischemia in patients with small bowel neuroendocrine tumor who present with acute abdominal pain.


Connective tissue disease features after thallium poisoning.
We present 5 patients in whom thallium poisoning (1) mimicked systemic lupus erythematosus (SLE) with positive antinuclear antibodies; (2) caused a SLE-like illness with positive antinuclear antibodies and rheumatoid factor that was followed by a persistent chronic polyarthritis; (3) mimicked SLE with negative antinuclear antibodies and no residual disease; (4) caused arthralgia, Raynaud's phenomenon and palmar erythema with negative antinuclear antibodies followed by keratoconjunctivitis sicca; and (5) triggered the onset of SLE with diffuse proliferative glomerulonephritis. Although the notion exists that thallium poisoning may simulate seronegative SLE, these associations between connective tissue diseases and thallium poisoning have not been previously recorded.


Perception and use of balance measures for stroke patients among physical therapists in South Korea.
[Purpose] The purpose of this study looked into physical therapists' perception and use of balance measures for stroke patients. [Subjects and Methods] Three hundred eighty two physical therapists who understood the purpose of this study, agreed on their participation in this study, were treating or treated stroke patients. A Cross-sectional study based on self-administered questionnaire that had a total of 41 questions was performed in South Korea. 382 questionnaires were used for analysis. [Results] Regarding the questions about their perception and of personal measures, 287 persons (75.1%) replied that Single Leg Stance test was the most useful. According to the data analysis on their use of balance measures, Single Leg Stance Test was used by 254 persons (66.5%, the highest percentage), Functional Reach Test by 199 (52.1%). Also, stepwise multiple regression analysis was conducted. As a result, the most influential factor was physical therapists' perception of personal measures, and their use was also influenced by their comprehensive perception of measurement and their perception of balance factors. [Conclusion] This study revealed physical therapists' perception and use of balance measures for stroke patients and showed that their perception of balance measures for stroke patients affected their use of personal measures.


Reduction of D-lactate content in sauerkraut using starter cultures of recombinant Leuconostoc mesenteroides expressing the ldhL gene.
The D-form of lactate, which causes metabolic stress upon excessive dietary intake, is mainly produced by Leuconostoc sp., the predominant species in sauerkraut. To shift the metabolic flux of d-lactate from pyruvate to l-lactate, we expressed the l-lactate dehydrogenase (ldhL) gene in Leuconostoc mesenteroides ATCC 8293. The ldhL gene from Lactobacillus plantarum was introduced into L. mesenteroides using the shuttle vectors pLeuCM and pLeuCM42. To elevate the expression level of ldhL in L. mesenteroides, the nucleotides for pyruvate kinase promoter were fused to ldhL and cloned into above vectors to construct pLC18pkL and pLC42pkL. As results, introduction of pLC42pkL in L. mesenteroides significantly improved both l-LDH activity and l-lactate productivity during fermentation, decreasing the d-/l-lactate ratio. When used as a starter culture for sauerkraut fermentation, recombinant L. mesenteroides harboring pLC42pkL increased l-lactate concentration and decreased d-lactate concentration compared to the wild type strain. We newly developed a recombinant L. mesenteroides which has high l-lactate dehydrogenase activity and applied this strain to minimize the harmful effect of d-lactate during the sauerkraut fermentation. To the best of our knowledge, we demonstrate for the first time the effective use of recombinant Leuconostoc sp. for quality improvement of fermented foods.


Effects of density and perch availability on the immune status of broilers.
This study attempted to evaluate the effect of various housing densities and perch availability on the immune status of commercial broilers. Birds were raised from hatch to 42 d of age with 10, 15, and 20 birds/m2 in pens, with and without the availability of horizontal perches. The immune parameters that were assessed were lymphoid organ weights, antibody response to SRBC in the last 10 d of growth, heterophil:lymphocyte ratios at 32 and 42 d of age, and lymphocyte blastogenesis of peripheral blood lymphocytes collected at 32 and 42 d of age. As density increased, bursa weight and bursa/body weight ratios decreased significantly (P < 0.05). Addition of perches to the pens also significantly decreased the bursa weights and bursa/body weight index (P < 0.01). No other significant effects were observed for the flock performance, morphometric data, or immunological tests between treatments. We concluded that under the conditions of this study, which tried to simulate commercial conditions, the bursal weight was the best indicator of stress that was related to housing density. Addition of perches appeared to increase this level of stress because the birds used the perches infrequently, and therefore there might have been a further reduction in the availability of floor space to the birds.


Decision-making in surgical neonatal necrotizing enterocolitis.
To know whether laboratory or clinical parameters can predict disease progression, need for laparotomy in patients managed with peritoneal drain and mortality in surgical neonatal necrotizing enterocolitis patients. The study was retrospectively carried out on 27 neonates over a period of one and a half year. All neonates who had surgical neonatal necrotizing enterocolitis in the form of bowel perforation, positive paracentesis, abdominal wall erythema and abdominal lump were included. Patients with Bell's stage I and those developing enterocolitis after surgery were excluded. The patients were evaluated with parameters, namely, clinical, laboratory and radiological. These included age and stage at presentation, primary symptom/sign at presentation with laboratory parameters of blood counts, pH, base deficit, platelet counts, electrolytes and random blood sugar levels. A comparison was done between survivors and nonsurvivors, patients with primary peritoneal drainage versus those requiring laparotomy after drain, Bell' stage II versus III patients and operated versus nonoperated patients. Statistical significance was observed in the above mentioned comparisons. There were 22 male and 5 females patients with mean birth weight of 1.85 kg. Age at presentation ranged from 2 to 19 days, mean 9.25 days. Mortality was 37% (10/27). Majority of the stage II patients presented with feed intolerance and abdominal distension. The neonates with severe disease had abdominal distension with wall erythema. Sixty percent of the patients had shock at the time of admission. In the comparison of peritoneal drain only and patients with peritoneal drain followed by laparotomy patients, it was observed that neonates who were acidotic and had higher base deficit had more chances of requirement of laparotomy. They also had progressive fall in platelets counts. There was no difference in the birth weight, gestational age, total counts, serum electrolytes, blood sugar and other measured parameters; thus, these carry negligible predictive value to judge deteriorating neonate. In the remaining of the comparison, patients not presenting with shock were more likely to survive. In the present study, neonate with persistently low pH, higher base deficit and presentation with shock predicted need for laparotomy in drain managed patients as well as chances of survival.


Understanding the relationship between data breaches and hospital advertising expenditures.
To estimate the relationship between data breaches and hospital advertising expenditures. Observational data on hospital expenditures were analyzed using a propensity score-matched regression. The regression was specified as a generalized linear model using a gamma distribution and log link. The study sample included Medicare hospitals captured by a survey of traditional media outlets. Hospitals included were nonfederal acute care inpatient hospitals from 2011 to 2014. Voicetrak provided data on hospital advertising expenditures. The Healthcare Cost Report Information System provided data on hospital characteristics and financial variables. Study groups were matched using observable characteristics, such as revenue, number of beds, discharges, ownership, and teaching status. The study excluded hospitals in Maryland and the US territories for financial reporting consistency. Data breaches included theft, loss, unauthorized access/disclosure, improper disposal, and hacking. Advertising expenditures were collected from media outlets including television, radio, newspapers and business journals, and local magazines in a city/metropolitan area. Breached hospitals (n = 72) were more likely to be large, teaching, and urban hospitals relative to the control group (unweighted n = 915). A data breach was associated with a 64% (95% CI, 7.2%-252%; P = .023) increase in annual advertising expenditures, holding observable characteristics constant. Breached hospitals were associated with significantly higher advertising expenditures in the 2 years after the breach. Efforts to repair the hospital's image and minimize patient loss to competitors are potential drivers of the increased spending. Advertising costs subsequent to a breach are another cost to the healthcare system that could be avoided with better data security.


Drug induced pseudolymphoma.
Atypical lymphocytic infiltrates of the skin comprise a broad spectrum of entities ranging from benign infiltrates to those that are malignant. Many of these infiltrates are in fact reactive lymphomatoid ones related to drug therapy falling under the general category of drug associated pseudolymphoma. Within this nosologic umbrella are nodular and diffuse infiltrates resembling low grade T and B cell lymphoma consistent with lymphocytoma cutis, drug associated reversible T cell dyscrasias which draw a strong morphologic and phenotypic parallel with mycosis fungoides and the various pre-lymphomatous T cell dyscrasias, and angiocentric CD30 positive infiltrates mirroring lymphomatoid papulosis. The implicated drug classes are quite varied and include antidepressants, antihistamines, calcium channel blockers, statins, anticonvulsants, and various biologic drugs. The drugs from these various drug classes exert certain effects on lymphoid function including evoking overzealous responses to other antigenic stimuli. As the adverse effect on lymphocyte function may be cumulative over years and or reflect the interplay of other drugs, a temporal association may not exist between the onset of the rash/lesion and the initiation of the drug. In certain lymphomatoid reactions however such as DRESS syndrome the drug may function as both an antigen as well as an immune dysregulating agent. It is critical that the pathologist works carefully with the clinician in the evaluation of all atypical cutaneous lymphoid infiltrates where the distinction between pseudolymphoma versus lymphoma cannot be reliably made based on pathologic analysis alone.


Interventions for intimate partner violence during the perinatal period: a scoping review protocol.
Globally, the prevalence and incidence of perinatal intimate partner violence (IPV) are well documented and substantiated; however, there is an urgent need to identify interventions to prevent recurrence or revictimisation, and decrease the harms of perinatal IPV. This scoping review is designed to broadly capture all potential interventions for the secondary prevention of IPV, review them in detail, and assess what can reduce revictimisation and foster improvements in both maternal and neonatal outcomes. With the structure of the Joanna Briggs Institute and Arksey and O'Malley methodology for scoping reviews, the search will be conducted in: MEDLINE(R) ALL (OvidSP), Embase (OvidSP), CINAHL (EBSCOHost), APA PsycInfo (OvidSP), Cochrane Central Register of Controlled Trials (OvidSP), Web of Science, and Applied Social Sciences Index & Abstracts (ProQuest). A manual search of the reference lists of the retrieved articles will be conducted to capture all relevant studies for potential inclusion. A year limit of January 2000-June 2022 will be applied to retrieve most current peer-reviewed articles. No search filters or language limits will be used, but only publications in English and French will be eligible for inclusion. Interventions include but are not limited to: psychotherapy, educational sessions, home visitation, etc. Outcomes include but are not limited to: (1) harms of IPV among survivors (eg, revictimisation) and (2) adverse perinatal outcomes (eg, preterm birth). Interventions will be excluded if they target the perpetrator or child(ren) alone. Titles and abstracts of included studies will be screened in duplicate. Full-text documents will be extracted and reviewed by two independent reviewers. Conflicts between reviewers will be resolved by a third independent reviewer. Findings will be presented with descriptive statistics and narrative synthesis. Ethics approval is not required for this scoping review. The results will be disseminated through peer-reviewed publication and conference presentations. Open Science Framework (OSF) registry (https://osf.io/e294r) in Centre for Open Science (OSF) on 27 May 2022.


Validation of the substance abuse screener in American Sign Language (SAS--ASL).
The study objectives were to adapt and validate a substance use disorder (SUD) screening instrument in American Sign Language (ASL) to be used to identify those deaf individuals who have a high probability of having an SUD. The goal was to develop an accurate screening instrument that balanced sensitivity and specificity while imposing minimal response burden on respondents. A sample of 198 deaf participants in behavioral health, family social service, and educational programs that provide specialized services for deaf individuals was interviewed to obtain clinical diagnoses for current (past 12 months) SUD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and completed a 42-item version of the Substance Abuse Screener in American Sign Language (SAS-ASL). We used Rasch and discriminant function analyses to reduce the instrument to 28 items, then divided the sample into a development subsample, used to formulate a scoring routine, and a validation subsample to assess correspondence with clinical diagnoses. To provide validation data on the shortened SAS-ASL, an independent sample of 62 respondents was diagnosed and completed the screener. The SAS-ASL instrument demonstrated good person reliability (.85), sensitivity (.90), and specificity (.84) in the primary validation sample, and 100% screening accuracy with 62 respondents in the second validation sample. The SAS-ASL provides a standardized SUD screening for the deaf population. The adaptability of the instrument to electronic administration lends itself to a continuum of technologically supported services for a high-risk population that is disenfranchised for most community-based behavioral health services.


Subjective experiences and the psychopathological dimensions in schizophrenia.
The aim of this article was to explore the relationships between subjective experience (SE) and objective symptoms in schizophrenia. Exploratory principal component analysis was used to determine the latent organization of the variables. A group of 310 chronic patients with schizophrenia who met ICD-10 criteria for F20 schizophrenic disorder were included in the study. SE and objective symptoms were rated using, respectively, the 24-item version of the Frankfurt Complaint Questionnaire (FCQ-24) and the Positive and Negative Syndrome Scale (PANSS). An exploratory principal component analysis was performed on the correlation matrix comprising items from both the FCQ-24 and the PANSS. Using several guidelines to select the number of factors, the exploratory principal component analysis yielded a six-factor solution with no overlap of the significant factor loadings for the items from each scale. These six factors represent, respectively, the subjective, negative, positive, disorganization, hostility and anxious-depressive dimensions of the schizophrenic phenomenology. The findings support the view that SE is a construct that is separate and distinct from the objective symptomatology in schizophrenia.


Biological correlation between HER-2/neu and proliferative activity in human breast cancer.
HER-2neu alterations (amplification and overexpression), proliferative activity (3H-Thymidine-Labeling Index, 3H-Tdr-LI) and tumor ploidy (flow-cytometry) were analyzed in a human breast cancer series. Overexpressed tumors showed a significantly higher median 3H-Tdr-LI than normally expressed (p = 0.04), as also did amplified/overexpressed with respect to non-amplified/normally expressed (p less than 0.04). These differences were confirmed only in N-primary tumors. In fact, high expressed cases demonstrated a median 3H-Tdr-LI of 5.5% with respect to 1.9% for low expressed cases (p = 0.04) and amplified/overexpressed had a 3H-Tdr-LI of 9% with respect to 2% for non amplified/low expressed (p = 0.009). HER-2/neu alterations were not correlated with tumor DNA content.


Lipid and fatty acid profile of Geobacillus kaustophilus in response to abiotic stress.
Geobacillus kaustophilus is an important food-borne, spore-forming, thermotolerant bacterium. It has a good potential for biotransformation of steroid hormones, such as progesterone and testosterone. In this study, we report G. kaustophilus membrane lipid modifications in response to temperature shock, salinity, incubation time, and pH. Total lipids significantly increased in response to increasing temperature, incubation time, and salt concentration. However, the bacterium presented a significant decrease in the accumulation of total lipids in response to pH shock. The ratio of branched-chain fatty acids/straight-chain fatty acids decreased significantly under all stress conditions. With an increase in temperature, incubation time, and salt concentration, the ratio of iso-fatty acids/anteiso-fatty acids increased significantly, while this ratio remained unaffected by changes in the pH of the growth medium. Our results suggest a modification occurs in the bacterial membrane structure in response to temperature, salinity, incubation time, and pH shock. The variable abiotic stress resulted in a multiple increase in odd-numbered-carbon and low-melting-point anteiso-branched-chain fatty acids, helping the membrane keep its integrity, fluidity, and function for growth of the bacteria under abiotic stress conditions.


Study of chromatographic retention of natural terpenoids by chemoinformatic tools.
The study of chromatographic retention of natural products can be used to increase their identification speed in complex biological matrices. In this work, six variables were used to study the retention behavior in reversed phase liquid chromatography of 39 sesquiterpene lactones (SL) from an in-house database using chemoinformatics tools. To evaluate the retention of the SL, retention parameters on an ODS C-18 column in two different solvent systems were experimentally obtained, namely, MeOH-H2O 55:45 and MeCN-H2O 35:75. The chemoinformatics approach involved three descriptor type sets (one 2D and two 3D) comprising three groups of each (four, five, and six descriptors), two different training and test sets, four algorithms for variable selection (best first, linear forward, greedy stepwise, and genetic algorithm), and two modeling methods (partial least-squares regression and back-propagation artificial neural network). The influence of the six variables used in this study was assessed in a holistic context, and influences on the best model for each solvent system were analyzed. The best set for MeOH-H2O showed acceptable correlation statistics with training R(2) = 0.91, cross-validation Q(2) = 0.88, and external validation P(2) = 0.80, and the best MeCN-H2O model showed much higher correlation statistics with training R(2) = 0.96, cross-validation Q(2) = 0.92, and external validation P(2) = 0.91. Consensus models were built for each chromatographic system, and although all of them showed an improved statistical performance, only one for the MeCN-H2O system was able to separate isomers as well as to improve the performance. The approach described herein can therefore be used to generate reproducible and robust models for QSRR studies of natural products as well as an aid for dereplication of complex biological matrices using plant metabolomics-based techniques.


Subgroup analysis in therapeutic trials.
Therapy in cardiology must be based on solid scientific evidence, obtained in randomized controlled trials (RCTs), since this is the best design that proves causality in medicine. The applicability of clinical trial results to the individual patient depends on a rigorous set of rules that can be summarized in the question "Could my patient have been enrolled in this trial?" If the answer to this question is affirmative, then the possibility of applying the trial results is greater. If it is negative, then the cardiologist should exercise caution in his or her decision. In an RCT--of whatever size--it is almost always possible to identify subgroups of patients that show significant differences in treatment effect: for example, studies have shown that, in patients with non-rheumatic atrial fibrillation, oral anticoagulants should be given to prevent stroke, except in those younger than 65 years with no additional risk factors, for whom aspirin is a better option. Subgroup analysis is important because, when the magnitude of the difference is both real and large, it may influence patient management. This analysis should be done with great care, since it has the potential to lead to major errors in data interpretation, identifying differences in treatment effects that are due to chance alone or, more frequently, have no clinical significance. In this article we present a set of guidelines that enable the cardiologist to assess the credibility of an analysis that shows apparent differences in treatment effects across subgroups.


Penicillin-binding proteins of bdellovibrios.
We examined the predacious gram-negative bacterium Bdellovibrio bacteriovorous 109J and free-living strains 109J-A1 and 109J-KA1 derived therefrom for penicillin-binding proteins (PBPs). We compared their PBPs with those of the host bacterium, Escherichia coli, and with those of a facultatively predacious bdellovibrio, B. stolpii UKi2, grown axenically. The multiple PBPs of the 109J strains and of UKi2 differed from each other and from those of E. coli, which suggests that screening for PBPs may be a convenient way to determine to what extent the bdellovibrios may represent a diverse group of organisms. A method for labeling furazlocillin and cefaperizone with iodine-125 is also described.


Two classes of excitatory synaptic responses in rat thalamic reticular neurons.
The thalamic reticular nucleus (nRt), composed of GABAergic cells providing inhibition of relay neurons in the dorsal thalamus, receives excitation from the neocortex and thalamus. The two excitatory pathways promoting feedback or feedforward inhibition of thalamocortical neurons contribute to sensory processing and rhythm generation. While synaptic inhibition within the nRt has been carefully characterized, little is known regarding the biophysics of synaptic excitation. To characterize the functional properties of thalamocortical and corticothalamic connections to the nRt, we recorded minimal electrically evoked excitatory postsynaptic currents from nRt cells in vitro. A hierarchical clustering algorithm distinguished two types of events. Type 1 events had larger amplitudes and faster kinetics, largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, whereas type 2 responses had more prominent N-methyl-d-aspartate (NMDA) receptor contribution. Type 1 responses showed subnormal axonal propagation and paired pulse depression, consistent with thalamocortical inputs. Furthermore, responses kinetically similar to type 1 events were evoked by glutamate-mediated activation of thalamic neurons. Type 2 responses, in contrast, likely arise from corticothalamic inputs, with larger NMDA conductance and weak Mg(2+)-dependent block, suggesting that NMDA receptors are critical for the cortical excitation of reticular neurons. The long-lasting action of NMDA receptors would promote reticular cell burst firing and produce powerful inhibitory output to relay neurons proposed to be important in triggering epilepsy. This work provides the first complete voltage-clamp analysis of the kinetics and voltage dependence of AMPA and NMDA responses of thalamocortical and corticothalamic synapses in the nRt and will be critical in optimizing biologically realistic neural network models of thalamocortical circuits relevant to sensory processing and thalamocortical oscillations.


Effect of propranolol hydrochloride on blood cell lipids in relation to partition coefficient and biological activity.
Considering the high lipophilicity of propranolol (log P = 3.56), its interactions with the cell membrane lipids of goat blood have been investigated. It is observed that lipid loss after incubation of blood cells with propranolol hydrochloride in salt glucose medium for varying periods of time was accompanied with significant increases in PUFAs. Amongst the PUFAs studied the omega 3 and omega 6 fatty acids, the two important precursors of eicosenoids, have shown increase in varying amounts. This phenomenon is presumably responsible for the significant cardiovascular activity of this drug.


Calcium-channel blocking agents and chest pain.
Calcium-channel blocking agents can relieve anginal and chest pain associated with hypermotility of the esophagus. Although calcium-channel antagonists differ in their effects on the esophageal body and the lower esophageal sphincter, reduction of lower esophageal sphincter pressure theoretically could result in gastroesophageal reflux and pain. This pain may be difficult to differentiate from chest pain of cardiac origin. An association between calcium-channel blocking agents and chest pain is speculative at this time. However, the possibility of such an effect should be considered by clinicians in the total management of patients. Future clinical studies are warranted to address the issue of the incidence of such an effect and to define more precisely the potential interrelationship among the calcium-channel antagonists, their efficacy in relieving cardiac pain, and their potential liability in inducing chest pain of noncardiac origin.