Accuracy of frozen section remote subspecialty consultation using real-time telepathology and whole-slide imaging in gynecologic cases.
Intrapathology consultation is recommended for complex cases during frozen section (FS) as routine practice. In our institution, solicited second opinions were traditionally provided by in-person consultation (IPC). Whole-slide imaging (WSI) was implemented in 2018 as an alternative but replaced by videoconferencing in 2020. Here, we assess the accuracy of remote FS consultation using these digital modalities vs IPC. Gynecologic FS cases over a 4-year period overseen by 2 intraoperative consultants were grouped by consultation method: (1) IPC, (2) WSI, and (3) videoconferencing. Accuracy was determined by concordance between the FS and final report diagnoses. Turnaround time between the 3 groups was analyzed using SPSS statistical software (IBM). Using WSI and videoconferencing, 100% concordance was observed, while the IPC group had a 98.5% concordance rate. Videoconferencing, however, showed longer turnaround times (mean, 45.59 minutes) than IPC (mean, 33.36 minutes). Although turnaround time positively correlated with the number of FS specimens, blocks, and H&E slides per case, no statistically significant differences in the number of specimens, blocks, and H&E slides generated were found among the consultation methods. Even though turnaround time using videoconferencing is longer, the accuracy of WSI and videoconferencing for remote FS consultation is equivalent to IPC. It is therefore a safe method for conducting intrapathology FS consultation in challenging surgical cases.


Unusual head metastasis of kidney cancer.
Renal cell carcinoma (RCC) metastasis can involve any organ. Head metastasis are rare, namely tongue, scalp and nose and only a few cases have been described. The authors describe three cases of unusual presentation of head metastasis of RCC. In case 1, a 50-year-old man with RCC underwent left nephrectomy, and presented 16 months later with nasal metastasis. In case 2, a 64-year-old woman with RCC operated 12 years ago, relapsed at multiple sites including scalp, which was treated surgically. In case 3, a 47-year-old man with RCC developed metastasis in multiple organs including a mass on the tongue that was operated and was compatible with primary tumour metastasis. These cases show the importance of correct diagnosis of rare presentations and local treatment of metastasis of RCC.


Coupled reactions versus connected reactions: Coupling concepts with terms.
A hallmark of living matter is its ability to extract and transform energy from the environment. Not surprisingly, biology students are required to take thermodynamics. The necessity of coupling exergonic reactions to endergonic processes is easily grasped by most undergraduate students. However, when addressing the thermodynamic concept of coupled reactions, both students and textbook authors often make claims that clash with the Second Law of Thermodynamics. Herein, I point out the most common flaws, analyze the causes leading to these mistakes, and suggest a few rules to avoid them.


Transition planning for youth with traumatic brain injury: findings from the National Longitudinal Transition Survey-2.
Despite of a growing body of research on vocational and educational difficulties for students with traumatic brain injury (TBI), only limited empirical studies specifically examined how school transition services facilitate later employment outcomes. This exploratory, prospective longitudinal study examined the prevalence of employment and characteristics of transition planning practices that promoted positive school-to-work transition for students with TBI. The participants (n = 200) was drawn from the National Longitudinal Transition Study-2 (NLTS-2), a ten-year study which followed a large nationally representative sample of youth with disabilities through secondary education in into young adulthood. Logistic regression was used to investigate the associations between student, school, and collaborative engagement in the planning process and employment outcomes up to 8 years after high school. Among youth with TBI, 51% held current employment at the time of interview and 73% had been employed at any time after high school. Findings showed that students with TBI who had transition goals for postsecondary education were more likely to be employed at some point since leaving high school. The findings also support active student engagement and leadership in the transition planning process, and the inclusion of outside organizations and individuals. Findings indicate the impact of student, school and adult service agency engagement in transition planning processes. Implications for educational practices and future research are discussed.


EZH2 Is Essential for Fate Determination in the Mammalian Isthmic Area.
The polycomb group proteins (PcGs) are a group of epigenetic factors associated with gene silencing. They are found in several families of multiprotein complexes, including polycomb repressive complex 2 (PRC2). EZH2, EED and SUZ12 form the core components of the PRC2 complex, which is responsible for the mono, di- and trimethylation of lysine 27 of histone 3 (H3K27Me3), the chromatin mark associated with gene silencing. Loss-of-function studies of Ezh2, the catalytic subunit of PRC2, have shown that PRC2 plays a role in regulating developmental transitions of neuronal progenitor cells (NPCs); from self-renewal to differentiation and the neurogenic-to-gliogenic fate switch. To further address the function of EZH2 and H3K27me3 during neuronal development, we generated a conditional mutant in which Ezh2 was removed in the mammalian isthmic (mid-hindbrain) region from E10.5 onward. Loss of Ezh2 changed the molecular coding of the anterior ventral hindbrain leading to a fate switch and the appearance of ectopic dopaminergic (DA) neurons. The correct specification of the isthmic region is dependent on the signaling factors produced by the Isthmic organizer (IsO), located at the border of the mid- and hindbrain. We propose that the change of cellular fate is a result of the presence of Otx2 in the hindbrain of Ezh2 conditional knock-outs (cKOs) and a dysfunctional IsO, as represented by the loss of Fgf8 and Wnt1. Our work implies that next to controlling developmental transitions, EZH2 mediated gene silencing is important for specification of the isthmic region by influencing IsO functioning and repressing Otx2 in the hindbrain.


Evolution of therapy for locally advanced rectal cancer.
Rectal cancer is a prevalent disease worldwide. The standard treatment of locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy followed by surgery and adjuvant systemic chemotherapy. Studies have been done to determine the best sequence of treatments to improve survival, cure rate and long term toxicity profile. In this paper, we will review the literature regarding the evolution of LARC treatment.


[Amplification of portions of the genome in mammalian somatic cells resistant to colchicine. VI. Restriction analysis of the amplified DNA sequences].
Fragments specific for the amplified regions in DNA of Djungarian hamster colchicine-resistant cells were studied after restriction endonuclease digestion. We used three different methods of detection of these fragments: a) comparison of the wild type and resistant cell DNA electroforegramms stained by ethidium bromide; b) blotting of DNA from sensitive and resistant variants onto nitrocellulose filters and their hybridization with nick-translated DNA from resistant cells, in the presence of the excess of unlabelled DNA from the wild type cells (competitive hybridization); c) investigation of autonomously replicating DNA from sensitive and colchicine-resistant sublines. The highest resolution was found using the third method. However, the competitive hybridization is evidently a more universal approach to restriction analysis of DNA amplified sequences, because it gives quite high resolution and may be used for studying both autonomously and non-autonomously replicating sequences.


Superheating effects on metal-silicate partitioning of siderophile elements.
Uquid metal-liquid silicate partition coefficients for several elements at 100 kilobars and temperatures up to about 3000 kelvin in carbon capsules experimentally converge on unity with increasing temperature. The sense of change of the partition coefficients with temperature resembles the extrapolation of Murthy and may partially contribute to, but by no means provide a complete resolution of, the "excess" siderophile problem in the Earth's mantle. Sulfur and perhaps carbon successfully compete with oxygen for sites in the metallic liquid at these temperatures and pressures. This observation casts doubt upon the hypothesis that oxygen is the light element in the Earth's core.


Clinical study to evaluate the use of electronic anesthesia during dental hygiene procedures.
The purpose of this study was to determine if the 3M Dental Electronic Anesthesia System 8670 would decrease patients' pain/discomfort levels during scaling and root planing procedures. Forty-nine patients possessing hypersensitive teeth and/or 4-6 mm periodontal pockets requiring scaling and root planing were selected as subjects. Patients received treatment using an inactive and then an active stimulator in paired quadrants. The patients scored their pain/discomfort levels after each procedure. They were contacted by telephone 1-2 days following treatment to determine if they experienced any symptoms or discomfort following electronic dental anesthesia. The overall results for the assessment of pain/discomfort indicated that treatment using the active stimulator resulted in significantly lower pain scores for the total patient population. This study found the 3M Dental Electronic Anesthesia System 8670 to be effective for controlling pain during the dental hygiene procedures specified.


Treatable Leigh-like encephalopathy presenting in adolescence.
Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency. A rare genetic defect of thiamine transporter-2 may lead to similar clinical features, biotin-thiamine responsive basal ganglia disease (BTBGD). A 15-year-old girl developed rapid onset ptosis and ophthalmoplegia evolving into a subacute encephalopathy. Neuroimaging demonstrated symmetrical basal ganglia and mid-brain lesions reminiscent of Leigh's subacute necrotising encephalomyelopathy. Oral biotin and thiamine were started, and symptoms improved dramatically the next day. The therapeutic response suggested SLC19A3, encoding thiamine transporter-2, as a strong candidate gene and Sanger sequencing revealed a novel homozygous c.517A>G;p.Asn173Asp mutation, which segregated with disease within the family. BTBGD is a potentially treatable neurological disorder and should be considered in the differential diagnosis of Leigh syndrome and Wernicke's encephalopathy. Since delayed treatment results in permanent neurological dysfunction or death, prompt diagnosis and early initiation of biotin and thiamine therapy are essential.


Sensitivity to hymenoptera in adult males.
The authors studied the sera of 86 selected adult male office workers for IgE antibodies to yellow jacket and honey bee venoms and to environmental inhalants and foods. Structured histories provide information about the experiences of these men with the Hymenoptera and other immunological information. Three men (3%) gave a history of a local or general reaction to the Hymenoptera but no antibodies were detected. Ten men (12%) had IgE antibodies to yellow jacket or honey bee venoms but none gave a history of a reaction. Nine of these men were atopic. The authors speculate that IgE antibodies to the Hymenoptera in atopic adult males may be more common than is currently recognized.


Morphofunctional changes in Leydig cells throughout the continuous spermatogenesis of the freshwater teleost fish, Serrasalmus spilopleura (Characiformes, Characidae): an ultrastructural and enzyme study.
The freshwater fish Serrasalmus spilopleura (piranha) has a continuous type of reproduction; gametes are constantly produced and released during the reproductive cycle. The testes do not undergo seasonal morphological changes but exhibit two constant regions throughout the year: the medullar region (involved with spermatogenesis) and the cortical region (involved with spermiation and sperm storage). We have evaluated the ultrastructure of the Leydig cells and the activity of 3beta-HSD (an essential enzyme related to steroid hormone biosynthesis) and acid phosphatase (AcPase; lysosomal marker enzyme) in these two regions. The activity of 3beta-HSD is stronger in the medullar region, and the Leydig cells in this region have a variety of cytological features that reflect differences in hormone synthesis and/or that could be linked to steroidogenic cells under various degrees of hormonal activity. In the cortical region, 3beta-HSD activity is weak and the Leydig cells exhibit signs of degeneration, as confirmed by their ultrastructure and intense AcPase activity. These degenerative signs are indicative of cytoplasmic remodelling to degrade steroidogenic enzymes, such as 3beta-HSD, that could lead to senescence or even to autophagic cell degeneration. S. spilopleura thus constitutes an interesting model for increasing our understanding of steroidogenesis control in freshwater teleost fish.


Learning to make collective decisions: the impact of confidence escalation.
Little is known about how people learn to take into account others' opinions in joint decisions. To address this question, we combined computational and empirical approaches. Human dyads made individual and joint visual perceptual decision and rated their confidence in those decisions (data previously published). We trained a reinforcement (temporal difference) learning agent to get the participants' confidence level and learn to arrive at a dyadic decision by finding the policy that either maximized the accuracy of the model decisions or maximally conformed to the empirical dyadic decisions. When confidences were shared visually without verbal interaction, RL agents successfully captured social learning. When participants exchanged confidences visually and interacted verbally, no collective benefit was achieved and the model failed to predict the dyadic behaviour. Behaviourally, dyad members' confidence increased progressively and verbal interaction accelerated this escalation. The success of the model in drawing collective benefit from dyad members was inversely related to confidence escalation rate. The findings show an automated learning agent can, in principle, combine individual opinions and achieve collective benefit but the same agent cannot discount the escalation suggesting that one cognitive component of collective decision making in human may involve discounting of overconfidence arising from interactions.


A neural substrate of compulsive alcohol use.
Alcohol intake remains controlled in a majority of users but becomes "compulsive," i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, we found that this behavior emerged as a stable trait in a subpopulation of rats and was associated with activity of a brain network that included central nucleus of the amygdala (CeA). Activity of PKCδ+ inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for ~75% of variance in punishment-resistant alcohol taking. Activity-dependent tagging, followed by chemogenetic inhibition of neurons activated during punishment-resistant self-administration, suppressed alcohol taking, as did a virally mediated shRNA knockdown of PKCδ in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.


Sexual risk typologies and their relationship with early parenthood and STI outcomes among urban African-American emerging adults: a cross-sectional latent profile analysis.
Identifying sexual risk patterns associated with HIV/sexually transmitted infections (STI) and early parenthood within population subgroups is critical for targeting risk reduction interventions. Latent Class Analysis (LCA) was used to identify sexual behaviour typologies to predict sexual risk outcomes among 274 (63% female) unmarried, sexually active African-American emerging adults (M age=19.31 years) living in disadvantaged urban neighbourhoods. Participants were enrolled in a larger cross-sectional observational study of risk and protective behaviours. LCA defined membership into discrete risk classes based on reported sex risk behaviours. Three groups were identified: The 'low contraception use' risk class (32%) had low rates of condom or other birth control use, moderate rates of sexual initiation before age 16 years, and the highest pregnancy/early parenthood and STI rates. The predominately male 'early sex' risk class (32%) had higher rates of early initiation and multiple partners, risks that were countered by higher contraception and condom use. Both these risk groups showed higher probability to use substances before sex relative to the 'low sex risk' class (36%), which showed low rates on all risk behaviours. LCA identified distinct risk clusters that predicted sexual health outcomes and can inform targeted interventions for a minority youth population disproportionately affected by HIV, other STIs, and early parenthood.


Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus.
Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus is a promising strategy for the prevention of perinatal infections caused by group B streptococci. To explore the feasibility of this strategy, we vaccinated 40 pregnant women at a mean gestation of 31 weeks with a single 50-microgram dose of the Type III capsular polysaccharide of group B streptococcus. The only adverse effect detected was a mild local reaction in nine women (22 percent). Of the 35 women with low or unprotective antibody levels before immunization (less than 2 micrograms per milliliter), 20 (57 percent) responded to the vaccine. The geometric mean antibody level rose from 1.3 to 7.1 micrograms per milliliter four weeks after vaccination (P less than 0.02), and these levels persisted at delivery and three months post partum. Sixty-two percent of the vaccine-induced immunoglobulin in the mothers was IgG, which readily crosses the placenta. Infant antibody levels in cord serum correlated directly with maternal antibody levels at delivery (r = 0.913, P less than 0.001). Of the 25 infants born to women who responded to the vaccine, 80 percent continued to have protective levels of antibody at one month of age and 64 percent had protective levels at three months. Serum samples from infants with greater than or equal to 2 micrograms of antibody to Type III group B streptococcus per milliliter uniformly promoted efficient opsonization, phagocytosis, and bacterial killing in vitro of Type III strains. This effect could be mediated exclusively by the alternative complement pathway. Although this vaccine with an overall response rate of 63 percent is not optimally immunogenic, we conclude that maternal immunization is feasible and can provide passive immunity against systemic infection with Type III group B streptococcus in the majority of newborns. Larger trials with better vaccines will be required to evaluate the safety and clinical effectiveness of this strategy.


Kinetics of ribosome dissociation and subunit association studied in a light-scattering stopped-flow apparatus.
The association-dissociation kinetics of ribosomes from Escherichia coli have been studied under various conditions in a light-scattering stopped-flow apparatus. The dissociation reaction at 2 mg/ml at 25 degrees C, induced by lowering the MgCl2 concentration from 18 to 3 mM, can best be described by three independent first-order processes with rate constants of 15 s-1, 0.9 s-u, and 3 X 10(-2) s-1, the slowest process comprising about 60% of the overall reaction. The fraction of ribosomes dissociating with the fastest rate (15 s-1) is concentration dependent and becomes negligible at 0.1 mg/ml9 Ribosomes treated with puromycin also show three dissociation rates with essentially the same rate constants as the nontreated samples. The dissociation induced by a high KCl concentration (0.85 MKCl, 18 mM MgCl) also shows three first-order phases with the same rate constants as for the dissociation induced by lowering the MgCl2 concentration. The formation of 70S ribosomes from 30S and 50S subunits, induced by increasing the MgCl2 concentration from 2 to 21 mM, follows second-order biphasic kinetics. A detailed analysis of the kinetic results shows that the two principal ribosomal forms must have one type of subunit in common. When the association data are analyzed assuming that the kinetic heterogeneity arises from two forms of only one subunit, the rate constants are found to be 6.4 X 10(6) and 1.05 X 10(6) M-1 s-1. Sequential flow experiments show that the rapid and slow association species are to be identified, respectively, with phases II (0.9 s-1) and III 0.03 s-1) of dissociation. Relaxation measurements show that these correspond to type B ("loose") and A ("tight") ribosomes, respectively. Tight and loose ribosomes were isolated by sucrose density centrifugation, and dissociation and association kinetic studies confirmed the above assignments. Furthermore, the rate constants for these ribosoems agreed within experimental error with rate constants derived from analysis of the multiphasic kinetic data. The association rate constants are for ribosomes dissociated by dilution with the appropriate buffer immediately before recording the kinetics of association. Ribosomes dissociated by dialysis overnight against 2 mM MgCl2 show an association rate constant for the slower association reaction (type-A ribosome) that is about four times smaller, whereas the rate constant for the faster process is roughly the same. The activation energies of the dissociation reactions, whether induced by lowering the MgCl2 concentration or increasing the KCl concentration, and the association raaction induced by increasing the MgCl2 concentration are less than 3.5 kcal/mol. The rate constants of the dissociation at 3 mM MgCl2 and of the association reaction at 21 mM MgCl2 do not vary between pH 7.2 and 8.4. When 30S and 50S subunits are flowed against buffer containing 20 mM spermidine, the association process is monophasic, with an association constant k - 6 X 10(6) M-1 s-1...


Association of blood pressure and hypertension with the risk of Parkinson disease: the National FINRISK Study.
Cardiovascular risk factors, such as diabetes mellitus and central obesity, have been associated with Parkinson disease (PD), but data on blood pressure and PD are lacking. We sought to examine the association of blood pressure and hypertension with the risk of PD among men and women. This study consisted of 7 surveys (1972-2002) on representative samples of the general population in Finland (National FINRISK Study). A total number of 59 540 participants (age 25 to 74 years; 51.8% women) who were free of PD and stroke at baseline were prospectively followed until December 31, 2006, to identify incident PD cases using the National Social Insurance Register database. Cox proportional hazards models were constructed to estimate the hazard ratio of PD associated with blood pressure. During a mean follow-up period of 18.8 years (SD: 10.2 years), 423 men and 371 women were ascertained to have developed PD. In women, compared with normotensive subjects (<130/80 mm Hg), the multivariable-adjusted hazard ratios of PD associated with high-normal blood pressure (130 to 139/80 to 89 mm Hg) and hypertension (≥140/90 mm Hg or use of antihypertensive agents) were 1.63 (95% CI: 1.07 to 2.47) and 1.62 (95% CI: 1.09 to 2.42). There was no significant association between blood pressure and PD risk in men. The multivariable-adjusted hazard ratios of PD associated with use of antihypertensive agents were 1.08 (95% CI: 0.79 to 1.48) in men and 1.03 (95% CI: 0.76 to 1.38) in women. This study suggests that, in women, above-optimal blood pressure, including high-normal blood pressure and hypertension, is associated with an increased risk of PD. Optimal control of blood pressure in women may reduce the incidence of PD.


Competition and natural selection in a mathematical model of cancer.
A malignant tumor is a dynamic amalgamation of various cell phenotypes, both cancerous (parenchyma) and healthy (stroma). These diverse cells compete over resources as well as cooperate to maintain tumor viability. Therefore, tumors are both an ecological community and an integrated tissue. An understanding of how natural selection operates in this unique ecological context should expose unappreciated vulnerabilities shared by all cancers. In this study I address natural selection's role in tumor evolution by developing and exploring a mathematical model of a heterogenous primary neoplasm. The model is a system of nonlinear ordinary differential equations tracking the mass of up to two different parenchyma cell types, the mass of vascular endothelial cells from which new tumor blood vessels are built and the total length of tumor microvessels. Results predict the possibility of a hypertumor-a focus of aggressively reproducing parenchyma cells that invade and destroy part or all of the tumor, perhaps before it becomes a clinical entity. If this phenomenon occurs, then we should see examples of tumors that develop an aggressive histology but are paradoxically prone to extinction. Neuroblastoma, a common childhood cancer, may sometimes fit this pattern. In addition, this model suggests that parenchyma cell diversity can be maintained by a tissue-like integration of cells specialized to provide different services.


Simple, Affordable, and Modular Patterning of Cells using DNA.
The relative positioning of cells is a key feature of the microenvironment that organizes cell-cell interactions. To study the interactions between cells of the same or different type, micropatterning techniques have proved useful. DNA Programmed Assembly of Cells (DPAC) is a micropatterning technique that targets the adhesion of cells to a substrate or other cells using DNA hybridization. The most basic operations in DPAC begin with decorating cell membranes with lipid-modified oligonucleotides, then flowing them over a substrate that has been patterned with complementary DNA sequences. Cells adhere selectively to the substrate only where they find a complementary DNA sequence. Non-adherent cells are washed away, revealing a pattern of adherent cells. Additional operations include further rounds of cell-substrate or cell-cell adhesion, as well as transferring the patterns formed by DPAC to an embedding hydrogel for long-term culture. Previously, methods for patterning oligonucleotides on surfaces and decorating cells with DNA sequences required specialized equipment and custom DNA synthesis, respectively. We report an updated version of the protocol, utilizing an inexpensive benchtop photolithography setup and commercially available cholesterol modified oligonucleotides (CMOs) deployed using a modular format. CMO-labeled cells adhere with high efficiency to DNA-patterned substrates. This approach can be used to pattern multiple cell types at once with high precision and to create arrays of microtissues embedded within an extracellular matrix. Advantages of this method include its high resolution, ability to embed cells into a three-dimensional microenvironment without disrupting the micropattern, and flexibility in patterning any cell type.


Change in hippocampal volume on magnetic resonance imaging and cognitive decline among older depressed and nondepressed subjects in the neurocognitive outcomes of depression in the elderly study.
previous studies have linked hippocampal volume change and cognitive decline in older adults with dementia. The authors examined hippocampal volume change and cognitive change in older nondemented adults with and without major depression. the sample consisted of 90 depressed individuals and 72 healthy, nondepressed individuals aged 60 years and older who completed at least 2 years of follow-up data. All patients underwent periodic clinical evaluation by a geriatric psychiatrist as well as baseline and 2-year magnetic resonance imaging. over 2 years, the depressed group showed a greater reduction in left hippocampal volume (normalized for total cerebral volume) compared with the nondepressed group (mean difference = 0.013 ± 0.0059, t = 2.18, df = 160, p <0.0305). The difference remained significant after controlling for age, sex, and baseline normalized left hippocampal volume. The authors also found that hippocampal change from baseline to 2 years was associated with subsequent change in Mini-Mental State Examination score from 2 years to 2½ years (left t = 2.81, df = 66, p = 0.0066; right t = 2.40, df = 66, p = 0.0193) among the depressed group. these findings add to the literature linking hippocampal volume loss and late-life depression. Depressed patients with hippocampal volume loss are at greater risk of cognitive decline.


Investigation into the seroprevalence of falcon herpesvirus antibodies in raptors in the UK using virus neutralization tests and different herpesvirus isolates.
Increasing numbers of reports of clinical falcon herpesvirus infection (Falconid herpesvirus-1; FHV-1) have been seen in the UK since 1996. The aim of this epidemiological study was to investigate the seroprevalence of FHV-1 and owl herpesvirus (Strigid herpesvirus-1; StHV-1) infection in the UK, using virus neutralization tests, and to evaluate the prevalence of herpesvirus infection in captive and wild raptor populations. The results, using the English FHV-1 CVL 32/93 isolate, revealed a seroprevalence of 3.97% (10/252). The seroprevalence for StHV-1 was 12.3% (8/65). Analysis of the data by captivity status, age and species revealed that the family Falconidae showed the highest seroprevalence with 6.7% (5/75), while only one of 104 captive Accipitridae was positive for FHV-1 (0.96%). The incidence of FHV-1 neutralizing antibodies in owls was 5.5% (4/73), representing only wild individuals. Eighty-nine serum samples were additionally tested using two other FHV-1 isolates, the German isolate Merlin 1869/92 and the Dutch isolate Peregrine Z100. The seroprevalences of FHV-1 were 28.1% (25/89) and 32.6% (29/89), respectively. All these samples, however, were negative using the CVL 32/92 isolate.


[Severe cartilage loss caused by metallic anchors in surgical treatment of a Bankart lesion: report of three cases].
Currently, arthroscopic modalities in the surgical treatment of shoulder instability using suture anchors are more popular than open surgery. However, there are some complications related to the metallic suture anchors used. One of the most common complications is cartilage loss due to shallow placement of the suture anchor. Herein, we report three cases with severe cartilage loss of the humeral head due to metallic proud anchors, including one of whom requiring total shoulder arthroplasty. In conclusion, it is essential to place the suture anchors in an appropriate position and deepness. In case of any doubt, they should be removed or in non-threaded anchors, they should be inserted fully inside the glenoid with an impactor and a hammer to avoid serious cartilage loss.


[Relationship between Chlamydia pneumoniae and classical risk factors of coronary heart disease].
In order to elucidate relationship between Chlamydia pneumonia infection and established risk factors of coronary heart disease (hypercholesterolemia, hyperglycemia, hyperfibrinogenemia, smoking, age) chlamydial IgA and IgG antibodies were determined by solid phase enzyme immunoassay in 122 patients with ischemic heart disease and 40 healthy subjects. Elevated titers of IgA class antibodies were found to be associated with presence of ischemic heart disease as well as with hypercholesterolemia, hyperglycemia, hyperfibrinogenemia, and smoking.


In vitro TSH and PRL secretion from eutopic and heterotopic rat pituitaries: effects of hypothyroidism.
Five adenohypophyses from donors of the same strain, age, and sex were transplanted under the renal capsule of young adult female rats. At least 3 wk later, enzymatically dispersed cells from eutopic or heterotopic adenohypophyses from the same rat were perifused in vitro in a small chamber. Thyrotropin (TSH) and prolactin (PRL) secretion per 10(6) cells were significantly less from heterotopic than from eutopic cells under all conditions. In cells from euthyroid animals, TRH induced TSH secretion only in the eutopic cells but induced PRL secretion in both eutopic and heterotopic cells. Hypothyroidism increased TRH-induced TSH secretion and content in the cell lysate in both eutopic and heterotopic cells but increased TRH-induced PRL secretion only in the eutopic cells. The increase in TSH secretion induced by hypothyroidism in the heterotopic cells was of borderline statistical significance. The inability of TRH to induce TSH secretion in heterotopic pituitary cells from euthyroid rats may be due to a lower set point for thyroid hormone inhibition of TSH secretion in the heterotopic thyrotrophs. Heterotopic pituitary TSH secretion is probably suppressed by the normal plasma thyroid hormone concentration maintained by the eutopic pituitary and may be stimulated by TRH only in the presence of a subnormal plasma thyroid hormone concentration.


Larvicidal Activity of Essential Oil Constituents Against Malaria Vector, Anopheles gambiae (Diptera: Culicidae).
Malaria is one of the most important public health problems worldwide. This illness is controlled, mainly, by combating the vector mosquitoes using chemical insecticides, but this use has caused environmental impact and the emergence of tolerance in adult mosquitoes. Herein, we report the larvicidal activity of nine chemical constituents found in essential oils against third-instar larvae of Anopheles gambiae. All the tested compounds showed larval toxicity. Among the nine effective components, citronellol exhibited a pronounced larvicidal effect against the larvae of An. gambiae, with LC₅₀ values of 96.1 and 55.6 ppm after 12 and 24 hours of treatment, respectively; however, hydroxycitronellal was the most potent compound after 48 and 72 h of exposure (LC₅₀=3.7 and 2.3 ppm, respectively), followed by citronellol (LCso= 16.7 and 6.3 ppm, respectively). Moreover, larval mortality was concentration- and time-dependent.


Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset.
Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95-1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86-0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71-0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82-0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset.


Women's experience of group prenatal care.
Group prenatal care (GPNC) is an innovative alternative to individual prenatal care. In this longitudinal study we used ethnographic methods to explore African American and Hispanic women's experiences of receiving GPNC in two urban clinics. Methods included individual, in-depth, semistructured interviews of women and group leaders in GPNC, participant observation of GPNC sessions, and medical record review. GPNC offered positive experiences and met many of women's expressed preferences regarding prenatal care. Six themes were identified, which represented separate aspects of women's experiences: investment, collaborative venture, a social gathering, relationships with boundaries, learning in the group, and changing self. Taken together, the themes conveyed the overall experience of GPNC. Women were especially enthusiastic about learning in groups, about their relationships with group leaders, and about having their pregnancy-related changes and fears normalized; however, there were also important boundaries on relationships between participants, and some women wished for greater privacy during physical examinations.


Principles for telemedicine and telecare: the perspective of a citizens' panel.
Ten delegates at the conference Voluntarism, Health and Social Care were recruited to form a panel of citizens to debate and offer direction for the future of technologically mediated health care. The panel suggested various principles for the development of telemedicine and telecare, concerning: patients, users and carers, approach to service delivery, research and knowledge, and conditions of use. Many of the principles echoed the founding values of the National Health Service, yet have arguably been absent from both policy pronouncements and the telemedicine literature, which largely views new health technologies themselves as 'value free', i.e. developed untouched by social and political relations. A programme of citizens' panels should be developed so that an informed debate can take place about the development of telemedicine and telecare, to underpin policy and practice.


Effects of simulated microgravity on the development and maturation of dissociated cortical neurons.
Although a wealth of evidence supports the hypothesis that some functions of the nervous system may be altered during exposure to microgravity, the possible changes in basic neuronal physiology are not easy to assess. Indeed, few studies have examined whether microgravity affects the development of neurons in culture. In the present study, a suspension of dissociated cortical cells from rat embryos were exposed to 24 h of simulated microgravity before plating in a normal adherent culture system. Both preexposed and control cells were used after a period of 7-10 d in vitro. The vitality and the level of reactive oxygen species of cultures previously exposed did not differ from those of normal cultures. Cellular characterization by immunostaining with a specific antibody displayed normal neuronal phenotype in control cells, whereas pretreatment in simulated microgravity revealed an increase of glial fibrillary acidic protein fluorescence in the elongated stellate glial cells. Electrophysiological recording indicated that the electrical properties of neurons preexposed were comparable with those of controls. Overall, our results indicate that a short time of simulated microgravity preexposure does not affect dramatically the ability of dissociated neural cells to develop and differentiate in an adherent culture system.


Adverse health outcomes and global quality of life in long-term testicular cancer survivors: a longitudinal 30-year perspective.
The aim of this study was to characterize the prevalence of self-reported adverse health outcomes (AHOs), track changes in AHOs, and examine their impact on health-related quality of life (HrQoL) in testicular cancer survivors (TCSs) who were diagnosed between 1980 and 1994. These assessments were conducted during two survey waves (SWs), with the first occurring ∼12 years after surgery-only or platinum-based chemotherapy (PBCT), and the second ∼28 years after initial treatment. The study primarily focused on 'typical AHOs', which included Peripheral Sensory Neuropathy (PSN), Raynaud's phenomenon, Tinnitus, and Hearing loss. A total of 427 TCSs were included in the evaluation, distributed as follows: surgery-only group (n = 155), PBCT-standard group with ≤850 mg cisplatin (n = 222), and PBCT-high group with >850 mg cisplatin (n = 50). For comparison of HrQoL, men from the general population served as a control group (referred to as 'Norms'). The statistical significance level was set at P < 0.05, and clinical importance, in terms of testing HrQoL differences, was defined as Δ ≥2.5 points. A higher number of TCSs who underwent PBCT reported experiencing typical AHOs compared with those who had surgery only. The highest prevalence rates were observed among TCSs who had undergone PBCT-high. Further, the number of TCSs describing typical AHOs, except Raynaud's phenomenon, increased during the observation period of 16 years. At the last SW, a median of 4 AHOs (any type) were reported after PBCT-high compared with a median of 2 AHOs after Surgery-only or after PBCT-standard. With Surgery-only as reference, PBCT-high, but not PBCT-standard, was associated with decreasing physical HrQoL in the last SW (A2 Regression coefficient: -4.3; P = 0.008). When comparing all TCSs with Norms no clinically important difference in physical and mental HrQoL was observed at either SW. However, at the last SW, TCSs after PBCT-high therapy represented a subgroup of TCSs with clinically important impairment of HRQoL. Of the typical AHOs, only PSN reduced HrQoL. Chronic fatigue, pain, anxiety/depression, sexual dysfunction, unemployment, being single, and low education were additional covariates. After a median of 28 years since their treatment, HrQoL in TCSs was found to be comparable to that of Norms. This similarity held true even though AHOs, especially after PBCT-high, were becoming more prevalent among TCSs. The study revealed that individuals with a history of PBCT-high are at a high risk of experiencing a significantly increased prevalence of long-term AHOs, which subsequently leads to diminished HrQoL. It is crucial to recognize and provide specialized attention to these TCSs during lifelong follow-up care.


Difficulties in the Treatment of Diabetic Foot and Research Progress of Combination of Traditional Chinese and Western Medicine.
A diabetic foot is any disorder directly attributable to peripheral arterial disease (PAD) and/or the sensory neuropathies influencing the diabetic foot; it is a long-term (or "chronic") complication of diabetes. Generally, it is a permanent (or "chronic") comorbidity of diabetes. The swallowing of peripheral neuropathy and peripheral vascular disease leads to damage to the soft tissue, bone, and joint system of the foot. In addition, diabetic feet are also susceptible to infection, which can lead to lameness and even amputation. The management of the diabetic foot can be both challenging and chronic; it may comprise orthoses, surgery, antibacterial medication, and topical dressings. Traditional Chinese medicine (TCM) has a variety of methods for the treatment of diabetic foot with obvious advantages, which can be divided into internal treatment and external treatment of TCM. These treatments include external foot bath, fumigation and washing stains, internal administration of traditional Chinese medicine, syndrome differentiation and staging treatment, empirical prescription, self-made prescription, internal use of proprietary Chinese medicine, massage, acupuncture, and paste powder application, which have significant value in the prevention and treatment of diabetic foot. Some studies have shown that modern medicine combined with herbal therapy can significantly improve the prognosis of diabetic foot. Therefore, this study summarized the difficulties in the therapeutic approaches to diabetic foot and the recent research progress in combining Chinese and Western medicine in the treatment of diabetic foot.


Biphasic Renal Sympathetic Response to Hemorrhagic Hypotension in Mice.
The inhibitory responses of renal sympathetic nerve activity (RSNA) and heart rate (HR) to sustained hemorrhagic shock occurred in anesthetized rats, but have not yet been determined in mice. Here, we investigated the responses of RSNA and HR to hemorrhagic hypotension in anesthetized mice, with an emphasis on the molecule-based mechanism for roles of afferent vagal nerves. RSNA, HR, and mean systemic arterial pressure were continuously measured in male pentobarbital-anesthetized C57BL/6N mice. Hemorrhagic hypotension of 50 mmHg was evoked and maintained for 10 min. During hemorrhagic hypotension, RSNA initially increased and then sustainedly decreased, while HR progressively decreased. Vagotomy eliminated the second-phase sympathoinhibition and bradycardia, and carotid sinus denervation with vagotomy abolished the initial renal sympathoexcitation. The renal sympathoinihibition during hemorrhagic hypotension of 50 mmHg was eliminated in mice pretreated with a transient receptor potential vanilloid type 1 channel (TRPV1) inhibitor, capsazepine, and in TRPV1 knockout (TRPV1) mice, but not in TRPV4 knockout mice. The bradycardia response to hemorrhagic hypotension was also absent in TRPV1 mice and mice pretreated with capsazepine. Hemorrhagic hypotension in anesthetized mice causes biphasic responses of RSNA with an initial increase, followed by a sustained decrease, and a progressive decrease in HR. The initial sympathoexcitation is mediated by carotid sinus baroreceptors, while the later sympathoinhibition and bradycardia are mediated via the TRPV1 signals of vagal afferents.


Establishment and proteomic characterization of NCC-LMS1-C1, a novel cell line of primary leiomyosarcoma of the bone.
Leiomyosarcoma (LMS) is one of most aggressive mesenchymal malignancies that differentiate towards smooth muscle. The clinical outcome of LMS patients is poor; as such, there is an urgent need for novel therapeutic approaches. Experimental models such as patient-derived cell lines are invaluable tools for pre-clinical studies. In the present study, we established a stable cell line from the tumor tissue of a patient with a primary LMS of the bone. Despite the urgent need for novel therapeutic strategies in LMS, there are only a few LMS cell lines available in public cell banks, none of which are primary to the bone. Bone primary LMS tumor tissues were sampled to establish cell lines. Morphological and proteomic analyses were performed and sensitivity to pazopanib was evaluated. NCC-LMS1-C1 cells were maintained for over 100 passages. The cells exhibited a spindle shape and aggressive growth; they also expressed smooth muscle actin, reflecting the original LMS tissue (i.e. smooth muscle cells). The cells also showed tumor characteristics such as colony formation on soft agar and sensitivity to pazopanib, doxorubicin and cisplatin, with half-maximal inhibitory concentrations of 4.5, 0.11 and 20 μM, respectively. Proteomic analyses by mass spectrometry and antibody array revealed some differences in the protein expression profiles of these cells as compared to the original tumor tissue. Our results indicate that the NCC-LMS1-C1 cell lines will be useful for LMS research.


The acyl-CoA binding protein is required for normal epidermal barrier function in mice.
The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP(-/-) mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling with age. Morphology and development of skin and appendages are normal in ACBP(-/-) mice; however, the stratum corneum display altered biophysical properties with reduced proton activity and decreased water content. Mass spectrometry analyses of lipids from epidermis and stratum corneum of ACBP(+/+) and ACBP(-/-) mice showed very similar composition, except for a significant and specific decrease in the very long chain free fatty acids (VLC-FFA) in stratum corneum of ACBP(-/-) mice. This finding indicates that ACBP is critically involved in the processes that lead to production of stratum corneum VLC-FFAs via complex phospholipids in the lamellar bodies. Importantly, we show that ACBP(-/-) mice display a ∼50% increased transepidermal water loss compared with ACBP(+/+) mice. Furthermore, skin and fur sebum monoalkyl diacylglycerol (MADAG) levels are significantly increased, suggesting that ACBP limits MADAG synthesis in sebaceous glands. In summary, our study shows that ACBP is required for production of VLC-FFA for stratum corneum and for maintaining normal epidermal barrier function.


Food Insecurity, Neighborhood Disadvantage, and Hospital Readmission in Health System Adults: A Population Health Study.
The purpose of the study was to examine the relationship between food insecurity, neighborhood disadvantage, and hospital readmission within 90 days of discharge for health system patients. The study used a retrospective, correlational design with a single cohort. Records of adult patients with a health system primary care provider and discharged from hospital to home were included. Data were obtained from health system billing database, medical record, and publicly available population databases. A time-to-readmission analysis was conducted with a Kaplan-Meier plot, log-rank test, and Cox regression analysis. The final sample included 41 566 records; the rate of food insecurity was 1.45%, and 90-day readmission rate was 16.7%. The mean area deprivation index score was 54.4 (SD, 26.0). After adjusting for patient demographics, comorbidity, and length of stay, food insecurity resulted in 1.94 times higher risk of readmission (hazard ratio, 1.94; 95% confidence interval, 1.69-2.23; P < .001). Neighborhood disadvantage and lower food access were not significant in final models. Food insecurity should be identified and addressed as part of transitional care to improve patient outcomes. Future research should focus on models of care that ensure connection to community resources to resolve food insecurity and evaluate the impact on patient outcomes.


Agenesis of the posterior arch of the atlas.
To illustrate the radiological findings and review the current literature concerning a rare congenital abnormality of the posterior arch of the atlas. An adult female without neurological symptoms presented with an absent posterior arch of the atlas, examined with plain films and helical computerized tomography. Complete agenesis of the posterior arch of the atlas is a rare entity that can be easily identified by means of plain films. Although it is generally asymptomatic, atlantoaxial instability and neurological deficits may occur because of structural instability. Computerized tomography provides a means of assessing the extent of this abnormality and can help evaluate the integrity of neural structures. Although considered to be rare entities, defects of the posterior arch of the atlas may be discovered as incidental asymptomatic findings in routine cervical radiographs. Familiarity with this abnormality may aid medical professionals in the correct management of these cases.


Availability, Quality, and Relevance of Toxicogenomics Data for Human Health Risk Assessment: A Scoping Review of the Literature on Trihalomethanes.
Human health risk assessment (HHRA) must be adapted to the challenges of the 21st century, and the use of toxicogenomics data in HHRA is among the changes that regulatory agencies worldwide are trying to implement. However, the use of toxicogenomics data in HHRA is still limited. The purpose of this study was to explore the availability, quality, and relevance to HHRA of toxicogenomics publications as potential barriers to their use in HHRA. We conducted a scoping review of available toxicogenomics literature, using trihalomethanes as a case study. Four bibliographic databases (including the Comparative Toxicogenomics Database) were assessed. An evaluation table was developed to characterize quality and relevance of studies included on the basis of criteria proposed in the literature. Studies were selected and analyzed by 2 independent reviewers. Only 9 studies, published between 1997 and 2015, were included in the analysis. Based on the selected criteria, critical methodological details were often missing; in fact, only 3 out of 9 studies were considered to be of adequate quality for HHRA. No studies met >3 (out of 7) criteria of relevance to HHRA (eg, adequate number of doses and sample size). This first scoping review of toxicogenomics publications on trihalomethanes shows that low availability, quality, and relevance to HHRA of toxicogenomics publications presents potential barriers to their use in HHRA. Improved reporting of methodological details and study design is needed in the future so that toxicogenomics studies can be appropriately assessed regarding their quality and value for HHRA.


Using a stick does not necessarily alter judged distances or reachability.
It has been reported that participants judge an object to be closer after a stick has been used to touch it than after touching it with the hand. In this study we try to find out why this is so. We showed six participants a cylindrical object on a table. On separate trials (randomly intermixed) participants either estimated verbally how far the object is from their body or they touched a remembered location. Touching was done either with the hand or with a stick (in separate blocks). In three different sessions, participants touched either the object location or the location halfway to the object location. Verbal judgments were given either in centimeters or in terms of whether the object would be reachable with the hand. No differences in verbal distance judgments or touching responses were found between the blocks in which the stick or the hand was used. Instead of finding out why the judged distance changes when using a tool, we found that using a stick does not necessarily alter judged distances or judgments about the reachability of objects.


Nephrotic syndrome, renal failure, and renal malignancy: an unusual tumor-associated glomerulonephritis.
The association between malignancy and glomerular disease has been appreciated for over three decades. Although the relationship between membranous glomerulonephritis or minimal-change nephrotic syndrome and carcinoma or lymphoma, respectively, are the most widely known, several other glomerular lesions have been described in patients with malignancy. In this article, a patient who presented with nephrotic syndrome, volume overload, and renal failure, who was subsequently found to have a renal mass, is described. Resection of the mass, which proved to be a renal cell carcinoma, led to resolution of proteinuria and improvement of renal function. Pathology on the noninvolved portion of the kidney revealed a membranoproliferative glomerular lesion, a lesion usually associated with lymphomas and not previously described with renal carcinoma. Although a role of tumor antigens and anti-tumor antibodies in producing glomerular immune deposits has been speculated upon, the evidence for this assertion was spotty. However, reports of remission of proteinuria after tumor treatment or removal support a role of tumor products in pathogenesis. Although the association between proteinuria and malignancy is rare, it should be kept in mind, particularly in older patients with membranous glomerulonephritis where the possibility of malignancy needs to be further evaluated.


Predisposing factors for recanalization of cerebral aneurysms after endovascular embolization: a multivariate study.
The recanalization of cerebral aneurysms after endovascular embolization (coiling or stent-assisted coiling) has been a matter of concern. To systematically evaluate the predisposing factors for cerebral aneurysm recanalization using multidimensional analysis in a large patient cohort. In 238 patients with 283 aneurysms, patient baseline characteristics, aneurysm morphological characteristics, treatment-related factors, and changes in flow hemodynamics after endovascular treatment (coiling or stent-assisted coiling) were compared between the recanalization and non-recanalization groups. Multivariate logistic regression analysis was performed to determine independent risk factors correlated with recanalization. 16 aneurysms treated by coiling recanalized, with a recurrence rate of 18.6%, and 24 recanalized in the lesions treated by stent-assisted coiling, with a recanalization rate of 12.2%. Large aneurysms (>10 mm, p=0.002) and a follow-up interval >1 year (p=0.027) were shown to be statistically significant between the recanalization and non-recanalization groups. For flow hemodynamic changes, three parameters (velocity on the neck plane, wall shear stress on the neck wall, and wall shear stress on the whole aneurysm) showed a relatively lower amplitude of decrease after endovascular treatment in the recanalization group. Interestingly, the velocity on the neck plane and wall shear stress on the neck wall may be elevated after treatment. Specifically, the reduction ratio (RR) of velocity on the neck plane showed significant difference between the groups in the multivariate analysis (p=0.013), and was considered an independent risk factor for recanalization. The aneurysm size, follow-up interval, and flow hemodynamic changes, especially the RR of velocity on the neck plane, have important roles in aneurysm recanalization.


Class III antiarrhythmic drugs block HERG, a human cardiac delayed rectifier K+ channel. Open-channel block by methanesulfonanilides.
We recently reported that mutations in HERG, a potassium channel gene, cause long QT syndrome. Heterologous expression of HERG in Xenopus oocytes revealed that this channel had biophysical properties nearly identical to a cardiac delayed rectifier K+ current I(Kr), but had dissimilar pharmacological properties. Class III antiarrhythmic drugs such as E-4031 and MK-499 are potent and specific blockers of I (Kr) in cardiac myocytes. Our initial studies indicated that these compounds did not block HERG at a concentration of 1 micromol/L. In the present study, we used standard two-microelectrode voltage-clamp techniques to further characterize the effects of these drugs on HERG channels expressed in oocytes. Consistent with initial findings, 1 micromol/L MK-499 and E-4031 had not effect on HERG when oocytes were voltage clamped at a negative potential and not pulsed during equilibration with the drug. However, MK-499 did block HERG current if oocytes were repetitively pulsed, or clamped at a voltage positive to the threshold potential for channel activation. This finding is in contrast to previous studies that showed significant block of I(Kr) in isolated myocytes by similar drugs, even in the absence of pulsing. This apparent discrepancy may be due to differences in channel characteristics (HERG versus guinea pig and mouse I (Kr)), tissue (oocytes versus myocytes), or specific drugs. Under steady state conditions, block of HERG by MK-499 was half maximal at 123 +/- 12 nmol/L at a test potential of -20 mV. MK-499 (150 nmol/L) did not affect the voltage dependence of activation and rectification nor the kinetics of activation and deactivation of HERG. These data indicate that MK-499 preferentially blocks open HERG channels and further support the conclusion that HERG subunits form I(Kr) channels in cardiac myocytes.


A homologue of EGL1 encoding endo-1,4-beta-glucanase in elongating pea stems.
A gene (EGL2) encoding an endo-1,4-beta-glucanase in peas has been cloned as a homologue of EGL1. EGL2 encodes a polypeptide of 506 amino acids, including a 24-mer putative signal polypeptide. The gene product contains a domain conserved in endo-1,4-beta-glucanase (family 9) showing 60% amino acid identity to EGL1. EGL2 mRNA was accumulated only in the elongating regions of pea stems, although EGL1 mRNA was abundant in both elongating and non-elongating tissues. However, the level of EGL2 mRNA was not increased by the treatment with sucrose and auxin in pea segments. These results suggest that the expression of EGL2 either requires the presence of other factors related to the auxin effect or occurs independent of auxin in the elongating pea stems.


A comparative study of the "superior mesenteric artery first" approach versus the conventional approach in short-term and long-term outcomes in patients with pancreatic ductal adenocarcinoma undergoing laparoscopic pancreaticoduodenectomy.
The use of laparoscopic pancreaticoduodenectomy (LPD) in pancreatic head cancer remains controversial, and an appropriate surgical approach can help improve perioperative safety and oncological outcomes. This study aimed to assess the short-term outcomes and long-term survival of the superior mesenteric artery first (SMA-first) approach in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing LPD. The data of 91 consecutive PDAC patients who underwent LPD from June 2014 to June 2021 were retrospectively analyzed. Patients were divided into two groups, the modified SMA-first approach group, using a combined posterior and anterior approach, and the conventional approach group. Perioperative outcomes, pathologic results, and overall survival (OS) were compared between groups, and propensity score-matched (PSM) analysis was performed. The number of lymph nodes harvested was greater in the SMA-first approach group (19 vs. 15, P = 0.021), as did the results in the matched cohort (21 vs. 15, P = 0.046). No significant difference was observed in the R0 resection rate (93.3% vs. 82.6%, P = 0.197), but the involvement of the SMA margin was indeed lower in the SMA-first approach group (0 vs. 13%). There were no obvious variances between the two groups in terms of intraoperative bleeding, operative time, overall and major postoperative complication rates, and mortality in either the original cohort or matched cohort. The median OS was 21.8 months in the SMA-first group, whereas it was 19.8 months in the conventional group (P = 0.900). Survival also did not differ in the matched cohort (P = 0.558). TNM stage, resection margin, overall complications, and adjuvant therapy were independent risk factors affecting OS. The modified SMA-first approach is safe and feasible for PDAC patients undergoing LPD. It had a slight advantage in specimen quality, but OS was not significantly prolonged.


Determination of 23 Amino Acids and Amines in Plasma and Cortex of C57BL/6 Mice with HPLC-FLD.
Using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as a pre-column derivatization reagent, optimized derivatization and chromatography parameters, a simple high-performance liquid chromatography fluorescence detector (HPLC-FLD) method was developed and validated to determine 23 related amines in plasma and cortex of C57BL/6 mice with cerebral ischemia-reperfusion injury. The prepared samples were separated on a ZORBAX SB-C18 column (4.6 mm × 250 mm, 5 μm) with 60% acetonitrile (ACN) and 20 mM sodium acetate solution (pH adjusted to 5.0 by phosphoric acid). All analytes achieved good separation within 1.2 h at a flow rate of 1 mL/min. The limits of detection and limits of detection quantitation of the method were ranged from (0.1-9.2) to (0.3-30.6) ng/mL, respectively. The analytical method was apt for simultaneously determining 23 amino acids in plasma and cortex. Our results revealed that the relevant amino acids were significantly altered (P < 0.05) in C57BL/6 mice.


Stereological studies of the effects of alpha-MSH and cAMP on melanosomes in melanoma cells.
The effects of alpha-MSH and cAMP on melanosomes in Cloudman S91 melanoma cells were investigated by modern stereological techniques. Cells were cultured for 4 days in medium containing alpha-MSH or cAMP, harvested at 24 hour intervals; some were frozen for melanin assay and the reminder embedded in Epon for light and electron microscopy. Cellular and melanosomal parameters were estimated by new stereological probes. We found that both stimulators induced increases in nuclear volume, cell volume, and the volume fractions and volumes of premelanosomes (V(Vpm,cell), Vpm) and mature melanosomes (V(Vmm,cell), Vmm), and the number of mature melanosomes (Nmm). Both stimulators also caused declines in the volume of individual mature melanosomes (V(Vimm)), the melanin content per mature melanosome unit volume and the melanin content per individual mature melanosome. The increases in the volume of individual premelanosomes and the number of premelanosomes were only induced by cAMP. The effect cAMP on some parameters occurred 24 hours prior to alpha-MSH and was more marked. The response of premelanosomes to the stimulators was more sensitive than mature melanosomes. These results suggest that both stimulators enhanced melanogenesis by increasing the V(Vpm,cell), V(Vmm,cell), Vpm, Vmm and Nmm. The melanogenic level did not depend on the V(Vimm) and melanin concentration in melanosomes. The maturation of premelanosomes was involved in melanogenesis induced by both stimulators, but, de novo synthesis and enlargement of premelanosomes were only stimulated by cAMP. It imply that exogenous cAMP may affect melanosomes, and hence melanogenesis in quantitatively or qualitatively different ways to alpha-MSH.


[Mechanisms of formation and biological role of protein carbamates].
Experimental data are presented evidencing for the fact that tissue proteins under conditions in vivo are subjected to enzymic carboxylation with formation of carbaminic groups. In this case a charge variation in definite sites of protein molecule is observed, which specifies variation of the protein conformation and biological properties. Basic regularities of protein carbamate formation reactions are revealed with factors affecting their intensity enumerated. The reactions are shown to be of great biological significance for the respiration processes, realization of hormonal effects of peptide and protein hormones as well as for regulation of tissue homeostasis under conditions of acidic-alkaline state variation in the organism.


Serologic markers associated with development of Crohn's disease after ileal pouch anal anastomosis for ulcerative colitis.
One of the causes of pouch failure after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) is the development of de novo Crohn's disease (CD). Our aim was to clearly define factors associated with post-IPAA CD. We conducted a cross-sectional study to compare demographic, clinical, and serological characteristics of patients with and without post-IPAA CD. All subjects underwent testing for anti-neutrophil cytoplasm antibodies, anti-Saccaromyces cerevisiae antibodies, anti-outer membrane porin C antibodies, and anti-CBir1 flagellin (anti-CBir1). A multivariable model assessed factors associated with post-IPAA CD. Thirty-nine subjects were enrolled in the study: 20 cases and 19 controls. Patients who developed post-IPAA CD were significantly younger (median 22 ± 9.9 vs. 30 ± 11.3, p = .027) at the time of UC diagnosis and exhibited more extraintestinal manifestations compared to controls (p = .023). No significant difference between the groups was found with respect to family history, smoking, duration of illness prior to colectomy, time to the onset of pouchitis, preoperative treatment, and indication for surgery. However, the post-operative serologic profile differed significantly with far more cases having elevated anti-CBir1 titers (p = .016, OR 8.81), the latter being the only independent predictor in the combined model. Patients with Crohn's disease of the pouch were more likely to have elevated CBir1 antibodies titers than those with simple pouchitis and healthy pouches. The stability of the CBir1 antibodies (pre- and post-colectomy) must be further assessed to establish its value as an independent predictor for development of post-IPAA CD.


Roles traditional healers play in cancer treatment in Malaysia: implications for health promotion and education.
For a number of reasons from cultural compatibility, to accessibility, to cost, traditional healers are a major source of health care in developing countries. In Malaysia, 'en estimated that upwards of 80% of the population consult traditional healers even if simultaneously seeking treatment from the Western medical system. Partially as a result of the widespread practice of visiting traditional healers, cancer diagnosis and treatment in Malaysia is often delayed or interrupted resulting in late presentation, advanced stage diagnosis, and a higher mortality rate than in Western countries. However, there is very little research on the role of traditional healers in cancer treatment in Malaysia. This qualitative study was designed to identify the roles traditional healers play in cancer diagnosis and treatment, with an eye to alleviating the cancer burden through educational responses with four publics in mind-policy makers, Western medical personnel, traditional healers, and the general public. In-depth interviews were conducted with 14 Malay traditional healers, 13 cancer survivors who had seen both traditional healers and Western doctors, and 12 cancer medical specialists. Analysis of the data from these 39 participants revealed four roles traditional healers play in cancer treatment-medicinal healer, emotional comforter, spiritual guide, and palliative caregiver. Three roles (emotional, spiritual, palliative) can be seen as complementary to the allopathic system. Emotional and spiritual roles may augment the effectiveness of biomedical treatment. Cancer awareness and education programs need to position traditional healers as complementary, rather than an alternative to Western medical treatment; Validating the roles Traditional Healers can play in cancer treatment in MY through health promotion and education will contribute to alleviating the nation's cancer burden.


Effects of anti-fibrillarin antibodies on building of functional nucleoli at the end of mitosis.
During mitosis some nuclear complexes are relocalized at the chromosome periphery and are then reintegrated into the re-forming nuclei in late telophase. To address questions concerning translocation from the chromosome periphery to nuclei, the dynamics of one nucleolar perichromosomal protein which is involved in the ribosomal RNA processing machinery, fibrillarin, was followed. In the same cells, the onset of the RNA polymerase I (RNA pol I) activity and translocation of fibrillarin were simultaneously investigated. In PtK1 cells, RNA pol I transcription was first detected at anaphase B. At the same mitotic stage, fibrillarin formed foci of increasing size around the chromosomes, these foci then gathered into prenucleolar bodies (PNBs) and later PNBs were targeted into the newly formed nucleoli. Electron microscopy studies enabled the visualization of the PNBs forming the dense fibrillar component (DFC) of new nucleoli. Anti-fibrillarin antibodies microinjected at different periods of mitosis blocked fibrillarin translocation at different steps, i.e. the formation of large foci, foci gathering in PNBs or PNB targeting into nucleoli, and thereby modified the ultrastructural organization of the nucleoli as well as of the PNBs. In addition, antibody-bound fibrillarin seemed localized with blocks of condensed chromatin in early G1 nuclei. It has been found that blocking fibrillarin translocation reduced or inhibited RNA pol I transcription. It is postulated that when translocation of proteins belonging to the processing machinery is inhibited or diminished, a negative feed-back effect is induced on nucleolar reassembly and transcriptional activity.


Orientation and structure of the Ndc80 complex on the microtubule lattice.
The four-subunit Ndc80 complex, comprised of Ndc80/Nuf2 and Spc24/Spc25 dimers, directly connects kinetochores to spindle microtubules. The complex is anchored to the kinetochore at the Spc24/25 end, and the Ndc80/Nuf2 dimer projects outward to bind to microtubules. Here, we use cryoelectron microscopy and helical image analysis to visualize the interaction of the Ndc80/Nuf2 dimer with microtubules. Our results, when combined with crystallography data, suggest that the globular domain of the Ndc80 subunit binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the protofilament axis. Such a binding mode, in which the Ndc80 complex interacts with sequential alpha/beta-tubulin heterodimers, may be important for stabilizing kinetochore-bound microtubules. Additionally, we define the binding of the Ndc80 complex relative to microtubule polarity, which reveals that the microtubule interaction surface is at a considerable distance from the opposite kinetochore-anchored end; this binding geometry may facilitate polymerization and depolymerization at kinetochore-attached microtubule ends.