Introduction to microcomputer hardware and software.
Although general purpose computers have been available for more than 40 years, the dramatic plunge in the cost of electronics in the past 10 years has finally made significant computing power affordable to almost anyone. However, a large number of people including professionals have little idea of how a computer really works or what it can and cannot do. Presented here is an introduction to the hardware and software of microcomputers which assumes no working knowledge of electronics or programming. The fundamental pieces of a microcomputer are explained, giving some insight into the reasons why present microcomputers are built the way they are. This is followed by a discussion of the fundamentals of how software is used to make the hardware compute. The various levels of software are discussed, then the most commonly used types of user application software are described, and finally some suggestions are made on how to choose a personal computer.


Endogenous lectin (RL-29) expression of the autonomic preganglionic neurons in the rat spinal cord.
Rat spinal neurons expressing lectin RL-29 are visualized immunohistochemically. RL-29 immunoreactive (RL-29 IR) neurons are found in the lateral parts of laminae V-VII, designated as the intermediolateral cell column (IML) in the thoracic cord, the sacral parasympathetic nucleus (SPN) in the lumbosacral cord, and the dorsomedial nucleus (DMN) of the ventral horn. The majority of RL-29 IR neurons in the SPN are also labeled by a retrograde tracer DAPI applied to the cut L6-S1 ventral roots. These data indicate that the majority of RL-29 IR neurons in the SPN are autonomic preganglionic neurons, thus suggesting that RL-29 can be a useful tool in marking this subpopulation of neurons. In addition, the presence of previously described RL-29 IR primary afferent fibers and terminals in the dorsal parts of the cord are confirmed.


Reconstruction of the amputated thumbtip with a narrow pedicled cross-finger flap.
We have achieved favorable results in our reconstruction of fingertips by using a narrow pedicled cross-finger flap, the shape of which resembles that of the so-called flag flap. We applied this technique in several patients with defects of the thumbtip and obtained satisfactory results.


Application of laminar screws to posterior fusion of cervical spine: measurement of the cervical vertebral arch diameter with a navigation system.
Morphometric analysis. For safe and solid fixation, it is necessary to measure the diameter of the vertebral arch to ascertain whether or not screws can be used and if so, the appropriate size of screws to be used. Cervical pedicle screws are the most biomechanically stable screws. However, their use carries a high risk of neurovascular complications during screw insertion. In 2004, a new method to avoid such vertebral artery injuries was reported by insertion of screws with crosswise to the lamina of C2. For safe and solid fixation, it is necessary to measure the diameter of the vertebral arch to ascertain whether or not screws can be used and if so, the appropriate size of screws to be used. There is no report of the diameter of the vertebral arch by a navigation system. Morphometric analysis was performed on 42 patients who had undergone a CT scan of the cervical spine for either surgery or diagnostic purposes. To examine the possibilities to insert laminar screws, the diameter of the vertebral arch was measured using a navigation system. The diameter of the vertebral arch in C2 was the largest in the cervical spine, individual differences ranging between 0.8 and 8.4 mm. In C2, insertion of screws with a diameter of 3 mm was possible in 80% of males and 63% of females. As for screws with a diameter of 4 mm, insertion was possible in 50% of the males and 24% of the females in C2. In C2, gender had a significant effect, but left-right differences and height did not. Laminar screws are useful as they can prevent vascular injuries, but a preoperative evaluation is necessary.


Competence, challenges and attitudes of bedside nurses caring for patients with left ventricular assist devices.
We aimed to describe the bedside registered nurses perceived competence, attitudes, and challenges surrounding the management of patients with left ventricular assist devices (LVAD) in the intensive care unit (ICU) and stepdown unit (SDU). An exploratory research was employed using a survey. Bedside participants were recruited via an electronic recruitment flyer circulated in online professional and social networking sites. Items consisted of a numeric rating scale, measuring competence and attitudes related to the management of patients with left ventricular assist devices. The one open-ended question asked the participants to write responses regarding challenges in left ventricular assist device care. Data were analysed using quantitative and qualitative analytics software. A total of 36 intensive care unit and 35 stepdown unit bedside nurse (n = 71) from six regions of the United States responded. Overall mean scores for competency and attitude domains were ≥ 7.0. Intensive care nurses scored higher in competence and attitude when compared to stepdown unit nurses care of short-term left ventricular assist devices. Competence and attitude were positively associated with years of experience. Five themes related to challenges in care were identified. Overall, bedside nurses had satisfactory competence and attitudes surrounding the care of hospitalised left ventricular assist device patients.


Effect of temperature on development of the free-living stages of Ostertagia circumcincta.
Hatching of the eggs of Ostertagia circumcincta was studied by recovering them from faeces and incubating them in distilled water at temperatures of 4, 16, 25 and 35 degrees C. Hatching occurred at all the temperatures. The rate of hatching increased with the rise in temperature. Development of larvae to the infective third stage (L3) was studied in faecal cultures incubated at 4, 16, 25, 30, 35, 40 and 45 degrees C. Except at 4 degrees C, L3 developed at all temperatures, the optimum temperature being 16 degrees C. The rate of development of L3 increased with the rise in temperature. This resulted in a corresponding decrease in the percentage recovery of larvae.


The infusion of trieicosapentaenoyl-glycerol into humans and the in vivo formation of prostaglandin I3 and thromboxane A3.
Thirty ml of an emulsion containing 3 g of trieicosapentaenoyl-glycerol (90% pure, containing 5% arachidonic acid (AA)) was infused intravenously in 2 male healthy volunteers. Urine samples were collected for 24 h before and 48 h after the infusion in 5 periods. Urinary metabolites of prostaglandin (PG) I2/3 and thromboxane (TX) A2/3 (PGI2/3-M and TXB2/3-M, respectively) were extracted from the urinary samples and measured by GC-MS. Excretion of PGI3-M was markedly enhanced right after the infusion. Because PGI3 was produced without involvement of intestinal absorption of eicosapentaenoic acid (EPA), enhanced PGI3 formation was strongly suggested to take place in the vasculature. From the marked increment in TXB2/3-M after the infusion it was calculated that conversion rate of EPA to TXA3 was 8% of that of AA to TXA2 in this in vivo condition.


Mycobacterium vaccae induces a population of pulmonary CD11c+ cells with regulatory potential in allergic mice.
The hygiene hypothesis proposes that common, harmless microorganisms, present throughout our evolutionary history, have helped to develop immunoregulatory mechanisms that prevent inappropriate immune responses by the host. Using a mouse model of allergic pulmonary inflammation, we report that treatment with an ubiquitous saprophytic mycobacterium, Mycobacterium vaccae, significantly reduces allergic inflammation by decreasing type 2 responses such as eosinophilia and IL-4 expression. Rather than observing an increase in type-1 cytokine expression, we found elevated production of IL-10 in the lungs suggesting a role for regulatory T cells. Since induction of these cells may be dependent on APC, we investigated the effects of M. vaccae treatment on pulmonary CD11c+ cells. Increased levels of IL-10, TGF-beta and IFN-alpha mRNA were detected in CD11c+ cells from M. vaccae-treated allergic mice. We propose that M. vaccae-induced CD11c+ cells have a potential regulatory role at the site of inflammation through their secretion of immunomodulatory cytokines.


Sodium-potassium ATPase inhibition potentiates compound 48/80-induced histamine secretion from mast cells.
The effect of ouabain on the histamine secretion induced by compound 48/80 has been studied using rat peritoneal mast cells. Ouabain did not modify histamine release in the presence of millimolar concentrations of extracellular calcium. However, when mast cells were previously washed with a calcium-free buffer, ouabain strongly potentiated histamine release elicited by compound 48/80. The full potentiation of mast cell secretion by ouabain required 30 min preincubation before adding compound 48/80. It was inhibited by lanthanum and EGTA. Potassium deprivation mimicked the effect of ouabain. A 30 min preincubation time without potassium was also required. Potassium concentrations below 2.7 mM increased the effect of ouabain whereas higher potassium concentrations reversed this effect. The potentiation of compound 48/80-induced histamine release by ouabain or potassium deprivation was not immediately reversed by washing away ouabain or by adding potassium, respectively. The data confirm that sodium-potassium ATPase is involved, through a calcium-dependent process, in the regulation of histamine release from mast cells.


Clomipramine-induced urinary dysfunction in an obsessive-compulsive adolescent.
Two episodes of urinary retention occurred in a 15-year-old male following administration of clomipramine given for obsessive-compulsive disorder. Improvement of behavioral symptoms along with side effects was clearly correlated with clomipramine dosage. Severity of side effects, and their resistance to bethanechol and to phenoxybenzamine, necessitated a complete withdrawal of clomipramine. This case demonstrates that clomipramine-induced urinary retention is not limited to older individuals. Possible involvement of noncholinergic and nonadrenergic mechanisms in this adverse drug reaction is suggested.


Eclipse effects in the ionosphere.
This article surveys some recent trends in the study of the ionospheric effects of solar eclipses.


[Effect of nucleophiles on the conversion of choline esters under the action of cholinesterase].
It is shown that effect of alcohols ROH on the hydrolysis of butyryl-choline and acetylcholine by choline esterase (E. C. 18.104.22.168) is complex; it included the concurrent and the unconcurrent inhibitions, the interaction with the acylenzyme to form more reactive triple complex, and the acyl migration. By titrometric method it is found that proportion of the transacylation and hydrolysis rates depends on hydrophobity of R only being independent on its electronegativity.


Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia.
A single intrathecal injection of capsaicin depletes substance P from primary sensory neurons and causes a prolonged increase in the thermal and chemical pain thresholds of the rat but no apparent change in responses to noxious mechanical stimuli.


Antimicrobial susceptibility of Mycoplasma bovis isolates from veal calves and dairy cattle in the Netherlands.
Control of Mycoplasma bovis infections depends on good husbandry practices and antibiotic treatment. To allow more prudent use of antimicrobial drugs, there is a need for information on the susceptibility profile of this pathogen. The objective of the present study was to analyse the in vitro antimicrobial susceptibility of clinical M. bovis isolates in the Netherlands. The collection comprised 95 bovine isolates, originating from lungs (n=56), mastitis milk (n=27), and synovial fluid (n=12), collected between 2008 and 2014. Minimal inhibitory concentrations (MICs) were assessed by broth microdilution, both by using in-house prepared MIC plates and by using commercially available MIC plates. For each antimicrobial agent, the range of MIC results, the MIC50, and MIC90 values were calculated. M. bovis strains recently isolated in the Netherlands appeared to be characterized by relatively high MIC values for antimicrobial agents that, until now, have been recommended by the Dutch Association of Veterinarians for treating pneumonia caused by Mycoplasma species. Fluoroquinolones appeared to be the most efficacious in inhibiting M. bovis growth, followed by tulathromycin and oxytetracycline. The highest MIC values were obtained for erythromycin, tilmicosin, and tylosin. Future studies should be done on determining M. bovis specific clinical breakpoints, standardization of methods to determine MIC values as well as molecular studies on detection of antimicrobial resistance mechanisms of M. bovis isolates to develop PCR assays for determining resistance.


Antidepressants promote formation of heterocomplexes of dopamine D2 and somatostatin subtype 5 receptors in the mouse striatum.
The interaction between the dopaminergic and somatostatinergic systems is considered to play a potential role in mood regulation. Chronic administration of antidepressants influences release of both neurotransmitters. The molecular basis of the functional cooperation may stem from the physical interaction of somatostatin receptor subtypes and dopamine D2 receptors since they colocalize in striatal interneurons and were shown to undergo ligand-dependent heterodimerization in heterologous expression systems. In present study we adapted in situ proximity ligation assay to investigate the occurrence of D2-Sst5 receptor heterocomplexes, and their possible alterations in the striatum of mice treated acutely and repeatedly (21days) with antidepressant drugs of different pharmacological profiles (escitalopram and desipramine). Additionally we analysed number of heterocomplexes in primary striatal neuronal cultures incubated with both antidepressant drugs for 1h and 6days. The studies revealed that antidepressants increase formation of D2-Sst5 receptors heterodimers. These findings provide interesting evidence that dopamine D2 and somatostatin Sst5 heterodimers may be considered as potential mediators of antidepressant effects, since the heterodimerization of these receptors occurs in native brain tissue as well as in primary striatal neuronal cultures where receptors are expressed at physiological levels.


Focal cortical dysplasia type IIIc associates with multiple cerebral cavernomas.
The distinction of isolated malformations and combined lesions constitutes a major novelty in the 2011 consensus classification of the International League against Epilepsy (ILAE) for focal cortical dysplasias (FCD). Cortical lamination abnormalities together with vascular lesions are subsumed as FCD IIIc. Little is known regarding frequency and etiology of this entity. Here, we systematically evaluated biopsy specimens from 72 drug-refractory epilepsy patients with cerebral cavernous malformations (CCM) regarding presence of associated FCD. Due to a non-perpendicular orientation of the cortical structures or absence of sufficient cortical tissue adjacent to the vascular lesion 25 samples were not classifiable. In the remaining 47 cases FCD IIIc was rare (4.3%), but significantly increased in patients with multiple CCM (28.6%; p<0.05 vs. single CCM). Association of FCD IIIc with multiple CCM may argue against FCD IIIc as an acquired lesion.


The assessment of vertebral bone macroarchitecture with X-ray computed tomography.
On a macroscopic scale, the structural characteristics of whole bone are likely dependent on the distribution of typically applied loads to the bone surface, the full bone shape, the thickness of the cortex at the various surface positions, and the distribution of cancellous bone material. X-ray computed tomography is presently the best available method for assessing the macroarchitecture of bone in-vivo. Fine detail, three-dimensional CT methods are available to measure regional bone mineral density (rBMD) in contiguously spaced small volumes and have been applied to the assessment of macroarchitecture in vertebrae. The more detailed rBMD methods produce radiation exposures to the subject similar to lumbar radiography and substantially higher than traditional QCT. The cancellous bone within lumbar vertebral bodies has been found in cross-sectional studies to have increased density in the inferior, posterior and lateral regions. Notably, regions with higher density at age 40 have a larger decline with age. The vertebral body cortex declines with age at a slower rate than observed for cancellous bone; however, the decline with age of cortical bone appears to vary substantially amongst subjects. The amount of cortical bone in the anterior portion of the body is less than in the lateral portion, which may explain previous discrepancies in assessing the fraction of vertebral body bone in the cortex.


Cholodny-Went revisited: a role for jasmonate in gravitropism of rice coleoptiles.
Gravitropism is explained by the Cholodny-Went hypothesis: the basipetal flow of auxin is diverted laterally. The resulting lateral auxin gradient triggers asymmetric growth. However, the Cholodny-Went hypothesis has been questioned repeatedly because the internal auxin gradient is too small to account for the observed growth asymmetry. Therefore, an additional gradient in indolyl-3-acetic acid (IAA) sensitivity has been suggested (Brauner and Hager in Planta 51:115-147, 1958). We challenged the Cholodny-Went hypothesis for gravitropism of rice coleoptiles (Oryza sativa L.) and found it to be essentially true. However, we observed, additionally, that the two halves of gravitropically stimulated coleoptiles responded differentially to the same amount of exogenous auxin: the auxin response is reduced in the upper flank but normal in the lower flank. This indicates that the auxin-gradient is amplified by a gradient of auxin responsiveness. Hormone contents were measured across the coleoptile by a GC-MS/MS technique and a gradient of jasmonate was detected opposing the auxin gradient. Furthermore, the total content of jasmonate increased during the gravitropic response. Jasmonate gradient and increase persist even when the lateral IAA gradient is inhibited by 1-N-naphtylphtalamic acid. Flooding with jasmonate delays the onset of gravitropic bending. Moreover, a jasmonate-deficient rice mutant bends more slowly and later than the wild type. We discuss a role of jasmonate as modulator of auxin responsiveness in gravitropism.


Analysis of non-ignorable missing and left-censored longitudinal data using a weighted random effects tobit model.
In a longitudinal study with response data collected during a hospital stay, observations may be missing because of the subject's discharge from the hospital prior to completion of the study or the death of the subject, resulting in non-ignorable missing data. In addition to non-ignorable missingness, there is left-censoring in the response measurements because of the inherent limit of detection. For analyzing non-ignorable missing and left-censored longitudinal data, we have proposed to extend the theory of random effects tobit regression model to weighted random effects tobit regression model. The weights are computed on the basis of inverse probability weighted augmented methodology. An extensive simulation study was performed to compare the performance of the proposed model with a number of competitive models. The simulation study shows that the estimates are consistent and that the root mean square errors of the estimates are minimal for the use of augmented inverse probability weights in the random effects tobit model. The proposed method is also applied to the non-ignorable missing and left-censored interleukin-6 biomarker data obtained from the Genetic and Inflammatory Markers of Sepsis study.


Compared analysis of the regulatory systems controlling lipogenesis in hepatocytes of mice and in maturing oilseeds of Arabidopsis.
Due to the high reduction level of the carbons in fatty acids, the oxidation of triacylglycerols (TAGs) releases much more energy than the oxidation of other storage compounds like carbohydrates or proteins. TAGs are synthesized in many animal and plant species to act as an energy reserve. Here, we review some of the studies that have contributed to decipher the metabolic and regulatory networks responsible for the biosynthesis of TAGs in two contrasted model systems: the liver of mice and the maturing oilseed of Arabidopsis. A comparison of the two systems illustrates how distinct transcriptional regulatory systems trigger lipogenesis in response to specific signals: a high carbohydrate diet induces TAG synthesis in the liver of mammalians whereas a developmental program initiates TAG accumulation at the onset of embryo maturation in Arabidopsis.


Guidelines from the International Conference on Harmonisation (ICH).
This article describes the development of international guidance on registration of technical dossiers supporting applications to market medicinal products. Aspects of guidance of particular relevance to the use of NMR spectroscopy in drug development and control are discussed.


Age-Related Development of Cardiac Remodeling and Dysfunction in Young Black and White Adults: The Coronary Artery Risk Development in Young Adults Study.
Little is known about the timing of preclinical heart failure (HF) development, particularly among blacks. The primary aims of this study were to delineate age-related left ventricular (LV) structure and function evolution in a biracial cohort and to test the hypothesis that young-adult LV parameters within normative ranges would be associated with incident stage B-defining LV abnormalities over 25 years, independent of cumulative risk factor burden. Data from the Coronary Artery Risk Development in Young Adults study were analyzed. Participants (n = 2,833) had a mean baseline age of 30.1 years; 45% were black, and 56% were women. Generalized estimating equation logistic regression was used to estimate age-related probabilities of stage B LV abnormalities (remodeling, hypertrophy, or dysfunction) and logistic regression to examine risk factor-adjusted associations between baseline LV parameters and incident abnormalities. Cox regression was used to assess whether baseline LV parameters associated with incident stage B LV abnormalities were also associated with incident clinical (stage C/D) HF events over >25 years' follow-up. Probabilities of stage B LV abnormalities at ages 25 and 60 years were 10.5% (95% CI, 9.4%-11.8%) and 45.0% (95% CI, 42.0%-48.1%), with significant race-sex disparities (e.g., at age 60, black men 52.7% [95% CI, 44.9%-60.3%], black women 59.4% [95% CI, 53.6%-65.0%], white men 39.1% [95% CI, 33.4%-45.0%], and white women 39.1% [95% CI, 33.9%-44.6%]). Over 25 years, baseline LV end-systolic dimension indexed to height was associated with incident systolic dysfunction (adjusted odds ratio per 1 SD higher, 2.56; 95% CI, 1.87-3.52), eccentric hypertrophy (1.34; 95% CI, 1.02-1.75), concentric hypertrophy (0.69; 95% CI, 0.51-0.91), and concentric remodeling (0.68; 95% CI, 0.58-0.79); baseline LV mass indexed to height2.7 was associated with incident eccentric hypertrophy (1.70; 95% CI, 1.25-2.32]), concentric hypertrophy (1.63; 95% CI, 1.19-2.24), and diastolic dysfunction (1.24; 95% CI, 1.01-1.52). Among the entire cohort with baseline echocardiographic data available (n = 4,097; 72 HF events), LV end-systolic dimension indexed to height and LV mass indexed to height2.7 were significantly associated with incident clinical HF (adjusted hazard ratios per 1 SD higher, 1.56 [95% CI, 1.26-1.93] and 1.42 [95% CI, 1.14-1.75], respectively). Stage B LV abnormalities and related racial disparities were present in young adulthood, increased with age, and were associated with baseline variation in indexed LV end-systolic dimension and mass. Baseline indexed LV end-systolic dimension and mass were also associated with incident clinical HF. Efforts to prevent the LV abnormalities underlying clinical HF should start from a young age.


[The characteristics of the behavior and brain lipid peroxidation function of rats in acute inhalation exposure to a hydrogen sulfide-containing gas condensate].
As a result of the effect of the gas condensate containing hydrogen sulfide a depression takes place of orienting-investigatory activity of Wistar male rats in conditions of open field, disturbance of elaboration and reproduction of conditioned reflex of two-way avoidance, surplus accumulation in the cerebral cortex tissue of products of peroxide lipids oxidation and depression of catalase. The changes were of cyclic character and returned to the level of the control animals in 48 h after the finishing of the effect.


Controlled comparison of percutaneous and microsurgical sperm retrieval in men with obstructive azoospermia.
A controlled comparison of the efficacy and reliability of sperm retrieval by testicular fine needle aspiration (TFNA), percutaneous testicular needle biopsy (PercBiopsy) and microsurgical epididymal sperm aspiration (MESA) was performed in nine patients with obstructive azoospermia. During a planned MESA procedure, sperm retrieval was attempted on the same testis with TFNA and PercBiopsy. Spermatozoa were obtained from all patients using MESA and PercBiopsy. Spermatozoa were retrieved using TFNA from 6/9 (67%) men. The mean number of epididymal spermatozoa retrieved with MESA (15 x 106) was significantly higher (P = 0.003) than that retrieved percutaneously from the testis. The mean number of spermatozoa obtained by PercBiopsy was 0.116 x 10(6) while TFNA recovered 0.014 x 106 spermatozoa (P = 0.025). MESA is the optimal choice to retrieve the greatest number of spermatozoa with highest motility for assisted reproduction and subsequent cryopreservation. However, percutaneous testicular retrieval does not require microsurgical expertise and is less invasive. Our results suggest that the optimal percutaneous procedure for sperm retrieval from the testis involves percutaneous testicular needle biopsy with an automatic biopsy gun.


Reactive oxygen species-mediated regulation of the Na+-H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers.
We have previously demonstrated that a slight increase in intracellular superoxide (O2*-) anion confers resistance to death stimuli. Using pharmacological and molecular approaches to manipulate intracellular O2*-, here we report that an increase in intracellular O2*- anion induces Na+/H+ exchanger 1 (NHE-1) gene promoter activity resulting in increased NHE-1 protein expression, which strongly correlates with the resistance of cells to death stimuli. In contrast, exposure to exogenous hydrogen peroxide suppressed NHE-1 promoter activity and gene expression, and increased cell sensitivity to death triggers. Furthermore, the increase in cell sensitivity to death upon downregulation of NHE-1 gene expression correlates with reduced capacity of cells to recover from an acid load, while survival upon overexpression of NHE-1 appears independent of its pump activity. These findings indicate that NHE-1 is a redox-regulated gene, and provide a novel intracellular target for the redox control of cell death sensitivity.


Affective pain modulation in fibromyalgia, somatoform pain disorder, back pain, and healthy controls.
Previous research suggested that patients with fibromyalgia (FM) experience a higher pain intensity (clinical pain) than do patients with musculoskeletal pain after negative emotional priming compared to positive priming. To further examine affective pain modulation in FM, we applied an experimental pain induction to compare 30 patients with FM with 30 healthy (pain-free) participants (HC), and 30 patients with back pain (BP). For another group of 30 patients with somatoform pain disorder (SF), we predicted the same pain modulation as for FM. As primes we presented positive, neutral, negative, and pain-related pictures and assessed pain intensity in response to a fixed pressure weight. Overall, picture valence modulated pain intensities (in the order of pain-related > negative pictures > neutral), but the pain intensities between neutral and positive pictures did not differ significantly. SF reported significantly higher pain intensities than did BP and HC; FM were in between, but did not differ significantly from the three other groups. There was no interaction of priming and group. Affective modulation of pain was not specifically altered in FM and SF, but SF were more sensitive to pressure pain than BP and HC.


Development and application of a quantitative real-time PCR assay to detect feline leukemia virus RNA.
We previously defined four categories of feline leukemia virus (FeLV) infection, designated as abortive, regressive, latent, and progressive. To determine if detectable viral DNA is transcriptionally active in the absence of antigenemia, we developed and validated a real-time viral RNA qPCR assay. This assay proved to be highly sensitive, specific, reproducible, and allowed reliable quantitation. We then applied this methodology, together with real-time DNA qPCR and p27 capsid antigen capture ELISA, to examine cats challenged with FeLV. We found that circulating viral RNA and DNA levels were highly correlated and the assays were almost in perfect agreement. This indicates that the vast majority of viral DNA is transcriptionally active, even in the absence of antigenemia. The real-time qPCR assays are more sensitive than the most commonly used FeLV diagnostic assay, the p27 capsid antigen capture ELISA. Application of qPCR assays may add greater depth in understanding of FeLV-host relationships.


Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma.
The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-protein kinase catalytic subunit (DNA-PKcs), influence the response to radiotherapy (RT) and outcome of treatment of nondisseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The overexpression of Ku70 or DNA-PKcs groups included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were performed to determine the prognostic factors that influenced locoregional control of NPC. The 5-year locoregional control rate was significantly higher in the low Ku70 group (Ku-) (85%) than in the high Ku70 group (Ku+) (42%) (p = 0.0042). However, there were no differences in the metastases-free survival rates between the 2 groups (Ku70+, 82%; Ku70- 78%; p = 0.8672). Univariate analysis indicated that the overexpression of Ku70 surpassed other well-known predictive clinicopathologic parameters as an independent prognostic factor for locoregional control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an overexpression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with nondisseminated NPC.


Population Pharmacokinetics and Exposure-Response of a Fixed-Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With Stage 2 Hypertension.
Population pharmacokinetic and exposure-response models for azilsartan medoxomil (AZL-M) and chlorthalidone (CLD) were developed using data from an 8-week placebo-controlled phase 3, factorial study of 20, 40, and 80 mg AZL-M every day (QD) and 12.5 and 25 mg CLD QD in fixed-dose combination (FDC) in subjects with moderate to severe essential hypertension. A 2-compartment model with first-order absorption and elimination was developed to describe pharmacokinetics. An Emax model for exposure-response analysis evaluated AZL-M/CLD effects on ambulatory systolic blood pressure (SBP). Estimated oral clearance and apparent volume of distribution (central compartment) were 1.47 L/h and 3.98 L for AZL, and 4.13 L/h and 62.1 L for CLD. Age as a covariate had the largest effect on AZL and CLD exposure (±20% change). Predicted maximal SBP responses (Emax ) were -15.6 and -23.9 mm Hg for AZL and CLD. Subgroup analysis identified statistically significant Emax differences for black vs nonblack subjects, whereby the reduced AZL response in black subjects was offset by greater response to CLD. The estimated Emax for AZL and CLD was generally greater in subjects with higher baseline BP. In conclusion, no dose adjustments to AZL-M or CLD are warranted based on identified covariates, and antihypertensive efficacy of AZL-M/CLD combination therapy is comparable in black and nonblack subjects.


[Access to origins for persons conceived by donation in France].
It was a strong and long-standing demand of people born of gamete donation: to know who is the person who allowed them to come into the world. The French legislator seemed to take this need into account during the last revision of the bioethics law. But if the rules have already changed for donors, for whom anonymity becomes fixed-term, for individuals born from a donation, access to their origins is far from being guaranteed to this day.


Renal artery diameter, renal function and resistant hypertension in patients with low-to-moderate renal artery stenosis.
Atherosclerotic renovascular disease is associated with resistant hypertension and chronic kidney disease, although the causal relationship is discussed. To date, the role of renal artery diameter on these pathological conditions was not clearly studied. We aimed to identify the association of reference diameter and minimal luminal renal artery diameter with glomerular filtration rate (GFR) and resistant hypertension in a high cardiovascular risk population. In this cross-sectional, single-center study, we enrolled 734 patients who underwent a renal angiography immediately after a coronary angiography indicated for a diagnosis of ischemic heart disease. Mean age was 64 ± 10 years (men 72%). GFR was 79 ± 22 ml/min per 1.73 m(2). Five hundred and eighteen patients had no luminal narrowing and 216 patients had low-to-moderate luminal narrowing (10-70%, mean 36%). A positive significant association between reference diameter and GFR was detected in patients without luminal narrowing [beta 2.2 ml/min per 1.73 m(2) for 1 mm increase, 95% confidence interval (CI) 0.3-4.0, P < 0.05] and in those with low-to-moderate luminal narrowing (beta 7.7 ml/min per 1.73 m(2) for 1 mm increase, 95% CI 4.2-11.1, P < 0.001). The lowest quartile of reference diameter (<5.2 mm) was associated with GFR less than 60 ml/min per 1.73 m(2) [odds ratio (OR) 3.18, 95% CI 1.61-6.29, P < 0.001]. Patients with resistant hypertension had low minimal diameter and reference diameter. Reference diameter less than 5.2 mm was associated with an increased risk of resistant hypertension (OR 2.63, 95% CI 1.02-6.77, P < 0.05). Small renal arteries, defined by a low reference diameter or minimal luminal diameter, are independently associated with low GFR and resistant hypertension, independent of the degree of stenosis and major confounders.


An investigation into whether changes in the posterior tibial slope affect the outcome of cruciate-retaining total knee arthroplasty by affecting tibiofemoral articular contact kinematics.
The outcomes of total knee arthroplasty (TKA) are affected by many factors. This study aims to evaluate whether changes in the posterior tibial slope (PTS) affect patients' outcomes after cruciate-retaining TKA by affecting tibiofemoral articular contact kinematics. It was hypothesized that changes in PTS affect the outcomes of PCR TKA by affecting tibiofemoral articular contact kinematics. A total of 60 knees (30 patients) that underwent posterior cruciate-retaining TKA (with the same size prosthesis) for medial osteoarthritis were assessed preoperatively and one year postoperatively. Before and after TKA, changes in the PTS, as seen on lateral radiographs, were noted. The knees were placed in groups according to these PTS changes (preoperative value - postoperative value): group 1 >3° change and group 2 ≤3° change. Knee kinematics were observed under mid-flexion weight-bearing conditions and were compared between the two groups using the two-dimensional/three-dimensional registration technique. Pain was measured using the visual analog scale, and knee function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Knee Society Score (KSS). Group 2 experienced paradoxical anterior motion of the medial femoral condyle postoperatively, but group 1 did not. A comparison of the results of the TKA between the two groups showed a significant difference in pain using the visual analog scale, and knee function of the KSS and the WOMAC (P < 0.05). The postoperative results were better in group 1 than in group 2. These results suggest that achieving a greater change in the PTS improves outcomes in patients undergoing posterior cruciate-retaining TKA because it reduces the paradoxical motion of the medial femoral condyle.


The adaptive significance of aggregation behaviour in the dogwhelk Nucella lapillus (L.).
Three kinds of aggregation behaviour were observed in an exposed shore population of Nucella lapillus. Aggregations on the open rock surface during the summer protected dogwhelks from water movement, and were not found on shores where the topography conferred protection. Feeding occurred mainly within these aggregations, probably because individuals experienced less disturbance there than when isolated. Physical contact was important in holding animals together.Winter and pre-breeding aggregations were usually found in clefts or pools. All age groups formed winter aggregations, but those of immature dogwhelks were not as permanent as those of adults, and the latter merged with the prebreeding aggregations. Winter aggregations protected dogwhelks from dislodgment when their ability to regain a foothold was reduced by low temperatures, while pre-breeding aggregations brought the sexes together for fertilization, but the permanence of adult winter aggregations suggested that reproductive activity may have been occurring within them.


Transmission dynamics of a novel HIV/AIDS model through a higher-order Galerkin time discretization scheme.
There are numerous contagious diseases caused by pathogenic microorganisms, including bacteria, viruses, fungi, and parasites, that have the propensity to culminate in fatal consequences. A communicable disease is an illness caused by a contagion agent or its toxins and spread directly or indirectly to a susceptible animal or human host by an infected person, animal, vector, or immaterial environment. Human immunodeficiency virus (HIV) infection, hepatitis A, B, and C, and measles are all examples of communicable diseases. Acquired immunodeficiency syndrome (AIDS) is a communicable disease caused by HIV infection that has become the most severe issue facing humanity. The research work in this paper is to numerically explore a mathematical model and demonstrate the dynamics of HIV/AIDS disease transmission using a continuous Galerkin-Petrov time discretization of a higher-order scheme, specifically the cGP(2)-scheme. Depict a graphical and tabular comparison between the outcomes of the mentioned scheme and those obtained through other classical schemes that exist in the literature. Further, a comparison is performed relative to the well-known fourth-order Ruge-Kutta (RK4) method with different step sizes. By contrast, the suggested approach provided more accurate results with a larger step size than RK4 with a smaller step size. After validation and confirmation of the suggested scheme and code, we implement the method to the extended model by introducing a treatment rate and show the impact of various non-linear source terms for the generation of new cells. We also determined the basic reproduction number and use the Routh-Hurwitz criterion to assess the stability of disease-free and unique endemic equilibrium states of the HIV model.


The volume density of cells and capillaries of the normal stria vascularis.
The purpose of this study was to provide morphometric (i.e. quantitative anatomical) data on the normal chinchilla stria vascularis. Five normal chinchillas were used in the present investigation and four regions of the cochlea were examined in each animal. The width, radial area and number of marginal cells across the stria's width increased from the cochlear apex toward the base. The increase in strial width and area appeared to be due to hyperplasia of the marginal cells. The mean total endolymphatic surface area of the stria vascularis was estimated to be 7.4 mm2 (S.E. = 1.23). The mean total volume of the stria vascularis was estimated to be 0.15 microliter (S.E. = 0.01). In addition, using a stereological method we found that the volume density of the cells and capillaries of the stria vascularis was constant along the length of the scala media. The mean (+/- S.E.) volume density of the stria cells and capillaries was estimated to be: marginal cells = 0.528 (0.013), intermediate cells = 0.212 (0.026), basal cells = 0.163 (0.009) and capillaries = 0.097 (0.009).


MicroRNA-221-5p Promotes Ricin Toxin-induced Inflammation via PI3K/Akt signaling pathway by targeting COL4a5.
Ricin toxin (RT) is one of the most lethal type II ribosome-inactivating proteins (RIP), and is classified as a potential bioterror agent due to its severe cytotoxicity and high availability. The toxicity of RT is dependent on both dose and route of exposure. Increasing evidence demonstrates that sub-lethal RT induces acute inflammation and increases the release of pro-inflammatory cytokines. However, current studies on mechanism of RT-induced inflammation are limited. In this study, to evaluate the relationship between miRNAs and RT-induced inflammation, RNA sequencing (RNA-Seq) was used to analyze the expression of miRNAs and mRNAs in RT-treated RAW264.7 macrophage cells. A total of 14 significantly differently expressed (DE) miRNAs and 323 miRNA-mRNA interaction pairs were predicted by bioinformatics analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that majority of those interaction pairs were involved in PI3K/Akt pathway. In addition, overexpression of miR-221-5p promoted the inflammatory response by inhibiting the mRNA expression of COL4a5. This work contributes to our understanding of RT-induced inflammation and demonstrates the potential role of miRNAs in innate immunity, which may be regarded as potential targets in developing therapies for RT poisoning.


Prevalence of metal hypersensitivity in total knee replacement.
Cutaneous and local reactions to metals used in orthopaedic implants have been well documented. The prevalence of metal sensitivity in general population is 10%-15%. Nickel, Cobalt and Chromium are the most common allergen. The association between cutaneous reactions and implants has been less understood. Hence, this study was taken up with the aim to assess the prevalence of metal hypersensitivity in Total Knee Replacement (TKR) patients and find the most prevalent allergen. Longitudinal study conducted during January-December 2017. We enrolled 233 subjects who were at least three months postoperative. Radiological assessment was done. CREDISOL® kit was used for patch test. Results were recorded using ICDRG grading at 48 hours and five days. Mean age was 59.59 years; 12.01% were symptomatic. Pain followed by loss of function were the most common symptoms. However, loss of function and patient dissatisfaction towards procedure were significantly associated with metal hypersensitivity (χ2 value > 3.84; p value < 0.05). In 66% subjects, pre-operative diagnosis was severe osteoarthritis, followed by rheumatoid arthritis (23%). None of the subjects had evidence of loosening on X-ray. Prevalence of Metal Hypersensitivity was found to be 15.87% (patch test positive). Chromium (11.58%) was found to be most common allergen followed by Nickel (8.58%) and then Cobalt (6.43%). Significant prevalence of metal hypersensitivity was found. Therefore, we recommend pre-operative patch test for detecting allergic reactions to implants. Alternatives like Titanium or Zirconium can be used to avoid complications.


Differential characteristics of HIV-infected penitentiary patients and HIV-infected community patients.
To identify particular characteristics of HIV+ patients from correctional facilities (CF) compared with an HIV+ population from the community to better detect variables for intervention. In our hospital, HIV+ patients are admitted to an infectious diseases ward (IDW) when they come from the community or to a penitentiary unit (PU) when they are transferred from CF. We retrospectively reviewed admissions of those patients in both areas during 1999. Admissions of HIV+ patients to IDW and PU generate 2.3% and 53.4% of hospital and PU stays, respectively. Both populations were equivalent in terms of mean age, CD4 count, viral load, prophylaxis for opportunistic infections, average stay, and death during stay. Male sex (91% vs. 74%), previous or current intravenous drug use (88% vs. 77%), and hepatitis C virus (HCV) seropositivity (97% vs. 82.6%) were more frequent in the PU than in the IDW. Multivariate analysis identified three factors as being independently related to admission from prison: longer time of known HIV infection (average 3.3 years; 95% CI 1.9-4.6), no previous antiretroviral treatment (odds ratio [OR] 2.95; 95% CI 1.46-6.0), and admission due to tuberculosis (OR 2.5; 95% CI 1.03-6.0). HIV infection is still a serious medical problem in CF. Although imprisonment can provide access to health programs, HIV-infected prison patients suffer more frequently from tuberculosis and take less antiretroviral treatment.


Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma.
To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.


Phylogenomic analysis of a metagenome-assembled genome indicates a new taxon of an anoxygenic phototroph bacterium in the family Chromatiaceae and the proposal of "Candidatus Thioaporhodococcus" gen. nov.
In this study, three metagenome-assembled genomes of a sediment sample were constructed. A Bin1 (JB001) genome was identified as a photo-litho-auto/heterotroph (purple sulfur bacteria) bacterium with the ability to fix nitrogen, tolerate salt, and to produce bacteriochlorophyll a. It has a genome length of 4.1 Mb and a G + C content of 64.9%. Phylogenetic studies based on concatenated 92 core genes and photosynthetic genes (pufLM and bchY) showed that Bin JB001 is related to Thiococcus pfennigii, "Thioflavicoccus mobilis" and to the Lamprocystis purpurea lineage. Bin JB001 and its closely related members were subjected to the genome-based study of phenotypic and phylogenomic analysis. Genomic similarity indices (dDDH and ANI) showed that Bin JB001 could be defined as a novel species. The average amino acid identity (AAI) and percentage of conserved proteins (POCP) values were below 60 and 50%, respectively. The pan-genome analysis indicated that the pan-genome was an open type wherein Bin JB001 had 855 core genes. This study shows that the binned genome, Bin JB001 could represent a novel species of a new genus under the family Chromatiaceae, for which the name "Candidatus Thioaporhodococcus sediminis" gen. nov. sp. nov. is proposed.


Interaction between enkephalin and GABA in the chicken retina: further analyses of coexisting relationships.
Previous studies have indicated an interactive relationship between enkephalin and gamma-aminobutyric acid (GABA) in the vertebrate retina. Among these studies are those that have demonstrated the colocalization of enkephalin and GABA in retinal amacrine cells. In the present study, enkephalin immunocytochemistry was combined with either autoradiography of tritiated GABA high-affinity uptake or GABA immunocytochemistry to further investigate the coexistence of GABA in enkephalin-amacrine cells of the chicken retina. A regional analysis revealed that the percentage colocalization of GABA high-affinity uptake in enkephalin-amacrine cells did not vary appreciably throughout the retina. Overall, 15.2% of enkephalin-amacrine cells exhibited high-affinity GABA uptake. Double-label immunofluorescence histochemistry revealed that 15.1% of enkephalin-amacrine cells express endogenous GABA-like immunoreactivity. These double-labelled cells were observed throughout central and peripheral regions of the retina. In each of the double-label analyses, only less intensely labelled enkephalin-amacrine cells expressed markers of GABA activity. The two double-label analyses reveal almost identical percentages of coexistence of GABA markers in chicken enkephalin-amacrine cells and therefore, provide supportive evidence for the GABAergic nature of these cells. These results suggest a functional diversity in the population of chicken enkephalin-amacrine cells and imply the possibility of multiple signalling through amacrine cells which contain enkephalin and GABA.


Induction of HepG2 cell apoptosis by Irgarol 1051 through mitochondrial dysfunction and oxidative stresses.
In this study, HepG2 cells were exposed to 0.04-40 mg/L Irgarol 1051. Results show that Irgarol 1051 can damage cell morphology and cause a significant decrease in cell viability. Positive staining by Annexin V, caspase-3 activity enhancement, and the damage in cell ultrastructure indicated an apoptotic mode of cell death for 4.0mg/L Irgarol 1051 treatment. At the same time, caspase-9 was also significantly induced by 0.4 and 4.0mg/L Irgarol 1051 at 72 h, which suggests that the intrinsic mitochondria pathway was involved in the apoptosis. The mitochondrial membrane potential decreased significantly after the HepG2 cells were exposed to Irgarol 1051 for 6 and 72 h. Especially, the translocation of cytochrome c from mitochondria to cytosol was recorded, supporting the idea that the mitochondrial pathway was involved in the apoptosis signal pathways induced by Irgarol 1051. The significantly increased levels of intracellular reactive oxygen species (ROS) and an immediate ROS burst were also recorded. The results here may imply that Irgarol 1051 induces HepG2 cell apoptosis through mitochondrial dysfunction and oxidative stresses. Although it is possible that this chemical has no detrimental effects on human health at the environmentally relevant concentration, it may cause problems to top coastal predators due to bio-accumulation through the food chain.


Predicting Fact-Checking Health Information Before Sharing Among People with Different Levels of Altruism: Based on the Influence of Presumed Media Influence.
Pervasive health misinformation on social media affects people's health. Fact-checking health information before it is shared is an altruistic behavior that effectively addresses health misinformation on social media. Based on the influence of presumed media influence (IPMI), this study serves two purposes: The first is to investigate factors that influence social media users' decisions to fact-check health information before sharing it in accordance with the IPMI model. The second is to explore different predictive powers of the IPMI model for individuals with different levels of altruism. This study conducted a questionnaire survey of 1045 Chinese adults. Participants were divided into either a low-altruism group (n = 545) or a high-altruism group (n = 500) at the median value of altruism. A multigroup analysis was conducted with R Lavaan package (Version 0.6-15). All of the hypotheses were supported, which confirms the applicability of the IPMI model in the context of fact-checking health information on social media before sharing. Notably, the IPMI model yielded different results for the low- and high-altruism groups. This study confirmed the IPMI model can be employed in the context of fact-checking health information. Paying attention to health misinformation can indirectly affect an individual's intention to fact-check health information before they share it on social media. Furthermore, this study demonstrated the IPMI model's varying predictive powers for individuals with different altruism levels and recommended specific strategies health-promotion officials can take to encourage others to fact-check health information.


Uncovering the expression of circPVT1 in the extracellular vesicles of acute myeloid leukemia patients.
Extracellular vesicles (EVs) act as molecular mediators in the tumor microenvironment, by shuttling information contained within malignant cells and functioning as regulators of the immune system. Circular (circ)RNAs are characterized by a closed loop-like structure that makes them more stable in the extracellular milieu and suitable to be packaged inside EVs. circPVT1 (hsa_circ_0001821) showed an oncogenic role in several cancer types and immunosuppressive properties in myeloid and lymphoid cell subsets. In this study, we characterized EVs from acute myeloid leukemia (AML) patients in terms of size, concentrations, surface markers and circPVT1 cargo. We showed that circPVT1 is overexpressed by primary blast cells from newly-diagnosed AML patients compared with hematopoietic stem-progenitor cells and is released as cell-free RNA in the plasma. We isolated EVs from the plasma of AML patients and healthy subjects by size exclusion chromatography and characterized them by nanoparticle tracking analysis. EVs from patients' plasma are larger compared with those from healthy subjects and their surface profile is characterized by higher levels of the leukemic cell markers CD133, CD105, CD49e and other immune-related epitopes, with differences according to AML molecular profile. Moreover, digital PCR analysis revealed that circPVT1 is more abundant inside EVs from the plasma of AML patients compared with healthy subjects. Our findings provide new insights on the features and content of AML EVs and suggest a role of circPVT1 in the crosstalk between AML cells and the tumor microenvironment.


Crystallization and X-ray diffraction studies of a 434 Cro-DNA complex.
Crystals have been obtained of the bacteriophage 434 Cro protein bound to a synthetic DNA operator. An analysis of the packing shows that the complexes stack end-to-end along crystallographic axis, forming long rods with non-crystallographic 11(3) screw symmetry. The average number of DNA base-pairs per turn is 10.27, which is somewhat more overwound as compared with the 434 repressor-DNA crystals of Anderson et al. Diffraction extends to 3 A along the rod direction and to 5 A in perpendicular directions.


Long-Term Voice Outcomes After Robotic Thyroidectomy.
The purpose of this study was to evaluate the long-term voice function after robotic thyroidectomy in comparison with conventional transcervical thyroidectomy. We prospectively evaluated the voice functions of 54 patients with thyroid nodules who underwent robotic thyroidectomy by a gasless unilateral axillary or axillo-breast approach and of 70 patients who underwent conventional thyroidectomy. Subjective voice symptom score (VSS) was evaluated in questionnaires before thyroidectomy and then at 3, 6, 12, and 24 months after surgery. Objective acoustic parameters analyzed during the same period included fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, highest frequency, frequency and intensity range, and maximal phonation time. At 3 months after surgery, VSS was better in the robotic group than in the conventional group. At 2 years after surgery, VSS had recovered to the pre-operative level in the robotic group, whereas it remained significantly worse at 2 years in the conventional group. The phonatory frequency range and highest frequency were significantly wider and higher, respectively, in the robotic group than the conventional group at 6, 12, and 24 months postoperatively.Within the robotic group, the frequency range and highest frequency recovered to pre-operative levels by 6 months, whereas in the conventional group they remained below the pre-operative levels at 2 years post-operatively. There were no differences in other acoustic parameters between the two groups of patients at any period. Up to 2 years post-operatively, robotic thyroidectomy has advantages in terms of recovery of voice symptoms and acoustic parameters over conventional thyroidectomy.


Endocrine therapy: defining the path of least resistance.
One of the best-characterized oncogenic mechanisms in breast cancer is the aberrant activation of phosphatidylinositol-3-kinase, protein kinase B, and mammalian target of rapamycin signaling. In both endocrine-resistant disease and breast cancer stem cells, this is commonly caused by specific genetic lesions or amplification of key pathway components or both. These observations have generated two interesting hypotheses. Firstly, do these genetic anomalies provide clinically significant biomarkers predictive of endocrine resistance? Secondly, do tamoxifen-resistant breast cancer cells emerge from a stem-like cell population? New studies, published in Breast Cancer Research, raise the possibility that these hypotheses are intrinsically linked.


Impact of multiple comparisons in randomized clinical trials.
The randomized clinical trial is the preferred research design for evaluating competing diagnostic and therapeutic alternatives, but confidence in the conclusions from a randomized clinical trial depends on the authors' attention to acknowledged methodologic and statistical standards. This survey assessed the level of attention to the problem of multiple comparisons in the analyses of contemporary randomized clinical trials. Of the 67 trials surveyed, 66 (99 percent) performed multiple comparisons with a mean of 30 therapeutic comparisons per trial. When criteria for statistical impairment were applied, 50 trials (75 percent) had the statistical significance of at least one comparison impaired by the problem of multiple comparisons, and 15 (22 percent) had the statistical significance of all comparisons impaired by the problem of multiple comparisons. Although some statistical techniques are available, there still exists a great need for future work to clarify further the problem of multiple comparisons and determine how the impact of this problem can best be minimized in subsequent research.


A carbon balance method for paper and wood products.
The approach used to track the flow of carbon sequestered in the forest through harvest, processing into products, and final disposition of products is described. The methodology is broadly flexible and applicable to forest-based carbon balance assessments. A carbon balance is computed across all forestland ownerships for the production facility of interest. The balance considers forest uptake, harvest, combustion of fuels, emissions from process steps and losses from product use, disposition and recycling. The method also allows for sensitivity and marginal assessments of a variety of real and hypothetical situations using variable assumptions. Example results for a vertically integrated pulp and paper mill are presented. Results suggest that integrated forest products facilities drawing their raw material from sustainably managed forests can achieve a net positive carbon balance over the product cycle. The amount of net carbon sequestration attributable to such facilities depends upon a number of factors. The most critical of these include net forest growth, the method for allocating the growth in forest carbon among all of those harvesting from the drain area of a given facility, and the use and disposal patterns for the paper or wood products manufactured.


Risky sexual behavior among college students With ADHD: is the mother-child relationship protective?
This study examined the extent to which ADHD was associated with risky sexual behaviors (RSBs) in a sample of 92 undergraduates with (n = 44) and without (n = 48) ADHD. Mother-child relationship quality was examined as a potential moderator. We conducted comprehensive assessments for ADHD and comorbid conditions and collected measures of RSB and mother-child relationship quality. Female students with ADHD were least likely to use condoms than males overall and females without ADHD. An interaction between ADHD and mother-child relationship quality accounted for significant variance in the number of past-year sexual partners, such that a high-quality relationship was protective only for students with ADHD. No other significant associations were found between ADHD and RSB. Results suggest that female college students with ADHD are at risk for unprotected sex. Moreover, a positive mother-child relationship may be protective for college students with ADHD in relation to RSB.


Pulse contour analysis of arterial waveform in a high fidelity human patient simulator.
The measurement of cardiac output (CO) may be useful to improve the assessment of hemodynamics during simulated scenarios. The purpose of this study was to evaluate the feasibility of introducing an uncalibrated pulse contour device (MostCare, Vytech, Vygon, Padova, Italy) into the simulation environment. MostCare device was plugged to a clinical monitor and connected to the METI human patient simulator (HPS) to obtain a continuous arterial waveform analysis and CO calculation. In six different simulated clinical scenarios (baseline, ventricular failure, vasoplegic shock, hypertensive crisis, hypovolemic shock and aortic stenosis), the HPS-CO and the MostCare-CO were simultaneously recorded. The level of concordance between the two methods was assessed by the Bland and Altman analysis. 150-paired CO values were obtained. The HPS-CO values ranged from 2.3 to 6.6 L min-1 and the MostCare-CO values from 2.8 to 6.4 L min-1. The mean difference between HPS-CO and MostCare-CO was - 0.3 L min-1 and the limits of agreement were - 1.5 and 0.9 L min-1. The percentage of error was 23%. A good correlation between HPS-CO and MostCare-CO was observed in each scenario of the study (r = 0.88). Although MostCare-CO tended to underestimate the CO over the study period, good agreements were found between the two methods. Therefore, a pulse contour device can be integrated into the simulation environment, offering the opportunity to create new simulated clinical settings.


Epidemiology of HBV infection in Asian blood donors: emphasis on occult HBV infection and the role of NAT.
Hepatitis B virus (HBV) infection is endemic in many Asian countries. Among many transmission routes, transfusion is the one that should be prevented. The first major success in enhancing transfusion safety came with the implementation of hepatitis B surface antigen (HBsAg) in the early 1970s. However, the studies quoted in this review demonstrate that transmission by blood components negative for HBsAg can still occur in the acute phase of infection during the seronegative window period, or during chronic stages of infection (i.c. "occult" HBV infection, OHB). OHB is defined as the presence of HBV DNA in blood or liver tissues in patients negative for HBsAg, with or without any HBV antibodies. Because of limitations in current blood screening practices, OHB is an overlooked source of HBV transmission. For policy development on screening for HBV infection in blood donors, it would be useful to assess the relative contribution of the above two sources of transfusion-transmitted HBV infection from HBsAg-negative donations. New screening policy should be evaluated on the basis of available data or newly designed studies. While anti-HBc screening can climinate residual risk of occult HBV transmission by transfusion in low-endemic areas, it would not be practical in most parts of the world where the prevalence of anti-HBc is >10% as too many otherwise healthy donors will be ineligible. On the contrary, studies mentioned in this paper indicate that nucleic acid amplification test (NAT) or new HBsAg tests of enhanced sensitivity would be effective in the screening of blood donors for OHB in highly endemic countries. However, the cost-effectiveness of blood screening tests is a major concern in Asia. We therefore have systemically reviewed the literature on prevalence and infectivity of OHB in Asian countries and the possible role of NAT for identifying blood donors in the pre-HBsAg window phase or in later stages of OHB.


Management of paratracheal lymph nodes in laryngeal cancer with subglottic involvement.
The purpose of this study was to present our findings on the involvement of paratracheal lymph nodes in laryngeal squamous cell carcinoma (SCC) with subglottis extension, which is controversial. We assessed 196 patients with laryngeal SCC involving the subglottis, treated with open laryngeal surgery with or without paratracheal neck dissection (PTND). The relationship of the paratracheal lymph node metastatic pattern with laterocervical nodal status and tumor location within different subglottic subsites was analyzed. The influence of PTND on regional disease control was assessed. Paratracheal lymph nodes were affected in 12.2% of cases. An increased frequency (P = .064) of paratracheal metastasis was noticed in case of anterior subglottis extension with respect to other subsites. A correlation (P < .001) between paratracheal lymph node and laterocervical node involvement was found among subjects with posterior subglottic extension. Prophylactic PTND is indicated in laryngeal SCC with anterior subglottic extension and/or posterior subglottis involvement with clinically apparent laterocervical node metastases.


Effect of larval host on life history traits of the mediterranean fruit fly, Ceratitis capitata.
Demographic parameters for the Mediterranean fruit fly reared on each of twenty four different hosts from sixteen different plant families are reported. These include cohort parameters of development, survival, pupal sizc, and fecundity as well as population parameters such as intrinsic rate of population increase (r) and mean generation time. Major findings include the following: i) no consistent quantitative relationships existed between r and its chief demographic determinants such as preadult developmental time and adult fecundity; and ii) few correlations existed among the cohort life history parameters themselves. The principle conclusion is that the medfly is a successful generalist frugivore because of its developmental ability to offset the effect of the value for a host-specific trait that tends to lower r with one that tends to increase r, the net result of which is to maintain a relatively high r.


The antiphospholipid syndrome: prevalence among patients with stroke and transient ischemic attacks.
The prevalence of the antiphospholipid syndrome was determined prospectively in patients presenting with stroke and transient ischemic attacks. An attempt was made to define a subset of stroke patients at risk for this syndrome on the basis of their clinical features. Fifty-one consecutive patients with stroke and transient ischemic attacks were assessed. Tests used for the laboratory diagnosis of the antiphospholipid syndrome included four phospholipid-dependent coagulation tests for detection of the lupus anticoagulant, and two enzyme-linked immunosorbent assays for antibodies to phospholipid. Three of 51 patients (6%, 95% confidence intervals 0% to 12.0%) had a lupus anticoagulant and the clinical features of the antiphospholipid syndrome. Seven patients had clinical features suggestive of the syndrome but negative laboratory tests. Those patients who were clinically unlikely to have this syndrome also had negative laboratory tests. In a series of 51 unselected patients presenting with stroke and transient ischemic attacks, three had the antiphospholipid syndrome. The clinical features of this syndrome are helpful in identifying this group of patients. The role of the lupus anticoagulant in the pathogenesis of stroke remains to be defined.


Total external ophthalmoplegia and orbital apex syndrome as first presenting feature of Rhabdomyosarcoma involving petrous part of the temporal bone: A case report.
Rhabdomyosarcoma (RMS) can have various unusual presentations. We report an unusual presentation of RMS as orbital apex syndrome in a six-year-old boy involving the petrous part of the temporal bone. A six-year-old boy presented with drooping of the left eyelid for seven days associated with headache, left-sided hearing loss, and nasal blockage. Contrast-enhanced magnetic resonance imaging (CE-MRI) brain and orbit revealed an ill-defined expansile vascular lesion centered at the petrous part of the left temporal bone with extension to the cavernous sinus, which was confirmed as RMS on histopathology and immunohistochemistry. The patient was managed by chemotherapy and radiotherapy. RMS is the most common aggressive malignant soft tissue tumor in the pediatric population. It accounts for 4-8 % of all malignancies in children below 15 years of age, with strong male preponderance. The most common site for RMS is head and neck (45 %), having maximum incidence during the first decade of life. Total external ophthalmoplegia in a child is an acute emergency; it should be properly worked up, and neuroimaging should always be advised. Prompt diagnosis and management by a multidisciplinary team can be both life and sight-saving.


Efficacy analysis of single-agent carboplatin AUC4 2-weekly as second-line therapy for methotrexate-resistant (MTX-R) low risk gestational trophoblastic neoplasia (GTN).
Approximately one-third of patients with low-risk Gestational Trophoblastic Neoplasia (WHO 0-6) develop methotrexate-resistance (MTX-R). In the UK, subsequent treatment with either actinomycin-D (ActD) or multi-agent combination chemotherapy has depended on whether the hCG was above or below an hCG threshold. To reduce exposure to combination chemotherapy (CC), over the years the UK service has raised this threshold as well as using single-agent carboplatin AUC6 3-weekly at MTX-R instead of CC. Updated results for carboplatin demonstrate an 86% complete hCG response (hCG CR) but associated with haematological dose-limiting toxicity. In 2017, single-agent carboplatin became the national standard second-line treatment following MTX-R at hCG of >3000 IU/L. Carboplatin was changed to two-weekly AUC4 scheduling and continued until normal hCG plus 3 consolidation cycles. For patients failing to respond, CC (Etoposide-Actinomycin-D or EMA-CO) was introduced. 22 evaluable patients with a median hCG at MTX-R of 10,147 IU/L (IQR 5527-19,639) received carboplatin AUC4 2-weekly (median no. of cycles = 6, IQR 2-8). Of these, 36% achieved a hCG CR. All 14 non-CR patients were cured with subsequent CC; 11 and 2 patients with 3rd line and 4th line CC respectively and 1 patient following 5th line CC and hysterectomy. Overall survival remains 100%. Carboplatin is not sufficiently active in the second-line treatment of low-risk MTX-resistant GTN. New strategies are required to increase hCG CR and spare more toxic CC regimens.


Determination of selected perfluorinated alkyl acids and persistent organic pollutants from a small volume human serum sample relevant for epidemiological studies.
A simple and fast method is presented for the determination of selected persistent organic pollutants (POPs) and perfluorinated alkyl acids (PFAAs), a subgroup of per- and polyfluorinated alkyl substances (PFAS) from a single 200μl aliquot of serum. Sample pretreatment starts with dispersive solid phase extraction of POPs to dichloromethane-hexane, which is immediately poured to cleanup column. POPs are eluted from column and concentrated for GC-MS/MS analysis. PFAAs are trapped to dispersant and are then extracted with ammonium acetate in methanol, concentrated and analysed with LC-MS/MS. For POPs, the limit of detection (LOD) ranged from 1.6 to 17pg/ml. Oxychlordane and dichlorodiphenyltrichloroethane had LODs in the upper end of this range as they were more labile and prone for interferences in the GC-MS/MS. For PFAAs, the LOD range from 0.027 to 0.068ng/ml. For POPs, the accuracy from Standard Reference Materials SRM 1589a and Arctic Monitoring and Assessment Programme (AMAP) intercalibration samples range from 74 to 127% and the repeatability (relative standard deviation, RSD%) from 2.0 to 15%. For PFAAs, the accuracy from AMAP samples ranged from 90 to 110% and from LOQ level spiked serum samples from 72 to 133%. Repeatability from AMAP and LOQ samples ranged from 1.6 to 7.3% and 5.5 to 15%, respectively. The presented method is useful in epidemiological studies where only limited amount of serum is available.


Evidence for H2O2 mediating the irreversible action of acetylenic inhibitors of prostaglandin biosynthesis.
Oxidizing intermediates formed during prostaglandin biosynthesis can be detected by ferrocytochrome c and epinephrine. Different intermediates were responsible for the oxidative colorimetric changes with epinephrine and ferrocytochrome c, and submicromolar amounts of oxidant were detectable. Catalase diminished the absorbance change with epinephrine, but it did not stop the conversion of arachidonate to prostaglandins. This result indicates that small amounts of H2O2 were formed when producing the colorimetric change, and these had no apparent effect upon the enzyme stability. No colorimetric changes were detected during the time-dependent loss of oxygenase activity caused by various acetylenic acids, indicating that negligible amounts of H2O2 were formed. Nevertheless, the destructive action of the acetylenic acid was prevented by catalase, and it thereby appeared due to small amounts of H2O2 generated in situ as a result of a metastable complex of enzyme, oxygen and the acetylenic substrate analog.


Interleukin-1, stromal cells, granulopoiesis, and the inflammatory response.
A number of in vitro studies carried out in our laboratory over the past ten years have led to some clarification of the role of mononuclear phagocytes in hematopoietic regulation. The results of these studies have demonstrated that mononuclear phagocytes produce proteins, notably interleukin-1 (IL-1), that induce the expression of multilineage hematopoietic growth factors by human vascular endothelial cells, fibroblasts, T-lymphocytes, and thymic epithelial cells. More recently we and others have identified these induced factors as G-CSF, GM-CSF, IL-6, and IL-1. Although IL-1 seems to stimulate expression of these genes by inducing the accumulation of gene transcripts, interestingly the accumulation results from prolongation of mRNA half-life. We propose that the inductive capacity of IL-1 results from its activation of ribonuclease inhibitory activity in the cytoplasm of IL-1 induced cells and hypothesize that this may be a general mechanism by which IL-1 induces gene expression.


[Colorimetric investigation of normal tongue and lip colors from 516 healthy adults by visible reflection spectrum].
Using the data from normal tongue and lip colors of normal people which were collected by the visible reflection spectrum, we analyzed the colorimetric parameters of tongue and lip colors. In this study, 516 healthy students aging from 19 to 26 from the colleges and universities of Guangdong Province of China were taken as research subjects. After collecting the data of tongue and lip colors of the 516 subjects using visible reflectance spectroscopy, CIE XYZ tristimulus values as defined by the International Commission on Illumination in 1964 were calculated, and the colorimetric parameters of the normal tongue and lip colors were obtained, such as the CIE 1964 chromaticity coordinate, brightness, dominant wavelength and excitation purity. The results of CIE 1964 chromaticity diagram calculated on the visible reflection spectrum showed that the normal tongue color chromaticity coordinate x(10) was 0.341 3±0.008 5 and y(10) was 0.332 6±0.005 1, and the normal lip color chromaticity coordinate x(10) was 0.357 7±0.009 2 and y(10) was 0.338 3±0.005 7; the brightness Y values of the normal tongue color and lip colors were 17.96±3.78 and 19.78±3.72, the dominant wavelength values of the normal tongue color and lip color were (626.3±51.6) nm and (600.4±18.2) nm, and the excitation purity values of the normal tongue color and lip color were 0.083±0.031 and 0.144±0.036, respectively. Application of the visible reflection spectrum is a standard way to collect colorimetric data for inspection of the complexion. The investigation of chromaticity coordinates, brightness, dominant wavelength and excitation purity of the normal tongue and lip colors may offer the basic reference for diagnosing morbid complexion on the tongue and lip colors in traditional Chinese medicine.


PacRAT: a program to improve barcode-variant mapping from PacBio long reads using multiple sequence alignment.
Use of PacBio sequencing for characterizing barcoded libraries of genetic variants is on the rise. However, current approaches in resolving PacBio sequencing artifacts can result in a high number of incorrectly identified or unusable reads. Here, we developed a PacBio Read Alignment Tool (PacRAT) that improves the accuracy of barcode-variant mapping through several steps of read alignment and consensus calling. To quantify the performance of our approach, we simulated PacBio reads from eight variant libraries of various lengths and showed that PacRAT improves the accuracy in pairing barcodes and variants across these libraries. Analysis of real (non-simulated) libraries also showed an increase in the number of reads that can be used for downstream analyses when using PacRAT. PacRAT is written in Python and is freely available (https://github.com/dunhamlab/PacRAT). Supplemental data are available at Bioinformatics online.


Effect of low-dose-rate irradiation on the division potential of cells in vitro. V. Human skin fibroblasts from donors with a high risk of cancer.
Skin fibroblasts from normal donors, donors with ataxia-telangiectasia or Fanconi's anemia, and from 1 cancer patient were treated with repeated gamma-radiation at about 16 rads per hour. The remaining division potential of all fibroblasts, except for the Fanconi's anemia cells, was reduced to different extents by radiation. The growth potential of Fanconi's anemia cells was increased in all the irradiated cultures. The increase was 54% in the group that survived the longest. These results were identical to those obtained with fibroblasts from certain species that have a high probability of transformation.


Rapid and improved gas-liquid chromatography technique for detection of hippurate hydrolysis by Campylobacter jejuni and Campylobacter coli.
A gas-liquid chromatographic method which requires no chloroform extraction of the split products has been investigated for the detection of hippurate hydrolysis by Campylobacter spp. This technique gave better reproducibility than other tests also used in this study and allows the routine use of the gas-liquid chromatographic method for identification of Campylobacter isolates.


Generalized Pressure Pain Hypersensitivity in the Cervical Muscles in Women with Migraine.
To investigate the differences in pressure sensitivity in the cervical musculature including the upper trapezius, sternocleidomastoid, suboccipital, levator scapulae, and anterior scalene muscles between women with migraine and healthy controls. Cross-sectional study. Thirty women with migraine and 30 healthy women participated. Pressure pain thresholds (PPT) were bilaterally assessed over upper trapezius, sternocleidomastoid, suboccipital, levator scapulae, and anterior scalene muscles in a blinded design. Mean values of both sides were pooled for statistical analysis. Comparison between groups was performed by unpaired Student t-test and correlation with headache features with Spearman's correlation test. Migraine patients exhibited lower PPT in all muscles compared with controls: upper trapezius (P = 0.046); suboccipital (P < 0.001); sternocleidomastoid (P < 0.001); anterior scalene (P < 0.001), and levator scapulae (P < 0001). No associations were observed between the frequency and the intensity of migraine or years with the disease and PPT. This study showed generalized pressure pain hypersensitivity in the cervical musculature in women with migraine. Our findings provide support for the physical therapy treatment and evaluation of musculoskeletal cervical spine disorders in individuals with migraine and reinforce that all cervical muscles should be evaluated.


Not so fast: Paradoxically increased variability in the glucose tolerance test due to food withdrawal in continuous glucose-monitored mice.
This study was performed to determine the effect of fasting on reproducibility of the glucose tolerance test. Due to individual variation in animal feeding behaviors, fasting animals prior to metabolic and behavioral experiments is widely held to reduce inter-subject variation in glucose and metabolic parameters of preclinical rodent models. Reducing variability is especially important for studies where initial metabolite levels can influence the magnitude of experimental interventions, but fasting also imposes stress that may distort the variables of interest. One such intervention is the glucose tolerance test (GTT) which measures the maximum response and recovery following a bolus of exogenous glucose. We sought to investigate how fasting affects the response of individual mice to a GTT. Using simultaneous continuous glucose monitoring (CGM) and indirect calorimetry, we quantified blood glucose, physical activity, body temperature, metabolic rates, and food consumption levels on a minute-to-minute basis in adult male mice for 4 weeks. We tested the effects of a 4-h or 18-h fast on the GTT to examine the effect of food withdrawal in light or dark photoperiods. Studies were also performed with 4-h fasting in additional mice without implanted CGM probes. Contrary to our expectations, a 4-h fast during the light photoperiod promotes a paradoxical increase in inter-animal variation in metabolic rate, physical activity, body temperature, glycemia, and glucose tolerance. This hyperglycemic and hyper-metabolic phenotype promotes increased corticosterone levels and is consistent with a behavioral stress response to food deprivation, even in well-fed mice. We find that mice undergoing an 18-h fast entered torpor, a hibernation-like state. In addition to low body temperature and metabolic rate, torpor is also associated with glucose levels 56 mg/dl lower than those seen in mice with ad libitum access to food. Moreover, the time spent in torpor affects the response to a GTT. Our results suggest fasting mice before glucose tolerance testing, and perhaps other experiments, can have the opposite of the intended effect where fasting can increase, rather than decrease, experimental variability.


A mammary stimulating mitogen(s) from rat muscle: its possible influence in mammary tumorigenesis.
A mitogen has been shown to be present in rat abdominal muscle tissue, which could stimulate rat mammary cells grown in culture. Studies on the in vivo-stimulatory effects on the rat mammary gland, taking increase in DNA synthesis, mitotic index and wholemount preparation as the parameters, affirmed the presence of a mammary stimulating factor in the muscle tissue. Treatment of rat mammary glands with the crude mitogen preparation before and after a single gastric dose of 9,10-dimethyl-1,2-benzanthracene (DMBA), increased the mammary tumor incidence suggesting its possible influence in carcinogen-induced tumorigenesis in rats.


Influenza immunization: serologic and clinical responses in military units.
Two inactivated influenza-virus vaccines were tested and compared in three army training units in Israel. The serological responses to the vaccines and the side-effects were assessed. The vaccines contained the influenza strains which were prevalent in 1974: A2/Port Chalmers/1/73 and B/Hong Kong/8/73. One of the vaccines also contained A2/England/42/72. Both vaccines caused a more than three-fold rise in geometric mean titers against influenza A strains, and about a twofold rise in geometric mean titers against influenza B/Hong Kong/5/73. Approximately 75%-80% of the vaccinees acquired protective hemagglutination-inhibition antibody titers against influenza A strains, while less than 30% acquired protective titers against B strains. In general, there were no significant differences between the serological responses to the two vaccines. More than 50% of the vaccinees experienced at least one systemic side-effect (50.3% with one vaccine and 61.0% with the other). The average number of side-effects per person was between 1.78 and 2.11. However, these side-effects were generally of short duration and caused minimal disability. On the whole, the two vaccines did not differ significantly with regard to the side-effects they caused.


Differentiation of stereoisomeric steroids by reactions with phosphenium ions.
A chemical ionization method is reported for distinction of diastereomeric hydroxysteroids by using Fourier-transform ion cyclotron mass spectrometry (FT-ICR). Certain phosphenium ions are demonstrated to react with stereoisomeric steroids to yield qualitatively different product ions. For example, 1,3,5(10)-estratriene-3,16beta,17beta-triol (cis-estriol) reacts with the dimethoxy phosphenium ion to form a diagnostic product ion (not formed for the trans-estriol) through addition followed by the loss of two molecules of methanol. In an analogous manner, the 1,3-dioxolan-2-phosphenium ion produces a diagnostic product ion through the loss of ethylene glycol from the adduct of cis-estriol only. The 1,3,5(10)-estratriene-3,16alpha,17beta-triol (trans-estriol), on the other hand, reacts with each phosphenium ion only via hydroxide abstraction-initiated pathways that indicate the presence of at least two hydroxyl groups in the molecule. These specific reactions take place for all hydroxysteroids examined, independent of their stereochemistry. Another isomer pair, cholestan-3alpha,5alpha-diol (cis-cholestandiol) and cholestan-3beta,5alpha-diol (trans-cholestandiol), is differentiated based on selective elimination of water only from the adduct of the cis-isomer. However, the method does not allow distinction between the stereoisomeric 5beta-pregnane-3alpha,17alpha,20alpha-triol and 5beta-pregnane-3alpha,17alpha,20beta-triol. The different reactivities of the three pairs of steroid isomers and of each diastereomeric compound pair are rationalized by reaction enthalpies and steric effects based on straightforward and predictable reaction mechanisms.


Two-step sequential management for hip arthroplasty after hip joint gunshot injury: A case report.
Combined fractures of the femoral head and acetabulum due to hip gunshot injuries (GSI) are rare, and there is no preferred treatment option. We present a 35-year-old male patient who sustained a right hip GSI. Delayed THA with a two-step sequential approach is a feasible management in this situation to manage soft tissue and decrease infection rate. At a 1-year follow-up visit, the pain was relieved, and the function improved significantly, and he had no complaints.


TGF-β activity in acid bone lysate adsorbs to titanium surface.
Osteoblasts lay down new bone on implant surfaces. The underlying cellular mechanism and the spatio-temporal mode of action, however, remain unclear. It can be proposed that growth factors released upon acidification by osteoclasts adsorb to the implant surface and control the early stages of osseointegration. To simulate bone lysis by osteoclasts, titanium discs were exposed to acid bone lysate (ABL) followed by vigorous washing and seeding of oral fibroblasts. The expression of TGF-β target genes interleukin 11 (IL11) and NADPH oxidase 4 (NOX4) was evaluated by reverse transcriptase polymerase chain reaction and IL11 ELISA. TGF-β signaling activation was assessed via Smad2/3 immunofluorescence. The impact of ABL on osteogenic differentiation was determined with murine ST2 mesenchymal stromal cells. We report here that ABL-conditioned titanium discs, independent of turned or rough surface, increased the expression of IL11 and NOX4. This increase was blocked by the TGF-β receptor 1 antagonist SB431542. Further support for the TGF-β signaling activation came from the translocation of Smad2/3 into the nucleus of oral fibroblasts. Moreover, titanium discs exposed to ABL decreased alkaline phosphatase and osteopontin in ST2 cells. These in vitro findings suggest that titanium can adsorb TGF-β from ABLs. The data provide a strong impetus for studies on the protein adsorption on implant surfaces in vitro and in vivo, specifically for growth factors including bone-derived TGF-β during successful and failed osseointegration.


Odor abnormalities caused by bilateral thalamic infarction.
Odor is the only sensation thought to be unrelated to the thalamus. However, accumulating evidence suggests that the dorsomedial nucleus (DM) of the thalamus is associated with odor. Although the thalamus is prone to ischemia, only a single patient with bilateral DM infarctions was reported to have odor abnormalities. We describe a second such patient with infarctions involving the left DM and the right ventral posterior nucleus and ventral lateral nucleus, nuclei adjacent to the DM, associated with transient edema. In contrast to the previous case, our patient had transient odor abnormality. These observations suggested that direct and/or indirect bilateral involvement of the DM might be associated with odor abnormalities in patients with thalamic infarction.


MiRNA-1 promotes pyroptosis of cardiomyocytes and release of inflammatory factors by downregulating the expression level of PIK3R1 through the FoxO3a pathway.
Pyroptosis can be seen in both physiological and pathological processes, and whether it plays a positive or negative role has not been fully clarified, especially in the study of cardiology, which deserves more attention. A model of cardiomyocyte Hypoxia/Reoxygenation was established to detect MicroRNA (miRNA) expression. The C57BL/6 mice and H9c2 cells were respectively treated with Ischemic/Reperfusion (I/R) and Hypoxia/Reoxygenation (H/R). Then, the concentrations of interleukin-1β (IL-1β) and IL-18 were detected in serum and culture medium supernatant, as well as the expression levels of FOXO3, Caspase1, and PIK3R1. In I/R group, the concentrations of IL-1β and IL-18 in the supernatant of H9c2 cell culture solution were significantly higher compared with the control group. Consistent with the supernatant concentrations of IL-1β and IL-18, IL-1β, and IL-18 were also increased at a high level in I/R group at the transcriptional level. Furthermore, the in vitro experiments showed that FOXO3 and Caspase1 were significantly upregulated in myocardial cells with the treatment of I/R group compared to sham group. Concerning pyroptosis, the expression of PIK3R1 was dramatically decreased and the expression of miRNA-1 was significantly increased in H9c2 cells. MiRNA-1 promoted pyroptosis of cardiomyocytes and release of inflammatory factors by downregulating the expression level of PIK3R1.


Clinical evaluation of the polypropylene-polyester knit used as a cranioplasty material.
The paper presents clinical evaluation of the polypropylene-polyester knit used as a cranioplasty material. Between year 1980 and 2002 275 cranioplastic procedures using the polypropylene-polyester plates Codubix were carried out in the Department of Neurosurgery of the Medical University of Łódź. There were 146 patients who primarily sustained head injuries and 129 non-traumatic patients with craniectomies carried out for various other reasons. In the majority of cases, i.e. in 158 patients, cranioplasty was performed later than 6 months after the primary surgery. The largest implant measured 430 cm2. Excellent and good outcome was achieved in 92% of the patients whereas the rate of local infection was 8%. Codubix knitted polypropylene-polyester implant proved to be useful and a safe cranioplastic material.


Prenatal buprenorphine exposure: effects on biochemical markers of hypoxia and early neonatal outcome.
To evaluate the possible association between prenatal buprenorphine exposure and compromised early neonatal outcome in view of markers of perinatal hypoxia. DESIGN, SETTING AND SAMPLE: The study group consisted of 27 full-term neonates exposed to buprenorphine prenatally and prospectively followed up at a special tertiary outpatient clinic for pregnant drug abusers. Serving as controls were 27 full-term neonates exposed prenatally to illicit substances other than opioids and 38 full-term neonates from uncomplicated pregnancies of healthy parturients. Apgar scores, cord pH and base excess were recorded. Cord serum samples were collected at birth for analysis of biochemical markers of fetal hypoxic stress: erythropoietin (EPO; chronic hypoxia), cardiac troponin T (cardiac involvement) and S100 (neural damage). All infants were born in good condition according to Apgar scores and pH of cord blood. No statistically significant differences were found between the three groups in cord serum concentrations of EPO (33.0 median, range: 9.0-476.0 U/L in the buprenorphine-exposed group vs 27.0, range: 8.0-114.0 U/L in substance-abusing controls vs 28.1, range: 11.6-260.0 U/L in healthy controls) or S100 (0.47, range: 0.25-0.91 microg/L vs 0.40, range: 0.12-1.22 microg/L vs 0.47, range: 0.20-2.15 microg/L). No significant differences existed in cardiac TnT levels (0.017, range: 0.010-0.072 U/L vs 0.010, range: 0.010-0.075 U/L vs 0.024, range: 0.010-0.075 U/L). While no significant differences in asphyxia markers were observed between the three groups, a tendency towards higher levels of EPO emerged in the buprenorphine-exposed group.


Painful Horner's syndrome due to spontaneous carotid artery dissection.
Spontaneous dissection of the internal carotid artery as a cause of Horner's syndrome has only been recognized in recent years. The authors describe three patients with this condition. Associated symptoms included ipsilateral orbital and frontal headache (3 patients), neck and facial pain (2), amaurosis fugax (1), and dysgeusia (1). The symptoms resolved in all patients within three months, yet oculosympathetic paralysis has persisted. Diagnosis of carotid dissection required cerebral arteriography, and the angiographic features are presented. Patients were treated with platelet antiaggregants, and they have remained neurologically stable during follow-up (mean, 12 months; range, 10-14 months).


Cancer classification based on multiple dimensions: SNV patterns.
The occurrence of cancer is closely related to single nucleotide variants (SNVs). However, in DNA samples collected from patients with distinct cancers, SNVs are detected in different patterns. Therefore, it is an important task to select the appropriate method by which to classify cancer to the greatest extent of SNV patterns, which will aid in cancer diagnosis and treatment. In traditional studies, researchers combined each SNV with its neighboring nucleotides to form a trinucleotide. Mutation signatures for cancer classification were extracted from the patterns of the trinucleotides, but the SNV feature extraction in a single dimension may result in partial information loss and poor model performance. In this study, we defined multidimensional SNV (M-SNV) features to classify cancer. M-SNV features considered first- and second-order neighboring nucleotides of one-dimensional SNVs and included six types of features. We validated the feasibility of M-SNV features using a dataset obtained from The Cancer Genome Atlas (TCGA) consisting of 2761 samples from 12 cancers. We performed preliminary screening of 562,321 DNA mutation sites in these samples. The remaining mutation sites were characterized by cancer type in six signatures. We found that the extracted features showed a similar distribution in the cluster center of the cancer type of the samples. After the preprocessing of raw data, samples were more focused on the cancer subtype distributions at the SNV level. We used KNN (k-nearest neighbors) to classify the extracted features and employed the leave-one-out cross to verify them. The accuracy of classifying is stable at approximately 97% and can reach 97.43% in the most optimal case. Furthermore, we found that the validated oncogenes in the loci of the features had the highest importance among the 8 cancers. It is feasible to classify cancers by the distribution of features we defined. Moreover, our methodology has potential implications for the discovery of oncogenes.