Cognitive improvement after cochlear implantation in deaf children with associated disabilities.
To monitor functional auditory and non-verbal cognitive skills in children with cochlear implants who had associated disabilities over a 24-month period and define how cochlear implantation may impact on non-verbal cognition by restoring functional auditory skills. Sixty-four children with cochlear implants (36 females, 28 males; mean age 4y 3mo, SD 3y 5mo, 9mo-14y 5mo) were recruited and divided into three groups: children with typical development group (TDG); children with associated disabilities not linked to non-verbal cognitive disorders group (ADG1); and children with associated disabilities linked to non-verbal cognitive disorders group (ADG2). Tests of functional auditory, communicative, and non-verbal cognitive skills were performed before cochlear implantation and at 12 and 24 months after cochlear implantation. Functional auditory and communicative skills improved similarly in the three groups at 12 and 24 months after implantation. An increase in non-verbal cognitive scores was present in children in the ADG2 from baseline to 12 and 24 months (p<0.01), whereas scores remained stable in children in the TDG and ADG1. The increased functional auditory skills scores after cochlear implantation corresponded to an increase in non-verbal cognitive scores (p=0.032) in children in the ADG2. Children with associated disabilities, especially if linked to non-verbal cognitive disorders, benefitted from cochlear implantation. They improved their comprehension of acoustic information inferred from the environment, improving not only functional auditory skills but also non-verbal cognition.


Serum concentration of AMDL DR-70 for the diagnosis and prognosis of carcinoma of the tongue.
The aim of this study was to discover the clinical value of the tumour marker AMDL DR-70 in a group of patients with cancer of the tongue. Serum concentrations of AMDL DR-70 were estimated by enzyme linked immuno-sorbent assay in 52 patients with carcinoma of the tongue and compared with 40 controls and 42 patients with benign lesions in the tongue. Thirty-nine patients with carcinoma of the tongue had results above 6 mg/L (75%), compared with 3/40 (7%) in healthy controls and 4/42 (10%) in those with benign tumours. The concentration of AMDL DR-70 in serum correlated significantly with 3-year survival.


Preparation of Human Kidney Progenitor Cultures and Their Differentiation into Podocytes.
Kidney diseases are a global health concern. Modeling of kidney disease for translational research is often challenging because of species specificities or the postmitotic status of kidney epithelial cells that make primary cultures, for example podocytes. Here, we report a protocol for preparing primary cultures of podocytes based on the isolation and in vitro propagation of immature kidney progenitor cells subsequently differentiated into mature podocytes. This protocol can be useful for studying physiology and pathophysiology of human kidney progenitors and to obtain differentiated podocytes for modeling podocytopathies and other kidney disorders involving podocytes.


A direct and continuous assay for the determination of thioredoxin reductase activity in cell lysates.
Thioredoxin reductase (TR) is an oxidoreductase responsible for maintaining thioredoxin in the reduced state, thereby contributing to proper cellular redox homeostasis. The C-terminal active site of mammalian TR contains the rare amino acid selenocysteine, which is essential to its activity. Alterations in TR activity due to changes in cellular redox homeostasis are found in clinical conditions such as cancer, viral infection, and various inflammatory processes; therefore, quantification of thioredoxin activity can be a valuable indicator of clinical conditions. Here we describe a new direct assay, termed the SC-TR assay, to determine the activity of TR based on the reduction of selenocystine, a diselenide-bridged amino acid. Rather than being an end-point assay as in older methods, the SC-TR assay directly monitors the continuous consumption of NADPH at 340 nm by TR as it reduces selenocystine. The SC-TR assay can be used in a cuvette using traditional spectrophotometry or as a 96-well plate-based format using a plate reader. In addition, the SC-TR assay is compatible with the use of nonionic detergents, making it more versatile than other methods using cell lysates.


Principles of physics in surgery: the laws of mechanics and vectors physics for surgeons-part 2.
In this sequel, to an earlier article, we discuss the laws of Mechanics, Thermodynamics and Vectors as they apply to soft and bony tissues. These include the Laplace's Law as applied to colonic perforation, compression therapy, parturition, variceal rupture, disc herniations etc. The Pascal's Law finds use in hernia repair and the Heimlich maneuver. Trigonometrically derived components of forces, acting after suturing, show ways to reduce cut-through; the thickness and the bite of suture determines the extent of tissue reaction. The heating effect of current explains the optimum gap between the prongs of a bipolar cautery and the use of law of transfer of heat in determining relation between healthy wound healing and ambient temperature.


Magnetotaxis.
The ability of magnetotactic bacteria to orientate and navigate along geomagnetic lines is due to intracellular magnetic particles. These are enclosed within a membrane to form a magnetosome, a specialized organelle of magnetotactic organisms. The magnetic crystallite of many of the magnetotactic bacteria and algae is the iron oxide magnetite (Fe3O4) but recently a multicellular bacterial aggregate has been found to contain magnetic iron sulphide. Magnetotactic bacteria are found in regions of low oxygen pressure. Those of the Northern hemisphere are north-seeking while those of the Southern hemisphere are south-seeking. The opposite polarity of their internal magnets enables both types to travel to the deeper, less oxygenated, regions of their aqueous environments.


Strategies for senolytic drug discovery.
Senolytics are a category of drugs that reduce the impact of cellular senescence, an effect associated with a range of chronic and age-related diseases. Since the discovery of the first senolytics in 2015, the number of known senolytic agents has grown dramatically. This review discusses the broad categories of known senolytics-kinase inhibitors, Bcl-2 family protein inhibitors, naturally occurring polyphenols, heat shock protein inhibitors, BET family protein inhibitors, P53 stabilizers, repurposed anti-cancer drugs, cardiac steroids, PPAR-alpha agonists, and antibiotics. The approaches used to screen for new senolytics are articulated including a range of methods to induce senescence, different target cell types, various senolytic assays, and markers. The choice of methods can greatly influence the outcomes of a screen, with high-quality screens featuring robust systems, adequate controls, and extensive validation in alternate assays. Recent advances in single-cell analysis and computational methods for senolytic identification are also discussed. There is significant potential for further drug discovery, but this will require additional research into drug targets and mechanisms of actions and their subsequent rigorous evaluation in pre-clinical models and human trials.


Seasonal influenza vaccine delivered by intradermal microinjection: A randomised controlled safety and immunogenicity trial in adults.
Influenza vaccines remain largely underused. A promising alternative to current intramuscular vaccines is a trivalent inactivated influenza vaccine (TIV) delivered using a microinjection system to offer a less invasive and possibly more acceptable vaccination. A phase II, multicentre, randomised open-label study in 978 healthy adults (18-57 years) evaluated the immunogenicity and safety of intradermal TIV. Subjects received a 0.1 ml injection of intradermal TIV, containing 9 microg of haemagglutinin (HA) per strain (n = 588) or a conventional 0.5 ml intramuscular vaccine (15 microg of HA/strain; n = 390). Intradermal TIV induced non-inferior humoral immune responses against all three strains and superior responses against both A strains (H1N1, H3N2) compared with the control. Both vaccines were well tolerated.


Ion permeation through a voltage- sensitive gating pore in brain sodium channels having voltage sensor mutations.
Voltage-gated sodium channels activate in response to depolarization, but it is unknown whether the voltage-sensing arginines in their S4 segments pivot across the lipid bilayer as voltage sensor paddles or move through the protein in a gating pore. Here we report that mutation of pairs of arginine gating charges to glutamine induces cation permeation through a gating pore in domain II of the Na(V)1.2a channel. Mutation of R850 and R853 induces a K(+)-selective inward cationic current in the resting state that is blocked by activation. Remarkably, mutation of R853 and R856 causes an outward cationic current with the opposite gating polarity. These results support a model in which the IIS4 gating charges move through a narrow constriction in a gating pore in the sodium channel protein during gating. Paired substitutions of glutamine allow cation movement through the constriction when appropriately positioned by the gating movements of the S4 segment.


Endogenous miRNA in the green alga Chlamydomonas regulates gene expression through CDS-targeting.
MicroRNAs (miRNAs) are 21-24-nucleotide RNAs present in many eukaryotes that regulate gene expression as part of the RNA-induced silencing complex. The sequence identity of the miRNA provides the specificity to guide the silencing effector Argonaute (AGO) protein to target mRNAs via a base-pairing process 1 . The AGO complex promotes translation repression and/or accelerated decay of this target mRNA 2 . There is overwhelming evidence both in vivo and in vitro that translation repression plays a major role 3-7 . However, there has been controversy about which of these three mechanisms is more significant in vivo, especially when effects of miRNA on endogenous genes cannot be faithfully represented by reporter systems in which, at least in metazoans, the observed repression vastly exceeds that typically observed for endogenous mRNAs 8,9 . Here, we provide a comprehensive global analysis of the evolutionarily distant unicellular green alga Chlamydomonas reinhardtii to quantify the effects of miRNA on protein synthesis and RNA abundance. We show that, similar to metazoan steady-state systems, endogenous miRNAs in Chlamydomonas can regulate gene expression both by destabilization of the mRNA and by translational repression. However, unlike metazoan miRNA where target site utilization localizes mainly to 3' UTRs, in Chlamydomonas utilized target sites lie predominantly within coding regions. These results demonstrate the evolutionarily conserved mode of action for miRNAs, but details of the mechanism diverge between the plant and metazoan kingdoms.


The Impact of Incidental Ultrasound Finding of Subchorionic and Retroplacental Hematoma in Early Pregnancy.
Chorionic hematomas can be caused by the separation of the chorion from the endometrium, with an incidence of 3.1% of all pregnancies. It is the most common sonographic abnormality and the most common cause of first-trimester bleeding. To evaluate the impact of subchorionic and retroplacental hematomas detected by ultrasound in the first trimester of pregnancy. A prospective observational case-control study was conducted at Elwiya Maternity Teaching Hospital on 100 pregnant ladies with subchorionic or retroplacental hematoma shown in ultrasound compared with 200 pregnant ladies without hematoma in the first trimester. The demographic feature, course of pregnancy, obstetric outcome, and neonatal outcome were analyzed. There was statistically significant difference between both groups regarding maternal and neonatal outcome. In regard to maternal outcome, there is increasing rate of miscarriage (20%, P = 0.004), preterm labor (18%, P = 0.005), intrauterine growth restriction (7%, P < 0.001), abruption (9%, P = 0.001), and cesarean section (60%, P < 0.001) compared to control group. Regarding neonatal outcome, there is increasing rate of low gestational age at birth (P = 0.004), low birth weight (P = 0.003), low Apgar score at 1 & 5 min (P < 0.001, P = 0.002, respectively), and more admission to NICU (P = 0.015) in study group when compared to control group. The presence and the characteristic of an intrauterine hematoma during the first trimester may identify a population of patients at increased risk of adverse pregnancy outcome as miscarriage, preterm delivery, IUGR, abruption, low birth weight, cesarean section rate, low Apgar score at 1 and 5 min, and NICU admissions in patients with intrauterine hematoma.The miscarriage rate with retroplacental hematoma is significantly higher than with subchorionic hematoma. The size of the hematoma is significantly greater in the miscarriage group.All subchorionic hematomas disappeared, but 2% of retroplacental hematomas did not disappear until the end of second trimester.


Acquired changes in stomatal characteristics in response to ozone during plant growth and leaf development of bush beans (Phaseolus vulgaris L.) indicate phenotypic plasticity.
Bush bean (Phaseolus vulgaris L.) lines 'S156' (O3-sensitive)/'R123' (O3-tolerant) and cultivars 'BBL 290' (O3-sensitive)/'BBL 274' (O3-tolerant) were used to study the effects of O3 on stomatal conductance (gs), density, and aperture size on leaf and pod surfaces with the objective of establishing links between the degree of plant sensitivity to O3 and plasticity of stomatal properties in response to O3. Studies in open-top chambers (OTCs) and in continuously stirred tank reactors (CSTRs) established a clear relationship between plant developmental stages, degrees of O3 sensitivity and gs: while 'S156' had higher gs rates than 'R123' earlier in development, similar differences between 'BBL 290' and 'BBL 274' were observed at later stages. Gs rates on the abaxial leaf surfaces of 'S156' and 'BBL 290', accompanied by low leaf temperatures, were significantly higher than their O3-tolerant counterparts. Exposure to O3 in CSTRs had greater and more consistent impacts on both stomatal densities and aperture sizes of O3-sensitive cultivars. Stomatal densities were highest on the abaxial leaf surfaces of 'S156' and 'BBL 290' at higher O3 concentrations (60 ppb), but the largest aperture sizes were recorded on the adaxial leaf surfaces at moderate O3 concentrations (30 ppb). Exposure to O3 eliminated aperture size differences on the adaxial leaf surfaces between sensitive and tolerant cultivars. Regardless of sensitivity to O3 and treatment regimes, the smallest aperture sizes and highest stomatal densities were found on the abaxial leaf surface. Our studies showed that O3 has the potential to affect stomatal plasticity and confirmed the presence of different control mechanisms for stomatal development on each leaf surface. This appeared to be more evident in O3-sensitive cultivars.


Determinants of the low uptake of HIV-related intervention services by female sex workers in Shenzhen, China: an observational study (2009-2012).
Background Female sex workers (FSWs) are highly vulnerable to HIV but make little use of HIV-related intervention services provided by the Chinese government. Determinants of the low uptake of HIV services by FSWs in Shenzhen, Guangdong province were investigated. FSWs were recruited by venue-based sampling; 1656 FSWs were interviewed about sociodemographics, behaviours and uptake of HIV-related intervention services. Determinants of no uptake of HIV testing, condom promotion, and peer education were determined through logistic regression. The association between uptake of HIV-related services, condom use and HIV-related knowledge was also assessed. The overall uptake of HIV testing, condom promotion, and peer education by FSWs was 21.5%, 47.8% and 28.0%, respectively. Young age and shorter duration of working in Shenzhen were statistically significantly correlated with no uptake of all three interventions. Uptake of these services was positively associated with consistent condom use and good HIV-related knowledge. The uptake of HIV-related intervention services by FSWs is low in Shenzhen. As their uptake is positively associated with condom use and HIV-related knowledge, it is necessary to intensify promotion of these, focusing on young and recently started FSWs.


[Super-resolution ultrasound imaging : Methods and applications].
The microvasculature plays an important role in many pathologic conditions but cannot be characterized in high resolution via conventional ultrasound methods. Doppler-based techniques, contrast-enhanced sonography as well as dynamic contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used to characterize tissue vascularization. However, these techniques cannot visualize the microvasculature adequately. Ultrasound localization microscopy (ULM) consists of contrast-enhanced ultrasound measurements in combination with a complex post-processing algorithm which detects microbubbles with high precision. The vasculature can then be visualized by accumulating the microbubble positions in a final image. Compared to conventional ultrasound techniques, ULM improves the image resolution by a factor of more than 10. This currently results in resolutions down to 10 µm and allows, therefore, the visualization of capillaries and the assessment of their perfusion. Also, this does not lead to a reduction of the penetration depth or the signal-to-noise ratio (SNR). The method enables the visualization of vascular structures in unsurpassed detail and has the potential to offer new possibilities for the diagnosis of various diseases and for gaining insights into physiological processes. However, ULM is not commercially available yet but is intensely being tested in clinical studies. ULM could potentially be applied to all fields in which the vasculature is relevant. Current fields of application include oncology, nephrology, and neurological research.


Activation of murine peritoneal macrophages by saikosaponin a, saikosaponin d and saikogenin d.
Macrophage activation by saikosaponins and saikogenins was investigated and compared with that by other saponins and macrophage stimulants. Saikosaponins a and d induced a marked cell accumulation in the peritoneal cavity when administered intraperitoneally. Among saikosaponins and saikogenins tested, saikosaponin d significantly activated peritoneal macrophages in terms of enhancement of phagocytic activity, increased level of cellular lysosomal enzyme (acid phosphatase), induction of cytostatic activity and expression of Ia antigen on the cell surface. The activities of saikosaponin d were much stronger than those of typical saponins ginsenoside Rg1 and glycyrrhizin and almost comparable with or somewhat weaker than those of lipopolysaccharide, a streptococcal preparation OK-432 and formalin-killed Propionibacterium acnes, indicating that saikosaponin d is a potent macrophage activator.


Sommerlad-Furlow modified palatoplasty: A retrospective study.
The purpose of this study was to introduce the surgical process of Sommerlad-Furlow modified (S-F) palatoplasty and compare its surgical and functional outcomes with conventional Sommerlad (S) palatoplasty. Patients with non-syndromic cleft palate who had undergone either S-F palatoplasty or S palatoplasty were retrospectively reviewed. Data on the outcomes of velopharyngeal function and postsurgical palatal fistula incidence were collected for all patients. Data for preselected factors, including gender, age at palatoplasty, and cleft type, were also collected. Chi-square tests were conducted. 1254 patients were included. The postsurgical velopharyngeal competence (VPC) rate after S-F palatoplasty was significantly higher than after S palatoplasty (total, 70.5% vs 57.9%, p < 0.0001; age ≤ 1, 87.0% vs 69.2%, p < 0.0001; 1 < age ≤ 2, 78.3% vs 69.3%, p = 0.0479). With regard to different types of cleft palate, the postsurgical VPC rates after S-F palatoplasty were all significantly higher than for S palatoplasty in all patients younger than 2 years of age (complete cleft palate, 78.7% vs 62.4%, p = 0.0016; hard and soft palate cleft, 84.4% vs 74.8%, p = 0.0172; submucosal cleft and soft palate cleft, 96.6% vs 68.4%, p = 0.0114). The postoperative fistula rate after S-F palatoplasty was 4.3%. This modified palatoplasty technique provided adequate cleft palate closure, with satisfactory speech outcomes and low fistula rates, while older age at palatoplasty may affect the postsurgical outcomes. Within the limitations of the study it seems that the Sommerlad-Furlow modified technique is an option for cleft palate repair.


Signet-ring cell carcinoma of the ileum: report of a case and review of the Japanese literature.
We report herein the extremely unusual case of a 71-year-old woman with signet-ring cell carcinoma of the ileum. She originally presented with a 6-month history of intermittent nausea and abdominal distention, but initial examinations, including gastrointestinal fiberscopy, ultrasonography, and computed tomography (CT) scan, failed to reveal any cause of her symptoms. A barium-enema study performed 11 months after her initial visit demonstrated a narrow portion of the terminal ileum. An ileocecal resection was subsequently performed, and an epigastric subcutaneous tumor was simultaneously excised. The specimen contained a tumor with a stenotic lumen resembling a "lead pipe", an ulcerative portion, and mucosa with a granular appearance adjoining its proximal site. Many small aphthous lesions with IIa + IIc appearance were seen in the apparently normal mucosa. Histopathological examination confirmed a diagnosis of signet-ring cell carcinoma. The small aphthous lesions seemed to be metastases spread via the lymphatic vessels. Our review of the medical literature revealed three cases of signet-ring cell carcinoma of the jejunum; however, this is the first reported case of signet-ring cell carcinoma of the ileum.


Serum MBP immunoreactivity and immunoglobulin level as markers of tumour type.
Forty three patients, admitted to the department of Neurological Surgery for management of central nervous system tumours, were studied pre-operatively for serum myelin basic protein immunoreactivity as a marker of central nervous system lesion and for circulating immunoglobulins and complement (C3) levels. Myelin basic protein concentration did not appear to correlate with tumour type or grade. Serum immunoglobulin levels were found to be within the normal range but the mean IgM level was significantly higher in the glioma group when compared with meningiomas.


Polyoxometalate-Surfactant Assemblies: Responsiveness to Orthogonal Stimuli.
Integrating different types of supramolecular interactions opens the possibility to generate nanoparticle surfactants (NPSs) at the liquid-liquid interface that are responsive to multiple stimuli. Here we develop a covalently modified polyoxometalate/β-cyclodextrin (POM/β-CD) organic-inorganic hybrid, consisting of a negatively charged POM cluster with β-CD host groups. The POM/β-CD hybrid can be dispersed in water and interacts at a water/oil interface with ligands dissolved in an oil phase through electrostatic or host-guest interactions, thereby generating POM-surfactants (POMSs) having pH, redox, and guest-competitive responsiveness, respectively. By taking advantage of the jamming of POMSs at the interface, a reconfigurable all-liquid system could be produced that is responsive to orthogonal changes in the external environment.


Pain and agitation treatment in severe dementia patients: The need for Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) pain scale translation, adaptation and validation with psychometric testing.
The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization-Observation-Behavior-Intensity-Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤ 12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach's α = 0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC = 0.902) reliability. The construct validity is high (Rho = 0.748 p < 0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p < 0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen's K = 0.744. The average execution time is of 5.8 min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers.


Morphological and morphometric analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: a retrospective study.
Recessive dystrophic epidermolysis bullosa is a highly disabling genodermatosis characterized by skin and mucosal fragility and blistering. Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications, having a high morbidity and mortality rate. Patients with recessive dystrophic epidermolysis bullosa were reported to have up to a 70-fold higher risk of developing cSCC than unaffected individuals. Immune cells play a role in cancer evolution. The aim of our study was to evaluate immunohistological differences between cSCC in patients with and without recessive dystrophic epidermolysis bullosa. A retrospective study of 25 consecutive cases was performed; five were biopsies of cSCC taken from five patients with recessive dystrophic epidermolysis bullosa; as controls we analysed 10 cSCC in subjects without recessive dystrophic epidermolysis bullosa (5 primitive, 3 postburns and 2 postradiotherapy), 5 cSCC in renal transplant recipients and 5 cutaneous pseudoepitheliomatous hyperplasia in patients with recessive dystrophic epidermolysis bullosa. A significant reduction of CD3+, CD4+ and CD68+ between the cSCC in patients with recessive dystrophic epidermolysis bullosa compared to primary cSCC and a significant reduction of CD3+, CD4+, CD8+ and CD20+ were observed in cSCC in patients with recessive dystrophic epidermolysis bullosa compared to secondary cSCC. On the contrary, there was no difference in CD3+, CD8+, CD20+ and CD68+ expression when comparing cSCC in patients with recessive dystrophic epidermolysis bullosa to cSCC in renal transplant recipients. No significant difference was found in size, histopathology, grading, number of mitoses and EGFR expression between the different groups. Our data show a reduction in immune cell peritumoral infiltration. Considering the well-known evolution of cSCC in patients with recessive dystrophic epidermolysis bullosa, as well as the younger age at diagnosis, it can be assumed that immune dysfunction might contribute to the cSCC aggressiveness in these patients.


The p.Cys1281Tyr variant in the hinge module/flap region of thyroglobulin causes intracellular transport disorder and congenital hypothyroidism.
Congenital hypothyroidism (CH) due to thyroglobulin (TG) variants causes very low serum TG levels with normal or enlarged thyroid glands, depending on the severity of the defect, and with autosomal recessive inheritance. The purpose of this study was to functionally characterize p.Cys1281Tyr variant in the TG gene in order to increase our knowledge of the molecular mechanisms associated with CH. In order to find evidence that support the hypothesis that the p.Cys1281Tyr variant would affect the TG folding were performed amino acid prediction, 3D modeling and transient expression analysis in HEK293T cells. 18 of the 21″in silico" algorithms predict a deleterious effect of the p.Cys1281Tyr variant. The full-length 3D model p.Cys1281Tyr TG showed disulfide bond cleavage between the cysteines at positions 1249 and 1281 and rearrangement of the TG structure, while transient expression analysis indicated that p.Cys1281Tyr causes retention of the protein inside the cell. Consequently, these results show that this pathogenic variant makes it impossible for TG to fulfill its function in the biosynthesis process of thyroid hormones, causing CH. In conclusion, our results confirm the pathophysiological importance of misfolding of TG as a consequence of p.Cys1281Tyr variant located in the hinge module/flap region of TG.


Endovascular repair with contralateral external-to-internal iliac artery bypass grafting: a case series.
To report a technique of keeping unilateral blood flow in the internal iliac artery in cases of an abdominal aortic aneurysm in achieving successful Endovascular abdominal aortic aneurysm repair using an external-to-internal artery bypass. 6 japanese patients with infra-renal abdominal aortic aneurysms were treated using the retroperitoneal approach via a left (right) paramedian incision followed by an external-to-internal artery bypass. Endovascular abdominal aortic aneurysm repair was conducted on mean postoperative day 29 ± 18 and was performed because the contralateral internal iliac artery, which was not involved in the external-to-internal artery bypass, was treated with a coil embolization. No complications developed during the postoperative follow-up period (17 ± 1.5 months). In all 6 patients, patent grafts were evident on computed tomography angiography scans even after 1-3 months. Endovascular abdominal aortic aneurysm repair with unilateral internal iliac artery embolization and contralateral external-to-internal artery bypass is feasible with a relatively low risk. It is a safe procedure and reduces the incidence of postoperative complications.


Nodular accumulation of type II cells and inflammatory lesions caused by inhalation of low cobalt concentrations.
Eight rabbits were exposed to 2 mg/m3 and eight to 0.4 mg/m3 of cobalt as CoCl2 for 14-16 weeks (5 days/week, 6 hr/day). Eight rabbits were used as controls. Light microscopic examination of the lungs showed nodular accumulation of alveolar type II cells in all cobalt-exposed rabbits. Abnormal macrophage reaction was observed in all eight rabbits exposed to the high dose and in five of the eight exposed to the low dose. Interstitial inflammation was present in all the rabbits exposed to the high dose and in half of the rabbits exposed to the low dose. Ultrastructural morphometric examination revealed no significant increase in the volume density of type II cells in the cobalt-exposed animals, as the nodular accumulation of these cells was balanced by an increased number of interjacent fields devoid of type II cells. In cobalt-exposed lungs, there was focal swelling of both type I and type II cells, and some of the latter lacked microvilli. The effect pattern after CoCl2 exposure was thus clearly different from those patterns seen after exposure to other toxic metals. We speculate that nodular accumulation of type II cells represents the primary lesion in CoCl2-exposed lungs and that the proliferation of such cells in interjacent areas might be suppressed by a feedback mechanism regulating surfactant production in the terminal airspaces.


A novel ELISA system for simultaneous detection of six subclasses of anti-phospholipid antibodies for prediction of thrombotic complications among SLE patients.
Anti-phospholipid antibodies (aPLs) are frequently associated with arterial and/or venous thromboembolic complications and recurrent fetal loss in patients with systemic lupus erythematosus (SLE). We recently reported that the clinical picture of SLE apparently depends on subclasses of aPLs in the patient's sera, but the contribution of each subclass remains uncertain. We newly developed an ELISA system for simultaneous detection of six specific categories of aPLs: anti-cardiolipin (aCL), anti-β2-glycoprotein I (aβ2GPI), anti-cardiolipin/β2-glycoprotein I (aCL/β2GPI), anti-phosphatidylserine (aPS), anti-prothrombin (aPT), and anti-phosphatidylserine/prothrombin (aPS/PT). They were measured in 331 patients with SLE including 63 patients with arterial thromboembolic complications, 64 with venous thromboembolic complications, and 43 with recurrent fetal loss. Lupus anticoagulant (LA) activity in their plasma was measured according to the guidelines recommended by the Subcommittee on Lupus Anticoagulant/Phospholipid-Dependent Antibodies. Multivariate logistic analysis revealed that the concentration of aPS/PT was most closely associated with arterial thrombosis. In contrast, the concentration of aβ2GPI was most closely related to venous thrombosis. Furthermore, both aCL/β2GPI and aPS/PT were independently associated with episodes of recurrent fetal loss. Regarding the relation between APLs and LA activity, aPS/PT, followed by aβ2GPI and aPT, showed the closest association with the presence of LA activity. Anti-phospholipid syndrome in patients with SLE can be classified by antigenic specificities of their aPLs as to their susceptibility to arterial and/or venous thromboembolic complications or obstetric complications.


[Minimal clinically important difference of the frequency of bowel movement for patients with chronic severe functional constipation treated with acupuncture].
To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision. In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients. The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively. The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.


Comparison of ultrasound-guided and digitally directed transrectal biopsy of palpable prostate lesions.
The role of ultrasound in the diagnosis of prostate cancer is still evolving. We used ultrasound to examine 202 patients with palpably abnormal prostates. Of 151 patients undergoing biopsy, ultrasound-guided biopsy was comparable to digitally directed biopsies in cancer detection (92% vs 90.7%). The two methods are complementary and should both be considered in patients with palpably abnormal prostates.


First experiences with contrast-enhanced first-pass MR perfusion imaging in patients with primary, benign cardiac masses and tumour-like lesions.
The aim of this study was to evaluate the diagnostic value of contrast-enhanced first-pass perfusion MRI in patients with suspected cardiac masses and tumour-like lesions. Twenty patients underwent contrast-enhanced first-pass saturation-recovery steady-state-free-precession perfusion MRI in addition to clinical MRI. Eleven diagnostic parameters were analysed blinded in consensus by three observers: localisation (paracardiac/mural/intracavitary), malignancy (benign/malignant) and first-pass enhancement pattern (homogeneous/heterogeneous as well as non-perfused/hypoperfused/iso-perfused/ hyperperfused). The results were compared to combined references comprising histology, cytology, medical and surgical reports, echocardiography, chest X-ray, coronary angiography and regular MRI. Also, we analysed if additional first-pass perfusion confirmed, changed or reduced the number of differential diagnoses compared to clinical MRI. All cardiac masses or tumour-like lesions were correctly localised and scored as benign lesions. For homogeneous perfused lesions the sensitivity, specificity, positive and negative predictive value was 94/100/100/67%, 100/94/67/100% for heterogeneous perfused lesions, 92/100/100/88% for non-perfused, 100/94/75/100 for hypoperfused, 100/100/100/100% for hyperperfused and for isoperfused lesions. In 17/2/1 cases perfusion MRI confirmed, reduced or increased the number of potential differentials. First-pass perfusion MRI provides valuable information in patients with benign cardiac masses or tumour-like lesions. Further experience is needed to underline these preliminary observations.


Two-dimensional echocardiographic identification of complicated aortic root endocarditis: implications for surgery.
Two-dimensional echocardiography successfully displayed the location and extent of aortic root complications, annular abscess or mycotic aneurysm in nine patients with aortic valve endocarditis. Five of the nine patients had prosthetic valve endocarditis and four had native valve endocarditis. The infective process extended into the paravalvular structures, including the interventricular septum (seven patients), right ventricular outflow tract (three patients), interatrial septum (one patient) and anterior mitral valve leaflet (four patients). The amount of aorto-left ventricular discontinuity caused by these complications was quantitated in degrees of annular circumference on the parasternal short axis image and in distance on the parasternal long axis image. The echocardiographic findings were confirmed at surgery and were helpful in the preoperative anticipation of the type of surgical procedure required: aortic valve replacement or composite aortic valve and root replacement. Five patients had prosthetic valve endocarditis with calculated aorto-left ventricular discontinuity of 173 +/- 55 degrees on parasternal short axis images and 1.36 +/- 0.72 cm on parasternal long axis images. Initial surgical repair included three composite aortic root-valve prosthesis implants, one reconstructive procedure with valve replacement and one simple aortic valve replacement. During a follow-up period of 18 months (range 1 to 35), a second reparative procedure was required for only one patient to repair an aortic conduit to coronary artery venous bypass graft. Four patients had native valve endocarditis with calculated aorto-left ventricular discontinuity of 100 +/- 17 degrees on parasternal short axis images and 0.88 +/- 63 cm on parasternal long axis images. Initial surgical repair included two reconstructive procedures with valve replacement and two simple aortic valve replacements. During a follow-up period of 30 months (range 16 to 42), three of these four patients required a second reparative procedure: one each for repair of a paraprosthetic leak, a ventricular septal defect and persistent aorto-left ventricular discontinuity. Two-dimensional echocardiography accurately detected aortic annular abscess and mycotic aneurysm complicating aortic valve endocarditis and the resultant degree of aorto-left ventricular discontinuity. Circumferential aorto-left ventricular discontinuity with these complications is greater for prosthetic than native valve endocarditis and predicts a more extensive surgical repair.(ABSTRACT TRUNCATED AT 400 WORDS)


Study of the safety of oral Triphala aqueous extract on healthy volunteers.
Triphala extract is a well known medicinal herbal formula which is usually prescribed by Thai traditional doctors to adjust the physiological functions of the body. Previous studies have reported that Triphala has antioxidant, anti-inflammatory, antihypercholesterolemia and anticancer properties. Though this herbal recipe is commonly used in Thailand, its human safety, especially in the oral form, has not been studied. We therefore conducted a clinical trial (Phase I). This study evaluated the safety of administering the aqueous extract of Triphala to healthy volunteers at 2500 mg/d. An open-label, single-arm trial was conducted at Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand, between July 2017 and July 2018. The study enrolled 10 male and 10 female healthy volunteers; all were given Triphala (water extract; five capsules of 500 mg each) orally, once a day, at bedtime, for four consecutive weeks. Signs and symptoms, physical examinations, hematology and blood chemistry were assessed at the beginning of the trial and every week thereafter, for four consecutive weeks. After finishing the trial, on day 28, all volunteers were invited to a follow-up session on day 35 to evaluate the safety of the herbal recipe using the same measurements. At the oral dose of 2500 mg/d, Triphala had no serious adverse effects in healthy volunteers. Moreover, it was found to have significantly improved the volunteers' high-density lipoprotein cholesterol (HDL-C) levels on day 35 and also reduced their blood sugar levels on days 14 and 35. We conclude that aqueous extract of Triphala is safe for healthy volunteers and that it elevates HDL-C levels and lowers blood sugar. Further clinical study should investigate its effects on HDL-C and blood sugar levels among the dyslipidemic and prediabetic groups. This trial was registered in the Thai Clinical Trial Registry with the identifier TCTR20180423002.


Plant phenotypic plasticity in the phytobiome: a volatile issue.
Plants live in a diverse and dynamic phytobiome, consisting of a microbiome as well as a macrobiome. They respond to arthropod herbivory with the emission of herbivore-induced plant volatiles (HIPV) that are public information and can be used by any member of the phytobiome. Other members of the phytobiome, which do not directly participate in the interaction, may both modulate the induction of HIPV in the plant, as well as respond to the volatiles. The use of HIPV by individual phytobiome members may have beneficial as well as detrimental consequences for the plant. The collective result of phytobiome-modulated HIPV emission on the responses of phytobiome members and the resulting phytobiome dynamics will determine whether and under which circumstances HIPV emission has a net benefit to the plant or not. Only when we understand HIPV emission in the total phytobiome context can we understand the evolutionary consequences of HIPV emission by plants.


Alloderm and Cortiva Have Similar Perioperative Wound Complications in Abdominal Wall Reconstruction.
Although controversial, the use of acellular dermal matrices (ADMs) for abdominal wall reconstruction (AWR) is increasing. There are now many different ADMs available, but there is a lack of studies directly comparing ADMs in terms of outcomes. A retrospective chart review was performed to compare perioperative wound complications (up to 120 d postoperatively) between patients who underwent AWR with the human noncrosslinked ADMs Alloderm or Cortiva from January 2012 to March 2020. Surgical technique uniformly consisted of open component separation, onlay implantation of ADM, and progressive tension suture fixation of ADM. After exclusions, 53 patients were in the Alloderm group, and 29 patients were in the Cortiva group. The overall perioperative wound complication rate between Alloderm (51.92%) and Cortiva (72.41%) was not significantly different (P = 0.09921). The average follow-up for Alloderm was 76.69 ± 29.52 d and for Cortiva was 66.93 ± 35.16 d (P = 0.2088). There were no cases that required explantation of ADM. Given the similar perioperative wound complication profiles, the more cost-effective ADM may be a consideration for use in AWR. The fact that there were zero instances of ADM explantation also supports the use of ADM in these high-risk cases.


Reduced sensitivity to pirenzepine-induced blockade of growth hormone responses to arginine, exercise, and growth hormone-releasing hormone in type I diabetic subjects.
The present study was performed to establish whether the mechanism by which the cholinergic system influences growth hormone (GH) release was altered in type I diabetic patients. Therefore, we investigated in a dose-response fashion the inhibitory effect of the muscarinic cholinergic receptor antagonist pirenzepine on the GH responses to arginine infusion (30 g infused intravenously (IV) in 30 minutes), exercise (bicycle ergometer test at an intensity of 75 W for 30 minutes), or 1-44 GH-releasing hormone (GHRH) (1 microgram/kg in an IV bolus). In a preliminary study, IV injection of 17.5 mg pirenzepine failed to produce modification in the GH response to arginine infusion in both diabetic (N = 4) and normal subjects (N = 4), and to exercise (diabetics, N = 4; normals, N = 4). Therefore, other subjects were tested without and with 20, 25, and 30 mg pirenzepine during arginine (diabetics, N = 7; normals, N = 7) or exercise (diabetics, N = 7; normals, N = 7) tests. Each subject was tested four times. Diabetic patients presented higher GH responses to stimulation with arginine or exercise than normal controls. In both groups, pirenzepine administered at doses ranging from 20 to 30 mg produced a dose-related inhibition of the GH response to arginine and exercise, which was almost complete when 30 mg pirenzepine was administered. However, the percent inhibition produced by 20 or 25 mg pirenzepine in the arginine test and by 20 mg in the exercise test was significantly lower in the diabetic patients than in the normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Physiopathology of premature progesterone elevation.
To determine the effects of the last hMG administration on plasma P and androgen profiles during controlled ovarian hyperstimulation (COH) for IVF-ET. Controlled clinical study. The IVF-ET program of a tertiary outpatient care center, Hôpital A. Béclère, Clamart, France. Nine IVF-ET candidates aged 25 to 36 years having presented normal responses to COH in previous IVF-ET cycles. Controlled ovarian hyperstimulation was induced for IVF-ET using hMG after endogenous gonadotropins were suppressed with a time-release GnRH agonist. Just before the last hMG administration (225 IU), the participants were hospitalized for 24 hours for serial blood sampling. These occurred before (baseline) and after hMG administration, every 30 minutes for 1 hour, hourly for 4 hours, and every 3 hours for the remaining part of a 24-hour post-hMG observation period. Measurement of P, T, androstenedione (A), E2, FSH, and LH. Plasma P and androgens (T and A) increased significantly, reaching peak values 12 to 15 hours after hMG administration and decreased progressively thereafter, to reach values not significantly different from baseline 24 hours after hMG administration. Plasma E2 levels increased progressively and steadily during the 24-hour observation period. Plasma FSH levels remained constant after hMG administration while LH stayed undetectable. In COH cycles induced for IVF-ET, the hormonal profile after the last hMG injection suggests that hMG triggers an increase in plasma P and androgens that culminates 12 to 15 hours after hMG administration. This elevation in plasma P and androgens observed after hMG administration is likely to reflect a direct action of the LH and/or FSH components of hMG on granulosa cells. In some women these hormonal consequences of hMG treatment may impair endometrial receptivity in IVF-ET cycles.


Medial antebrachial cutaneous nerve measurements to diagnose neurogenic thoracic outlet syndrome.
A reliable objective test is still needed to confirm the diagnosis of neurogenic thoracic outlet syndrome (NTOS). Over the past 20 years, it has been suggested that responses to medial antebrachial cutaneous nerve (MAC) and C8 nerve root stimulation could be used for this purpose. Herein, we explore this thesis. A clinical diagnosis of NTOS was established in 41 patients, all of whom underwent surgical decompression. Preoperatively, all patients were studied with MAC sensory neural action potential (SNAP) determinations and C8 nerve root stimulation. Controls were 19 asymptomatic, healthy volunteers. MAC sensory latency on 79 control sides was 1.5-2.4 msec, while latency in 41 symptomatic patients ranged 2.2-2.8 msec. Latency of 2.5 or greater was noted in 30 patients (specificity 99%, sensitivity 73%), confirming a diagnosis of NTOS, while the remaining 11 (27%) fell into the borderline zone of 2.2-2.4 msec. The latency difference between right and left sides in controls was 0-0.2 msec in 17 (89%), while in NTOS patients 31 had a difference of 0.3 msec or more (sensitivity 89%, specificity 63%). Amplitudes of 10 muV or more occurred in 77 of 79 control sides, whereas the amplitude was under 10 muV in 28 patients (specificity 97%, sensitivity 68%). Amplitude ratios between right and left sides in controls were 1.7 or less. Ratios of 2.0 or more were measured in 25 patients (specificity 100%, sensitivity 61%). Using the four diagnostic criteria (latency over 2.4 msec, latency difference between sides of 0.3 or more, amplitude under 10 muV, and amplitude ratios of 2.0 or more), 40 of the 41 patients had at least one of the four diagnostic criteria, 23 patients (56%) had three or four positive criteria, and 12 (29%) had two. C8 nerve root stimulation responses were below normal (56 M/sec) in 54%. MAC measurement is a fairly reliable technique for confirming the diagnosis of NTOS. Latency determination appeared to be a slightly more consistent measurement in this study, but amplitude and C8 nerve root stimulation were also helpful. A combination of these techniques seems to be the most reliable approach.


[Analysis of the inhibitory influence of whole human erythrocytes on plasma heparin activity].
The accelerating effect of intact human erythrocytes upon the thrombin time of plasma (deprothrombinized, thrombocyte depleted) was independent of the presence of calcium ions, preincubation, erythrocytes and plasma, and was not accompanied by a decrease of the free heparin level in the plasma. Acceleration of the process of plasma fibrinogen transformation into fibrin caused by the whole erythrocytes was not conditioned by the endogenous heparin inhibition, but reflected the cell fibrinoplastic activity. The results obtained are against the idea advanced in literature on the regulating influence of the whole erythrocytes upon the endogenous heparin level in the blood.


Social and delay discounting in autism spectrum disorder.
Current literature is divided over whether and how processes such as perspective taking and reward sensitivity differ between individuals with autism spectrum disorder (ASD) versus neurotypical individuals. Discounting tasks may provide novel insight into how these processes operate. In delay discounting tasks, participants choose between smaller immediate rewards and larger delayed rewards, and in social discounting tasks, participants choose between a smaller monetary rewards for themselves versus a larger reward for partners of varied social distance (e.g., a close friend vs. an acquaintance). Delay and social discounting tasks thus implicitly measure the subjective value of rewards given to one's future self and to others, capturing constructs such as perspective taking, reward processing, and social closeness, all of which have been discussed as core cognitive mechanisms underlying ASD. Despite extensive research on discounting in other clinical populations, few studies have examined delay discounting in ASD and no research has examined social discounting in ASD. The goal of the current study was to assess delay and social discounting for monetary rewards in a single sample of adolescents and adults with ASD compared to a matched neurotypical sample. Overall, adults and adolescents with ASD valued both future rewards and rewards given to others less than their typical counterparts did, but rates of discounting were not significantly correlated across temporal and social domains. These results extend an important behavioral paradigm for understanding both perspective taking and reward processing to autism. Autism Res 2019, 12: 870-877. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Discounting tasks-which experimentally measure the subjective value of different rewards-have been used with a variety of clinical populations, but are underexplored in ASD. We found that compared to neurotypical individuals, individuals with ASD showed diminished subjective value for future rewards (compared to immediate rewards) and rewards for others (compared to rewards for self). This finding has implications for understanding perspective taking, reward processing, and social closeness in ASD.


Diabetic hypoglycaemia and the dental patient.
Hypoglycaemic attacks in patients with insulin-treated diabetes are unpleasant and inconvenient at best, but may constitute a medical emergency at their most severe. This article provides the dental practitioner with an insight into the physiological processes which occur during such attacks, with clues to the recognition of the signs of impending hypoglycaemia. Steps which may be taken to avoid hypoglycaemia with the various forms of treatment are then considered against a background of their suitability for use in dental practice.


Sexual-incentive motivation and paced sexual behavior in female rats after treatment with drugs modifying dopaminergic neurotransmission.
The effects of the dopamine receptor agonist apomorphine, the dopamine releaser amphetamine, and the dopamine receptor antagonist cis(Z)-flupenthixol on sexual-incentive motivation and on paced-mating behavior were studied in female rats. Apomorphine, in the doses of 0.125 and 0.5 mg/kg, showed a tendency to reduce incentive motivation. Ambulatory activity was inhibited, evidenced both by diminished distance moved and reduced velocity of movement. Amphetamine (0.25 and 1 mg/kg) and flupenthixol (0.25 and 0.5 mg/kg) failed to modify incentive motivation while stimulating and reducing ambulatory activity, respectively. In the mating test, apomorphine enhanced the latency to enter the male's half and reduced the number of proceptive behaviors. However, these effects were associated with the appearance of stereotyped sniffing. Amphetamine increased the propensity to escape from the male after a mount without having other effects. Flupenthixol augmented the duration of the lordosis posture. Neither amphetamine nor flupenthixol affected sniffing. These data show that facilitated dopaminergic neurotransmission stimulates neither paced female sexual behavior nor sexual-incentive motivation. Dopamine receptor blockade has slight consequences. It is concluded that dopamine is not a transmitter of major importance for unconditioned female sexual motivation and behavior.


ABC of Surgical Teaching: Time to Consider a Global Blueprint for Holistic Education.
Educating and equipping students and trainees into clinicians capable of meeting healthcare demands and service provision needs is essential. Unprecedented events like COVID-19 pandemic, highlight urgent need for reformation of training to ensure high quality education is maintained. To this end, we describe an innovative and globally adaptable blueprint for establishing a surgical curriculum, aiming to optimize preparation of future surgeons. We used a structured protocol to synthesize evidence from previous systematic reviews focused on surgical education alongside a series of focused original educational studies. This approach allowed incorporation of prospectively applied novel ideas into the existing landscape of published evidence. All material used for this proof of concept derives from the outputs of a dedicated research network for surgical education (eMERG). We propose the foundation blueprint framework called "Omnigon iG4" as a globally applicable model. It allows adaptation to individual local educational environments for designing, appraising and/or refining surgical curricula. We also describe the "Omnigon iG4 Hexagon Pragmatic Model," a novel perspective model which assesses the performance of our blueprint in a multi-layer fashion. This "Hexagon" model is the first to introduce pragmatic outcomes in curricula performance assessment. This proof of concept, "Omnigon iG4," proposes an adaptable version of a curriculum blueprint. The framework allows educators to establish a surgical curriculum with the ability to map out competencies, permitting full control over their intended learning outcomes. This can form the basis for developing globally adaptable multifaceted Simulation-Based learning (SBL) courses or even surgical curricula for undergraduates.


[Value of extrapolating data in tumor registries. An instrument for a deeper knowledge of epidemiology].
The delay in creating an Italian tumour register is pointed out with emphasis on the importance of such registers for epidemiological and clinical purposes and for both prevention and treatment. The need for more widespread information collection in this area is emphasised.


Stabilization of blood platelet microtubular system by staurosporine.
The stimulative effects of phorbol myristate acetate (PMA) on rabbit platelet shape change and platelet adhesion were completely inhibited by staurosporine (STS)-pretreatment. When the platelets were observed by whole mount immuno transmission electron microscopy (TEM), STS was found to stabilize platelet microtubular cytoskeleton. Electrophoretic analysis of the isolated marginal bundles of cytoskeleton after STS-PMA treatment revealed a newly formed 200 K high molecular weight protein band accompanied with heavy losses of tubulin monomers. These bundles of STS-treated platelets as observed in immuno TEM responded poorly to the anti alpha- or beta-tubulin antibody as compared with those of the control platelets. The results suggest that sts favour the specific assembly of tubulin bundles with a possible involvement of the microtubular associated proteins (MAPs). The resultant tight marginal bundles (MB) of cytoskeleton will stabilize the platelets and resist the effects of exogeneously added stimulants such as PMA.


For which cancer types can neuron-specific enolase be clinically helpful in Turkish patients?
The aim of the present study was to evaluate the serum neuron-specific enolase (NSE) levels in patients with prostate cancer, Hodgkin lymphoma, lung cancer and peripheral nerve tumors. NSE levels were determined by ELISA in the sera of 100 prostate cancer, 47 Hodgkin lymphoma, 35 lung cancer and 35 peripheral nerve tumor patients and also in 132 healthy controls. The median levels of serum NSE were elevated in patients with lung cancer (p=0.018) and peripheral nerve tumors (p=0.008). NSE levels in prostate cancer and Hodgkin lymphoma patients were higher than the controls but there was no statistically significant difference (p>0.05). We conclude that NSE may be applied in routine to gain insight about the clinical statuses of various cancer patients, but more studies are needed to determine the organ specificity.


Vocal tract dimensional development of adolescents: an acoustic reflection study.
The purpose of the study was to investigate the effects of age and gender on adolescents' vocal tract dimensional development with acoustic reflection technology (ART). A total of ninety-five male and female adolescents aged between 10 and 18 divided into three age groups were tested with acoustic reflection technology (ART) and acoustic program to secure their vocal tract dimensional parameters and the vowel formant frequencies. Significant age and gender effects were found not only in vocal tract length, but also segmental volumetric measurements, as well as the vowel formant frequencies. The findings of this study have provided insights on the developmental trend of adolescents' vocal tracts. The study has also offered a preliminary anatomical database of adolescents' vocal tract dimensional growth for otolaryngologists, clinical anatomists, speech therapists and other health professionals of swallowing, respiration and communicative disorders.


Rapid diagnosis of Legionnaires' disease by bronchoalveolar lavage.
Legionella pneumophila has, in recent years, emerged as a common pulmonary pathogen in the normal and immuno-compromised patient (ICP). Making a specific etiologic diagnosis of pneumonia in the latter group is a common clinical dilemma often complicated by poor specimen availability and risks of invasive procedures. Improved staining and isolation techniques for L pneumophila would suggest that early diagnosis could be possible if adequate specimens were available. This report summarizes our experience with bronchoalveolar lavage (BAL) with which we have diagnosed L pneumophila in eight immunocompromised patients, well in advance of more traditional methods. On the basis of this experience, we would advocate early BAL in the ICP as a rapid, safe, moderately sensitive and specific diagnostic test to aid in the identification of L pneumophila.


The development of the gracile nucleus in the rat: the time of ingrowth of ascending primary sensory fibres and effect of early deafferentation.
An investigation was carried out of the time of ingrowth of primary sensory fibres in the medulla and of their penetration into the gracile nucleus, and of the effect of an early loss of these fibres upon the development of the nucleus in rats. After injection of the conjugate horseradish peroxidase-wheat germ agglutinin in the hind limbs of fetuses, a bundle of labelled fibres was seen in close proximity of the gracile nucleus at embryonic day 17. However, fibres did not appear to leave the bundle until embryonic day 19, when they were seen to project ventrally and penetrate the nucleus which, on embryonic day 20 and thereafter, contained an increasing number of labelled fibres. Synaptic contacts within the gracile nucleus were found at all stages of the observation; the presynaptic processes consisted of an electron-lucent matrix which contained round vesicles. Although no mature glomeruli were observed, an occasional terminal appeared to be presynaptic to more than one process. After transection of the primary sensory afferents at embryonic day 18 and 19, no degeneration was seen within the gracile nucleus; degenerated boutons were occasionally seen after deafferentation at embryonic day 20 and became more numerous thereafter; nerve cells in various stages of degeneration could also be seen. Removal of primary afferents to the gracile nucleus at the time they reach the nucleus or soon after was followed by a severe loss of nerve cells and a reduced increment in size of the remaining ones. Moreover, the results of the present investigation show that penetration of primary sensory fibres into the gracile nucleus takes place approximately 2 days after they have been seen in the medulla and are in keeping with observations made in other pathways of the nervous system of the rat as well as in other animals. The findings that mature glomeruli, previously described in 1-day-old rats, are not present shortly before birth, suggest a fast rate of maturation of these synapses.


Deciphering equity style returns: An analysis of size and value anomalies in the Pakistani stock exchange.
This study aims to identify the underlying causes of variation in the time series and cross-sectional equity style returns in the emerging stock market of Pakistan. We use asset pricing models and incorporate variables reflecting business cycle fluctuations to assess the time-varying size and value premiums. The methodology of this paper involves constructing style portfolios based on firm-specific characteristics such as market capitalization, price to earnings ratio, book-to-market equity ratio, momentum, and asset growth. We find that the style portfolios earn abnormal returns consistently which cannot be explained either through asset pricing models or business cycles variables. However, the size and value premiums are found to be subsided during the troughs of economic cycles. The results suggest that the abnormal returns for style portfolios are likely driven by firm-specific characteristics rather than macroeconomic factors. Overall, this study contributes to the literature on style investing by providing insights into the profitability of equity style portfolios in the Pakistani equity market. Our findings have implications for stock picking, investment management and risk factor analysis.


Silicon membrane interpositioning for the prevention of skull deformity following experimental craniosynostosis.
The interposition of various materials to complete suturectomy for the treatment of craniosynostosis has been used by many surgeons to prevent early postoperative reunion. Convincing scientific proof of the value of this procedure is still required, however. In this study a previously described model of experimental craniosynostosis was employed to examine the effects of an interposed silicon membrane in preventing skull deformity. Eighteen newborn rabbits had their right coronal sutures resected and the skulls were examined for shape and histology up to 6 months of age. The interposing of a silicon membrane was found to prevent formation of skull deformity during growth.


Transcriptional programming and gene regulation in WC1+ γδ T cell subpopulations.
γδ T cells represent a high proportion of lymphocytes in the blood of ruminants with the majority expressing lineage-specific glycoproteins from the WC1 family. WC1 receptors are coded for by a multigenic array whose genes have variegated but stable expression among cells in the γδ T cell population. WC1 molecules function as hybrid pattern recognition receptors as well as co-receptors for the TCR and are required for responses by the cells. Because of the variegated gene expression, WC1+ γδ T cells can be divided into two main populations known as WC1.1+ and WC1.2+ based on monoclonal antibody reactivity with the expressed WC1 molecules. These subpopulations differ in their ability to respond to specific pathogens. Here, we showed these populations are established in the thymus and that WC1.1+ and WC1.2+ subpopulations have transcriptional programming that is consistent with stratification towards Tγδ1 or Tγδ17. WC1.1+ cells exhibited the Tγδ1 phenotype with greater transcription of Tbx21 and production of more IFNγ while the WC1.2+ subpopulation tended towards Tγδ17 programming producing higher levels of IL-17 and had greater transcription of Rorc. However, when activated both WC1+ subpopulations' cells transcribed Tbx21 and secreted IFNγ and IL-17 reflecting the complexity of these subpopulations defined by WC1 gene expression. The gene networks involved in development of these two subpopulations including expression of their archetypal genes wc1-3 (WC1.1+) and wc1-4 (WC1.2+) were unknown but we report that SOX-13, a γδ T cell fate-determining transcription factor, has differential occupancy on these WC1 gene loci and suggest a model for development of these subpopulations.


Regioselective hydroxylation and glucosylation of flavanones with cultured plant cells of Eucalyptus perriniana.
Cultured plant cells of Eucalyptus perriniana catalyzed reduction, regioselective hydroxylation, and regioselective glycosylation of flavanones. (2S)-Flavanone was converted into (2S)-flavan-4-ol, (2S)-flavan-4,7-diol, (2S)-flavan-7-ol, (2S)-flavan-7-yl glucoside, and (2S)-flavan-7-yl gentiobioside. The cells glucosylated (2S)-flavan-6-ol to (2S)-flavan-6-yl glucoside. (2S)-Flavan-2'-ol was transformed to (2S)-flavan-2',4-diol, (2S)-flavan-2',7-diol, (2S)-flavan-2'-yl glucoside. In addition, (2S)-flavan-4'-ol was transformed to (2S)-flavan-4,4'-diol, (2S)-flavan-4',7-diol, (2S)-flavan-4'-yl glucoside.


Permeable tubes increase the length of the gap that regenerating axons can span.
After placement of stumps of transected rat sciatic nerve in an impermeable tube, the maximum gap the axons can span is 10 mm. The present study shows that the regenerating axons cross much longer gaps if the tube is made permeable. This improvement does not require another nerve as a transplant nor the preplacement of extracellular materials in the tube. Possible mechanisms for this improvement are discussed.


Comparative determinations of non SHBG-bound serum testosterone, using ammonium sulfate precipitation, Concanavalin A binding or calculation in men.
Testosterone (T) circulates tightly bound to sex hormone-binding globulin (SHBG) and weakly to albumin. Non-SHBG-bound T is considered as the bioavailable T (BT) and was recommended for the evaluation of androgen disorders. Two methods, BT calculating from T, SHBG and albumin or BT measurement using ammonium sulfate precipitation of [SHBG-T] complex have been widely used. Using SHBG separation with Concanavalin-A (ConA) was recently proposed as a more specific method. The aim of this work was to compare these three methods in male patients. Serum samples of 131 consecutive untreated men (15-81 years) referred for suspicion of hypogonadism were collected. Total T was measured by GC-MS, SHBG by immunoradiometric assay. Level of BT was assayed using ammonium sulfate precipitation, ConA separation and calculated using the Issam web calculator. Only few differences were found between ammonium sulfate or ConA BT measurements. However, we found much higher serum calculated BT than assayed BT with an increasing bias when BT levels increased. Measurement of BT using ConA separation could be recommended. The results are equivalent to those obtained using ammonium sulfate precipitation. This method eliminates the possible non specific albumin precipitation that can occur with ammonium sulfate when the assay conditions are not rigorously controlled.


Reconsiderations on the use of pipeline embolization device in the treatment of intracerebral aneurysms with special angioarchitecture: fetal PCA, AVM, V-B junction and DAVF.
Pipeline embolization device (PED) has proved its safety and efficacy in the treatment of intracranial large and giant side-wall aneurysms. With the accumulation of treatment experience, it is an inevitable trend to expand its off-label use on aneurysms. Whether flow diversion is safe and efficient in cases with special angioarchitecture has rarely been explored. We performed a retrospective analysis of 210 consecutive patients treated by PED for intracerebral aneurysms in our center. Except for aneurysm, those patients also presented with special angioarchitecture: Fetal PCA, AVM, V-B junction and DAVF. Nine patients were qualified for the study. 1 was with fetal PCA, the aneurysm remained patent on 4-month follow-up. 2 with ipsilateral AVMs, one patient died due to brain hemorrhage 20 days after the operation, the other one was only partially embolised on 6 month follow up. 3 aneurysms located at V-B junction, angiographic follow up on 3 months demonstrated no complete occlusion of both the aneurysms, the other patients were still on follow up. All of the 3 cases with concomitant DAVF are completely occluded during short to midterm follow up. PED for aneurysms incorporated the fetal PCA and V-B junction might meet a high propensity for incomplete occlusion during short term follow up. Aneurysm with ipsilateral AVM is not suitable for PED treatment due to the risk of hemorrhage and incomplete occlusion during midterm follow up. For aneurysm with concurrent DAVF, PED treatment is safe and efficient relatively in one session or by staged operation.


Zygomaticomaxillary suture maturation evaluation in patients with and without cleft lip and palate.
The zygomaticomaxillary suture (ZMS) maturation evaluation is a reliable method for predicting the optimal timing of maxillary protraction. The objective of this study was to compare age distribution patterns of ZMS maturation stages between cleft lip and palate (CLP) patients and non-cleft lip and palate (non-CLP) patients to aid our comprehension in choosing the optimal timing of maxillary protraction. Samples of 216 non-CLP and 220 CLP Asian patients without orthodontic and orthognathic treatment aged 5-25 years were scanned to evaluate the ZMS maturation stage by 2 evaluators blindly. Evaluators' agreements and bilateral ZMS maturation consistency were assessed by weighted kappa tests. Age distribution patterns of each ZMS maturation stage were described. Gender effect and age distribution differences between groups were analyzed using an independent t-test. Evaluators' agreements and bilateral ZMS maturation consistency were satisfying (weighted kappa coefficient >0.90). At stages A and B, patients with CLP were 1.3 and 0.4 years older than patients in the non-CLP group (P <0.001 and P = 0.01). In contrast, at stage C, patients with CLP were approximately 1.2 years younger (P = 0.004). Gender barely played a role in the divergence of ZMS maturation (P >0.05). No statistically significant difference was observed between ZMS maturation of patients with unilateral or bilateral cleft lip and palate (UBCLP) and patients with unilateral or bilateral cleft lip (UBCL) (P >0.05). The ZMS development of patients with CLP was premature at stage C, whereas delayed at stages A and B.


The protective effects of propofol against renal ischemia-reperfusion injury are potentiated by norisoboldine treatment via inhibition of oxidative stress pathways.
Acute kidney injury (AKI) is a significant worldwide health problem. The protective effects of norisoboldine (NOR) against ischemia/reperfusion (I/R) induced renal injury in a rat model were evaluated. AKI was induced in rats by I/R. Animals were treated with 20 mg/kg/h propofol, intraperitoneally administered and 10 mg/kg NOR 30 min before inducing renal ischemia. Biomarkers of kidney function, including cytokines and oxidative stress parameters, were measured in serum. The serum levels of creatinine and blood urea nitrogen in propofol- and NOR-treated rats were lower compared to the untreated I/R group. Moreover, treatment with propofol or NOR, alone and in combination, decreased the levels of cytokines and oxidative stress in rats with kidney injury. In conclusion, this study suggested that treatment with NOR potentiated the nephroprotective effects of propofol in rats with I/R-induced renal injury by ameliorating oxidative stress and apoptosis pathway.


[Surgical treatment of stiff massive knee endoprosthesis for bone tumors in children and adolescents].
Improved oncologic outcome and technical advances in limb salvage surgery have made limb salvage therapy a feasible and valuable treatment option. Nevertheless, resection of a bone tumor followed by a reconstruction knee endoprosthesis can create gait abnormalities, of which one of the most frequent is knee stiffness. The aim of this retrospective study was to assess the outcomes of revision surgery for a stiff knee following reconstruction of a segmental long bone defect. Between 1983 and 2005, 19 patients who had undergone wide resection of a tumor close to the knee followed by reconstruction with a massive endoprosthesis were revised for a diagnosis of stiffness. The mean age of the patients was 12 years (range: 7-19 years). Patients were followed for a mean five years (range: 1-21 years). Three patients were not assessed at the last follow up (two patients died, one patient was amputated for a local recurrence). The mean range of motion improved 80+/-24 degrees preoperatively to postoperatively. The Enneking score improved from 15+/-0.5 to 23+/-3 points at three months follow-up, and to 22+/-5 at last follow-up. Recurrent stiffness occurred three times and required a second operative release with a good final result. Outcome depends on the cause of the stiffness of the reconstruction knee arthroplasty. Stiffness can be caused by complications (trauma, implant failure, infection), and patient-related factors (lack of physiotherapy). Open arthrolysis is indicated for chronic stiffness in a motivated patient with an identified cause because failure to identify the cause of stiffness may result in recurrence of the problem.


Content of the Alternaria mycotoxin tenuazonic acid in food commodities determined by a stable isotope dilution assay.
The Alternaria mycotoxin tenuazonic acid (TA) was quantified in fruit juices (n = 50), cereals (n = 12) and spices (n = 38) using a recently developed stable isotope dilution assay (SIDA). [(13) C6,(15) N]-TA was used as the internal standard. Method validation revealed low limits of detection (LODs) of 0.15 μg/kg (fruit juices), 1.0 μg/kg (cereals) and 17 μg/kg (spices). The respective limits of quantitation were about three times higher. Recovery was about 100% for all matrices. The precision (relative standard deviation of replicate analyses of naturally contaminated samples) was 4.2% (grape juice; 1.7 μg/kg), 3.5% (whole wheat flour; 36 μg/kg) and 0.9% (curry powder; 215 μg/kg). The median content of TA in the analyzed samples was 1.8 μg/kg (fruit juices), 16 μg/kg (cereals) and 500 μg/kg (spices). Positive samples amounted to 86% (fruit juices), 92% (cereals) and 87% (spices).


Fertilization and early development of rat oocytes induced to mature by forskolin.
Forskolin has been shown to successfully induce maturation of rat oocytes as assessed by morphological markers. The present study was designed in an attempt to elucidate whether oocytes, induced to mature by forskolin (10(-4) M, group A) in a follicle-enclosed oocyte culture, are fertilizable and can further develop into two-cell embryos. Oocytes exposed in vitro to either luteinizing hormone (LH, 5 micrograms/ml, group B) or a GnRH agonist analogue (10(-7) M, group C) as well as oocytes that underwent maturation in vivo (group D), served as positive controls. We found that similar rates of fertilization were obtained in the experimental and all of the above mentioned control groups (A = 78.9 +/- 4.2%, B = 77.9 +/- 3.1%, C = 77.5 +/- 5.5% and D = 84.7 +/- 2.7%). Cleavage rate of fertilized eggs from group A was significantly higher than that of eggs from groups B & C, and similar to that of eggs from group D (A = 63.1 +/- 6.7%, B = 37.8 +/- 4.9%, C = 50.0 +/- 4.1%, D = 67.8 +/- 4.1%). Using functional parameters we hereby demonstrate that forskolin and LH are at least equally potent in producing fertilizable eggs that have a high potential of development into two cell embryos. These results further support the idea that cAMP is a mediator of LH action in inducing oocyte maturation.


Nicotinic acid promotes sleep through prostaglandin synthesis in mice.
Nicotinic acid has been used for decades for its antiatherogenic properties in humans. Its actions on lipid metabolism intersect with multiple sleep regulatory mechanisms, but its effects on sleep have never been documented. For the first time, we investigated the effects of acute systemic administration of nicotinic acid on sleep in mice. Intraperitoneal and oral gavage administration of nicotinic acid elicited robust increases in non-rapid-eye movement sleep (NREMS) and decreases in body temperature, energy expenditure and food intake. Preventing hypothermia did not affect its sleep-inducing actions suggesting that altered sleep is not secondary to decreased body temperature. Systemic administration of nicotinamide, a conversion product of nicotinic acid, did not affect sleep amounts and body temperature, indicating that it is not nicotinamide that underlies these actions. Systemic administration of monomethyl fumarate, another agonist of the nicotinic acid receptor GPR109A, fully recapitulated the somnogenic and thermoregulatory effects of nicotinic acid suggesting that they are mediated by the GPR109A receptor. The cyclooxygenase inhibitor indomethacin completely abolished the effects of nicotinic acid indicating that prostaglandins play a key role in mediating the sleep and thermoregulatory responses of nicotinic acid.


Comparison of polysaccharide synthesis between preimplantation stage mouse embryos and F9 embryonal carcinoma cells.
Polysaccharide synthesis was compared between preimplantation stage mouse embryos and F9 embryonal carcinoma cells. When cells were labelled with [3H]fucose, elution profiles of the pronase digest from a Sephacryl S-200 column were similar for the two cell types and both had characteristic large polysaccharides of the same size (Mr 20-500K), although embryos contained less large polysaccharide than F9 cells, and embryonic polysaccharides were less acidic, suggesting poor sialosylation. A significant proportion of [3H]mannose was incorporated into complex-type glycopeptides in F9 cells, whereas in the case of embryonic cells most glycopeptides remained as high mannose-type. The most striking difference was observed when cells were labelled with galactose. In the case of embryonic cells, 90% of the radioactivity was incorporated into glycogen, whereas only 0.1% of the incorporated galactose occurred in this molecule in F9 cells. These observations indicate that carbohydrate metabolism of morula-stage embryos is very different from that of F9 cells.


Correction to: Neighborhood's locality, road types, and residents' multimorbidity: evidence from China's middle-aged and older adults.
An amendment to this paper has been published and can be accessed via the original article.


A randomized clinical trial of feeder vessel photocoagulation of proliferative sickle cell retinopathy. I. Preliminary results.
A randomized prospective clinical trial of feeder vessel photocoagulation for proliferative sickle cell retinopathy was performed. In Chicago there were 34 argon laser-treated eyes and 30 control eyes. In Kingston there were 53 xenon arc treated eyes and 50 control eyes. Prolonged loss of visual acuity was rare in both photocoagulated and control eyes. Argon laser and xenon arc feeder vessel photocoagulation reduced the incidence of vitreous hemorrhage and visual loss from vitreous hemorrhage. However, photocoagulation was associated with an increased risk of choroidal neovascularization (xenon arc greater than argon laser) and retinal detachment (argon laser), although visual loss from these complications has not been seen in these patients so far.


Ecological determinants of food plant choice in the checkerspot butterfly Euphydryas editha in Colorado.
The larvae of Euphydryas editha in Gunnison County, Colorado, feed on Castilleja linariifolia. Two related plants, C. chromosa and Penstemon strictus, occur in the same area and are equally nutritious, but are not eaten. Restriction to C. linariifolia appears to be a case of ecological monophagy - survival on the other two species is less likely not because of their biochemical make-up but because of their ecological characteristics, primarily their phenologies.


Software and tools for microarray data analysis.
A typical microarray experiment results in series of images, depending on the experimental design and number of samples. Software analyses the images to obtain the intensity at each spot and quantify the expression for each transcript. This is followed by normalization, and then various data analysis techniques are applied on the data. The whole analysis pipeline requires a large number of software to accurately handle the massive amount of data. Fortunately, there are large number of freely available and commercial software to churn the massive amount of data to manageable sets of differentially expressed genes, functions, and pathways. This chapter describes the software and tools which can be used to analyze the gene expression data right from the image analysis to gene list, ontology, and pathways.


Protein cross talking through osmotic work: the free energy of formation of the MgADP-myosin complexes at the muscle protein osmotic pressure.
A method is presented to determine the energy of formation of the myosin-ADP complexes at the muscle protein osmotic pressure. It is found that, at 18 kP, the putative protein osmotic pressure in skeletal muscle, the increase of MgADP from 0.05 to 2 mmolal, increases the free energy of myosin-ADP and of myosin-(ADP)2 by 0. 756 and by 9.85 kJ/mol, respectively, and decreases the free energy of myosin by 8.34 kJ erg/mol. It is pointed out that the local changes of water chemical potential, induced by the binding of MgADP to myosin, can be sensed by other structures of the contractile machinery, which per se may even be insensitive to MgADP. Cross talking between macromolecules can thus be achieved by changes of the water chemical potential.


Heterogeneity in Palaeolithic Population Continuity and Neolithic Expansion in North Africa.
North Africa is located at the crossroads of the Mediterranean Sea, the Middle East, and the Sahara Desert. Extensive migrations and gene flow in the region have shaped many different cultures and ancestral genetic components through time [1-6]. DNA data from ancient Moroccan sites [7, 8] has recently shed some light to the population continuity-versus-replacement debate, i.e., the question of whether current North African populations descend from Palaeolithic groups or, on the contrary, subsequent migrations swept away all pre-existing genetic signal in the region. In the present study, we analyze 21 complete North African genomes and compare them with extant and ancient genome data in order to address the demographic continuity-versus-replacement debate, to assess whether these demographic events were homogeneous (including Berber and Arabic-speaking groups), and to explore the effect of Neolithization and posterior migration waves. The North African genetic pool is defined as a melting pot of genetic components, including an endemic North African Epipalaeolithic component at low frequency that forms a declining gradient from Western to Eastern North Africa. This scenario is consistent with Neolithization having shaped most of the current genetic variation in the region when compared to posterior back-to-North-Africa migration waves such as the Arabization. A common and distinct genetic history of the region is shown, with internal different proportions of genetic components owing to differential admixture with surrounding groups as well as to genetic drift due to isolation and endogamy in certain populations.


A mouse model system for genetic analysis of sociability: C57BL/6J versus BALB/cJ inbred mouse strains.
Impairments in social behaviors are highly disabling symptoms of autism, schizophrenia, and other psychiatric disorders. Mouse model systems are useful for identifying the many genes and environmental factors likely to affect complex behaviors, such as sociability (the tendency to seek social interaction). To progress toward developing such a model system, we tested the hypothesis that C57BL/6J inbred mice show higher levels of sociability than BALB/cJ inbred mice. Mice tested for sociability were 4- and 9-week-old, male and female C57BL/6J and BALB/cJ mice. On 2 consecutive days, the sociability of each test mouse toward an unfamiliar 4-week-old DBA/2J stimulus mouse was assessed with a social choice paradigm conducted in a three-chambered apparatus. Measures of sociability included the time that the test mouse spent near versus far from the stimulus mouse, the time spent directly sniffing the stimulus mouse, and the time spent in contact between test and stimulus mice in a free interaction. C57BL/6J mice showed higher levels of sociability than BALB/cJ mice overall in each of these measures. We propose that C57BL/6J and BALB/cJ mice will be a useful mouse model system for future genetic and neurobiological studies of sociability.


Trypan Blue as a marker of plasma membrane permeability in alloxan-treated mouse islet cells.
Suspensions of pancreatic islet cells from noninbred ob/ob-mice were incubated with Trypan Blue. Microscope photometry showed that apparently viable cells excluded the dye completely, whereas the nuclei of nonviable cells accumulated Trypan Blue by a saturable process. The nucleus-to-medium dye gradient was more then 30:1 in media containing 0.1% or less Trypan Blue. The apparent affinity constant for nuclear binding of the dye was 3.1 X 10(4)l/mol. Albumin partially inhibited the nuclear staining. More than 0.5% Trypan Blue in the medium was toxic per se. In the absence of albumin, 0.5 or 20 mmol/l alloxan, 1 mmol/l N-ethylmaleimide, or 0.1 mmol/l chloromercuribenzene-p-sulphonic acid, but not 20 mmol/l streptozotocin, increased the frequency of islet cells stained with 0.1% Trypan Blue. The absorbance of nuceli was also increased in cells treated with alloxan or N-ethylmaleimide, but not in those treated with chloromercuribenze-p-sulphonic acid. It is concluded that alloxan rapidly increases the permeability of the plasma membrane in mouse beta-cells. This action of alloxan appears to be more acute than any such effect of streptozotocin.


Pregnancy issues in Takayasu arteritis.
Takayasu arteritis (TAK) is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches. TAK usually affects young women and the management of pregnancy during this vasculitis may be a challenging situation. After a review of the literature, we analysed the data of 505 pregnancies in 373 TAK patients. We discuss main results to clarify if the pregnancy outcome is affected by TAK, especially during disease clinical onset or disease activity. We also discuss the potential impact of pregnancy on TAK prognosis. Disease activity of TAK appears independently associated with a poor pregnancy outcome. More than 5% of pregnant women with TAK develop a life-threatening maternal cardiovascular complication. A good control of TAK disease activity and arterial hypertension before conception and during pregnancy is critical to improve both maternal and foetal outcomes. Pregnancies in the setting of TAK should be considered high-risk, requiring a close collaboration between specialists involved in the care of TAK and obstetricians.


Ecological genetics of the cave beetle Neaphaenops tellkampfii (Coleoptera: Carabidae).
Genetic variability and similarity were examined in eight populations of the Kentucky cave beetle Neaphaenops tellkampfii (Coleoptera: Carabidae) using the technique of polyacrylamide gel electrophoresis. Results indicate that N. tellkampfii has high genetic variation within and high genetic similarity among local populations. These results are in sharp contrast to the patterns of low variability and similarity reported for other cave dwelling species in the same region. It is concluded that the differences in genetical population structure among cave species in the Central Kentucky Karst are related to ecological differences among the species.


Approach to the patient with recurrent infections.
Children with a history of recurrent or unusual infections present a diagnostic challenge. Differentiation between frequent infections caused by common risk factors, versus primary immune dysfunction should be based on a detailed history and physical examination and, if indicated, followed by appropriate laboratory studies. A high index of suspicion could lead to an early diagnosis and treatment of an underlying immune deficiency disease. This article presents to physicians an approach to the evaluation of children with recurrent infections. Important details from the history and physical examination, and an appropriate choice of screening laboratory test to be ordered in a given situation are discussed.


Correlation between scalp high-frequency oscillations and prognosis in patients with benign epilepsy of childhood with centrotemporal spikes.
The study aimed to explore whether high-frequency oscillations (HFOs) can predict seizure risk and atypical manifestations of benign epilepsy of childhood with centrotemporal spikes (BECTS). We recruited 60 patients and divided them into three groups: (1) seizure-free BECTS, (2) active typical BECTS, and (3) active atypical forms of BECTS. Electroencephalogram was used to record the number, location, average amplitude, and duration of spikes, and spike ripples were analyzed using time-frequency technology. Multivariable logistic regression analysis was used to investigate independent predictive factors for prognosis. The number of sleep spike ripples, rather than spikes, was an independent risk factor for the active period of the disease (odds ratio [OR] = 4.714, p = 0.003) and atypical forms of BECTS (OR = 1.455, p = 0.049); the optimal thresholds for the spike ripple rate were >0 (area under the curve [AUC] = 0.885, sensitivity = 96.15%, specificity = 73.33%) and >0.6/min (AUC = 0.936, sensitivity = 84.21%, specificity = 96.15%), respectively. Furthermore, in typical BECTS, the spike ripple rate showed significant negative correlations with time since the last seizure (ρ = -0.409, p = 0.009) and age (ρ = -0.379, p = 0.016), while the spike rate did not. Spike ripple was a marker for distinguishing typical and atypical forms of BECTS and reflected the risk of seizure recurrence better than the spike alone. The present findings might assist clinicians in BECTS treatment.


Synthesis, radiolabelling and biological characteristics of a bombesin peptide analog as a tumor imaging agent.
Several human cancers, including small cell lung, prostate, breast, gastric, colon and pancreatic cancers, express receptors for bombesin-like peptides. Bombesin (BN) peptides that bind specifically to these receptors are useful for detection of bombesin receptor-expressing cancers in vivo. A new 99mTc-labelled-BN peptide for targeting bombesin receptor-expressing cancers was prepared and characterized. MAG3-coupled BN peptide (MAG3-BN) was prepared by solid-phase synthesis and radiolabelled with 99mTc by an exchange method. In vitro cell binding assays were conducted on human breast cancer cell lines, MDA-MB-231 and MCF-7. In vivo biodistribution studies were performed in normal and nude mice bearing bombesin receptor-positive tumors. Radiolabelling of MAG3-BN with 99mTc produces a single radioactive species (> 95%). In vitro cell-binding indicated the affinity and specificity of 99mTc-MAG3-BN towards bombesin receptors. In vivo biodistribution in mice demonstrated that 99mTc-MAG3-BN cleared rapidly from the blood and most non-targeted tissues and was excreted mainly via the kidneys. Uptake in bombesin receptor-positive tissues and in the tumor was low to moderate. 99mTc-MAG3-BN displays good radiolabelling together with certain favorable biological characteristics and might be a useful peptide radiopharmaceutical in the detection of bombesin receptor-expressing cancers in vivo.


Brønsted acidic ionic liquid-catalyzed tandem reaction: an efficient and sustainable approach towards the regioselective synthesis and molecular docking studies of 4-hydroxycoumarin-substituted indoles bearing lower E-factors.
1-Butane sulfonic acid-3-methylimidazolium tosylate, [BSMIM]OTs, is a remarkable catalyst for the cascade synthesis of coumarin-functionalized indole derivatives via a tandem cyclization reaction of aniline and phenylglyoxal monohydrate. This reaction possibly proceeds through imine formation/nucleophilic addition/cyclization. In addition, this method shows lower E-factors. A clean reaction, easily accessible reactants, metal-free and environmentally friendly reaction conditions, and reusability of the catalyst are the notable advantages of this procedure. In addition, molecular docking studies show the theoretical possibility of binding these types of synthesized compounds to key proteins in tumorigenesis.


Epidemiology, antimicrobial resistance and outcomes of Staphylococcus aureus bacteraemia in a tertiary hospital in Fiji: A prospective cohort study.
Staphylococcus aureus bacteraemia (SAB) is one of the commonest bloodstream infections globally and is associated with a high mortality rate. Most published data comes from temperate, high-income countries. We describe the clinical epidemiology, microbiology, management and outcomes of patients with SAB treated in a tropical, middle-income setting at Fiji's largest hospital. A prospective, observational study was performed of consecutive SAB cases admitted to Colonial War Memorial Hospital (CWMH) in Suva, between July 2020 and February 2021. Detailed demographic, clinical and microbiological data were collected, including the key outcome of in-patient mortality. To estimate the population incidence, all SAB cases diagnosed at the CWMH laboratory were included - even if not admitted to CWMH - with the population of Fiji's Central Division used as the denominator. A total of 176 cases of SAB were detected over eight-months, which equated to an incidence of 68.8 cases per 100,000 population per year. Of these, 95 cases were admitted to CWMH within 48 h of index culture. Approximately 8.4% (8/95) of admitted cases were caused by methicillin-resistant Staphylococcus aureus (MRSA). All cause in-patient mortality was 25.3%, increasing to 55% among patients aged 60 or older. This reported incidence of SAB in central Fiji is one of the highest in the world. SAB was associated with significant mortality, especially in those over 60 years of age, despite a relatively low frequency of methicillin resistance. Supported by the National Health and Medical Research Council (Australia) and the GRAM (Global Research on Antimicrobial Resistance) Project, Oxford University (United Kingdom).


[Swallowing-induced supraventricular tachycardias in an asymptomatic young man (author's transl)].
Three patterns of swallowing-induced supraventricular tachycardia in an asymptomatic young man are described. The patient had no esophageal disease. The electrophysiologic mechanism of arrhythmias remains speculative. Vagal stimulation produced by swallowing appears to cause tachcardias because atropine (1,5 mg iv) prevents their occurrrence.