Congenital graves disease. Four familial cases with long-term follow-up and perspective.
Congenital Graves disease has been described as a transient disorder in which the mother has or has had hyperthyroidism. Experience with four affected children to ages 5 to 9 years and a review of published cases led us to conclude that long-acting thyroid stimulator (half-life, six days) is not the cause of the disease. This disease occurs in infants from families with a high incidence of Graves disease, and, in many, hyperthyroidism persists for months or years. The pathogenesis of Graves disease is unknown, and the simplistic maternal-to-fetal humoral theory is not a suitable explanation for congenital Graves disease. If Graves disease is considered in the larger perspective than the maternal-fetal unit, a pattern of inheritance is apparent, ie, an autosomal-dominant trait with a predilection for the female individual.


Resection for extrahepatic recurrence of hepatocellular carcinoma.
A total of 277 patients with hepatocellular carcinoma (HCC) underwent hepatic resection over a 20-year period. Twelve of 36 patients with recurrence confined to extrahepatic organs underwent surgical resection. There were no complications but one patient died in hospital from secondary intrahepatic recurrence. The 1-, 2- and 5-year survival rates for these 12 patients after hepatic resection were 92, 52 and 26 per cent respectively and were better than those of 24 patients who did not undergo resection for recurrence. The mean survival following resection for recurrent disease was 19.7 months and the longest survival time was nearly 8 years. Secondary recurrence after resection of metastases developed more commonly in the liver than in extrahepatic organs. Among the eight patients who survived for more than 4 months after the second operation, secondary recurrence developed in the liver and extrahepatic organs in eight and four patients respectively. In selected patients with isolated extrahepatic recurrence of HCC, surgery is effective in controlling extrahepatic disease and offers the only chance of long-term survival.


Expression and secretion of albumin in male turkey (Meleagris gallopavo) reproductive tract in relation to yellow semen syndrome1.
Yellow semen syndrome (YSS) is the most widely recognized problem among male turkeys. Yellow semen is of low quality and, when used for insemination, results in reduction of fertility and hatchability. Elevated level of serum albumin-like protein accession no. XP_003205725 is a characteristic feature of yellow seminal plasma suggesting albumin role in YSS pathology. However, knowledge regarding the expression of albumin in the reproductive tract in relation to YSS is very limited. The aim of this study was to identify albumin secretion and localization sites in the turkey reproductive tract in relation to YSS. Reproductive tract tissues and liver originating from turkeys producing white semen (WS) and YSS were used for analysis of albumin mRNA expression and its localization using immunohistochemistry. Moreover, albumin abundance in tissues, blood and seminal plasma was analyzed using two dimensional electrophoresis and western blot analysis. Albumin mRNA expression was found in all parts of the reproductive tract. Apart from the liver, the highest expression of albumin was found in the ductus deferens in YSS turkeys. The testicular spermatids, Leydig, and myoid cells and the epithelium of the epididymis and ductus deferens were the main secretion sites of albumin in the reproductive tract in turkeys. Higher albumin abundance was found in the reproductive tract and seminal plasma of YSS toms compared to WS toms. Our results demonstrated that germ cells from spermatocytes to spermatids, Leydig cells, and myoid cells synthesized and secreted albumin in turkey testis, and epithelial cells are the main secretion sites in epididymis and ductus deferens. Ductus deferens secretion of albumin seems to be mostly responsible for YSS. Over-secretion by the ductus deferens may be the main origin of albumin abundance in YSS semen. Knowledge regarding disturbances of albumin secretion in relation to YSS may be useful for future work on studies related to better understanding the molecular basis of YSS.


Epidemiological aspects of tardive dyskinesia.
Although there continues to be some debate as to the extent to which neuroleptic drug treatment is either necessary or sufficient to produce abnormal involuntary movements in various psychiatric populations, the consensus at present is that neuroleptics do play a major role in producing, precipitating or evoking abnormal involuntary movements. No doubt a variety of other factors play a critical role in predisposing particular individuals to the development of the condition. Numerous prevalence surveys have been conducted and extensively reviewed. In general, prevalence surveys have helped to identify populations at particular risk, to suggest factors which contribute to risk and to establish the overall scope of the problem. The strategy of estimating prevalence in a specific population has limitations, however, and further advances in our understanding of tardive dyskinesia (TD) will require a different type of methodology. Important progress has been made in the last several years involving prospective studies of TD development. Current estimates of incidence suggest that TD develops in about 5% of patients with each year of cumulative neuroleptic exposure. These data are derived from relatively young patients (average age 28); the incidence in older individuals is likely to be higher. Further data on the epidemiology of TD will be presented.


Long-term risk of dementia after acute respiratory failure requiring intensive care unit admission.
This retrospective, population-based cohort study aims to investigate the long-term risk of newly diagnosed dementia in patients discharged for acute respiratory failure that required mechanical ventilation (MV) and intensive care unit (ICU) admission. From the Taiwan National Health Insurance Research Database, first-time ICU patients using MV between June 1, 1998, and December 31, 2012, were enrolled, and they were followed-up until the earliest onset of one of our two endpoints: a new diagnosis of dementia (primary endpoint), or the end of the study. A total of 18,033 patients were enrolled and thirteen hundred eighty-seven patients had been newly diagnosed with dementia (mean onset: 3.2 years post-discharge). Patients ≥ 85 years old had the highest risk (multivariate analysis). Males had a lower risk than did females in both models (HR: 0.81, 95% CI: 0.72-0.9 in model 1; HR: 0.80, 95% CI: 0.72-0.89 in model 2). ICU stays > 5 days, hospital stays > 14 days, and more ICU readmissions were associated with a higher risk of developing dementia. In conclusion, the long-term risks of a subsequent diagnosis of dementia for acute respiratory failure with MV patients who survive to discharge increase with age and are higher in women than in men. Additionally, the longer the ICU or hospital stay is, and the more ICU readmissions a patient has, are both significantly associated with developing dementia.


Complex regional pain syndrome.
This paper provides a review of the current concepts of complex regional pain syndrome (CRPS) and current diagnostic criteria are presented. Etiology and pathophysiological mechanisms of painful disorders, previously addressed as reflex sympathetic dystrophy (RSD) remain doubtful. The supposition of a sympathetic hyperactivity in the development of this syndrome could not be confirmed. Up to now no diagnostic test that would be specific for the diagnosis of CRPS is available. The diagnosis relies on clinical findings and the exclusion of conditions that could account for the degree of pain and dysfunction. Pain relief and functional restoration are the primary goals of all therapeutic intervention and should start as early as possible.


Application of ganglioside-sensitized liposomes in a flow injection immunoanalytical system for the determination of cholera toxin.
Cholera, an acute infectious disease associated with water and seafood contamination, is caused by the bacterium Vibrio cholerae, which lives and colonizes in the small intestine and secretes cholera toxin (CT), a causative agent for diarrhea in humans. Based on earlier lateral flow assays, a flow injection liposome immunoanalysis (FILIA) system with excellent sensitivity was developed in this study for the determination of CT at zeptomole levels. Ganglioside (GM1), found to have specific affinity toward CT, was inserted into the phospholipid bilayer during the liposome synthesis. These GM1-sensitized, sulforhodamine B (SRB) dye-entrapping liposomes were used as probes in the FILIA system. Anti-CT antibodies were immobilized in its microcapillary. CT was detected by the formation of a sandwich complex between the immobilized antibody and GM1 liposomes. During the assay, the sample was introduced first into the column, and then liposomes were injected to bind to all CT captured by the antibody in the microcapillary. Subsequently, the SRB dye molecules were released from the bound liposomes via the addition of the detergent octyl glucopyranoside. The released dye molecules were transported to a flow-through fluorescence detector for quantification. The FILIA system was optimized with respect to flow rate, antibody concentration, liposome concentration, and injected sample volume. The calibration curve for CT had a linear range of 10-16 to 10-14 g mL-1. The detection limit of this immunosensor was 6.6 x 10(-17) g mL-1 in 200-microL samples (equivalent to 13 ag or 1.1 zmol).


Wireless Handheld Computers in the Preclinical Undergraduate Curriculum.
This report presents the results of a pilot project using wireless PDAs as teaching tools in an undergraduate medical curriculum. This technology was used to foster a transition from a passive to an interactive learning environment in the classroom and provided a solution for the implementation of computer-based exams for a large class. Wayne State Medical School recently provided model e570 Toshiba PocketPCs® (personal digital assistants or PDAs), network interface cards, and application software developed by CampusMobility® to 20 sophomore medical students. The pilot group of preclinical students used the PDAs to access web-based course content, for communication, scheduling, to participate in interactive teaching sessions, and to complete course evaluations. Another part of this pilot has been to utilize the PDAs for computer-based exams in a wireless environment. Server authentication that restricted access during the exams and a proctoring console to monitor and record the PDA screens will be described in this report. Results of a student satisfaction survey will be presented.


[Bacterial sacroiliitis caused by group B streptococci].
A 12-year-old girl was admitted to the paediatric department due to a short history of severe pain in the right hip, inability to walk and fever, 39 °C. She had had no previous trauma or ongoing infection elsewhere. Examination showed a septic girl with pain of the right sacroiliac joint. Laboratory findings showed a marginally raised white blood cell count and C-reactive protein. A magnetic resonance imaging was performed and showed effusion of the right sacroiliac joint without root compression. Three days later blood cultures showed group B streptococci and the patient received intravenous antibiotic treatment for two weeks and continued with oral antibiotics for four weeks.


[Clinical characteristics and imaging diagnosis of early cancer in the hepatobiliary and pancreatic region].
For the present, we don't have any reliable definition of the early cancer in hepato-biliary and pancreatic region. In this paper three examples of comparatively early cancer were taken up; (1) among hepatocellular carcinoma, so called, small liver cancer; (2) among gallbladder carcinoma and bile duct carcinoma, those whose extent of infiltration within pm and fm respectively; (3) among pancreatic carcinoma, those whose maximum diameter are 2 cm. And the system of imaging diagnosis was discussed as well as the discussion of their clinical characteristics, imaging diagnosis and the differential diagnosis.


Adaptation of cyanobacteria to the sulfide-rich microenvironment of black band disease of coral.
Black band disease (BBD) is a cyanobacteria-dominated microbial mat that migrates across living coral colonies lysing coral tissue and leaving behind exposed coral skeleton. The mat is sulfide-rich due to the presence of sulfate-reducing bacteria, integral members of the BBD microbial community, and the sulfide they produce is lethal to corals. The effect of sulfide, normally toxic to cyanobacteria, on the photosynthetic capabilities of five BBD cyanobacterial isolates of the genera Geitlerinema (3), Leptolyngbya (1), and Oscillatoria (1) and six non-BBD cyanobacteria of the genera Leptolyngbya (3), Pseudanabaena (2), and Phormidium (1) was examined. Photosynthetic experiments were performed by measuring the photoincorporation of [(14)C] NaHCO(3) under the following conditions: (1) aerobic (no sulfide), (2) anaerobic with 0.5 mM sulfide, and (3) anaerobic with 0.5 mM sulfide and 10 microM 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU). All five BBD cyanobacterial isolates tolerated sulfide by conducting sulfide-resistant oxygenic photosynthesis. Five of the non-BBD cyanobacterial isolates did not tolerate sulfide, although one Pseudanabaena isolate continued to photosynthesize in the presence of sulfide at a considerably reduced rate. None of the isolates conducted anoxygenic photosynthesis with sulfide as an electron donor. This is the first report on the physiology of a culture of Oscillatoria sp. found globally in BBD.


Hollow waveguide-miniaturized quantum cascade laser heterodyne spectro-radiometer.
A miniature thermal infrared laser heterodyne spectro-radiometer based on hybrid optical integration is demonstrated. A quantum cascade laser emitting at 953 cm-1 (10.5 μm) is used as the local oscillator. Integration is achieved using hollow waveguides inscribed in a copper substrate, with slot-encapsulated optical components positioned to maintain fundamental hybrid mode coupling. The demonstrator performances are studied in the laboratory and show a noise level within 1.6 times of the ideal case. Atmospheric high-resolution transmittance spectroscopy of carbon dioxide and water vapor in solar occultation is demonstrated. The total column concentrations are derived as well as measurement uncertainties, 399.5 ± 2.2 ppm for CO2 and 1066 ± 62 ppm for H2O. The miniature laser heterodyne spectro-radiometer demonstration opens the prospect for nanosatellite-based high spectral resolution thermal infrared atmospheric sounding.


DNA-free genome editing in plants with preassembled CRISPR-Cas9 ribonucleoproteins.
Editing plant genomes without introducing foreign DNA into cells may alleviate regulatory concerns related to genetically modified plants. We transfected preassembled complexes of purified Cas9 protein and guide RNA into plant protoplasts of Arabidopsis thaliana, tobacco, lettuce and rice and achieved targeted mutagenesis in regenerated plants at frequencies of up to 46%. The targeted sites contained germline-transmissible small insertions or deletions that are indistinguishable from naturally occurring genetic variation.


[Variability in the clinical presentation of Pompe disease in infancy: two case reports and response to treatment with human recombinant enzyme].
Pompe disease/glycogen storage disease type II is a congenital metabolic disorder. It is an autosomal recessive disease where there is a deficiency of acid alpha-glucosidase (GAA), an enzyme required for lysosomal glycogen degradation. We describe two infantile onset cases with heterogeneous presentations. The first case is a newborn with maintained bradycardia, a cardiologic study revealed severe biventricular hypertrophy. The second case is a 14 months old patient with motor delay and arreflexic hypotonia. Creatine kinase, lactate dehydrogenase, glutamic-oxaloacetic transaminase and glutamic-pyruvic trans aminase were high. The electromyogram showed myopathic alteration and the muscle biopsy vacuolar myopathy with glycogen accumulation. In both of them, GAA activity was decreased and the genetic exam of the GAA gene revealed heterozygous mutations already described in Pompe disease. They started enzyme replacement therapy at 1 month old and 18 months old respectively, improving the cardiomyopathy hypertrophy, motor wise however less advance was seen. At the present time, the patients are 9 months and 5 years old respectively, the last one has a Gross Motor Function Measure (GMFM) III level. GAA is the only authorized option for Pompe disease treatment; the effects observed are similar to the ones described in the literature, with excellent outcome in the hypertrophic cardiomyopathy but less effective in the skeletal muscle.


Improved cloning vectors for Bifidobacterium spp.
The recombinant plasmids pDLI41, pDGA7 and pDCO7 were constructed by cloning in pDG7, a vector based on Bifidobacterium longum replicon pMB1, the following heterologous genes: Pseudomonas fluorescens lipase, Bacillus licheniformis alpha-amylase and Streptomyces sp. cholesterol oxidase. The hybrid plasmids efficiently transformed Bifidobacterium belonging to five different species. A novel Escherichia coli-Bifidobacterium set of shuttle vectors based on the replicon pMB1 (pLF5, pCLJ15, pSPEC1) featuring chloramphenicol, erythromycin and spectinomycin resistance genetic determinants as selection marker for bifidobacteria, was developed. The plasmid pTRE3, a derivative of pLF5, was the smallest (2.8 kb) Bifidobacterium vector, possessed a convenient multicloning site and presented high structural and segregational stability.


Human hair keratin network and curvature.
In human hair, very little is known about the substructures relating to the curl pattern. The interpretation of the macroscopic shape of the fiber at the molecular and cellular scales is still unclear. A comparative and multiscale study was carried out on a set of human hair samples, ranging in shape from straight to tightly curled, in order to investigate structural elements that might be related to hair curl pattern. At the macroscopic level, the frequency and amplitude of cross-sectional rotations were found to be crucial for an accurate description of curliness. At the cellular level, transmission electron microscopy experiments made it possible to confirm that macrofibril organization was strongly related to hair curliness. The curly hair follicles exhibited retrocurvature, independent of ethnic origin. A direct comparison of straight hair and curly hair highlighted an intrinsic asymmetry in the proliferative compartment that clearly extended above the Auber line on the convex side of the curvature. This phenomenon caused delayed differentiation of both inner and outer root sheaths. The hair cortex itself was elliptical and asymmetric, as evidenced by hHa8 keratin. In curly hair, this hair keratin accumulated on the concave side of the curvature, whereas, in straight hair, positive cortical cells were evenly distributed throughout the circular fiber. The curly shape of the hair shaft seems to result from the asymmetric differentiation of the precortex. Hair fiber can thus be considered as a shape memory material.


Viscocanalostomy combined with trabeculotomy and mitomycin C in the treatment of primary congenital glaucoma.
To evaluate the long-term outcome of viscocanalostomy combined with trabeculotomy and mitomycin C in the treatment of primary congenital glaucoma. This is a retrospective study. Forty-two eyes of 26 patients with primary congenital glaucoma were enrolled. Intraocular pressure (IOP), corneal diameter (mm) and cup/disc (C/D) were measured before and after the surgery respectively. Follow-up period was 30mo. The mean preoperative IOP was 30.6±7.35 mm Hg. Of the 42 eyes, 2 eyes were required conversion to trabeculectomy for the absence of Schlemm's canal. Of remained 40 eyes, 38 eyes (95%) achieved successful IOP control. The average postoperative IOP was 11.69±4.18 mm Hg at 12mo. The mean reduction was 18.91 mm Hg (P<0.0001). Eighteen (75%) eyes presented a reduction in corneal diameter, and 25 (62.5%) eyes presented a C/D ratio reversal after the surgery. There was no serious complication in any patients over the follow-up period. Viscocanalostomy combined with trabeculotomy and mitomycin C is useful in the management of primary congenital glaucoma.


Response to crystalline 1alpha-hydroxyvitamin D3 in vitamin D dependency.
The therapeutic response to chemically synthesized 1alpha-hydroxycholecalciferol (1alpha-OH-D3) was studied in three patients with autosomal recessive vitamin D dependency (ARVDD). The daily maintenance dose for vitamin D2, to prevent signs of vitamin D deficiency in these patients, was 40-54.4 mug/kg, or about 100 times normal (Table 1). Withdrawal of maintenance therapy with vitamin D2 resulted in the ultimate reappearance of the vitamin D depletion syndrome in patients 1 and 2 (Figs. 1 and 2). The third patient presented with the deficiency syndrome despite adequate vitamin D nutrition and was recognized to have ARVDD. Treatment with 1alpha-OH-D3 by mouth in all three patients at dose levels of 1-3 mug/24 hr (80-100 ng/kg) corrected hypocalcemia and suppressed parathyroid hormone-dependent renal loss of amino acids (Figs. 1, 2, and 4). Rickets healed in 7-9 weeks on 1alpha-OH-D3 alone (Fig. 3). The therapeutic response was rapid. It was usually seen first in the rise of serum calcium (Figs. 5 and 6). Withdrawal of 1alpha-OH-D3 was followed first by a fall of serum phosphorus, then by a fall in serum calcium; the latter occurred within about 2 weeks of withdrawal. Because the synthesis of 1alpha-OH-D3 is simpler than for 1alpha,25-dihydroxycholecalciferol and because the former is an effective therapeutic analog of vitamin D hormone, we believe these studies in ARVDD reveal 1alpha-OH-D3 to be the agent of choice for treatment of this and analogous diseases.


Ophthalmoplegic migraine with reversible thalamic ischemia shown by brain SPECT.
Two patients who presented with ophthalmoplegic migraine underwent electroencephalography, brain magnetic resonance imaging, cerebral angiography, and technetium Tc 99m ethyl cysteinate dimer single photon emission computed tomography (SPECT) during an attack. Follow-up SPECT was performed after neurologic symptoms resolved. In both patients, SPECT during an attack of ophthalmoplegia and headache demonstrated significantly decreased regional cerebral blood flow (rCBF) in the thalamus on the side of the ophthalmoplegia; rCBF reverted to normal on a follow-up SPECT during the symptom-free period. These findings suggest reversible ischemia in the territories of perforating branches of the posterior cerebral artery may accompany ophthalmoplegic migraine and possibly bear some relationship to the clinical features.


XK endo B is preferentially expressed in several induced embryonic tissues during the development of Xenopus laevis.
XK endo B is a type I keratin that was originally identified by its preferential expression in the embryonic notochord of the amphibian Xenopus laevis. A peptide identical to a short region of its predicted amino acid sequence was used to generate antibodies against the XK endo B protein. This paper reports an immunocytochemical study of the spatial expression pattern of XK endo B during development. The protein was observed in the notochord and endoderm as predicted from previous RNA analysis. In addition, XK endo B was detected in the cement gland, in the pituitary, olfactory and pharyngeal pouch rudiments, and in a nonuniform distribution in the neural tube as well as the inner sensorial layer of the ectoderm. XK endo B expression is not limited to any germ layer or any particular cell type, but is nevertheless highly restricted in its distribution in the embryo. Its expression in several different embryonic tissues requiring inductive interactions for differentiation makes XK endo B a valuable tool with which to study the regulation of induced gene expression during embryogenesis.


Pharmaceutical care outcomes in an outpatient human immunodeficiency virus treatment center in Jos, Nigeria.
Pharmacotherapy for patients infected with human immunodeficiency virus (HIV) is complex and increases the potential for drug therapy problems (DTPs). We described the frequency and type of DTPs in a Nigerian cohort of HIV infected patients on antiretroviral therapy (ART), as well as the changes in HIV clinical outcomes after pharmacists' intervention. A prospective 1-year descriptive study was conducted from July 2010 to June 2011, at the adult HIV clinic of Jos University Teaching Hospital, Nigeria. DTPs and the associated pharmacist-initiated interventions were documented. Chi-square and Wilcoxon signed ranks test was used as appropriate, to compare the main outcome measures of pre- and post-intervention levels of viral load and CD+ cell count. A total of 64,839 prescriptions were dispensed to 9320 patients. Interventions were documented for 85 unique patients (incidence of 1.31 interventions/1000 prescriptions), of which 62 (73%) and 3 (3.5%) were on first- and second-line ART, respectively, while 20 (23.5%) were yet to commence ART. Reasons for pharmacist intervention included failure to initiate therapy for HIV or hepatitis B infection; therapeutic failure (25.9%); and drug toxicity (24.7%). After intervention, the percentage of patients with HIV ribonucleic acid level <400 copies/mL rose from 29.4% to 67.1% (P < 0.001), while median (interquartile range) CD4+ cell count increased from 200 (123-351) to 361 (221-470) cells/mm(3) (P < 0.001). Pharmacist intervention resulted in clinically significant improvements in patients HIV virological and immunological outcomes. This highlights an important role for the pharmacist in the treatment and care of HIV-infected patients, in a multidisciplinary team.


A practical and reliable method of measuring blood pressure in the neonate by pulse oximetry.
We investigated the reliability of the plethysmographic waveform of the pulse oximeter to measure systolic blood pressure in sick neonates. Fifty infants admitted to the neonatal intensive care unit, with indwelling arterial catheters placed for their ongoing care, were enrolled. Median gestational age was 31 weeks (range, 24 to 40 weeks), and the mean birth weight was 1711 gm (range, 546 to 3856 gm). Blood pressure was recorded by an oscillometric method as well as from a transducer connected to an arterial catheter. Additionally, pulse oximeter blood pressures were obtained by gradually inflating an appropriately sized blood pressure cuff in increments of 2 to 5 mm Hg, on the same extremity as the oximeter probe, until the waveform just disappeared. The cuff was then rapidly inflated another 20 mm Hg and then gradually deflated in increments of 2 to 5 mm Hg until the waveform reappeared on the oximeter screen display. The pulse oximeter blood pressures were calculated both as the blood pressure noted at disappearance of the pulse oximeter waveform and as the blood pressure noted by the average pulse oximeter blood pressure at the disappearance and reappearance of the waveform. The mean intraarterial systolic blood pressure was 54 mm Hg (range, 36 to 82 mm Hg). Blood pressures obtained by pulse oximetry showed a significantly better correlation with intraarterial measurements in comparison with those obtained by oscillometric instruments. Additionally, the limits of agreement (mean difference +/- 2 SD) between blood pressures obtained by intraarterial measurements and those obtained by pulse oximetry were within a clinically acceptable range as opposed to those obtained by the comparison of intraarterial and oscillometric methods. Measurements of blood pressure in the neonate by means of pulse oximetry waveform analysis are easily obtainable and more accurate than those obtained by the oscillometric method.


Subtotal petrosectomy: Surgical technique, indications, outcomes, and comprehensive review of literature.
To describe the technique of subtotal petrosectomy (STP), to analyze the outcomes, and to review the literature STUDY DESIGN: A retrospective review. Four hundred sixty cases of STP performed for various indications were included in the study, which was conducted at a quaternary referral center for otology and skull base surgery. Surgical and audiological parameters, and complications were evaluated. Our results were compared with the existing literature on the subject. Two hundred ninety-seven (64.6%) patients had been subjected to multiple surgeries before an STP was performed. The most common indication for STP was recurrent chronic otitis with or without cholesteatoma, with 165 (35.9%) patients. Difficult cases of cochlear implantation, temporal bone fractures, and class B3 tympanomastoid paragangliomas were the next most common indications, with 91 (19.8%), 43 (9.4%), and 38 (8.3%) cases, respectively. The median follow-up of the patient pool was 36 ± 19 months. Recidivism and postauricular wound fistula were the most common complications, seen in five (1.1%) patients each. This series of STP is the largest reported in the literature CONCLUSIONS: STP is a very useful and safe surgical tool in the management of a variety of problematic situations in otology, as it offers the possibility of a definitive cure by offering radical clearance. This procedure can be combined safely with hearing implantation procedures. 4. Laryngoscope, 127:2833-2842, 2017.


Apneic oxygenation provides incremental benefit during intubation of patients in the emergency medicine and critical care settings.
Clinical questionShould I use apneic oxygenation when intubating patients in the emergency department to increase peri-intubation oxygen saturation and first-pass success?Article chosenOliveira JE, Silva L, Cabrera D, Barrionuevo P, et al. Effectiveness of apneic oxygenation during intubation: a systematic review and meta-analysis. Ann Emerg Med 2017;70(4):483-94. The purpose of this study was to synthesize and appraise the apneic oxygenation literature for its effect on peri-intubation outcomes.


5-Episinuleptolide acetate, a norcembranoidal diterpene from the formosan soft coral Sinularia sp., induces leukemia cell apoptosis through Hsp90 inhibition.
5-Episinuleptolide acetate (5EPA), a cytotoxic norcembranoidal diterpene recently identified from the Formosan soft coral Sinularia sp., exhibited potent activity against the K562, Molt 4 and HL 60 cancer cell lines. The antiproliferative assay, as well as the annexin V-FITC/propidium iodide (PI) apoptotic assay, indicated that the HL 60 cell line is the most sensitive one towards 5EPA. This diterpenoid led to caspases -3, -8, and -9 activation as well as PARP cleavage. It also induced ROS generation, calcium accumulation and disruption of mitochondrial membrane potential. Additionally, the expression levels of Hsp90 protein and several client proteins were downregulated in response to 5EPA treatment. These results suggest that 5EPA's cytotoxic effect on HL 60 cells may be attributed to the inhibition of Hsp90 as well as the induction of mitochondrial stress which finally results in apoptotic cell death.


Effect of pneumatic compression on fibrinolysis after total hip arthroplasty.
The purpose of this prospective randomized clinical study was to investigate the enhanced systemic fibrinolysis mechanism of venous thrombosis prevention by pneumatic compression after total hip arthroplasty. Fifty patients were randomized into one of two groups (one with pneumatic compression [n=25] and one without [n=25]). Blood was drawn from a radial arterial line immediately preoperatively (baseline), at skin closure, and 8 hours and 22 hours after the baseline sample. Serum determinations of antigen of tissue plasminogen activator and plasminogen activator inhibitor-1 were done using enzyme-linked immunosorbent assays. These data do not support the enhancement of systemic fibrinolysis mechanism for lowering thromboembolic risk after total hip arthroplasty by pneumatic compression devices. The results of this study showed no differences that were statistically significant between the two groups. The greatest difference was observed 8 hours after surgery for the plasminogen activator inhibitor-1 marker, (28.12 with compression versus 22.07 ng/mL without); however, this result was not statistically significant. The beneficial effect of mechanical compression is more likely achieved through increased flow, local fibrinolytic effects, or both.


Cryofibrinogen in patients with hepatitis C virus infection.
Mixed cryoglobulin is usually associated with hepatitis C virus (HCV) infection and might cause systemic vasculitis. The presence and impact of cryofibrinogen, another cryoprotein, in the serum of HCV-infected patients have not yet been evaluated. The objective was to study the prevalence and the clinical and therapeutic impacts of cryofibrinogen in HCV-infected patients. A total of 143 consecutive HCV-infected (RNA+) patients (including 57 patients with HCV-related vasculitis) were screened for cryofibrinogen and cryoglobulin (positive if >0.05 g/L). The main characteristics and outcome were evaluated according to the cryofibrinogen/cryoglobulin status at baseline. At baseline, 53 of 143 patients (37%) were cryofibrinogen positive, most of whom (47/53 [89%]) were also cryoglobulin positive. Only 37 of 90 cryofibrinogen-negative patients (41%) were cryoglobulin positive (P<.001). In patients with HCV-related vasculitis, 28 of 57 (49%) were cryofibrinogen positive compared with 25 of 86 patients (29%) without vasculitis (P=.03). There was a higher rate of renal involvement in cryofibrinogen-negative/cryoglobulin-positive patients than in cryofibrinogen-positive/cryoglobulin-positive patients (10/25 [40%] vs 3/27 [11%], respectively; P=.02). After a mean follow-up of 32.6 months, among patients who were cryofibrinogen positive at baseline, 12 of 26 (46%) of those who received an HCV treatment were cryofibrinogen negative at the end of follow-up compared with 4 of 16 (25%) of those who did not receive antiviral drugs. Most patients who became cryofibrinogen negative also became cryoglobulin negative (93%). Cryoproteins, including cryoglobulin and cryofibrinogen, are frequently found in the serum of HCV-infected patients. In such patients, a positive cryofibrinogen status is closely related to the presence of cryoglobulin at baseline and after antiviral therapy.


Post-enucleation socket syndrome-a novel pathophysiological definition.
The last definition of the post-enucleation socket syndrome (PESS) by Tyers and Collin-formulated almost 40 years ago in 1982-is predominantly based on the clinical characteristics and does not include the insights of newer studies into the pathophysiological mechanism of the PESS. A systematic PubMed literature review regarding the pathophysiological mechanism of the PESS was performed, and results were comprised to give an overview of the current knowledge of the PESS including the exact pathophysiological mechanism. The primarily postulated pathophysiological mechanism of the PESS was the atrophy of orbital tissues, especially of fat, resulting in variable clinical findings. Newer studies using high-resolution computed tomography and magnetic resonance imaging or performing histopathological analyses found no orbital fat atrophy but rather a rotatory displacement of the orbital tissues from superior to posterior and from posterior to inferior together with the retraction of the extraocular muscles and a possible volume loss of the orbital implant by resorption if it is manufactured from hydroxyapatite. PESS results in a backward tilt of the superior fornix, a deep superior sulcus, a pseudo-ptosis, a lower eyelid elongation and laxity, a shallower inferior fornix, as well as enophthalmos and may lead to an inability of wearing ocular prostheses. A novel and comprehensive definition of the PESS is proposed: PESS is a multifactorial and variable syndrome caused by a rotatory displacement of orbital contents together with the retraction of the extraocular muscles and possible resorption of the orbital implant if it is manufactured from hydroxyapatite.


Co-infections of SARS-CoV-2 with multiple common respiratory pathogens in infected children: A retrospective study.
Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to summarize and investigate the co-infection of SARS-CoV-2 in children.We retrospectively reviewed the clinical manifestations, laboratory findings, and imaging characteristics of COVID-19 patients in co-infection group (CI, n = 27) and single infection group (SI, n = 54). Samples were tested for multiple pathogens.A high incidence (27/81, 33%) of co-infection in children with COVID-19 was revealed. The most frequent co-infected pathogen was mycoplasma pneumoniae (MP, 20/81, 25%), followed by virus (6/81, 7%), and bacteria (4/81, 5%). No significant difference in clinical characteristics, laboratory examinations, or hospital stay was observed between the patients with co-infections and those with monomicrobial, only lower in white blood cell counts (CI: 5.54 ± 0.36 vs SI: 7.38 ± 0.37, P = .002), neutrophil counts (CI: 2.20 ± 0.20 vs SI: 2.92 ± 0.23, P = .024) and lymphocyte counts (CI: 2.72 ± 0.024 vs SI: 3.87 ± 0.28, P = .006). Compared with the patients with monomicrobial, chest imaging of those with co-infections showed consolidation in more cases (CI: 29.6% vs SI: 11.1%, P = .038) and duration of positive in nucleic acid was shorter (CI: 6.69 ± 0.82 vs SI: 9.69 ± 0.74, P = .015).Co-infection was relatively common in children with COVID-19, almost 1/3 had co-infection, most commonly caused by MP. Co-infection did not cause a significant exacerbation in clinical manifestations.


Surgical treatment of respiratory insufficiency due to tracheobronchial compression by aneurysms of the ascending aorta and innominate artery.
Two patients with life-threatening respiratory insufficiency resulting from tracheobronchial compression by expanding aneurysms of the ascending aorta and innominate artery were successfully treated by cardiopulmonary bypass, even in the presence of significant aortic regurgitation. The pertinent surgical procedures are described.


A matched case-control study of circumstances of occupational same-level falls and risk of wrist, ankle and hip fracture in women over 45 years of age.
This study examined the association between circumstances of occupational same-level falls and the risk of wrist, ankle and hip fracture in women over 45 years of age. Cases of fractures and matched controls who suffered non-fracture injuries, all from same-level falls, were selected from workers' compensation claims data. Cases and controls were matched on age, season of fall, industry and state. Information was obtained about manual material handling, fall hazard, initiating event and fall location. Falls during pushing/pulling were associated with increased wrist fracture risk. Falls due to tripping were associated with increased wrist fracture risk, but decreased risk of ankle fracture. Falling outdoors was associated with increased wrist and ankle fracture risk. Increasing age was associated with increased injury risk from tripping-initiated vs. slipping-initiated falls. Few circumstances increased risk of fracture at multiple sites, indicating that they affect risk of fracture by primarily affecting point of impact. The proportion of female workers over 45 years of age, who are at increased risk of fracture, is increasing in developed countries. This study examined the associations between circumstances of falls and wrist, ankle and hip fracture risks among these workers and found that the associations differed by fracture sites.


Numerical study of domain coarsening in anisotropic stripe patterns.
We study the coarsening of two-dimensional smectic polycrystals characterized by grains of oblique stripes with only two possible orientations. For this purpose, an anisotropic Swift-Hohenberg equation is solved. For quenches close enough to the onset of stripe formation, the average domain size increases with time as t(1/2). Further from onset, anisotropic pinning forces similar to Peierls stresses in solid crystals slow down defects, and growth becomes anisotropic. In a wide range of quench depths, dislocation arrays remain mobile and dislocation density roughly decays as t(-1/3), while chevron boundaries are totally pinned. We discuss some agreements and disagreements found with recent experimental results on the coarsening of anisotropic electroconvection patterns.


Association Between Parental Barriers to Accessing a Usual Source of Care and Children's Receipt of Preventive Services.
Preventive health services are important for child development, and parents play a key role in facilitating access to services. This study examined how parents' reasons for not having a usual source of care were associated with their children's receipt of preventive services. We used pooled data from the 2011-2014 National Health Interview Survey (n = 34 843 participants). Parents' reasons for not having a usual source of care were framed within the Penchansky and Thomas model of access and measured through 3 dichotomous indicators: financial barriers (affordability), attitudes and beliefs about health care (acceptability), and all other nonfinancial barriers (accessibility, accommodation, and availability). We used multivariable logistic regression models to test associations between parental barriers and children's receipt of past-year well-child care visits and influenza vaccinations, controlling for other child, family, and contextual factors. In 2014, 14.3% (weighted percentage) of children had at least 1 parent without a usual source of care. Children of parents without a usual source of care because they "don't need a doctor and/or haven't had any problems" or they "don't like, trust, or believe in doctors" had 35% lower odds of receiving well-child care (adjusted odds ratio = 0.65; 95% CI, 0.56-0.74) and 23% lower odds of receiving influenza vaccination (adjusted odds ratio = 0.77; 95% CI, 0.69-0.86) than children of parents without those attitudes and beliefs about health care. Financial and other nonfinancial parental barriers were not associated with children's receipt of preventive services. Results were independent of several factors relevant to children's access to preventive health care, including whether the child had a usual source of care. Parents' attitudes and beliefs about having a usual source of care were strongly associated with their children's receipt of recommended preventive health services. Rates of receipt of child preventive services may be improved by addressing parents' attitudes and beliefs about having a usual source of care. Future studies should assess causes of these associations.


PSITTACOSIS-INFECTED CELL SYSTEM FOR STUDIES ON RADIATION DAMAGE.
Sharon, Nehama (University of Notre Dame, Notre Dame, Ind.), Morris Pollard, and W. R. Klemm. Psittacosis-infected cell system for studies on radiation damage. J. Bacteriol. 86:1139-1144. 1963.-The unique replication pattern of the agent of psittacosis in cells provides a means for studying biological effects of radiation and the influence of radioprotective drugs on this cell virus system. Intracellular psittacosis virus (strain TT) showed a distinctive sensitivity to X irradiation at 3 to 9 hr after onset of infection. This sensitivity to X rays disappeared later in the replication cycle when the virus-orientated ribonucleic acid matrix appeared in the infected cell. The effect of X rays was on the early stages of the virus, since evidence of subsequent developmental stages could not be observed. During the sensitive stage, the amount of surviving virus was related to the dose of X rays. Irradiation caused an irreversible reaction on sensitive virus. The progeny of surviving virus were unaltered in susceptibility to X rays. Addition of glutathione to infected cultures before irradiation increased the amount of surviving virus. Cysteine.HCl and heat-inactivated calf serum were only protective to the virus. Cysteamine was toxic to the cells, and low concentrations gave no protection. Other compounds tested failed to protect the viral agent against the effect of X rays.


Development of the Scottish Walkability Assessment Tool (SWAT).
The Scottish Walkability Assessment Tool (SWAT) was designed to objectively record aspects of the physical environment believed to be related to walking in urban Scotland. Reliability was assessed by three pairs of trained raters auditing 30 street segments on two occasions. Eighteen items were reliably audited and displayed adequate environmental variability, 25 items proved unreliable, and 69 items lacked adequate environmental variability. The large number of items that lacked environmental variability indicates a relatively uniform environment in terms of characteristics, which the literature indicates might be used to differentiate walkability; however, the 18 reliable items can potentially be used to differentiate walkability.


Surface plasmon resonance evaluation of various aminoglycoside-RNA hairpin interactions reveals low degree of selectivity.
Aminoglycoside antibiotics, which are able to selectively bind to RNA, are considered to be an important lead in RNA-targeting drug discovery. In this study, surface plasmon resonance (SPR) was employed to explore the interaction of aminoglycosides with known tobramycin-binding RNA hairpins (aptamers) and an unrelated RNA hairpin. It was established that aminoglycosides have multiple interactions with RNA hairpins. Unexpectedly, the different hairpins showed comparable affinity for a set of related aminoglycosides. The observed absence of selectivity presents an extra hurdle in the discovery of novel aminoglycosides as specific drugs that target defined RNA hairpins.


The phenomenology of Erwin Straus and the epistemology of psychoanalysis.
The contributions of Erwin Straus, a phenomenologist psychiatrist of reknown in Europe but little known in the United States are summarized. His emphasis on the wholeness of the world as it unfolds in its sensory splendor, as opposed to the traditional psychiatric efforts toward the reduction of psychic experience into quasi-mathematical and medical categories is explained.


Association of homozygous C4B deficiency with bacterial meningitis.
The fourth component of complement (C4) is encoded by two separate but linked loci (C4A and C4B), each of which produces functionally active C4. Although C4A and C4B share certain antigenic and functional characteristics that identify them as C4, they differ with respect to other structural and functional properties. For example, C4B possesses four times the functional hemolytic activity of C4A. This suggests that homozygous deficiency of C4B might be associated with an increased susceptibility to infection. Forty-six children with bacterial meningitis were examined. Of these, 5 (10.9%) were homozygous deficient for C4B versus 7 (3.1%) of 223 controls (P = 0.038). There was no relation between the prevalence of heterozygous C4B deficiency and meningitis or between the prevalence of either homozygous or heterozygous C4A deficiency and meningitis. These results suggest that homozygous C4B deficiency is a relatively common immunodeficiency disorder that is clinically significant and predisposes children to bacterial meningitis.


Visible-Light-Driven Photocatalysis-Enhanced Nanozyme of TiO2 Nanotubes@MoS2 Nanoflowers for Efficient Wound Healing Infected with Multidrug-Resistant Bacteria.
To enhance the catalytic activity of the nanozymes for efficient wound healing infected with multidrug-resistant bacteria, photo-based motivations have been suggested, but attention is mainly focused on the external stimulus of near-infrared light, while the inexhaustible visible one is promising but lack of study. Herein, an efficient visible light-stimulated peroxidase-like nanozyme system, TiO2 nanotubes coated with MoS2 nanoflowers (TiO2 NTs@MoS2 ), is discovered for efficient bacterial treatment. Based on the synergetic effects between the two components, the bandgap of the TiO2 NTs can be narrowed from 3.2 to 2.97 eV due to the MoS2 loading, which extended the light response of TiO2 to visible-light range and enhanced the photocatalytic activity accordingly. Meanwhile, the peroxidase-like activity of MoS2 can be significantly enhanced due to the combination with TiO2 NTs in return. Especially, the peroxidase-like activity of the TiO2 NTs@MoS2 nanocomposite can be further improved under the sunlight irradiation, rendering much more hydroxyl radical (•OH) generation. Accordingly, the as-obtained TiO2 NTs@MoS2 shows an outstanding antibacterial effect against drug-resistance extended spectrum β-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus under the visible light. In vivo wound healing test further confirms the high antimicrobial efficiency and good biocompatibility of the synergistic antimicrobial system.


Pure transvaginal natural orifice transluminal endoscopic surgery right hemicolectomy for colon cancer: A case report.
Pure natural orifice transluminal endoscopic surgery (NOTES) for colorectal cancer is a complex procedure and rarely used in clinical practice because of the ethical concerns and technical challenges, including loss of triangulation, in-line orientation, and instrument collision. Transvaginal (v) NOTES, however, can overcome these technical challenges. We report a case of pure vNOTES right hemicolectomy for colon cancer, attached with surgical video. A 65-year-old woman with a 2-year history of intermittent diarrhea was diagnosed with ascending colon adenocarcinoma by colonoscopy and biopsy. Pure vNOTES right hemicolectomy was performed with complete mesocolic excision by well-experienced surgeons. The operative time was 200 min and the estimated blood loss was 30 mL. No intraoperative or postoperative complications occurred within 30 d after the surgery. The visual analog scale pain score on postoperative day 1 was 1 and dropped to 0 on postoperative days 2 and 3. The patient was discharged at postoperative day 6. The pathologic specimen had sufficient clear resection margins and 14 negative harvested lymph nodes. vNOTES right hemicolectomy, performed by well-experienced surgeons, overcomes the technical challenges of pure NOTES and may be feasible for colon cancer.


Study of lead phytoavailability for atmospheric industrial micronic and sub-micronic particles in relation with lead speciation.
Particles from channelled emissions of a battery recycling facility were size-segregated and investigated to correlate their speciation and morphology with their transfer towards lettuce. Microculture experiments carried out with various calcareous soils spiked with micronic and sub-micronic particles (1650+/-20mg Pb kg(-1)) highlighted a greater transfer in soils mixed with the finest particles. According to XRD and Raman spectroscopy results, the two fractions presented differences in the amount of minor lead compounds like carbonates, but their speciation was quite similar, in decreasing order of abundance: PbS, PbSO(4), PbSO(4) x PbO, alpha-PbO and Pb(0). Morphology investigations revealed that PM(2.5) (i.e. Particulate Matter 2.5 composed of particles suspended in air with aerodynamic diameters of 2.5 microm or less) contained many Pb nanoballs and nanocrystals which could influence lead availability. The soil-plant transfer of lead was mainly influenced by size and was very well estimated by 0.01M CaCl(2) extraction.


[Priapism--pathogenesis and therapy].
Priapism can occur when pathologic stimuli (e.g. lesions of the cervical spinal cord) cause prolonged erection, and when normal stimuli under pathologic circumstances (e.g. sickle cell disease, leukemia) produce prolonged erection. As any priapism eventually leads to permanent impotentia coeundi, immediate therapy is absolutely indicated. All unspecific procedures are useless and merely waste time. The priapism in connection with hematologic diseases must be countered by conservative specific therapy (sickle cell disease by blood transfusions; leukemias by cytostatic drugs). All other forms of priapism must be treated by surgery as soon as possible. The operation of choice today perineal bilateral shunt between the corpus cavernosum and the corpus spongiosum


Fabrication of bulk nanostructured permanent magnets with high energy density: challenges and approaches.
Nanostructured permanent magnetic materials, including exchange-coupled nanocomposite permanent magnets, are considered as the next generation of high-strength magnets for future applications in energy-saving and renewable energy technologies. However, fabrication of bulk nanostructured magnets remains very challenging because conventional compaction and sintering techniques cannot be used for nanostructured bulk material processing. In this paper we review recent efforts at producing bulk nanostructured single-phase and composite magnetic materials with emphasis on grain size control, anisotropy generation and interface modification.


Effect of Chloride on Microstructure in Cu Filled Microscale Through Silicon Vias.
The microstructure of copper filled through silicon vias deposited in a CuSO4 + H2SO4 electrolyte containing micromolar concentrations of deposition rate suppressing poloxamine and chloride additives is explored using electron backscatter diffraction. Regions with distinct microstructures are observed in the vias, including conformal deposition and seam formation localized adjacent to the bottom that can transition to bottom-up filling higher in the features. The presence and extent of each microstructure depends on applied potential as well as additive concentration. Deposition in the presence of higher chloride concentration yields a strong (110) growth texture in regions where bottom-up filling exhibits a horizontal growth front profile while (110) textured or untextured growth is observed for different conditions where upward growth proceeds with a v-notch profile.


[UV irradiation devices for the treatment of psoriasis. Desirable spectra and various criteria for selection].
Special fluorescent lamps as well as filtered high pressure lamps are used for photo- and photochemotherapy of psoriasis. The spectra of the lamps offered for phototherapy are compared with the antipsoriatic range of action (lambda ca.295-315 nm) and judged by their therapeutic effect. The spectra offered for photochemotherapy should be free of UVB-radiation. Visible and infrared rays are not effective with psoriasis. The production of heat may stress the patient and require heat removal. On the skin surface the distribution of irradiation should be as even as possible. PUVA treatments of longer duration are preferably performed in a lying position. Closed irradiation units may produce claustrophobia . Open irradiation units require remote control. The most decisive economic factors are the duration of a single exposure as well as space requirements.


An OX40/OX40L interaction directs successful immunity to hepatitis B virus.
Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4+ T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB.


Beneficial Effects of Selective Orexin-A Receptor Antagonist in 4-aminopyridine-induced Seizures in Male Rats.
Orexins are excitatory neuropeptides which stimulate the central regulatory pathways. Orexins increase the penicillin-induced epileptic activity in rats. Orexin-A increases in different types of seizures and its elevated level is the characteristic feature in the epileptic children during polysomnography. Recently, the orexin receptor blockage has been reported to increase seizure threshold in mice; however, effect of the selective orexin-A receptor antagonist (SB-334867) on 4-aminopyridine (4-AP)-induced seizures has not been investigated. We used the intraperitoneal injection of 4-AP to induce seizure in male rats. Under urethane anesthesia, SB-334867 (50 and 100 nmol) was injected stereotaxically into the ventral hippocampal commissure. Using video recording, the effects of SB-334867 on electroencephalogram and tonic-clonic convulsions were compared to those that received diazepam or dimethyl sulfoxide (DMSO). SB-334867 significantly decreased the duration of spike trains compared to DMSO-treated rats (P < 0.001) and reduced the duration of convulsive seizures (P < 0.05). Seizure onset was increased significantly by SB-334867, 50 nmol, compared to DMSO (P < 0.05) and diazepam (P < 0.01) treated rats. Antagonism of orexin-A receptor by a low-dose SB-334867 showed protective effects in 4-AP-induced seizure-like activities in anesthetized rats.


The role of tongue-tie in breastfeeding problems-A prospective observational study.
We evaluated what determined breastfeeding problems in a non-selected mother-infant cohort, with special reference to tongue-tie and improvements in breastfeeding following frenulotomy. This 2014-2015 prospective, observational study was carried out in a tertiary level maternity unit affiliated to the University of Freiburg, Germany, using a breastfeeding questionnaire, standardised breastfeeding scores and the Assessment Tool For Lingual Frenulum Function (ATLFF). The standard intervention was breastfeeding support, a frenulotomy for tongue-tie was performed if necessary. All cases of breastfeeding problems and, or tongue-tie, were followed up by telephone 2.5 weeks after birth. We enrolled 776 newborn-mother dyads: 345 had breastfeeding problems, 116 had a tongue-tie and 30 underwent a frenulotomy. In the multivariate analysis, severe breastfeeding problems were more frequent in newborn infants with tongue-tie, with an odds ratio (OR) of 2.6 (P= 0.014). Other risk factors were: no breastfeeding experience (OR 4.4, P = 0.001), low birth weight (OR 2.9, P = 0.001), prematurity (OR 3.6, P = 0.000) and Caesarean section (OR 1.6, P = 0.023). There was a significant reduction in breastfeeding problems after frenulotomy (P = 0.01). Tongue-tie had a significant impact on breastfeeding and so did low birth weights and prematurity. Frenulotomy proved helpful when breastfeeding problems were reported.


Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes.
Because of the ability of certain long-chain polyunsaturated fatty acids (PUFAs) to prevent lethal cardiac arrhythmias, we have examined the effects of various long-chain fatty acids on the contraction of spontaneously beating, isolated, neonatal rat cardiac myocytes. The omega 3 PUFA from fish oils, eicosapentaenoic acid [EPA; C20:5 (n-3)] and docosahexaenoic acid [DHA; C22:6 (n-3)], at 2-10 microM profoundly reduced the contraction rate of the cells without a significant change in the amplitude of the contractions. The fatty acid-induced reduction in the beating rate could be readily reversed by cell perfusion with fatty acid-free bovine serum albumin. Addition of either oxygenase inhibitors or antioxidants did not alter the effect of the fatty acids. Arachidonic acid [AA; C20:4 (n-6)] produced two different effects on the beating rate, an increase or a decrease, or it produced no change. In the case of the increased or unchanged beating rate in the presence of AA, addition of AA oxygenase inhibitors subsequently reduced the contraction rate. The nonmetabolizable AA analog eicosatetraynoic acid (ETYA) always reduced the beating rate, as did EPA or DHA. Two other PUFAs, linoleic acid [C18:2 (n-6)] and linolenic acid [C18:3 (n-3)] also exhibited similar but less potent effects compared with EPA or ETYA. In contrast, neither the monounsaturated fatty acid oleic acid [C18:1 (n-9)] nor the saturated fatty acids stearic acid (C18:0), myristic acid (C14:0), and lauric acid (C12:0) affected the contraction rate. The inhibitory effect of these PUFAs on the contraction rate was similar to that produced by the class I antiarrhythmic drug lidocaine. The fatty acids that are able to reduce the beating rate, particularly EPA and DHA, could effectively prevent and terminate lethal tachyarrhythmias (contracture/fibrillation) induced by high extracellular calcium concentrations or ouabain. These results suggest that free PUFAs can suppress the automaticity of cardiac contraction and thereby exert their antiarrhythmic effects.


A learning-based approach for biomedical word sense disambiguation.
In the biomedical domain, word sense ambiguity is a widely spread problem with bioinformatics research effort devoted to it being not commensurate and allowing for more development. This paper presents and evaluates a learning-based approach for sense disambiguation within the biomedical domain. The main limitation with supervised methods is the need for a corpus of manually disambiguated instances of the ambiguous words. However, the advances in automatic text annotation and tagging techniques with the help of the plethora of knowledge sources like ontologies and text literature in the biomedical domain will help lessen this limitation. The proposed method utilizes the interaction model (mutual information) between the context words and the senses of the target word to induce reliable learning models for sense disambiguation. The method has been evaluated with the benchmark dataset NLM-WSD with various settings and in biomedical entity species disambiguation. The evaluation results showed that the approach is very competitive and outperforms recently reported results of other published techniques.


Biotherapeutic Effect of Gingival Stem Cells Conditioned Medium in Bone Tissue Restoration.
Bone tissue engineering is one of the main branches of regenerative medicine. In this field, the use of a scaffold, which supported bone development, in combination with mesenchymal stem cells (MSCs), has promised better outcomes for bone regeneration. In particular, human gingival mesenchymal stem cells (hGMSCs) may present advantages compared to other MSCs, including the easier isolation. However, MSCs' secretome has attracted much attention for its potential use in tissue regeneration, such as conditioned medium (CM) that contains different soluble factors proved to be useful for the regenerative purposes. In this study, we evaluated the osteogenic capacity of a poly-(lactide) (3D-PLA) scaffold enriched with hGMSCs and hGMSCs derived CM and its ability to regenerate bone defects in rat calvarias. 3D-PLA alone, 3D-PLA + CM or 3D-PLA + hGMSCs with/without CM were implanted in Wistar male rats subjected to calvarial defects. We observed that 3D-PLA scaffold enriched with hGMSCs and CM showed a better osteogenic capacity, being able to repair the calvarial defect as revealed in vivo by morphological evaluation. Moreover, transcriptomic analysis in vitro revealed the upregulation of genes involved in ossification and regulation of ossification in the 3D-PLA + CM + hGMSCs group. All of these results indicate the great osteogenic ability of 3D-PLA + CM + hGMSCs supporting its use in bone regenerative medicine, in particular in the repair of cranial bone defects. Especially, hGMSCs derived CM played a key role in the induction of the osteogenic process and in bone regeneration.


The Differential Diagnosis of Lymphocyte-rich Classical Hodgkin's Lymphoma and Lymphocyte Predominant Hodgkin's Lymphoma Using the R.E.A.L. Criteria. An Immunohistochemical Study on 45 Cases.
In the present study, the two types, lymphocyte-rich classical HL (LRCHL) and nodular lymphocytepredominant type (NLPHL), which were grouped together before the R.E.A.L. classification, were questioned on the basis of differential criteria and 45 cases were retrieved from last ten years' archival material. On histopathological examination, nodular pattern, the cytological features and intensity of Reed- Sternberg (RS) cells, the pattern and intensity of histiocytes, the presence of germinal centers with progressive transformation were analysed. An immunohistochemical study was performed using antibodies against CD20, CD45RO, CD3, CD30, CD15 antigens and streptavidin-biotin procedure. The cases were classified into three groups according to the histologic pattern and immunophenotypical features ofthe RS cells: I) diffuse, LRCHL (CD20-, CD30+/-, CD15+/-): n= 28; II) NLPHL (CD20+, CD30-, CD15-): n= 11; III) cases which could not be evaluated in former groups: n= 6. Four cases in the latter group showed a nodular pattern with RS cells negative for all markers, except for one case, which expressed both CD20 and CD15. The remaining two cases exhibited a diffuse pattern and the RS cells were CD20+, coexpressing CD30 in one. These findings suggest that, differential diagnosis according to the R.E.A.L. criteria is not distinctive between the two categories of HL in about 13% of cases, and further criteria need to be established to define the grey zone between the two entities which might lead to further therapeutic trials.


MTA3 regulates malignant progression of colorectal cancer through Wnt signaling pathway.
MTA3 overexpression has been implicated in carcinogenesis. The aim of the present study was to explore the clinical significance and biological roles of MTA3 in human colorectal cancer and colorectal cancer cells. A total of 80 cases of colorectal cancer tissues were examined by immunohistochemistry for MTA3 protein expression. We analyzed the relationship between MTA3 and clinical factors and the results showed that MTA3 was overexpressed in 51.25% (41/80) cancer cases. There was significant associations between MTA3 overexpression and advanced TNM stage (p = 0.0086) and Ki67 index (p = 0.001). We overexpressed MTA3 in LoVo cells and depleted its expression in HCT15 cells. The results showed that MTA3 promoted cancer cell proliferation, invasion, migration, and cell cycle progression, and inhibited 5-fluorouracil-induced apoptosis in LoVo cell line. MTA3 depletion in HCT15 cell line showed the opposite effects. In addition, we found that MTA3 positively regulated cell cycle proteins including cyclin D1 and cyclin E. It also upregulated Bcl2 and downregulated Bax expression. Furthermore, we found that MTA3 could activate Wnt signaling pathway by upregulating Wnt target proteins. Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer.


Isolation and structural elucidation of chondrosterins F-H from the marine fungus Chondrostereum sp.
The marine fungus Chondrostereum sp. was collected from a soft coral of the species Sarcophyton tortuosum from the South China Sea. Three new compounds, chondrosterins F-H (1, 4 and 5), together with three known compounds, incarnal (2), arthrosporone (3), and (2E)-decene-4,6,8-triyn-1-ol (6), were isolated. Their structures were elucidated primarily based on NMR and MS data. Incarnal (2) exhibited potent cytotoxic activity against various cancer cell lines.


High-efficiency broadband excitation and propagation of second-mode spoof surface plasmon polaritons by a complementary structure.
A complementary structure based on coplanar waveguides (CPWs) with periodical etching slots is proposed to support spoof surface plasmon polaritons (SSPPs). In contrast to the traditional slotline-based complementary SSPP structure, a dispersion curve of the second mode by the proposed structure has a much lower starting point from the origin which exhibits greatly improved operating bandwidth. Moreover, tighter confinements of SSPPs in the region of small wave vectors corresponding to lower frequencies can be predicted from the dispersion analysis, which means enhancement of transmission efficiency. Then a simple and efficient transition structure with tapered CPWs and gradient slots is proposed to realize high-efficiency and broadband excitation of the second mode of SSPPs for the first time, to the best of our knowledge. Based on the proposed structure, a seamless connection between CPWs and the SSPP structure can be achieved. The measured insertion loss and return loss below 6.6 GHz is better than -0.86 and -13.62 dB, respectively. Furthermore, it can be seen from the measurement results that a 3 dB bandwidth ranges from 0 to 10.57 GHz, and the return loss is better than -10 dB from 0 to 8.96 GHz. The proposed structure can promote the development of plasmonic integrate circuits and functional devices at microwave frequencies.


Cs4 Zn5 P6 S18 I2 : the Largest Birefringence in Chalcohalide Achieved by Highly Polarizable Nonlinear Optical Functional Motifs.
Chalcohalides not only keep the balance between the nonlinear optical (NLO) coefficient and wide band gap, but also provide a promising solution to achieve sufficient birefringence for phase-matching ability in NLO crystals. In this study, a novel chalcohalide, Cs4 Zn5 P6 S18 I2 (1) is successfully synthesized, by incorporating the highly electropositive Cs and the large electronegative I element into the zinc thiophosphate. Its 3D open framework features an edge-shared by distorted [ZnS4 ], ethanol-like [P2 S6 ], and unusual [ZnS2 I2 ] polyhedrons, which is inconsistent with the soft-hard-acids-bases theory. Remarkably, compound 1 simultaneously exhibits the large second-harmonic generation (SHG, 1.1×AgGaS2 , @1.3 µm) and a wide band gap (3.75 eV) toward a high laser-induced damage threshold (16.7×AgGaS2 , @1.06 µm), satisfying the rigorous requirements for a prominent infrared NLO material with concurrent SHG intensity (≥0.5×AGS) and band gap (≥3.5 eV). Moreover, to the best of the knowledge, the experimental result shows that phase 1 has the largest birefringence (0.108, @546 nm) in chalcohalide and meets phase-matching behavior demand originating from the polarizable anisotropy of NLO-functional motifs. This finding may provide great opportunities for designing birefringent chalcohalides.


Older adults living through and with their computers.
Using computers and the Internet to alleviate or reduce loneliness and social isolation and using online methods of data collection in the forms of online surveys and chat room interviews are in their infancy and require a descriptive qualitative study of the experiences of older adults who are online. The purpose of this pilot study was twofold: (1) to describe the experiences of completing an online questionnaire and participating in an online interview and (2) to determine if the methodology of collecting interview data in a chat room setting can yield thick rich qualitative data to support future qualitative investigations into the Internet's potential use as a deterrent to social and emotional isolation. This study used a Web page questionnaire and chat room interviews with online participants aged 65 years and older living alone. Seven of the 10 participants used the computer to combat loneliness. The participants found the questionnaire easy to locate, answer, and submit. They enjoyed the chat and believed that future interviews could be conducted on the Internet. The participants successfully completed the online questionnaire and chat room interviews with minimal difficulties attributed to a conflict with their Internet service provider. Themes evolving from the interviews were: computer life, online life, living alone, and living life.


Current and future trials of the EORTC brain tumor group.
The EORTC Brain Tumor Group (BTG) is dedicated to clinical research of neoplasms of the brain. In the past years the BTG has carried out phase II and phase III trials on glial tumors, brain metastases and primary CNS lymphomas. Future studies will investigate novel drugs in combination with chemo-radiotherapy in glioblastoma multiforme, radiotherapy in meningioma, and chemotherapy in medulloblastoma. The BTG will also start a new phase III trial on newly diagnosed low-grade glioma comparing radiotherapy to temozolomide. In all our trials translational research is getting more and more important, often this is one of the most important ways to get useful conclusions from clinical trials. The wide recognition of the importance of translational research for clinical trials and in particular with targeted therapies implies that this type of research will become a mandatory element in many of our future trials.


Medical evidence and proof of cause of death in Nigerian courts.
Medical evidence has continued to be given and evaluated in Nigerian courts since Nigeria's independence from Britain. The attitudes of the courts have been largely varied against a background of the individual judge's appreciation of forensic science and who should be considered an expert witness. The prosecution and defence lawyers equally display limited knowledge of forensic science. This paper reviews some of the decided cases, the reasons for the verdicts, forensic concerns and recommendations for the improvement of the criminal justice system. There is need to improve the knowledge base of the bar and the bench.


Cytokine regulation of the balance between alloindifferent and allospecific suppressor induction in mixed lymphocyte cultures.
The effects of exogenous cytokines on the generation of alloindifferent, MHC-unrestricted suppressive activity early on in mixed lymphocyte culture interactions have been investigated. Interleukin 4 strongly blocked the generation of suppression, whereas IL-1, IL-2, and IL-6 enhanced it to some extent. Tumor necrosis factor-alpha, interferons-alpha and -gamma, granulocyte/macrophage colony-stimulating factor, granulocyte CSF, IL-3 and IL-5, and a number of combinations of these factors were without effect in this system. Insofar as the alloindifferent suppression studied here also inhibited the development of allospecific, MHC restricted suppressive activity later in MLC, reduction by IL-4 of its development may have relevance for the use of this cytokine to facilitate the induction of specific suppressor cell-mediated transplantation tolerance in vivo.


[DNA-duplexes with phosphoamide bond: interaction with restriction endonucleases EcoRII and SsoII].
We studied the interaction of EcoRII and SsoII restriction endonucleases with synthetic DNA duplexes, containing 3'N----5'P and 3'P----5'N phosphoamide internucleotide bonds in one of the cleavage points. Enzymatic hydrolysis of the modified strand of the duplexes is blocked in all cases. The presence of phosphoamide bonds was found to reduce the rate of cleavage of the natural strand by EcoRII and to have no influence in case of SsoII. Properties of the EcoRII endonuclease complex with its substrate, containing non-cleavable 3'N----5'P internucleotide bonds in each cleavage point, were examined. In the presence of Mg2+ ions the equilibrium association constant of the enzyme-substrate complex is 3-fold reduced, and the dissociation rate constant of the complex is increased by 1.5 times.


Biolistic expression of the macrophage colony stimulating factor receptor in organotypic cultures induces an inflammatory response.
The receptor for macrophage colony-stimulating factor (M-CSFR; c-fms) is expressed at increased levels by microglia in Alzheimer's disease (AD) and in mouse models for AD. Increased expression of M-CSFR on cultured microglia results in a strong proinflammatory response, but the relevance of this cell culture finding to intact brain is unknown. To determine the effects of increased microglial expression of M-CSFR in a complex organotypic environment, we developed a system for biolistic transfection of microglia in hippocampal slice cultures. The promoter for the Mac-1 integrin alpha subunit CD11b is active in cells of myeloid origin. In the brain, CD11b expression is restricted to microglia. Constructs consisting of the promoter for CD11b and a c-fms cDNA or an enhanced green fluorescent protein (EGFP) cDNA were introduced into monotypic cultures of microglia, neurons, and astrocytes. Strong CD11b promoter activity was observed in microglia, whereas little activity was observed in other cell types. Biolistic transfection of organotypic hippocampal cultures with the CD11b/c-fms construct resulted in expression of the c-fms mRNA and protein that was localized to microglia. Furthermore, biolistic overexpression of M-CSFR on microglia resulted in significantly increased production by the hippocampal cultures of the proinflammatory cytokines interleukin (IL)-1alpha macrophage inflammatory protein (MIP-1alpha), and trends toward increased production of IL-6 and M-CSF. These findings demonstrate that microglial overexpression of M-CSFR in an organotypic environment induces an inflammatory response, and suggest that increased microglial expression of M-CSFR could contribute to the inflammatory response observed in AD brain.


[A study of ECG combination detection algorithm based on wavelet transform and morphological method].
In order to deal with the disadvantages in ECG waveform detection by wavelet harr transform at level 3, we put forward a new set of algorithm which combines wavelet transform (WT) and morphological peak and valley detection. The combination algorithm can make up the limitation in detecting ECG swing by WT and improve the accuracy of ECG waveform detection effectively.


Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue.
Osteocyte apoptosis is spatially and temporally linked to bone fatigue-induced microdamage and to subsequent intracortical remodeling. Specifically, osteocytes surrounding fatigue microcracks in bone undergo apoptosis, and those regions containing apoptotic osteocytes co-localize exactly with areas subsequently resorbed by osteoclasts. Here we tested the hypothesis that osteocyte apoptosis is a key controlling step in the activation and/or targeting of osteoclastic resorption after bone fatigue. We carried out in vivo fatigue loading of ulna from 4- to 5-mo-old Sprague-Dawley rats treated with an apoptosis inhibitor (the pan-caspase inhibitor Q-VD-OPh) or with vehicle. Intracortical bone remodeling and osteocyte apoptosis were quantitatively assessed by standard histomorphometric techniques on day 14 after fatigue. Continuous exposure to Q-VD-OPh completely blocked both fatigue-induced apoptosis and the activation of osteoclastic resorption, whereas short-term caspase inhibition during only the first 2 days after fatigue resulted in >50% reductions in both osteocyte apoptosis and bone resorption. These results (1) show that osteocyte apoptosis is necessary to initiate intracortical bone remodeling in response to fatigue microdamage, (2) indicate a possible dose-response relationship between the two processes, and (3) suggest that early apoptotic events after fatigue-induced microdamage may play a substantial role in determining the subsequent course of tissue remodeling.


The erythrocyte adhesiveness/aggregation test for the detection of an acute phase response and for the assessment of its intensity.
We have developed a simple slide test and image analysis to reveal the state of erythrocyte adhesiveness/aggregation in the peripheral blood of patients with various degrees of the humoral acute phase response. The significant correlation between the results of the erythrocyte adhesiveness/aggregation test (EAAT), the erythrocyte sedimentation rate and fibrinogen concentration support the notion that it is possible to use the EAAT as a marker for the intensity of the acute phase response. Within a group of 860 individuals, we were able to differentiate effectively between groups of patients with a different intensity of humoral acute phase response. The present study confirms previous observations that support the applicability of the EAAT to routine clinical practice.


Change of psychotropic drug prescription for schizophrenia in a psychiatric institution in Beijing, China between 1999 and 2008.
To date, no study has investigated how prescription patterns change over time in Chinese patients with schizophrenia. This study aimed to determine psychotropic drug prescription patterns and the use of electroconvulsive therapy (ECT) for schizophrenia and their changes over time in a large psychiatric institution in Beijing, China. The case notes of inpatients with schizophrenia were scrutinized to identify psychotropic drug prescription patterns and the use of ECT on November 10, 1999 and the same calendar day in 2008 and to compare the two surveys. In 1999, 45.1% of inpatients with schizophrenia were on first-generation antipsychotic drugs (FGA), while 52.9% were on second-generation antipsychotic drugs (SGA). In 2008, the percentage of patients on FGAs decreased to 15.1%, while those on SGAs increased to 77.2%. The proportion of schizophrenia patients on mood stabilizers and antidepressants rose from 3.3% and 4.3% in 1999 to 18% and 9.5% by 2008, respectively. Use of ECT grew from 0.5% in 1999 to 5.6% by 2008. The proportion of schizophrenia patients not prescribed antipsychotic drugs changed from 5.6% in 1999 to 13.7% in 2008. The prescription pattern of psychotropic drugs changes considerably over time, even in the same clinical setting. Mental health professionals need to keep up with changes in the prescription patterns of psychotropic drugs in order to serve their patients at the best possible level. The socio-economic reasons for not prescribing antipsychotic drugs to schizophrenia patients should be further explored.


MALE EFFECTS ON FECUNDITY IN DROSOPHILA MELANOGASTER.
Effects of male Drosophila melanogaster on female fecundity and productivity were examined, considering both females held in containers with males and females exposed to male effects not involving contact. Females were more fecund when male effects were present, and the largest increase was recorded when vials were previously conditioned by males. This effect was probably due to the growth of transmitted microorganisms, which were observed on the laying surface, as further experiments with vials conditioned by virgin females showed a similar increase in fecundity. A male-specific effect was isolated by conditioning bottles containing only agar with males and virgin females. The observation of a male factor that stimulates oviposition without mating is novel and suggests complicated fertility interactions between the sexes.


Perspectives on Current Challenges and Opportunities for Bovine Viral Diarrhoea Virus Eradication in Australia and New Zealand.
This review outlines the history of bovine viral diarrhoea virus (BVDV) and the current situation in Australia and New Zealand. BVDV has been reported as present in cattle from both countries for close to 60 years. It rates as the second most economically significant disease afflicting cattle, and is highly prevalent and spread throughout the beef and dairy industries. While other cattle diseases have been the subject of government control and eradication, infection with BVDV is presently not. Eradication has been undertaken in many other countries and been judged to be a good investment, resulting in positive economic returns. Presently, Australia and New Zealand have adopted a non-compulsory approach to control schemes, initiated and managed by farmers and veterinarians without the ultimate goal of eradication. Moving towards eradication is possible with the infrastructure both countries possess, but will require additional resources, coordination, and funding from stakeholders to move to full eradication.


Categorical biases in spatial memory: the role of certainty.
Memories for spatial locations often show systematic errors toward the central value of the surrounding region. The Category Adjustment (CA) model suggests that this bias is due to a Bayesian combination of categorical and metric information, which offers an optimal solution under conditions of uncertainty (Huttenlocher, Hedges, & Duncan, 1991). A fundamental assumption of this model is that representations of locations are unbiased but uncertain; during combination, greater metric uncertainty results in relatively greater emphasis on categorical information, ultimately leading to increased bias (but also minimizing error across multiple estimates). Sampaio and Wang (2009) have demonstrated that metric information is not lost during this combination process, supporting the CA model's assumption that underlying spatial representations are undistorted. Here, we examine the 2nd half of the CA model's central assumption: that increasing metric uncertainty drives the combination process. Participants recognized point locations within visually complex images in a 4-choice task. Our results indicate that individuals recognized the correct location over other, biased alternatives, confirming that metric information is unbiased at the time of retrieval. In addition, we found that, when participants make errors, they are more likely to select locations that are biased toward the category prototype. In Experiment 2, we demonstrate that categorically biased locations are most likely to be chosen under conditions of uncertainty. Indeed, under these conditions, categorically biased locations were chosen more frequently than the correct location. These results suggest that systematic errors are the result of combination across multiple levels of spatial representations that are undistorted but somewhat uncertain.


Mice lacking urea transporter UT-B display depression-like behavior.
Urea transporter B is one of urea transporters that selectively transport urea driven by urea gradient across membrane and expressed abundantly in brain. To determine the physiological role of UT-B in brain, UT-B localization, urea concentration, tissue morphology of brain, and behavioral phenotypes were studied in UT-B heterozygous mice via UT-B null mice. UT-B mRNA was expressed in olfactory bulb, cortex, caudate nucleus, hippocampus and hypothalamus of UT-B heterozygous mice. UT-B null mice exhibited depression-like behavior, with urea accumulation, nitric oxide reduction, and selective neuronal nitric oxide synthase level increase in hippocampus. After acute urea loading, the urea level increased, NO production decreased in hippocampus from both types of mice. Moreover, urea level was higher, and NO concentration was lower consistently in UT-B null hippocampus than that in heterozygous hippocampus. In vitro, 25 mM urea inhibited NO production too. Furthermore, UT-B knockout induced a long-lasting notable decrease in regional cerebral blood flow and altered morphology, such as loss of neurons in CA3 region, swelling, and membranous myelin-like structure formation within myelinated and unmyelinated fibers in hippocampus. These results suggest that urea accumulation in the hippocampus induced by UT-B deletion can cause depression-like behavior, which possibly attribute to disturbance in NOS/NO system.


Coexpression Analysis of Transcriptome on AIDS and Other Human Disease Pathways by Canonical Correlation Analysis.
Acquired immune deficiency syndrome is a severe disease in humans caused by human immunodeficiency virus. Several human genes were characterized as host genetic factors that impact the processes of AIDS disease. Recent studies on AIDS patients revealed a series disease is complicating with AIDS. To resolve gene interaction between AIDS and complicating diseases, a canonical correlation analysis was used to identify the global correlation between AIDS and other disease pathway genes expression. The results showed that HLA-B, HLA-A, MH9, ZNED1, IRF1, TLR8, TSG101, NCOR2, and GML are the key AIDS-restricted genes highly correlated with other disease pathway genes. Furthermore, pathway genes in several diseases such as asthma, autoimmune thyroid disease, and malaria were globally correlated with ARGs. It suggests that these diseases are a high risk in AIDS patients as complicating diseases.


Functional study of 14-3-3 protein epsilon (YWHAE) in keratinocytes: microarray integrating bioinformatics approaches.
Previously, we detected that 14-3-3 protein epsilon (YWHAE) was involved in the pathogenesis of atopic dermatitis (AD) and tyrosinase-mediated pigmentation. In this study, we aimed to identify critical factors associated with YWHAE in human keratinocytes using high-throughput screening (HTS) approaches to reveal its functions in skin. We overexpressed YWHAE in human HaCaT keratinocytes and then conducted serial HTS studies, including RNA sequencing integrated with antibody arrays and the implementation of bioinformatics algorithms. Cumulatively, these approaches identified several novel genes in keratinocytes associated with the function of YWHAE including KRT9, KRT1, KRT6C, BST2, CIB2, APH1B, ACTC1, IFI27, TUBA1A, CAPN6, UTY, MX2, and MAPK15, based on RNA sequencing data, and MAPK1, MMP2, TYK2, NOS3, and CASP3, based on antibody array data. In particular, CD37 is a unique gene that was detected and validated in all the methods applied in this study. By integrating the datasets obtained from these HTS studies and utilizing the strengths of each method, we obtained new insights into the functional role of YWHAE in skin keratinocytes. The approach used here could contribute to the clinical understanding of YWHAE-associated applications in the treatment of AD disease. AbbreviationsDAVIDthe database for annotation, visualization and integrated discoveryHTSHigh-throughput screeningKEGGKyoto Encyclopedia of Genes and GenomesPPIprotein-protein interactionsCommunicated by Ramaswamy H. Sarma.


Involvement of Type I Interferon Signaling in Muscle Stem Cell Proliferation During Dermatomyositis.
The idiopathic inflammatory myopathy dermatomyositis is an acquired disease that involves muscle, lung, and skin impairments. Patients with dermatomyositis show a wide range of severity of proximal skeletal muscle weakness, associated with inflammatory infiltrates, vasculitis, capillary dropout, and perifascicular myofiber atrophy. Muscles of patients with dermatomyositis show signs of muscle regeneration. Because muscle stem cells (MuSCs) are responsible for myofiber repair, we wondered whether the proliferative properties of MuSCs are altered in dermatomyositis muscle. We investigated the role of type I interferon (IFN-I) in this process because dermatomyositis is associated with sustained inflammation with high IFN-I levels. MuSCs isolated from normal muscles and those from adult and juvenile patients with dermatomyositis were grown in culture and analyzed in vitro for their proliferating properties, myogenic capacities, and senescence. Gain- and loss-of-function experiments were performed to assess the role of IFN-I signaling in the proliferative capacities of MuSCs. MuSCs derived from 8 adult patients with dermatomyositis (DM-MuSCs) (5 severe form and 3 mild form, established from histologic evaluation), from 3 patients with juvenile dermatomyositis, and from normal muscle were used to analyze their myogenesis in vitro. DM-MuSCs exhibited strongly reduced proliferating capacities as compared with healthy MuSCs (-31% to -43% for mild and severe dermatomyositis, respectively), leading to poor myotube formation (-36% to -71%). DM-MuSCs were enriched in senescent, β-galactosidase-positive cells, partly explaining the proliferation defect. Gain- and loss-of-function experiments were performed to assess the role of IFN-I on the proliferative capacity of MuSCs. High concentrations of IFN-I decreased the proliferation of healthy MuSCs. Similarly, conditioned medium from DM-MuSCs decreased the proliferation of healthy MuSCs (-15% to -22%), suggesting the delivery of an autocrine effector. Pharmacologic blockade of IFN signaling (using ruxolitinib or anti-IFN receptor antibodies) in DM-MuSCs rescued their proliferation up to the control values. These results show that autocrine IFN-I signaling prevents MuSC expansion, leading to muscle repair deficit. This process may explain the persistent muscle weakness observed in patients with severe dermatomyositis.


Synthesis, physico-chemical investigations of Co(II), Ni(II) and Cu(II) complexes and their in vitro microbial, cytotoxic, DNA cleavage studies.
A series of metal complexes of cobalt(II), nickel(II), and copper(II) have been synthesized with newly derived biologically active ligands. These ligands were synthesized by the condensation of 2-amino-4-phenyl-1,3-thiazole with 8-formyl-7-hydroxy- 4-methylcoumarin. The probable structure of the complexes has been proposed on the basis of analytical and spectroscopic data (IR, UV-Vis, ESR, FAB-mass, and thermoanalytical). Electrochemical study of the complexes is also reported. Elemental analysis of the complexes confined them to stoichiometry of the type ML(2).2H(2)O [M = Co(II), Ni(II), and Cu(II)]. The Schiff base and its metal(II) complexes have been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Staphylococcus pyogenes, and Pseudomonas aeruginosa) and antifungal activities (Aspergillus niger, Aspergillus flavus, and Cladosporium) by the MIC method. The brine shrimp bioassay was carried out to study their in vitro cytotoxic properties, and also the Schiff base and its metal(II) complexes have been studied for DNA cleavage.


Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study.
The tuber of Corydalis yanhusuo is a famous traditional Chinese medicine and found to have potent pharmacological effects, such as antinociceptive, antitumor, antibacterial, anti-inflammatory, and anti-depressive activities. Although there are several methods to be developed for the analysis and detection of the bioactive ingredients' alkaloids, so far, only few prominent alkaloids could be quantified, and in vitro and in vivo changes of comprehensive alkaloids after oral administration are still little known. In this study, we first developed a simple and sensitive high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to quantify the comprehensive alkaloids of extracts of C. yanhusuo in mouse plasma, using nitidine chloride as an internal standard. As results, at least fourteen alkaloids, including an aporphine (oxoglaucine), a protopine (protopine), five tertiary alkaloids (corydaline, tetrahydroberberine, tetrahydropalmatine, tetrahydrocolumbamine, and tetrahydrocoptisine) and seven quaternary alkaloids (columbamine, palmatine, berberine, epiberberine, coptisine, jatrorrhizine, and dehydrocorydaline) could be well quantified simultaneously in mouse plasma. The lower limits of quantification were greater than, or equal to, 0.67 ng/mL, and the average matrix effects ranged from 96.4% to 114.3%. The mean extraction recoveries of quality control samples were over 71.40%, and the precision and accuracy were within the acceptable limits. All the analytes were shown to be stable under different storage conditions. Then the established method was successfully applied to investigate the pharmacokinetics of these alkaloids after oral administration of the extract of Corydalis yanhusuo in mice. To the best of our knowledge, this is the first document to report the comprehensive and simultaneous analyses of alkaloids of C. yanhusuo in mouse plasma. It was efficient and useful for comprehensive pharmacokinetic and metabolomic analyses of these complex alkaloids after drug administration.


Roles of GR Isoforms and Hsp90-binding Immunophilins in the Modulation of Glucocorticoid Biological Responses.
Glucocorticoid steroids play cardinal roles during the life span of an individual, modulating almost all aspects of the physiology, including the metabolism of carbohydrates, lipids and amino acids, as well as the immune response, neurological biology, stress adaptation, apoptosis, cell division, cell fate, inflammatory responses, etc. Glucocorticoids exert their biological effects by activation of the glucocorticoid receptor (GR), a bona fide ligand-activated transcription factor belonging to the nuclear receptor superfamily. The GR is expressed in virtually all cells of the human body showing isoformic versions and also transcription variants. GR forms oligomeric heterocomplexes that include the 90-kDa heat-shock protein (Hsp90) as an essential hub of the chaperone oligomer. The nature of chaperones associated with this heterocomplex is responsible for the modulation of the subcellular localization of the GR and its biological actions in a given tissue or cell type. In this sense, the discovery that immunophilins containing tetratricopeptide repeats (TPR) domains are responsible for the GR cytoplasmic transport mechanism and the nuclear retention half-time of the receptor opened new trends in our understanding of its complex mechanism of action. Because the properties of GR ligands influence these protein-protein interactions, specific steroid•receptor complexes may confer the GR different features providing new therapeutic opportunities to manage the disease. In this article, we analyze multiple aspects of the GR mechanism of action, some properties of the GR isoforms, and the latest findings revealing the roles of Hsp90-binding immunophilins to manage the glucocorticoid biological response.