Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer.
To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic +/- paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.


Characterization of annexin A2 in chicken follicle development: Evidence for its involvement in angiogenesis.
Annexin A2 (ANXA2) is a calcium-dependent, phospholipid-binding protein found in various cells and tissues. ANXA2 plays multiple roles in regulating cellular functions and is often over-expressed in different types of tumors including ovarian cancer. Others and we previously found that ANXA2 was up-regulated in the ovaries of hens with higher laying rate, indicated that ANXA2 is involved in avian follicle development. In this study, we found that ANXA2 mRNA expression increased during chicken ovary maturation and follicle development. In the pre-ovulatory follicles, ANXA2 expression level was significantly higher in theca cells than granulosa cells. In theca cells, ANXA2 expression could be stimulated by follicle-stimulating hormone (FSH) and estrogen but not luteinizing hormone (LH) or progesterone. The core promoter regions control the basal and FSH-induced ANXA2 gene expression were identified. Forced expression of ANXA2 could induce the expression of angiogenic factors and receptors in theca cells. Furthermore, ANXA2 overexpression resulted increased vascular endothelial growth factor A (VEGFA) secretion and theca cell proliferation. Current study not only provides the first evidence of expression and regulation of ANXA2 in chicken ovary, but also suggests that ANXA2 is involved in follicular angiogenesis and contributes to successful follicle development and ovulation.


Nanocomposites coated with xyloglucan for drug delivery: In vitro studies.
Enalaprilate (Enal), an active pharmaceutical component, was intercalated into a layered double hydroxide (Mg/Al-LDH) by an ion exchange reaction. The use of a layered double hydroxide (LDH) to release active drugs is limited by the low pH of the stomach (pH approximately 1.2), in whose condition it is readily dissolved. To overcome this limitation, xyloglucan (XG) extracted from Hymenaea courbaril (jatobá) seeds, Brazilian species, was used to protect the LDH and allow the drug to pass through the gastrointestinal tract. All the materials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, elemental analyses, transmission electronic microscopy, thermal analyses, and a kinetic study of the in vitro release was monitored by ultraviolet spectroscopy. The resulting hybrid system containing HDL-Enal-XG(3) slowly released the Enal. In an 8-h of test, the system protected 40% (w/v) of the drug. The kinetic profile showed that the drug release was a co-effect behavior, involving dissolution of inorganic material and ion exchange between the intercalated anions in the lamella and those of phosphate in the buffer solution. The nanocomposite coated protection with XG was therefore efficient in obtaining a slow release of Enal.


Factors influencing compliance with public health directives and support for government's actions against COVID-19: A Nigerian case study.
Because COVID-19 is a novel viral pandemic, there is a dearth of research in the body of evidence that explore factors that can influence compliance with public health recommendations and Nigerian government's actions to prevent the spread of COVID-19. Hence, this study's aim is to address this gap to help inform policymakers and the actions of public health leaders in Nigeria. The study included a sample of 336 adult Nigerians who responded to an online Qualtrics survey. Descriptive and linear regression analyses were conducted to determine the predictors of compliance with COVID-19 public health directives and support for government's action against COVID-19 spread. Perceived risk of stigmatization, perceived threat of COVID-19, town/city, gender, and confidence in government's ability to curb the spread and impact of COVID-19 were found to be significantly associated with compliance with COVID-19 public-health directives, and support for governments action against COVID-19. Given Nigeria's weak health system and high level of poverty, there is need to ensure the public health responses to the pandemic are effective and contextually relevant. Nigerians and other concerned global health stakeholders will benefit from research that provides more information on issues of non-compliance with COVID-19 public health directives and government actions.


Enhancement of melatonin's antigonadal action by daily injections of the serotonin uptake inhibitor fluoxetine in male hamsters.
The antigonadal effects of daily melatonin injections in golden hamsters are known to be dependent on the time of day when injections are given. As the serotonergic system of the brain has been shown to undergo daily variations, and to influence gonadotrophic activity, it was decided to investigate the relationship between melatonin effects and brain serotonergic function by employing the selective inhibitor of serotonin uptake fluoxetine (Lilly 110140). Daily injections of fluoxetine (5 mg/kg) were administered at two different times of day (late scotophase or late photophase) in combination with or without melatonin (25 micrograms) at either early or late photophase. Following nine weeks on a long photoperiod (14L/10D) testicular widths and weights in all groups receiving late-photophase melatonin were significantly diminished. Average testicular widths and weights in groups receiving fluoxetine plus late-photophase melatonin were smaller than those groups receiving late-photophase melatonin alone. Furthermore, animals receiving fluoxetine plus early-photophase melatonin also showed signs of gonadal regression. These results support the hypothesis that altered serotonergic function is a component of melatonin-induced gonadal inhibition in the male hamster.


Facile synthesis of hierarchical mesoporous weirds-like morphological MnO2 thin films on carbon cloth for high performance supercapacitor application.
The mesoporous nanostructured metal oxides have a lot of capabilities to upsurge the energy storing capacity of the supercapacitor. In present work, different nanostructured morphologies of MnO2 have been successfully fabricated on flexible carbon cloth by simple but capable hydrothermal method at different deposition temperatures. The deposition temperature has strong influence on reaction kinetics, which subsequently alters the morphology and electrochemical performance. Among different nanostructured MnO2 thin films, the mesoporous weirds composed thin film obtained at temperature of 453K exhibits excellent physical and electrochemical features for supercapacitor application. The weirds composed MnO2 thin film exhibits specific surface area of 109m2g-1, high specific capacitance of 595Fg-1 with areal capacitance of 4.16Fcm-2 at a scan rate of 5mVs-1 and high specific energy of 56.32Whkg-1. In addition to this, MnO2 weirds attain capacity retention of 87 % over 2000 CV cycles, representing better cycling stability. The enhanced electrochemical performance could be ascribed to direct growth of highly porous MnO2 weirds on carbon cloth which provide more pathways for easy diffusion of electrolyte into the interior of electroactive material. The as-fabricated electrode with improved performance could be ascribed as a potential electrode material for energy storage devices.


Possible role of carbonic anhydrase, V-H(+)-ATPase, and Cl(-)/HCO3- exchanger in electrogenic ion transport across the gills of the euryhaline crab Chasmagnathus granulatus.
We studied the participation of carbonic anhydrase (CA), V-H(+)-ATPase, and Cl(-)/HCO3- exchanger in electrogenic ion absorption through the gills of Chasmagnathus granulatus. CA activity was measured in anterior gills and posterior gills after acclimation to 2 per thousand, 10 per thousand, 30 per thousand (about seawater), and 45 per thousand salinity. The highest CA specific activity was detected in the microsomal fraction in anterior gills, and in the cytosolic fraction, in posterior ones. Both fractions were strongly induced by decreasing salinity only in posterior gills. Perfusion of posterior gills from crabs acclimated to either 2 per thousand or 10 per thousand with acetazolamide inhibited CA activity almost completely. In posterior gills from crabs acclimated to 2 per thousand and perfused with 20 per thousand saline (iso-osmotic for these crabs), acetazolamide reduced transepithelial potential difference (V(te)) by 47%, further addition of ouabain enhanced the effect to 88%. Acetazolamide had no effect in the same gills perfused with 30 per thousand saline (iso-osmotic for seawater acclimated crabs). Bafilomycin A1 and SITS (inhibitors of V-H(+)-ATPase and Cl(-)/HCO3-) reduced V(te) by 15-16% in gills perfused with normal 20 per thousand saline, and by 77% and 45%, respectively when they were applied in Na-free 20 per thousand saline, suggesting the participation of those transporters and cytosolic CA in electrogenic ion absorption.


Insulin-like growth factor-I predicts sinusoidal obstruction syndrome following pediatric hematopoietic stem cell transplantation.
Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT) initiated through damage of sinusoidal endothelium and inflammation. Insulin-like growth factor-l (IGF-l) maintains and repairs endothelium and intestinal mucosa. We hypothesized that low IGF-l levels may increase the risk of inflammatory complications, such as SOS, in HSCT-patients. We prospectively measured IGF-l concentrations in 121 pediatric patients before, during, and after allogeneic HSCT. Overall, IGF-l levels were significantly reduced compared with healthy sex- and age-matched children. IGF-I levels pre-HSCT and at day 0 were inversely associated with C-reactive protein levels, hyperbilirubinemia, and number of platelet transfusions within the first 21 days post-transplant. Low levels of IGF-I before conditioning and at day of transplant were associated with increased risk of SOS diagnosed by the modified Seattle criteria (pre-HSCT: OR = 1.7 (95% CI: 1.2-2.6, p = 0.01), and the pediatric EBMT criteria (pre-HSCT: 1.7 (1.2-2.5, p = 0.009) and day 0: 1.7 (1.3-2.5, p = 0.001)/SDS decrease in IGF-1). These data suggest that IGF-I is protective against cytotoxic damage and SOS, most likely through trophic effects on endothelial cells and anti-inflammatory properties, and may prove useful as a predictive biomarker of SOS.


Biologic heterogeneity of human immunodeficiency virus type 2 (HIV-2) strains.
Seven HIV-2 isolates recovered from peripheral blood mononuclear cells (PBMC) of patients from the Ivory Coast have been biologically characterized. All seven strains replicated well in primary human lymphocyte and macrophage cultures and in established human T cell lines. They showed differences in infectivity and replicating ability in primary PBMC cultures from chimpanzees, rhesus macaques, and baboons. Moreover, variations in levels of virus replication in PBMC from 13 seronegative donors were observed. Four strains (UC2, UC3, UC7, and UC8) were highly cytopathic and caused extensive surface CD4 antigen depletion in acutely infected PBMC and SupT1 cells. Two strains (UC1 and UC6) showed minimal or no cytopathology, no CD4 down-modulation, and much lower levels of virus protein expression in SupT1 cells. These findings reflect the heterogeneity of HIV-2 strains and suggest that these biological properties could influence pathogenesis in the host.


Linomide suppresses chronic-relapsing experimental autoimmune encephalomyelitis in DA rats.
Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on chronic progressive and/or relapsing experimental autoimmune encephalomyelitis (PR-EAE), a CD4+ T cell mediated animal model of multiple sclerosis (MS). PR-EAE induced in DA rats by inoculation with homogenized guinea pig spinal cord and Freund's complete adjuvant, was strongly suppressed by Linomide administered daily subcutaneously from the day of inoculation. Linomide dose-dependently delayed the interval between immunization and onset of clinical PR-EAE, reduced severity and relapse of clinical PR-EAE, and shortened clinical PR-EAE. These clinical effects were associated with the down-modulation of CNS antigen-induced T cell responses and production of proinflammatory cytokines (IFN-gamma and TNF-alpha) as well as with upregulation of IL-4 (except in spleen MNC), IL-10 and TGF-beta in both spleen MNC and the spinal cord. These effects indicate that Linomide can suppress PR-EAE and may mediate its suppressive effects by regulation of cytokines.


Regionally defective colonization of the terminal bowel by the precursors of enteric neurons in lethal spotted mutant mice.
In order to gain insight into the process of colonization of the bowel by the neural crest-derived precursors of enteric neurons, the development of the enteric nervous system was examined in lethal spotted mutant mice, a strain in which a segment of bowel is congenitally aganglionic. In addition, nerve fibers within the ganglionic and aganglionic zones of the gut of adult mutant mice were investigated with respect to their content of acetylcholinesterase, immunoreactive substance P, vasoactive intestinal polypeptide and serotonin, and their ability to take up [3H]serotonin. In both the fetal gut of developing mutant mice and in the mature bowel of adult animals abnormalities were limited to the terminal 2 mm of colon. The enteric nervous system in the proximal alimentary tract was indistinguishable from that of control animals for all of the parameters examined. In the terminal bowel, the normal plexiform pattern of the innervation and ganglion cell bodies were replaced by a coarse reticulum of nerve fibers that stained for acetylcholineserase and were continuous with extrinsic nerves running between the colon and the pelvic plexus. These coarse nerve bundles contained greatly reduced numbers of fibers that displayed substance P- and vasoactive intestinal polypeptide-like immunoreactivity, but a serotonergic innervation was totally missing from the aganglionic bowel. During development, acetylcholineserase and uptake of [3H]serotonin appeared in neural elements in the forgut of mutant mice on the 12th day of embryonic life (E12), about the same time these markers appeared in the forgut in normal mice. By day E14, neurons expressing one or the other marker were recognizable as far distally as about 2 mm from the anus. The appearance of neurons in segments of gut grown for 2 weeks as explants in culture was used as an assay for the presence of neuronal progenitor cells in the segments of fetal bowel at the time of explantation. Both acetylcholinesterase activity and uptake of [3H]serotonin developed in neurons in vitro in explants of proximal bowel between days E10 and E17. At all times, however, the terminal 2 mm of mutant but not normal fetal gut gave rise to aneuronal cultures. In some mutant mice rare, small, ectopically-situated pelvic ganglia were found just outside aganglionic segments of fetal colon. Uptake of [3H]serotonin, normally a marker for intrinsic enteric neurites, was found in these ganglia. The experiments support the hypothesis that the terminal 2 mm of the gut in lethal spotted mutant mice is intrinsically abnormal and thus cannot be colonized by the precursors of enteric neurons.(ABSTRACT TRUNCATED AT 400 WORDS)


Report of dental society program activity regarding liaison with dental assisting, hygiene, and laboratory technology organizations. Council on Dental Practice.
With underlying changes in population demographics and dental practice patterns, as discussed in the joint report (Reports 1988: 117), there appears to be an increased need to continue to monitor and develop activities related to dental staff manpower. Results of this liaison survey can be used to assist in that manpower planning. It can be seen from these survey responses that constituent and component dental societies are logically dividing the program activities among the ADA, state, and local groups. For example, ADA and national resources are available for overall problem identification and membership surveys. States are primarily conducting committee meetings with organizations, publishing articles and presenting seminars. Activities such as health fairs and scholarship programs are easily developed and conducted locally. States are urged to communicate freely with local and ADA organizations to ensure that duplication of activities and resources is minimized.


An improved method for sampling and analytical measurement of aerosol platinum in ambient air and workplace environments.
In this study we critically examined with both field and laboratory experiments key components of extant methods for measurement of aerosol soluble platinum in ambient air and workplace environments. Our goal was to develop an improved method for soluble platinum measurement that could be readily implemented in the field and laboratory using readily available modern analytical tools, and in parallel provide insight into factors influencing the robustness of specific aspects of measurement methods for soluble platinum. Experiments addressed sampler type, filter media and pre-cleaning, extraction solvent and volume, extraction time & energy and materials composition, with the objective of optimizing each specific component and promulgating strategies for improving signal/noise and precision. We used basic clean-room protocols and applied ICPMS tools to address these objectives. We document a method that provides for measurement of soluble platinum at the 0.02 ng/m3 level (8-h sample at 2 L/min). Of the four samplers evaluated (IOM, closed-face cassette, and two parallel particle impactors), the IOM exhibited the best precision. The three filter substrates evaluated (Teflon, MCE, PVC) performed similarly in most challenges, however, overall, we conclude that MCE media is the most robust collection substrate for soluble platinum measurements. To achieve the lowest detection levels, it is critical to pre-clean the filter substrates. The use of a 0.07 M HCl extractant (in preference to a water extractant) is recommended - platinum recoveries, particularly from real-world samples, are higher and more consistent with the HCl extractant. The outcomes of the extraction kinetics experiments suggest that an extraction time of 60 min may improve the method performance with 0.07 M HCl but degrade the performance with water, in comparison with a 30-min extraction period. The use of sonication in preference to a table-top shaker is recommended for energy input during extraction.


GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3.
The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guérin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse is determined. Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaffected. The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-surface gangliosides. The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.


Effects of Different Freezing Protocols on Motility, Viability, Mitochondrial Membrane Potential, Intracellular Calcium Level, and DNA Integrity of Cryopreserved Equine Epididymal Sperm.
The aim of the present study was to evaluate the effect of different freezing procedures on sperm motion, viability, the acrosome status, mitochondrial membrane potential (MMP), intracellular calcium content, and DNA integrity on epididymal stallion sperm. Therefore, the sperm of 10 healthy stallions was harvested by retrograde flushing after testectomy, diluted with a semen extender containing defined milk proteins and a freezing extender containing egg yolk and glycerol and frozen according to 4 different protocols, using a programmable freezer and a floating rack performing a slow (processes 1 and 2) or a fast cooling rate (processes 3 and 4, respectively). Post-thaw total motility and slow sperm values were lower when using process 4 compared with processes 1 and 2 (P < .05) after 1 hour of incubation. Progressive motility was lower in process 4 compared with process 1 immediately after thawing and after 1 hour of incubation (P < .05). The amount of rapid sperm was lower when using process 4 compared with process 1 immediately after thawing (P < .05). After 1 hour of incubation, the amount of rapid sperm was lower when using process 4 compared with processes 1 and 2 (P < .05). Higher values for viable sperm were seen in processes 1 and 2 compared with process 4 (P < .05) after 1 hour of incubation. Immediately after thawing, more viable sperm with high MMP (hMMP) were observed when using process 3 compared with process 2 (P < .05). After 1 hour of incubation, a significantly higher amount of viable hMMP sperm were detected when using processes 1 and 2 compared with process 4 (P < .05). Process 2 yielded a lower percentage of sperm containing low calcium (lCa) than process 3 immediately after thawing (P < .05). After 1 hour of incubation, the lowest amount of lCa sperm was observed using process 4 (P < .05). The subpopulation of viable/hMMP/lCa sperm was higher when using process 3 compared with process 2 immediately after thawing (P < .05). After 1 hour of incubation, the lowest amount of this subpopulation was detected in process 4 (P < .05). The DNA integrity was similar in all groups. In conclusion, a slow cooling rate with a controlled rate freezer resulted in best sperm quality after thawing. Using a floating rack in nitrogen vapor as an alternative to a programmable freezer, equilibration in a cooled environment is advantageous.


Synthesis and identification of a new class of antileukemic agents containing 2-(arylcarboxamide)-(S)-6-amino-4,5,6,7-tetrahydrobenzo[d]thiazole.
Recently we have reported the effect of (S)-6-aryl urea/thiourea substituted-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazole derivatives as potent anti-leukemic agents. To elucidate further the Structure Activity Relationship (SAR) studies on the anti-leukemic activity of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzo[d]thiazole moiety, a series of 2-arlycarboxamide substituted-(S)-6-amino-4,5,6,7-tetrahydrobenzo[d]thiazole were designed, synthesized and evaluated for their anti-leukemic activity by trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) assays and cell cycle analysis. Results suggest that the position, number and bulkiness of the substituent on the phenyl ring of aryl carboxamide moiety at 2nd position of 6-amino-4,5,6,7-tetrhydrobenzo[d]thiazole play a key role in inhibiting the proliferation of leukemia cells. Compounds with ortho substitution showed poor activity and with meta and para substitution showed good activity.


Origin of phasic synaptic inhibition in myotomal motoneurons during fictive locomotion in the lamprey.
The periodic membrane potential fluctuations in motoneurons during fictive locomotion in the lamprey, a primitive vertebrate, involve phasic synaptic excitation and inhibition. This paper investigates the origin of the phasic synaptic input to lamprey myotomal motoneurons in the in vitro spinal cord preparation with regard to the relative contribution of descending propriospinal input from interneurons in the local segment. The synaptic drive to myotomal motoneurons in the most rostral and the most caudal part of the spinal cord preparation are compared before and after selective spinal cord lesions. Current clamp recordings of the same cell before and after lesion showed that neither the excitatory phase nor the inhibitory phase was abolished after interruption of the descending or the ascending ipsilateral input, or after interrupting crossing segmental input by a local longitudinal midline incision. None of these sources thus appears to be alone responsible for the phasic synaptic drive. To quantitatively evaluate these effects, and in particular the contribution from the descending propriospinal fibres to the inhibitory phase, voltage clamp recordings were made in combination with a spinal cord hemisection just rostral to the motoneuron. The input from propriospinal interneurons in approximately 15 rostral segments may be responsible for as much as 70% of the phase of inhibitory current during the locomotor cycle. In accordance with these findings, a similar voltage clamp analysis of rostrally and caudally located motoneurons showed that the average peak-to-peak amplitude of the current fluctuations in rostral cells was approximately 50% of that in caudal cells.


IgG4-Related Disease Manifested as Cutaneous Plasmacytosis: A Case Report.
IgG4-related disease (IgG4-RD) is a rare fibroinflammatory disease that has a high tendency to misdiagnosis in clinics. A 48-year-old man developed a rash with progressive itching 3 years ago after hormone therapy for an ocular "inflammatory pseudotumor". The disease condition of this patient involved multiple organs which involved the skin. The patient was misdiagnosed with other diseases during the period of hospitalization, leading to poor therapeutic effects and repeated skin lesions. The dermatopathological report indicated plasma cell proliferative disorder, with IgG4/IgG exceeding 40% and abnormally elevated serum IgG4 levels. After the patient was diagnosed with IgG4-RD, a series of treatments improved skin lesions, relieved other symptoms, and decreased serum IgG4 levels. IgG4-RD is a highly misdiagnosed disease that deserves the attention of physicians. The patient we reported could be considered a representative case of IgG4-RD that presents with skin lesions. For patients with suspected IgG4-RD, serum IgG4 testing should be performed, and further imaging, serological tests, and pathology examinations are needed to exclude malignancy, infection, and autoimmune diseases.


Wisconsin's laboratory evaluation and certification program.
A review of methods used in the evaluation of test performance and certification of laboratories in Wisconsin.


Qi-Wei-Du-Qi-Wan and its major constituents exert an anti-asthmatic effect by inhibiting mast cell degranulation.
In Asia, Qi-Wei-Du-Qi-Wan (QWDQW) is a traditional Chinese medicine that has been used to treat chest tightness, cough, shortness of breath, night sweats, frequent urination and asthma. QWDQW is recorded in Yi Zong Yi Ren Pian (Medical Physician's Compilation), which was written by Yang Cheng Liu during the Qing Dynasty. The traditional Chinese medicine QWDQW is composed of 7 ingredients and has been used in the treatment of asthma in Asia for hundreds of years. However, the mechanism through which QWDQW affects the immune system in the treatment of asthma is not known. Therefore, this study aimed to investigate whether QWDQW alleviates asthmatic symptoms in mice with chronic asthma induced by repeated stimulation with Dermatophagoides pteronyssinus (Der p) and to explore the underlying immune modulatory mechanism. BALB/c mice were stimulated intratracheally (i.t.) with Der p (40 μl, 2.5 μg/μl) once weekly for 6 weeks. Thirty minutes prior to Der p stimulation, the mice were treated with QWDQW (0.5 g/kg and 0.17 g/kg) orally. Three days after the last stimulation, the mice were sacrificed, and infiltration of inflammatory cells, lung histological characteristics, gene expression of lung and serum total IgE were assessed. In other experiments, RBL-2H3 cells were stimulated with DNP-IgE/DNP-BSA and then treated with QWDQW, quercetin, β-carotene, luteolin or a mixture of the three chemicals (Mix13) for 30 min, and the effects of the drugs on RBL-2H3 cell degranulation after DNP stimulation were determined. QWDQW significantly reduced Der p-induced airway hyperreactivity (AHR) and decreased total serum IgE and Der p-specific IgE levels. Histopathological examination showed that QWDQW reduced inflammatory cell infiltration and sputum secretion from goblet cells in the lungs. Gene expression analysis indicated that QWDQW reduced overproduction of IL-12、IFN-γ、IL-13、IL-4、RNATES、Eotaxin and MCP-1in lung. Additionally, QWDQW and Mix13 suppressed DNP induced RBL-2H3 degranulation, and the effect was maximal when quercetin, β-carotene and luteolin were administered together. These results indicate that QWDQW plays a role in suppressing excessive airway reaction and in specific immune modulation in a mouse model of chronic asthma and that QWDQW suppresses mast cell degranulation at defined doses of quercetin, β-carotene and luteolin.


The formation of reactive intermediates in the MAO-catalyzed oxidation of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Oxidation of MPTP by monoamine oxidase (MAO), leading to the formation of reactive metabolites, is a critical step in the expression of the nigrostriatal toxicity of this molecule. A catalytic mechanism for the 2-electron oxidation of MPTP to MPDP+ and for the further 2-electron oxidation of MPDP+ to MPP+ is proposed, involving the formation of carbon-centered radical intermediates. These radical species appear to be involved in the mechanism-based inactivation of MAO by MPTP, possibly by generating 1,4-dihydropyridine adducts with the enzyme apoprotein or its coenzyme FAD. The pathways of metabolism of MPTP in brain and peripheral tissues and the active accumulation of metabolites of MPTP in dopaminergic neurons are discussed in terms of their possible contribution to the selective cytotoxicity of the compound.


The nuclear localization of Drosophila Hsp27 is dependent on a monopartite arginine-rich NLS and is uncoupled from its association to nuclear speckles.
Drosophila Hsp27 is a small heat shock protein displaying exclusive nuclear localization both before and after heat shock. However, the mechanism implicated in this nuclear localization as well as the required sequences, are undefined. This study identifies the Hsp27 sequences mediating its nuclear localization. The generation of chimeric fusions between Hsp27 and Hsp23, a small heat shock protein displaying exclusive cytoplasmic localization, delineated a stretch of 15 amino acids containing a nuclear-targeting activity. Site-directed mutagenesis within this region unveiled the implication of three arginine residues (R54-R55-R56), which differentially combine to form a novel kind of nuclear localization signal (NLS). Abrogation of the nuclear localization signal activity indicated that Drosophila Hsp27 could still enter the nucleus to associate with nuclear speckles in a NLS-independent fashion. Mutagenesis of a putative nuclear export signal unveiled two leucine residues (L50 and L52) specifically involved in the association of Hsp27 to nuclear speckles and revealed novel nuclear structures formed by this Hsp27 mutant. The present study identifies two distinct sets of sequences respectively mediating the nuclear import of Hsp27 and its association to nuclear speckles. These two phenomena are uncoupled and can be separately abrogated.


Response of bacterial diversity and community structure to metals in mangrove sediments from South China.
Human activities have given rise to metal contamination in the constituents of mangrove ecosystems, posing a critical threat to sediment microorganisms; hence, it is of great importance to comprehend the effects of metals on the microbial communities in mangrove sediments. This study was the first to explore the response of the bacterial diversity and community structure to nine metals (As, Co, Cr, Cu, Mn, Ni, Pb, V and Zn) and organic matter fractions (including total organic carbon (TOC), total nitrogen (TN), and total sulfur (TS)) in mangrove wetlands from Zhanjiang, China, using 16S rRNA high-throughput sequencing technology and Spearman correlation analysis. The results showed that these nine metals were scattered differently in different mangrove sediments, and the metals and organic matter fractions jointly affected the bacterial communities in the sediments. Several metals displayed significant positive correlations with the abundances of the phylum Bacteroidetes and the genera Actibacter and Sphingobacterium but significant negative correlations with the abundances of two genera Holophaga and Caldithrix. Furthermore, the abundances of the phylum Actinobacteria and many bacterial genera showed significant positive or negative responses to the levels of the three organic matter fractions. Interestingly, the levels of a number of bacterial genera that exhibited increased abundance with high levels of metals and TS might be reduced with high TOC and TN, and vice versa: the levels of genera that exhibited decreased abundance with high levels of metals and TS might be increased with high TOC and TN. Overall, many bacterial groups showed different response patterns to each metal or organic matter fraction, and these metals together with organic matter fractions influenced the bacterial diversity and community structure in mangrove sediments.


A parametric imaging approach for the segmentation of ultrasound data.
When an ultrasonic examination is performed, a segmentation tool would often be very useful, either for the detection of pathologies, the early diagnosis of cancer or the follow-up of the lesions. Such a tool must be both reliable and accurate. However, because of the relatively reduced quality of ultrasound images due to the speckled texture, the segmentation of ultrasound data is a difficult task. We have previously proposed to tackle the problem using a multiresolution Bayesian region-based algorithm. For computation time purposes, a multiresolution version has been implemented. In order to improve the quality of the segmentation, we propose to perform the segmentation not only from the envelope image but to combine more information about the properties of the tissues in the segmentation process. Several acoustical parameters have thus been computed, either directly from the images or from the radio-frequency (RF) signal. In a previous study, two parametric images were involved in the segmentation process. The parameter represented the integrated backscatter (IBS) and the mean central frequency (MCF), which is a measurement related to the attenuation of ultrasound waves in the media. In this study, parameters representative of the scattering conditions in the tissue are evaluated in the multiparametric segmentation process. They are extracted from the K-distribution (alpha,b) and the Nakagami distribution (m,Omega) and are related to the local density of scatterers (alpha,m), the size of the scatterers (b) and the backscattering properties of the medium (Omega). The acoustical features are calculated locally on a sliding window. This procedure allows to built parametric mapping representing the particular characteristics of the medium. To test the influence of the acoustical parameters in the segmentation process, a set of numerical phantoms has been computed using the Field software developed by J.A. Jensen. Each phantom consists in two regions with two different acoustical properties: the density of scatterers and the scattering amplitude. From both the simulated RF signals and envelope images, the parameters have been computed; their relevance to represent a particular characteristic of the medium is evaluated. The segmentation has been processed for each phantom. The ability of each parameter to improve the segmentation results is validated. A agar-gel phantom has also been created, in order to test the accuracy of the parameters in conditions closer to the in vivo ultrasound imaging. This phantom contains four inclusions with different concentrations of silica. A B&K ultrasound device provides the RF data. The quantification of the segmentation quality is based on the rate of correctly classified pixels and it has been computed for all the parameters either from the field images or the phantom images. The large improvement in the segmentation results obtained reveals that the multiparametric segmentation scheme proposed in this study can be a reliable tool for the processing of noisy ultrasound data.


Pairwise shared genomic segment analysis in high-risk pedigrees: application to Genetic Analysis Workshop 17 exome-sequencing SNP data.
We applied our method of pairwise shared genomic segment (pSGS) analysis to high-risk pedigrees identified from the Genetic Analysis Workshop 17 (GAW17) mini-exome sequencing data set. The original shared genomic segment method focused on identifying regions shared by all case subjects in a pedigree; thus it can be sensitive to sporadic cases. Our new method examines sharing among all pairs of case subjects in a high-risk pedigree and then uses the mean sharing as the test statistic; in addition, the significance is assessed empirically based on the pedigree structure and linkage disequilibrium pattern of the single-nucleotide polymorphisms. Using all GAW17 replicates, we identified 18 unilineal high-risk pedigrees that contained excess disease (p < 0.01) and at least 15 meioses between case subjects. Eighteen rare causal variants were polymorphic in this set of pedigrees. Based on a significance threshold of 0.001, 72.2% (13/18) of these pedigrees were successfully identified with at least one region that contains a true causal variant. The regions identified included 4 of the possible 18 polymorphic causal variants. On average, 1.1 true positives and 1.7 false positives were identified per pedigree. In conclusion, we have demonstrated the potential of our new pSGS method for localizing rare disease causal variants in common disease using high-risk pedigrees and exome sequence data.


Testosterone metabolism in neuroendocrine organs in male rats under atrazine and deethylatrazine influence.
The inhibitory influence of atrazine and deethylatrazine on testosterone metabolism in male rat anterior pituitary and hypothalamus were studied under in vivo and in vitro experimental conditions. In vivo strong influence of atrazine (12 mg/100 g by wt. daily during 7 days) on 5 alpha-R, 3 alpha- and 17 beta-HSD activities was detected in the anterior pituitary. This dose provokes a significant increase in the weight of the pituitary gland, with hyperemia and hypertrophy of chromophobic cells with vacuolar degeneration. In vivo treatment of male rats with the same dose of deethylatrazine markedly inhibited 5 alpha-R activity in the anterior pituitary. The rate of 5 alpha-R activity inhibition in the anterior pituitary was the same after in vivo treatment with atrazine (37.3%) as with deethylatrazine (33.9%). This could suggest that the mechanism of inhibition of deethylatrazine is similar to that of atrazine. In vitro atrazine or deethylatrazine addition into the incubation medium significantly (P less than 0.01) inhibited 5 alpha-R, 3 alpha- and 17 beta-HSD activities in the anterior pituitary. The inhibition of 5 alpha-R activity was marked more by atrazine than deethylatrazine, while 3 alpha- and 17 beta-HSD activities were inhibited at the same rate. In vivo treatment with the same dose of atrazine or deethylatrazine (12 mg/100 g by wt daily 7 days) significantly inhibited (P less than 0.01) 5 alpha-R and 17 beta-HSD at the male rat hypothalamic level. 3 alpha-HSD activity inhibition was not significant for either compound. The in vitro addition of deethylatrazine was much more effective (P less than 0.01) in inhibiting 5 alpha-R, 3 alpha- and 17 beta-HSD in male rat hypothalamus than atrazine. In spite of this, deethylatrazine seems to be less toxic in in vivo experiments due to its higher polarity and faster biodegradation.


Short-term variability of pulmonary function tests in infants with bronchopulmonary dysplasia.
We determined the short-term variability of pulmonary function in infants recovering from bronchopulmonary dysplasia. Sixteen infants with birth weight of 1,231 +/- 929 grams (mean +/- SD) and gestational age of 29 +/- 4 weeks were studied twice at 17 +/- 8 weeks postnatally at intervals of 4 to 8 days during a period of clinical stability. The infants were still on supplemental oxygen but were off diuretics and bronchodilators. We used a modification of the rapid thoracic compression method to measure forced expiratory flow (Vmax FRC) and the time constant (tau) of expiratory flow at functional residual capacity. Thoracic gas volume (TGV), mean and total airway resistance (RawM and RawT), and mean and total specific airway conductance (SGawM and SGawT) were measured in a whole body pressure plethysmograph. An esophageal balloon was used to measure dynamic pulmonary compliance (Cdyn). Variabilities were defined as the standard deviation of percent changes between the first and second tests. They were 30% for VmaxFRC, 23% for tau, 12% for TGV, 20% for RawM, 35% for RawT, 25% for SGawM, 72% for SGawT, and 23% for Cdyn. All these tests are useful in assessing pulmonary function of infants with BPD; however, their variability must be taken into account when interpreting short-term changes.


Forward-reflected-backward method with variance reduction.
We propose a variance reduced algorithm for solving monotone variational inequalities. Without assuming strong monotonicity, cocoercivity, or boundedness of the domain, we prove almost sure convergence of the iterates generated by the algorithm to a solution. In the monotone case, the ergodic average converges with the optimal O(1/k) rate of convergence. When strong monotonicity is assumed, the algorithm converges linearly, without requiring the knowledge of strong monotonicity constant. We finalize with extensions and applications of our results to monotone inclusions, a class of non-monotone variational inequalities and Bregman projections.


Prognosis of women with primary breast cancer diagnosed during pregnancy: results from an international collaborative study.
We aimed to determine the prognosis of patients with breast cancer diagnosed during pregnancy (BCP). In this cohort study, a multicentric registry of patients with BCP (from Cancer in Pregnancy, Leuven, Belgium, and GBG 29/BIG 02-03) compiled pro- and retrospectively between 2003 and 2011 was compared with patients who did not have associated pregnancies, using an age limit of 45 years. Patients with a diagnosis postpartum were excluded. The main analysis was performed using Cox proportional hazards regression of disease-free survival (DFS) and overall survival (OS) on exposure (pregnant or not), adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status, histology, type of chemotherapy, use of trastuzumab, radiotherapy, and hormone therapy. The registry contained 447 women with BCP, mainly originating from Germany and Belgium, of whom 311 (69.6%) were eligible for analysis. The nonpregnant group consisted of 865 women. Median age was 33 years for the pregnant and 41 years for the nonpregnant patients. Median follow-up was 61 months. The hazard ratio of pregnancy was 1.34 (95% CI, 0.93 to 1.91; P = .14) for DFS and 1.19 (95% CI, 0.73 to 1.93; P = .51) for OS. Cox regression estimated that the 5-year DFS rate for pregnant patients would have increased from 65% to 71% if these patients had not been pregnant. Likewise, the 5-year OS rate would have increased from 78% to 81%. The results show similar OS for patients diagnosed with BCP compared with nonpregnant patients. This information is important when patients are counseled and supports the option to start treatment with continuation of pregnancy.


The use of a non-lethal tool for evaluating toxicological hazard of organochlorine contaminants in Mediterranean cetaceans: new data 10 years after the first paper published in MPB.
In the Mediterranean Sea, top predators, and particularly cetacean odontocetes, accumulate high concentrations of organochlorine contaminants and toxic metals, incurring high toxicological risk. In this paper we investigate the use of the skin biopsies as a non-lethal tool for evaluating toxicological hazard of organochlorines in Mediterranean cetaceans, presenting new data 10 years after the paper published by Fossi and co-workers [Mar. Poll. Bull. 24 (9) (1992) 459] in which this new methodology was first presented. Some organochlorine compounds, now with worldwide distribution, are known as endocrine disrupting chemicals (EDCs). Here the unexplored hypothesis that Mediterranean cetaceans are potentially at risk due to organochlorines with endocrine disrupting capacity is investigated. High concentrations of DDT metabolites and PCB congeners (known as EDCs) were found in the different Mediterranean species (Stenella coeruleoalba, Delphinus delphis, Tursiops truncatus and Balaenoptera physalus). In this paper we also propose benzo(a)pyrene monooxygenase (BPMO) activity in marine mammal skin biopsies (non-lethal biomarker) as a potential indicator of exposure to organochlorines, with special reference to the compounds with endocrine disrupting capacity. A statistically significant correlation was found between BPMO activity and organochlorine levels (DDTs, pp(')DDT, op(')DDT, PCBs and PCB99) in skin biopsies of males of B. physalus. Moreover a statistical correlation was also found between BPMO activity and DDT levels in skin biopsies of the endangered Mediterranean population of D. delphis. These results suggest that BPMO induction may be an early sign of exposure to organochlorine EDCs and can be used for periodic monitoring of Mediterranean marine mammal toxicological status.


Cardiac death in mucocutaneous lymph node syndrome.
A 12 year old boy had 4 symptom-free years after hospitalization for acute febrile mucocutaneous lymph node syndrome before he died suddenly from extensive myocardial infarction. Current evidence suggests that many patients with this syndrome have coronary artery disease and that those with significant cardiac findings should be studied with coronary angiography. Serial studies are recommended because of the danger of sudden death.


Segmental Testicular Infarction: Case Series and Literature Review of a Rare Diagnosis in Men with Acute Testicular Pain.
The incidence of segmental testicular infarction (STI) is very low. Such a disorder most often affects young men. The most common symptom is sudden testicular pain. We report 6 cases of men diagnosed with STI. Clinical examination, blood test, urine analysis, and ultrasound examination with colour Doppler were performed. Furthermore, tissue sonoelastography or MRI was performed in selected patients. All men underwent surgical exploration. In all but one man, the affected testis was preserved. Although STI is a rare condition, it should be taken into account if testicular pain prior to suspicious ultrasound imaging occurs. To be aware of this benign testicular pathology and its clinical and imaging features is important to avoid unnecessary orchiectomies in young patients.


Neuropathology of epilepsy.
Epilepsy is one of the most common neurologic disorders, affecting about 50 million people worldwide. The disease is characterized by recurrent seizures, which are due to aberrant neuronal networks resulting in synchronous discharges. The term epilepsy encompasses a large spectrum of syndromes and diseases with different etiopathogenesis. The recent development of imaging and epilepsy surgery techniques is now enabling the identification of structural abnormalities that are part of the epileptic network, and the removal of these lesions may result in control of seizures. Access of this clinically well-characterized neurosurgical material has provided neuropathologists with the opportunity to study a variety of structural brain abnormalities associated with epilepsy, by combining traditional routine histopathologic methods with molecular genetics and functional analysis of the resected tissue. This approach has contributed greatly to a better diagnosis and classification of these structural lesions, and has provided important new insights into their pathogenesis and epileptogenesis. The present chapter provides a detailed description of the large spectrum of histopathologic findings encountered in epilepsy surgery patients, addressing in particular the nonneoplastic pathologies, including hippocampal sclerosis, malformations of cortical development, Sturge-Weber syndrome, and Rasmussen encephalitis, and reviews current knowledge regarding the underlying molecular pathomechanisms and cellular mechanisms mediating hyperexcitability.


Diastereomer-differentiating hydrolysis of 1,3-diol-acetonides: a simplified procedure for the separation of syn- and anti-1,3-diols.
[reaction: see text] A new method to facilitate the separation of diastereomeric syn- and anti-1,3-diols is described. The method relies on the different hydrolysis rates of the corresponding diastereomeric acetonides. Treatment of a dichloromethane solution of syn- and anti-1,3-diol-acetonide with a catalytic amount of diluted aqueous hydrochloric acid leads to the selective cleavage of the anti diastereomer. The resulting anti-1,3-diol can be easily separated from the unchanged syn-1,3-diol-acetonide.


Evaluation of staining techniques, antigen detection and nested PCR for the diagnosis of cryptosporidiosis in HIV seropositive and seronegative patients.
The study was designed to determine the efficacy of modified Ziehl-Neelsen (ZN), safranine methylene blue (SM) staining, antigen detection ELISA and a nested PCR assay (specific for Cryptosporidium parvum) for detection of Cryptosporidium in HIV seropositive and seronegative patients with diarrhoea. Cryptosporidium was detected in 10 (4.9%), 9 (4.4%), 39 (18.9%) and 27 (13.1%) of 206 HIV seropositive and 7 (4.6%), 6 (3.9%), 21 (13.7%) and 17 (11.1%) of 153 HIV seronegative patients by ZN staining, SM staining, antigen detection ELISA and PCR, respectively. None of the 50 apparently healthy control subjects was found to be infected with Cryptosporidium by any of the techniques. Based on the criteria of 'true positive' samples positive by at least any two techniques out of ZN staining, antigen detection and PCR, sensitivity of ZN and SM staining techniques was 37% and 33.3% in HIV seropositive and 41.2% and 35.3% in seronegative patients, respectively. Sensitivity of antigen detection ELISA was 92.6% and 94.1% in HIV seropositive and seronegative patients, respectively, while sensitivity of PCR was 100% each in HIV seropositive and seronegative patients. Specificity of all three techniques, i.e. ZN, SM staining and PCR was 100% in both HIV seropositive and seronegative patients while specificity of antigen detection was 92.2% and 96.3% in HIV seropositive and seronegative patients, respectively. The staining techniques were found less sensitive as compared to antigen detection and PCR for detection of Cryptosporidium in HIV seropositive patients with CD4 count >200cells/microl.


Updates in the Pharmacologic Prophylaxis and Treatment of Invasive Candidiasis in the Pediatric and Neonatal Intensive Care Units: Updates in the Pharmacologic Prophylaxis.
The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United States Food and Drug Administration (FDA) for use in infants < 4 months of age. Prophylactic strategies in the PICU could include zinc and vitamin D. Anidulafungin has recent non-comparative data supporting use in pediatric patients older than 1 month of age and also has a recent FDA approval for use in children 1 month of age and older. Fluconazole prophylaxis remains a reasonable strategy in select NICU patients, although further analyses of resistance and the optimal dosage regimen are needed. Echinocandins are potential therapeutic options for non-meningitis or urinary tract infections in both the neonatal and pediatric population.


[Unilateral benign choanal polyp: review of 51 patients].
Choanal polyps are a benign pathology arising in the sinusal mucosa and entering the nasal fossa heading for the choana. It is a unilateral condition mainly affecting young people. It must be surgically removed, with exeresis of both the nasal and the sinusal lesions. A retrospective review has been made of 51 patients treated for choanal polyp at our centre. They were diagnosed through physical examination, nasal endoscopy, nasosinusal CT, and histological examination of biopsy from the mass in selected cases. The choanal polyps originated in the maxillary sinus in 46 cases, in the ethmoidal sinus of 5 patients, and only 1 in the sphenoid sinus. Antrochoanal and ethmoidochoanal polyps were simultaneously found in 1 patient. Unilateral nasal obstruction was the main clinical presentation in our series. Nasal discharge, epistaxis, and snoring were other initial clinical findings. Eighty-five per cent (39/46) of antrochoanal polyps (ACP) emerged into the nasal fossa through Giraldés's accessory orifice, and 15% (7/46) through the natural ostium of the sinus. The origin in the maxillary sinus was adequately documented in 18 cases. The endoscopic approach was used in 46 patients. Other options employed were the Caldwell-Luc approach and a combination of limited antrostomy and endoscopic nasal surgery; these were among the first cases seen and therefore the oldest. Two of them relapsed and were treated again with an endoscopic nasosinusal approach. Endoscopic nasosinusal surgery is a safe and effective option and represents the approach of choice for the treatment of this pathology.


Surface Engineering of Triboelectric Nanogenerator with an Electrodeposited Gold Nanoflower Structure.
A triboelectric nanogenerator composed of gold nanoflowers is demonstrated. The proposed triboelectric nanogenerator creates electricity by contact-separation-based electrification between an anodic metal and a cathodic polymer. For the improvement of output power via the enlargement of the effective surface area in the anodic metal, gold nanoflowers that produce a hierarchical morphology at a micro-to-nano scale by electrodeposition are utilized. The hierarchical morphology is controlled by the applied voltage and deposition time. Even though the triboelectric coefficient of gold is inferior to those of other metals, gold is very attractive to make a flower-like structure by electrodeposition. Moreover, gold is stable against oxidation by oxygen in air. From a reliability and practicality point of view, the aforementioned stability against oxidation is preferred.


Anti-crease finishing of cotton fabrics based on crosslinking of cellulose with acryloyl malic acid.
Maleic acid (MA) has been explored to replace formaldehyde-based dimethylol dihydroxy ethylene urea (DMDHEU) for cotton anti-crease finishing. However, the resilience of treated fabrics was not satisfactorily improved. In this study, acryloyl malic acid (AMA) was synthesized and applied on fabrics as a novel crosslinking agent. The results showed that both crease recovery angle and whiteness index of treated samples were higher than those of MA in the presence/absence of catalyst sodium hypophosphite (SHP). Chemical structure of AMA was confirmed by NMR and MS spectra. The possible crosslinking mechanism between AMA and cellulose was investigated by means of (13)C NMR, MS, FTIR and phosphorus content analyses. It was found that AMA could form ester bonds with cellulose by formation of anhydride intermediate. Meanwhile, additional reaction of double bonds on AMA with another molecule or PH of SHP residual has also contributed to the crosslinking. A reaction equation was proposed based on the analyses.


American Society for Transplantation and Cellular Therapy Guidelines for Fellowship Training in Hematopoietic Cell Transplantation and Immune Effector Cell Therapy.
Rapid advances in the field of hematopoietic cell transplantation (HCT), as well as the advent of immune effector cell therapy (IEC), have resulted in an increasing number of patients undergoing these therapies and an increasing level of expertise required to manage them. Previous guidelines for the training of HCT physicians were last published in 2012. In recognition of the expanding knowledge base and increasing skill set essential to the delivery of these treatment modalities, the American Society for Transplantation and Cellular Therapy Committee on Education has updated these guidelines to reflect nearly a decade of new knowledge in the field of HCT, as well as the evolution of IEC from an experimental modality to a widely used and mainstream therapy. The resulting document reflects the Committee on Education's recommended educational structure for programs engaged in the training, evaluation, and mentorship of HCT/IEC trainees.


Correlation of central visual function and ROP risk factors in prematures with and without acute ROP at the age of 6-13 years: the Giessen long-term ROP study.
To correlate light increment sensitivity (LIS) and visual acuity (VA) with birth weight (BW), gestational age (GA) and stage of acute retinopathy of prematurity (ROP) (STG) in premature children at school age. 180 children (150 former prematures and 30 age-matched term-born children) were enrolled at age 6-13 years. Former prematures were categorised by the results of the initial ROP screening based on digital wide-field fundus imaging: absence of ROP (n=100) and spontaneously resolved ROP (n=50). The latter group was further subdivided according to their STG (Stg 1; Stg 2; Stg 3). Both groups were categorised into sectors by BW (<1000 g; 1000-1500 g; >1500 g), and GA (≤28 weeks; >28<32 weeks; ≥32 weeks). VA was assessed with Early Treatment of Diabetic Retinopathy Study letters, LIS was measured at 0°, 2.8° and 8° in the visual field (Microperimeter MP1, Nidek Technologies), and spherical equivalent refraction assessed with a Nidek autorefractor (Nidek, Italy). Central and pericentral LIS (0° and 2.8°) and VA were significantly lower in all groups and sectors compared with term-born controls except for BW >1500 g for LIS and GA >28 to <32 W for VA. No significant differences were found for LIS at 8° in all groups. No correlation was found between LIS and VA on an individual basis. Low BW, GA and increasing severity of spontaneously resolving ROP were associated with significantly decreased central visual function. In addition to VA, LIS measurement further describes foveal function and is a unique parameter to assess parafoveal function.


Complications of ureteroscopy: a complete overview.
The aim of this paper was to give a complete overview of all published complications associated with ureteroscopy and their according management and prevention in current urological practice. This review was registered in PROSPERO with registration number CRD42018116273. A bibliographic search of the Medline, Scopus, Embase and Web of Science databases was performed by two authors (V.D.C. and E.X.K.). According to the Population, Intervention, Comparator, Outcome (PICO) study design approach and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) standards, a consensus between these authors was found relating to the thematic structure of this review. Ureteral stent discomfort, ureteral wall injury and stone migration are the most frequently reported complications. The worst complications include urosepsis, multi-organ failure and death. Incidence rates on these and other complications varied extensively between the reviewed reports. Ureteroscopy seems to be associated with more complications than currently reported. The present overview may help urologists to prevent, recognize and solve complications of ureteroscopy. It may also stimulate colleagues to perform prospective studies using standardized systems for classifying complications. These are warranted to compare results among different studies, to conduct meta-analyses, to inform health care workers and to counsel patients correctly about possible risks of ureteroscopy.


[Correlative study of nuclear factor-kappa B subunit p50 activity and IL-4 gamma-IFN expression in nasal polyps].
To explore the possible regulation mechanism of nuclear factor-kappa B subunit p50 on Th1/Th2 cytokine in nasal polyps. The expression of IL-4, gamma-IFN and p50 were examined by the method of immunohistochemistry staining in 40 cases of nasal polyps and 20 normal subjects, and the linear correlations between activity of p50 and IL-4, gamma-IFN were evaluated. The expression of p50 mainly distribute in the cytoplasm of epithelia, inflammatory cell and the epithelia of gland. The expression of IL-4 and the activity of p50 was increased significantly in nasal polyps (all P<0.01). But the expression of gamma-IFN had no significant difference between the groups (P>0.05). Pearson correlation analysis demonstrated that p50 nuclear-presented closely correlation with IL-4 level, but not gamma-IFN. The correlation coefficient was 0.70 for p50 and IL-4 (P<0.01), 0.14 for p50 and gamma-IFN (P>0.05). The activity of p50 in nasal polyps is increased significantly. The activation of p50 may play an important role in the imbalance of Th1/Th2-typed cytokines by upregulating the level of IL-4.


Amplification of intermediate-size DNA sequences from formalin and B-5 fixed tissue by polymerase chain reaction.
Retrospective analysis of DNA from paraffin-embedded fixed bone marrow biopsy specimens is possible if preceded by amplification of the DNA sequences of interest by the polymerase chain reaction (PCR). These fixed specimens yield degraded DNA that may not be suitable for direct analysis by conventional digestion and hybridization methods. This limitation is circumvented by PCR amplification and subsequent analysis of the amplified products. The model used in this study is the amplification of a 725 base-pair (bp) beta-globin gene sequence encompassing the sickle-cell anemia point mutation, followed by Cvn I digestion. The beta A beta A, beta A beta S, and beta S beta S genotypes are derived from analysis of the allele-specific digestion patterns. Two fixatives were compared: neutral-buffered formalin and a mercury-based fixative (B-5) routinely used for bone marrow biopsies. DNA extracted from B-5-fixed bone marrow specimens was found to be more degraded than DNA from neutral-buffered, formalin-fixed bone marrow aliquots from the same specimens. PCR amplification of the 725 bp beta-globin gene sequence was successful with DNA from formalin-fixed bone marrow specimens, but not with DNA from B-5-fixed identical specimens. Analysis of the amplified product by Cvn I digestion resulted in correct genotype derivation for all patients, normal controls and positive controls (patients diagnosed with sickle-cell anemia or trait). These results indicate that intermediate-size DNA sequences can be amplified and analyzed when DNA is extracted from formalin-fixed bone marrow specimens.(ABSTRACT TRUNCATED AT 250 WORDS)


A chromosomal abnormality (21q-) in primary thrombocytosis.
A patient with thrombocytosis was found to present an acquired deletion of the long arm of chrosome 21 (21q-). A similar observation reported in the literature is hereby confirmed.


Selective increase in cytokeratin synthesis in cultured rat hepatocytes in response to hormonal stimulation.
Addition of a combination of insulin, dexamethasone and EGF at seeding time to cultured rat hepatocytes in serum-free medium caused a selective increase in the biosynthesis of particular cytokeratin components. This increase was prominent during the first day in culture. No significant increases were detected in the absence of hormones or in the presence of either hormones added alone or in pairs, except in the case of insulin plus dexamethasone, which yielded an effect close to that obtained with the three factors. Interestingly, the latter condition also maintained a high level of albumin production over a 6-day period in culture.


Gel filtration analysis of vanadium in Ascidia nigra blood cell lysate.
Fractions from a Sephadex gel filtration of homogenized Ascidia nigra blood cell lysate were analyzed for vanadium by atomic absorption spectroscopy. The results were unaffected by temperature from 4-21 degrees C, and by ionic strength in the range 0.09-1.0 M (NaCl). Appreciable loss of vanadium in the supernatant was experienced above pH 2.2. Experiments at pH 2.1 under anaerobic conditions show that the green chromogen and the vanadium-containing bands elute separately. Under these experimental conditions, the vanadium-containing species is of relatively low (congruent to 1,000) molecular weight.


Tay-Sachs disease in an Arab family due to c.78G>A HEXA nonsense mutation encoding a p.W26X early truncation enzyme peptide.
Tay-Sachs disease (TSD), a pan-ethnic, autosomal recessive, neurodegenerative, lysosomal disease, results from deficient β-hexosaminidase A activity due to β-hexosaminidase α-subunit (HEXA) mutations. Prenatal/premarital carrier screening programs in the Ashkenazi Jewish community have markedly reduced disease occurrence. We report the first Jordanian Arab TSD patient diagnosed by deficient β-hexosaminidase A activity. HEXA mutation analysis revealed homozygosity for a nonsense mutation, c.78G>A (p.W26X). Previously reported in Arab patients, this mutation is a candidate for TSD screening in Arab populations.


Modified AJCC staging of gastric neuroendocrine carcinoma based on T staging can improve the capacity of prognosis assessment.
This study was designed to determine the value of AJCC staging 7th edition and improved AJCC staging in assessing the prognosis of gastric neuroendocrine carcinoma (GNEC). In total, GNEC 475 patients in the Surveillance, Epidemiology, and End Results (SEER) database and 129 GNEC patients in our department undergoing resection were included. The former served as the test group, and the latter served as the validation group. Those with stage IIIb disease were allocated into four subgroups, and improved AJCC staging was established. The AIC and C indices were used to evaluate the capacities of different TNM staging. Significant overlap between stages IIIb and IIIa in both the test and validation groups was found. In the test group, T staging and age at disease diagnosis were independent prognostic factors for patients with stage IIIb. Stage IIIb was divided into T1N1, T2N1, T3N1 and T4N1, and the improved AJCC staging-mTNM staging was created. In mTNM staging, the IIIb survival curve did not cross those of stages IIIa and IIb, which had a smaller AIC (2490 vs. 2507) value and larger C index (0.7624 vs. 0.7450, P = 0.228). Similar results were obtained for the validation group. T stage was an independent factor influencing the prognosis of stage IIIb GNEC patients, and the improved AJCC staging proposed here has good prognostic value.


Transition Metal Free Intermolecular Direct Oxidative C-N Bond Formation to Polysubstituted Pyrimidines Using Molecular Oxygen as the Sole Oxidant.
Various polysubstituted pyrimidines are smoothly formed via a base-promoted intermolecular oxidation C-N bond formation of allylic C(sp(3))-H and vinylic C(sp(2))-H of allyllic compounds with amidines using O2 as the sole oxidant. This protocol features protecting group free nitrogen sources, good functional group tolerance, high atom economy, and environmental advantages.


IL-10-producing regulatory B cells and plasmocytes: Molecular mechanisms and disease relevance.
It has long been assumed that the functions of B cells reflected the roles of antibodies. However, B cells also decisively influence immunity via antibody-independent mechanisms including the presentation of antigen to T cells and the secretion of cytokines. In fact, B cell depletion therapy improves the course of autoimmune diseases such as multiple sclerosis by removing pro-inflammatory cytokine-producing B cells rather than by reducing autoantibody levels. Remarkably, B cells can also produce anti-inflammatory cytokines, and subsequently suppress immunity, providing protection from autoimmune diseases while interfering with beneficial responses against pathogens and cancers. A major mediator of this B cell regulatory function is their secretion of IL-10. There is considerable interest in identifying the mechanisms inducing the expression of IL-10 in B cells during the course of their activation. Here, we review the molecular mechanisms controlling IL-10 expression in B cells, and the evidence that IL-10-producing B cells play a protective role in human autoimmune diseases, underlying the relevance of this immunosuppressive axis for therapy.


Sickness allowance histories among disability retirees due to mental disorders: A retrospective case-control study.
The aim was to describe sickness allowance histories before disability retirement due to mental disorders and to examine whether receiving sickness allowance due to mental disorders and somatic conditions predicts future disability retirement. Pre-retirement sickness allowance histories were traced backwards for 7 years among Finnish residents aged 25-64 years who had retired due to mental disorders in 2011 (n=5.544). For each retiree, five sex- and age-matched controls were drawn from the non-retired population. Conditional logistic regression was used to calculate the risk for disability retirement by sickness allowance history and to control for the effects of educational level, social class, marital status and the urbanisation level of the municipality. The proportion of sickness allowance recipients increased steadily during the years preceding disability retirement, and was highest among those who retired due to bipolar disorders or depression. Those who had received sickness allowance due to mental disorders 6-7 years earlier had 6.5 times higher risk and those with sickness allowance 1-2 years earlier 11.7 times higher risk for disability retirement. Sickness allowance due to somatic conditions increased the risk for disability retirement 1.6-1.9 times. Sickness allowance most strongly predicted retirement due to bipolar disorders and depression. Adjustment for covariates had little effect. Those who retired due to mental disorders more often had sickness allowance due to both mental disorders and somatic conditions, but in particular sickness allowance due to mental disorders predicted disability retirement due to mental disorders.


Cognitive costs of decision-making strategies: A resource demand decomposition analysis with a cognitive architecture.
Several theories of cognition distinguish between strategies that differ in the mental effort that their use requires. But how can the effort-or cognitive costs-associated with a strategy be conceptualized and measured? We propose an approach that decomposes the effort a strategy requires into the time costs associated with the demands for using specific cognitive resources. We refer to this approach as resource demand decomposition analysis (RDDA) and instantiate it in the cognitive architecture Adaptive Control of Thought-Rational (ACT-R). ACT-R provides the means to develop computer simulations of the strategies. These simulations take into account how strategies interact with quantitative implementations of cognitive resources and incorporate the possibility of parallel processing. Using this approach, we quantified, decomposed, and compared the time costs of two prominent strategies for decision making, take-the-best and tallying. Because take-the-best often ignores information and foregoes information integration, it has been considered simpler than strategies like tallying. However, in both ACT-R simulations and an empirical study we found that under increasing cognitive demands the response times (i.e., time costs) of take-the-best sometimes exceeded those of tallying. The RDDA suggested that this pattern is driven by greater requirements for working memory updates, memory retrievals, and the coordination of mental actions when using take-the-best compared to tallying. The results illustrate that assessing the relative simplicity of strategies requires consideration of the overall cognitive system in which the strategies are embedded.


Caregiver perceptions of psychotropic medication in residential facilities.
Direct caregivers (designated as "psychopaedic nurses" in New Zealand) in two public residential facilities were surveyed regarding their perceptions, opinions, and knowledge of psychotropic drugs. Of 276 individuals contacted, 227 (82%) returned usable questionnaires. The results indicated that unit supervisors (charge nurses) and unit doctors were perceived as wielding most influence on decisions regarding psychotropic drugs, whereas caregivers based outside residential units were seen as having little influence. Aggressive/destructive behavior and, to a smaller extent, self-injurious behavior were seen as the most likely problem behaviors to lead to medication use. Subjective measures were generally favored for assessing drug effects although, in a hypothetical "ideal" situation, nurses gave increasing priority to more objective indices. Endorsement of behavior modification as an alternative to pharmacotherapy was generally high. A large majority of these caregivers (85%) expressed dissatisfaction with their training concerning psychotropic drugs. Finally, data were presented on drug topics about which respondents wanted to learn more and about changes they wished to see instated in their facilities. Our principal conclusion was that these data indicate a need for more education on a variety of social, pharmacological, and behavioral issues as they relate to medication use.


Platelet and Cancer-Cell Interactions Modulate Cancer-Associated Thrombosis Risk in Different Cancer Types.
The first cause of death in cancer patients, after tumoral progression itself, is thrombo-embolic disease. This cancer-associated hypercoagulability state is known as Trousseau's syndrome, and the risk for developing thrombotic events differs according to cancer type and stage, as well as within patients. Massive platelet activation by tumor cells is the key mediator of thrombus formation in Trousseau's syndrome. In this literature review, we aimed to compare the interactions between cancer cells and platelets in three different cancer types, with low, medium and high thrombotic risk. We chose oral squamous cell carcinoma for the low-thrombotic-risk, colorectal adenocarcinoma for the medium-thrombotic-risk, and pancreatic carcinoma for the high-thrombotic-risk cancer type. We showcase that understanding these interactions is of the highest importance to find new biomarkers and therapeutic targets for cancer-associated thrombosis.


Cue competition in evaluative conditioning as a function of the learning process.
Evaluative conditioning (EC) is the change in the valence of a stimulus resulting from pairings with an affective (unconditioned) stimulus (US). With some exceptions, previous work has indicated that this form of conditioning might be insensitive to cue competition effects such as blocking and overshadowing. Here we assessed whether the extent of cue competition in EC depends upon the type of contingency learning during conditioning. Specifically, we contrasted a learning task that biased participants toward cognitive/inferential learning (i.e., predicting the US) with a learning task that prevented prolonged introspection (i.e., a rapid response made to the US). In all cases, standard EC effects were observed, with the subjective liking of stimuli changed in the direction of the valence of the US. More importantly, when inferential learning was likely, larger EC effects occurred for isolated stimuli than for compounds (indicating overshadowing). No blocking effects on explicit evaluations were observed for either learning task. Contingency judgments and implicit evaluations, however, were sensitive to blocking, indicating that the absence of a blocking effect on explicit evaluations might be due to inferences that occur during testing.


High-content imaging as a tool to quantify and characterize malaria parasites.
In 2021, Plasmodium falciparum was responsible for 619,000 reported malaria-related deaths. Resistance has been detected to every clinically used antimalarial, urging the development of novel antimalarials with uncompromised mechanisms of actions. High-content imaging allows researchers to collect and quantify numerous phenotypic properties at the single-cell level, and machine learning-based approaches enable automated classification and clustering of cell populations. By combining these technologies, we developed a method capable of robustly differentiating and quantifying P. falciparum asexual blood stages. These phenotypic properties also allow for the quantification of changes in parasite morphology. Here, we demonstrate that our analysis can be used to quantify schizont nuclei, a phenotype that previously had to be enumerated manually. By monitoring stage progression and quantifying parasite phenotypes, our method can discern stage specificity of new compounds, thus providing insight into the compound's mode of action.


Distribution, source apportionment and health risk assessment of phthalate esters in outdoor dust samples on Tibetan Plateau, China.
The urbanization of Tibetan Plateau (TP) probably results in a significant contamination of organic pollutants in the area, such as phthalate esters (PAEs). However, there is a lack of monitoring and evaluation of their occurrence and risks in the outdoor dust on TP. This study for the first time investigated the concentrations, distributions and health risk of PAEs in outdoor dust samples on TP, China. A total of 132 outdoor dust samples were collected from five different functional areas, and results showed the ubiquitous detection of all PAEs in the samples. The Σ6PAEs concentrations ranged from 0.08 to 31.49 μg·g-1 with a mean of 3.57 μg·g-1. High concentrations of Σ6PAEs in the outdoor dust were found in commercial districts, which were attributed to the heavy use of PAEs in the public commerce such as consumer products, commodities, and building materials. Di-n-butyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) were the dominant components accounting for 30.65% and 53.19% of the Σ6PAEs. Principal component analysis, positive matrix factorization, and correlation analysis were used to apportion the potential sources of PAEs in outdoor dust samples. The PAEs in the outdoor dust originated mainly from wide application of plasticizers as well as cosmetics and personal care products. The main pathways of human exposure to PAEs in the outdoor dust were ingestion and dermal absorption of dust particles. The total intakes of PAEs from outdoor dusts for children and adults were 1.50 × 10-5 and 2.47 × 10-6 mg·kg-1·d-1, respectively. Children were more susceptible to the PAEs intake than the adults. Although the estimated health risks of the six PAEs are currently acceptable, caution is needed given the likely future increase in use of these PAEs and the currently unknown contribution to human exposure by other medium.


Neuropeptide expression and morphometric differences in crushed alveolar inferior nerve of rats: Effects of photobiomodulation.
Inferior alveolar nerve (IAN) injuries may occur during various dental routine procedures, especially in the removal of impacted lower third molars, and nerve recovery in these cases is a great challenge in dentistry. Here, the IAN crush injury model was used to assess the efficacy of photobiomodulation (PBM) in the recovery of the IAN in rats following crushing injury (a partial lesion). Rats were divided into four experimental groups: without any procedure, IAN crush injury, and IAN crush injury with PBM and sham group with PBM. Treatment was started 2 days after surgery, above the site of injury, and was performed every other day, totaling 10 sessions. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 70 mWpk, beam spot size at target ∼0.1 cm2, a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6 J/cm2. Nerve recovery was investigated by measuring the morphometric data of the IAN using TEM and by the expression of laminin, neurofilaments (NFs), and myelin protein zero (MPZ) using Western blot analysis. We found that IAN-injured rats which received PBM had a significant improvement of IAN morphometry when compared to IAN-injured rats without PBM. In parallel, all MPZ, laminin, and NFs exhibited a decrease after PBM. The results of this study indicate that the correlation between the peripheral nerve ultrastructure and the associated protein expression shows the beneficial effects of PBM.


T cell immunity to SARS-CoV-2.
Exceptional efforts have been undertaken to shed light into the biology of adaptive immune responses to SARS-CoV-2. T cells occupy a central role in adaptive immunity to mediate helper functions to different arms of the immune system and are fundamental to mediate protection, control, and clearance of most viral infections. Even though many questions remain unsolved, there is a growing literature linking specific T cell characteristics to differential COVID-19 severity and vaccine outcome. In this review, we summarize our current understanding of CD4+ and CD8+ T cell responses in acute and convalescent COVID-19. Further, we discuss the T cell literature coupled to pre-existing immunity and vaccines and highlight the need to look beyond blood to fully understand how T cells function in the tissue space.


Immunocompromised Patients with Protracted COVID-19: a Review of "Long Persisters".
Certain immunocompromised individuals are at risk for protracted COVID-19, in which SARS-CoV-2 leads to a chronic viral infection. However, the pathogenesis, diagnosis, and management of this phenomenon remain ill-defined. Herein, we review key aspects of protracted SARS-CoV-2 infection in immunocompromised individuals, or the so-called long persisters, and describe the clinical presentation, risk factors, diagnosis, and treatment modalities of this condition, as well as intra-host viral evolution. Based on the available data, we also propose a framework of criteria with which to approach this syndrome. Protracted COVID-19 is an uncharacterized syndrome affecting patients with B-cell depletion; our proposed diagnostic approach and definitions will inform much needed future research.


Roundworm in a chest drain.
A 19 year old man who suffered a stab injury in the epigastric region and had a chest drain was referred to our accident and emergency department. A chest x-ray showed left sided opacities with fundic gas in the region of the left hemithorax.A roundworm was seen in the chest tube. An exploratory laparotomy revealed a diaphragmatic tear with a laceration of the anterior wall of the stomach from which multiple roundworms were coming out and had entered the pleural cavity and then the chest drain. The tears were repaired and abdomen closed. The patient is doing well.


The Management of Metastatic Spinal Cord Compression in Routine Clinical Practice.
(1) Background: Whether clinical management of spinal metastatic disease (SMD) matches evidence-based recommendations is largely unknown. (2) Patients and Methods: A questionnaire was distributed through Spanish Medical Societies, exploring routine practice, interpretation of the SINS and ESCC scores and agreement with items in the Tokuhashi and SINS scales, and NICE guideline recommendations. Questionnaires were completed voluntarily and anonymously, without compensation. (3) Results: Eighty specialists participated in the study. A protocol for patients with SMD existed in 33.7% of the hospitals, a specific multidisciplinary board in 33.7%, 40% of radiological reports included the ESCC score, and a prognostic scoring method was used in 73.7%. While 77.5% of the participants were familiar with SINS, only 60% used it. The different SINS and ESCC scores were interpreted correctly by 57.5-70.0% and 30.0-37.5% of the participants, respectively. Over 70% agreed with the items included in the SINS and Tokuhashi scores and with the recommendations from the NICE guideline. Differences were found across private/public sectors, hospital complexity, number of years of experience, number of patients with SMD seen annually and especially across specialties. (4) Conclusions: Most specialists know and agree with features defining the gold standard treatment for patients with SCC, but many do not apply them.


Clinical analysis of the prognostic value of ultrastructural abnormalities of plasma cells in patients with multiple myeloma.
The prognostic value of ultrastructural abnormalities of plasma, cells was analyzed in 61 patients with multiple myeloma treated in our hospitals from 1985 to 1996. The survival curves demonstrated significant differences by stratification of ultrastructural abnormalities, such as irregular contour of the nuclear membrane, nuclear body, budding, disarrangement of organelles, fibrillar formation, intramitochondrial granules, multilamellar body, single-sac loop-like structure, and vacuole. However, categorizing by nuclear inclusion body, cytoplasmic inclusion body and dense body showed no significant difference in survival curves. Abnormalities, as well as maturity, may be useful in predicting the prognosis of myeloma patients.


The effect of interleukin 1β and interleukin 6 on estradiol-17β secretion in the endometrium of pig during early pregnancy and the estrous cycle.
Estrogens are produced by porcine embryos during early pregnancy. It was found that the uterus of pigs might be a source of steroid hormones, including estrogens. However, the factors involved in the regulation of endometrial steroidogenesis remain unknown. We hypothesize that interleukin (IL) 1β and IL6, which are cytokines produced by porcine embryos and uterine cells, might be involved in the regulation of endometrial estrogen synthesis. Porcine endometrial explants were harvested from gravid (N = 15) and cyclic (N = 15) pigs on days 10 to 11, 12 to 13, and 15 to 16. Samples were analyzed to determine: (1) the expression of CYP19 mRNA and the presence of aromatase cytochrome P450 protein in the tissue; and (2) the release of endometrial estradiol-17β (E2) in response to IL1β and IL6 after 6 and 12 hours of in vitro incubation. The effects observed in pregnant gilts were compared with the effects in nonpregnant gilts on corresponding days of the estrous cycle. On days 15 to 16 of pregnancy the expression of CYP19 in the endometrium was markedly decreased when compared with other periods, and the quantity of endometrial P450 aromatase protein was higher on these days than on days 12 to 13. In nongravid pigs, the expression of CYP19 was lower on days 15 to 16 when compared with days 12 to 13 and the quantity of P450 aromatase protein did not differ during the studied days of the estrous cycle. Basal endometrial E2 release was higher in pregnant gilts when compared with cyclic gilts only on days 15 to 16. In gravid pigs IL1β and IL6 did not affect endometrial E2 release on days 10 to 11 and 12 to 13 of pregnancy (P > 0.05); however, increased E2 release was observed on days 15 to 16 (P < 0.05). In cyclic pigs neither IL1β, nor IL6 affected endometrial E2 release (P > 0.05). These results provide evidence that: (1) the endometrium possesses a potential for steroidogenesis and produces E2in vitro in gravid and nongravid pigs between days 10 to 16; and (2) IL1β and IL6 increase in vitro endometrial synthesis of E2 in pregnant pigs on days 15 to 16. Therefore, IL1β and IL6 might act as stimulators of endometrial E2 secretion in vitro during the time of decreased production of embryonic estrogens. This correlates with a rapid remodeling of the endometrial tissue and the beginning of hemotrophic nutrition of the embryos occurring on days 15 to 16 of pregnancy.


3D surgical printing for preoperative planning of trabecular augments in acetabular fracture sequel.
We describe the methodical and possibilities of 3D surgical printing in preoperative planning for a total hip arthroplasty in acetabular deformity after acetabular fractures, showing a case of a 43-year-old with posttraumatic arthritis after both column fracture of the left acetabulum that was treated non operatively, supporting the do it yourself mode.


The prosthetic group of milk lactoperoxidase is protoheme IX.
The prosthetic group of milk lactoperoxidase has been isolated from a Pronase hydrolysate of the enzyme and identified spectroscopically and chromatographically as protoheme IX. Partial degradation of the heme occurred during the proteolysis, possibly as a result of coupled oxidation in the presence of glycine and oxygen. The heme is assumed to be buried in the protein molecule in a crevice, which allows ligands to bind to the iron on one side only. The pyridine hemochrome of lactoperoxidase with alpha-band at 563 nm is interpreted as a mixed ligand complex with pyridine on one side of the heme and a ligand originating from the protein on the other. No experimental evidence supports the view that the heme is covalently bound to the protein through an ester linkage.


Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE autoradiographic, immunohistochemical and flow cytometric studies in apoE-deficient mice.
The rupture of atherosclerotic plaques is triggered by inflammation. Specific detection of inflammation is therefore the focus of many investigations. Noninvasive imaging methods, such as positron emission tomography (PET), also are suited for this purpose. (68)Ga-DOTATATE is a (68)Ga-labeled radiotracer with specific affinity to somatostatin receptor subtype-2 (SSTR-2). SSTR-2 was found specifically expressed on human macrophages/monocytes. We aimed to confirm the distribution of SSTR-2 in inflammatory plaques, and to assess its co-localization with macrophages within the plaques. We also assessed (68)Ga-DOTATATE uptakes in plaques by autoradiography. Apolipoprotein E (ApoE)-/- mice on a high-cholesterol diet were injected with (68)Ga-DOTATATE. The animals were sacrificed and aorta sections were examined using autoradiography and immunohistochemistry. Furthermore, expression of SSTR-2 was analyzed by flow cytometry. Western blot was conducted to assess SSTR-2 regulation in basal and lipopolysaccharide (LPS)-activated state. To evaluate the specificity of the (68)Ga-DOTATATE, the sections were pre-incubated with monoclonal SSTR-2 antibody before autoradiography. Autoradiographic imaging showed uptake of (68)Ga-DOTATATE co-localized with the macrophage-rich plaques by immunohistochemical examination. A high expression of SSTR-2 on macrophages was found by flow cytometry and western blot. Stimulation with lipopolysaccharide did not alter expression of SSTR-2 in macrophages. Due to its specific binding to macrophages, (68)Ga-DOTATATE might be a suitable radiotracer for the evaluation of inflammatory activity in unstable plaques.


Higher order structure in metaphase chromosomes. II. The relationship between the 250 A fiber, superbeads and beads-on-a-string.
The morphology of metaphase chromosome-derived chromatin fibers released from cells by non-ionic detergent cell lysis in the presence of divalent cations has been studied by electron microscopy. In these preparations the euchromatic arms appear as a series of loops, 200-300 A in diameter, which are composed of closely-apposed nucleosome arrays. The higher order fiber in chromosomes derived from detergent-lysed cells appears to be less stable than chromatin fibers obtained by mechanical cell lysis. The fiber breaks down into a series of non-uniform nucleosome aggregates (superbeads) and finally to chromatin in a beads-on-a-string morphology upon incubation at 31 degrees for 20 min. These observations allow us to suggest a relationship between uniform thick fibers, superbead-containing fibers, and beads-on-a-string chromatin within metaphase chromosomes.


Combined spectroscopic, biochemical and chemometric approach toward finding of biochemical markers of obesity.
Early-stage detection of subclinical obesity-driven systemic changes is a challenging area of medical diagnostics, where the most popular existing measures - such as body mass index - BMI - often fall short of providing a realistic estimate of adiposity and, therefore, of ongoing pathologies at the systemic, tissue and cellular level. In the quest for identifying new more robust diagnostic markers, whole-organ analysis of chemical elements is a promising approach for identifying candidate proxies of obesity status in the system. Total Reflection X-ray fluorescence (TXRF) coupled with biochemical assays, chemometrics and statistical validation was used as a new integrated pipeline for marker identification in external ear samples of obese animals. The specimens were taken from obese animals fed a high calorie diet as well as from lean intact animals fed a standard diet. The most significant differences in the content of K, Fe, Br, and Rb between the studied groups of the animals were identified. However, with the methodology applied Rb was found the most robust biochemical discriminator of early-stage obesity effects, as validated by the logistic regression model. We observed no relationship between the levels of the elements consumed by the animals and their apparent content in the earlobe tissue samples. Our preliminary study confirms that obesity alters tissue trace metal metabolism and shows the proposed new approach as an accurate and reliable methodology for detecting tissue elemental obesity-related alterations. This result can be of practical significance for designing new point-of-care systems for obesity screening tests, taking advantage of direct/indirect Rb measurements.


Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract.
The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle.


Retardation of brain myelination by malnourishment and feeding low protein irradiated diet in rats.
The effect of feeding low protein diet, and the low protein irradiated diet on the deposition of myelin in the brains of rats over two generations showed that malnourishment lowered the CNP enzyme activity when compared to the normal (high protein) diet fed control rats during early postnatal period. Irradiated low protein diet, when fed within 21 days of irradiaton (15 Krads Gamma radiation, 60Co rays), produced still lower CNP enzyme activity. This also enhanced other effects of retarding the brain development, by lowering the protein and lipid contents of the brain during a period from the 4th to 25th day of postnatal development. This suggests the possibility that feeding irradiated low protein food to malnourished developing mammals could cause serious problems like mental retardation.