Clinical features and pathomechanisms of syringomyelia associated with spinal arachnoiditis.
Syringomyelia is a common intramedullary lesion associated with spinal arachnoiditis and obstruction of the foramen magnum such as in Chiari's malformation. Disturbance of cerebrospinal fluid flow around the spinal cord has an important role in the development of syringomyelia due to spinal arachnoiditis; however, the exact mechanisms have not been clarified. The purpose of this retrospective study is to understand the clinical features and pathomechanisms of syringomyelia secondary to spinal arachnoiditis and to provide the current choice of surgical treatment in this difficult clinical entity. Clinical and radiological findings in 15 patients with syringomyelia associated with spinal arachnoiditis who underwent surgical treatment in our institutes between 1982 and 2000 were reviewed. All patients presented with paraparesis or tetraparesis on admission. Magnetic resonance imaging (MRI) or computed tomography-myelography revealed that the syrinx predominantly existed at the thoracic levels. Five patients showed complete block of the thoracic subarachnoid space by conventional myelography. T2-weighted MRI showed diffuse intramedullary hyperintensity at the level of arachnoiditis. As the first surgical treatment, 10 patients underwent syringo-peritoneal shunt placement. Three patients were treated with a syringo-subarachnoid shunt, and 2 patients were treated with a ventriculoperitoneal shunt. Eight patients required further shunting operations for syringomyelia 2 months to 12 years after the first surgery. Neurologic improvement was obtained in 9 patients (60%) with decreased size of the syrinx. One patient remained stable; 5 patients showed gradual deterioration. The syrinx originated from the thoracic levels where severe adhesion of the subarachnoid space was present. The mechanisms of syrinx formation may be based on the increased interstitial fluid in the spinal cord. Shunting procedures were effective in some population of the patients. Decompression procedures of the spinal subarachnoid space may be an alternative primary surgical treatment except for patients with longitudinally extensive arachnoiditis.


Sterilization in a liquid of a specific starch makes it slowly digestible in vitro and low glycemic in rats.
Diabetics are recommended to eat a balanced diet containing normal amounts of carbohydrates, preferably those with a low glycemic index. For solid foods, this can be achieved by choosing whole-grain, fiber-rich products. For (sterilized) liquid products, such as meal replacers, the choices for carbohydrate sources are restricted due to technological limitations. Starches usually have a high glycemic index after sterilization in liquids, whereas low glycemic sugars and sugar replacers can only be used in limited amounts. Using an in vitro digestion assay, we identified a resistant starch (RS) source [modified high amylose starch (mHAS)] that might enable the production of a sterilized liquid product with a low glycemic index. Heating mHAS for 4-5 min in liquid increased the slowly digestible starch (SDS) fraction at the expense of the RS portion. The effect was temperature dependent and reached its maximum above 120 degrees C. Heating at 130 degrees C significantly reduced the RS fraction from 49 to 22%. The product remained stable for at least several months when stored at 4 degrees C. To investigate whether a higher SDS fraction would result in a lower postprandial glycemic response, the sterilized mHAS solution was compared with rapidly digestible maltodextrin. Male Wistar rats received an i.g. bolus of 2.0 g available carbohydrate/kg body weight. Ingestion of heat-treated mHAS resulted in a significant attenuation of the postprandial plasma glucose and insulin responses compared with maltodextrin. mHAS appears to be a starch source which, after sterilization in a liquid product, acquires slow-release properties. The long-term stability of mHAS solutions indicates that this may provide a suitable carbohydrate source for low glycemic index liquid products for inclusion in a diabetes-specific diet.


First observation of B(s)(0) → J/ψη and B(s)(0) → J/ψη'.
We report first observations of B(s)(0) → J/ψη and B(s)(0) → J/ψη'. The results are obtained from 121.4 fb(-1) of data collected at the Υ(5S) resonance with the Belle detector at the KEKB e+ e- collider. We obtain the branching fractions B(B(s)(0) → J/ψη)=[5.10±0.50(stat)±0.25(syst)(-0.79)(+1.14)(N(B(s)(*) B(s)(*))]×10(-4), and B(B(s)(0) → J/ψη')=[3.71±0.61(stat)±0.18(syst)(-0.57)(+0.83)(N(B(s)(*) B(s)(*))]×10(-4). The ratio of the two branching fractions is measured to be (B(B(s) → J/ψη'))/(B(B(s) → J/ψη))=0.73±0.14(stat)±0.02(syst).


Gas permeability in polymer- and surfactant-stabilized bubble films.
The gas permeabilities of thin liquid films stabilized by poly(N-isopropylacrylamide) (PNIPAM) and PNIPAM-SDS (sodium dodecyl sulfate) mixtures are studied using the "diminishing bubble" method. The method consists of forming a microbubble on the surface of the polymer solution and measuring the shrinking rates of the bubble and the bubble film as the gas diffuses from the interior to the exterior of the bubble. PNIPAM-stabilized films exhibit variable thicknesses and homogeneities. Interestingly, despite these variable features, the gas permeability of the film is determined principally by the structure of the adsorbed polymer layer that provides an efficient gas barrier with a value of gas permeability coefficient that is comparable to that of an SDS Newton black film. In the presence of SDS, both the film homogeneity and the gas permeability coefficient increase. These changes are related to interactions of PNIPAM with SDS in the solution and at the interface, where coadsorption of the two species forms mixed layers that are stable but that are more porous to gas transfer. The mixed PNIPAM-SDS layers, studied previously for a single water-air interface by neutron reflectivity, are further characterized here in a vertical free-draining film using X-ray reflectivity.


Associations of ERCC4 rs1800067 polymorphism with cancer risk: an updated meta-analysis.
RESULTS from previous studies concerning the association of ERCC4 rs1800067 polymorphism with risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the present meta-analysis. Literature of electronic databases including PubMed, Web of Science, EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORs and their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancer risk. There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overall risk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888- 1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG) genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition, no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and altered cancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggested that AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-type GG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele of ERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer compared with G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). This meta-analysis indicated that ERCC4 rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with the AA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype; The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future large- scale studies performed in multiple populations are warranted to confirm our results.


The Interpersonal Needs Questionnaire: Statistical Considerations for Improved Clinical Application.
The interpersonal theory of suicide (ITS) has accumulated empirical support; however, less research has investigated the clinical utility of ITS constructs in suicide risk assessment. The current study sought to increase the clinical utility of the Interpersonal Needs Questionnaire (INQ), an assessment of thwarted belongingness (TB) and perceived burdensomeness (PB), among 318 adult psychiatric outpatients while considering statistical methodology (i.e., multicollinearity and partialling). Results emphasized PB in the prediction of concurrent desire for death/suicide when TB was simultaneously considered. The interaction between TB and PB did not enhance prediction of concurrent desire for death/suicide. Independently, PB was a stronger predictor than TB of concurrent desire for death/suicide in the total sample and gender subsamples. Estimated probabilities of concurrent desire for death/suicide across INQ scores and preliminary INQ clinical cutoff scores are provided to enhance clinical application. These findings suggest the INQ could provide valuable information for suicide risk assessment and conceptualization.


Transgenic animal models.
Exercise adaptations induce the differential expression of genes that encode components of the contractile apparatus, metabolic pathways, organelle systems, and membrane components. These changes in gene expression are presumably brought about by the activation of intracellular signaling pathways. The use of transgenic technology is particularly well suited for exercise studies because it uniquely allows investigators to evaluate gene regulatory mechanisms in the intact animal at all stages of the life cycle. Transgenic mice can be generated that harbor any of the varied genes involved in exercise adaptation, for the purpose of determining what sequences within this gene regulate the response to any exercise regimen. Once the corresponding transcriptional factor(s) have been identified and the gene(s) cloned, a series of similar studies (gene networking) could be undertaken to determine the signal transduction pathway. Alternatively, transgenics can be produced that overexpress a particular protein or express an isoform of a protein in a tissue where it is not normally expressed. The goal of these studies would be to determine if function is improved and if exercise adaptation is enhanced or facilitated. Ultimately, gene targeting can be used to either mutate or knock out a gene to determine whether its gene product is indispensable for function, exercise performance, and/or adaptation.


The importance of subsyndromal symptoms in bipolar disorder.
Bipolar disorder continues to be characterized by poor clinical and functional outcomes in many patients. Poor outcomes may be related to subsyndromal symptoms, defined as symptoms that fail to meet the full diagnostic criteria for a mood episode. Several recent studies indicate that subsyndromal symptoms in bipolar disorder are strongly associated with deficits in both social and occupational functioning. Furthermore, subsyndromal symptoms appear to increase the risk of relapse. Combined, these factors emphasize the importance of aggressive treatment strategies at the onset of subsyndromal symptoms. In addition, the use of subsyndromal symptoms to broaden the diagnostic criteria for bipolar disorder is receiving increased attention. This article reviews and discusses these important issues.


Delayed Diagnosis of Tuberculous Meningitis Misdiagnosed as Herpes Simplex Virus-1 Encephalitis With the FilmArray Syndromic Polymerase Chain Reaction Panel.
The FilmArray meningitis/encephalitis (ME) panel is a novel syndromic, nucleic acid amplification test for diagnosis of acute meningitis and encephalitis. Emerging data on its performance are concerning for false-positive results. We present a case of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with the FilmArray ME panel. Strategies to mitigate erroneous results are discussed.


2012 and beyond: potential for the start of a second pre-antibiotic era?
The past decade has seen an alarming confluence of circumstances antithetical to development of new antibacterials, and most of the very few new drugs under development have problems with their microbiology, toxicity, or pharmacokinetics and pharmacodynamics. Most large pharmaceutical companies have divested themselves of their antibiotic portfolios, and the promise that start-up companies would fill the niche has not been fulfilled. What is left of the field is being stifled by bureaucratic regulations, problems with approval, lack of expertise and a general lack of understanding of how serious the situation is. In paediatrics, in particular, there is no sign of any new antibacterial in the foreseeable future. Waiting for initiatives and deliberations will probably take too long, and a vigorous and deliberate effort to educate the public-who in their turn can apply the needed pressure--seems to be the only way of achieving a rapid turnaround of this most dangerous situation.


Neonates with congenital diaphragmatic hernia have smaller neck veins than other neonates-An alternative route for ECMO cannulation.
The aim of this study was to compare the size of the right internal jugular vein between neonates with congenital diaphragmatic hernia (CDH) who need extracorporeal membrane oxygenation (ECMO) and non-CDH neonates. The purpose also was to describe a method for cannulation of the right brachiocephalic vein if the internal jugular vein was too small for ECMO cannulation. Birth weight and size of the right internal jugular vein were compared between CDH and non-CDH neonates subjected to ECMO treatment. A corrected venous size was calculated, estimating the venous size if the patient's birth weight was 3,000 g. The mean birth weight of the CDH patients (3,214 g) was lower than that of the non-CDH patients (3,497 g; P <.04). The mean venous size of the CDH patients (12.1 Charierre [Ch]) was significantly smaller (P <<.001) than that of non CDH patients (13.6 Ch). The corrected venous size also was significantly (P <.001) smaller among CDH patients. Severely affected neonates with CDH have significantly smaller right internal jugular veins than other neonates. If the patient needs ECMO and if the internal jugular vein is too small for cannulation, the right brachiocephalic vein can be successfully cannulated from the neck instead.


Chemical sensitivity and the immune system: a paradigm to approach potential immune involvement.
This paper approaches the issue of chemical sensitivity and the immune system though a consideration of established environmentally-induced immune alterations which have particular relevance to the broader topic of chemical sensitivity. Additionally, the report discusses the potential problems associated with prior narrow evaluation strategies for the assessment of environmentally-induced inflammation. A combined approach to assessment drawing upon biomarkers of both the immune and neurological systems is suggested. Such an approach recognizes the key roles which mediators of these two systems play in facilitating host inflammatory responses. The paper concludes with a discussion of the types of specific immune alterations which, from a mechanistic perspective, are likely to be involved with any linkage of chemical sensitivity to the immune system.


Evaluation of chitooligosaccharide application on mineral accumulation and plant growth in Phaseolus vulgaris.
Chitooligosaccharides (COS) - water soluble derivatives from chitin, are an interesting group of molecules for several biological applications, for they can enter plant cells and bind negatively charged molecules. Several studies reported an enhanced plant growth and higher crop yield due to chitosan application in soil grown plants, but no studies have looked on the effect of COS application on plant mineral nutrient dynamics in hydroponically grown plants. In this study, Phaseolus vulgaris was grown in hydroponic culture and the effect of three different concentrations of COS on plant growth and mineral accumulation was assessed. There were significant changes in mineral allocations for Mo, B, Zn, P, Pb, Cd, Mn, Fe, Mg, Ca, Cu, Na, Al and K among treatments. Plant morphology was severely affected in high doses of COS, as well as lignin concentration in the stem and the leaves, but not in the roots. Chlorophyll A, B and carotenoid concentrations did not change significantly among treatments, suggesting that even at higher concentrations, COS application did not affect photosynthetic pigment accumulation. Plants grown at high COS levels had shorter shoots and roots, suggesting that COS can be phytotoxic to the plant. The present study is the first detailed report on the effect of COS application on mineral nutrition in plants, and opens the door for future studies that aim at utilizing COS in biofortification or phytoremediation programs.


Bilateral coronoid hyperplasia: a report of six cases.
Bilateral coronoid process hyperplasia is a rare condition defined as an abnormal elongation of the mandibular coronoid process, formed of histologically normal bone. Coronoid process hyperplasia usually develops progressively, and the clinical symptoms are often similar to those of temporomandibular joint disorders (TMD). Therefore, it is often misdiagnosed as TMD initially. From 2013 to 2016, six patients were referred to our maxillofacial surgery unit by their dentist, to evaluate mouth opening with suspected TMJ disorder. Average age was 30 years No hypertrophy of the masseter muscles was found and the patient had no history of pain and/or dysfunction of the temporomandibular joint. Average maximal incisal opening was 16.3 mm. (Rance 13-20 mm). At the end of surgery the average mouth opening achieved was of 40.3 mm. After 6 months from surgery an average mouth opening of 41 mm was obtained, with no recidivism in the coronoid process growth or decrease in the mouth opening. The only successful treatment to restore the mouth opening caused by coronoid process hyperplasia is surgical correction of coronoid-malar interference by coronoidectomy or coronoidotomy. Commencement of physiotherapy is recommended to begin between three days and one week after surgery. We also recommend the use of the TeraBite®, a simple manual physiotherapy device.


Fate of 14C-ethion insecticide in the presence of deltamethrin and dimilin pesticides in cotton seeds and oils, removal of ethion residues in oils, and bioavailability of its bound residues to experimental animals.
Ethyl-1-(14)C-ethion and some of its degradation products have been prepared for comparison purposes. Cotton plants were treated with (14)C-ethion alone and in the presence of deltamethrin and dimilin pesticides under conditions simulating local agricultural practice. (14)C-Residues in seeds were determined at harvest time; about 47.5% of (14)C-activity was associated with oil. After further extraction of seeds with ethanol, the ethanol-soluble (14)C-residues accounted for 10.6% of the total seed residues, whereas the cake contained about 37.3% of the total residues as bound residues in the case of ethion only. The bound residues decreased in the presence of deltamethrin and dimilin pesticides and amounted to 8.1 and 10.4% of the total residues, respectively. About 95% of the (14)C-activity in the crude oil could be eliminated by simulated commercial processes locally used for oil refining. Chromatographic analysis of crude cotton oil revealed the presence of ethion monooxon, O,O-diethyl phosphorothioate, and O,O-diethyl phosphoric acid in addition to one unknown compound in the case of ethion alone or ethion and dimilin. The same degradation products are found in the case of ethion and deltamethrin in addition to ethion dioxon, whereas ethanol extract revealed the presence of ethion dioxon and O,O-diethyl phosphoric acid as free metabolites. Acid hydrolysis of the conjugated metabolites in the ethanol extract yielded O,O-diethyl S-hydroxymethyl phosphorodithioate. The bound residues were quite readily bioavailable to the rats. After feeding rats with the cake containing ethion-bound residues, a substantial amount (60%) of (14)C-residues was eliminated in the urine, whereas the (14)C-residues excreted in expired air and feces were 10 and 9%, respectively. About 11% of the radioactive residues were distributed among various organs.


The distribution of pressure behind a soft contact lens.
We determine the pressure distribution behind a soft contact lens that is necessary to keep the lens in conformity with an axisymmetric substrate. The substrate consists of two regions: a central portion, the cornea, supposed to be an ellipsoid; and a peripheral region, the sclera, taken to be a sphere. The pressure is obtained as part of a numerical solution of the axisymmetric equilibrium equations for an initially curved, linearly elastic membrane. The relaxed shape of the lens is assumed to be an axisymmetric ellipsoid with a central curvature and a shape factor different from those of the cornea. The variation in the thickness of the lens from its center to edge is approximated by a polynomial. Pressure distributions are obtained for several typical soft contact lens fittings.


Herpes simplex virus, cytomegalovirus and Epstein-Barr virus antibody titres in sera from schizophrenic patients.
Serum antibody titres to herpes-simplex (HSV-1, 2), cytomegalovirus (CMV), and Epstein-Barr virus capsid antigen (EBV-VCA) were determined in 38 unrelated chronic schizophrenic patients, 11 nuclear families with at least 2 schizophrenic members, and 2 control groups. The distributions of antibody titres to herpes simplex and cytomegalovirus were similar among all groups. Patients had higher anti-EBV-VCA titres than non-hospitalized controls; however, hospital staff members in contact with the patients also had significantly higher antibody titres to EBV-VCA. Antibodies to EBV early antigen (EBV-EA) were also determined for 27 unrelated patients and 24 mental hospital employees. The schizophrenic patients had significantly higher antibody titres to EBV-EA than the hospital worker control group. These data do not support the hypothesis that herpes viruses are associated with the aetiology of schizophrenia. Although elevated anti-EBV early antigen titres may suggest persistent active EBV infection, it is unlikely to be related to the aetiology of the disorder, since discordance for EBV seropositivity was present among sibling pairs concordant for schizophrenia.


Superior Mesenteric Artery Syndrome: The Dark Side of Weight Loss.
Superior mesenteric artery (SMA) syndrome is a rare cause of small bowel obstruction (SBO) resulting from compression of the duodenum by the SMA. Patients at risk of developing SMA syndrome include those who have experienced rapid weight loss from chronic illnesses, malignancy, bariatric surgery, eating disorders, burns, trauma, or substance abuse. We present the case of a 54-year-old cachectic female patient who presented with sudden onset nausea, vomiting, and severe epigastric pain. Imaging studies revealed distention of the stomach and proximal portion of the duodenum with abrupt narrowing of the third part of the duodenum consistent with SMA syndrome. A laparoscopy confirmed the diagnosis and duodenojejunostomy resulted in resolution of the symptoms.


Lung cancer classification: the relationship of disease extent and cell type to survival in a clinical trials population.
The staging and histologic cell type of patients in the Lung Cancer Study Group (LCSG) clinical trials program are reviewed and confirmed or resolved at the reference center for anatomic and pathologic classification of lung cancer. A high level of consistency in classification has been achieved through the use of criteria that minimize intraobserver variability. The data obtained from the review project have been used to characterize the relationship of disease extent and cell type to survival in the clinical trials population. Survival characteristics were generated for 1,121 patients who underwent apparent complete resection of nonsmall cell lung cancer and were subsequently entered into various protocols to receive either adjuvant treatment or no further therapy. The end results study provides some insight regarding the biological behavior of squamous cell carcinoma and adenocarcinoma of the lung in terms of the anatomic extent of disease at the time of apparent complete resection. Patients with squamous cell carcinoma had an outcome superior to that of patients with adenocarcinoma in every TNM subset. The differences in survival according to these major cell types were significant overall and in the T1 N0, T1 N1, and T2 N1 subsets but not in the TNM subsets in stage III disease. Histologic cell type and extent of disease are important factors in survival expectations; thus the accuracy and reproducibility of these classifications plays a significant role in the evaluation of differing modalities of treatment.


The Social Before Sociocognitive Theory: Explaining Hypnotic Suggestion in German-Speaking Europe, 1900-1960.
The article intends to retrace and review German discourse on hypnotic suggestion from 1900 onward, demonstrating the variety of arguments advanced to account for the social relationship in the hypnotic setting well before the emergence of sociocognitive theory. Using Spanos's distinction between "happenings" and "doings," it shows how, in the case of the "social" in early 20th century German texts on (hypnotic) suggestion, the passive observer, recipient, or victim of hypnosis, a trope familiar to the discipline for many decades, was called into question. This image, however, was not called into question by scientists experimenting in laboratories. On the contrary, the neurologists, psychologists, and philosophers who proffered a new way of seeing suggestion, one that privileged the hypnotic as well as the reciprocity between hypnotist and hypnotic, were part of a wider movement within the social sciences (grounded in hermeneutics, phenomenology, and Gestalt theory) that distanced itself from "positivistic" methodologies and "scientistic" verities. The article, then, seeks to remind readers that the sociocognitive perspective does not define the sociopsychological study of hypnosis.


Cost-effectiveness of Descemet stripping automated endothelial keratoplasty versus penetrating keratoplasty in patients with endothelial dysfunction in India.
The aim of this study was to compare the cost-effectiveness and perform cost-utility analysis of Descemet stripping automated endothelial keratoplasty (DSAEK) vs. penetrating keratoplasty (PK) in Indian population. This was an institutional, ambispective, observational study. Patients who underwent PK or DSAEK for endothelial dysfunction were included and followed up for 2 years; those with other ocular comorbidities were excluded. The analysis was performed from the patient's perspective receiving subsidized treatment at a tertiary care hospital. Detailed history, ophthalmic examination, total expenditure by patient, and clinical outcomes were recorded. The main outcome measures were best spectacle-corrected visual acuity (BSCVA), graft survival (Kaplan-Meier survival estimates), incremental cost-effectiveness ratio (ICER), and incremental cost-utility ratio (ICUR). Utility values were based on quality-adjusted life years (QALYs) associated with visual acuity outcomes. Statistical analysis was performed using SPSS software package, version 12.1; a value of P < 0.05 was considered statistically significant. A total of 120 patients (PK: 60, DSAEK: 60) were included. At 2 years, for a similar logMAR BSCVA, [PK (0.32 ± 0.02), DSAEK (0.25 ± 0.02); P = 0.078], the overall cost for PK (13511.1 ± 803.3 INR) was significantly more than DSAEK (11092.9 ± 492.1 INR) (difference = 1952.6 INR; P = 0.01). ICER of DSAEK relative to PK was -39,052 INR for improvement in 1 logMAR unit BSCVA. ICUR of DSAEK relative to PK was -1,95,260 INR for improvement in 1 QALY. DSAEK was more cost-effective than PK in patients with endothelial dysfunction at 2 years.


[Determination of the mitotic index in tumors by using cell suspensions].
A new variant of the method for mitotic index determination is offered. For this, a tumor cell suspension is obtained by treating the tumor with a 0.3% trypsin solution. Then the cells are transferred to a hypotonic solution where these undergo lysis and, in result, the nuclei are seen to be released in the medium. The ratio of nuclei being in meta- and anaphase is determined. Determination of the mitotic index in tumors using this method allows to avoid a technical error associated with the fact that the proliferative activity is not uniform in different parts of the tumor.


Course of pain and fluctuations in pain related to suspected early hip osteoarthritis: the CHECK study.
To evaluate the prevalence during a 10-year follow-up of clinically relevant fluctuations in pain and the course of hip pain in participants with hip complaints suspected to be early stage hip osteoarthritis (OA). To distinguish between participants with relevant fluctuations in pain and those without based on baseline characteristics. Data were collected at baseline and after 2, 5, 8, and 10 years on 495 participants from the Cohort Hip and Cohort Knee Study (CHECK) with hip pain at baseline. Baseline demographic, anamnestic, and physical-examination characteristics were assessed. The primary outcome was levels of pain in the past week (scored using 0-10 Numeric Rating Scale) at follow-up assessments. Relevant fluctuation was defined as average absolute residuals greater than 1 after fitting a straight line to the participant's pain scores over time. The majority of the participants (76%) had stable or decreasing pain. Relevant fluctuations were found in 37% of the participants. The following baseline variables were positively associated with the presence of relevant fluctuations: higher levels of pain in the past week, use of pain transformation as a coping style, higher number of comorbidities, use of pain medication, and higher levels of high-sensitivity C-reactive protein. No associations were found for baseline radiographic hip OA or clinical hip OA. During a 10-year follow-up, the majority of participants had stable or decreasing pain levels. In those participants with relevant fluctuation (37%), a limited number of baseline variables were associated with increased odds of having relevant fluctuations in pain.


Delta Opioid Peptide [d-Ala2, d-Leu5] Enkephalin (DADLE) Exerts a Cytoprotective Effect in Astrocytes Exposed to Oxygen-Glucose Deprivation by Inducing Autophagy.
Astrocytes protection and functional regulation are important strategies to protect against neuronal damage caused by ischemia. Activation of the delta opioid receptor (DOR) could reduce astrocytes damage, although the mechanism remains unclear. The present study aimed to test the effect of DOR activation on autophagy in astrocytes exposed to oxygen-glucose deprivation (OGD), and to further investigate whether this effect has a protective effect on astrocytes. Primary cultured rat cortical astrocytes were treated with various doses of [d-Ala2, d-Leu5]-Enkephalin (DADLE, a selective DOR agonist) followed by 6 h OGD. Cell viability was evaluated by CCK-8 assay and lactate dehydrogenase release. Autophagic vacuole was analyzed with LC3 immunofluorescent staining. The levels of autophagy and apoptosis-related proteins were analyzed by western blot. Results demonstrated that treatment with 10 nM DADLE was sufficient to increase cell viability and induced autophagy in astrocytes. The DADLE-induced autophagy displayed a cytoprotective effect on astrocytes. Inhibition of autophagy by 3-methyladenine (3-MA, an autophagy inhibitor) reversed the protective effect of DADLE. Naltrindole (a DOR antagonist) only partially antagonized the role of DADLE, which indicated that DADLE might have a cytoprotective mechanism independent of DOR. Further results showed that DADLE significantly enhanced the level of Bcl-2 protein and reduced the level of Bax protein in astrocytes exposed to OGD. Our results suggest a novel mechanism in which DADLE induces autophagy in astrocytes and exerts cytoprotective effects by inhibiting apoptosis.


Predominant expression of N-acetylglucosaminyltransferase V (GnT-V) in neural stem/progenitor cells.
Neural stem/progenitor cells (NPCs) express a variety of asparagine-linked oligosaccharide chains, called N-glycans, on the cell surface, and mainly produce hybrid-type and complex-type N-glycans. However, the expression profiles and roles of N-acetylglucosaminyltransferase-V (GnT-V), an enzyme that forms β1,6-branched N-glycans, in NPCs remain unknown. In this study, cultured NPCs were prepared from adult or embryo cortex, and were maintained as either proliferating NPCs or differentiated cells in vitro. Analysis using reverse-transcriptase polymerase chain reaction, Western blot and lectin blot revealed that GnT-V and its reaction products were distinctly expressed in proliferating NPCs; moreover expression of GnT-V and its reaction products were markedly diminished in differentiated cells. In brain slices, many GnT-V-positive neurogenic cells were detected throughout the cerebral cortex on embryonic day 13, while only a few doublecortin (Dcx)- and GnT-V-double positive NPCs were detected around the subventricular zone of the lateral ventricle in the adult brain. However, in the mice in which motor function was spontaneously recovered after cryoinjury to the motor cortex, many Dcx- and GnT-V-double positive NPCs were found to have accumulated around the brain lesion of the adult cerebral cortex compared with the mice in which the function did not recover. These results indicate that GnT-V expression is under rigorous control during NPC differentiation. Furthermore, expression of GnT-V and its reaction products in NPCs may be necessary for the functional recovery after brain injury, and could be used as a marker for visualization of NPCs.


Early diagnosis of the papillorenal syndrome by optic disc morphology.
The morphology of optic disc dysplasia is the most consistent finding in the papillorenal syndrome, an autosomal-dominant syndrome of eye and kidney maldevelopment often associated with the PAX2 mutation. In the absence of a recognized family history, the diagnosis is typically not made until renal disease is evident. We report an infant whose characteristic fundus findings led to the early diagnosis of the papillorenal syndrome before the potential development of renal dysfunction.


Dental trauma in children in Budapest. A retrospective study.
Traumatic dental injuries (TDIs) are among the most serious dental public health problems in childhood. This study aimed to determine the prevalence of anterior tooth TDIs in 7- to 18-year-old children who presented for treatment over a period between January 2007 and December 2016, and to survey the effect of an increased health awareness and educational campaign about the risk of TDIs and the importance of prevention methods in decreasing their prevalence compared with data published in the years 1985-1999. The current study was carried out on 454 children who presented for treatment at the Department of Paediatric Dentistry and Orthodontics in Budapest, Hungary. The prevalence of TDIs was 1%. Males experienced more dental injuries than females. The incidence of dental trauma peaked at 9 years of age. The most observed injury was luxation. Most accidents occurred during playtime at home. TDIs occurred most frequently in the spring. The increased health awareness, a wide educational campaign about the risk of TDIs and the importance of prevention methods have essentially contributed to the decrease in the prevalence of TDIs, with an increase of luxation injuries and a decrease of teeth fractures.


Selenoamino Acid-Enriched Green Pea as a Value-Added Plant Protein Source for Humans and Livestock.
Selenium deficiency in various degrees affects around 15% of the world's population, contributing to a variety of health problems. In this study, we examined the accumulation and biotransformation of soil applied Se-supplementation (sodium selenite and sodium selenate forms) at different concentrations, along with growth and yield formation of green pea, in a greenhouse experiment. Biotransformation of inorganic Se was evaluated using HPLC-ICP-MS for Se-species separation in the above ground parts of green pea. Results showed 3 mg kg-1 SeIV increased green pea growth biomarkers and also caused an increase in protein content in leaves by 17%. Selenomethionine represented 65% of the total selenium content in shoots, but was lower in pods and seeds (54 and 38%, respectively). Selenomethionine was the major species in all plant parts and the only organic selenium form in the lower SeIV concentration range. Elevating the dose of SeIV (≥30 mg kg-1) triggered detrimental effects on growth and protein content and caused higher accumulation of inorganic Se in forms of SeVI and SeIV. Selenocysteine, another organic form of proteinogenic amino acid, was determined when SeIV (≥10 mg kg-1) was applied in higher concentrations. Thus, agronomic biofortification using the appropriate chemical form and concentration of Se will have positive effects on green pea growth and its enriched shoots and seeds provide a value-added protein source for livestock and humans with significant increased selenomethionine.


[Identification of ectomesenchymal stem cells of human fetal facial processes and spontaneous differentiation to smooth muscle cells].
To investigate the characteristic and phenotype of ectomesenchymal stem cells of human fetal facial processes and the procedure of spontaneous differentiation to smooth muscle cells. The primary ectomesenchymal cells of E 50 human fetal facial processes were isolated by 2.5 g/L trypsin and cultured with DMEM/F 12 with 10(-6) U/L leukemia inhibitor factor(LIF). The morphology and growth rate were observed by inverted microscop. After being withdrawn LIF, the characteristic of cells were identified by immunohistochemistry and RT-PCR. Ultrastructure was observed by transmission electron microscope. The cultured cells displayed monolayer growth and were fibroblast-like with 2-4 processes. The cells were stainely positived for anti-human natural killer cell marker-1, Vimentin, S-100, neuron specific enolase, myoglobin and VIII factor, but negatively for glial fibrillary acidic protein, neural fiblament, alpha-SMA and cytokeratin in immunohistochemistry. Two days after being withdrawn the LIF, cells expressed alpha-SMA in protein and mRNA levels. The cells were rich in muscular filament-like structure and dense bodies under transmission electron microscope. Cultured cells are undifferentiated ectomesenchymal stem cells. The cells have the potential for differentiating spontaneously to smooth muscle cell.


How neuropsychology can inform our understanding of preschool ADHD: Clinical and research implications.
Neuropsychological assessments in preschoolers have not received as much attention as in older children and adults. Attention-deficit/hyperactivity disorder (ADHD) is a common disorder that occurs in early childhood associated with poor academic and personal outcomes, such as learning and social difficulties. Preschoolers with ADHD may present cognitive deficits that are related with the ADHD symptoms of inattention, hyperactivity, and impulsivity, but may also interfere, beyond and above the ADHD symptoms, with everyday functioning. Most importantly, cognitive deficits in preschoolers seem to predict future ADHD symptoms. Yet, the practice of neuropsychological assessment in this age-group has been limited. The present selective review highlights the contribution of comprehensive neuropsychological assessments to the early identification of symptomatic preschoolers and to our understanding of the nature and developmental trajectory of ADHD.


Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups.
To perform a health maintenance organization-based case-control study to evaluate the association of total and high density lipoprotein (HDL) cholesterol with the risk of stroke subtypes and in patient subgroups. Cases had a confirmed incident ischemic stroke (n = 1,242) or hemorrhagic stroke (n = 313). Controls (n = 6,455) were identified in a companion myocardial infarction study. Risk of stroke was modeled using logistic regression. The highest total cholesterol quintile was associated with an increased risk of ischemic stroke compared to the lowest quintile (OR = 1.6, 95% CI 1.3 to 2.0) with the strongest subtype associations for atherosclerotic stroke (OR = 3.2) and lacunar stroke (OR = 2.4). The highest HDL cholesterol quintile was associated with a decreased risk of ischemic stroke compared to the lowest quintile (OR = 0.8, CI 0.6 to 1.0). Subgroup analyses suggested that the total cholesterol association was more important for patients < 66 years of age and those with HDL < 50 mg/dL; the HDL association was more important for patients without diabetes or atrial fibrillation. The second through fourth total cholesterol quintiles were associated with a decreased risk of hemorrhagic stroke compared to the lowest quintile (OR = 0.7, CI 0.5 to 1.0). Higher total and lower HDL cholesterol levels were associated with increased risk of ischemic stroke, especially certain stroke subtypes and patient subgroups. The lowest levels of total cholesterol were associated with an increased risk of all hemorrhagic strokes.


Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen.
Treatment with the CXCR4 antagonist, plerixafor (AMD3100), has been proposed for clinical use in patients with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and in pulmonary fibrosis. However, there is controversy with respect to the impact of plerixafor on neutrophil dynamics in the lung, which may affect its safety profile. In this study, we investigated the kinetics of endogenous neutrophils by direct imaging, using confocal intravital microscopy in mouse bone marrow, spleen, and lungs. Neutrophils are observed increasing their velocity and exiting the bone marrow following plerixafor administration, with a concomitant increase in neutrophil numbers in the blood and spleen, while the marginated pool of neutrophils in the lung microvasculature remained unchanged in terms of numbers and cell velocity. Use of autologous radiolabeled neutrophils and SPECT/CT imaging in healthy volunteers showed that plerixafor did not affect GM-CSF-primed neutrophil entrapment or release in the lungs. Taken together, these data suggest that plerixafor causes neutrophil mobilization from the bone marrow but does not impact on lung marginated neutrophil dynamics and thus is unlikely to compromise respiratory host defense both in humans and mice.


Successful treatment of meningitis caused by highly-penicillin-resistant Streptococcus mitis in a leukemic child.
In recent years, viridans streptococci have been reported with increasing frequency to cause infections in neutropenic cancer patients. Streptococcus mitis, one of the species included among viridans streptococci, is the most resistant to beta-lactam antibiotics in this group. Bacterial meningitis presenting without pleocytosis in the cerebrospinal fluid (CSF) is rare, and this situation could be confusing to physicians. It is also an uncommon infectious complication in leukemic patients with neutropenia. In patients with leukopenia caused by myelosuppression after chemotherapy, bacterial meningitis must be considered a possibility when a patient develops meningeal signs, even if no pleocytosis is found in the CSF. We report on a 6-year-old boy with leukemia and neutropenia who developed sepsis and meningitis caused by S. mitis with high-level resistance to penicillin and cephalosporins (MIC of both, >2 mg/l); he was a long-term survivor receiving chronic trimethoprim-sulfamethoxazole prophylaxis. The patient was successfully treated with a combination of vancomycin, ceftriaxone, and granulocyte-colony-stimulating factor.


Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action.
Midazolam is a short-acting benzodiazepine that is widely used in anesthesia. Despite its widespread clinical use, detailed information about cardiac side effects of midazolam is largely lacking. Using the double-electrode voltage clamp technique, we studied pharmacological effects of midazolam on heterologously expressed Kv1.5 channels underlying atrial repolarizing current I(Kur). Midazolam dose-dependently inhibited Kv1.5 current, yielding an IC50 of 17 μM in an HEK cell line and an IC50 of 104 μM in Xenopus oocytes. We further showed that midazolam did not affect the half-maximal activation voltage of Kv1.5 channels. However, a small negative shift of the inactivation curve could be observed. Midazolam acted as a typical open-channel inhibitor with rapid onset of block and without frequency dependence of block. Taken together, midazolam is an open channel inhibitor of cardiac Kv1.5 channels. These data add to the current understanding of the pharmacological profile of midazolam.


Bradykinin receptor antagonists in cerebral ischemia and trauma.
Bradykinin, an endogenous nonapeptide produced by activation of the kallikrein-kinin system, promotes neuronal tissue damage as well as disturbances in blood-brain barrier function, mainly through the activation of B2 receptors. Both cerebral ischemia and trauma are associated with an activation of the kallikrein-kinin system, resulting in a sustained production of kinins. This is strong evidence supporting an involvement of bradykinin-mediated secondary brain damage following cerebral ischemia and trauma. Accordingly, specific inhibition of bradykinin B2 receptors attenuates brain swelling and limits tissue damage, indicating its potential in patients with acute cerebral ischemia and trauma.


[Regulation of cell deformation induced by RhoA/ROCK signaling pathway in osteogenic differentiation of human mesenchymal stem cells].
Objective: To investigate whether the cell deformation induced by RhoA/ROCK signaling pathway plays a regulatory role in the osteogenic differentiation in human mesenchymal stem cells (hMSCs). Methods: The primary hMSCs were cultured until the P3 generation was added to the osteogenic induction solution for 14 days, and the expression levels of RhoA and ROCK-1 proteins were detected by immunofluorescence. Another P3 generation hMSCs cells were divided into induction group, blank plus drug group and medicated group, and the induction group was induced by simple osteogenic induction; the blank drug-added group was added to the osteogenic induction solution and the solvent dimethyl sulfoxide (DMSO) for induction culture; the medicinal group was added with osteogenic induction solution and Y-27632 (RhoA/ROCK signaling pathway inhibitor) dissolved in DMSO for induction culture. The proliferation of the cells was detected by CCK-8 methods. The changes of cytoskeleton in each group were observed by fluorescence microscope. The expression changes of osteogenic genes alkaline phosphatase (ALP), osteocalcin (OCN) and runt-relatedtranscriptionfactor-2 (RUNX-2) in each group were detected by real time polymerase chain reaction (RT-PCR) and ALP staining. The t test was used for data comparison between the two groups. Results: There were significant differences in the expression of RhoA and ROCK-1 protein before and after osteogenic induction of hMSCs (22.7±2.1 vs 14.7±0.6 and 24.3±1.5 vs 20.3±0.6, t=-6.414, -4.243, both P<0.05). Mesenchymal stem cell proliferation on day 1, 5, 9 and day 14 in the medicated group were comparable with those in the induction group (F=0.427, 1.000, 0.298, 1.314, all P>0.05). The cytoskeleton of the medicated group showed obvious spindle-shaped changes, and the cell spreading area became smaller. From the three groups of ALP staining on the 14th day, it can be seen that the color of the medicated group was significantly lighter than that of the induction group. The results of RT-PCR showed that the expression of osteogenic phenotypic genes increased with the induction time in the induction group and the blank drug-treated group, the expression levels of osteogenic phenotype genes ALP, OCN and RUNX-2 in the drug-treated group were gradually decreased with the induction time. The expression of ALP in the drug-treated group was significantly lower than those in the other two groups at 14th day (F=25.891, P=0.001); the expression of OCN in the drug-treated group was significantly lower than those in the other two groups at 11th and 14th days (F=5.773, 25.382, both P<0.05); the expression of RUNX-2 in the drug group was significantly lower than those in the other two groups at 11th and 14th days (F=34.972,10.808, both P<0.05). Conclusion: The RhoA/ROCK signaling pathway may play a role in promoting osteogenic differentiation of hMSCs through mediating cytoskeletal deformation.


Differential cooperation between heterochromatin protein HP1 isoforms and MyoD in myoblasts.
Mechanisms of transcriptional repression are important during cell differentiation. Mammalian heterochromatin protein 1 isoforms HP1alpha, HP1beta, and HP1gamma play important roles in the regulation of chromatin structure and function. We explored the possibility of different roles for the three HP1 isoforms in an integrated system, skeletal muscle terminal differentiation. In this system, terminal differentiation is initiated by the transcription factor MyoD, whose target genes remain mainly silent until myoblasts are induced to differentiate. Here we show that HP1alpha and HP1beta isoforms, but not HP1gamma, interact with MyoD in myoblasts. This interaction is direct, as shown using recombinant proteins in vitro. A gene reporter assay revealed that HP1alpha and HP1beta, but not HP1gamma, inhibit MyoD transcriptional activity, suggesting a model in which MyoD could serve as a bridge between nucleosomes and chromatin-binding proteins such as HDACs and HP1. Chromatin immunoprecipitation assays show a preferential recruitment of HP1 proteins on MyoD target genes in proliferating myoblasts. Finally, modulation of HP1 protein level impairs MyoD target gene expression and muscle terminal differentiation. Together, our data show a nonconventional interaction between HP1 and a tissue-specific transcription factor, MyoD. In addition, they strongly suggest that HP1 isoforms play important roles during muscle terminal differentiation in an isoform-dependent manner.


Biomechanical comparison of single- and two-level cervical arthroplasty versus arthrodesis: effect on adjacent-level spinal kinematics.
The use of motion-preserving spinal implants versus conventional arthrodesis instrumentation systems, which stabilize operative segments, necessitates improved understanding of their effect on spinal kinematics and the biomechanically optimal method for surgical reconstruction. The primary objective of this study was to measure operative- and adjacent-level kinematics after single- and two-level cervical arthroplasty and compare them with those after anterior cervical arthrodesis. A secondary objective was to locate the centers of intervertebral rotation at the operative and adjacent levels after arthroplasty and compare them to those after arthrodesis. This biomechanical study used an in vitro human cadaveric model to compare the multidirectional flexibility kinematics of single- versus two-level cervical disc arthroplasty reconstructions. Eight cadaveric cervical spines (C2-T2) were biomechanically evaluated between Levels C4 and T1 in the intact condition and under the following reconstructions: single-level arthroplasty (C6-C7) using porous coated motion (PCM) device; single-level arthrodesis (C6-C7) using interbody cage with anterior plate; two-level arthroplasty (C5-C7) using PCM devices; two-level hybrid treatment of arthroplasty (C5-C6) using PCM device and arthrodesis (C6-C7) using cage/plate; and two-level arthrodesis (C5-C7) using cage/plate. Multidirectional flexibility testing used the Panjabi hybrid testing protocol, including pure moments for the intact condition with overall spinal motion replicated under displacement control for subsequent reconstructions. Unconstrained intact moments of +/-3.0 Nm were used for axial rotation, flexion-extension, and lateral bending testing with quantification of the operative- and adjacent-level range of motion (ROM) and neutral zone. The calculated centers of intervertebral rotation were compared for all intervertebral levels under flexion-extension conditions. Axial rotation loading demonstrated a significant decrease in the C6-C7 ROM for the single-level arthrodesis group compared with the intact spine and the single-level arthroplasty group (p<.05). No differences were observed between the intact and single-level arthroplasty groups (p>.05). For the two-level hybrid treatment group, the C5-C6 ROM significantly increased compared with the intact, single-level arthroplasty, and two-level arthrodesis groups (p<.05). Moreover, a significant increase was observed in the adjacent-level (C7-T1) ROM for the two-level arthrodesis group compared with all other treatment groups (p<.05). Under flexion-extension, no differences were observed in C6-C7 ROM between the intact spine and single-level arthroplasty groups (p>.05). However, as expected, the single-level arthrodesis and two-level hybrid treatment groups demonstrated a decreased ROM at C6-C7 versus the intact spine and arthroplasty treatments (p<.05). In terms of adjacent-level effects, two-level arthrodesis (C5-C7) led to increased ROM in the inferior level (C7-T1) in axial rotation and flexion-extension compared with the intact spine and all other treatment groups (p<0.05). Lateral bending loading conditions demonstrated no significant difference among the treatment groups (p>.05). In flexion-extension, the centers of intervertebral rotation for the intact spine and single-level arthroplasty groups were localized in the central to posterior one-third of the inferior vertebral body for each motion segment: C5-C6, C6-C7, and C7-T1. The single-level arthrodesis group produced more diffuse centers of rotation, particularly at the operative (C6-C7) and inferior adjacent levels (C7-T1). This study highlights the biomechanical effects of single- and two-level cervical arthroplasty versus single- and two-level arthrodesis on four functional spinal levels (C4-T1). Operative-level ROM was preserved with single- and two-level arthroplasty under all loading modes. The distal adjacent level (C7-T1) demonstrated the greatest increase among the four levels in ROM compared with the intact condition after two-level arthrodesis. These kinematic findings were corroborated by changes in the adjacent-level centers of rotation after arthrodesis and may suggest a biomechanical cause of adjacent-level disease secondary to cervical arthrodesis.


Pericardial effusions in patients with malignant diseases.
Six consecutive patients with malignant disease who developed a pericardial effusion were successfully treated with a single pericardiocentesis (two patients) or with indwelling pericardial cather drainage (four patients). There were no complications in either group. Short-term catheter drainage appears to be a safe and effective alternative to surgical establishment of a pericardial window.


Advances in cataract surgery: preserving the corneal endothelium.
Cataract surgery is known to lead to some degree of corneal endothelial cell loss (ECL). The purpose of this review is to describe how recent technological advancements such as femtosecond laser-assisted cataract surgery (FLACS) affect corneal endothelium during cataract surgery. It has been suggested that FLACS may reduce the amount of required ultrasound energy used in cataract surgery, a factor known to be directly related to ECL. Several recent studies demonstrate either no difference or less ECL with FLACS than with standard phacoemulsification 1-3 months after surgery. However, results at 6 months show comparable ECL between the two techniques. Other recent advancements in surgical technique, such as biaxial microincision surgery, result in similar ECL rates to that of standard phacoemulsification. The use of ultraviolet light in the newly developing light-adjustable intraocular lenses does not increase ECL. Studies show either similar results or less ECL with the use of the newer viscous-dispersives when compared with other viscoelastic devices. Other aspects such as the use of intracameral injections have no adverse effects on corneal endothelium. Newly emerging cataract surgical techniques cause comparable ECL to that of conventional phacoemulsification. Femtosecond laser-assistance may reduce ECL, but likely only in the early postoperative period. Further studies are needed to better elucidate short and long-term effects of FLACS on the corneal endothelium. Viscous dispersives may offer equal or increased protection of the corneal endothelium during surgery compared with viscoelastic devices currently in wide use, but further studies are required to support these results.


Membrane polarity in epithelial cells: protein sorting and establishment of polarized domains.
Epithelial cells go to great trouble to organize the subdomains of their plasma membranes. The apical and basolateral surfaces of polarized epithelia are equipped with markedly distinct populations of channels, carriers, and pumps. This anisotropy is an absolute prerequisite for vectorial solute and fluid transport. The physiological properties of an individual epithelial cell type are determined not only by its census of transport proteins but also by the manner in which these proteins are segregated between the apical and basolateral portions of the plasmalemma (Curr. Top. Membr. 39: 37-86, 1991). To achieve this asymmetry, an epithelial cell must be able to establish distinct surface domains, to target newly synthesized transport proteins to their appropriate sites of functional residence, and to retain them there following their delivery. Studies of the cellular pathways involved in generating and maintaining the polarized state have begun to illuminate an elegant network of cell biological specializations that may be involved not only in establishing the distributions of transport proteins but in dynamically regulating their function as well.


111Indium-labelled red-cell scintigraphy to detect intermittent gastrointestinal bleeding from synchronous small- and large-bowel adenocarcinomas.
A 70-year-old woman presented with symptoms of profound anaemia and evidence of intermittent gastrointestinal haemorrhage. Oesophagogastroduodenoscopy, colonoscopy, abdominal computerised tomography, sulphur colloid scintigraphy and selective mesenteric angiography were non-diagnostic. An indium-labelled red-cell scan was performed, which suggested bleeding from the ileum at 36 h. At laparotomy, a primary small-bowel adenocarcinoma was resected. Six weeks later, she was again anaemic. Repeat colonoscopy showed a synchronous primary colonic adenocarcinoma, which had been masked by intraluminal blood during the original indium scan. The lesion was impalpable, even after full mobilisation of the colon. A right hemicolectomy was performed. Indium has a longer half-life (67 h) than the more commonly used technetium isotope (18 h). This allows serial imaging for up to 5 days, which may increase diagnostic efficiency in intermittent gastrointestinal bleeding. Clinicians should be aware that persisting activity from intraluminal blood may mask synchronous lesions.


MOG-specific T cell response amplified in para- and post-SAR-CoV-2 infection in myelin oligodendrocyte glycoprotein antibody-associated disease.
We describe clinical characteristics and deep immunophenotypes in two patients with myelin-oligodendrocyte-glycoprotein (MOG)-antibody-associated-disease after COVID-19. The para-COVID case was a 74-year-old man who developed optic neuritis two days after COVID-19. Immunological assays revealed reduced absolute CD8+ T- and B-cell counts with increased frequency of NK cells. Post-COVID case was a 63-year-old man with optic neuritis six months after COVID-19, a frequency of CD8+ T-cells was elevated with a relatively low fraction of naïve and a high fraction of effector memory CD8+ T-cells. There was increased frequency of CD8+CD38+HLA-DR+ T-cells in the para-COVID case; interestingly, CD4+CD38+HLA-DR+ T cell frequency was increased in the post-COVID case. Both had increased SARS-CoV-2-specific and MOG-specific T-cell responses.


Drug adherence and treatment duration for denosumab and mortality risk among hip fracture patients.
This study aimed to assess the impact of drug adherence and treatment duration for denosumab on mortality risk after hip fracture surgery. Lower all-cause mortality risk was associated with drug intervals of 7 months or less and longer treatment duration. The study highlights the importance of proper denosumab administration. Prescription of anti-osteoporotic medications (AOMs) after osteoporotic hip fracture may increase bone mineral density (BMD) and decrease mortality risk. However, few studies have been conducted on drug adherence and treatment duration for denosumab, a popular choice among AOMs. This study aimed to assess the impact of denosumab adherence and treatment duration on the mortality risk of hip fracture patients after surgery. We conducted a cohort study using nationwide population data from National Health Insurance Research Database (NHIRD) in Taiwan. Patients newly diagnosed with osteoporosis and hip fracture between 2008 and 2019 who used denosumab after surgery were included. We assessed drug adherence, treatment duration, and other parameters associated with patient outcomes. A total of 21,316 patients diagnosed with osteoporotic hip fractures were included. Compared with a > 7-month drug interval for denosumab, an interval of ≤ 7 months led to lower all-cause mortality risk (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.57 ~ 0.64). Patients with denosumab treatment for over 1, 2, and 3 years had lower all-cause mortality risk (HR&CI: 0.68 (0.64 ~ 0.73), 0.48 (0.43 ~ 0.53), 0.29 (0.26 ~ 0.33)) than those with treatment duration < 1 year. Analysis after excluding short-term death yielded similar results. Analysis of causes of death also showed that good adherence and longer duration were associated with reduced mortality due to cancer and cardiovascular disease. Better drug adherence and longer duration of denosumab treatment are associated with lower all-cause mortality risk among hip fracture patients after surgery. Our study highlights the benefits of a proper time interval of denosumab administration. These findings provide important insight into management of osteoporotic hip fractures and may inform clinical practice and development of guidelines.


Investigating the Variation of TREC/KREC in Combined Immunodeficiencies.
T-cell receptor excision circles (TREC)/Kappa-deleting recombination excision circles (KREC) assay has been recently recognized for detecting patients with primary (T- and/or B-cell) immunodeficiency (PID). We aimed to investigate the alterations of these biomarkers in some combined immunodeficiency patients compared to the healthy controls in different age groups. TREC and KREC were assessed in a total of 82 PID patients, most of them with exact genetic diagnosis (3 months to 42 years); using quantitative real-time-polymerase chain reaction (PCR). Patients had a final diagnosis of common variable immunodeficiency (n=23), ataxia-telangiectasia (AT) (n=17), hyper-IgE syndrome (HIES) (7 with DOCK8 deficiency, 4 with signal transducer and activator of transcription 3 (STAT3) deficiency, and 8 children with unknown genetic defects), Wiskott-Aldrich syndrome (WAS) (n=20), purine nucleoside phosphorylase (PNP)deficiency(n=1), dedicator of cytokinesis2 (DOCK2) deficiency (n=1), recombinase activating gene1 (RAG1) deficiency (n=1). Very low to zero amounts of TREC and/or KREC were detected in 14 out of 23 cases of common variable immunodeficiency (CVID), 14 out of 17 cases of AT, 8 out of 20 cases of WAS, 6 out of 7 cases of DOCK8-deficiency patients, 4 out of 8 cases of HIES with unknown genetic defects and all patients with defects in DOCK2, PNP, and RAG1. STAT3-deficient patients were normal for both biomarkers. All patients showed a significant difference in both markers compared to age-matched healthy controls. Our findings highlight that apart from severe types of T/B cell defects, this assay can also be used for early diagnosis the patients with late-onset of disease and even PIDs without a positive family history.


Determination of the maturity and functionality of tumor vasculature by MRI: correlation between BOLD-MRI and DCE-MRI using P792 in experimental fibrosarcoma tumors.
Using hypercapnia and carbogen as functional markers of vessel maturation and function, we compared blood oxygen level-dependent (BOLD) contrast with standard dynamic contrast-enhanced (DCE)-MRI quantitative parameters in murine fibrosarcoma. Our results show that there was no correlation between vessel maturity and contrast-agent uptake rate (K(in) (Trans)) or contrast agent efflux rate (k(ep)). In addition, DCE-MRI provided higher estimates of the fraction of functional tumor compared to BOLD-MRI. The two putative markers of regional vascular density, i.e., the magnitude of BOLD signal change during carbogen challenge (VF) and the fractional plasma volume found by DCE-MRI (V(p)), were only weakly correlated (r(2) = 0.02-0.14). Furthermore, VF showed no correlation with K(in) (Trans). A positive correlation was observed (r(2) = 0.75) between mean tumor VF and k(ep), but only when averaged over the whole tumor (which includes tumor regions completely unperfused by the gadolinium (Gd) contrast agent). This would merely reveal a relationship between perfusion status and the capacity to respond to carbogen breathing. In conclusion, characterizations of tumor microvasculature imaging using BOLD-MRI and DCE-MRI appear to be largely complementary, given the weak correlations between their corresponding derived parameters.


[Controversies surrounding on hormone replacement therapy during menopause].
During the menopausal transition and the early postmenopausal stage diverse symptoms may appear, but only hot flashes and night sweats are inequivocally related to the hormonal changes, constituting the main indication for the use of systemic hormone therapy. In the absence of vasomotor symptoms, the prescription of hormone therapy to either ameliorate psychologic disorders or improve quality of life still is a controversial issue. In order to improve treatment individualization, more information regarding the hormonal effects on peri- and postmenopausal women suffering from chronic diseases such as high blood pressure, obesity and diabetes, is needed. The use of low doses of estrogens and progestins is highly desirable, but the lack of knowledge and availability of appropriate formulations seems to hinder it. Even though it has been demonstrated that hormone therapy does not prevent cardiovascular diseases in postmenopausal women, there are some products that are improperly promoted for this purpose. The benefits of hormone therapy on bone mineral density and osteoporosis prevention are unquestionable. However, because of its potentially deleterious effects on breast tissue its long-term use for bone protection has been restricted. Several studies to assess risks and benefits of low-dose formulations are ongoing. It is expected that better results will be obtained with these new formulations.


Mechanical and material properties of the subchondral bone plate from the femoral head of patients with osteoarthritis or osteoporosis.
To determine the material properties of the subchondral bone plate in patients with osteoarthritis or osteoporosis. Femoral heads were obtained after surgical removal from age and sex matched groups of patients with either osteoporosis (OP), after a fractured neck of femur, or osteoarthritis (OA) and compared with a normal group. The mechanical stiffness, density, and composition of the subchondral bone plate from sites selected to represent areas of heavy, intermittent, and light loading were measured. Overall, OP bone was the least stiff and dense, followed by OA bone; normal bone was stiffer and more dense (p < 0.05). Though OP bone contained less mineral, the organic and water contents were increased in proportion suggesting no change in the relative amount of organic matrix. OA bone was also hypomineralised (p < 0.05) but had different organic and water fractions suggesting a defect in the matrix. Site variation of most properties was small, though across all the groups the superior region was significantly stiffer than the inferior. This study shows that subchondral bone plate is less stiff than normal in both OP and OA and so cannot, by itself, explain the preserving of the overlying cartilage in OP while aiding its destruction in OA. However, the subchondral bone plate is only one part of the bony structure of the femoral head and changes in the cancellous bone need to be considered. The generalised changes in bone composition found in patients with OA support the hypothesis that the disease could involve the bone in the primary pathogenesis.


Use of group monitoring data in lung dose estimation for intakes of uranium.
This paper describes an internal dosimetry program developed for Canadian uranium processing facilities. The recently adopted recommendations of ICRP Publication 60 have made it extremely difficult to detect intakes of insoluble forms of natural uranium by in vivo methods (lung counting). A type S intake of UO2 corresponding to a 20 mSv effective dose has a lung burden that is a factor of 2-3 lower than the MDA, 6 months after the intake occurred. A new methodology, approved in principle by the Canadian Nuclear Safety Commission, has been designed to overcome this problem by summing sequential, but separate, lung counts for an individual, or summing lung counts from a group of workers performing similar tasks. This summing technique effectively increases the counting time and, therefore, reduces the MDA to a value below the dose limit. Doses will be assigned to the individual or work group based on the average lung burden.


Cancer stem-like cell related protein CD166 degrades through E3 ubiquitin ligase CHIP in head and neck cancer.
Our previous studies have identified that CD166 works as a cancer stem-like cell (CSC) marker in epithelial cancers with a large repertoire of cellular functions. However, the post-translational regulatory mechanisms underlying CD166 turnover remain elusive. Several independent studies have reported that E3 ubiquitin ligase CHIP revealed significant biological effects through ubiquitin proteasome pathway on some kinds of malignant tumors. With analyzing the effects of CHIP expressions on stem-like cell populations, we found that CHIP represses CSC characteristics mainly targeting the CSC related protein CD166 in head and neck cancer (HNC). To investigate the role and relationship between CD166 and CHIP, HNC tissues and cell lines were used in this study. A significant negative correlation was observed between the expression levels of CHIP and CD166 in HNC patient samples. We also found that CHIP directly regulates the stability of CD166 protein through the ubiquitin proteasome system, which was also identified participating in the regulation of CSC behaviors in HNCs. Our findings demonstrate that CHIP-CD166-proteasome axis participates in regulating CSC properties in HNCs, suggesting that the regulation of CD166 by CHIP could provide new options for diagnosing and treating in the patients with HNCs.


Dietary sulfated polysaccharides extracted from Caulerpa sp. and Padina sp. modulated physiological performance, antibacterial activity and ammonia challenge test in juvenile rainbow trout (Oncorhynchus mykiss).
Nowadays, the use of seaweed derivatives in aquaculture has drawn attention for their potential as an immunostimulant and growth promotor. The sulfated polysaccharide extracted (SPE ) from green (Caulerpa sp.; SPC) and brown (Padina sp.; SPP) seaweeds with two concentrations (0.05% and 0.1%); nominated in four groups: SPC0.05 , SPC0.1 , SPP0.05 , SPP0.1 and control group (free of SPE ) were used for juvenile rainbow trout (Oncorhynchus mykiss) diet. Fish (N: 150; 8.5 ± 0.2 g) were selected aleatory distributed in 15 circular tanks (triplicate for the group) and fed test diets for 56 days. The outcomes revealed that the supplementation of SPE up to 1 g kg-1 failed to show significant differences in the organosomatic indices as compared to the control group. The most inferior protein value of dress-out fish composition was observed in the fish fed the control diet, which was statistically lower than the SCP0.1 group (p < 0.05), while no significant difference was observed in other macronutrient composition among the treatments. Total monounsaturated fatty acid (MUFA) had lower trend in the carcass of fish fed SPE supplemented diets, so that lowest MUFA were observed in SPC0.05 group (p < 0.05; 25.22 ± 4.29%). The lowest value of docosahexaenoic acid was observed in the control diet compared to the SPE -supplemented diets (p < 0.05). The serum alternative complement pathway levels in all treatments tend to promote compared to the control treatment. A similar trend was observed for lysozyme activity. According to the results, the superoxide dismutase (SOD) value were highest in SPC0.05 and SPC0.1 compared to the other treatments (p < 0.05), while a further elevation of the SPE Padina sp. extracted level (SPP0.1 ) leads to a decrease in SOD value. Thiobarbituric acid reactive substances of plasma was indicated not to influence by sulfated polysaccharide extracts in the refrigerated storage. The lowest serum stress indicators were observed in fish fed SPP0.05 group postchallenge test. Taken together, our outcomes revealed that SPE of two species of seaweeds bestows benefits in some of the immunity and antioxidant system. Also, notable elevations in HUFA were observed in juvenile rainbow trout fed supplemented with SPE .


The more closed the bypass system the better: a pilot study on the effects of reduction of cardiotomy suction and passive venting on hemostatic activation during on-pump coronary artery bypass grafting.
Cardiac surgery with cardiopulmonary bypass (CPB) leads to a powerful activation of the hemostatic system. We assessed to what extent this activation can be attenuated by comparing three different perfusion regimens for on-pump coronary artery bypass grafting (CABG): 1) use of a closed CPB system with aspiration of blood from the operation field via the cardiotomy suction line and active venting of the heart via a roller pump; 2) use of a closed CPB system avoiding aspiration of blood from the operation field via the cardiotomy suction line, but with active venting of the heart; and 3) use of a closed system, avoidance of aspiration of blood from the operation field via the cardiotomy suction line and with passive venting of the heart into the collapsible venous reservoir. Our data show that avoidance of aspiration of blood via the cardiotomy suction line significantly reduces hemostatic activation during on-pump CABG. However, further attenuation of hemostatic activation can be achieved by further closing the system and minimizing the blood/air interface by passive venting of the heart.


Biodegradable poly(D, L-lactide-co-glycolide) (PLGA) microspheres for sustained release of risperidone: Zero-order release formulation.
The preparation and investigation of sustained-release risperidone-encapsulated microspheres using erodible poly(D, L-lactide-co-glycolide) (PLGA) of lower molecular weight were performed and compared to that of commercial Risperdal Consta™ for the treatment of schizophrenia. The research included screening and optimizing of suitable commercial polymers of lower molecular weight PLGA50/50 or the blends of these PLGA polymers to prepare microspheres with zero-order release kinetics properties. Solvent evaporation method was applied here while studies of the risperidone loaded microsphere were carried out on its drug encapsulation capacity, morphology, particle size, as well as in vitro release profiles. Results showed that microspheres prepared using 50504A PLGA or blends of 5050-type PLGAs exerted spherical and smooth morphology, with a higher encapsulation efficiency and nearly zero-order release kinetics. These optimized microspheres showed great potential for a better depot preparation than the marketed Risperdal Consta™, which could further improve the patient compliance.


Silvano Arieti's novel The Parnas: a scene from the Holocaust.
Silvano Arieti was an Italian psychoanalyst who undertook psychoanalysis of schizophrenic patients in the 1960s and 1970s. He left Italy in 1939 at the age of twenty-four following the Race Laws of 1938, and moved to New York until his death in 1981. A training analyst and author of several psychoanalytic and academic books, Arieti kept his research open in a wide variety of directions, giving equal weight to the internal world--as it seen from the psychoanalytic viewpoint--and to the organic functioning of the brain, as viewed from the perspective of the neurosciences. Arieti's interpretation of schizophrenia helped to overcome the dichotomies between the classical psychoanalytic approach, neurobiological research, and research into cognition, and opened up new paths for an interdisciplinary understanding of mental functioning and creative processes. This paper examines Arieti's book The Parnas (1979); this is a partly-fictionalised account of a pre-eminent figure (Parnas in Hebrew means "head") in the Jewish community in Pisa, Giuseppe Pardo Roques, in the 1930s and early 1940s, who experienced mental illness and was killed in the Nazi extermination of Jews. The paper examines Arieti?s reflections on what he sees as the 'insights' provided by mental illness, which are considered through the figure of Giuseppe Pardo Roques, and in the context of the trauma of the Shoah in Italy.


Modulating acetyl-CoA binding in the GCN5 family of histone acetyltransferases.
The histone acetyltransferase (HAT) GCN5 is the founding member for a family of chromatin remodeling enzymes. GCN5 is the catalytic subunit of a large multi-subunit complex that functions in the regulation of gene activation via acetylation of lysine residues within the N-terminal tails of core histone proteins. Using acetyl-CoA as a co-substrate, the high affinity binding of acetyl-CoA is a critical first step in the reaction. Here, we examine the biochemical and biological importance of a conserved hydroxyl-bearing residue in signature motif A. Interestingly, one major exception is the Saccharomyces cerevisiae GCN5, where an alanine (Ala(190)) is located in the corresponding position. In related GCN5 family structures, a hydroxyl-containing side chain residue is hydrogen-bonded to the alpha-phosphate oxygen of CoA. We demonstrate that this key hydrogen bond contributes approximately 10-fold to the binding affinity of GCN5 HATs for acetyl-CoA. Human p300/CBP-associating factor, human GCN5, and tetrahymena GCN5 displayed dissociation constants (K(d)) for acetyl-CoA of 0.64 +/- 0.12, 0.56 +/- 0.15, and 0.62 +/- 0.17 microm, respectively. In contrast, S. cerevisiae GCN5 displayed a K(d) of 8.5 microm. When Ala(190) was replaced with threonine, the A190T derivative yielded a K(d) value of 0.56 +/- 0.1 microm for acetyl-CoA, completely restoring the higher affinity binding seen with the GCN5 homologs that naturally harbor a threonine at this position. Detailed kinetic analyses revealed that the A190T derivative was otherwise catalytically indistinguishable from wild type GCN5. We also demonstrate that the A190T allele rescued the slow growth phenotype and the defect in HO transcription caused by a deletion of GCN5. Furthermore, the A190T allele supported wild type levels of transcriptionally targeted and global histone H3 acetylation. In each case, the A190T derivative behaved similarly to wild type GCN5, suggesting that the efficacy of HAT activity by GCN5 is not limited by the availability of nuclear acetyl-CoA pools.


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced down-regulation of glucose transporting activities in mouse 3T3-L1 preadipocyte.
The possibility that 3T3-L1 preadipocytes, while the level of its glucose uptake activity is relatively low, may offer a useful tool for studying the cause for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced "lipolytic response" was studied. It was established first, that TCDD causes reduction of glucose uptake, one of the hallmark events of the lipolytic process. Then the function of c-Src was investigated. The antisense c-src oligonucleotide decreased the inhibitory action of TCDD on glucose uptake activity in a sequence specific manner. Since antisense oligonucleotides are known to own their blocking effects to their ability to reduce translation of proteins, Western blotting analysis was performed to verify their effectiveness. As expected, the treatment of pre-adipocytes with antisense c-src oligonucleotide reduced c-Src in a sequence specific manner. The treatment of antisense c-src oligonucleotide alone was sufficient to diminish the inhibitory action of TCDD on glucose uptake activity in 3T3-L1 cells, indicating that c-Src is somehow involved in the action of TCDD. In a similar manner, the contribution of c-Fos was investigated using antisense c-fos oligonucleotide, since c-Fos is known to be one of the most affected proteins by c-Src activation among AP-1 members. The treatment of antisense c-fos oligonucleotide did not block the effect of TCDD on glucose uptake activity in 3T3-L1 cells. Therefore, it is unlikely that c-Fos is very important in the lipolytic signal transduction of TCDD mediated through c-Src. In order to determine the relationship between c-Src and c-Myc in the mitotic signal transduction pathway, the effect of antisense c-myc oligonucleotide was investigated. Basically the same result as antisense c-src oligonucleotide experiment was obtained thereby, suggesting the importance of c-Myc as well as c-Src in the signal transduction of TCDD. To show the effect of antisense c-myc oligonucleotide treatment, the level of c-Myc protein by Western blotting and electrophoretic gel-mobility shift assay was assessed. However, antisense c-myc oligonucleotide treatment increased the activity of c-Myc in a sequence specific manner. This may be the result of cellular compensatory response to the initial suppression of c-Myc by antisense treatment. The observation that antisense c-fos oligonucleotide could not block the effect of TCDD indicates that this preadipocyte model is different from the adipocyte differentiation model.


Evaluation of Micronutrient (Zinc, Magnesium, and Copper) Levels in Serum and Glycemic Status after Nonsurgical Periodontal Therapy in Type 2 Diabetic Patients with Chronic Periodontitis.
To find out the effect of nonsurgical periodontal therapy on serum zinc (Zn), magnesium (Mg), and copper (Cu) concentration and glycemic status in type 2 diabetes with chronic periodontitis (CP). One hundred and twenty patients were included in this study, which was further divided into three groups. Group 1 consisted of forty patients with CP, Group 2 consisted of forty patients of CP with controlled diabetes, and Group 3 consisted of forty patients of CP with uncontrolled diabetes. Periodontal parameters such as plaque index, gingival index, bleeding on probing, pocket depth, and clinical attachment levels (CALs) were evaluated. Blood samples were collected to assess the levels of fasting blood sugar, glycosylated hemoglobin, Zn, Mg, and Cu. All parameters were evaluated at baseline and 3 months after nonsurgical periodontal therapy. The results showed statistically significant reduction in all the clinical parameters within the groups except for the CAL in group 1 patients (P = 0.05). The glycemic status also showed a statistically significant reduction after treatment (P < 0.001). The intragroup comparison was taken between the values of micronutrients, showed substantial increase in the levels of both Zn and Mg and decrease in the level of Cu after nonsurgical periodontal treatment (P < 0.001). Patients with diabetes and periodontitis had altered metabolism of Zn, Mg, and Cu contributing to the progression and complication of diabetes mellitus and periodontitis. Nonsurgical periodontal treatment improved the variation and concentration of plasma micronutrients and also the periodontal status and glycemic level.


Efficiency of colored modified box traps for sampling of tabanids.
The efficiency of ten differently colored modified box traps for collecting tabanids was studied in the Monjoroš Forest in eastern Croatia. A total of 5,436 specimens belonging to 16 species of tabanids grouped into six genera were collected. The genus Tabanus was the most represented with 98% of all collected tabanids. Tabanus bromius comprised 90% of tabanids collected, and was the most abundant species collected in all box traps. The majority of tabanids (74%) were collected from black, brown, bordeaux, red, and blue traps (dark group), whereas 26% were collected from green, light violet, white, orange, and yellow traps (light group). The black modified trap was the most successful and collected 20% of all collected tabanids, whereas the yellow trap was the least effective with 1%. The number of collected specimens of species T. bromius differed significantly between the dark and light group of traps. Traps with lower reflectance from green color collected 77% of T. bromius. The most species of tabanids (12) was collected in the brown trap, whereas the least number of species (6) was collected in the yellow trap.


Lessons Learned From Transitioning PEPFAR Track 1.0 Care and Treatment Programs: Case Studies in Financial Management Capacity Building in Zambia and Botswana.
In 2008, the United States government mandated transition of internationally managed HIV care and treatment programs to local country ownership. Three case studies illustrate the US Health Resources Services Administration's fiscal assessment and technical assistance (TA) processes to strengthen local organizations' capabilities to absorb and manage United States government funding. Review of initial, TA and follow-up reports reveal that the 1 Botswanan and 2 Zambian organizations closed 10 of 17 financial capacity gaps, with Health Resources Services Administration assisting on 2. Zambian organizations requested and absorbed targeted TA on the basis of the consultant's desk review, their finance staff revised fiscal policies and procedures, and accordingly trained other staff. In Botswana, delays in integrating recommendations necessitated on-site TA for knowledge building and role modeling. Organizational maturity may explain differences in responsiveness, ownership, and required TA approaches. Clarifying expectations of capacity building, funding agreement, and nonmonetary donor involvement can help new organizations determine and act on intervening actions.


Evaluation of Distortion in the Posterior Palatal Seal Area of Maxillary Cast by Different Adaptation Techniques of Denture Bases.
To evaluate and compare the amount of distortion in the posterior palatal seal area in V-shaped and U-shaped palatal form of maxillary cast by different adaptation techniques of maxillary denture bases. A total of 60 stone casts were made, out of which 30 identical stone casts of U-shaped palatal form and 30 identical stone casts of V-shaped palatal form of maxillary casts were prepared. The 30 stone casts of U-shaped palatal form and 30 stone casts of V-shaped palatal forms were divided into three groups for measurements to be done. Data were statistically analyzed by using two-way analysis of variance (ANOVA) without replication. Discrepancies of fit of dentures on U-shaped casts and V-shaped casts of Groups 1, 2, and 3 in transverse and sagittal sections were measured, and comparative statistical analysis between Group 1&2, Group 1&3, and Group 2&3 was done for statistical significant values. Discrepancy in the central region was maximum, and the anchoring methods Group 2 and Group 3 produced a significantly better adaptation than the conventional method (Group 1). The adaptations for V-shaped palate were better when compared with U-shaped palate in the central region.


Feasibility analysis of magnetic resonance imaging-based radiomics features for preoperative prediction of nuclear grading of ductal carcinoma in situ.
The nuclear grading of ductal carcinoma in situ (DCIS) affects its clinical risk. The aim of this study was to investigate the possibility of predicting the nuclear grading of DCIS, by magnetic resonance imaging (MRI)-based radiomics features. And to develop a nomogram combining radiomics features and MRI semantic features to explore the potential role of MRI radiomic features in the assessment of DCIS nuclear grading. A total of 156 patients (159 lesions) with DCIS and DCIS with microinvasive (DCIS-MI) were enrolled in this retrospective study, with 112 lesions included in the training cohort and 47 lesions included in the validation cohort. Radiomics features were extracted from Dynamic contrast-enhanced MRI (DCE-MRI) phases 1st and 5th. After feature selection, radiomics signature was constructed and radiomics score (Rad-score) was calculated. Multivariate analysis was used to identify MRI semantic features that were significantly associated with DCIS nuclear grading and combined with Rad-score to construct a Nomogram. Receiver operating characteristic curves were used to evaluate the predictive performance of Rad-score and Nomogram, and decision curve analysis (DCA) was used to evaluate the clinical utility. In multivariate analyses of MRI semantic features, larger tumor size and heterogeneous enhancement pattern were significantly associated with high-nuclear grade DCIS (HNG DCIS). In the training cohort, Nomogram had an area under curve (AUC) of 0.879 and Rad-score had an AUC of 0.828. Similarly, in the independent validation cohort, Nomogram had an AUC value of 0.828 and Rad-score had an AUC of 0.772. In both the training and validation cohorts, Nomogram had a significantly higher AUC value than Rad-score (P<0.05). DCA confirmed that Nomogram had a higher net clinical benefit. MRI-based radiomic features can be used as potential biomarkers for assessing nuclear grading of DCIS. The nomogram constructed by radiomic features combined with semantic features is feasible in discriminating non-HNG and HNG DCIS.


A Rare Case of Pulmonary Emboli Presenting With ST Elevation on ECG.
Pulmonary embolism is a common medical emergency and often life threatening but can be misdiagnosed frequently leading to fatal outcomes. Changes in electrocardiogram (ECG) are common in pulmonary embolism and rarely they can present with ST elevation. We here describe a 79-year-old woman who presented after a cardiac arrest and was found have ST-segment elevation on ECG with normal coronary angiogram while CT scan revealing pulmonary embolism.


Phenotypic and microRNA transcriptomic profiling of the MDA-MB-231 spheroid-enriched CSCs with comparison of MCF-7 microRNA profiling dataset.
Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.


Impact of EBV essential nuclear protein EBNA-3C on B-cell proliferation and apoptosis.
For over 40 years, EBV infection has been implicated in the etiology of a variety of lymphoid malignancies with the exceptional ability to drive resting B cells to continuously proliferate by successfully overriding cellular apoptotic stimuli. EBV utilizes the normal physiology of B-cell differentiation to persist within the memory B-cell pool of the immunocompetent host and subsequently establishes a life-long latent infection. During latency, out of a subset of viral genes expressed, EBNA-3C is one of the essential antigens required for in vitro primary B-cell transformation. EBNA-3C acts as a transcriptional coregulator by interacting with various cellular and viral factors. For the last 10 years, we have been actively engaged in discerning the biological significance of these interactions and revealed that EBNA-3C primarily targets two important cellular pathways - cell cycle and apoptosis. This review aims to summarize our current knowledge on EBNA-3C-mediated functions and describe how EBNA-3C seizes these cellular pathways that eventually promote B-cell lymphomagenesis. A scrupulous understanding of the critical relationship between EBNA-3C and these cellular machineries will not only aid in elucidating EBV pathogenesis, but also largely facilitate the development of novel diagnostic, as well as therapeutic, strategies against a vast range of EBV-associated B-cell lymphomas.


The ability of hens to regulate phosphorus intake when offered diets containing different levels of phosphorus.
Two experiments were conducted to determine the extent and ability of laying hens to regulate their phosphorus (P) intake when offered a choice of diets containing different levels of phosphorus. In the first experiment, Babcock B-300 hens, 72 weeks old, received a choice of diets offered in each of two plastic cups. The dietary choices of P levels included: 0.75 percent P vs. 0.75 percent P diet (control), 0.19 percent vs. 0.46 percent P, 1.00 percent vs. 2.43 percent P and 0.19 percent vs. 2.43 percent P diet. The cups were weighed and replenished every three days. After one month, the calcium level in all diets was increased from 3.00 to 6.00 percent calcium and the experiment continued for a second month. The second experiment involved the same dietary choices of P with a constant level of 3.00 percent calcium. Hens in this experiment were 48 weeks old. In both Experiments 1 and 2 the daily feed consumption was determined by weighing all cups at two hour intervals for two days. This procedure was performed after hens had been on the experimental regime for one month. Hens in both experiments clearly regulated their intake of P when offered the above choices. Hens avoided the consumption of the 2.43 percent P diet in favor of the diet containing less P. Consumption of the 2.43 percent P diet, even when avoided to a large extent, reduced both egg production and egg specific gravity. Increased calcium levels in the diets resulted in an increase in consumption of the 2.43 percent P diet. Young hens demonstrated a significant increase in consumption of the 0.46 percent P diet over the 0.19 percent P diet. Both old and young hens in the 0.46 percent P vs. 0.19 percent P group in both experiments maintained egg specific gravity, egg weight and egg production at levels comparable to controls. Results of the two hour feed weighings showed that laying hens in the 0.19% vs. 2.43% P group exhibited a noon-time peak in preferential consumption of P, followed by a marked afternoon-evening decline. This decline occurs both for relative and absolute P intake.


Relation between hemostatic parameters and prognostic/predictive factors in breast cancer.
In our study, we searched for a relation between various prognostic and predictive factors and hemostatic parameters. One hundred women with newly diagnosed breast cancer after surgery were included. Patients did not receive systemic therapy or radiotherapy. The control group included 100 healthy, age-matched women. In the patient group, age, menopausal status, tumor size, grade, axillary lymph node status, steroid receptor status, p53, and HER2/neu were evaluated. Plasma levels of factor VIII, factor IX, D-dimer, fibrinogen, protein C, protein S, vWF, and antithrombin III were measured in both groups. Plasma levels of factor VIII, factor IX, vWF, and CRP in patients with breast cancer were higher than those in controls. Protein S levels in patients were lower than in controls. There was no significant difference in other hemostatic parameters between the groups. In patients with axillary lymph node metastasis, factor VIII levels were significantly higher than in node-negative patients. There was a strong correlation between axillary lymph node status, number of metastatic nodes, and factor VIII levels. There was no correlation between factor VIII levels and CRP. Factor VIII levels were higher in the group having high HER2/neu (3+) than in the group with negativity for HER2/neu. There was a strong correlation between axillary lymph node involvement, number of metastatic nodules, overexpression of HER2/neu, hemostatic parameters, and factor VIII levels. Our study showed that factor VIII level measurement can provide additional data for evaluation of breast cancer patients' prognosis.