Ultrasonographic and Doppler study of the thyroid gland in Graves' disease before and after treatment with antithyroid drugs.
To determine the effects of medical treatment on the thyroid gland, peripheral circulation, and laboratory findings in patients with Graves' disease. Twenty patients with Graves' disease were treated with either carbimazole and propranolol (group I) or carbimazole only (group II). Serum free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and thyrotropin-binding inhibitory immunoglobulins (TBII) were estimated before and after 6 weeks of treatment. Duplex Doppler ultrasonographic examination of the thyroid, inferior thyroid artery (ITA), and common carotid artery (CCA) was performed before and after 2, 4, and 6 weeks of therapy. Serum FT(4) and TBII decreased after treatment in both groups, whereas serum TSH increased in group I only. The volume of the thyroid gland and parenchymal blood velocity were increased in these patients and diminished only with addition of propranolol to carbimazole. A diffuse hypoechogenic pattern in the thyroid gland and increased ITA blood flow and peak velocity were observed in all patients and persisted throughout treatment. The mean CCA peak blood velocity was accelerated in Graves' disease and diminished after 6 weeks of therapy in both groups, whereas increased CCA blood flow diminished only in group I. A 6-week period of therapy with carbimazole and propranolol has no effect on the diffuse low echogenic pattern in the thyroid gland and the accelerated ITA blood flow in Graves' disease. The addition of propranolol is associated with early decrements in thyroid volume, parenchymal vascularity, and CCA blood flow as well as early recovery of TSH suppression, but it has no additional effect on thyroid hormone secretion or TBII levels.


Effect of a clinical pharmacist's interventions on duration of antiretroviral-related errors in hospitalized patients.
The effect of a clinical pharmacist's interventions on the duration of antiretroviral-related errors in hospitalized patients was studied. Between August 4, 2005, and February 4, 2006, all patients at least 18 years of age who were admitted to a 651-bed tertiary care teaching hospital and prescribed highly active antiretroviral therapy (HAART) were identified by one clinical pharmacist. If a HAART error was suspected, the pharmacist intervened with the house staff or outpatient physician to discuss and resolve the problem. The pharmacist also retrospectively identified potential HAART errors among patients with human immunodeficiency virus (HIV) admitted between January 2 and June 30, 2005. HAART errors included the following: incomplete regimen, incorrect dosage, incorrect schedule, medication-disease interaction, incorrect formulation, incorrect antiretroviral, duplication of therapy, and drug-drug interaction. The duration of each error was measured from the time of the initial incorrect order until a correct order was placed or until the patient was discharged. A total of 199 admissions for patients with an order for HAART were identified during the study periods. A total of 73 HAART errors were confirmed in 41 patients. The most common type of error was incomplete regimen. There was no significant difference in the frequency or type of prescribing when comparing the preintervention and intervention phases. The median length of time until an error was corrected, however, was significantly shorter during the intervention phase (15.5 hours) than the preintervention phase (84 hours) (p < 0.0001). The duration of prescribing errors was decreased when a clinical pharmacist monitoring patients receiving HAART intervened to resolve errors.


A novel T→G splice site mutation of CRYBA1/A3 associated with autosomal dominant nuclear cataracts in a Chinese family.
The purpose of this study was to identify the disease-causing mutation and the molecular phenotype that are responsible for the presence of an autosomal dominant congenital nuclear cataract disease in a Chinese family. The family history and clinical data were recorded. The patients were given a physical examination and their blood samples were collected for DNA extraction. Direct sequencing was used to detect the mutation. Transcription analysis of the mutant crystallin, beta A1 (CRYBA1/A3) gene was performed to verify whether the defective mutation had influenced the splice of the mature mRNA. The phenotype of the congenital cataract in the family was identified as a nuclear cataract type, by using slit-lamp photography. Direct sequencing revealed a novel mutation IVS3+2 T→G in CRYBA1/A3. This mutation co-segregated with all affected individuals in the family, but was not found in unaffected family members nor in the 100 unrelated controls. Transcription analysis of the mutant CRYBA1/A3 gene indicated that this mutation had influenced the splice of the mature mRNA. Our study identified a novel splice site mutation in CRYBA1/A3. This mutation was responsible for aberrant splicing of the mature mRNA and had caused the congenital nuclear cataracts in the family. This is the first report relating an IVS3+2 T→G mutation of CRYBA1/A3 to congenital cataracts.


p21-activated kinase-1 signaling mediates cyclin D1 expression in mammary epithelial and cancer cells.
p21-activated kinase 1 (Pak1) has been shown recently to induce hyperplasia in the mammary epithelium, a phenotype also manifested by overexpression of cyclin D1, a known indicator of the proliferative stage. Here we investigated the role of the Pak1 pathway in the expression of cyclin D1 using tissue culture models and transgenic mice expressing activated Pak1 in mammary glands. We found that hyperplastic mammary glands from catalytically active Pak1 transgenic mice exhibit a 5- to 7-fold increased expression of cyclin D1 as compared with stage-matched wild-type mice. In addition, Pak1 levels were elevated in human breast tumors and also correlated well with increased cyclin D1 expression. Increased expression of Pak1 in breast cancer cells stimulated cyclin D1 promoter activity, elevated levels of cyclin D1 mRNA, protein, and nuclear accumulation of cyclin D1. Conversely, Pak1 inhibition by an auto-inhibitory peptide (amino acids 83-149) or Pak1 knockdown by short interference RNA markedly reduced the expression of cyclin D1, suggesting a requirement of a functional Pak1 pathway for optimal expression of cyclin D1. Results from deletion and mutant analysis indicate that Pak1 regulates cyclin D1 transcription by means of an NF-kappaB-dependent pathway. Together, these findings suggest a model wherein Pak1 regulation of cyclin D1 expression might involve an NF-kappaB-dependent pathway and that hyperplasia in the mammary glands of Pak1-TG mice may be associated, at least in part, with the up-regulation of cyclin D1, and that Pak1 is up-regulated in human breast tumors.


Low density neutrophils are increased in patients with Behçet's disease but do not explain differences in neutrophil function.
Behçet's disease (BD) is a multisystem autoinflammatory disease characterised by mucosal ulceration, ocular, neural, joint and skin inflammation. The cause of BD is not known but there is a strong genetic association with HLA-B*51, IL10 and IL23R. Neutrophils are a first line of defence against invading pathogens and have been described as activated in patients with BD. Neutrophils can now be separated into different subsets, such as low density (LDN) and normal density (NDN) that have diverse functional roles. We wished to address neutrophil heterogeneity in patients with BD. Peripheral blood neutrophils were obtained from 32 BD patients and 37 healthy aged-matched controls. Percoll isolation was used to isolate all neutrophils, while Ficol-Hypaque was used to obtain LDN and NDN. Phagocytic capacity and production of reactive oxygen species (ROS), and neutrophil extracellular traps (NET) stimulated with phorbol 12-myristate 13-acetate (PMA) and Escherichia coli (E.coli) were assessed in both groups. We have demonstrated reduced phagocytic capacity and ROS production but greater NET production by total neutrophils stimulated with PMA or E.coli from BD patients in comparison with healthy controls. Patients with BD had elevated numbers of LDN and lower number of NDN compared with healthy controls. However, both neutrophil subsets showed the same reduced ROS production and phagocytic function as total neutrophils in both groups. Our novel findings indicate that the neutrophil population in BD is heterogeneous and the increased number of LDN in combination with greater NET production may contribute to the inflammatory response and pathogenesis.


Calcium release from porcine thyroid microsomes by phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate.
We have demonstrated Ca2+ mobilization induced by inositol compounds from intracellular stores of isolated porcine thyroid cells that were permeabilized with saponin and from fractionated thyroid microsomes that were preloaded with Ca2+. In the presence of saponin and antimycin A, a mitochondrial inhibitor, the Ca2+ concentration in the cell suspension decreased after the addition of ATP; the addition of inositol 1,4,5-trisphosphate (IP3) elicited transient elevations in Ca2+. The half-effective concentration (EC50) of IP3 was about 1 microM. TSH, acetylcholine, and norepinephrine had no effect on the Ca2+ movement, but phosphatidylinositol 4,5-bisphosphate (PIP2) induced a similar Ca2+ release (EC50 = 3 microM). PIP2-induced release decreased as the Mg2+ concentration was raised. After the release induced by a maximal amount of IP3, PIP2 could induce a further Ca2+ release. We also measured Ca2+ efflux from fractionated microsomes preloaded with 45Ca2+ by ATP-dependent transport. IP3 induced a small efflux of 45Ca2+, but PIP2 was much more effective at low Mg2+ concentrations. More than half of the loaded 45Ca2+ was released by 10 microM PIP2 within 30 sec, and the EC50 was 0.7 microM. These results suggest that Ca2+ mobilization from the microsomes mediated by inositol compounds participates in the regulation of thyroid cell functions.


Fluorescence-quenching studies on a conformational transition within a domain of the beta 2 subunit of Escherichia coli tryptophan synthase.
The fluorescence quenching by acrylamide of the single tryptophan residue in the beta 2 subunit of tryptophan synthase from Escherichia coli K12 is studied for different states of the protein: the native apo-enzyme and holo-enzyme, the nicked apo-protein and holo-protein and the isolated proteolytic fragment F1 corresponding to the N-terminal two thirds of beta 2. The quenching constants measured are used to estimate the accessibility of the tryptophan residue in these different forms. The results are discussed in terms of conformational transition within the F1 domain, occurring in the presence of the cofactor, pyridoxal 5'-phosphate, in the native enzyme. The proteolytic cleavage of the native enzyme is shown to render the nicked protein unable to undergo this conformational change.


Emerging principles of cancer biophysics.
Cancer is a multi-step process where normal cells become transformed, grow, and may disseminate to establish new lesions within the body. In recent years, the physical properties of individual cells and the tissue microenvironment have been shown to be potent determinants of cancer progression. Biophysical tools have long been used to examine cell and tissue mechanics, morphology, and migration. However, exciting developments have linked these physical traits to gene expression changes that drive metastatic seeding, organ selectivity, and tumor growth. Here, we present some vignettes to address recent studies to show progress in harnessing biophysical tools and concepts to gain insights into metastasis.


Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis.
Cognitive behavioral therapies (CBT) have been demonstrated efficacious in treating perinatal depression (PND). This has been demonstrated in several meta-analyses of randomized controlled trials and quasi-experimental studies. However, there is a need for up-to-date meta-analytical evidence providing reliable estimates for CBT's effectiveness in treating and preventing PND. Furthermore, with the world moving toward precision medicine, approaches require a critical synthesis of psychotherapies, especially to unpack their mechanisms of action and to understand what approaches work best for whom. Therefore, the present systematic review and meta-regression analyses aim to answer these research questions. We searched six academic databases through February 2022 and identified 56 studies for an in-depth review. Using pretested data extraction sheets, we extracted patient-level and intervention-level characteristics and effect size data from each study. Random-effects meta-analyses and mixed-effect subgroup analyses were run to delineate the effectiveness and moderators of CBT interventions for PND, respectively. CBT-based interventions yielded a strong effect size (SMD = -0.74, 95% confidence interval [CI]: -0.91 to -0.56, n = 9,722) in alleviating depressive symptoms. These interventions were effective across different delivery formats (individual, group, and electronic) and could be delivered effectively by specialists and nonspecialists. Longer duration CBT interventions may not necessarily be more effective than shorter ones. Moreover, CBT-based interventions should consider including various behavioral ingredients to maximize intervention benefits.


Effect of fluoride on the secretion of insulin in the rat.
Sodium fluoride (CAS 7681-49-4) 5-20 micromol/L in the extracellular space inhibited insulin secretion by isolated Langerhans islets stimulated with glucose. Insulin secretion followed a negative exponential function. This phenomenon is rapidly reversible. Perfusion of pancreatic tissue (rat) in vivo with stimulatory levels of glucose revealed that 20 micromol/L fluoride in the perfusion fluid inhibited the initial and sustained phases of insulin secretion to 15% of that of controls. The stimulatory effects of the ionophore A23187, phorbol-ester and forskolin on the secretion of insulin of isolated rat Langerhans islets in vitro were inhibited by 20 micromol/L fluoride. The results suggested that fluoride affects some stage of insulin secretion situated below the cascade of events that include the participation of calmodulin, protein-kinase C and cyclic AMP.


Existence of renal alpha 1- and alpha 2-adrenoceptors in the human kidney: radioligand binding study in membranes from the human renal cortex and medulla.
We investigated alpha 1- and alpha 2-adrenoceptors by radioligand binding studies in plasma membranes from the human renal cortex and medulla using a new alpha 1-adrenoceptor antagonist, 3H-bunazosin, and an alpha 2-adrenoceptor antagonist, 3H-rauwolscine. Human kidneys were obtained post-mortem (n = 4) or at surgery for carcinoma of the kidney (n = 10). The specific binding of both radioligands was rapid, saturable, reversible and specific. Scatchard analysis of 3H-bunazosin binding showed that the renal cortex had a KD of 4.6 nmol/l and a Bmax of 34.7 fmol/mg of protein, and the medulla a KD of 2.4 nmol/l and a Bmax of 23.2 fmol/mg. The specific binding of 3H-rauwolscine had a KD of 5.6 nmol/l and Bmax of 22.4 fmol/mg of protein for the cortex and values of 5.1 and 42.0, respectively, for the medulla. Competitive inhibition studies suggested that the binding of both radioligands was to sites with alpha 1 and alpha 2 specificity, respectively. The present studies demonstrate that human renal plasma membranes from both the cortex and medulla contain binding sites with both alpha 1- and alpha 2-adrenoceptors.


CTLA-4 activation of phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death.
The balance of T-cell proliferation, anergy and apoptosis is central to immune function. In this regard, co-receptor CTLA-4 is needed for the induction of anergy and tolerance. One central question concerns the mechanism by which CTLA-4 can induce T-cell non-responsiveness without a concurrent induction of antigen induced cell death (AICD). In this study, we show that CTLA-4 activation of the phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death. CTLA-4 ligation induced PI 3K activation as evidenced by the phosphorylation of PKB/AKT that in turn inactivated GSK-3. The level of activation was similar to that observed with CD28. CTLA-4 induced PI 3K and AKT activation also led to phosphorylation of the pro-apoptotic factor BAD as well as the up-regulation of BcL-XL. In keeping with this, CD3/CTLA-4 co-ligation prevented apoptosis under the same conditions where T-cell non-responsiveness was induced. This effect was PI 3K and PKB/AKT dependent since inhibition of these enzymes under conditions of anti-CD3/CTLA-4 co-ligation resulted in cell death. Our findings therefore define a mechanism by which CTLA-4 can induce anergy (and possibly peripheral tolerance) by preventing the induction of cell death.


Does fluoridation reduce the use of dental services among adults?
The authors determine whether prevention influences the use of health services. Fluoridation's effect on restorative dental demand among 972 Washington state employees and spouses, aged 20 to 34 years, in two fluoridated communities and a nonfluoridated community was examined. At baseline, adults were interviewed by telephone, and oral assessments were conducted to measure personal characteristics, lifetime exposure to fluoridated water, oral disease, and the quality of restorations. Adults were followed for 2 years to measure dental demand from dental claims. Each adult's baseline and claims data were linked with provider and practice variables collected from the dentist who provided treatment. Relative to adults with no lifetime exposure to fluoridated water, adults drinking fluoridated water for half or more of their lives had less disease at baseline and a lower but nonsignificant probability of receiving a restoration in the follow-up period. In the 2-year follow-up period, however, more than half of the restorations were performed to replace fillings of satisfactory or ideal quality at baseline. When only teeth with decay and unsatisfactory fillings at baseline were considered, adults with high fluoridation exposure had a lower probability of receiving a restoration than adults with no exposure. Market effects also were detected in demand equations; relative to adults in the nonfluoridated community, adults residing in the fluoridated community with a large dentist supply received a greater number of restorations, suggesting potential supplier-induced demand from less disease and fewer patients. Among adults aged 20 to 34 years with private dental insurance, fluoridation reduces oral disease but may or may not reduce use of restorative services, depending on dentists' clinical decisions.


Testicular leiomyosarcoma and marked alopecia in a cryptorchid ferret (Mustela putorius furo).
A 3.5-year-old male ferret, bought as male castrated, was presented to the veterinarian with marked alopecia of back, neck, abdomen and tail, a pronounced sexual behaviour and weight loss. An inguinal mass of about 2.5 cm in diameter was diagnosed as potentially tumorous inguinal testicle by ultrasound and fine-needle aspiration. Adrenal glands and prostate were ultrasonographically unremarkable. The surgically removed cryptorchid testicle contained a greyish tumour that was histologically composed of spindle-shaped cells with elongated nuclei, embedded in a fibro-vascular stroma. Up to two mitotic figures per high power field were noted. Additionally, an interstitial cell hyperplasia and marked reactive proliferation of a collagen-rich fibrous tissue were observed. Tumour cells were positive for α-smooth muscle actin, desmin, and occasionally vimentin and S-100, leading to the diagnosis of an intratesticular leiomyosarcoma. As an adrenal-associated endocrinopathy was excluded and a complete fur recovery was observed after removal of the cryptorchid testicle the alopecia was eventually due to hormones produced by the hyperplastic interstitial (Leydig) cells.


Inhomogeneous carrier transport at contact/GaN interfaces and thermal instability of vertical light-emitting diodes.
The carrier-transport behavior at the interface of a contact and n-type GaN was investigated for group III nitride vertical light-emitting diodes (LEDs). Three types of samples were investigated including dry-etched flat Ga-polar n-GaN (GA), dry-etched flat N-polar n-GaN (NF), and wet-etched roughened N-polar n-GaN (NR). Schottky diodes fabricated using a palladium contact revealed that carrier transport at the contact/GaN interface could be understood in terms of the barrier inhomogeneity model, in which the local shallow barriers dominated the overall carrier transport. Kelvin probe force microscopy showed that the peculiar crystallographic structures and native defects (acting as the local shallow barriers) led to the largest tunneling probability of the NR samples. The study was followed up by forming a TiN/Al contact on the NR surfaces to study the thermal instability of the vertical LEDs, revealing that the vertical LEDs were degraded after a thermal annealing process. This could be related to the n-contact size, indicating that the degradation of vertical LEDs was likely due to the failure of Ohmic patches (contacts formed on the defects and/or the tip/edge of hexagonal cones) at elevated temperature.


The prognostic value of the serum level of C-reactive protein for the survival of patients with a primary sarcoma of bone.
The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing's sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival.


Gas phase transesterification reactions catalyzed by lipolytic enzymes.
Porcine pancreatic lipase and Fusarium solani cutinase were used to catalyze transesterification reactions between methyl propionate, ethyl propionate, and a series of primary alcohols at high temperatures in a continuous packed-bed gas-solid reactor, in which the solid phase is composed of the enzyme and the substrates and products are in a gaseous form. In this type of system, enzyme activity was found to depend essentially on the water activity (A(w)) of the enzyme preparation.


Aphasic status epilepticus: a case report.
Complex partial status epilepticus with aphasia as the sole manifestation has been reported only twice before. We studied a 60-year-old diabetic who was aphasic for 12 days. The diagnosis of aphasic status was supported by electroencephalographic seizure patterns in the left hemisphere.


Threats to Belonging, Immune Function, and Eating Behavior: an Examination of Sex and Gender Differences.
The first goal of this review is to discuss the evidence linking belonging threats to immune function and food intake. The second goal is to evaluate whether the links among belonging threats, immune function, and eating behavior differ based on gender. Threats to belonging are linked to elevated herpesvirus antibody titers, dysregulated appetite-relevant hormones, and increased food consumption. Furthermore, these relationships are largely consistent for both men and women. Threats to belonging are also linked to elevated inflammation. However, some studies showed that these effects were stronger among women, others demonstrated that they were stronger among men, and others determined that the links were consistent for men and women. Understanding why belonging threats are inconsistently linked to inflammation across men and women is an important next step. We conclude the review with four concrete recommendations for researchers studying belonging threats, immune function, and eating behavior.


Unraveling enterohemorrhagic Escherichia coli infection: the promising role of dietary compounds and probiotics in bacterial elimination and host innate immunity boosting.
The innate immune system has developed sophisticated strategies to defense against infections. Host cells utilize the recognition machineries such as toll-like receptors and nucleotide binding and oligomerization domain-like receptors to identify the pathogens and alert immune system. However, some pathogens have developed tactics to evade host defenses, including manipulation of host inflammatory response, interference with cell death pathway, and highjack of phagocytosis signaling for a better survival and colonization in host. Enterohemorrhagic Escherichia coli (EHEC) is a notorious foodborne pathogen that causes severe tissue damages and gastrointestinal diseases, which has been reported to disturb host immune responses. Diverse bioactive compounds such as flavonoids, phenolic acids, alkaloids, saccharides, and terpenoids derived from food varieties and probiotics have been discovered and investigated for their capability of combating bacterial infections. Some of them serve as novel antimicrobial agents and act as immune boosters that harness host immune system. In this review, we will discuss how EHEC, specifically E. coli O157:H7, hijacks the host immune system and interferes with host signaling pathway; and highlight the promising role of food-derived bioactive compounds and probiotics in harnessing host innate immunity and eliminating E. coli O157:H7 infection with multiple strategies.


[4-aminobutyrophenones with hypotensive activity].
A series of new butyrophenones was synthesized, the aim being to reduce neuroleptic activity and enhance the hypotensive effects of this class of drugs. The compounds were screened for toxicity according to the Irwin scheme and tested in anaesthetized cats for their effects on systemic arterial pressure. The most interesting compound, i.e. 1-(4'-fluorobenzoyl)-3-pyrrolidinyl-propane, was tested also in anaesthetized rabbits, cats, and dogs and in concious dogs. Moreover its central nervous system effects were tested in rats and mice. The compound proved practically devoid of neurological effects and showed interesting hypotensive activity.


Is the KTP laser effective in tonsillectomy?
Thirty-eight patients underwent a randomized double-blind trial using the KTP laser for tonsillectomy on one tonsil and standard dissection tonsillectomy on the other tonsil. Blood loss was less on the laser side. However, pain though initially slightly less on the laser side (days 1 and 2 post-operation) was worse on the laser side at 2 weeks due to delayed healing of the tonsillar bed. There were no primary or reactionary haemorrhages but a 15% incidence of secondary haemorrhage on the laser side.


Arrhythmogenic Risk Assessment Following Four-Week Pretreatment With Nicotine and Black Tea in Rat.
There is the controversy concerning the main component of tobacco, which is responsible for its arrhythmogenesis. In addition, there is the lack of adequate information about the influence of combination of black tea and nicotine on heart rhythm. This study aimed to examine whether pretreatment with black tea and nicotine could modulate the susceptibility to lethal ventricular arrhythmias. Animals were randomized to control, black tea, nicotine, and black tea plus nicotine groups. Test groups were treated with black tea brewed (orally) and nicotine (2 mg/kg, subcutaneous), alone and in combination for four weeks. On day 29, aconitine was infused intravenously for induction of cardiac arrhythmia. In comparison with the control group, each of tea and nicotine significantly decreased the duration of the ventricular tachycardia (VT) plus ventricular fibrillation (VF) and the score of arrhythmia severity (P < 0.05 and P < 0.01, respectively,). The latency for the first VT event was significantly longer in the all test groups, but VF latency was significant only in tea and nicotine groups compared with control group (P < 0.05 and P < 0.01, respectively).Threshold dose of aconitine for inducing VT and VF increased in all test groups, but only VT showed a significant difference in comparison to the control group (P < 0.001). The findings suggest that sub-chronic consumption of nicotine or black tea alone with appropriate doses could potentially be antiarrhythmic and its combination regimen does not increase the risk of fatal ventricular arrhythmias during four-week consumption period in rats.


CD38 expression on CD8(+) T cells as a prognostic marker in vertically HIV-infected pediatric patients.
Increased expression of CD38 on CD8(+) T cells is associated with activation of the immune system, progression of HIV disease, and death in adults. The prognostic significance of these cells in HIV-infected children, where the picture is complicated by age-related differences in CD38 expression, remains controversial. Measuring the unimodal expression of CD38 on CD8(+) T cells in adults and children by flow cytometry is best accomplished by quantitating the antigen on the cell surface. To our knowledge, this technique has not previously been reported in a pediatric population. Vertically HIV-infected children were age matched for mild (n = 26) and severe (n = 23) clinical disease. Eleven age-matched HIV-negative controls were included for comparison. Quantitation of CD38 on CD8(+) T cells was performed at baseline and 1 y later. The ages of the children in the three clinical groups did not differ significantly (p = 0.6004). HIV-infected children had significantly increased CD38 measurements in comparison with the HIV-negative controls (p = 0.0131), and the severe disease group tended to have higher measurements than the mild disease group. Increased CD38(+)CD8(+) T cells were significant predictors of death within the first year (p = 0.043). These findings support the view that increased CD38 expression on CD8(+) T cells has the same prognostic significance in pediatric as in adult HIV disease.


Incidental cervical metastases from thyroid carcinoma during neck dissection.
To quantify and discuss the prevalence of unsuspected thyroid lymph node metastases discovered in specimens from neck dissection for head and neck squamous cell carcinoma (HNSCC) and discuss the impact on patient management. Retrospective study between May 2004 and January 2007. University hospital. Pathological analysis of cervical lymph node dissection performed during surgery for HNSCC in a total of 349 neck dissections in 266 consecutive patients. Twenty-one patients showed metastatic lymph nodes from thyroid cancer (prevalence 7.9%): 13 cases were metastatic from a papillary thyroid carcinoma and 8 cases from a follicular carcinoma. In 5 of the 21 patients, classical dissection was associated to recurrent nerve dissection and unilateral lobectomy; no thyroid carcinoma was found. Thirteen patients received radiotherapy for HNSCC. Follow-up comprised annual ultrasonographic examination of the neck and thyroid in these 21 patients. Total thyroidectomy was decided on in 5, with discovery of 3 micro-papillary thyroid carcinomas, in a single patient (complementary 131I treatment). No thyroid carcinomas were found for the other 4 patients. No patients died from thyroid carcinoma during follow-up (mean: 41 months). The prevalence of lymph node metastasis from thyroid carcinoma in cervical lymph node dissection during treatment of HNSCC seems higher (7.9%) than rates reported in the literature (0.3 to 1.6%). This may be due to the histopathological methods employed. Management of patients should be discussed in the light of thyroid ultrasonography and prognosis of HNSCC.


Decrease of miR-622 expression suppresses migration and invasion by targeting regulation of DYRK2 in colorectal cancer cells.
More and more evidence indicates that microRNAs are present and involved in many tumor-related diseases. The function of microRNA-622 (miR-622) in colorectal cancer (CRC) remains controversial. Dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) has been reported as a tumor suppressor gene in different cancers. The detailed regulation mechanism of DYRK2 in CRC remains unclear. miR-622 and DYRK2 expression levels were detected at tissue and cellular level respectively by using real time polymerase chain reaction (PCR), Western blot, and immunohistochemical staining. Pearson's correlation analysis was used to evaluate the correlation between miR-622 and DYRK2. Transwell assay was applied to measure the effect of miR-622 on migration and invasion of SW1116 and SW480. We used dual luciferase reporter assay to confirm the targeted binding effect of miR-622 and DYRK2 3'-untranslated region (3'UTR). An antisense experiment was executed to further confirm the role miR-622 had played with regard to migration and invasion by targeting regulation of DYRK2 pathway in CRC cells. In our research, we found that the expression of miR-622 was elevated in CRC tissues and cell lines compared to that of nonCRC tissues and the normal human colon epithelial cell line NCM460. Correspondingly, the expression of DYRK2 in CRC tissues and cell lines showed a contrary tendency. The different expression level of DYRK2 was closely correlated with clinicopathological characteristics of CRC patients. We demonstrated that down-regulation of miR-622 could inhibit the ability of migration and invasion of CRC cell lines SW1116 and SW480. Also, we confirmed that DYRK2 was negatively regulated by miR-622 via a specific targeted binding site within the 3'UTR. We finally verified that the migration and invasion ability of CRC cells in the conducted DYRK2 3'UTR defect plasmid transfection group were lower compared to miR-622 and cotransfection group. The findings of this study indicate that a decrease of miR-622 expression could suppress migration and invasion by targeting regulation of DYRK2 and miR-622/DYRK2 could be a potential molecular treating target of CRC.


The Association of Coronary Fat Attenuation Index Quantified by Automated Software on Coronary Computed Tomography Angiography with Adverse Events in Patients with Less than Moderate Coronary Artery Stenosis.
This study analyzed the relationship between the coronary FAI on CCTA and coronary adverse events in patients with moderate coronary artery disease based on machine learning. A total of 172 patients with coronary artery disease with moderate or lower coronary artery stenosis were included. According to whether the patients had coronary adverse events, the patients were divided into an adverse group and a non-adverse group. The coronary FAI of patients was quantified via machine learning, and significant differences between the two groups were analyzed via t-test. The age difference between the two groups was statistically significant (p < 0.001). The group that had adverse reactions was older, and there was no statistically significant difference between the two groups in terms of sex and smoking status. There was no statistical significance in the blood biochemical indexes between the two groups (p > 0.05). There was a significant difference in the FAIs between the two groups (p < 0.05), with the FAI of the defective group being greater than that of the nonperforming group. Taking the age of patients as a covariate, an analysis of covariance showed that after excluding the influence of age, the FAIs between the two groups were still significantly different (p < 0.001).


Development of a novel mineral based haemostatic agent consisting of a combination of bentonite and zeolite minerals.
Haemorrhage remains the greatest threat to life on the battlefield, accounting for half of all deaths. Over the past decade the US army has widely studied new technologies for stopping sever haemorrhages and has introduced an effective zeolite based haemostatic agent. In this paper the bio-stimulatory effect of burned radioactive lantern mantles powder as well as two minerals; bentonite and zeolite are presented. In this experimental study, 50 male Wistar rats were divided randomly into 5 groups of 10 animals each. Following anaesthesia, animals' tails were cut off at a thickness of 5 mm by using a pair of surgical scissors. No intervention was made on the animals of the 1st group. The 2nd to 5th group received topical nonradioactive lantern mantle powder, radioactive lantern mantle powder, Bentonite mineral or a mixture of bentonite-zeolite minerals respectively. After treatment with above mentioned agents, the volume of blood loss was measured using a scaled test-tube. The bleeding time (BT) and clotting time (CT) were also measured using a chronometer. Analysis of variance (ANOVA) was used for comparing the means of each parameter in the 5 groups. The volume of blood loss, bleeding and clotting time in control animals were 4.39 +/- 1.92 ml, 112.10 +/- 39.60 sec and 94.9 +/- 54.26 sec respectively. In the 2nd group, in which the animals were treated with a nonradioactive lantern mantle, the volume of blood loss, bleeding and clotting time were 2.34 +/- 0.35 ml, 54.50 +/- 14.77 sec and 22.9 +/- 6.54 sec, respectively. In the 3rd group, in which the animals were treated with a radioactive lantern mantle, the volume of blood loss, bleeding and clotting time were 1.50 +/- 0.58 ml, 37.10 +/- 7.81 sec and 33.5 +/- 15.76 sec respectively. In the 4th group, in which the animals were treated with bentonite mineral, the volume of blood loss, bleeding and clotting time were 1.81 +/- 0.62 ml, 55.70 +/- 16.73 sec and 45.9 +/- 32.17 sec, respectively. In the 5th group, in which the animals were treated with a mixture of bentonite-zeolite minerals, the volume of blood loss, bleeding and clotting time were 1.31 +/- 0.60 ml, 34.50 +/- 4.65 sec and 24.2 +/- 4.61 sec, respectively. To our knowledge, this is the 1st study to investigate the alterations of bleeding and clotting time following the use of lantern mantle powder as well as bentonite or the mixture of bentonite-zeolite minerals. The results obtained in this study clearly show the significant alterations in the volume of blood loss as well as the bleeding or clotting time following the topical use of the mixture of bentonite-zeolite minerals. Controlling the generation of heat was a great achievement in development of the novel haemostatic agent produced in this study.


Effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin in humans.
Cimetidine reduces the appetite and weight in healthy overweight subjects. Gastrointestinal regulatory peptides such as cholecystokinin (CCK) have been proposed to mediate the satiety signal from gut to brain. Therefore, the effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin was studied. After an overnight fast, 12 healthy volunteers were given cimetidine (400 mg) on day 1, breakfast on day 2, and cimetidine 20 min before breakfast on day 3. Plasma concentrations of cholecystokinin and gastrin were measured by radioimmunoassay. Plasma cholecystokinin concentration increased with one major peak observed 30 min and one smaller peak observed 120 min after intake of cimetidine. The meal induced an increase in the plasma concentration of cholecystokinin, while cimetidine prior to the meal elicited a sustained postprandial cholecystokinin response. Cimetidine had no effect on the basal plasma concentration of gastrin. The meal induced an increase in the plasma concentration of gastrin, while cimetidine prior to the meal elicited a sustained postprandial gastrin response. In conclusion, cimetidine increases the basal concentration of plasma cholecystokinin and elicits a sustained postprandial response of both cholecystokinin and gastrin. At least the cholecystokinin response may be one mechanism by which cimetidine reduces the appetite.


Cord blood CD4+ CD45RA+ T cells achieve a lower magnitude of activation when compared with their adult counterparts.
Highly purified CD4+ CD45RA+ cells from cord blood and peripheral blood from healthy adults were studied. The levels of expression of the CD2, CD3, CD4 and CD28 antigens were similar; however, CD45 and CD45RA antigen expression were slightly lower in cord cells. The reduced expression of the CD45RA antigen on cord CD4+ T cells was confirmed in whole blood. Functional assessment revealed deficiencies in cord CD4+ CD45RA+ T cells. Interleukin-2 (IL-2) production in response to specific triggering via CD2 monoclonal antibody (mAb) alone, or CD2 mAb in combination with CD28 mAb showed marked underproduction (about 10% of adult production). When CD25 expression was examined, it was observed that the proportion of activated CD4+ CD45RA+ T cells in cord blood was lower than in adult (about 20% of adult expression). Proliferation to CD2 mAbs or CD2 + 28 mAbs of cord blood native cells was similarly depressed. Investigation of IL-2 mRNA expression under these stimulatory conditions paralleled the results observed for CD25 expression, IL-2 production and proliferation. When phorbol 12-myristate 13-acetate (PMA) was added to the cells triggered with CD2 + 28mAbs, the responses examined were enhanced in both cord and adult blood with no significant differences between the groups. These findings suggest that under identical conditions of stimulation, purified cord blood CD4+ CD45RA+ T cells do not acquire similar activation status as their adult counterparts. These findings may help in understanding the reduced graft-versus-host disease (GVHD) observed in cord blood stem cell transplantation.


Cramps and minimal EMG abnormalities as preclinical manifestations of spinal muscular atrophy patients with homozygous deletions of the SMN gene.
The characterization of deletions in the SMN gene provides a helpful tool to confirm the diagnosis of spinal muscular atrophy (SMA). However, there may be homozygous deletions of the SMN gene in some unaffected siblings of SMA type II and III patients. We present two SMA families with affected siblings demonstrating a homozygous deletion of the SMN gene with extremely different phenotypes. We propose a preclinical category of an SMA patient with homozygous deletion of the SMN gene: those with minimal expression of the disease including cramps and EMG abnormalities that may develop the complete SMA phenotype in the future.


Lytic xylan oxidases from wood-decay fungi unlock biomass degradation.
Wood biomass is the most abundant feedstock envisioned for the development of modern biorefineries. However, the cost-effective conversion of this form of biomass into commodity products is limited by its resistance to enzymatic degradation. Here we describe a new family of fungal lytic polysaccharide monooxygenases (LPMOs) prevalent among white-rot and brown-rot basidiomycetes that is active on xylans-a recalcitrant polysaccharide abundant in wood biomass. Two AA14 LPMO members from the white-rot fungus Pycnoporus coccineus substantially increase the efficiency of wood saccharification through oxidative cleavage of highly refractory xylan-coated cellulose fibers. The discovery of this unique enzyme activity advances our knowledge on the degradation of woody biomass in nature and offers an innovative solution for improving enzyme cocktails for biorefinery applications.


Ultrasound diagnosis of transverse sinus hypoplasia using flow profiles of the internal jugular vein.
Accurate diagnosis of subtypes of transverse sinus (TS) hypoplasia requires more expensive methods like magnetic resonance (MR) imaging. We hypothesized ultrasound findings of the internal jugular vein (IJV) can be surrogate indicators for diagnosis of TS hypoplasia. MR images were reviewed in 131 subjects to evaluate TS diameter and the location and degree of venous flow stenosis and obstruction. Ultrasound parameters including the cross-sectional lumen area (CSA), time-average-mean velocity (TAMV), and flow volume (FV) at each IJV segment were also evaluated. Sixty-nine subjects had TS hypoplasia based on MRV criteria, of which 39 TS hypoplasia were considered a subtype of TS hypoplasia, which is secondary to the downstream venous compression/stenosis or left brachiocephalic vein. In the ultrasound study, the CSA of the IJV ipsilateral to TS hypoplasia was significantly smaller. Further, a contralateral/ipsilateral IJV CSA ratio >1.55 provided good sensitivity, specificity, and positive predictive value for discriminating TS hypoplasia.


[Effects of glutamine on changes of nuclear factor-kappa B in acute lipopolysaccharide lung injury: experiment with rats].
To investigate the effects of glutamine on the changes of nuclear factor (NF)-kappaB and lung pathology in acute lung injury. Forty SD rats underwent injection of lipopolysaccharide (LPS) 5 mg/kg into the femoral vein, and were randomly divided into 4 equal groups: Group B: undergoing injection of glutamine 0.75 g/kg into the femoral vein 1 h before LPS injection, Group C undergoing injection of glutamine and LPS simultaneously, and Group D undergoing injection of glutamine 1 h after LPS injection, and Group E without glutamine injection. Another 10 rats underwent injection of normal saline to be used as controls (Group A). Four hours after the LPS injection the rats were killed with their lungs taken out RT-PCR was used to detect the level of nuclear factor (NF)-kappaB mRNA expression. ELISA was used to detect the tumor necrosis factor (TNF) - in lung. The activity of superoxide dismutase (SOD) was examined by hydroxylamine method, and the malondialdehyde level was determined by thiobarbituric acid (TBA) method. The lung NF-kappaB mRNA expression levels and TNF- levels of Groups B, C, D, and E were all significantly higher than that of Group A (all P < 0.01). The lung NF-kappaB mRNA expression levels and TNF- levels of Groups C and D were all significantly lower than those of Group B (P < 0.01). However, there were no significant differences in lung NF-kappaB mRNA expression level and TNF- level between Group B and Group E (both P > 0.05). The SOD activity of Group B was significantly lower than that of Group A and the MDA content of Group B was significantly higher than that of Group A (both P < 0.05). The SOD activity levels of Groups C and D were significantly higher than that of Group B and the MDA content of Groups C and D were significantly lower than that of Group B (P < 0.01 or P < 0.05). However there were no significant differences in lung SDD activity and MDA content between Groups B and E (both P > 0.05). Obvious inflammatory changes were seen in the lungs of Groups B and E at the similar extent. Only slight infiltration could be seen in Groups C and D. The lung of Group A was normal. Early glutamine administration protects the lung against acute LPS injury. The mechanism may be inhibition of the overexpression of NF-kappaB mRNA.


Knockdown of Nrf2 inhibits angiogenesis by downregulating VEGF expression through PI3K/Akt signaling pathway in cerebral microvascular endothelial cells under hypoxic conditions.
Ischemic stroke is a major cerebrovascular disease resulting from a transient or permanent local reduction of cerebral blood flow. Angiogenesis plays an important role in cerebral microvascular repair after ischemic stroke. This study aimed at investigating the effect of NF-E2-related factor 2 (Nrf2) on the angiogenesis of mouse cerebral microvascular endothelial bEnd.3 cells in a hypoxic environment. We found that Nrf2 expression was temporarily increased in hypoxia-induced bEnd.3 cells. Knockdown of Nrf2 inhibited the proliferation, migration, as well as tube formation in hypoxia-induced bEnd.3 cells. Meanwhile, vascular endothelial growth factor and PI3K/Akt signaling pathways were identified to be regulated by Nrf2 in hypoxia-induced bEnd.3 cells. It was found that silencing of Nrf2 downregulated the expression levels of NAD(P)H:quinine oxidoreductase-1, vascular endothelial growth factor, p-Akt, and heme oxygenase-1 in hypoxia-induced bEnd.3 cells. Data suggested that hypoxia induced the transient increase of Nrf2, which plays a key role in the angiogenesis of cerebral microangiogenesis, and that Nrf2 regulates the proliferation, migration, as well as tube formation likely through PI3K/Akt signaling pathway in hypoxia-induced bEnd.3 cells. Our study provides proof of concept for the modulation of Nrf2, so as to tilt the balance toward angiogenesis, representing a therapeutic strategy for hypoxia or ischemia disorders such as stroke.


The use of trastuzumab in the treatment of hormone refractory prostate cancer; phase II trial.
To investigate the efficacy and toxicity of the antibody to the HER-2/neu receptor (trastuzumab, Herceptin) in the treatment of advanced hormone-refractory prostate cancer (HRPC). Eighteen patients with HRPC were recruited for this phase II trial in which they received trastuzumab for 12 weeks or until disease progression or unacceptable toxicity was documented. HER-2 receptor overexpression was evaluated using immunohistochemistry (IHC) and dual-color fluorescence in-situ hybridization (FISH) assays. Trastuzumab as a single agent demonstrated little efficacy in treating HRPC. Two patients demonstrated stable disease based on a decrease in PSA level to less than 50% of baseline. No patient demonstrated a regression of radiographic bony or soft tissue metastatic disease. The medication was well tolerated in 16 patients (89%), and 2 patients (11%) had to be hospitalized for cardiac complications. Trastuzumab (Herceptin) as a single agent demonstrated poor efficacy in treating HRPC. Based on promising results in treating breast cancer with regimens using Herceptin and cytotoxic agents, a similar combination approach might demonstrate better efficacy in treating HRPC.


Reevaluation of recent criteria for blood exchange transfusion in term infants with hyperbilirubinemia.
For hyperbilirubinemic infants treated according to the higher criterion for a blood exchange transfusion (BET), auditory brainstem response (ABR) was performed to evaluate whether the treatment was adequate. Twenty hyperbilirubinemic infants were collected as the study group. They were divided into 2 groups; group A consisted of 17 infants receiving intensive phototherapy only, while group B consisted of 3 infants receiving BET plus phototherapy. Fourteen healthy neonates were collected as the control group. Language development was evaluated with "language/communication development milestone: infancy through school-age" at the age of 5 months to 3 years old. Wave V at 30 dB HL was clearly identified in all infants in group A and in the control group. There was no significant difference in the latency between them (p > 0.05). In group A, peak bilirubin levels of 16 cases reached the former criteria for BET Their ABRs were normal. Language development was normal in 12 cases, while 4 cases were lost to follow-up. In group B, 2 cases had abnormal ABRs, while the third had normal ABR and language development. By analyzing the condition of these babies, we could conclude that in addition to peak bilirubin level and age, other factors such as anemia, the duration of hyperbilirubinemia, and the decline rate of bilirubin in response to intensive phototherapy should also be taken into consideration. For infants with borderline bilirubin levels for BET, we suggest performing BET if they have severe anemia or if intensive phototherapy fails to produce a proper decline in bilirubin.


Unclassified renal cell carcinoma: an analysis of 85 cases.
To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype. Eighty-five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan-Meier and life-table analyses were used to address RCC-specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC-specific survival in unmatched samples. Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC-specific mortality rate was 1.6 times higher (P = 0.04) in matched analyses and 1.7 times higher (P = 0.001) in multivariate analyses. These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6-1.7 times the mortality of CRCC.


Receptor "cross talk" in innate immunity.
Toll-like receptors (TLRs) recognize microbial molecular signatures and can initiate innate immune responses against invading pathogens. A new study (see the related article beginning on page 1234) reports how TLR2 expression by endothelia is locally upregulated by the action of activated polymorphonuclear neutrophils via an unprecedented mechanism involving cell-cell interaction and NAD(P)H oxidase. The report reveals yet another way in which the primordial innate immune system is remarkably complex.


Relationship between plasma homocysteine level and lipid profiles in a community-based Chinese population.
Previous studies established a possible link among hyperhomocysteinemia (HHcy), dyslipidemia, and atherosclerosis. However, there was limited epidemic data concerning the relation between HHcy and lipid profiles, especially in community-based Chinese populations. This study aim to investigate the association of plasma homocysteine (Hcy) level with lipid profiles in a Chinese community-based population without lipid-lowering treatment. A total of 4660 Chinese subjects from a cohort of the Shijingshan district in Beijing were included in the analysis. Plasma total Hcy, serum lipid files including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) as well as relevant metabolic risk factors were measured. Multivariate regression models adjusting for age, gender, smoking, drinking, physical activity, vitamin B supplement, body mass index, fasting blood glucose level, serum creatinine, systolic and diastolic blood pressure were used to evaluate associations of Hcy and lipid profiles. Subjects were 56.75 ± 8.91 years old, and 38.15% were male. Median (IQR) Hcy was 11.98 (10.00-14.93) μmol/L, and 24.4% had HHcy (defined as Hcy ≥ 15 μmol/L). Mean (SD) baseline TC was 5.34 ± 0.98 mmol/L, LDL-C was 3.27 ± 0.81 mmol/L, and HDL-C was 1.43 ± 0.38 mmol/L. Median (IQR) of TG was 1.28 (0.91-1.85) mmol/L. In multivariable linear-regression analyses, lnHcy (ln transformation for Hcy) level was positively associated with lnTG (adjusted β = 0.075, SE = 0.021, P = 0.001). Using Hcy < 15 μmol/L as a reference, HHcy was independently associated with both lnTG (adjusted β = 0.056, SE = 0.020, P = 0.004) and lnHDL (adjusted β = -0.018, SE = 0.009, P = 0.038). In multivariable logistic-regression analyses, HHcy was associated with increasing risk of low HDL-C (HDL-C < 1.04 mmol/L; adjusted odds ratio [OR] =1.406, 95% confidence interval [CI]: 1.143 - 1.728, P = 0.001) and hypertriglyceridemia (TG ≥ 1.7 mmol/L; adjusted OR = 1.293, 95% CI: 1.096-1.524, P = 0.002) after adjusting the confounders. However, there were no significant associations between Hcy and TC or LDL-C. The present study showed that HHcy was independently associated with hypertriglyceridemia and low levels of HDL-C, which provides evidence that Hcy levels might affect HDL-C and TG metabolism.


Limited Top-Down Influence from Recognition to Same-Different Matching of Chinese Characters.
We investigated the extent to which recognition of Chinese characters influenced same-different matching performance that did not require recognition. In each experimental trial, two partially occluded characters were shown sequentially, and participants decided whether or not they were the same. The two characters were either both upright or both inverted and mirror-reflected. The participants' Chinese reading fluency spanned the full range, from not knowing any characters to native speakers. The participants who could recognize some characters (defined as readers) were subsequently tested with character recognition in a naming task. Interestingly, although the readers' recognition accuracies well correlated with their years of Chinese language schooling, they were uncorrelated with the matching accuracies in the same-different task with upright characters. The only indication of top-down influence was the readers' higher accuracy in matching upright than inverted and reflected characters. However, the magnitude of this effect was small, to the extent that the average same-different accuracies were comparable for readers and non-readers alike. This small effect was further confirmed with native speakers in China, who should give rise to the largest possible effect. We conclude that top-down influence from character recognition was present but very limited, at least with the task and stimuli used.


SW-UNet: a U-Net fusing sliding window transformer block with CNN for segmentation of lung nodules.
Medical images are information carriers that visually reflect and record the anatomical structure of the human body, and play an important role in clinical diagnosis, teaching and research, etc. Modern medicine has become increasingly inseparable from the intelligent processing of medical images. In recent years, there have been more and more attempts to apply deep learning theory to medical image segmentation tasks, and it is imperative to explore a simple and efficient deep learning algorithm for medical image segmentation. In this paper, we investigate the segmentation of lung nodule images. We address the above-mentioned problems of medical image segmentation algorithms and conduct research on medical image fusion algorithms based on a hybrid channel-space attention mechanism and medical image segmentation algorithms with a hybrid architecture of Convolutional Neural Networks (CNN) and Visual Transformer. To the problem that medical image segmentation algorithms are difficult to capture long-range feature dependencies, this paper proposes a medical image segmentation model SW-UNet based on a hybrid CNN and Vision Transformer (ViT) framework. Self-attention mechanism and sliding window design of Visual Transformer are used to capture global feature associations and break the perceptual field limitation of convolutional operations due to inductive bias. At the same time, a widened self-attentive vector is used to streamline the number of modules and compress the model size so as to fit the characteristics of a small amount of medical data, which makes the model easy to be overfitted. Experiments on the LUNA16 lung nodule image dataset validate the algorithm and show that the proposed network can achieve efficient medical image segmentation on a lightweight scale. In addition, to validate the migratability of the model, we performed additional validation on other tumor datasets with desirable results. Our research addresses the crucial need for improved medical image segmentation algorithms. By introducing the SW-UNet model, which combines CNN and ViT, we successfully capture long-range feature dependencies and break the perceptual field limitations of traditional convolutional operations. This approach not only enhances the efficiency of medical image segmentation but also maintains model scalability and adaptability to small medical datasets. The positive outcomes on various tumor datasets emphasize the potential migratability and broad applicability of our proposed model in the field of medical image analysis.


Non-invasive transcranial alternating current stimulation of spatially resolved phosphenes.
This study focused on the use of Non-Invasive Transcranial Alternating Current Stimulation (NITACS) to induce and map phosphenes (spark-like percepts in the visual field) in healthy individuals. The study found optimal stimulation parameters to induce reliable phosphenes without skin irritation or pain. The results suggest NITACS can be used as a tool to investigate the relationship between facial stimulation location and phosphene localization within the field of vision (FOV) and raise questions about the origin of phosphenes generated through NITACS. The outcomes of this study could serve as a source of inspiration for creating non-invasive visual aids in the future.


Jeune's syndrome (asphyxiating thoracic dystrophy): congenital and acquired.
Familial asphyxiating thoracic dystrophy (ATD), also known as Jeune's syndrome, is a rare autosomal recessive disorder with variable severity and multiple musculo-skeletal manifestations. Respiratory distress may be severe, resulting in death during infancy. Surgical repair techniques have typically involved median sternotomy (with graft interposition), resulting in poor outcomes. Acquired ATD may rarely result from impairment of chest wall growth following "open" (Ravitch-type) repair of pectus excavatum or carinatum deformities. Symptomatic patients may have profound restriction of pulmonary function. Repair techniques typically involve re-do Ravitch-type procedures or median sternotomy with rib graft interposition. Mild to moderate improvements in pulmonary function tests have been documented.


Single cell analysis of PKC activation during proliferation and apoptosis induced by laser irradiation.
Laser irradiation has been shown to trigger cellular proliferation and apoptosis in various cell types. Studying the signaling pathways involved in the laser irradiation is important for understanding these processes. In present study, to monitor the protein kinase Cs (PKCs) activity in living cells in real time, we transfected and screened human lung adenocarcinoma cells (ASTC-a-1) stably expressing C kinase activity reporter (CKAR) constructed based on fluorescence resonance energy transfer (FRET) technique. The CKAR is a specific, reversible reporter of phosphorylation by PKCs and it can monitor the ongoing balance between PKCs and phosphatases. The increasing dynamics of PKCs activity is monitored during cell proliferation induced by low-power laser irradiation (LPLI) (0.8 J/cm2) in serum-starved ASTC-a-1 cells stably expressing CKAR reporter using FRET imaging on laser scanning confocal microscope and using spectrofluorometric analysis on a luminescence spectrometer, respectively. However, the decreasing dynamics of PKCs activity has been monitored in real time using FRET imaging for the cells treated with high fluence LPLI (60 J/cm2), which was previously found to induce cell apoptosis. Taken together, LPLI induces the ASTC-a-1 cell proliferation by specifically activating PKCs. However, PKCs activity decreases during cell apoptosis induced by high fluence LPLI. Our results indicate that PKCs play an important role in the laser irradiation-induced biological effects.


Variability of Emaravirus Species Associated with Sterility Mosaic Disease of Pigeonpea in India Provides Evidence of Segment Reassortment.
Sterility mosaic disease (SMD) of pigeonpea is a serious constraint for cultivation of pigeonpea in India and other South Asian countries. SMD of pigeonpea is associated with two distinct emaraviruses, Pigeonpea sterility mosaic virus 1 (PPSMV-1) and Pigeonpea sterility mosaic virus 2 (PPSMV-2), with genomes consisting of five and six negative-sense RNA segments, respectively. The recently published genome sequences of both PPSMV-1 and PPSMV-2 are from a single location, Patancheru from the state of Telangana in India. However, here we present the first report of sequence variability among 23 isolates of PPSMV-1 and PPSMV-2, collected from ten locations representing six states of India. Both PPSMV-1 and PPSMV-2 are shown to be present across India and to exhibit considerable sequence variability. Variability of RNA3 sequences was higher than the RNA4 sequences for both PPSMV-1 and PPSMV-2. Additionally, the sixth RNA segment (RNA6), previously reported to be associated with only PPSMV-2, is also associated with isolates of PPSMV-1. Multiplex reverse transcription PCR (RT-PCR) analyses show that PPSMV-1 and PPSMV-2 frequently occur as mixed infections. Further sequence analyses indicated the presence of reassortment of RNA4 between isolates of PPSMV-1 and PPSMV-2.


Does the genotype for schizophrenia often remain unexpressed because of canalization and stochastic events during development?
It has been well established in the literature that a strong genetic component exists for schizophrenia. Available data are compatible with the hypothesis that for most cases of schizophrenia, the genetic component consists of multiple genes acting in an additive manner with the genotype for schizophrenia being present when the number of genes is greater than a threshold number. Twin studies suggest that the genotype for schizophrenia is unexpressed in some individuals who carry it. This phenomenon of reduced penetrance has led to a diversity of hypotheses concerning the aetiology of schizophrenia. Based on a review of the literature a neurodevelopmental model is proposed for schizophrenia that involves the actions of the schizophrenia genotype, canalization and stochastic events. The schizophrenia genotype is programmed to disrupt the migration of neuronal cells in the developing cortex during the second trimester, resulting in impaired embryogenesis. The presence of a specific lesion is the reason for the onset of schizophrenia later in life. The genotype for schizophrenia often remains unexpressed, or demonstrates variable expressivity, because of the actions of canalization and stochastic events that may allow migrating neuronal cells to reach or approach the target data. Stochastic events also influence whether canalization will be successful, therefore, chance plays a major role under normal conditions in determining whether the schizophrenia genotype will be expressed. Certain environmental factors acting during early development, such as high temperature resulting from maternal illness, may increase the penetrance of the schizophrenia genotype.


Introduction to the special section: Why we should highlight the outstanding contributions of young investigators in the field of eating disorders.
This introduction presents the context in which the Journal of Abnormal Psychology created a special section to highlight outstanding contributions by young investigators in the field of eating disorders. The first motivating factor relates to our field's approach to mentoring and supporting its next generation of researchers. The second motivating factor addresses a broader need to ensure that the Journal of Abnormal Psychology remains an outlet in which this and future generations share their innovative and important work. (PsycINFO Database Record


Science to practice: opening the blood-brain barrier with focused ultrasound-a potential treatment for Alzheimer disease?
Burgess et al ( 1 ) present intriguing results of repetitive transient opening of the blood-brain barrier (BBB) in a transgenic mouse model of advanced Alzheimer disease (AD). The results underscore the potential of using magnetic resonance (MR) imaging-guided focused ultrasound and microbubble ultrasonography (US) contrast agents for the disruption of the BBB as a potential long-term therapy to reduce amyloid plaque burden and improve cognitive performance. This daring conclusion that is based on an experimental animal model should now be confirmed in humans. Considering that the technology is commercially available and given the immense clinical need, clinical trials in this AD treatment should be initiated as soon as possible.


Treatment of calcinosis cutis by extracorporeal shock-wave lithotripsy.
Calcinosis cutis (CC) encompasses debilitating complications of connective tissue disorders and chronic venous insufficiency. Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment for urolithiasis, pancreatolithiasis, and calcified tendinitis. This study prospectively evaluated ESWL efficacy and tolerance for patients with CC. This monocentric prospective study included all consecutive patients with CC progressing for at least 3 months, while their underlying causal disease was not. They underwent 3 ESWL sessions at 3-week intervals. The CC area and associated pain (visual analog scale score and analgesic consumption) were recorded before and 6 months after ESWL. Eight patients were included: 4 with chronic venous insufficiency, 3 with systemic scleroderma, and one with dermatomyositis. ESWL was used to treat 10 CC lesions. Seven patients completed 3 ESWL sessions. Six months after ESWL, the median CC area had decreased from 3.1 to 1.9 cm(2). visual analog scale-assessed pain scores declined dramatically, from 7 to 2 of 10, as did analgesia consumption, without any difference according to the causal disease. Only 8 consecutive patients have been included and treated by ESWL during our study. This evaluation of ESWL efficacy and tolerance for the treatment of CC found no difference between the different underlying CC causal diseases in terms of efficacy. Based on our observations, ESWL efficacy was better against small, ulcerated, and radiopaque CC, and it had an analgesic effect that might make subsequent surgical excision of CC fragments easier. Ergonomic adaptations are required to facilitate and expand ESWL use in dermatology.


Open anterior hip dislocation in a young adult with exposed femoral head and no neurovascular damage.
Anterior hip dislocation is common in younger adults and is the result of severe, high energy trauma such as high-velocity motor vehicle accidents or falls from great heights. A similar mechanism of injury would cause a femur neck fracture in older patients. Of these, open anterior hip dislocations are extremely rare and are usually associated with other soft tissue and bony injuries. We report a case of an open anterior hip dislocation with normal neurovascular status in a third world setting. trauma, open anterior, dislocation, hip, femoral head, osteonecrosis.


Multi-scale semi-analytical model for fatigue life prediction of trans-tibial prosthetic sockets.
The trans-tibial socket is an essential component of the prosthesis that connects it to the residual limb. Socket misalignments and permanent deformations reduce the comfort of the amputee. In order to forestall such issues, sufficient information about the socket lifespan needs to be acquired, which is fairly difficult given the lack of calculation methods that estimate the fatigue life in the literature. In this paper a semi-analytical model is proposed based on experimental results. It highlights the effects of the amputee average daily walking time on the socket fatigue life. A proportionality relationship is demonstrated linking the Burgers model parameters at the structural scale to those at the macroscopic scale. Hence, it becomes possible to evaluate the permanent deformation that induces a misalignment in the socket. These results are useful for the designers to predict the fatigue life of the socket, and also for clinicians to monitor the mechanical degradation of the trans-tibial socket and schedule maintenance or replacement.


Inability of the acidic fibroblast growth factor mutant K132E to stimulate DNA synthesis after translocation into cells.
Acidic fibroblast growth factor (aFGF) is a potent mitogen. It acts through activation of specific cell surface receptors leading to intracellular tyrosine phosphorylation cascades, but several reports also indicate that aFGF enters cells and that it has an intracellular function as well. The aFGF(K132E) mutant binds to and activates fibroblast growth factor receptors equally strongly as the wild-type, but it is a poor mitogen. We demonstrate that aFGF(K132E) enters NIH 3T3 cells and is transported to the nuclear fraction like wild-type aFGF. A fusion protein of aFGF(K132E) and diphtheria toxin A-fragment (aFGF(K132E)-DT-A) and a similar fusion protein containing wild-type aFGF (aFGF-DT-A) were reconstituted with diphtheria toxin B-fragment. Both fusion proteins were translocated to the cytosol by the diphtheria toxin pathway and subsequently recovered from the nuclear fraction. Whereas translocation of aFGF-DT-A stimulated DNA synthesis in U2OSDR1 cells lacking functional fibroblast growth factor receptors, aFGF(K132E)-DT-A did not. The mutation disrupts a protein kinase C phosphorylation site in the growth factor making it unable to be phosphorylated. The data indicate that a defect in the intracellular action of aFGF(K132E) is the reason for its strongly reduced mitogenicity, possibly due to inability to be phosphorylated.


Primary hypoparathyroidism in the dog. Report of 15 cases and review of 13 previously reported cases.
Fifteen dogs with primary hypoparathyroidism diagnosed at the University of California Veterinary Medical Teaching Hospital were compared with 13 previously reported cases. Age, sex, breed, and historical and physical findings were similar in both groups of dogs. Middle-aged females were affected primarily. A history of neurologic or neuromuscular disease was present in all 28 dogs, with 18 dogs having seizures. Posterior lenticular cataract formation secondary to hypocalcemia was suspected in six dogs. The most characteristic biochemical finding in all dogs was profound hypocalcemia (less than 6.5 mg/dl) and mild hyperphosphatemia. Serum magnesium concentrations were decreased in two dogs. Serum parathyroid hormone concentrations were consistent with the diagnosis of primary hypoparathyroidism in eight of nine dogs. Lymphocytic parathyroiditis was diagnosed in the 12 dogs from which tissue was submitted for histopathology. Successful management of the patient depended on frequent monitoring of the serum calcium concentration during initial and maintenance therapy.


Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal malignancy: preliminary results of a multi-disciplinary teamwork model in Asia.
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an emerging surgical procedure for peritoneal carcinomatosis (PC). CRS/HIPEC is a complicated treatment that requires multi-disciplinary teamwork (MDT), which may be lacking when establishing a CRS/HIPEC programme. Herein, we report our preliminary treatment outcomes with the early implementation of an MDT model for CRS/HIPEC. From April 2015 to December 2016, 45 patients with a diagnosis of PC who received CRS/HIPEC were reviewed retrospectively in a single institution in Taiwan. Among the 45 patients, CRS was mainly performed by laparotomy (n = 42), and only three patients with limited PC underwent laparoscopic CRS. The first 13 patients received treatment before the MDT had been established (group 1), and the other 32 patients were treated after the MDT had been established (group 2). The highest peri-HIPEC body temperature in group 2 was significantly lower than that in group 1 (36.8 °C vs. 37.5 °C, p < 0.001). Overall, eight patients experienced major complications. The trend of a lower major complication rate was observed after the MDT model had been implemented (30.7% in group 1 vs. 12.4% in group 2, p = 0.202). Pre-CRS/HIPEC abdominal pain significantly increased the risk of post-operative major complications (p = 0.017). Our experience suggests that the early implementation of an MDT model when establishing a CRS/HIPEC programme at a single institution may result in a higher complete cytoreduction rate and lower major complication rate, and also shorten the learning curve of this complicated procedure.


African American women and breastfeeding: an integrative literature review.
The purpose of this article is to present a review of literature regarding factors that influence breastfeeding intentions, initiation, and duration in the African American population. Research related to health disparities experienced by African Americans in the United States, as well as research regarding the protective benefits of breastfeeding for those specific health disparities, are also presented. Community and institutional interventions and promotional campaigns aimed at increasing initiation and duration of breastfeeding in the African American population are discussed. Future research regarding African American women's breastfeeding experiences using Black feminist thought as a theoretical foundation is recommended.


Myocardial infarction related to valve replacement surgery.
Fifty consecutive patients, 25 undergoing aortic valve replacement and 25 mitral valve replacement, were studied by serial electrocardiography, preoperative and postoperative technetium-99m pyrophosphate radionuclide scanning, and serial measurement of enzymes (creatine kinase, aspartate aminotransferase, urea stable lactic dehydrogenase) and the MB isoenzyme of creatine kinase to define the incidence of preoperative myocardial infarction and to identify the most appropriate diagnostic techniques. The use of myocardial scanning and measurement of peak enzyme activity proved to be accurate indicators of myocardial infarction, but the electrocardiogram was of limited value. The measurement of creatine kinase MB isoenzyme had no diagnostic advantage over that of the other enzymes. There were two deaths in the series, one due to acute pancreatitis after aortic valve replacement and the other due to myocardial injury after mitral valve replacement. There were four non-fatal myocardial infarctions after aortic valve replacement, giving an incidence of 16%, and none after mitral valve replacement, giving an incidence of 4%.


Spontaneous bacterial peritonitis in patients with cirrhosis: incidence, outcomes, and treatment strategies.
Spontaneous bacterial peritonitis is the most frequent bacterial infection in patients with cirrhosis. The reported incidence varies between 7% and 30% in hospitalized patients with cirrhosis and ascites, representing one of their main complications. Outcomes in patients with spontaneous bacterial peritonitis are poor since acute kidney injury, acute-on-chronic liver failure, and death occur in as much as 54%, 60%, and 40% of the patients, respectively, at midterm. Early antibiotic treatment of spontaneous bacterial peritonitis is crucial. However, the landscape of microbiological resistance is continuously changing, with an increasing spread of multidrug-resistant organisms that make its current management more challenging. Thus, the selection of the empirical antibiotic treatment should be guided by the severity and location where the infection was acquired, the risk factors for multidrug-resistant organisms, and the available information on the local expected bacteriology. The use of albumin as a complementary therapy for selected high-risk patients with spontaneous bacterial peritonitis is recommended in addition to antibiotics. Even though antibiotic prophylaxis has proven to be effective to prevent spontaneous bacterial peritonitis, a careful selection of high-risk candidates is crucial to avoid antibiotic overuse. In this article we review the pathogenesis, risk factors, and prognosis of spontaneous bacterial peritonitis, as well as the current evidence regarding its treatment and prophylaxis.


Infectious hematopoietic necrosis virus truncated G protein effect on survival, immune response, and disease resistance in rainbow trout.
The major antigenic protein of infectious hematopoietic necrosis virus (IHNV) is the surface glycoprotein G, which contains neutralizing epitopes that induce the production of immune neutralizing antibodies. In this study, the IHNV G gene sequence was truncated according to bioinformatics principles and then recombinantly expressed via an E. coli expression system. We then assessed the specific antibody immunoglobin M (IgM) levels of rainbow trout immunized with recombinant truncated G protein (emulsified with Freund's incomplete adjuvant), and showed that antibody IgM levels of immunized fish were significantly higher than in the control group (p < 0.01). The mRNA expression levels of interferon 1 (IFN1) and interleukin-8 (IL-8) were also up-regulated significantly (p < 0.01) in head kidneys and spleens of rainbow trout immunized with recombinant truncated G protein. Also, after challenge with wild-type IHNV HLJ-09 virus on Day 28, rainbow trout immunized with recombinant truncated G protein showed cumulative survival rates of 60%. These results indicate that the truncated G protein of IHNV expressed by the E. coli prokaryotic expression system can be used as a candidate immunogen for an IHNV subunit vaccine, which lays a theoretical foundation for the study of further potential IHNV subunit vaccines.


Genetic diversities of MT-ND1 and MT-ND2 genes are associated with high-altitude adaptation in yak.
Tibetan yak (Bos grunniens) inhabiting the Qinghai-Tibet Plateau (QTP) where the average altitude is 4000 m, is specially adapted to live at these altitudes. Conversely, cattle (B. taurus) has been found to suffer from high-altitude hypertension or heart failure when exposed to these high altitudes. Two mitochondrial genes, MT-ND1 and MT-ND2, encode two subunits of NADH dehydrogenase play an essential role in the electron transport chain of oxidative phosphorylation (OXPHOS). We sequenced these two mitochondrial genes in two bovine groups (70 Tibetan yaks and 70 Xuanhan cattle) and downloaded 300 sequences of B. taurus (cattle), 93 sequences of B. grunniens (domestic yak), and 2 sequences of B. mutus (wild yak) from NCBI to increase our understanding of the mechanisms of adaptability to hypoxia at high altitudes in yaks compared to cattle. MT-ND1 SNP m.3907 C > T, present in all Tibetan yaks, was positively associated with high-altitude adaptation (p < .0006). Specially, mutation m.3638 A > G present in all cattle, resulting in the termination of transcription, was negatively associated with high-altitude adaptation (p < .0006). Additionally, MT-ND2 SNPs m.4351 G > A and m.5218 C > T also showed positive associations with high-altitude adaptation (p < .0004). MT-ND1 haplotypes H2, H3, H4, H6, and H7 showed positive associations but haplotype H20 had a negative association with high-altitude adaptation (p < .0008). Similarly, MT-ND2 haplotypes Ha1 Ha8, Ha10, and Ha11 were positively associated whereas haplotype Ha2 was negatively associated with adaptability to high-altitudes (p < .0008). Thus, MT-ND1 and MT-ND2 can be considered as candidate genes associated with adaptation to high-altitude environments.


Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole.
In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. Prolactinoma coinciding with psychosis can represent a therapeutic challenge.In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels.Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis.


Effect of the enrichment medium on the detection and diversity of Salmonella from porcine duodenal content.
This study assesses the effect of the enrichment medium used on the isolation of Salmonella from the duodenal content of naturally infected slaughter pigs. At six slaughterhouses, the duodenum was collected from 458 randomly chosen pigs and examined in the laboratory. Three semi-solid enrichment media (modified semi-solid Rappaport-Vassiliadis medium [MSRV], diagnostic semi-solid Salmonella medium [DIASALM], and Simple Method Salmonella [SMS] agar) and three enrichment broths (Rappaport-Vassiliadis, Rappaport Vassiliadis broth with Soya [RVS], and Muller Kauffmann Tetrathionate novobiocin broth [MKTTn]) were evaluated. If a migration zone was present on the semi-solid media, a loopful was taken both near the inoculation drop and at the edge of the migration zone and streaked on a Xylose Lysine Desoxycholate (XLD) agar plate. Each enrichment broth was streaked on XLD, and three presumptive colonies were further examined. Detection rate was calculated, and isolates were, after serotyping, genotyped by performing pulsed-field gel electrophoresis (PFGE). The overall frequency of Salmonella isolated in at least one of the six different media was 15.5% (71/458). No significant differences in relative sensitivity were obtained within semi-solid media and within liquid media. Semi-solid media showed a significant higher relative sensitivity than the one obtained with liquid media. A relative sensitivity higher than 83.1%, namely of 94.4%, could only be obtained by combining three different enrichment media (MSRV or DIASALM+RVS+MKTTn). In 13.4% of the positive pigs, more than one serotype was found within the duodenum of one pig. In 12.9% of the duodenal contents, different genotypes were found within the same serotype. Differences in serotypes and genotypes were found predominantly within the same enrichment medium. In conclusion, to obtain the highest Salmonella detection rate in naturally contaminated pig samples, MSRV should be used as enrichment medium. However, to obtain a realistic picture of the sero- and genotypes present, different samples per enrichment medium and different enrichment media should be tested.


Sclerosing stromal tumor of the ovary: MR-pathologic correlation in three cases.
Sclerosing stromal tumor (SST) of the ovary is a very rare sex cord stromal tumor occurring in a younger age group than other types of stromal tumors and most commonly accompanied by menstrual irregularity. Several unique histologic features including pseudolobulation, sclerosis and prominent vascularity are clearly reflected at ultrasonography and MRI. We report the ultrasonographic and MR features of three cases of histologically confirmed SSTs, and relate them to the pathological findings.


Response of plasma matrix metalloproteinase-9 to conventional abdominal aortic aneurysm repair or endovascular exclusion: implications for endoleak.
Matrix metalloproteinases are enzymes capable of breaking down all of the components of the extracellular matrix and have been implicated in the development of aneurysm formation. Because matrix metalloproteinase-9 (MMP-9) levels are elevated in aortic aneurysmal tissue and in that patient plasma, we hypothesized that plasma MMP-9 levels should decrease significantly after conventional and endovascular infrarenal abdominal aortic aneurysm (AAA) repair but that plasma MMP-9 levels would remain elevated in patients with endoleaks. A sandwich enzyme-linked immunosorbent assay was used to measure plasma levels of MMP-9 in patients with AAA who underwent conventional (n = 26; mean age, 71.5 years) and endovascular (n = 25; mean age, 76.4 years) AAA repair. Levels were drawn before surgery and at 1 month and 3 months after surgery. Eight patients for endovascular repair had endoleaks identified on postoperative computed axial tomographic scans. No correlation existed between preoperative plasma MMP-9 levels when compared with age, gender, or aneurysm diameter. No significant difference in preoperative plasma MMP-9 levels or AAA diameter was identified between patients with conventional repair compared with endovascular repair. Of the 51 patients, 33 had follow-up samples available for analysis. A significant increase in mean plasma MMP-9 levels was noted 1 month (149.5 +/- 40.1 ng/mL) after conventional AAA repair compared with preoperative levels (83.9 +/- 26.1 ng/mL; P <.05) and remained elevated 3 months after surgery (129.8 +/- 56.6 ng/mL). In those patients who underwent endovascular aneurysm exclusion without endoleak, a significant decrease in mean plasma MMP-9 levels was noted at 3 months (27.4 +/- 5.2 ng/mL) when compared with preoperative values (60.8 +/- 8.8 ng/mL; P <.01). In contrast, patients with endoleak after endovascular exclusion did not have a significant decrease in plasma MMP-9 levels at 3 months. Plasma MMP-9 levels remain elevated for as much as 3 months after conventional AAA repair, whereas successful endovascular exclusion of an AAA results in decreased plasma MMP-9 levels by 3 months. MMP-9 may have clinical value as an enzymatic marker for endoleak after endovascular AAA exclusion.


A new isolate of Iris severe mosaic virus causing yellow mosaic in Iris ensata Thunb.
Severe mosaic disease was observed on Iris ensata Thunb. in Spring 2008, in Hangzhou, China and it was found to be widely distributed in that region. Detection of viruses by electron microscopy resulted in the occurrence of a potyvirus in most symptomatic seedlings. Sequencing 1745 nucleotides of the 3'-terminal region of the genome of the typical viral isolate revealed that it was a new isolate of Iris severe mosaic potyvirus (ISMV), tentatively named ISMV-PHz .This strain shared high nucleotide identity with ISMV. Phylogenetic analysis also showed that this isolate clustered with iris severe mosaic potyvirus (ISMV) and onion yellow dwarf virus (OYDV) into a monophyletic group, and was closest in similarity to ISMV. The divergence of potyvirus-infecting iris species had a higher degree of relevance with natural host but not with the region from which it was isolated. This is the first report of ISMV isolated from I. ensata in China.


Structural basis for nucleic acid and toxin recognition of the bacterial antitoxin CcdA.
Toxin-antitoxin systems are highly abundant in plasmids and bacterial chromosomes. They ensure plasmid maintenance by killing bacteria that have lost the plasmid. Their expression is autoregulated at the level of transcription. Here, we present the solution structure of CcdA, the antitoxin of the ccd system, as a free protein (16.7 kDa) and in complex with its cognate DNA (25.3 kDa). CcdA is composed of two distinct and independent domains: the N-terminal domain, responsible for DNA binding, which establishes a new family of the ribbon-helix-helix fold and the C-terminal region, which is responsible for the interaction with the toxin CcdB. The C-terminal domain is intrinsically unstructured and forms a tight complex with the toxin. We show that CcdA specifically recognizes a 6 bp palindromic DNA sequence within the operator-promoter (OP) region of the ccd operon and binds to DNA by insertion of the positively charged N-terminal beta-sheet into the major groove. The binding of up to three CcdA dimers to a 33mer DNA of its operator-promoter region was studied by NMR spectroscopy, isothermal titration calorimetry and single point mutation. The highly flexible C-terminal region of free CcdA explains its susceptibility to proteolysis by the Lon ATP-dependent protease.


Coronary endothelial damage after crystalloid cardioplegia.
There is considerable clinical experience to suggest that damage to the myocardium during ischaemic arrest can be prevented by cardioplegic solutions. However, very little is known about the effects of these cardioplegic solutions on the coronary endothelium. The effects of three different cardioplegic solutions on the coronary endothelium are reported here. Preservation of the myocardium was studied with biochemical assays. Blood cardioplegia did not damage the coronary endothelium. Crystalloid cardioplegia caused disappearance of the endothelial cells and gross deformity of the flow surface. The addition of albumin to the crystalloid solution preserved most of the endothelial lining. Preservation of the myocardial high energy compounds seemed to be dependent only on the cooling effect of the cardioplegia and not on the composition of the solution. There was no correlation between high energy compounds and endothelial changes. The present study favours the use of cold blood cardioplegia which preserves both the coronary endothelium and the myocardial energy sources during ischaemic cardiac arrest.


A simple method of intra-articular antibiotic delivery in infected hip arthroplasty.
Intra-articular delivery of antibiotics is known to be important in the treatment of infected hip arthroplasty. We describe a simple, inexpensive, and convenient method of obtaining high levels of local antibiotics when the femoral component is not removed or when an articulating spacer is utilized. A case example is given in which this type of treatment resulted in a good outcome.


Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life.
The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, the antibody appeared to adhere to pipette tips, requiring tips to be changed during serial dilution to accurately measure potency. Second, during production scale-up, proteolytic cleavage was discovered to target an extended heavy chain loop, which was attributed to a protease in spent medium from 2-week culture. To enable large scale production, we altered the site of cleavage via a single amino acid change, K100mA. The resultant antibody retained potency and breadth while avoiding protease cleavage. We also added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS on a 208-virus panel. The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.


Effects of inhaled corticosteroids on systemic blood pressure in preterm infants.
To assess the effect of inhaled fluticasone propionate on (i) systemic blood pressure, and (ii) the need for volume expanders (crystalloids and colloids) and inotropes for blood pressure support in preterm, very low birth weight (VLBW) infants. Ventilated VLBW infants, less than 32 weeks of gestation, with respiratory distress syndrome were randomised to receive a 14-day course of either fluticasone propionate (500 microg/puff, 2 puffs every 12 h; n=27) or placebo (n=26) with a metered dose inhaler-spacer device. The response of treatment was assessed by comparing the use of volume expanders, inotropes, and the average and the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups. There were no significant differences in the average or the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups. However, the total volume of crystalloids and colloids requirement was significantly greater in control than in treated infants (p=0.03). There was also a trend towards greater consumption of the total cumulative dose of dopamine in the control infants (p=0.10). Fluticasone-treated infants required significantly less volume of crystalloids and colloids for blood pressure support compared with control infants. Further larger scale studies are required to determine whether inhaled corticosteroids could minimise the use of volume replacement therapy and inotropes in the treatment of hypotension in preterm infants in the early postnatal period.