Lung and pleural "free-cell responses" to the intrapulmonary deposition of particles in the rat.
Deposition of a high lung burden of particulate carbon or latex in the mouse elicits a biphasic macrophagic response, with the early increase in the size of the population of the alveolar macrophages (AM) being mainly due to an influx of mononuclear phagocytes from the blood compartment and the later phase being due to the egression of interstitial macrophages (IM). In the present study, we investigated the lung's free-cell response in the rat to the intrapulmonary instillation of microspheres and determined the contributions of newly arrived blood monocytes to the macrophagic response over a 30-d period. As of 24 h after deposition, the lavageable population size increased approximately fivefold. Most of the increase in the free cell population was due to a recruitment of polymorphonucleated leukocytes (PMN), although the size of the AM population nearly doubled. Only about 13% of the AM on d 1 were positive for myeloperoxidase activity, suggesting that recruitment of mononuclear phagocytes from the blood compartment plays a limited role in the early expansion of the AM pool in the rat. As of 14 and 30 d after particle deposition, lavaged AM numbers continued to be elevated; the enlarged sizes of the AM populations at these times could be explained, in part, by a continuing influx of blood monocytes. In a parallel component of the study, we also investigated how the pleural cell population might be affected during the lung's free-cell response to the particulate burden. No acute influx of PMN into the pleural space (PS) accompanied the early free-cell response; the chemotactic factors initially involved in recruitment of the PMN into the lung apparently did not reach the PS in significant or biologically active concentrations, or they were inoperable in the pleural compartment. On the other hand, the numbers of macrophages in the PS were significantly elevated on d 1 and 14 after particle deposition in the lung. The macrophagic response in the PS subsided by d 30, but at this latter sacrifice time, pleural mast-cell and lymphocyte numbers were significantly increased and decreased, respectively. These results indicate that the deposition of particles into the lung can lead to numerical alterations in the cell types composing pleural cell populations.


Blood and intrauterine leukocyte profile and function in dairy cows that spontaneously recovered from postpartum endometritis.
The profile and function of blood and uterine leukocytes were evaluated in 14 dairy cows that spontaneously recovered from postpartum endometritis (mild, n=6 and heavy, n=8; general health not affected). From a minimum of 2 weeks before parturition until 6 weeks postpartum, blood samples were obtained twice weekly for leukocyte counts and leukogram determination and once weekly for flow cytometry assessment of polimorphonuclear neutrophils (PMN) phagocytic capacity and oxidative burst activity. Uterine fluid-stained smears, obtained twice weekly from parturition until fluid was present in the uterus, were used for determination of the percentage of PMN, of phagocytizing PMN (phago-PMN) and of the mean number of phagocyted bacteria per phagocytizing PMN (phagocytic index; PI). Uterine swabs were obtained twice weekly from parturition until 35 days postpartum for bacteriological examination. The time of endometritis diagnosis was similar in cows with mild or heavy endometritis but the latter cows had a significantly longer persistence of the infection and of the isolation of Gram-negative anaerobes from the uterus. However, the effect of group (mild versus heavy) was not significant for all the blood and uterine parameters analysed. The effect of sampling day (within group effect) was significant (p<0.01 to p<0.00001) for all parameters, except for the blood monocyte count and the blood PMN phagocytic capacity, in which only a tendency for significance was observed (p<0.1). The effect of the interaction group x sampling day was significant only for the blood monocyte count. The phago-PMN and the PI were significantly correlated (r=0.70, p<0.001). A significant correlation was also observed between the uterine fluid phago-PMN and the blood PMN oxidative burst activity (r=-0.41, p<0.05). At the spontaneous recovery, the blood PMN oxidative burst activity was significantly higher (p<0.05) and the percentage of intrauterine phago-PMN and the PI were significantly lower (p<0.001 and p<0.01, respectively) than at diagnosis of endometritis. These results suggest that a decrease in blood PMN oxidative burst activity until the first week postpartum could be associated with an increased susceptibility to early postpartum endometritis. The later increase in this parameter as well as the increase in the intrauterine fluid phago-PMN and PI, might favour the spontaneous resolution of endometritis.


[Heparin-induced thrombocytopenia. Case report].
This article deals with the causality between perioperative heparin thrombosis prophylaxis and the appearance of acute vessel occlusion. Already 1948 Fidlar and Jaques described this relationship. Today heparin-induced thrombocytopenia (HIT) is a well known illness, but nevertheless vascular complications occur regularly. By means of three case reports problems in diagnosis and therapy of HIT are discussed. Because of the possibility of serious complications including death of the patient prevention methods and early diagnosis of HIT are recommended.


Influence of High-fat and High-cholesterol Diet on Major CYP Activities in the Liver.
We previously reported that a high-fat and high-cholesterol (HFHC) diet for 12 weeks induced non-alcoholic steatohepatitis (NASH) and influenced major CYP subtype gene expression levels and activities in a mouse model. In the present study, we determined the effects of the HFHC diet on CYP expression levels and activities prior to the establishment of NASH. When male C57BL/6J mice were fed the HFHC or a normal chow diet (Control) ad libitum for 4 weeks, body weights were significantly lower, whereas liver weights and hepatic lipid contents were significantly higher in the HFHC group than in the Control group. Under these conditions, hepatic microsomal luciferin-H (human CYP2C9 substrate) hydroxylation activity was significantly lower in the HFHC group than in the Control group. In order to investigate drug efficacy in mice fed the HFHC diet, an intraperitoneal glucose tolerance test was conducted with or without a pretreatment with tolbutamide (a CYP2C substrate) after 4 weeks of feeding. The plasma glucose-lowering effects of tolbutamide were attenuated in the HFHC group even though luciferin-H hydroxylation activity was suppressed in this group. The reason for this discrepancy was attributed to the mRNA expression levels of Cyp2c44 being lower and those of Cyp2c29 and Cyp2c66, which are involved in the metabolism of tolbutamide, being higher in the HFHC group than in the Control group. These results indicate that the expression of Cyp2c in the liver is influenced by the HFHC diet prior to the establishment of NASH and its regulation differed among the subtypes examined.


Malignant solitary fibrous tumor arising in the right buttock associated with metastatic parietal pleural and intrapulmonary tumors in addition to pleural effusion.
A malignant solitary fibrous tumor arising in the right buttock associated with metastatic parietal pleural and intrapulmonary tumors and pleural effusion was found in a 59-year-old man. A chest computed tomogram revealed three tumors attached to the parietal pleura with rib destruction, and a tumor in the left lower lung field. Histologically, the tumors of the buttock and parietal pleura were characterized by proliferation of bundles of spindle-shaped or oval cells separated by wavy hyalinized collagen tissue with no expression of cytokeratin, S-100 protein, muscle actin or epithelial membrane antigen, but these cells weakly expressed CD34 and strongly expressed vimentin.


Phosphine and phosphonite complexes of a Ru(II) porphyrin. 2. Photophysical and electrochemical studies.
The photophysical and electrochemical properties of a series of mono- and bis-phosphine complexes of a 5,15-diphenyl-substituted ruthenium porphyrin, (MeOH)Ru(II)(CO)(DPP) 1, were investigated. The ligands used were diphenyl(phenylacetenyl)phosphine (DPAP), diethyl (phenylacetenyl)phosphonite [PAP(OEt)(2)], tris(phenylacetenyl)phosphine [(PA)(3)P], and bis(diphenylphosphino)acetylene (DPPA). All complexes display two reversible one-electron oxidations at: 0.61 and 1.0 V vs SCE (1), 0.42-0.51 and 0.97-1.05 V [(PR(3))Ru(II)(CO)(DPP)], and 0.06-0.25 and 0.82-0.95 V [(PR(3))(2)Ru(II)(DPP)]. As predicted by EHMO calculations, the first oxidation is porphyrin or phosphorus centered, whereas the second one is ruthenium centered. Bulk electrolysis at the first oxidation potential yields stable monocations. Simulation of the cyclic voltammogram of (DPAP)Ru(II)(CO)(DPP) in CH(2)Cl(2) demonstrates the kinetic lability of the complex, and the association constant found (K = 1.27 x 10(6) M(-1)) is in accordance with the value determined by UV-vis titration (K = 1.2 +/- 0.3 x 10(6) M(-1)). Coordination of one phosphine ligand to Ru(II)(CO)(DPP) leads to a red shift in both the absorption and luminescence spectra. Shifts are typically 10 nm for the B- and Q-band absorptions and are not affected by the nature of the phosphorus ligand. The intense luminescence of (PR(3))Ru(II)(CO)(DPP), red-shifted by 21-28 nm compared to 1, can be attributed to originate from a (3)(pi,pi) excited state, and it exhibits lifetimes from 150 to 240 micros. In the bis-phosphine complexes (PR(3))(2)Ru(II)(DPP), the Q-band absorption is broadened and does not show any distinct peak. Judged from EHMO calculation, this could arise from a low-energy charge-transfer state involving the phosphorus ligand. The luminescence is efficiently quenched due to radiationless decay from a charge-transfer excited state, involving either the metal center or the phosphorus ligand; an unambiguous assignment could not be made.


Phenotypic and Molecular Alterations in the Mammary Tissue of R-Spondin1 Knock-Out Mice during Pregnancy.
R-spondin1 (Rspo1) is a member of a secreted protein family which has pleiotropic functions in development and stem cell growth. Rspo1 knock-out mice are sex-reversed, but some remain sub-fertile, so they fail to nurse their pups. A lack of Rspo1 expression in the mammary gland results in an absence of duct side-branching development and defective alveolar formation. The aim of this study was to characterize the phenotypic and molecular alterations of mammary gland due to Rspo1 knock-out. Using the transcriptional profiling of mammary tissues, we identified misregulated genes in the mammary gland of Rspo1 knock-out mice during pregnancy. A stronger expression of mesenchymal markers was observed, without modifications to the structure of mammary epithelial tissue. Mammary epithelial cell immunohistochemical analysis revealed a persistence of virgin markers, which signify a delay in cell differentiation. Moreover, serial transplantation experiments showed that Rspo1 is associated with a regenerative potential of mammary epithelial cell control. Our finding also highlights the negatively regulated expression of Rspo1's partners, Lgr4 and RNF43, in the mammary gland during pregnancy. Moreover, we offer evidence that Tgf-β signalling is modified in the absence of Rspo1. Taken together, our results show an abrupt halt or delay to mammary development during pregnancy due to the loss of a further differentiated function.


Testosterone replacement therapy and the risk of adverse cardiovascular outcomes and mortality.
The risk of adverse cardiovascular events and mortality associated with testosterone replacement therapy is controversial. The purpose of this report was to evaluate the effect of testosterone replacement therapy (TRT) in men with secondary hypogonadism on the risk of myocardial infarction (MI), stroke (CVA) or all-cause mortality. A retrospective cohort study was conducted using the Cleveland Clinic's electronic health record. Men ≥40 years of age, with at least two testosterone levels < 220 ng/dL, with one level obtained between 7 am and 10 am, were identified. Men with primary hypogonadism, secondary hypogonadism related to overt hypothalamic pituitary pathology, human immunodeficiency virus infection, metastatic cancer, and select contraindications to TRT, were excluded. Men exposed to TRT were matched to controls that were not exposed. A survival analysis was performed on the composite outcome of MI, CVA, or all-cause mortality. One hundred sixty-five patients exposed to TRT (treatment group) were matched with 210 not exposed to TRT (comparison group). The prevalence of established cardiovascular disease (CVD) was 20.0% in the treatment group vs. 17.1% in the comparison group (P = 0.478). The median [interquartile range (IQR)] age (years) and BMI (kg/m2) were 55 (49, 62) and 35.6 (32.1, 40.1) in the treatment group, and 55 (49, 61.7) and 36.3 (32.1, 40.8) in the comparison group, respectively. There were 12 (7.3%) events observed in the treatment group, and 16 (7.6%) in the comparison group. The median time (years) to the composite event was 2.1 (IQR 0.9, 4.6) and 1.8 (IQR 0.6, 3.4) for treatment and comparison groups, respectively. No difference in the risk of the combined cardiovascular endpoint was observed between the treatment group vs the comparison group, hazard ratio (HR) 0.81 (95% Confidence Interval [CI]: 0.38-1.71; P = 0.57). In hypogonadal men with a modest prevalence of established CVD, TRT was not observed to confer a protective or adverse effect on the risk of MI, CVA or all-cause mortality.


Lymph Drainage from the Chylocyst-Induced Hemodilution in an In Vivo Rabbit Study.
To confirm our previous study that abdominal respiration has induced hemodilution in human subjects, we performed in-vivo experiments involving anesthetized rabbits. Fifteen 6- to 7-month-old male Japanese white rabbits were used in the animal experiments. Anesthesia was maintained with 2.5%-3.0% isoflurane under N2O + 100% O2 inhalation. Ventilation was maintained at 40 mL/breath for 20 breaths/min. Physiological saline solution was administered at rated 18 mL/h during the experiments. First, we attempted to evaluate lymph flow through the thoracic duct using Sonazoid-based contrast-enhanced ultrasound (CEUS)-guided method and then investigated the effects of manual lymph drainage of the chylocyst on the numbers of red blood cells (RBC), hematocrit (Ht) levels, and the blood concentrations of total protein (TP) and hemoglobin (Hb). In this study, we established surgical methods for identifying the left venous angle and chylocyst using Evans blue dye in anesthetized rabbits. We also confirmed that a Sonazoid-based CEUS-guided method was the most useful technique for producing real-time images of lymph flow through the thoracic duct in anesthetized rabbits. In addition, in present experiments involving anesthetized rabbits, we confirmed that manually massaging the chylocyst produced significant hemodilution. Thus, the procedure produced significant reductions of TP, RBC, Hb, and Ht level in the rabbits.


Quantification of the push-pull effect in tolanes and a revaluation of the factors affecting the 13C chemical shifts of the carbon atoms of the CC triple bond.
Variously substituted tolanes were employed to show that the push-pull effect is also active in CC triple bonds by the successful correlation of the occupation quotient pi/pi of the pi orbital in resonance with the substituted phenyl moieties of tolanes versus the bond length of the CC triple bond. In addition, the influences of the ortho phenyl ring substituents on the 13C chemical shifts of the triple bond carbon atoms, which were estimated by Rubin et al.(4) to be "inapplicable for describing triple bond polarization", were re-evaluated, leading to the conclusion that, while anisotropic effects of ortho substituents are negligible, the steric ortho-substituent effects do in fact dominate the deviations obtained. A detailed theoretical NBO/NCS study has been employed to illuminate the facts of this case.


[Advantages and evidences research on Chinese medicine for treatment of pelvic inflammatory disease].
Pelvic inflammatory disease is an infectious disease. At present, Western medicine is mainly treated with antibiotics. However, the situation of antibiotics abuse is so grim that the potential risks such as the imbalance of bacteria, the resistance of bacteria, the production of super bacteria and the increase of adverse reactions are becoming more and more serious. Therefore, it is urgent to find a way to supplement or substitute antibiotics for the treatment of this disease. Traditional Chinese medicine treatment of the disease is effective and has its unique advantages. This paper mainly discusses the advantages and evidences of traditional Chinese medicine (TCM) treatment of pelvic inflammatory disease, to further prove the effectiveness and safety of TCM treatment and to provide medical evidence of reducing antibiotics use.


Potential therapeutic applications of infusions and hydroalcoholic extracts of Romanian glutinous sage (Salvia glutinosa L.).
Ethnopharmacological relevance: Salvia glutinosa, also known as the glutinous sage, has been used in Romanian folk medicine in the treatment of inflammation, injuries, and mild infections. However, there is no direct scientific evidence to demonstrate these activities. Aim of the Study: The present research was based on evaluating antioxidant, antiproliferative, and α-glucosidase inhibitory activity of S. glutinosa extracts, as well as the in vivo anti-inflammatory activity. Materials and Methods: Infusions and 70% (v:v) ethanol solution extracts of S. glutinosa stems and leaves, collected from two different locations in Romania, were prepared. Ten phenolic compounds were identified and quantified using the LC-DAD-ESI/MSn method, and total phenolic and flavonoid content, as well as in vitro antioxidant (DPPH, ABTS, and FRAP assays), antiproliferative, anti-inflammatory and alpha-glucosidase inhibitory activities were determined. A rat model of induced inflammation with turpentine oil was used for the examination of in vivo effects of the extracts, using diclofenac as an anti-inflammatory control. Results: The highest inhibitory α-glucosidase activity was determined to be IC50 = 0.546 mg/ml for the hydroalcoholic extract made with plant material collected on the road to Sighișoara. The highest cytotoxic activity against HepG2 cell line was determined to be GI50 = 131.68 ± 5.03 μg/ml, for the hydroalcoholic extract made with plant material from Sighișoara. In vivo administration of extract (200 mg lyophilized powder/ml) showed a significant reduction of NO production. Conclusion: Our findings indicate that S. glutinosa extracts exhibit antioxidant, α-glucosidase inhibitory activity, as well as a modest cytotoxic effect on HepG2 cell line. By in vivo administration, the extracts show anti-inflammatory and antioxidant activity, which correlates with the traditional use of the species. The environmental conditions seemed to induce important changes in the chemical composition and the bioactivity of the herbal preparations derived from S. glutinosa.


Risk factors for supraglottoplasty failure.
To review outcomes after supraglottoplasty for laryngomalacia and identify risk factors for supraglottoplasty failure. Case series with chart review. Tertiary care children's hospital. Retrospective case series evaluating patient outcomes after supraglottoplasty at an academic medical center between 2004 and 2010. Surgical failure was defined as need for revision surgery, tracheostomy tube placement, or gastrostomy tube insertion. Multivariable logistic regression was performed to identify risk factors for failure. The authors identified 95 children who underwent supraglottoplasty. After excluding patients with inadequate follow-up data, 74 patients were included. On the basis of chart review, 12 (16%) of those patients were defined as failures according to the criteria above. Age, history of prematurity (<34 weeks' gestational age), weight, growth curve percentile, neurologic/developmental problems, genetic syndrome, cardiac abnormality, synchronous airway lesions, and surgical technique were considered in risk factor analysis. Multivariable logistic regression was performed, revealing history of prematurity to be the only independent risk factor for failure (odds ratio = 4.85; 95% confidence interval, 1.07-22.1; P = .041). Outcomes after supraglottoplasty were comparable to previous reports in the literature. History of prematurity should be considered a risk factor for surgical failure.


[Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer].
The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.


[Anti-tumor effect of lentivirus-mediated MUCI antibody-targeted gene therapy with VP22-TK system on MUC1(+) human ovarian cancer transplanted intraperitoneally in nude mice].
To investigate the anti-tumor effect of anti-MUCI single-chain variable fragment (ScFv)-targeted and lentivirus-mediated herpes simplex virus structural protein VP22 and thymidinre kinase (TK) therapy on MUC1(+) human ovarian epithelial carcinoma tumor in mice transplanted intraperitoneally. Lentiviruses scFv-VP22-TK and VP22-TK were constorted Ten female BABL/c mice were injected intraperitoneally with MUC1+ human ovarian epithelial carcinoma cells line 3AO and then pathological examination was done to those mice that died of tumor. A human ovarian epithelial carcinoma model was established in another 30 female mice and they were randomly divided into 6 groups of 5 mice: NS (normal saline) + NS group (injected intraperitoneally with NS once per day for 3 days and then with NS 24 h after once a day for 5 days), VP22-TK + NS group (injected with herpes simplex virus structural protein VP22 and TK once a day for three days and then with NS 24 h after once a day for 5 days), scFv-VP22-TK + NS group (injected with scFv-VP22-TK and then NS in the same way), NS + ganciclovir (GCV) group (injected with NS and then with GCV), VP22-TK + GCV group (injected with VP22-TK and then GCV), and scFv-VP22-TK + GCV group (injected with scFv-VP22-TK and then GCV). The survival time was observed. Ten female nude mice without injection of tumor cells were injected with scFv-VP22-TK or VP22-TK, each for 5 mice; 3 weeks later their abdominal organs were examined to observe the effects of lentivirus on organs. All of the first ten mice injected with human ovarian epithelial carcinoma cells died of tumor. The mean survival times of the six experimental groups were 18.4 d +/- 2.9 d, 18.8 d +/- 1.5 d, 17.6 d +/- 1.1 d, 18.5 d +/- 1.6 d, 24 d +/- 5 d, and 46 d +/- 22 d respectively with significant differences between the VP22-TK + GCV group and NS + GCV group (chi(2) = 6.71, P = 0.009), between the scFv-VP22-TK + GCV group and NS + GCV group (chi(2) = 9.7, P = 0.002), and between the scFv-VP22-TK + GCV group and the VP22-TK + GCV group (chi(2) = 7.43, P = 0.006). Necrosis and apoptosis could be seen in the tumors in the VP22-TK + GCV group and scFV-VP22-TK + GCV group. No toxicity was observed in the mice injected with only scFv-VP22-TK or VP22-TK. The anti-MUCI ScFv-targeted and lentivirus-mediated herpes simplex virus VP22 and thymidinre kinase (TK) gene therapy has a significant anti-tumor effect on MUC1+ human ovarian epithelial carcinoma.


Hypersensitivity to cyclooxygenase inhibitory drugs in children: a study of 164 cases.
Hypersensitivity to cyclooxygenase (COX) inhibitors is rare in children. We studied 164 children reporting 213 reactions to paracetamol, ibuprofen and/or acetylsalicylic acid (ASA). Most reactions were cutaneous, either isolated or associated with respiratory symptoms and/or anaphylaxis. Based on a convincing clinical history or positive responses in challenges with the drug(s), hypersensitivity to one or several drug(s) was diagnosed in 49.4% of the children (60, 76.5 and 23.2% of the children reporting reactions to ASA, ibuprofen and paracetamol respectively). Cross-reactivity between nonsteroidal anti-inflammatory drugs (NSAIDs) was frequent (69.1%), but only 10.6% of the NSAID-sensitive children reacted to paracetamol. In contrast, all paracetamol-sensitive children reacted to NSAIDs. Anaphylaxis, immediate and accelerated reactions, atopy, older age and chronic/recurrent urticaria were risk factors for hypersensitivity and/or cross-reactivity between ASA, ibuprofen and paracetamol. In conclusion, hypersensitivity to COX inhibitors was frequent, especially in children reporting severe and/or immediate and accelerated reactions, and in older and atopic children. Cross-reactivity was frequent, suggesting that most reactions resulted from a non allergic hypersensitivity linked to the pharmacological properties of the drugs. However, in a few children, the reactions may result from allergic hypersensitivity to selective (families of) drugs, with tolerance to other drugs.


Autosomal aberrations associated with testicular dysgenesis or spermatogenic arrest in Chinese patients.
To analyze the relationship between autosomal aberrations and testicular dysgenesis or spermatogenic arrest in Chinese patients and to map the corresponding regions on each autosome in regard to the recorded aberrations accompanying these distubances. One hundred and nineteen cases of aberrant karyotypes with testicular dysgenesis, azoospermia or oligozoospermia reported in five Chinese journals and one monograph were analyzed. For each autosome, the type and frequency of chromosomal aberrations were counted and the regions corresponding to the disturbances were mapped out. Chromosomes 13, 14, 9, 21 exhibited a high frequency of aberration and bands 14q11 and 13p11 were the two regions showing the highest linkage to testicular dysgenesis or infertility. The frequency of chromosomal aberrations was higher in bands 9p11 and 22q than in others. Autosomes 13, 14, 9 and 21 in the order of importance play a critical role in testicular development and spermatogenesis and other autosomes may also contribute; the following regions, 14q11, 13p11,9p11, and 22q, are of high significance.


Biosecurity policies at international life science journals.
The prospect of bioterrorism has raised concerns about the potential abuse of scientific information for malign purposes and the pressure on scientific publishers to prevent the publication of "recipes" for weapons of mass destruction. Here we present the results of a survey of 28 major life science journals--20 English-language international journals and 3 Chinese and 5 Russian journals--with regard to their biosecurity policies and procedures. The survey addressed the extent to which life science journals have implemented biosecurity procedures in recent years, how authors and reviewers are advised about these procedures and the underlying concerns, and what the practical experiences have been. Few of the English-language publishers and none of the Russian and Chinese publishers surveyed implement formal biosecurity policies or inform their authors and reviewers about potentially sensitive issues in this area.


The Interplay of Diet Quality and Alzheimer's Disease Genetic Risk Score in Relation to Cognitive Performance Among Urban African Americans.
We examined the interactive associations of poor diet quality and Alzheimer's Disease (AD) genetic risk with cognitive performance among 304 African American adults (mean age~57 years) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. In this cross-sectional study, selected participants had complete predictors and covariate data with 13 cognitive test scores as outcomes. Healthy Eating Index-2010 (HEI-2010), Dietary Approaches to Stop Hypertension (DASH), and mean adequacy ratio (MAR) were measured. A genetic risk score for AD in HANDLS (hAlzScore) was computed from 12 selected single nucleotide polymorphisms (SNPs). Our key hypotheses were tested using linear regression models. The hAlzScore was directly associated with poor performance in verbal memory (-0.4 ± 0.2, 0.01) and immediate visual memory (0.4 ± 0.2, 0.03) measured in seconds, in women only. The hAlzScore interacted synergistically with poorer diet quality to determine lower cognitive performance on a test of verbal fluency. Among numerous SNP × diet quality interactions for models of cognitive performance as outcomes, only one passed correction for multiple testing, namely verbal fluency. Our results suggest that improved diet quality can potentially modify performance on cognitive tests of verbal fluency among individuals with higher AD genetic risk.


Multicentric peripheral ossifying fibroma: A case report and review of the literature.
A peripheral cement-ossifying fibroma is a benign fibro-osseous lesion of a reactive rather than a neoplastic nature, whose pathogenesis is uncertain. It predominantly affects adolescents and young adults, with the peak prevalence between 10 and 19 years, especially affecting females (two to four times more). Such lesions are commonly found on the maxillary bone. We hereby present and discuss a unique case of multicentric Peripheral Ossifying Fibroma (POF) affecting both the maxillary and the mandibular gingiva in an 11-year-old boy, with a disease duration of two months. This case is probably one of the first few cases discovered, which demonstrates that there may be a multicentric variant of the Peripheral Ossifying Fibroma. The purpose of this article is to present a case of POF and to briefly review the current literature on this condition.


Prostaglandin synthesis and response to alcoholism treatment.
Serum prostaglandin F2 (PGF2) was assayed in 27 alcoholic patients and in 18 control subjects. No significant difference was observed in mean basal PGF2 titers of patients and controls. However, patients who completed four months of alcoholism treatment had a mean titer that was significantly higher than that of treatment dropouts. Patients who maintained continuous abstinence for 2 years following treatment had a mean titer that was significantly higher than that of patients who returned to pre-treatment drinking levels.


Sublingual Buprenorphine Efficacy in Renal Colic Pain Relief: A Randomized Placebo-Controlled Clinical Trial.
This study was designed to compare the analgesic efficacy of sublingual (SL) buprenorphine and intravenous (IV) ketorolac for renal colic pain relief. The present study was carried out as a double-blind, double-dummy randomized clinical trial in patients diagnosed with acute renal colic attending the emergency department. The study subjects were 63 patients with confirmed renal stones. The subjects were randomly divided into two groups. One group, which included 32 patients, received SL buprenorphine tablets (2 mg) with an IV placebo, and another group, including 31 patients, received ketorolac tromethamine (30 mg) with a SL placebo. After medication, the pain of subjects was measured by a standard visual pain analogous scale (VPAS) in minutes 0, 20, 40, and 60 of study. Also, probable adverse effects were recorded. In 28.1% of patients in the buprenorphine group, the mean pain score decreased from 9.2 to 5.9, 2.8, and 1.5 after 20, 40, and 60 min, respectively, as determined by VPAS. Also, in 38.7% of patients in the ketorolac group, the mean pain score decreased from 9.1 to 5.5, 3.0, and 1.6 after 20, 40, and 60 min, respectively, as determined by VPAS. The two groups did not significantly differ for pain reduction at 20, 40, and 60 min (P value = 0.16, 0.34, and 0.3, respectively). No adverse effects were seen in the ketorolac group, but vomiting (18.8%), nausea (18.8%), and dizziness (21.9%) were detected in the buprenorphine group. We found no difference between SL buprenorphine and intravenous ketorolac in renal colic pain relief but more adverse effects in the buprenorphine group. Trial Registration Iranian Registry of Clinical trials identifier, IRCT2015041421773N1.


Microcirculation patterns in different stages of melanoma growth.
Several microcirculation patterns in tumors have been reported, including vasculogenic mimicry (VM), mosaic vessels (MV) and endothelium-dependent vessels. To investigate the sources of blood supply during different tumor stages, we studied the correlation between expression of vasculogenic mimicry (VM), mosaic vessels (MV) and endothelium-dependent vessels in a mouse melanoma xenograph. Sixty C57 mice were divided into 12 groups (5 mice per group) and inoculated with B16 melanoma cells. Eleven days later, the average tumor size was approximately 0.2 to 0.3 cm. From days 11 to 22, one group per day was randomly sacrificed, and the density of vasculogenic mimicry, mosaic vessels and endothelium-dependent vessels was measured in tumor tissue sections. Immunohistochemical dual-staining and electronic microscopy were also used to confirm the vessel types. All three types of microcirculation patterns were observed during tumor development. In the early stage of tumor growth, vasculogenic mimicry is the main pattern of blood supply. As the area of tumor tissue expands and the number of endothelium increase, vasculogenic mimicry is replaced by endothelium-dependent vessels. Mosaic vessels might be the interim state between vasculogenic mimicry and endothelium-dependent vessels. The number of endothelium-dependent vessels correlated with the size of the tumor (r=0.718, P=0.009), while the number of vasculogenic mimicry was inversely correlated (r=0.77, P=0.003). In conclusion, the number of vasculogenic mimicry decreased and the number of endothelial-dependent vessels increased during tumor growth.


[Growth rates of gastric cancer in the aged].
Yamashiro et al reported "growth patterns of gastric cancers in the aged" in 1991 using 219 autopsy cases and 33 followup cases of gastric cancer in the natural course without operations obtained for 16 years. They also showed a certain curve of cancer area and ordinal number of tumor size on the logarithmic scale of both axes obtained from 120 gastric cancer cases from autopsy. We considered the curve by Yamashiro as a model curve of cancer growth by regarding ordinal numbers of tumor size as course times of tumor growth. Then we re-examined the 33 follow-up cases and calculated the tumor growth rate in each case by means of comparing case data with the model curve described above. In the result, the follow-up cases were grossly divided into 5 groups of ratios of growth rate 2(0), 2(1), 2(2), 2(3) and 2(4). In some articles about the cancer growth-rate of digestive organs, their data-values of doubling-time are suggestive of an arrangement with groups and gaps in it, respectively. They seem supportive of our results above.


OPTIC NERVE MENINGOCELE SIMULATING EXTRAOCULAR EXTENSION OF CHOROIDAL MELANOMA.
To report a case of optic nerve meningocele simulating massive, recurrent extraocular extension of choroidal melanoma. Case report. A 53-year-old white man with choroidal melanoma in his left eye of 7.3-mm thickness was treated with plaque radiotherapy and transpupillary thermotherapy. On 1-year follow-up examination, visual acuity was 20/20 in the right eye and 20/30 in the left eye. The regressed choroidal melanoma scar in the left eye measured 1.5 mm in thickness with stable margins. The optic disk was normal. Ultrasonography demonstrated regressed echogenic choroidal scar, with an echolucent multilobulated retrobulbar mass, suspicious for extraocular extension. On magnetic resonance imaging, the retrobulbar mass corresponded to a distended and kinked optic nerve sheath, filled with extensive subarachnoid fluid and normal-size optic nerve with apposition against the posterior globe. There was no extraocular extension of tumor. Similar but less distended right optic nerve sheath was documented, consistent with optic nerve sheath meningocele in both eyes. Observation was advised and the findings remained stable. Optic nerve sheath meningocele is a benign dilatation of the optic nerve sheath that can simulate orbital tumor or extraocular extension of intraocular tumor. Magnetic resonance imaging can reliably differentiate these conditions.


Fabrication of Co3O4 from Cobalt/2,6-Napthalenedicarboxylic Acid Metal-Organic Framework as Electrode for Supercapacitor Application.
In this study, cobalt-based metal-organic framework (MOF) powder was prepared via the solvothermal method using 2,6-naphthalenedicarboxylic acid (NDC) as the organic linker and N,N-dimethylformamide (DMF) as the solvent. The thermal decomposition of the pristine cobalt-based MOF sample (CN-R) was identified using a thermogravimetric examination (TGA). The morphology and structure of the MOFs were modified during the pyrolysis process at three different temperatures: 300, 400, and 500 °C, which labeled as CN-300, CN-400, and CN-500, respectively. The results were evidenced via field-emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The crystallite size of all samples was calculated using Scherrer's equation. The smallest crystallite size of 7.77 nm was calculated for the CN-300 sample. Fourier transform infrared spectroscopy (FTIR) spectra were acquired for all the samples. The graphical study of the cyclic voltammogram (CV) gave the reduction and oxidation peaks. The charge transfer resistance and ionic conductivity were studied using electrical impedance spectroscopy (EIS). The galvanostatic charge-discharge (GCD) responses of all samples were analyzed. The relatively high specific capacitance of 229 F g-1 at 0.5 A g-1 was achieved in the sample CN-300, whereby 110% of capacitance was retained after 5000 cycles. These findings highlighted the durability of the electrode materials at high current densities over a long cycle.


Evaluation of remote assessment reliability in the follow-up of patients with diabetic macular edema.
To compare the reliability of office versus remote assessments in the decision to use intravitreal injection for patients with diabetic macular edema (DME). We retrospectively evaluated office and remote assessments for decision agreement regarding treatment by intravitreal injection or non-treatment for DME. Remote assessment consisted in remote evaluation of patient medical data by three reviewers with different skills. Two OCT analysis strategies were performed with the same office assessment data: 1) macular mapping with only two OCT B-scans passing through the fovea, and 2) macular mapping with complete macular scans. Agreement for treatment decisions and OCT analysis strategies were analysed using Cohen's Kappa coefficient (κ). Data from 49 patients (96 eyes) were included. Treatment decision agreement with two OCT B-scans passing through the fovea was considered excellent for all reviewers (κ between 0.80 and 0.85, varying between reviewers). Treatment decision agreement with complete macular scans was considered excellent (κ between 0.85 and 0.93, varying between reviewers). Agreement between the two OCT analysis strategies and reviewers was considered excellent. Remote assessment in a telemedicine model can be a useful alternative for DME patient follow-up.


Clinical outcome of patients with intermediate probability lung scans during six-month follow-up.
A retrospective review of a consecutive series of patients with intermediate probability (IP) ventilation/perfusion lung scans was performed to evaluate: the frequency of documented thromboembolic (TE) disease, either pulmonary embolism (PE) or deep-venous thrombosis (DVT), at time of presentation; the prevalence of new diagnoses of TE disease during 6-mo follow-up; and occurrence of mortality during the same follow-up interval. Radiologic and clinical records for all patients who had ventilation/perfusion lung scans reported as IP or indeterminate during a 7-yr period were reviewed. TE disease at presentation or during follow-up was identified from results of pulmonary angiography, chest CT, lower extremity Doppler ultrasound and venography, and repeat lung scans. Occurrence of mortality and cause of death were determined by medical record review. Of 164 patients studied, 36 (22%) had TE disease confirmed at initial presentation (PE = 19; DVT only = 17), and four others (2%) developed evidence of TE disease during follow-up, two with PE and two with DVT. Prevalence of TE disease was significantly greater in patients with matching perfusion/chest radiographic abnormalities and ventilation/perfusion mismatches (0.5-1.5 segmental equivalents) than in those with various patterns of matching ventilation/perfusion defects (31% versus 14%, p < 0.01). Twenty-eight patients (18%) died during follow-up, but recurrent PE was implicated in only one death in a patient with angiographically-confirmed PE at initial presentation. Among the 116 patients who did not receive long-term anticoagulation after their initial lung scans, 22 (19%) died, none of whom had PE confirmed or suspected as a contributing cause. The prevalence of new or recurrent TE disease is low in patients with IP lung scans who are appropriately evaluated and managed after their initial presentation. No evidence of significant mortality secondary to untreated PE was found in the study group.


Investigation of the arterial stiffness on renal artery Doppler sonograms.
This study aims to identify the effect of stiffness on renal artery Doppler sonograms by using a curve fitting approach. The study includes 20 patients with suspected renovascular hypertension. Each patient underwent recordings during renal artery examinations before and after administration of Captopril 25 mg (Kapril tablet, MN Pharmaceuticals, Istanbul, Turkey). Doppler signals were analyzed with short time Fourier transformation, followed by curve fitting to sonograms using Savitzky-Golay method. Doppler parameters obtained from pre- and post-Captopril curve-fitted sonograms were statistically compared with "Paired-Samples t-Test". Captopril administration resulted in a significant decrease in the mean frequency and a significant increase in Pulsatility Index of the periods. No significant difference was detected between maximum systolic and minimum diastolic frequencies, Resistivity Index, and the Acceleration Index. The computational approach in this study appears to be promising.


The amino acid sequence of the outer coat protein VP2 of neutralizing monoclonal antibody-resistant, virulent and attenuated bluetongue viruses.
Monoclonal antibodies which reacted with four different epitopes were used to select neutralization-resistant variants of Australian bluetongue virus serotype 1 (BTV1AUS; isolate CS156). Nucleotide sequencing of the VP2 outer coat protein gene of these variants showed that two of them contained alterations within the previously defined neutralization site at amino acids 328 to 335 (Gould et al., 1988). Comparison of VP2 sequences of several BTV serotypes, in addition to nucleotide sequence changes in a number of variants, suggested that this neutralization site was larger and contained 19 amino acids, the conformation of which could be affected by other regions of the VP2 protein. Nucleotide sequencing of neutralization-resistant variants revealed a total of four other regions of VP2 affecting the ability of monoclonal antibodies to neutralize the virus and these results support the notion that the neutralization site in VP2 was conformation dependent. The complete nucleotide sequence of the VP2 gene of virulent BTV1AUS (C5156) was determined directly from viral nucleic acid isolated from the blood of a sheep suffering clinical bluetongue disease. Comparison of the VP2 sequence of this virulent virus with that previously published for an avirulent, laboratory strain (Gould, 1988), indicated that the passage of virulent virus approximately 20 times in tissue culture over the last decade, not only led to attenuation but resulted in the appearance of ten nucleotide changes in the VP2 gene. Six of these nucleotide changes were silent, two resulted in conservative amino acid substitutions and two generated radical amino acid changes. However, in a separate experiment, a single passage of the virulent virus in tissue culture while leading to attenuation did not result in a nucleotide change in the VP2 outer coat protein gene.


Visual outcomes following orbital biopsy.
The risks of orbital biopsy depend on the lesion's location and relationship with surrounding structures. Complications include reduced vision, although visual outcomes following orbital biopsy are not widely reported. To determine visual outcomes following orbital biopsy in Gartnavel General Hospital's Oculoplastic and Oncology Service. Case note review of 50 consecutive patients undergoing orbital incision or excision biopsy between January 2006 and December 2010. Data collected included preoperative clinical examination, radiological and histological features, preoperative and postoperative corrected distance visual acuity (CDVA) and surgical complications. The main outcome measure was change in CDVA. Mean follow-up duration was 1.32 years. Histological diagnoses following biopsy included idiopathic orbital inflammation (n = 13) and lymphoma (n = 9). Of the radiologically defined lesions, 86.7% were extraconal (13.3% intraconal). Extraconal lesions were anterior in 59.0% (41.0% posterior). Mean preoperative LogMAR CDVA was 0.10 which was maintained at day one post-biopsy, indicating the absence of immediate sight-threatening complications such as retrobulbar haemorrhage or optic nerve compression, and there was no significant reduction at one-year follow-up (p = 0.239). Further analysis of change in CDVA showed no difference between: anterior and posterior lesions; extraconal and intraconal lesions; incision and excision biopsies; anterior and lateral surgical approaches. CDVA is retained for one year following orbital biopsy. Significant visual loss is a very rare complication of this procedure.


Free-Standing Ultrafine Nanofiber Papers with High PM0.3 Mechanical Filtration Efficiency by Scalable Blow and Electro-Blow Spinning.
Particulate matter of 0.3 μm in diameter (PM0.3) poses a serious threat to the environment and human beings. Ultrathin and -light nanofibrous filters with excellent filtration properties can significantly prevent the detrimental effects of these particles. Here, we develop free-standing polyamide PA-66 ultrafine nanofiber papers for PM0.3 filtration using effective and scalable blow and electro-blow spinning techniques. The smallest average fiber diameter is 61.7 nm, which is 2-3 orders of magnitude smaller than that of conventional textiles. Poly(ethylene terephthalate) nonwovens are selected to fabricate free-standing nanofiber papers of various polymers, including polyamide, poly(methyl methacrylate), poly(vinylpyrrolidone), and poly(ethylene oxide) owing to the smooth surfaces of the nonwovens. This underlying principle can be used to create similar free-standing nanofiber papers from other commodity polymers in the future. Mechanisms of capturing particulate matter with different nanofiber morphologies are discussed. Salt and oil particulates are used to characterize the filtration properties. PA-66 papers are promising reusable filters owing to their mechanical particle-capture mechanism. The blow-spun PA-66 papers show filtration performance of 98.75% efficiency and a pressure drop of 125.44 Pa owing to the "slip" effect caused by the ultrasmall diameter. In the electro-blow spinning process, a supplementary voltage supply is conducive to separating nanofiber bundles into random-oriented nanofibers. Electro-blown spun papers possess an ultrahigh efficiency of 99.99% with a reduced areal density of 0.9 g m-2. These PA-66 papers can be used in a variety of applications, such as reusable personal protective equipment, industrial waste gas treatment, and central ventilation purification systems.


Prenatal diagnosis and perinatal outcome in congenital diaphragmatic hernia. Single tertiary center report.
To evaluate the perinatal results for fetuses and neonates with left-sided congenital diaphragmatic hernia (CDH) and the role of the prenatal diagnosis in the pregnancy outcome. We reviewed data from fetuses and neonates with left-sided CDH, managed from January 2009 and December 2013 in the University Clinic Hospital, Craiova, Romania. The following data were analyzed: the gestational age at the time of diagnosis, fetal karyotyping, presence of associated structural malformations, ultrasound (US) data (circumference and area of right lung, lung-to-head ratio - LHR, observed/expected LHR, hepatic herniation), the type of antenatal care, the pregnancy outcome, the place of birth and the conventional autopsy data, if performed. Perinatal outcomes were obtained by reviewing hospital documents. Twenty-one cases were identified. No fetal surgery was performed in our series. Mean gestational age at time of diagnosis was 29 weeks of amenorrhea (WA) (range, 16-37 WA). Associated structural malformations were noticed in nine (42.8%) cases, in which three fetuses had a normal karyotype and two had chromosomal abnormalities, and four fetuses were not investigated. Isolated congenital diaphragmatic hernia was confirmed in 12 (57.1%) cases. All early second trimester diagnosed cases were terminated. The overall mortality rate was 61.9%. Rates of fetal deaths, early neonatal deaths, late neonatal deaths, and survival were 28.5%, 19%, 14.2%, and 38%, respectively. The perinatal mortality rate was 19% in cases with isolated congenital diaphragmatic hernia. The overall and perinatal mortality rate in congenital diaphragmatic hernia was still high in our series. Early perinatal deaths are associated with early diagnosis and with the presence of other structural defects. The prevalence of chromosomal abnormalities in perinatal death could not be determined from these data. In isolated congenital diaphragmatic hernia, mortality is related to the presence of herniated liver and severe pulmonary hypoplasia, this being well correlated with antenatal ultrasound parameters used for the estimation of fetal lung volumes. The antenatal diagnosis allowed better counseling of the parents, description of associations and improving the neonatal care.


Nerve-guided laparoscopic total mesorectal excision for distal rectal cancer.
Urogenital dysfunctions are well-recognized problems after rectal cancer surgery and are often due to autonomic nerve damage. Although following holy planes during total mesorectal excision (TME) reduces the possibility of damage to the autonomic nerve fibers, these could still be affected in some critical areas.1 (,) 2 To improve the quality of surgery and prevent nerve damage, accurate intraoperative anatomical orientation of autonomic nerve is essential.3 Thanks to advancement of the high-definition laparoscopic technology, even the finest nerve fibers deep in the pelvic cavity can be identified through illumination and magnification.4 We aim to present a surgical technique of using the autonomic nerves as landmarks to guide laparoscopic TME for distal rectal cancer, with the purpose of preventing autonomic nerve damage to the largest extent. The video describes the technique of performing nerve-guided laparoscopic TME in a 50-year-old man with a rectal cancer (7 cm from anal verge). Preoperative staging by endorectal ultrasound and pelvic magnetic resonance imaging is stage I rectal cancer (cT2N0M0). Five trocars (two 12 mm and three 5 mm) are used. All procedures are performed with conventional laparoscopic instruments. The sigmoid colon is mobilized using a medial approach. The superior hypogastric plexus lies just posterior to the inferior mesenteric artery (IMA) are clearly identified and protected. Then the root of the IMA is ligated and cut. The left Toldt space is dissected, followed by complete mobilization of the sigmoid colon. The superior hypogastric plexus nerve fibers combine to a strong pair of hypogastric nerves as they enter the pelvic cavity, and can be clearly identified when the mesorectum is lifted. Then the mesorectum is separated from the hypogastric nerves by sliding down along the nerves. Dissection of the mesorectum is continued in the loose areolar plane along the midline down to the sacrococcygeal junction. Then the mesorectum is dissected laterally from posterior midline up to 9 o'clock on the left and to 3 o'clock on the right side. The splanchnic nerves can be identified as they swing from the sacrum and straight into the pelvic plexus. The peritoneum is dissected in an arc line about 0.5 cm above the line of rectovesical pouch. After the anterior side of the rectum is mobilized, the mesorectum is dissected along the seminal vesicles downward and sideward to the lateral margin. The neurovascular bundle of Walsh at the anterolateral side of the rectum is clearly identified and protected. The mobilization of the mesorectum ceases at the tendinous arch of levator ani. Then the rectum is only fixed to the pelvic side wall by its lateral ligaments, which are consisted by rectal branch of the inferior pelvic plexus and vessels. Thus care should be taken to cut only those rectal nerve fibers, leaving the inferior pelvic plexus intact. The mesorectum is divided 5 cm distal to the lesion with one firing of an endoscopic stapler. The specimen is extracted through a 3 cm transumbilical laparotomy. End-to-end anastomosis using a circular stapler is performed intra-abdominally. There were no intraoperative complications. The operating time was 160 min. Blood loss was 20 mL. The patient underwent an uneventful recovery and was discharged home on postoperative day 6. Final pathology was pT2N0M0. At 6-month follow-up, the patient had no urogenital dysfunctions. Nerve-guided laparoscopic total mesorectal excision for distal rectal cancer is safe and feasible. This technique should be considered whenever possible as a means to prevent autonomic nerve damage and subsequent loss of urogenital function.


The treatment of hypertension: a therapeutic philosophy for the 1990s.
To date, a range of drugs are available that are generally well tolerated and effective in lowering blood pressure. Although they are successful in reducing stroke, renal failure, and cardiac failure, they have a disappointing and less than expected influence on coronary artery disease and its manifestations. The genetic and environmental factors determining susceptibility to atherosclerosis and coronary artery disease are now more clearly defined and interactions between risk factors and protective mechanisms recognized. Drug treatment of hypertension must become a part of the overall approach to prevention of cardiovascular disease and possible health promotion. Dietary and hygienic measures (cessation of smoking and control of alcohol intake) should be combined where necessary with specific treatment of hypertension and hyperlipidemia. Future drug treatment must not only be effective and well tolerated but should complement other preventive approaches. In view of the increasing recognition that blood pressure treatment with a single drug is unlikely to be successful in all patients, there is likely to be a role in the future for pharmacologically coherent low-dose combinations of antihypertensive drugs.


A percolation theory for designing corrosion-resistant alloys.
Iron-chromium and nickel-chromium binary alloys containing sufficient quantities of chromium serve as the prototypical corrosion-resistant metals owing to the presence of a nanometre-thick protective passive oxide film1-8. Should this film be compromised by a scratch or abrasive wear, it reforms with little accompanying metal dissolution, a key criterion for good passive behaviour. This is a principal reason that stainless steels and other chromium-containing alloys are used in critical applications ranging from biomedical implants to nuclear reactor components9,10. Unravelling the compositional dependence of this electrochemical behaviour is a long-standing unanswered question in corrosion science. Herein, we develop a percolation theory of alloy passivation based on two-dimensional to three-dimensional crossover effects that accounts for selective dissolution and the quantity of metal dissolved during the initial stage of passive film formation. We validate this theory both experimentally and by kinetic Monte Carlo simulation. Our results reveal a path forward for the design of corrosion-resistant metallic alloys.


PET-Based Human Dosimetry of 68Ga-NODAGA-Exendin-4, a Tracer for β-Cell Imaging.
68Ga-NODAGA-exendin-4 is a promising tracer for β-cell imaging using PET/CT. Possible applications include preoperative visualization of insulinomas and discrimination between focal and diffuse forms of congenital hyperinsulinism. There is also a significant role for this tracer in extending our knowledge on the role of β-cell mass in the pathophysiology of type 1 and type 2 diabetes by enabling noninvasive quantification of tracer uptake as a measure for β-cell mass. Calculating radiation doses from this tracer is important to assess its safety for use in patients (including young children) with benign diseases and healthy individuals. Methods: Six patients with hyperinsulinemic hypoglycemia were included. After intravenous injection of 100 MBq of the tracer, 4 successive PET/CT scans were obtained at 30, 60, 120, and 240 min after injection. Tracer activity in the pancreas, kidneys, duodenum, and remainder of the body were determined, and time-integrated activity coefficients for the measured organs were calculated. OLINDA/EXM software, version 1.1, was applied to calculate radiation doses using the reference adult male and female models and to estimate radiation doses to children. Results: The mean total effective dose for adults was very low (0.71 ± 0.07 mSv for a standard injected dose of 100 MBq). The organ with the highest absorbed dose was the kidney (47.3 ± 10.2 mGy/100 MBq). The estimated effective dose was 2.32 ± 0.32 mSv for an injected dose of 20 MBq in newborns. This dose decreased to 0.77 ± 0.11 mSv/20 MBq for 1-y-old children and 0.59 ± 0.05 mSv for an injected dose of 30 MBq in 5-y-old children. Conclusion: Our human PET/CT-based dosimetric calculations show that the effective radiation doses from the novel tracer 68Ga-NODAGA-exendin-4 are very low for adults and children. The doses are lower than reported for other polypeptide tracers such as somatostatin analogs (2.1-2.6 mSv/100 MBq) and are beneficial for application as a research tool, especially when repeated examinations are needed.


Coordination of cell proliferation and cell expansion mediated by ribosome-related processes in the leaves of Arabidopsis thaliana.
Co-ordination of cell proliferation and cell expansion is a key regulatory process in leaf-size determination, but its molecular details are unknown. In Arabidopsis thaliana, mutations in a positive regulator of cell proliferation often trigger excessive cell enlargement post-mitotically in leaves. This phenomenon, called compensation syndrome, is seen in the mutant angustifolia3 (an3), which is defective in a transcription co-activator. Such compensation, however, does not occur in response to a decrease in cell number in oligocellula (oli). oli2, oli5 and oli7 did not exhibit compensation and the reduction in cell number in these mutants was moderate. However, when an oli mutation was combined with a different oli mutation to create a double mutant, cell number was further reduced and compensation was induced. Similarly, weak suppression of AN3 expression reduced cell number moderately but did not induce compensation compared with an an3 null mutant. Furthermore, double mutants of either oli2, oli5 or oli7 and an3 showed markedly enhanced compensation. These results suggest that compensation is triggered when cell proliferation regulated by OLI2/OLI5/OLI7 and AN3 is compromised in a threshold-dependent manner. OLI2 encodes a Nop2 homolog in Saccharomyces cerevisiae that is involved in ribosome biogenesis, whereas OLI5 and OLI7 encode ribosome proteins RPL5A and RPL5B, respectively. This suggests that a factor involved in the induction of compensation may be under the dual control of AN3 and a ribosome-related process.


Vaccination of chickens against Newcastle disease with a food pellet vaccine.
The Australian, heat-resistant, a virulent V4 strain of Newcastle disease (ND) virus was selected for further heat resistance to give a variant designated V4-UPM. V4-UPM was sprayed on to food pellets which were fed to chickens in amounts calculated to give about 10(6) EID50 per chicken. Chickens vaccinated only once by feeding developed no haemagglutination-inhibition (HI) antibodies and were not protected against challenge with a viscerotropic velogenic strain of ND virus. Chickens given food pellet vaccine at 3 and 6 weeks of age developed HI antibodies and were substantially protected against parenteral and contact challenge with virulent ND virus. Similar protection was achieved when the V4-UPM vaccine was given intranasally on two occasions or when the vaccine virus was allowed to spread by contact from intranasally vaccinated chickens to nonvaccinated chickens. Heat resistant ND vaccine incorporated in food pellets may provide a method for protecting village chickens against ND in tropical countries.


Oral lesions in HIV infection in developing countries: an overview.
HIV infection is a major global health problem affecting developing and developed countries alike. Oral lesions that are associated with this disease are important, since they affect the quality of life of the patient and are useful markers of disease progression and immunosuppression. Oral lesions in HIV infection have been well-documented in developed countries, but there are fewer reports on oral lesions from developing countries. Oral candidiasis is the most common opportunistic infection seen in all continents. Kaposi's sarcoma has been reported only from Africa and Latin America, while histoplasmosis and penicilliosis were reported in patients with advanced disease from Thailand. HIV-associated salivary gland disease has a high prevalence in Africa and Latin America, especially in the pediatric group. It is clear that there are considerable regional variations in the oral manifestations of HIV infection, depending both on the populations studied and on the clinical expertise available, among other factors. Well-designed and -documented studies are necessary for the correct assessment of the nature and magnitude of the problem in developing countries, if oral health measures are to be effectively formulated for the HIV-infected.


Emotional and physical intimacy in coping with lupus: women's dilemmas of disclosure and approach.
This study examined whether self-rated physical and emotional intimacy of 74 women with their heterosexual partner, during an illness episode of lupus, was related to their affect and relationship satisfaction. It was predicted that greater intimacy would be related to better psychosocial adjustment. Women who engaged in physically intimate behavior with their partner more often reported greater relationship satisfaction. Women who frequently avoided or who were often the initiators of physical intimacy, however, reported greater negative affect. Concerning emotional intimacy, women who disclosed more information about illness symptoms and women who concealed more information about their symptoms and feelings experienced the highest levels of negative affect. Results identify dilemmas that women with recurrent illness may face when trying to maintain intimacy during illness periods.


Resilience and Anxiety Among Healthcare Workers During the Spread of the SARS-CoV-2 Delta Variant: A Moderated Mediation Model.
The B.1.617.2 (Delta) variant of SARS-COV-2 has caused a surge in COVID-19 cases worldwide, placing a great burden on the health care system under the zero-tolerance epidemic prevention policy in China. The present study aimed to investigate the prevalence of anxiety among health care workers during the spread of the SARS-CoV-2 Delta variant, and to discuss the mediating role of positive coping style between resilience and anxiety, and the moderating role of general self-efficacy. Connor-Davidson Resilience scale (CD-RISC), Generalized Anxiety Disorder Scale (GAD-7), General Self-efficacy Scale (GSES) and Simplified Coping Style Questionnaire (SCSQ) were used in this cross-sectional study among 390 healthcare workers in Jiangsu Province, China. Mackinnon's four-step procedure was applied to test the mediation effect, and Hayes PROCESS macro was conducted to examine the moderated mediation model. The prevalence of anxiety among Chinese healthcare workers during the spread of the SARS-CoV-2 Delta variant was 41.8%. Male, unmarried, childless and younger subjects reported higher levels of anxiety. Positive coping partially mediated the effect of resilience on anxiety among healthcare workers and the indirect effect was stronger with the increase of general self-efficacy. Anxiety was prevalent among healthcare workers during the spread of SARS-CoV-2 Delta variant. This research sheds new light on the potential mechanism underlying the association between resilience and anxiety and provides new insight into the prevention of anxiety among healthcare workers during the spread of the SARS-CoV-2 Delta variant.


Current management review of thoracolumbar cord syndromes.
Injuries to the thoracolumbar spine may lead to a complex array of clinical syndromes that result from dysfunction of the anterior motor units, lumbosacral nerve roots, and/or spinal cord. Neurologic dysfunction may manifest in the lower extremities as loss of fine and gross motor function, touch, pain, temperature, and proprioceptive and vibratory sense deficits. Two clinical syndromes sometimes associated with these injuries are conus medullaris syndrome (CMS) and cauda equina syndrome (CES). To review the current management of thoracolumbar spinal cord injuries. Literature review. Index Medicus was used to search the primary literature for articles on thoracolumbar injuries. An emphasis was placed on the current management, controversies, and newer treatment options. After blunt trauma, these syndromes may reflect a continuum of dysfunction rather than a distinct clinical entity. The transitional anatomy at the thoracolumbar junction, where the conus medullaris is present, makes it less likely that a "pure" CMS or CES syndrome will occur and more likely that a "mixed" injury will. Surgical decompression is the mainstay of treatment for incomplete spinal cord injury (SCI) and incomplete CMS and CES. The value of timing of surgical intervention in the setting of incomplete SCI is unclear at this time. This review summarizes the recent information on epidemiology, pathophysiology, diagnosis, and controversies in the management of thoracolumbar neurologic injury syndromes.


Keeping warfarin patients safe during the COVID-19 pandemic: review of an INR self-testing programme.
Anticoagulation clinics faced an unprecedented challenge during the COVID-19 pandemic to safely manage patients on warfarin therapy. A London teaching hospital trust received INR point-of-care (POC) testing devices from its clinical commissioning group. The Trust distributed the devices to patients who were cognitively and physically able to self-test and evaluated clinical outcomes and patient experience. A significant improvement in warfarin control (mean time in therapeutic range (TTR) before POC 52%, standard deviation (SD) 24.8, vs mean after 60.7%, SD 19.7; P>0.009) and a 39% reduction in missed appointments were seen in self-testing patients. Positive patient satisfaction and lifestyle outcomes were identified through a telephone survey. A minority of patients struggled with the technique, leading to frustration. Some patients used many test strips through unsuccessful and additional tests. POC testing in a carefully selected group of patients on warfarin therapy resulted in positive clinical and patient satisfaction outcomes. Appropriate governance processes are needed, and clinical expertise is required to support patients. Cost-effectiveness of POC testing needs careful monitoring.


Astaxanthin Relieves Testicular Ischemia-Reperfusion Injury-Immunohistochemical and Biochemical Analyses.
Testicular torsion potentially leads to acute scrotum and testicle loss, and requires prompt surgical intervention to restore testicular blood flow, despite the paradoxical negative effect of reperfusion. While no drug is yet approved for this condition, antioxidants are promising candidates. This study aimed to determine astaxanthin's (ASX), a potent antioxidant, effect on rat testicular torsion-detorsion injury. Thirty-two prepubertal male Fischer rats were divided into four groups. Group 1 underwent sham surgery. In group 2, the right testis was twisted at 720° for 90 min. After 90 min of reperfusion, the testis was removed. ASX was administered intraperitoneally at the time of detorsion (group 3) and 45 min after detorsion (group 4). Quantification of caspase-3 positive cells and oxidative stress markers detection were determined immunohistochemically, while the malondialdehyde (MDA) value, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were determined by colorimetric assays. The number of apoptotic caspase-3 positive cells and the MDA value were lower in group 4 compared to group 2. A significant increase in the SOD and GPx activity was observed in group 4 compared to groups 2 and 3. We conclude that ASX has a favorable effect on testicular ischemia-reperfusion injury in rats.


Least to most restrictive interventions. A continuum for mental health care facilities.
While this article does not propose to provide answers to the many questions prompted by the new Patient's Rights CoP (1999) or the newly revised JCAHO standards on seclusion and restraint (JCAHO, 2000), a prudent plan of action for any organization serving patients with a behavioral component to their treatment would be to adopt a policy of least restrictive intervention prior to consideration of seclusion and restraint in response to emergency patient care needs. It was the authors' intent to present a representative sample of the available literature and from that to develop a continuum of intervention possibilities ranging from least to most restrictive. In addition, suggestions found in the literature for implementation of least to most restrictive programs have been provided.


Vegetables, fruit and risk of gastric cancer in Japan: a 10-year follow-up of the JPHC Study Cohort I.
The association between vegetables and fruit consumption and gastric cancer risk was investigated in a population-based prospective study in 4 public health center areas in Japan. Dietary and other exposure data were obtained in 1990 from a cohort of 19,304 men and 20,689 women with a self-administered questionnaire. After 10 years of follow-up, a total of 404 cases of gastric cancer were documented among them. After adjustment for age, gender, areas and other potential confounding factors and after exclusion of the cases diagnosed in first and second follow-up years, the relative risk associated with intake 1 or more days per week compared to less than 1 day per week was 0.64 (95% CI 0.45-0.92) for yellow vegetable, 0.48 (95% CI 0.25-0.89) for white vegetable and 0.70 (95% CI 0.49-1.00) for fruit. Relative risks associated with quintile of total vegetable consumption were 1.00, 0.86, 0.75, 0.90 and 0.75 (p for trend = 0.17). In the differentiated type of gastric cancer, the association became clearer: 1.00, 0.96, 0.78, 0.88 and 0.53 (p for trend = 0.03). This prospective study suggests that vegetable and fruit intake, even in low amounts, is associated with a lower risk of gastric cancer. Although no striking differences in the association were seen between cardia and noncardia cancer, an inverse association was higher in differentiated rather than in undifferentiated types of gastric cancer.


Effect of trunk stabilization on quadriceps femoris muscle torque.
The purpose of this study was to determine if differences exist in angle-specific torque, torque-velocity relationships, and power-velocity relationships of the quadriceps femoris muscle group when the trunk was and was not stabilized and the starting position was varied. We calculated isokinetic torques from seven adult men while the trunk was and was not stabilized for nine combinations of velocity of movement 0, 30, and 105 degrees/sec) and starting position (40, 60, and 100 degrees of knee flexion). The results suggest that peak angle-specific torques and instantaneous power are greater when the trunk is stabilized, the increase in the trunk-stabilized torque and power was greater at the higher velocity and for the larger ranges of motion, and the testing movement should not begin beyond 30 degrees of the angle of interest.


Di(2-ethylhexyl)phthalate impairs erythropoiesis via inducing Klotho expression and not via bioenergetic reprogramming.
Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate to manufacture various plastic products. However, the potential effects of DEHP on erythropoiesis have not been investigated comprehensively. Here, we aimed to investigate whether DEHP modulated the function of hematopoietic stem and progenitor cells (HSPCs) to influence erythropoiesis, and to explore the associated mechanisms. In the present study, human cell lines with a capacity to differentiate into erythroid cells and murine bone marrow cells were treated with DEHP. DEHP not only impaired HSPC function, but also suppressed erythroid differentiation in a dose-dependent manner. In addition, DEHP removal restored HSPC activity. To explore how DEHP interfered with erythroid differentiation, we focused on energy metabolism and Klotho expression. DEHP suppressed erythroid differentiation via upregulating Klotho expression, while it did not via modulating cellular bioenergetics. Therefore, our results provided a novel insight into the pathophysiological link between phthalates and dysregulated erythroid differentiation.


Apatinib as non-first-line treatment in patients with Intrahepatic Cholangiocarcinoma.
Purpose: There is limited standard treatment for patients with advanced cholangiocarcinoma after refractory of chemotherapy. Apatinib is a tyrosine kinase inhibitor targeting VEGFR-2, which exhibited broad-spectrum antitumor activities in previous studies. We aim to evaluate the efficacy and safety of apatinib as non-first-line treatment in patients with advanced cholangiocarcinoma. Methods: This was a prospective open-label phase II trial (NCT03251443). Patients with pathology-confirmed cholangiocarcinoma after prior systemic therapy were enrolled. Participants were treated with apatinib 500 mg orally once daily. The primary end point was overall response rate (ORR). Results: Between August 8, 2017 and November 13, 2018, 30 patients participated in this study, and 26 patients received apatinib treatment except 4 patients withdrew consent before the first dosage. For full analysis set, the ORR was 11.5% and the disease control rate was 50.0%. 3 patients (11.5%) achieved partial response and no patients achieved complete response. The median progression free time was 2.0 (95% CI: 0.7-3.3) months and median overall survival was 9. 0 (95% CI: 4.6-13.4) months. The most common adverse events of any grade were fatigue (80.8%), hypertension (73.1%) and decreased appetite (38.5%). Grade 3 adverse events occurred in 23.1% patients and no grade 4 adverse events occurred. The most common grade 3 adverse events were hypertension (23.1%) and elevated transaminase (11.5%). Conclusion: Apatinib as non-first-line monotherapy has potential therapeutic efficacy in patients with advanced cholangiocarcinoma.


Safety investigation on total steroid saponins extracts from Dioscorea zingiberensis C.H. Wright: Sub-acute and chronic toxicity studies on dogs.
Sub-acute and chronic toxic effects of total steroidal saponins (TSSN) extracts from Dioscorea zingiberensis C.H. Wright on various internal organs and biochemical indicators have never been studied before and this study is the first of its kind to demonstrate sub-acute and chronic toxicities of TSSN on dogs. Administration of TSSN extracts at doses up to 3000 mg/Kg daily for 14 days, no biochemical and organ changes were observed on the experimental groups of dogs. Further, chronic toxicity study through oral administration of TSSN extracts at the gradual doses of 50, 250 and 500 mg/Kg for 90 days followed by a 2-week recovery assay revealed absence of significant architectural and morphological changes in internal organs which were confirmed through histopathological examination and merely no significant alteration in the biochemical indicators including hematologic and urine analysis and electrocardiogram compared to the control dogs. This toxicological evaluation came across with the finding that the herbal preparation can be considered as nontoxic and animals could tolerate the extracts at doses up to 500 mg/Kg with LD50 greater than 3000 mg/Kg. It may serve as a preliminary scientific evidence for further therapeutic investigations.


The belief in a just world and perceptions of discrimination.
We examined the relationship between the belief in a just world and frequency of self-reported acts of personal discrimination. American adults with a strong belief in a just world reported fewer acts of personal discrimination against themselves than those with a weak belief in a just world. Among the various domains of discrimination, the belief in a just world correlated most strongly with religious discrimination. People with a strong belief in a just world felt that they would be less likely to provide special programs and funding based solely on a person's age; they did not feel that age discrimination was prevalent in American society.


Expression of bcl-2 in uveal malignant melanoma.
To evaluate the expression of the bcl-2 proto-oncogene in uveal malignant melanomas. We studied 20 uveal malignant melanomas (19 choroidal and 1 ciliary body) by immunohistochemistry with the bcl-2 oncoprotein monoclonal antibody and the cell proliferation marker, MIB-1. Expression of bcl-2 was found in 100% of cases and was not correlated with the histologic subtype of melanoma or the MIB-1 proliferative index. Normal choroidal melanocytes were negative for bcl-2. Our results suggest that altered expression of bcl-2 is common in uveal melanomas and is not related to histologic grade.


[The analysis of hepatitis B virus genetic characterization from immuned children and their mother].
In order to investigate the characterization of mother to children transmission, the sequences of HBV were analyzed to offer the information about the effect of interrupt. The sera of 75 mother with positive HBsAg are collected from 2003, and the ELISA was performed to determine the HBV infection of the child. The Large S sequence of HBV including preS and S gene are amplified and sequenced. The genotype was determined with the standard genotype sequence. The mutation ratios of group successfully interrupted and failed compared. The sera of 4 pairs mother-children were HBsAg positive, including one twins. The virus genes are successful amplified. Four of HBV genotype is B and one is C. Gene of twins has mutation of T143M. 43 HBV of successfully interrupted group were sequenced. There are 37 of genotype B and 6 of genotype C. Three have the mutation in "a" dominant, and the percentage is 7%. Most failed interrupted child have the same sequence with their mother, and the ratio is higher than the mother of successful group, however there have no statistical significance.


Head and neck surgery during the coronavirus-19 pandemic: The University of California San Francisco experience.
Guidelines regarding head and neck surgical care have evolved during the coronavirus-19 (COVID-19) pandemic. Data on operative management have been limited. We compared two cohorts of patients undergoing head and neck or reconstructive surgery between March 16, 2019 and April 16, 2019 (pre-COVID-19) and March 16, 2020 and April 16, 2020 (COVID-19) at an academic center. Perioperative, intraoperative, and postoperative outcomes were recorded. There were 63 operations during COVID-19 and 84 operations during pre-COVID-19. During COVID-19, a smaller proportion of patients had benign pathology (12% vs 20%, respectively) and underwent thyroid procedures (2% vs 23%) while a greater proportion of patients underwent microvascular reconstruction±ablation (24% vs 12%,). Operative times increased, especially among patients undergoing microvascular reconstruction±ablation (687 ± 112 vs 596 ± 91 minutes, P = .04). Complication rates and length of stay were similar. During COVID-19, perioperative outcomes were similar, operative time increased, and there were no recorded transmissions to staff or patients. Continued surgical management of head and neck cancer patients can be provided safely.


[Responses of tomato leaf photosynthesis to rapid water stress].
By using polyethylene glycol (PEG-6000) solution to regulate the water potential of tomato (Lycopersicon esculentum) rhizosphere to simulate water stress, this paper studied the dynamic changes of net photosynthetic rate, dark respiratory rate and CO2 compensatory concentration of detached tomato leaves in the process of photosynthetic induction. Under 1000 micromol m-2 s-1 of light induction, the time required to reach the maximum net photosynthetic rate of water-stressed tomato leaves was shortened by 1/3, while the stomatal conductance was increased by 1.5 times, as compared to the non-stress control. Also, the light saturation point (LSP) of water-stressed tomato leaves was lowered by 65% to 85%, and the light compensation point (LCP) was increased by 75% to 100%, suggesting that the effective range of light utilized by tomato leaves was reduced. Furthermore, water stress decreased the maximum photosynthetic capacity of tomato leaves by 40%, but increased the dark respiration rate by about 45% . It was suggested that rapid water stress made the stomata of tomato leaves quickly opened, without initial photosynthetic induction stage. In conclusion, water stress could induce the decrease of plant light-energy use efficiency and potential, being the main reason for the decrease of plant productivity, and stomatal regulation could be the main physiological mechanism of tomato plants to adapt to rapid water stress.


Intrauterine programming of ageing.
Ageing is an unavoidable corollary to being alive; the most intuitive interpretation of ageing being that it is the consequence of progressive body degeneration. In agreement with this, current models propose that ageing occurs through a stepwise accumulation of DNA damage, which ultimately limits the regenerative capacity of tissues. On the other hand, there is increasing evidence that fetal distress can influence the development of disease in adult life, a phenomenon known as 'intrauterine programming'. The extent to which an intrauterine exposure to DNA damage can compromise lifespan remains unclear. My group has recently generated a murine model of a human syndrome linked to defective DNA repair and observed that these animals age prematurely, but the accumulation of DNA damage is restricted mostly to the embryonic period. Here, I discuss the implications of this finding and propose that ageing can be influenced by fetal distress.


MRI sagittal abdominal diameter is a stronger predictor of metabolic syndrome than visceral fat area or waist circumference in a high-risk vascular cohort.
To determine whether sagittal abdominal diameter (SAD) is associated with the metabolic syndrome independently of visceral fat area (VFA) and waist circumference (WC). Forty-three high-risk vascular patients were evaluated for metabolic syndrome criteria and underwent magnetic resonance imaging (MRI) to quantify SAD and VFA at the L4-L5 disc. COMPARISONS: 1. Baseline differences in patients with and without the metabolic syndrome 2. Forward binary logistic regression analysis of predictors of the metabolic syndrome with SAD, VFA and WC as independents 3. Correlates of SAD. Patients with metabolic syndrome had greater SAD, VFA and WC than patients without the metabolic syndrome (P < 0.01). Of SAD, VFA and WC, only SAD was associated with metabolic syndrome on forward binary logistic regression; beta 0.68, Wald's statistic 10.8 (P = 0.001) and c-statistic 0.89 (P < 0.001). A > 22.7 cm SAD threshold identified metabolic syndrome with a 91% sensitivity and 80% specificity. SAD correlated with waist circumference (r = 0.918), high-density lipoprotein-cholesterol (r = -0.363), triglyceride (r = 0.401), fasting glucose (r = 0.428) and the QUICK index of insulin sensitivity (r = -0.667) (all P < 0.05). MRI-measured SAD is associated with the metabolic syndrome and renders the current gold standard of VFA redundant. This measure of obesity-related cardiovascular risk requires validation and evaluation in a prospective cohort.


Flow cytometric study of neutrophilic granulopoiesis in normal bone marrow using an expanded panel of antibodies: correlation with morphologic assessments.
Flow cytometry studies of surface markers of neutrophils have been performed mostly on peripheral blood, and for a limited spectrum of diseases. Studying maturation defects on developing neutrophils in the bone marrow (BM) may be helpful in BM diseases, such as myelodysplastic syndromes and Shwachman-Diamond syndrome. We applied an expanded panel of antibodies to examine normal maturation patterns in 26 control samples of BM together with microscopic correlation. Promyelocytes correlated well with the CD24(-) and CD11b(-) populations, and metamyelocytes correlated well with the CD16(+) population (intermediate positivity). An excellent correlation was also identified between the sum of bands and segmented neutrophils and each of the following: CD16(++) (strong positivity), CD35(+), CD87(+), and CD64(-). Although visually identified segmented neutrophils paralleled CD10 positivity, there was an appreciable difference between both methods. We conclude that neutrophilic granulocyte maturation in the BM is accompanied by a change in surface antigens that reflects certain stages of development. A successful strategy for detecting maturation defects is to include several antibodies that are known to be expressed or absent at the same stage of maturation, such as CD16, CD35, CD64, and CD87.


Medicare and Medicaid programs; program integrity--HCFA. Final rule.
This document removes rules pertaining to responsibilities delegated to the Department's Office of the Inspector General (OIG) and conforms other rules accordingly. Most of the content removed from HCFA rules is being included in a new Chapter V of this title--Office of the Inspector General--Health Care--Department of Health and Human Services. The new Chapter V is published elsewhere in this issue of the Federal Register.


Glucocorticoid receptors participate in epilepsy in FCDII patients and MP model rats: A potential therapeutic target for epilepsy in patients with focal cortical dysplasia II (FCDII).
Glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) are involved in neuronal excitability, neurogenesis, and neuroinflammation. However, the roles of GRs and MRs in epilepsy in focal cortical dysplasia II (FCDII) have not been reported. We evaluated GRs and MRs expression and distribution in FCDII patients and methylazoxymethanol-pilocarpine-induced epilepsy model rats (MP rats), and the effects of a GR agonist on neurons in human FCDII and investigated the electrophysiological properties of rats' neurons after lentivirus-mediated GR knockdown or overexpression and GR agonist or antagonist administration. GR expression (not MR) was decreased in specimens from FCDII patients and model rats. GR agonist dexamethasone reduced neuronal excitatory transmission and increased neuronal inhibitory transmission in FCDII. GR knockdown increased the excitability of cultured neurons, and GR overexpression rescued the hyperexcitability of MP-treated neurons. Moreover, dexamethasone decreased neuronal excitability and excitatory transmission in MP rats, while GR antagonist exerted the opposite effects. Dexamethasone reduced the seizure number and duration by approximately 85% and 60% in MP rats within one to two hours. These results suggested that GRs play an important role in epilepsy in FCDII and GR activation may have protective and antiepileptic effects in FCDII.


Evaluation of the shadow effect in terahertz kinoform gratings.
The experimental and numerical evaluation of the shadow effect in kinoform diffractive gratings for the terahertz (THz) range is given. This effect limits the diffractive efficiency of dense gratings, which are the base of the elements suited for convenient beam focusing and imaging in THz. The observed effect of redirecting most of the incident energy into stray -1st diffractive order is observed and discussed. The presented results show the great significance of the shadow effect in selected kinoform gratings and prove the utility of the used methodology of numerical simulations.


Regulation of osteoblast growth by interactions between transforming growth factor-beta and 1alpha,25-dihydroxyvitamin D3.
Osteoblast growth and differentiation encompass a series of events including proliferation, changes in cell shape, and expression of the markers specific for osteoblast phenotype. Both transforming growth factor-beta (TGF-beta) and 1alpha,25-dihydroxyvitamin D3 (1alpha,25[OH]2D3) are effective in regulating osteoblast proliferation, differentiation, bone matrix maturation and cell-specific gene expression. Although there is some degree of controversy regarding the influences on osteoblasts in vitro, it is generally agreed that TGF-beta stimulates osteoblast proliferation and growth, and inhibits the expression of the markers characteristic of the osteoblast phenotype such as osteocalcin. In contrast, 1alpha,25(OH)2D3 causes inhibition of the proliferation of osteoblasts, arrests their growth, and stimulates expression of specific markers. In many studies, complex interactions have been demonstrated between TGF-beta and 1alpha,25(OH)2D3 modulating their receptor expression, synthesis, and effects on osteoblast-specific gene expression. The cooperative actions of TGF-beta and 1alpha,25(OH)2D3 can be synergistic or antagonistic. It has recently been established that Smad proteins that transduce signals downstream the TGF-beta stimulation may mediate the crosstalk between TGF-beta and 1alpha,25(OH)2D3 signaling. Future studies should focus on the explanation of the molecular basis of these interactions and the in vivo consequences of the regulation of osteoblast growth and differentiation by TGF-beta and 1alpha,25(OH)2D3.


Differential effect of tungsten on the development of endogenous and nitrate-induced nitrate reductase activities in soybean leaves.
The effect of tungsten on the development of endogenous and nitrate-induced NADH- and FMNH(2)-linked nitrate reductase activities in primary leaves of 10-day-old soybean (Glycine max [L.] Merr.) seedlings was studied. The seedlings were grown with or without exogenous nitrate. High levels of endogenous nitrate reductase activities developed in leaves of seedlings grown without nitrate. However, no endogenous nitrite reductase activity was detected in such seedlings. The FMNH(2)-linked nitrate reductase activity was about 40% of NADH-linked activity. Tungsten had little or no effect on the development of endogenous NADH- and FMNH(2)-linked nitrate reductase activities, respectively. By contrast, in nitrate-grown seedlings, tungsten only inhibited the nitrate-induced portion of NADH-linked nitrate reductase activity, whereas the FMNH(2)-linked activity was inhibited completely. Tungsten had no effect on the development of nitrate-induced nitrite reductase activity. The complete inhibition of FMNH(2)-linked nitrate reductase activity by tungsten in nitrate-grown plants was apparently an artifact caused by the reduction of nitrite by nitrite reductase in the assay system. The results suggest that in soybean leaves either the endogenous nitrate reductase does not require molybdenum or the molybdenum present in the seed is preferentially utilized by the enzyme complex as compared to nitrate-induced nitrate reductase.


[Integrated therapy in panic attack disorders].
For the past years or so, studies on panic attack disorders (PAD) have accounted for a large proportion of psychiatric research. In spite of the attempts to clarify the etiopathogenesis of PAD, its characteristic psychopathological aspects and the evolutionary stages of its development, its nosographic status is still controversial (despite its inclusion in DSM III-R) and the same is true of the therapeutical approach. Using these observation as their starting point, the authors have divided the present paper into four parts. In the first they attempt to classify PAD in nosographical terms, whereas the second reviews all pharmacological therapies put forward over the past ten years. The third part consists of a short summary of the most widely used psychotherapeutic approaches, and in the last the authors suggest a model of integrated PAD therapy which is still being clinically experimented. The practice of associating pharmacological therapy with a psychotherapeutic approach has certainly been widely used for some time, but the authors underline that the two methods are only fully integrated in the presence of a therapeutic project resulting in a treatment protocol with controls during the course and at the end of treatment. In this context, the psychodiagnostic stage before therapy is particularly important since it provides as precise as possible a picture of the subject's basic personality and psychopathological state. These factors can lead to a wide varation in the choice of drug therapy, and even jeopardise therapeutic success. On the other hand, an exclusively psychotherapeutic approach to PAD does not rule out the onset of recurrent episodes during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of bone marrow T lymphocytes treated with CAMPATH 1G on megakaryocyte colony formation.
Specific populations of lymphocytes play a significant role in the regulation of megakaryocyte (MK) development. CAMPATH 1G (C1G) and CAMPATH 1M (C1M) are T lymphocyte (TL)-specific monoclonal antibodies (MABs) that are routinely employed to reduce graft-vs.-host disease (GVHD) in allogeneic bone marrow transplantation (BMT). Following BMT, engraftment of the erythroid and myeloid lineages is prompt, but prolonged thrombocytopenia often prevails. We therefore studied the effect on MK colony formation of treating donor bone marrow (BM) with the CAMPATH MABs. MK colonies were grown in plasma clots using postirradiation aplastic canine serum (PICS-J) as MK colony-stimulating factor (MK-CSF). C1M, which causes TL destruction by complement-dependent lysis, had no effect on MK cloning efficiency. C1G is not lytic but causes the elimination of TL in the BMT recipients via antibody-dependent cell cytotoxicity (ADCC). Treatment of donor BM with C1G significantly enhanced the number of early burst-forming units (BFU-MK) and late colony-forming units (CFU-MK) and had no effect on granulocyte-macrophage (CFU-GM) or erythroid (BFU-E) colonies. Enhancement of MK cloning efficiency was concentration-dependent between 0.03 and 3 micrograms MAB/10(6) BM mononuclear cells (MNC). Similar results were observed when C1G-treated TL or purified CD4+ TL were co-cultured with untreated autologous BMMNC or peripheral blood (PB) MNC. Conditioned medium (CM) from C1G-treated TL and CD4+ TL contained soluble factors that, when combined with suboptimal doses of PICS-J, potentiated MK growth. C1G in combination with PICS-J also stimulated TL proliferation in a dose-dependent manner. The T cell CM did not contain elevated levels of interleukin-3 (IL-3), IL-6, IL-1 beta, or GM-CSF. Our data provide additional evidence for the involvement of activated TL, and perhaps novel soluble T cell products, in the immunomodulation of megakaryocytopoiesis.