Higher Binding Affinity and in vitro Potency of Reslizumab for Interleukin-5 Compared With Mepolizumab.
Reslizumab and mepolizumab are recently approved monoclonal antibodies for the treatment of severe (uncontrolled) eosinophilic asthma. Both are effective in neutralizing the function of interleukin-5 (IL-5). This study is the first to compare the binding affinity and in vitro potency of both antibodies in head-to-head assays. Two assays assessed binding affinity (using the equilibrium dissociation constant [KD]) of each drug for human IL-5. In the Biacore surface plasmon resonance assay, the association constant (kon) values for human IL-5 for reslizumab and mepolizumab were 3.93 × 10⁶ and 1.83 × 10⁵, respectively. The dissociation constant (koff) values were 4.29 × 10⁻⁴ and 2.14 × 10⁻⁴, respectively. Calculated KD values for human IL-5 for reslizumab and mepolizumab were 109 and 1,170 pM, respectively, representing an approximately 11-fold stronger binding affinity with reslizumab. In the Kinetic Exclusion Assay, the kon values for human IL-5 for reslizumab and mepolizumab were 3.17 × 10⁶ and 1.32 × 10⁵, respectively. The koff values were 1.36 × 10⁻⁵ and 1.48 × 10⁻⁵, respectively. Measured KD values for human IL-5 for reslizumab and mepolizumab were 4.3 and 112 pM, respectively, representing an approximately 26-fold stronger binding affinity for reslizumab. A human-IL-5-dependent cell proliferation assay was developed to assess in vitro potency, based on a human cell line selected for enhanced surface expression of IL-5 receptor-alpha and consistent proliferation response to IL-5. The concentration at which 50% inhibition occurred (IC₅₀) was determined for both antibodies. Reslizumab and mepolizumab inhibited IL-5-dependent cell proliferation, with IC₅₀ values of approximately 91.1 and 286.5 pM, respectively, representing on average 3.1-fold higher potency with reslizumab. In conclusion, comparative assays show that reslizumab has higher affinity binding for and in vitro potency against human IL-5 compared with mepolizumab. However, these results do not take into consideration the different methods of administration of reslizumab and mepolizumab.


The role of the parent in adolescent substance use.
The overall goal of adolescent development is personal emancipation through individuation. The parent is considered an adolescent's most powerful formative influence and role model regarding health attitudes, behavioral norms, and social boundaries. For adolescents, engaging in risk-taking behaviors can be a normal maturational "rewarding" response or a strategy to cope with perceived stress and express emotions. Effective stress management is an important skill set for the developing adolescent who may experiment with a range of unhealthy strategies for coping or personal expression despite their high potential for hazardous consequences. Parenting the adolescent poses the immense challenge of promoting the adolescent's development of life skills while enabling stimulating healthy opportunities during a time of increased access and vulnerability to risky choices, including substance use. Effective parenting includes consistency, communication, respect and safety-based boundaries as well as monitoring the adolescents' friends and activities, particularly media use. Not only are parents important in deterring, suspecting, and at times detecting their adolescents' substance use, they can facilitate the evaluation or interventions that may be needed to stop substance use, start recovery, and sustain it. The role of parents is to guide adolescents in developing strengths and resilience, and fulfilling their fullest life potential.


Tomato Yellow Leaf Curl Virus V2 Protein Plays a Critical Role in the Nuclear Export of V1 Protein and Viral Systemic Infection.
Geminiviruses are an important group of circular, single-stranded DNA viruses that cause devastating diseases in crops. Geminiviruses replicate their genomic DNA in the nucleus and the newly synthesized viral DNA is subsequently transported to the cytoplasm for further cell-to-cell and long-distance movement to establish systemic infection. Thus, nucleocytoplasmic transportation is crucial for successful infection by geminiviruses. For Tomato yellow leaf curl virus (TYLCV), the V1 protein is known to bind and shuttle viral genomic DNA, however, the role of the V2 protein in this process is still unclear. Here, we report that the V1 protein is primarily localized in the nucleus when expressed but the nucleus-localized V1 protein dramatically decreases when co-expressed with V2 protein. Moreover, the V2-facilitated nuclear export of V1 protein depends on host exportin-α and a specific V1-V2 interaction. Chemical inhibition of exportin-α or a substitution at cysteine 85 of the V2 protein, which abolishes the V1-V2 interaction, blocks redistribution of the V1 protein to the perinuclear region and the cytoplasm. When the V2C85S mutation is incorporated into a TYLCV infectious clone, the TYLCV-C85S causes delayed onset of very mild symptoms compared to wild-type TYLCV, suggesting that the V1-V2 interaction and, thus, the V2-mediated nuclear export of the V1 protein is crucial for viral spread and systemic infection. Our data point to a critical role of the V2 protein in promoting the nuclear export of the V1 protein and viral systemic infection, likely by promoting V1 protein-mediated nucleocytoplasmic transportation of TYLCV genomic DNA.


HPV prevention in women aged 30-65 in Istanbul: Effect of early diagnosis of cervical cancer.
Earlier detection and timely interventions against cancers are well known to reduce the morbidity and mortality. Screening programs provide opportunity to detect cancers as early as precancerous stages. Cancers of cervix of uterus are one of the cancers that have widely applicable screening methods and are one of the three cancer types that have population-based screening program in Turkiye. In this article, it is aimed to evaluate cervical cancer screenings in Istanbul. The study methodology for cervical cancer screening conducted between 2015 and 2020 in Istanbul, Turkiye's largest city, was introduced. The results obtained in the first round of screening of 723,068 women with the human papillomavirus (HPV) method as a new methodology are discussed. As a summary of results, the HPV positivity ratio was found to be 6.5% and the positivity rate was higher in younger women. The results also show that majority of the subjects with positive result were infected with more than 1 strains of HPV. Most prevalent subtypes detected were HPV16, HPV51, HPV31, HPV52, and HPV66, respectively. Total detection rate for any of the high-risk HPV subtypes was 29.95%. Although HPV-16 is the highest subtype to be infected and total percentage of infection with any high-risk strains is approximating to one-third of the total positivity, cytological results revealed only 8.1% meaningful results.


A patient with an unusual complication of sliding inguinal hernia: Stercoral appendiceal fistula.
An unusual case of sliding inguinal hernia complicated by stercoral appendicular fistula as a result of acute appendicitis was reported in a 3-month-old boy. A diagnosis was made using barium enema. Elective appendectomy and narrowing of the internal ring using a purse-string suture were carried out safely via a right transverse infraumblical incision. Postoperative follow-up was uneventful.


Volume-sensitive chloride channels are involved in cisplatin treatment of osteosarcoma.
Chemotherapy is the most common therapeutic strategy used to treat osteosarcoma. The present study aimed to investigate the effects of functionally activated chloride channels on cisplatin‑induced apoptosis of MG‑63 human osteosarcoma cells. An MTT assay and flow cytometry were used to detect proliferation and apoptosis of the cells, respectively. Live cell imaging was used to detect volume changes in response to treatment with cisplatin and/or chloride channel blockers. The effects of these treatments on chloride currents were also assayed using the patch‑clamp technique. The results of the present study indicate that chloride channel blockers may suppress cisplatin‑induced apoptosis. The MG‑63 cells cultured with cisplatin demonstrated an apoptotic volume decrease, as well as suppression of cell proliferation; which were reversed by co‑treatment with chloride channel blockers. These results suggest that cisplatin may activate chloride channels, and that channel activation is an early signal in the pathways that lead to cisplatin‑induced apoptosis and inhibition of proliferation in MG‑63 cells. In conclusion, these results indicate that chloride channels have an important role in cisplatin treatment of osteosarcoma.


Inhibition of mitogen-activated protein kinase signaling by chloroquine.
Previously, we demonstrated that the anti-inflammatory drug chloroquine (CQ) inhibited LPS-induced TNF-alpha transcription. To define further the mechanism of CQ, we studied the effect of this drug on mitogen-activated protein kinase signaling pathways involved in regulation of TNF production. CQ interfered with phosphorylation of extracellular signal-regulated kinases (ERK)1/2 and the ERK-activating kinases mitogen-activating protein/ERK kinase (MEK)1/2. Both CQ and PD98059, a MEK1 inhibitor, reduced luciferase reporter activity driven by human TNF promoter sequences. However, CQ appeared to mediate these effects by deactivating Raf, the upstream activator of MEK. These findings were supported by functional data demonstrating that CQ and PD98059 interfered with TNF expression in several human and murine cell types while neither inhibitor blocked TNF production in murine RAW264.7 macrophages, a cell line that does not require MEK-ERK signaling for TNF production. Finally, we evaluated whether CQ could sensitize HeLa cells to undergo anti-Fas-mediated apoptosis, an effect observed when ERK activation is interrupted in this cell line. CQ rendered HeLa cells sensitive to anti-Fas treatment in a manner similar to PD98059. Taken together, these data argue that therapeutic concentrations of CQ interfere with ERK activation by a novel mechanism, an effect that could be responsible, at least in part, for the potent anti-inflammatory effects of this drug.


Mechanisms of direct and TiO2-photocatalysed UV degradation of phenylurea herbicides.
Phenylurea herbicides undergo low-yield (phi(PI) <15 %) monophotonic photoionisation upon 193-nm laser flash excitation. The so-formed radical cations (phenylurea.+) are highly acidic (-1.5 < pKa <0.5) and deprotonate readily to yield the corresponding neutral radical (phenylurea.). Pulse radiolysis experiments allowed limitation of the reduction potential of phenylurea.+ within 2.22 V versus the normal hydrogen electrode (NHE) < E degrees (phenylurea.+/phenylurea) < 2.43 V versus NHE. The main photoproducts of UVC (lambda=193 nm) photodegradation of phenylureas correspond to a photo-Fries rearrangement. One-electron reduction with e-(aq) yields the corresponding radical anions (phenylurea.-), for which 4.3< pKa < 5.33. The rate constants for reaction with e-(aq) show that in photocatalysis the generation of phenylurea.- and O2.- on the surface of the photocatalyst may be competitive. High reactivity toward e-(aq) is predicted from linear free-energy relationships (LFER) for phenylureas bearing electron-withdrawing groups. Reaction with HO. takes place mainly via addition to the aromatic ring and/or H. abstraction from a saturated carbon atom (98 %), rather than one-electron oxidation (2 %). High reactivity toward oxidation by HO. is predicted from LFER for phenylureas bearing electron-donating groups. Adsorption studies for TiO2 in its polymorphic forms of rutile and anatase, as well as with the commercial mixture Degussa P-25, show photocatalysis is independent of the specific area of the catalyst. A variety of compounds are generated during the photocatalytic degradation of Diuron, while only two hydroxychloro derivatives are observed upon prolonged direct 365 nm irradiation. The photocatalytic degradation proceeds mainly by oxidation of the Me group of the side chain, hydroxylation of the aromatic ring, and dechlorination. The photoproducts of photocatalytic degradation differ from one polymorphic form of TiO2 to another.


Evaluation of newborn hearing screening program.
To evaluate Newborn Hearing Screening Program of Hospital Regional de Sobradinho, from January 2016 to December 2017, according to Multiprofessional Committee on Auditory Health parameters and Joint Committee on Infant Hearing (JCIH) recommendations, as well as to describe the prevalence of risk factors for hearing loss within the study population and their impact on the respective program. This is a quantitative, cross-sectional and retrospective study that carefully analyzed registration books of screened newborns. It was established the prevalence of "pass" and "fail" in test and retest, retest percentage of attendance and referral for audiological diagnosis. Risk factors for hearing loss were described, as well as their influence on "pass" and "fail" rates. Inferential statistical analysis was performed using chi-square test and Anderson-Darling test, with 5% reliability index. A total of 3,981 newborns were screened; 2,963 (74.4%) presented no risk factors whereas 1,018 (25.6%) did, prematurity being the most frequent (51.6%). In the test, 166 (4.2%) failed and 118 (71.1%) attended the retest. The referral rate for diagnosis was 0.3%. Regarding the percentage of referral for diagnosis, the program reached indexes recommended by the Joint Committee on Infant Hearing and Multiprofessional Committee on Auditory Health. The most prevalent risk factor within the population was prematurity.


Exploring and visualizing the small-area-level socioeconomic factors, alcohol availability and built environment influences of alcohol expenditure for the City of Toronto: a spatial analysis approach.
Many Canadians continue to drink alcohol in excess of the recommended low-risk guidelines. In this study, we visualized the geographic variation of licensed premises alcohol expenditures in Toronto and examined the effects of area-level socioeconomic characteristics, alcohol availability and built environment influences on alcohol expenditures at the Dissemination Area (DA) level. Dissemination Area average total household expenditures on alcohol from licensed premises, from the 2010 Survey of Household Spending, was the main outcome variable. Moran's I and Local Moran's I were used to quantify geographic variation and determine hot spots and cold spots of expenditure. We used DA-level socioeconomic characteristics from the 2006 Census of Canada, and the density of licensed premises and other built environment characteristics from the 2008 DMTI Spatial and 2010 CanMap datasets to predict alcohol expenditures in multivariate spatial regression models. The results indicated that the most significant area-level predictors of alcohol expenditure were the percentage of individuals in management or finance occupations and the percentage with postsecondary education (one-unit increases associated with 78.6% and 35.0% increases in expenditures respectively). Presence of subway lines in the immediate and neighbouring areas was also significant (one-unit increases resulted in 5% and 28% increases respectively). Alcohol outlet density was also positively associated with alcohol expenditures. The associations identified between licensed premises alcohol expenditures and small-area-level characteristics highlight the potential importance of small-area-level factors in understanding alcohol use. Understanding the small-area-level characteristics of expenditures and geographic variation of alcohol expenditures may provide avenues for alcohol use reduction initiatives and policies.


Computer-aided Discovery of Peptides that Specifically Attack Bacterial Biofilms.
Biofilms represent a multicellular growth state of bacteria that are intrinsically resistant to conventional antibiotics. It was recently shown that a synthetic immunomodulatory cationic peptide, 1018 (VRLIVAVRIWRR-NH2), exhibits broad-spectrum antibiofilm activity but the sequence determinants of antibiofilm peptides have not been systematically studied. In the present work, a peptide library consisting of 96 single amino acid substituted variants of 1018 was SPOT-synthesized on cellulose arrays and evaluated against methicillin resistant Staphylococcus aureus (MRSA) biofilms. This dataset was used to establish quantitative structure-activity relationship (QSAR) models relating the antibiofilm activity of these peptides to hundreds of molecular descriptors derived from their sequences. The developed 3D QSAR models then predicted the probability that a peptide would possess antibiofilm activity from a library of 100,000 virtual peptide sequences in silico. A subset of these variants were SPOT-synthesized and their activity assessed, revealing that the QSAR models resulted in ~85% prediction accuracy. Notably, peptide 3002 (ILVRWIRWRIQW-NH2) was identified that exhibited an 8-fold increased antibiofilm potency in vitro compared to 1018 and proved effective in vivo, significantly reducing abscess size in a chronic MRSA mouse infection model. This study demonstrates that QSAR modeling can successfully be used to identify antibiofilm specific peptides with therapeutic potential.


Optical method to measure the surface of objects by using only one photo.
What we believe is a novel method to measure the dimension of an object with one defocused photo of an object is presented in this paper. To do this, a photo of the object is taken by a camera. The focal plane is chosen as a reference plane. The coordinates of the object surface are obtained by using the camera's parameters and corresponding defocused distance. The depth from the reference plane is obtained by evaluating the confusion degree of the photo around an edge. The relationship between the confusion degree and the distance from the reference plane has been given theoretically and experimentally. Several objects have been measured with the method, and it is shown that the results obtained are reliable. For nontextured surfaces, the edges of objects can be used to make the measurement.


Perioperative immunosuppression in cancer patients.
Cancer patients commonly undergo surgical procedures. The perioperative period is characterized by immunosuppression and may predispose already immunosupressed cancer patients to tumor spread. Cancer patients typically show depression of both cellular and humoral immune functions. Possible mediating factors for immunosuppression during the perioperative period include anesthetic agents, opioids, surgery, blood transfusions, temperature changes, pain, and psychological stress. A surgically mediated decrease in natural killer (NK) cell activity has been implicated as the major contributing factor associated with an increase in metastasis. The decreased NK cell activity during the perioperative period is associated with increased risk of mortality and cancer. Commonly used anesthetic agents and opioids are known to inhibit NK cell activity. Despite the in vivo evidence of anesthetic- and analgesic-agent-mediated immunosupression, surgery by itself results in a three- to four-fold increase in retention of metastasis when compared to the groups in which anesthesia and analgesia were combined. The negative consequences associated with perioperative immunosuppression may be decreased by several strategies, including aggressive pain control, selection of specific anesthetic and analgesic agents, avoidance of unnecessary transfusions, and delay of elective surgeries until the patient's nutritional and immune status is optimized. Recognizing and neutralizing its mediating factors, perioperative immunosuppression in cancer patients may be reduced.


Simultaneous Detection of Both RNA and DNA Viruses Infecting Dry Bean and Occurrence of Mixed Infections by BGYMV, BCMV and BCMNV in the Central-West Region of Mexico.
A multiplex reverse transcription polymerase chain reaction (RT-PCR) assay was developed to simultaneously detect bean common mosaic virus (BCMV), bean common mosaic necrotic virus (BCMNV), and bean golden yellow mosaic virus (BGYMV) from common bean leaves dried with silica gel using a single total nucleic acid extraction cetyl trimethyl ammonium bromide (CTAB) method. A mixture of five specific primers was used to amplify three distinct fragments corresponding to 272 bp from the AC1 gene of BGYMV as well as 469 bp and 746 bp from the CP gene of BCMV and BCMNV, respectively. The three viruses were detected in a single plant or in a bulk of five plants. The multiplex RT-PCR was successfully applied to detect these three viruses from 187 field samples collected from 23 municipalities from the states of Guanajuato, Nayarit and Jalisco, Mexico. Rates of single infections were 14/187 (7.5%), 41/187 (21.9%), and 35/187 (18.7%), for BGYMV, BCMV, and BCMNV, respectively; 29/187 (15.5%) samples were co-infected with two of these viruses and 10/187 (5.3%) with the three viruses. This multiplex RT-PCR assay is a simple, rapid, sensitive, and cost-effective method for detecting these viruses in the common bean and can be used for routine molecular diagnosis and epidemiological studies.


Activation of latent collagenase from polymorphonuclear leukocytes by oxygen radicals.
Polymorphonuclear leukocytes (PMN) accumulating at inflammatory sites have the potential to degrade collagen by releasing the metalloproteinase collagenase (EC 22.214.171.124), which is stored within the specific granules of these cells in a latent, inactive, form. In order to elucidate the activation mechanism the latent enzyme (molecular weight 91,000) was purified from human PMN and incubated with the oxygen radical-generating system of xanthine oxidase (EC 184.108.40.206) and hypoxanthine. This coincubation resulted in the activation of the latent enzyme as assessed by the collagenolytic attack on human and bovine cartilaginous tissue. Two parameters for collagenolysis were used: loss of hydroxyproline-containing fragments, and mechanical measurements reflecting the stability of tissue specimens. Superoxide dismutase (EC 126.96.36.199) as well as catalase (EC 220.127.116.11) were capable of inhibiting the activation of latent PMN collagenase by the oxygen radical-generating system. The results indicate the hydroxyl radical to be the final oxidant responsible for the activation of latent PMN collagenase. Thus a new activation mechanism of latent collagenase is presented in this paper and discussed together with the potential relevance in pathophysiologic states of acute and chronic inflammation.


Concurrent Overexpression of Arabidopsis thaliana Cystathionine γ-Synthase and Silencing of Endogenous Methionine γ-Lyase Enhance Tuber Methionine Content in Solanum tuberosum.
Potatoes (Solanum tuberosum) are deficient in methionine, an essential amino acid in human and animal diets. Higher methionine levels increase the nutritional quality and promote the typically pleasant aroma associated with baked and fried potatoes. Several attempts have been made to elevate tuber methionine levels by genetic engineering of methionine biosynthesis and catabolism. Overexpressing Arabidopsis thaliana cystathionine γ-synthase (AtCGS) in S. tuberosum up-regulates a rate-limiting step of methionine biosynthesis and increases tuber methionine levels. Alternatively, silencing S. tuberosum methionine γ-lyase (StMGL), which causes decreased degradation of methionine into 2-ketobutyrate, also increases methionine levels. Concurrently enhancing biosynthesis and reducing degradation were predicted to provide further increases in tuber methionine content. Here we report that S. tuberosum cv. Désirée plants with AtCGS overexpression and StMGL silenced by RNA interference are morphologically normal and accumulate higher free methionine levels than either single-transgenic line.


Impaired esophageal motor function in eosinophilic esophagitis.
Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.


Trauma in the rural setting.
This article provides an overview of rural trauma, focusing on the challenges that exist for rural providers compared with those who work in urban trauma centers. The authors outline the role of a Certified Registered Nurse Anesthetist working in trauma care at rural hospitals and address responsibilities involved in this expanded role.


Exploring project management as a practical solution to long-term care service.
The main purpose of this study is to explore the project management methodology as a practical solution for the field of long-term care management. This research was conducted by gathering data from reviewed literature and written documents. The conclusion suggests that project management methodology is applicable for long-term care service implementation. Moreover, the project management methodology discussed in this article could be applied to other Medicare practices to prove its validity in the future.


Relationships among direct-acting mutagenicity, nitro group orientation and polarographic reduction potential of 6-nitrobenzo[a]pyrene, 7-nitrobenz[a]anthracene and their derivatives.
The direct-acting mutagenicity in Salmonella typhimurium strains TA98 and TA100 and the half-wave reduction potentials of 6-nitrobenzo[a]pyrene (6-nitro-BaP), 7-nitrobenz[a]anthracene (7-nitro-BA), and a series of their derivatives were compared. The common structural feature of these compounds is that their nitro substituents, in order to minimize steric hindrance, preferentially adopt an orientation perpendicular or nearly perpendicular to the aromatic rings. All of the compounds, except 7-hydroxy-6-nitro-BaP and 7-acetoxy-6-nitro-BaP, were found to exhibit very weak or no direct-acting mutagenicity. 7-Acetoxy-6-nitro-BaP and 7-hydroxy-6-nitro-BaP were also found to have the lowest reduction potentials among the tested compounds. The results suggest that a combination of the orientation of the nitro substituent and the first half-wave reduction potential of the compound may correlate with the direct-acting bacterial mutagenicity of nitro-polycyclic aromatic hydrocarbons.


An isolate of Bacillus circulans toxic to mosquito larvae.
A new strain of Bacillus circulans isolated from a larva of Culex quinquefasciatus showed larvicidal activity on 3 mosquitoes of medical importance. Compared to Bacillus sphaericus strain 2362, this B. circulans isolate proved less toxic to Cx. quinquefasciatus and Anopheles gambiae but was 107 times more toxic to Aedes aegypti. Moreover, in comparison to other studies, B. circulans was at least as pathogenic as B. thuringiensis var. israelensis in Ae. aegypti. The tests have showed that the toxicity of the bacterial culture of B. circulans resulted from its spores and not from the insecticidal effect of chitinases or exotoxins.


Fabrication of Li4Ti5O12@CN Composite With Enhanced Rate Properties.
Folic acid is first time applied as a carbon-nitrogen precursor to fabricate Li4Ti5O12@CN composites via ball milling Nano-TiO2, Li2CO3 and folic acid with ethanol as solvent, and then followed by heating treatment in argon. XRD, SEM, TEM, XPS, charge-discharge test and EIS are used to evaluate the influence of N-doped carbon coating on its structure, morphologies and electrochemical property. It is demonstrated that the N-doped carbon coated Li4Ti5O12 composite exhibits superior high-rate performance compared with pure Li4Ti5O12. It possesses a high discharge capacity of 174, 165 mAh g-1 at 0.5 and 10 C, respectively. Additionally, an initial specific capacity of 96.2% is obtained after 200 cycles at 10 C. The remarkable performance might be put down to the N-doped carbon layer providing efficiently electron conductive network and nanosized decreasing lithium ion diffusion path.


The Role of Osthole on TGF-β-Induced Lung Epithelium Apoptosis Injury and Epithelial-Mesenchymal Transition-Mediated Airway Remodeling in Pediatric Asthma.
Osthole, a coumarin compound derived from Fructus Cnidii, exerts anti-inflammatory effects in an asthma model. But the effect of osthole on epithelial injury and epithelial-mesenchymal transition (EMT) in asthma remains unclear. 16HBE cells were incubated with TGF-β1 with or without osthole in vitro. Ovalbumin (OVA)-induced asthmatic mouse model was established in vivo. Cell counting kit-8 was carried out to evaluate the viability of 16HBE cells. The impact of osthole on TGF-β1-evoked cell apoptosis and EMT process was measured by flow cytometry based on Annexin V-FITC/PI staining, transwell assay, immunofluorescence, and Western blot. The regulatory role of osthole in TGF-β1/Smad and p38, ERK1/2, and JNK MAPK signaling was detected via Western blot. Osthole treatment significantly suppressed TGF-β1-induced 16HBE cell apoptosis, verified by a reduced percentage of apoptotic cells, decreased expression of proapoptotic proteins (cleaved-caspase3 and Bax), and enhanced antiapoptotic factor (Bcl-2) expression. In addition, the promotive impact of TGF-β1 on the migration of 16HBE cells was reversed by osthole, accompanied by elevated E-cadherin expression and reduced Snail and N-cadherin expression. The activation of the Smad2/3 and MAPKs pathway evoked by TGF-β1 was inhibited by osthole in 16HBE cells. We also found that osthole mitigated airway epithelium injury and subepithelial fibrosis in OVA-challenged asthmatic mice in vivo. Osthole could mitigate TGF-β1-induced epithelial cell injury and EMT process by suppressing the activation of MAPK and Smad2/3 pathways separately. Our present study showed a new insight into understanding the underlying mechanism of osthole injury on epithelium injury and subepithelial fibrosis in airway remodeling. Asthma, epithelial injury, epithelial-mesenchymal transition, and airway remodeling are the effects of osthole on airway remodeling.


Personal and organizational predictors of workplace sexual harassment of women by men.
The authors investigated the predictors of workplace sexual harassment in 278 male university faculty and staff (M age = 45 years). Workplace variables (perceptions of organizational sanctions against harassment and perceptions of a sexualized workplace) and personal variables (adversarial sexual beliefs, sexual harassment beliefs, perspective taking, and self-esteem) were studied as predictors of sexualized and gender harassment. Social desirability was controlled. Both organizational variables and beliefs about sexual harassment predicted gender harassment and sexualized harassment. Perspective taking, adversarial sexual beliefs, and sexual harassment beliefs moderated the effects of perceived organizational sanctions against harassment on sexualized harassment. Findings are discussed as they relate to organizational efforts to reduce or prevent sexual harassment.


Could changes in the regulation of the PI3K/PKB/Akt signaling pathway and cell cycle be involved in astrocytic tumor pathogenesis and progression?
The most frequent alterations found in astrocytomas are two major groups of signaling proteins: the cell cycle and the growth factor-regulated signaling pathways. The aim of our study was to detect changes in expression of the following proteins: the tumor suppressors PTEN, p53, and p21Waf1/Cip1, glial fibrillary acidic protein (GFAP, as a marker of astroglial differentiation), the phosphorylated form of protein kinase B/Akt (PKB/Akt), which is downstream to the epidermal growth factor receptor (EGFR), and MDM2, which degrades p53. Paraffin-embedded astrocytoma tissue samples from 89 patients were divided into low grade (grade I-II; 42 samples) and high grade astrocytomas (grade III-IV; 47 samples). Mouse monoclonal antibodies against GFAP, PTEN, PKB/Akt phosphorylated on serine 473, EGFR, p53, p21Waf1/Cip1 and MDM2 were used, followed by standard indirect immunohistochemical method. EGFR protein was detected in 29 % of low grade and in 60 % of high grade astrocytomas. The expression of phosphorylated PKB/Akt was found in roughly the same proportions: in 86% of low grade and in 79% of high grade astrocytomas. PTEN was not found in most of astrocytomas, 64% of low grade and 74% of high grade tumors showed no PTEN staining. Overexpression of the mutated form of p53 or loss of p53 expression, however, was found in about 63% in both groups of astrocytomas with no differences between them. GFAP expression was decreased in tumor astrocytes compared to normal astrocytes and this decreased with grading. GFAP positive tumor cells were detected in only 50% of low grade, and 32% of high grade astrocytomas. The level of MDM2 expression was similar in both grades. Loss of p21Waf1/Cip1 expression was shown in 20% of low and in 45% of high grade tumors. In the subgroup of high grade tumors with wild type p53, 86% showed p21Waf1/Cip1 expression, whereas in the subgroup of high grade tumors with altered p53, only 35% displayed p21Waf1/Cip1. We conclude that EGFR expression increases with astrocytoma grading. EGFR activation may subsequently lead to stimulation of the PKB/Akt survival pathway. PTEN defects may also participate in aggressive tumor behaviour through activation of the PKB/Akt pathway. The alteration of p53 supports the finding that the cell cycle regulation is also disrupted during development of astrocytomas. The changes in PTEN and p53 expression, and activation of PKB/Akt are events in the early stages of astrocytomagenesis. EGFR is one of the factors, which drives the progression of astrocytomas from low to high grade stage.


Comparison between the vasoactive actions of endothelin and arginine vasopressin in pithed rats after pretreatment with BAY K 8644, nifedipine or pertussis toxin.
Both human endothelin 1 (ET1) and rat endothelin 3 (ET3) produced dose-dependent pressor effects in the pithed rat. The pressor actions of ET3 and arginine vasopressin (AVP) were compared with one another in pithed rats in the presence of the calcium channel activator BAY K 8644 or the calcium channel antagonist nifedipine i.a. and also after pretreatment with pertussis toxin i.v. The diastolic pressure recorded in animals treated with the vehicle was 41 +/- 1 mm Hg, and administration of BAY K 8644 increased the diastolic pressure to 53 +/- 3 mm Hg, whereas nifedipine caused a decrease in diastolic pressure to 33 +/- 2 mm Hg. AVP, ET1 and ET3 dose-dependently increased diastolic blood pressure, with AVP being the most potent and producing the greatest total increase in pressure. ET1 was more potent than ET3; however, the maximal increases produced by the endothelins were identical. The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644. Furthermore, nifedipine significantly impaired responses induced by endothelin but not those produced by AVP. It was observed that animals treated with pertussis toxin 3 days before the conduction of the experiments had a significantly lower diastolic blood pressure as compared with saline-treated animals. Treatment with pertussis toxin caused the dose-diastolic pressure response curve to ET to be displaced to the right, whereas the dose-diastolic pressure response to AVP was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)


Tinnitus Annoyance in Normal-Hearing Individuals: Correlation With Depression and Anxiety.
To assess and correlate tinnitus annoyance in normal-hearing patients with auditory brainstem response and with anxiety/depression. A sample of 84 individuals with tinnitus and normal hearing levels (pure-tone thresholds ≤25 dB HL) was compared to a matched control group of 47 normal-hearing individuals without tinnitus. All participants underwent auditory brainstem response testing. Tinnitus annoyance was assessed using the Tinnitus Handicap Inventory and depression and anxiety using the Beck Depression Inventory and Beck Anxiety Inventory, respectively. We compared auditory brainstem response and anxiety/depression symptoms between groups. In the study group, we correlated the degree of tinnitus annoyance with normal/abnormal auditory brainstem response and presence/level of anxiety/depression symptoms. All controls had normal auditory brainstem response; 30 patients with tinnitus had abnormal results. Thirty-five patients with tinnitus had depression and 41 anxiety, while only 2 controls had depression and none had anxiety, with a significant between-group difference (P < .001). Normal/abnormal auditory brainstem response showed no association with tinnitus annoyance, anxiety, or depression. A higher degree of tinnitus annoyance was associated with severity of depression and anxiety. Increased tinnitus annoyance was positively correlated with greater severity of anxiety and depression in normal-hearing patients but was unrelated to normal/abnormal auditory brainstem response.


Implementing technical refinement in high-level athletics: exploring the knowledge schemas of coaches.
This paper explores the approaches adopted by high-level field athletics coaches when attempting to refine an athlete's already well-established technique (long and triple jump and javelin throwing). Six coaches, who had all coached multiple athletes to multiple major championships, took part in semi-structured interviews focused upon a recent example of technique refinement. Data were analysed using a thematic content analysis. The coaching tools reported were generally consistent with those advised by the existing literature, focusing on attaining "buy-in", utilising part-practice, restoring movement automaticity and securing performance under pressure. Five of the six coaches reported using a systematic sequence of stages to implement the refinement, although the number and content of these stages varied between them. Notably, however, there were no formal sources of knowledge (e.g., coach education or training) provided to inform coaches' decision making. Instead, coaches' decisions were largely based on experience both within and outside the sporting domain. Data offer a useful stimulus for reflection amongst sport practitioners confronted by the problem of technique refinement. Certainly the limited awareness of existing guidelines on technique refinement expressed by the coaches emphasises a need for further collaborative work by researchers and coach educators to disseminate best practice.


Indoxyl sulfate counteracts endothelial effects of erythropoietin through suppression of Akt phosphorylation.
Erythropoietin (EPO) is used to treat anemia in patients with chronic kidney disease (CKD). A wide variation in individual response to EPO, however, is often observed, causing EPO resistance. EPO exhibits not only hematopoietic but also extra-hematopoietic functions such as endothelial effects. Indoxyl sulfate, a uremic toxin, is involved in endothelial dysfunction, and consequently, the pathogenesis of CKD-associated cardiovascular disease. The aim of the present study was to determine the effect of indoxyl sulfate on the extra-hematopoietic functions of EPO in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with or without indoxyl sulfate or an Akt inhibitor, and then stimulated with or without EPO. Indoxyl sulfate suppressed EPO-induced survival/proliferation, anti-apoptosis function, phosphorylation of endothelial nitric oxide synthase, and the expression of thrombospondin-1, an erythroid-stimulating factor, in HUVECs. Although EPO induced phosphorylation of both Akt and extracellular signal-regulated kinases (ERK) in HUVECs, indoxyl sulfate suppressed phosphorylation of Akt but not ERK. An Akt kinase inhibitor or Akt small interfering RNA suppressed all the EPO-induced cellular effects in HUVECs. As a site of action of indoxyl sulfate on EPO signaling, indoxyl sulfate attenuated EPO-induced tyrosine phosphorylation of EPO receptor (EPOR) in HUVECs. Indoxyl sulfate negatively regulates the EPOR-Akt pathway in endothelial cells, and might contribute to EPO resistance and endothelial dysfunction in patients with CKD.


Hemodialysis for lithium intoxication: preliminary guidelines for emergency.
In Japan, 9 cases of severe lithium intoxication have been treated by hemodialysis so far, and the usefulness and indications of this procedure are not yet understood fully. We have recently experienced a case of lithium intoxication treated by hemodialysis. Considering this case together with those reported previously, we have prepared some preliminary guidelines for the application of hemodialysis to patients with lithium intoxication. The blood concentration of lithium, renal function, the severity of consciousness disturbance and clinical symptoms such as somatic complications are, of course, important indices for the application of this therapy. We think that the signs of intoxication and the time interval between the onset and the beginning of treatment also serve as useful indices for application of hemodialysis.


A pH-Responsive Detachable PEG Shielding Strategy for Gene Delivery System in Cancer Therapy.
In this study, a pH-responsive detachable polyethylene glycol (PEG) shielding strategy was designed for gene delivery in cancer therapy. Polyethylenimine/DNA complex (PEI/DNA) was in situ shielded by aldehyde group-modified PEG derivatives. The aldehyde groups of PEG could react with the amino groups of PEI by Schiff base reaction. The Schiff base bond was stable in neutral pH but labile in slightly acidic pH, which made the PEG sheddable in tumors. PEG-coated nanoparticles (NPs) had distinct advantages compared to their mPEG counterpart, possessing decreased zeta potential, more compressed size, and enhanced stability. PEG/PEI/DNA NPs showed not only high tumor cell uptake and transfection efficiency in vitro but also efficient accumulation and gene expression in solid tumors in vivo. This pH-responsive detachable PEG shielding system has the potential to be applied to other polycationic nanoparticles that contain amino groups on their surfaces, which will have broad prospects in cancer therapy.


Association between extracellular water, left ventricular mass and hypertension in haemodialysis patients.
Hypertension and left ventricular hypertrophy (LVH) are present in the majority of patients undergoing haemodialysis (HD). These two pathologies persist after dialysis onset, and pharmacological therapy is often required for adequate control of blood pressure (BP). Although fluid overload is a determinant of hypertension, clinical assessment of this parameter remains difficult and unsatisfactory. Bioimpedance analysis (BIA) spectroscopy and the relative determination of extracellular water (ECW%) may provide a simple and inexpensive tool for investigating fluid overload. We studied 110 patients on thrice-weekly HD to determine whether ECW body content correlates with hypertension and LVH in this patient population. Hypertension was determined according to the WHO criteria (office BP >/= 140/90 and/or the use of antihypertensive therapy). Twenty-four hour BP monitoring and echocardiography were performed on midweek inter-HD days. Blood chemistries, dialysis dose (spKt/V) and bioimpedance were analysed on midweek HD days. Hypertension was present in 74.5% of patients. There were no differences for age, spKt/V, haemoglobin, serum creatinine and residual renal function between normotensive and hypertensive patients. Twenty-four hour systolic BP (SBP), 24 h diastolic BP and 24 h pulse pressure were higher in hypertensive patients, in spite of antihypertensive therapy. LVH was present in 61.8% of patients. BIA revealed that ECW% was increased in LVH+ patients (LVH+ = 47.5 +/- 7.9%, LVH- = 42.4 +/- 6.2%, P = 0.01) and in hypertensive patients compared with normotensives (46.5 +/- 7.7% vs 43 +/- 7.2%, P = 0.02). Dry body weights and inter-HD body weight increases did not differ between hypertensive and normotensive patients nor between patients with or without LVH. ECW was correlated with SBP (r = 0.35, P < 0.01) and with left ventricular mass index (LVMi(g/sqm)) (r = 0.49, P < 0.001). A stepwise multiple linear regression model revealed that LVMi(g/sqm) was significantly correlated with ECW%, SBP and male gender (r = 0.65, P < 0.001). LVH and hypertension are present in a majority of HD patients and they are closely correlated with one another. We found associations between fluid load, measured by BIA and expressed as ECW, and BP and LVM.


Stimulating effect of alpha-adrenoceptor agonists on isoproterenol-induced amylase release in rat parotid tissue.
Isoproterenol (ISO)-induced amylase release from rat parotid slices was increased by the addition of methoxamine to either a normal or a calcium (Ca)-free medium. The potentiating effect of methoxamine was completely blocked by the addition of phentolamine, irrespective of whether the slices were incubated in the normal or the Ca-free medium; and the effect also disappeared after prolonged preincubation (60 min) of the slices in the Ca-free medium. Both verapamil and procaine reduced methoxamine-induced amylase release, but only verapamil blocked the stimulating effect of methoxamine in the normal medium. ISO-induced accumulation of cyclic AMP in the slices was unaffected by methoxamine or phenylephrine. The results suggest a possibility that the potentiating effect of methoxamine on ISO-induced amylase release may be independent of the presence of extracellular Ca and the increased accumulation of cyclic AMP in the tissue is unnecessary.


Focus group interviews in health-care research.
The focus group interview allows researchers to obtain data about participants' feelings and opinions on a particular topic. Careful consideration must be given to the size of the group, the participants' backgrounds, the venue and the choice of moderator. It is not always appropriate to generalise the findings of focus group interviews on to a larger population.


Early activation of heat shock genes in H2O2-treated Drosophila cells.
Drosophila cells of a diploid clone derived from line Kc were treated with 1 mM H2O2 for 1 to 20 minutes. Dot blot and Northern blot analysis of RNAs extracted from control and treated cells showed that the transcriptional activation of the 6 heat-shock genes tested was early, and maximal within 5 minutes of H2O2 treatment. Analysis of the kinetics of induction of the heat-shock proteins (hsps) after an exposure to H2O2 of 2 or 5 minutes, followed by removal, suggests that this brief treatment was sufficient to trigger the synthesis of all the hsps, which was maximal 1.5 to 3h after this short H2O2 treatment.


The patterns of children poisoning cases in community teaching hospital in Riyadh, Saudi Arabia.
Although the majority of poisoning-related cases can be managed in home settings, reduction of hospital visits and admissions are still important challenge. Thousands of interventions are involved and the appropriate management of poisoning is therefore a major task and burden to any institution. Therefore, the present study was aimed to identify the most common classes of toxic substances and route of poisoning in children and to investigate the pattern of drug and chemical poisoning in suspected case fatalities, the subsequent need for hospital admission and arrival time to hospital. A retrospective cross-sectional descriptive study of all registered poisoning cases of children reported to drug and poison information center at King Khaled University Hospital Riyadh, Saudi Arabia during the period of January 2010-December 2016. A total of 735 children presented to Pediatric Emergency Medicine with poisoning. Most of the cases were asymptomatic, and majority of children were arrived to the hospital in less than 3 h. The drugs were the most common cause of poisoning (70%) followed by chemical materials (29%), which is more common in children under 2 years comparing to other groups (p < 0.001). The route of poisoning was oral in the majority of cases (98.8%). The drugs most frequently ingested were analgesic (18.8%). Among the chemicals, pesticide products involved in (39.6%) of the cases, followed by cleaning products (25.9%) and cosmetic (22.8%). The results found that the majority of poisoning cases occurred in children under the age of six and required only observation without treatment. These results necessitate the need for close cooperation between different governmental health-sectors to establish national epidemiological surveillance of poisoning events in Saudi Arabia to help to develop national plans to decrease the financial burden of emergency department congestion and hospital crowding.


Effects of Parity and Postpartum Depression on Mother-Infant Bonding in the First Month Postpartum: A Retrospective Study.
Objective This study aimed to examine the relationship between parity, postpartum depression (PPD), and mother-infant bonding (MIB) failure in the first month postpartum. Methods The study included 1,509 Japanese patients (748 primiparous and 761 multiparous). MIB was assessed using the Mother-to-Infant Bonding Scale Japanese version (MIBS-J), which was translated in 2012, and its subscales, including lack of affection (LA) and anger and rejection (AR). Postpartum depression (PPD) was assessed using the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS) and its subscales, including anxiety (ANX), anhedonia (ANH), and depression (DEP). Multiple regression analyses using interaction terms were performed to examine the association of parity with the MIBS-J and EPDS. Results Parity was significantly associated with AR. ANX and ANH were strongly associated with LA, and ANX and DEP were strongly associated with AR. The interaction term "parity×EPDS total" was significantly associated with MIBS-J total, LA, and AR scores. Conclusions Primiparas and mothers with high ANX had more negative emotions toward their children during the first month postpartum, and mothers with high ANX or ANH had less interest in their children.


[Supratentorial extradural hematomas following posterior fossa craniectomy (author's transl)].
Five cases of the supratentorial extradural hematomas secondary to the posterior fossa craniectomy were reported. The site of the hematoma was far from the operative field and two cases showed acute course and three were rather mild. The symptoms of this complication were the unsuspected sensorium disturbance, anisocoria and the non-functioning ventricular drainage. Two cases died of this complication and two were severely disabled. The mechanism of this complication is not clearly understood. The lowering of the ventricular pressure by the ventricular tap during the operation may play significant role in the formation of the extradural hematoma. The younger age of the cases and the long history of increased intracranial pressure were stressed in the literature. The significance of the management of the ventricular pressure during the operation was emphasized. The prevention is the best treatment.


Economic Evaluation of Complete Revascularization for Patients with Multivessel Disease Undergoing Primary Percutaneous Coronary Intervention.
To determine the cost-effectiveness of complete revascularization at index admission compared with infarct-related artery (IRA) treatment only, in patients with multivessel disease undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction. An economic evaluation of a multicenter randomized trial was conducted, comparing complete revascularization at index admission to IRA-only P-PCI in patients with multivessel disease (12-month follow-up). Overall hospital costs (costs for P-PCI procedure(s), hospital length of stay, and any subsequent re-admissions) were estimated. Outcomes were major adverse cardiac events (MACEs, a composite of all-cause death, recurrent myocardial infarction, heart failure, and ischemia-driven revascularization) and quality-adjusted life-years (QALYs) derived from the three-level EuroQol five-dimensional questionnaire. Multiple imputation was undertaken. The mean incremental cost and effect, with associated 95% confidence intervals, the incremental cost-effectiveness ratio, and the cost-effectiveness acceptability curve were estimated. On the basis of 296 patients, the mean incremental overall hospital cost for complete revascularization was estimated to be -£215.96 (-£1390.20 to £958.29), compared with IRA-only, with a per-patient mean reduction in MACEs of 0.170 (0.044 to 0.296) and a QALY gain of 0.011 (-0.019 to 0.041). According to the cost-effectiveness acceptability curve, the probability of complete revascularization being cost-effective was estimated to be 72.0% at a willingness-to-pay threshold value of £20,000 per QALY. Complete revascularization at index admission was estimated to be more effective (in terms of MACEs and QALYs) and cost-effective (overall costs were estimated to be lower and complete revascularization thereby dominated IRA-only). There was, however, some uncertainty associated with this decision.


Persistence Among Patients with Crohn Disease Previously Treated with an Anti-tumor Necrosis Factor Inhibitor and Switching or Cycling to Another Biologic Agent.
Nonresponse to an anti-tumor necrosis factor (TNF) agent in patients with Crohn disease (CD) is often managed by either a switch to a different class of biologic (ie, ustekinumab, vedolizumab) or by cycling to another anti-TNF agent (ie, adalimumab, infliximab, certolizumab pegol). Persistence after a switch to a different biologic class or after cycling within the anti-TNF class was assessed in patients with nonresponse to an anti-TNF agent. Adults with CD who discontinued from an anti-TNF agent and either switched to a different class of biologic (ie, anti-interleukin/integrin; the switching cohort) or cycled within the anti-TNF class (the cycling cohort) between September 23, 2016, and August 1, 2019, were selected from a commercial database. The index date was defined as the date of the first claim of the subsequent-line biologic (index biologic) after an anti-TNF. The switching and cycling cohorts were balanced with regard to baseline characteristics, using inverse probability of treatment weights-average treatment effect (IPTW-ATE). Persistence with the index biologic was defined as consistent use with no gaps of >120 days (ustekinumab, vedolizumab, infliximab) or of >60 days (adalimumab, certolizumab pegol) in biologic supply. Composite end points were persistence while being corticosteroid-free (defined as no use of corticosteroids with ≥14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/nonindex biologics). Weighted Kaplan-Meier and Cox models were used to assess outcomes at 12 months post-index. There were 444 patients in the weighted switching cohort (mean age, 40.4 years; 56.3% female) and 441 in the weighted cycling cohort (mean age, 39.5 years; 58.4% female). At 12 months post-index, the rate of persistence with the index biologic was 75.7% in the switching cohort compared to 67.5% in the cycling cohort (log-rank P = 0.023); the rate of persistence while on monotherapy was 58.2% compared to 44.2%, respectively (log-rank P < 0.001). The rate of persistence was 44% greater in the switching compared to that in the cycling cohort (hazard ratio [HR] = 1.44; 95% CI, 1.11-1.88; P = 0.007); the rate of persistence while on monotherapy was 56% greater in the switching cohort (HR = 1.56; 95% CI, 1.28-1.90; P < 0.001). The between-cohort difference in persistence while being corticosteroid-free was not statistically significant (HR = 1.08; 95% CI, 0.89-1.32; P = 0.426). Patients with CD who switched to a different biologic class were more persistent than were patients who cycled to another anti-TNF agent. These findings may be useful for physicians when considering the treatment of patients who have experienced nonresponse or loss of response to the first-line anti-TNF agent.


Predictors of Acute Postoperative Urinary Retention after Transvaginal Uterosacral Suspension Surgery.
To investigate the rate of postoperative urinary retention (POUR) and identify the risk factors for this complication in women who underwent transvaginal uterosacral suspension surgery. A retrospective chart review was conducted for 75 women who underwent transvaginal uterosacral suspension surgery with vaginal hysterectomy, repair of cystocele, and levator myorrhaphy with/without transobturator anti-incontinence surgery. POUR was defined as a need for continuous intermittent catheterization on the third day subsequent to removal of the urethral indwelling catheter. Acute POUR was reported in 18 women (24.0%). Thirty-six of the 75 patients (48.0%) had undergone anti-incontinence surgery. Crude analysis revealed significant association between the following variables and the risk of POUR: hypertension, the lower average flow rate in the pressure-flow study (PFS), greater post-void residual (PVR) urine volume in PFS, and PVR >30% of the total bladder capacity (TBC) in PFS. In the logistic regression analysis, PVR >30% of the TBC in PFS was identified as the only significant predictor of POUR (odds ratio, 15.4; 95% confidence interval, 2.5-90.9; P = 0.003). The PVR >30% of the TBC in PFS was identified as the only predictive factor of acute POUR in women who underwent transvaginal uterosacral suspension surgery.


Psychiatric specialty training in Greece.
The reform and development of psychiatric services require, in addition to financial resources, reserves in specialized human resources. The role of psychiatrists in this process, and at reducing the consequences of mental morbidity is evident. Psychiatrists are required to play a multifaceted role as clinicians, as experts in multidisciplinary team environments and as advisors in the recognition of public needs in mental health issues, as teachers and mentors for students and other health professionals, as researchers in order to enrich our knowledge in the scientific field of psychiatry, and as public health specialists in the development of the mental health services system. This multifaceted role requires the continuous education of modern psychiatrists, but above all a broad, substantial and comprehensive training regime in the initial stage of their professional career, that is to say during specialization. Training in Psychiatry, as indeed has happened in all other medical specialties, has evolved considerably in recent decades, both in the content of education due to scientific advances in the fields of neurobiology, cognitive neuroscience, genetics, psychopharmacology, epidemiology and psychiatric nosology, and also because of advances in the educational process itself. Simple apprenticeship next to an experienced clinician, despite its importance in the clinical training of young psychiatrists, is no longer sufficient to meet the increased demands of the modern role of psychiatrists, resulting in the creation of educational programs defined by setting and pursuing minimum, though comprehensive educational objectives. This development has created the global need to develop organizations intended to supervise training programs. These organizations have various forms worldwide. In the European Union, the competent supervising body for medical specialties is the UEMS (European Union of Medical Specialities) and particularly in the case of the psychiatric specialty, the European Board of Psychiatry. In the US, the supervising bodies are the Accreditation Council on Graduate Medical Education (ACGME) and the American Board of Psychiatry and Neurology, in the United Kingdom the Royal College of Psychiatrists, in Canada the Royal College of Physicians and Surgeons, etc. In our country, the debate on the need to reform the institutional framework for Psychiatric training has been underway since the mid-90s, with initiatives especially by the Hellenic Psychiatric Association, aiming to raise awareness and concern among psychiatrists while responding to requests from competent central bodies of the state, as well as establishing Panhellenic training programs for psychiatric trainees and continuing education programs. But what is the situation of the educational map in the country today, what would be the objectives, and how might we proceed? These questions we will try to answer in an effort initiated by Hellenic Psychiatric Association (HPA) and the journal "Psychiatriki" with the publication of thematic articles starting by presenting in the next issue of "Psychiatriki"a comparative study of the training in the specialty of psychiatry at two distinct periods of time (2000 and 2014). These time-frames are of great importance, since the first is a period that in retrospect can be considered as wealthier yet missing robust priorities, while the second, at the peak of the economic crisis, constitutes a difficult environment with limited resources. Already in the year 2000, psychiatric residency training in our country had major difficulties due to its outdated framework and its fragmentation. All areas in which training is assessed (clinical experience, theoretical training and training in psychotherapy exhibited inadequacies and limited convergence with European golden standards, in the absence of a plan and the implementation of a national education curriculum. Certain university clinics constituted an important exception, though the bulk of the country's future psychiatrists were lagging behind in educational opportunities. Fifteen years later and under the weight of the consequences of the financial crisis, the institutional framework has not yet changed, and the overall situation seems to have worsened dramatically. Nevertheless, there are positive aspects to be evaluated, reinforced, and utilized in order to minimize the adverse effects of the economic crisis and lay sound foundations for the future. Preparations of a national framework is imperative today more than ever and initiatives to amend the legislation on medical specialties as far as it concerns the field of Psychiatry, could benefit from the evidence, from the willingness of the trainers and trainees concerned, as well as from the elaborated proposals of the Hellenic Psychiatric Association (HPA).


Precision of stereoscopic depth perception from double images.
The increment depth discrimination function was originally described by Ogle [(1953) Journal of the Optical Society of America, 43, 906-913] as a single exponential function. In contrast, recent studies have suggested that a two-component function better describes increment depth discrimination. To determine the relative effects of stereoscopic and non-stereoscopic width cues on the form of the function, we measured increment depth discrimination under conditions where both stereoscopic and dichoptic width cues were available. We found that increment depth discrimination data were well described by two-segment functions if both stereoscopic and dichoptic width cues were available. However, when dichoptic width cues were eliminated, by randomizing the pedestal disparity (crossed or uncrossed disparity) between trials, the increment depth discrimination function was better described by a single exponential function. This result has important implications for models of stereoscopic depth processing because it shows that stereoscopic depth discrimination thresholds progressively increase as a function of distance from the horopter.


Recurrent empty follicle syndrome.
We report a case of a recurrent empty follicle syndrome. The patient was admitted to our intracytoplasmic injection program because of her partner's azoospermia. Ovarian stimulation was accomplished using gonadotrophin therapy after treatment with oral contraceptive pills followed by gonadotrophin-releasing hormone agonist. Thirty-six hours after the administration of HCG (human chorionic gonadotrophins), transvaginal oocyte retrieval yielded no oocytes despite the aspiration and flushing of all available follicles. Two years later, a second treatment cycle was started using the same pituitary desensitisation and ovarian stimulation regimens. HCG from a different batch with respect to that used in the first treatment cycle was administered. Aspiration and repeated flushing of all follicles of one ovary failed to yield any identifiable oocyte. The beta-HCG and progesterone serum concentrations on the day of retrieval were 181 mIU/mL and 3.79 ng/mL, respectively. New oocyte retrieval was planned 6 h after the first attempt for aspiration of follicles. Again, no ova were obtained at this second trial despite the aspiration of the all follicles. As to our knowledge this is the first report of recurrent EFS (empty follicle syndrome) and managed without repeating the HCG injection on the day of unsuccessful oocyte retrieval.


Effects of PPP1R1B (DARPP-32) Polymorphism on Feedback-Related Brain Potentials Across the Life Span.
Maximizing gains during probabilistic reinforcement learning requires the updating of choice - outcome expectations at the time when the feedback about a specific choice or action is given. Extant theories and evidence suggest that dopaminergic modulation plays a crucial role in reinforcement learning and the updating of choice - outcome expectations. Furthermore, recently a positive component of the event-related potential about 200 ms (P2) after feedback has been suggested to reflect such updating. The efficacy of dopaminergic modulation changes across the life span. However, to date investigations of age-related differences in feedback-related P2 during reinforcement learning are still scarce. The present study thus aims to investigate whether individual differences in the feedback-related P2 would be associated with polymorphic variations in a dopamine relevant gene PPP1R1B (also known as DARPP-32) and whether the genetic effect may differ between age groups. We observed larger P2 amplitudes in individuals carrying the genotype associated with higher dopamine receptor efficacy, i.e., a allele homozygotes of a single nucleotide polymorphism (rs907094) of the PPP1R1B gene. Moreover, this effect was more pronounced in children and older adults in comparison to adolescents and younger adults. Together, our findings indicate that polymorphic variations in a dopamine relevant gene are associated with individual differences in brain-evoked potentials of outcome updating and hint at the possibility that genotype effects on neurocognitive phenotypes may vary as a function of brain maturation and aging.


Investigational therapies for the treatment of narcolepsy.
Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy. Expert opinion: Currently there is no cure for narcolepsy, with treatment focusing on symptoms control. However, these symptomatic treatments are often unsatisfactory. The research is leading to a better understanding of narcolepsy and its symptoms. New classes of compounds with possible applications in the development of novel stimulant/anticataplectic medications are described. H3 receptor antagonists represent a new therapeutic option for EDS in narcolepsy. JZP-110, with its distinct mechanism of action, would be a new therapeutic option for the treatment of EDS in the coming years. In the future, hypocretin-based therapies and immune-based therapies, could modify the clinical course of the disease. However, more information would be necessary to completely understand the autoimmune process and also how this process can be altered for therapeutic benefits.


Histamine: A mediator of inflammation.
Histamine and its receptors, including the recently discovered receptors (H(3) and H(4)), novel sources of histamine, and the place of histamine in mediator networks continue to be areas of great interest. The 4 major subtypes of histamine receptors, H(1) to H(4), differ in their location, second messengers, and histamine-binding characteristics. In addition, it would appear that different histamine receptor agonists and antagonists bind to different portions of the receptor complex. A fifth receptor subtype, the intracellular H(IC), has only been defined by its location within cell types that are not traditionally associated with histamine. In airway tissue, most cells express at least 1 subtype of histamine receptor; however, blockade of these receptors does not completely abolish the inflammatory response. In addition, some H(1)-antihistamines might also exert anti-inflammatory effects by pathways independent of H(1)-receptor binding. Studies of selected second-generation H(1)-antihistamines have shown that these agents inhibit the release of certain cytokines from basophils, acting at a point downstream from the calcium signaling pathway. It has not yet been determined whether this action represents a class effect.


The R2R3-MYB Factor FhMYB5 From Freesia hybrida Contributes to the Regulation of Anthocyanin and Proanthocyanidin Biosynthesis.
The flavonoids are important and nourishing compounds for plants and human. The transcription regulation of anthocyanin and proanthocyanidin (PA) biosynthesis was extensively studied in dicot compared with monocot plants. In this study, we characterized the functionality of an R2R3-MYB gene FhMYB5 from the monocotyledonous flowering plant of Iridaceae, Freesia hybrida. Multiple sequence alignment and phylogenetic analysis implied that FhMYB5 was clustered into grapevine VvMYB5b subclade. Correlation analysis indicated that the spatio-temporal expression patterns of FhMYB5 coincided well with anthocyanin and PA accumulations in Freesia per se. Furthermore, transient transfection assays in Freesia protoplasts revealed that the late flavonoid biosynthetic genes (e.g., DFR and LDOX) were slightly up-regulated by FhMYB5 alone, whereas both early and late biosynthetic genes were significantly activated when FhMYB5 were co-infected with either of the two IIIf clade bHLH genes, FhTT8L and FhGL3L. Moreover, these results were further confirmed by co-transfection of FhMYB5 with either of the bHLH genes aforementioned into protoplasts expressing GUS reporter gene driven by Freesia promoters. In addition, the overexpression of FhMYB5 in tobacco and Arabidopsis could also significantly up-regulate the expression of genes participating in the general flavonoid pathway. In conclusion, FhMYB5 was proved to function in the general flavonoid pathway in Freesia. The results implied a function conservation of flavonoid biosynthesis related MYB regulators in angiosperm plants.


Extension of NCRP 129 to short-lived radionuclides.
NCRP 129 contains dose conversion factors for 200 radionuclides that allow one to estimate the maximum dose to an individual based on the concentration of the radionuclide in the soil and the way in which the land is used. The methodology of NCRP 129 has been extended to be applicable to 28 common short-lived radionuclides and their progeny, and dose conversion factors were obtained for these radionuclides. In addition to applying the NCRP 129 calculational methodology to these radionuclides, holdup times from harvest or slaughter until consumption have been incorporated into the decay correction equations used to determine the maximum annual dose due to the significance of the holdup time with respect to the dose from short-lived radionuclides. These holdup times were included in the Monte Carlo sampling regimen used in NCRP 129. A test using emission rates proportional to those of the Chernobyl event indicated that areas of high dose, where rainout occurs, more than doubled in areas where short-lived radionuclides from this study were included.


SCN lesions abolish ultradian and circadian components of activity rhythms in LEW/Ztm rats.
A trimodal locomotor activity pattern has been observed in LEW/Ztm rats. Complete and partial lesions of the suprachiasmatic nucleus (SCN) were used to determine whether the same neural substrate may underlie the circadian rhythms and the ultradian modulation of wheel-running activity in these rats. Whereas sham lesions had little or no effect on the wheel-running activity pattern, complete SCN lesions resulted in a complete loss of circadian and ultradian activity components under free-running or 12:12 h light-dark cycle (12:12 LD) conditions. Ultradian and circadian activity components were still present after partial SCN lesions. Periodogram analysis for any given animal revealed that the ultradian periods were always submultiples of the entrained or free-running circadian period. Furthermore there was a high correlation between the amplitudes of circadian and ultradian spectral estimates, but with a different slope in males and females. These results indicate that in LEW/Ztm rats the SCN contributes to the control of both the circadian wheel-running rhythm and the trimodal ultradian modulation of that behavior.


Three-dimensional structure of kappa-conotoxin PVIIA, a novel potassium channel-blocking toxin from cone snails.
kappa-Conotoxin PVIIA from the venom of Conus purpurascens is the first cone snail toxin that was described to block potassium channels. We synthesized chemically this toxin and showed that its disulfide bridge pattern is similar to those of omega- and delta-conotoxins. kappa-conotoxin competes with radioactive alpha-dendrotoxin for binding to rat brain synaptosomes, confirming its capacity to bind to potassium channels; however, it behaves as a weak competitor. The three-dimensional structure of kappa-conotoxin PVIIA, as elucidated by NMR spectroscopy and molecular modeling, comprises two large parallel loops stabilized by a triple-stranded antiparallel beta-sheet and three disulfide bridges. The overall fold of kappa-conotoxin is similar to that of calcium channel-blocking omega-conotoxins but differs from those of potassium channel-blocking toxins from sea anemones, scorpions, and snakes. Local topographies of kappa-conotoxin PVIIA that might account for its capacity to recognize Kv1-type potassium channels are discussed.


Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells.
Neuroblastoma is the most common extracranial solid tumor of childhood. The heterogeneous microenvironment of solid tumors contains hypoxic regions associated with poor prognosis and chemoresistance. Hypoxia implicates the actin cytoskeleton through its essential roles in motility, invasion and proliferation. However, hypoxia-induced changes in the actin cytoskeleton have only recently been observed in human cells. Tropomyosins are key regulators of the actin cytoskeleton and we hypothesized that tropomyosins may mediate hypoxic phenotypes. Neuroblastoma (SH-EP) cells were incubated ± hypoxia (1 % O2, 5 % CO2) for up to 144 h, before examining the cytoskeleton by confocal microscopy and Western blotting. Hypoxic cells were characterized by a more organized actin cytoskeleton and a reduced ability to degrade gelatin substrates. Hypoxia significantly increased mean actin filament bundle width (72 h) and actin filament length (72-96 h). This correlated with increased hypoxic expression and filamentous organization of stabilizing tropomyosins Tm1 and Tm2. However, isoform specific changes in tropomyosin expression were more evident at 96 h. This study demonstrates hypoxia-induced changes in the recruitment of high molecular weight tropomyosins into the actin stress fibres of a human cancer. While hypoxia induced clear changes in actin organization compared with parallel normoxic cultures of neuroblastoma, the precise role of tropomyosins in this hypoxic actin reorganization remains to be determined.


Predictors of clinical performance of new graduate nurses participating in preceptor orientation programs.
Orientation programs providing designated preceptors for graduate nurses are used widely, but few studies support their success in assisting graduates to assume staff nurse positions. This study addressed the research question: What variables are related to clinical performance among new nursing graduates? Self-evaluations of clinical performance, preceptor evaluations, and demographic information were collected from a sample of 65 new graduates. The most useful predictors of clinical performance scores were support provided by other nurse friends, preceptor skills, and emotional support provided by preceptors. Participation in formal support groups, however, was not found to be a predictor.


<Editors' Choice> Differential effects of combination therapy on the components of the risk stratification table in patients with idiopathic or heritable pulmonary arterial hypertension in a Japanese population.
Risk stratification by ESC/ERS guideline is recommended to estimate the vital prognosis and select the treatment strategy in patients with idiopathic or heritable pulmonary arterial hypertension (IPAH/HPAH). However, we are not confident whether we can achieve low-risk status in the risk table at the follow-up shortly after combination therapy. Therefore, we aimed to verify the effects of combination therapy in IPAH/HPAH on each category of the risk table at diagnosis and at the first follow-up. We retrospectively analyzed 10 consecutive patients with IPAH/HPAH with no previous treatment history diagnosed at Nagoya University Hospital between October 2014 and January 2019. Four categories including symptoms, exercise tolerance, BNP levels and hemodynamics were validated both at baseline and at the first follow-up of right heart catheterization. Score of 1, 2 and 3 were assigned to the low risk, intermediate risk and high risk, respectively. In each category the highest score was adopted. The scores at diagnosis were compared with those at the first follow-up. The result shows that all patients were female, median age was 32 years old, and were treated with initial combination therapy. The median total risk score also was improved from 2.6 to 1.4 (p<0.01). However, the score in exercise tolerance was not improved (3 to 2.5 p=0.16). In conclusion, at the first follow up shortly after the initial combination therapy of IPAH/HPAH, the mean total risk score was significantly improved, however, even patients in the low-risk status may not achieve improvement in exercise tolerance.


Building China's municipal healthcare performance evaluation system: a Tuscan perspective.
Regional healthcare performance evaluation systems can help optimize healthcare resources on regional basis and improve the performance of healthcare services provided. The Tuscany region in Italy is a good example of an institution which meets these requirements. China has yet to build such a system based on international experience. In this paper, based on comparative studies between Tuscany and China, we propose that the managing institutions in China's experimental cities can select and commission a third-party agency to, respectively, evaluate the performance of their affiliated hospitals and community health service centers. Following some features of the Tuscan experience, the Chinese municipal healthcare performance evaluation system can be built by focusing on the selection of an appropriate performance evaluation agency, the design of an adequate performance evaluation mechanism and the formulation of a complete set of laws, rules and regulations. When a performance evaluation system at city level is formed, the provincial government can extend the successful experience to other cities.


Cancer treatment, symptom monitoring, and self-care in adults: pilot study.
A descriptive study was conducted on self-reported symptoms and self-care by 37 adults receiving chemotherapy primarily for leukemia, lymphomas, or breast cancer or radiation therapy for head and neck or lung cancers. The Therapy-Related Symptom Checklist and demographic and interview forms on self-care for identified symptoms were used. Severe symptoms on the Therapy-Related Symptom Checklist subscales fatigue, eating, nausea, pain, numbness in fingers/toes, hair loss, and constipation were reported by patients on chemotherapy. Those on radiation therapy reported severe symptoms on the eating, fatigue, skin changes, oropharynx, and constipation subscales.Self-care strategies were in the following categories, using complementary medicine as framework: diet/nutrition/lifestyle change (eg, use of nutritional supplements; modifications of food and of eating habits; naps, sleep, and rest); mind/body control (eg, relaxation methods, prayer, music, attending granddaughter's sports events); biologic treatments (vitamins); herbal treatments (green mint tea); and ethnomedicine (lime juice and garlic). The first category was predominantly used by patients in both treatment types. Medications were prescribed also to help control symptoms (eg, pain and nausea). Symptom monitoring and self-care for symptoms identified may be facilitated by the Therapy-Related Symptom Checklist; based on reported symptom severity, care providers may prioritize interventions. A larger study needs to be done on (a) the use of the Therapy-Related Symptom Checklist as a clinical tool to assess symptoms that oncology patients experience during therapy; (b) whether care providers, based on patient-reported symptom severity, can prioritize interventions--and how this influences the efficiency of care; (c) the self-care strategies used by patients on chemotherapy or radiation therapy or both; and (d) how useful these strategies are in alleviating symptoms.


Functional characterization of single-domain cystatin-like cysteine proteinase inhibitors expressed by the trematode Fasciola hepatica.
Cystatins are small, phylogenetically conserved proteins that are tight-binding inhibitors of cysteine proteinases. The liver fluke Fasciola hepatica uses a diverse set of cysteine proteinases of the papain superfamily for host invasion, immune evasion and nutrition, but little is known about the regulation of these enzymes. The aim of this work is to characterize the cystatin repertoire of F. hepatica. For this purpose, we first surveyed the available sequence databases, identifying three different F. hepatica single-domain cystatins. In agreement with the in silico predictions, at least three small proteins with cysteine proteinase binding activity were identified. Phylogenetic analyses showed that the three cystatins (named FhStf-1, -2 and -3) are members of the I25A subfamily (stefins). Whereas FhStf-1 grouped with classical stefins, FhStf-2 and 3 fell in a divergent stefin subgroup unusually featuring signal peptides. Recombinant rFhStf-1, -2 and -3 had potent inhibitory activity against F. hepatica cathepsin L cysteine proteinases but differed in their capacity to inhibit mammalian cathepsin B, L and C. FhStf-1 was localized in the F. hepatica reproductive organs (testes and ovary), and at the surface lamella of the adult gut, where it may regulate cysteine proteinases related with reproduction and digestion, respectively. FhStf-1 was also detected among F. hepatica excretion-secretion (E/S) products of adult flukes. This suggests that it is secreted by non-classical secretory pathway and that it may interact with host lysosomal cysteine proteinases.


Rectal cancer.
This synthesis of the literature on radiotherapy for rectal cancer is based on 73 scientific articles, including 1 meta-analysis, 32 randomized studies, 22 prospective studies, and 1 retrospective study. These studies involve 15042 patients. The reviewed studies show that adjuvant radiotherapy for operable rectal cancer can reduce the risk for local recurrence. A meta-analysis of 11 randomized studies reported a 25% risk reduction. The same meta-analysis suggests that adjuvant radiotherapy can reduce mortality by 10%, but this has not been statistically confirmed. The clinical effects of radiotherapy may depend on when it is given in relation to surgery. The issue of preoperative or postoperative radiotherapy is being investigated in several prospective randomized studies. Fractionation, administration of anticancer drugs during radiotherapy, and surgical methods, including associated radicality, also appear to be of importance. Local recurrence of rectal cancer is accompanied by severe suffering for the patient, eg, severe pain that is difficult to control by medication and surgery. Hence, there are major benefits from avoiding local recurrence. Given current knowledge, radiotherapy (preferably preoperative) is indicated in conjunction with operable rectal cancer, mainly Dukes' group C. External radiotherapy provides valuable palliation in many patients with locally advanced rectal cancer. In isolated cases, treatment appears to lead to prolonged disease-free survival, mainly in patients with local recurrence who have not already received pre- or postoperative radiotherapy. Experiences from different models of combination therapy involving chemotherapy and intraoperative radiotherapy are too limited to permit reliable conclusions: mainly since observation times are relatively short.


The effect of telephone consultation on the quality of life of patients receiving interferon therapy: a quasi-experimental study.
The aim of this study was to compare the effects of telephone consultation and attendance education on the quality of life of patients with hepatitis B or C receiving interferon therapy. Through a quasi-experimental study, 80 hepatitis patients were randomly assigned to one of the two educational methods. Patients completed the Quality of Life Questionnaire once upon entering the study and also 4 and 12 weeks after the treatment. Then, the results were compared. One group received education during monthly visits at the center, and another group got counseling over the telephone for 3 months. The data were analyzed using SPSS software (IBM, Armonk, NY). The results showed that the overall quality of life in both groups 4 weeks and 12 weeks after the intervention had significant differences from the pre-intervention period; however, these differences were more significant in the telephone counseling group. By virtue of the fact that no significant difference was found between the results of traditional education and telephone consultation and considering the high volume of patients in centers, remote distance between patients and centers, and also limited staff time, telephone advice can take the place of traditional education methods.


[Musculoskeletal rehabilitation and bone. Musculoskeletal atrophy, and rehabilitation medicine].
Weightless environments such as prolonged bed rest and spaceflight are associated with dramatic losses of muscle volume and bone mass that hinder patients' or astronauts' health and reintegration into daily life. It is important that the countermeasure is effective for slow twitch fiber, and adds mechanical stress to a bone. So, we developed the hybrid training method (HYB) as a countermeasure of this musculoskeletal atrophy, which uses the contraction produced in a muscle by electrical stimulation of antagonist to resist the volitional contraction of agonist. HYB has several features. These include ; 1) simple device, 2) simultaneous contractions both agonist and antagonist musculature, 3) volitional contraction of deep layers of muscle, 4) longitudinal bone force loads. Several studies reported that, this HYB was tested successfully for increasing muscles strength and hypertrophy in the upper and lower extremities. And, a wearable HYB apparatus with a virtual reality control system was developed. Now, we are developing the hybrid ergometer with virtual reality system, which training can play while playing a game at home.


Clinical evaluation of hysterectomy for the treatment of invasive mole in Southern Vietnam.
This study aimed to determine the rate of salvage chemotherapy and review associated factors in invasive mole patients treated by primary or delayed hysterectomy. This study was carried out at the Tu Du Hospital, where a total of 189 patients were diagnosed with invasive mole based on histologic examination by hysterectomy between 01/2016 to 12/2020. We used the life table method to estimate the cumulative rate. We applied the Cox proportional hazard model to determine the factors associated with the need for salvage chemotherapy. At 12-month follow-up, 47 patients had required salvage chemotherapy. The incidence was 24.87% (95% CI: 18.88-31.66). Applying the multivariate model, prophylactic chemotherapy (HR = 2.75, 95% Cl: 1.20-6.30) and two weeks postoperative hCG value greater than 1,900 mIU/mL (HR = 4.30, 95% Cl: 2.08-8.87) increased the risk of requiring salvage chemotherapy. Postoperative chemotherapy decreased the risk of requiring salvage chemotherapy (HR = 0.43, 95% Cl: 0.22-0.83). Hysterectomy can be considered safe and effective in treating invasive mole patients. Although patients were treated by hysterectomy, 24.87% of patients needed salvage chemotherapy to achieve remission. This study affirms the malignant nature of invasive mole, a subtype of gestational trophoblastic neoplasia (GTN). It is not purely a local invasion of molar villi. Postoperative chemotherapy plays an essential role in reducing the risk of requiring salvage chemotherapy.


A single-molecule Förster resonance energy transfer analysis of fluorescent DNA-protein conjugates for nanobiotechnology.
The development of nanobiotechnological devices requires the ability to build various components with nanometer accuracy. DNA is a well-established nanoscale building block that self assembles due to specific interactions that are encoded in its sequence. Recently, it has become possible to couple proteins to DNA, thereby expanding the capabilities of DNA for use with molecular photonics and bioelectronics. Here, we present the design and characterization of a supramolecular Förster resonance energy transfer (FRET) system by using a fluorescent protein bound to single-stranded DNA (ssDNA), a fluorophore attached to a second ssDNA molecule, and a complementary strand for hybridizing the two fluorophores together. The FRET efficiency was studied by using both ensemble and single-pair FRET measurements. The distance between the two fluorophores was determined from the single-pair FRET efficiency and could be described by a simple cylindrical model for the DNA. Hence, DNA can be used as a scaffold for positioning fluorescent proteins, as well as traditional fluorophores, with nanometer accuracy and shows great potential for use in the future of nanobiotechnology.


[A Cognitive Behavioural Group Therapy Manual for Elderly People with Type 2 Diabetes and Minor Depression].
Diabetes in the elderly is often associated with depressive symptoms. This comorbidity leads to a higher risk for diabetes related complications, disability and mortality and can be observed not only in major depression but also in subthreshold or minor depression. Specific psychological interventions for this high-risk patient group were not available yet. Therefore, we developed a diabetes specific cognitive behavioral group intervention for elderly outpatients with subthreshold or minor depression and type 2 diabetes within a randomized controlled trial. The treatment goals focus on improvement in health related quality of life, depression symptoms, glycemic control and cost effectiveness. In this article we give an overview of the manualized treatment program.


Early and mid-term outcomes of a novel Endovascular Aneurysm Sealing (EVAS) system in patients with infrarenal abdominal aortic aneurysms.
Endovascular aneurysm sealing (EVAS) using the Nellix system is a promising technology for Abdominal Aortic Aneurysm (AAA) treatment. Long-term data is unavailable regarding the potential modifications of the EndoBags and their content, and the polymer behavior over time. We present our initial clinical experience with this sac anchoring endoprosthesis in 24 patients with a maximum 12 months follow-up. From December 2013 to March 2015, 24 patients with an infrarenal AAA were treated with the Nellix™ System. Computed tomography angiography (CTA) scan control was performed at 30 days, and follow-up magnetic resonance angiography (MRA) and ultrasounds were performed at 30 days, 6 and 12 months. Median and peak systolic velocities in the suprarenal aorta were measured preoperatively and during follow-up using phase contrast sequences and Argus (Siemens, Erlangen, Germany) software of the MRA. We achieved 100% technical success, 0% aneurysm-related mortality and 0% endoleaks. One patient (4%) experienced early acute thrombosis of a single Nellix stent, successfully treated with thrombolysis. Sac shrinkage occurred in 80% of cases with 12-months follow-up. Our preliminary clinical experience is promising, with 100% early technical success and satisfactory sealing of the aneurysm sac. Postprocedural controls during 1-year follow-up revealed no morphologic changes of the aneurysm wall, stable device and endobag position, and gradual dissolution of the air initially trapped within the EndoBags. Aneurysmal sac shrinkage occurs and probably is due to the remodeling of the thrombus around the EndoBags and the dissipation of the air bubbles into the EndoBags.


Pancreatic response to percutaneous biliary drainage: a prospective study.
To evaluate the effects of percutaneous biliary drainage (PBD) on the pancreas, serum amylase levels were measured for 7 consecutive days after PBD and compared with baseline values in 50 patients who underwent a total of 53 PBD procedures. Of the 45 patients with normal baseline serum amylase levels, 12 patients (24%) developed postprocedural hyperamylasemia without clinical symptoms and five patients (10%) developed postprocedural hyperamylasemia with clinical signs of pancreatitis. Five patients who presented with elevated baseline serum amylase levels demonstrated decreases into the normal range after placement of stents without initiation of bowel rest or liquid diet. The level of biliary obstruction proved insignificant, as did the nature of the obstructing disease, in determining which patients would experience hyperamylasemia or pancreatitis after PBD. It is concluded that the frequency of pancreatic insult from PBD may be more common than previously reported and that patient susceptibility is not dependent on the level of biliary obstruction or the nature of the disease.


Immunoglobulins: 25 years of immunoinformatics and IMGT-ONTOLOGY.
IMGT®, the international ImMunoGeneTics information system® (CNRS and Montpellier University) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and IgSF and MhSF superfamilies. IMGT® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences and three-dimensional (3D) structures. The concepts include the IMGT® standardized keywords (identification), IMGT® standardized labels (description), IMGT® standardized nomenclature (classification), IMGT unique numbering and IMGT Colliers de Perles (numerotation). IMGT® comprises seven databases, 15,000 pages of web resources and 17 tools. IMGT® tools and databases provide a high-quality analysis of the IG from fish to humans, for basic, veterinary and medical research, and for antibody engineering and humanization. They include, as examples: IMGT/V-QUEST and IMGT/JunctionAnalysis for nucleotide sequence analysis and their high-throughput version IMGT/HighV-QUEST for next generation sequencing, IMGT/DomainGapAlign for amino acid sequence analysis of IG domains, IMGT/3Dstructure-DB for 3D structures, contact analysis and paratope/epitope interactions of IG/antigen complexes, and the IMGT/mAb-DB interface for therapeutic antibodies and fusion proteins for immunological applications (FPIA).


Dengue-3 Virus Entry into Vero Cells: Role of Clathrin-Mediated Endocytosis in the Outcome of Infection.
The endocytic uptake and intracellular trafficking for penetration of DENV-3 strain H-87 into Vero cells was analyzed by using several biochemical inhibitors and dominant negative mutants of cellular proteins. The results presented show that the infective entry of DENV-3 into Vero cells occurs through a non-classical endocytosis pathway dependent on low pH and dynamin, but non-mediated by clathrin. After uptake, DENV-3 transits through early endosomes to reach Rab 7-regulated late endosomes, and according with the half-time for ammonium chloride resistance viral nucleocapsid is released into the cytosol approximately at 12 min post-infection. Furthermore, the influence of the clathrin pathway in DENV-3 infective entry in other mammalian cell lines of human origin, such as A549, HepG2 and U937 cells, was evaluated demonstrating that variable entry pathways are employed depending on the host cell. Results show for the first time the simultaneous coexistence of infective and non -infective routes for DENV entry into the host cell, depending on the usage of clathrin-mediated endocytosis.