In vitro susceptibilities of bacterial isolates from conjunctival flora to gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin.
To evaluate and compare the in vitro susceptibilities of various fluoroquinolones (i.e., gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin) against conjunctival bacterial flora. Two hundred sixty-six bacterial isolates were collected from the conjunctival sacs of 251 eyes of 224 patients (118 females and 106 males) ranging in age from 6 to 91 years old, who were scheduled for intraocular surgery at National Tokyo Medical Center. The minimum inhibitory concentration (MIC) was determined by broth dilution testing. Of 266 isolates, 258 (97.0%) strains were gram-positive bacteria and eight (3.0%) strains were gram-negative bacteria. The MIC90 values of gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin against alpha-hemolytic streptococci were 0.39 microg/mL, 1.56 microg/mL, 0.39 microg/mL, and 0.20 microg/mL, respectively. The MIC90 values of gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin against Staphylococcus aureus were 1.56 microg/mL, 3.13 microg/mL, 0.78 microg/mL, and 0.78 microg/mL, respectively. The MIC90 values of gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin against Staphylococcus epidermidis were 1.56 microg/mL, 3.13 microg/mL, 3.13 microg/mL, and 0.78 microg/mL, respectively. Although the clinical usefulness and efficacy of newer fluoroquinolones remains to be defined by clinical outcomes, the current study provides data for predicting relative in vivo potency among the fluoroquinolones.


Surface and branching of placental villi in early abortion: relationship to karyotype. Scanning electron microscopic study.
The placental villi of 61 early abortions with known karyotype and 7 legally induced abortions were investigated by scanning electron microscopy and documented in standardised enlargements. Five groups were established from the findings: uniformly branched villi with a velvety surface (group A) were found in 4 of the 7 induced abortions, abundant syncytial sprouts (group B) in 4 of the 6 cases with monosomy X; all 5 cases of triploidy were classified in the group bulbous or spherical villi (group C); 13 out of 25 cases of trisomy were found to have little branching and a surface densely covered with microvilli (group D), while 14 out of the 25 cases of euploidy belonged in the group with slender villi and surface with focal areas of denudation (group E). Forty of the 68 cases were properly assignable to the correct groups (58.8%). The non-uniformity of the villous morphology in the case of induced abortions shows that there is no uniform development of the (early) placenta. The variable morphology seen in abortions with euploidy reflects the various mechanisms of abortion applicable to this group.


Adhesion of oral Candida albicans isolates to denture acrylic following limited exposure to antifungal agents.
Candidal adherence to denture acrylic surfaces is implicated as the first step in the pathogenesis of Candida-associated denture stomatitis, the most prevalent form of oral candidosis in the West. This condition is treated by topically administered antifungal agents, mainly belonging to the polyenes and azoles. As the intraoral concentrations of antifungals fluctuate considerably due to the dynamics of the oral environment, the effect of short exposure to sublethal concentrations of antifungals on the adhesion of Candida albicans to denture acrylic surfaces was investigated. Seven oral C. albicans isolates were exposed to four-eight times minimum inhibitory concentrations (MIC) of five antifungal drugs, nystatin, amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole, for 1 h. After removing the drug (by repeated washing) the adhesion of these isolates to acrylic strips was assessed by an in vitro adhesion assay. Exposure to antifungal agents significantly reduced the adherence of all seven C. albicans isolates to denture acrylic. The mean percentage reductions of adhesion after limited exposure to nystatin, amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole were 86.48, 90.85, 66.72, 65.88 and 47.42%, respectively. These findings indicate that subtherapeutic doses of antifungals may modulate oral candidal colonization. Further, these results may have an important bearing on dosage regimens currently employed in treating oral candidosis.


Recent Advances and Current Role of Transperineal Prostate Biopsy.
"Approximately 1 million prostate biopsies are performed each year in the United States. This procedure has traditionally been performed using a transrectal approach, which is associated with a significant risk of infectious complications including sepsis. In recent years, transperineal prostate biopsy has been increasingly adopted due to its lower associated infectious risk. In this review, we explore the benefits of the transperineal approach for performing prostate biopsy and detail technical advancements that have allowed for this procedure to now be routinely performed in the outpatient settings under local anesthesia."


Oral squamous cell carcinoma: review of prognostic and predictive factors.
Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. In this review article, the authors approach the factors that may exert influence on the prognosis and eventually guide the selection of patients for more aggressive therapies. Published scientific data was collected, selected, and grouped into 3 main clusters: patient-, tumor-, and treatment-related factors. Well established aspects are discussed, but also those less common or with only supposed usefulness. Disease staging, extracapsular dissemination, resection margin free of disease, and tumor thickness are factors with high influence on the prognosis. There has been an increasing interest in the study of tumor molecular factors, and some have been strongly correlated with the outcome, showing promising pathways for the future development of more effective prognosis systems and anticancer therapies.


On the population genetics of the red cell glyoxalase I (GLO).
The GLO phenotype distribution was studied in the population from the Rostock area (n = 233). The gene frequencies of GLO alleles were estimated to be GLO1 = 0.4249, GLO2 = 0.5751. The electrophoretic separation was achieved on horizontal starch gel.


The effect of heparin and of acid-citrate-dextrose solution on screen filtration pressure of blood in experimental hypotension.
Anticoagulation with heparin may not always adequately protect an ischaemic vascular bed. A screen filtration device has been employed to study the in vitro actions of acid-citrate-dextrose (ACD) and heparin on blood from the dog in haemorrhagic shock. With both anticoagulants, blood obtained during shock caused greater filter obstruction than blood taken before shock. However, the increased obstruction was nearly four times greater with heparinized blood than with acid-citrate-dextrose blood. These findings suggest that the anticoagulant action of heparin may be markedly diminished in low blood flow states.


Comparative study on the effects of EGF and bFGF on the healing of human large traumatic perforations of the tympanic membrane.
We evaluated the effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on the healing of large traumatic tympanic membrane perforations (TMPs). Prospective clinical study. Tertiary university hospital. A randomized, prospective analysis was performed between June 2013 and August 2014 on the treatment of traumatic TMPs larger than 25% of the TM. Closure rate, closure time, hearing gain, and rate of otorrhea were compared between EGF and bFGF groups, as well as to an observation-only group. Final analysis was performed on 86 patients at 3 months. The closure rates of perforation in the EGF, bFGF, and observation groups were 86.2%, 89.3%, and 72.4%, respectively. The closure rates in the EGF and bFGF groups were 14% to 17% higher than in the observation group, although the difference was not statistically significant for the total closure rate among the three groups (P = 0.200). The average closure time was significantly longer (P < 0.01) in the observation group than in the EGF and bFGF groups. However, the closure times in the EGF and bFGF groups were not significantly different (P = 0.92). In addition, differences in purulent otorrhea rates among the groups were not statistically significant (P = 0.82). Both EGF and bFGF can accelerate the closure of human large traumatic TMPs. The healing outcomes among the two growth factors were not significantly different.


Epirubicin-loaded beads transarterial prostatic arterial chemoembolization is a promising treatment for advanced prostate cancer with lower urinary tract obstruction or hematuria-a case series report.
Prostatic arterial embolization (PAE) is an effective minimally invasive treatment for lower urinary tract obstruction and hematuria in patients with benign prostatic hyperplasia (BPH). This study was aim to evaluate the safety and short-term efficacy of drug epirubicin-loaded beads transarterial prostatic arterial chemoembolization (DEB-PACE) for the treatment of advanced prostate cancer (PC) with lower urinary tract obstruction or hematuria. A total of 8 patients with advanced PC undergoing DEB-PACE from August 2020 to February 2022 were retrospectively enrolled. The patients were followed up at 1 week, 1, 3, 6 and 12 months after DEB-PACE. The origin of prostatic arteries, technical success, clinical success rate, duration of the indwelling urinary catheter, International Prostate Symptom Score (IPSS), QoL score (quality of life), prostate volume (PV), prostate-specific antigen (PSA) level and complications were recorded. The short-term efficacy (changes in IPSS, PV and QoL value from baseline to 3 months) were analysed. There were 17 prostatic arteries in 8 patients, which mainly originated from internal pudendal artery (11/17, 64.7%), the technical success rate is 100%. After treatment, the symptoms of lower urethral obstruction in 8 patients were significantly improved that PSA, PV, IPSS and QoL level were significantly reduced. The catheter was successfully removed within 1 week on average, and 2 patients with hematuria disappeared within 5 days. The clinical success rate is 100%. At 1 month postoperatively, mean PV reduction was 30.28±6.963 cm3 (P=0.0457), mean IPSS reduction was 21.13±2.887 points (P=0.0042), mean QoL reduction was 3.75±0.366 points (P=0.006). At 3 months postoperatively, mean PV reduction was 46.14±8.906 cm3 (P=0.0112), mean IPSS reduction was 24.5±2.398 points (P=0.0003), mean QoL reduction was 4.25±0.25 points (P=0.0003). There were no serious complications occurred in all patients. DEB-PACE is a promising treatment for advanced PC with lower urinary tract obstruction or hematuria. However, the efficacy and safety of DEB-PACE for advanced PC is needed to validated by prospective large sample randomized controlled study.


Role of fluoroquinolone prophylaxis in allogeneic hematopoietic cell transplantation in regions with a high prevalence of fluoroquinolone resistance.
The role of fluoroquinolone (FQ) prophylaxis in preventing gram-negative bacilli (GNB) bacteremia, graft-versus-host disease (GVHD), and overall survival (OS) after allogeneic hematopoietic cell transplantation (allo-HCT) is debatable and may differ in settings with low and high prevalences of FQ resistance. In this study, we aimed to answer this question in regions with high FQ resistance. This single-center retrospective study included all consecutive allo-HCT recipients aged ≥12 years from 2012 to 2021. Allo-HCT recipients until 2016 were administered FQ prophylaxis (levofloxacin). After 2016, the institutional protocol was modified to no antibiotic prophylaxis. Data were retrieved from patient records for disease and transplant characteristics, the incidence of GNB bacteremia, duration of parenteral antibiotics, hospitalization duration, acute GVHD, and OS. A total of 135 allo-HCT recipients (43 in the FQ-prophylaxis cohort and 92 in the no-antibiotic prophylaxis cohort) were analyzed in this study. The two cohorts were matched for age (median, 26 vs. 24.5 years; p = 0.8). The no-antibiotic prophylaxis cohort had a higher proportion of malignant diagnoses (80% vs. 58%, p = 0.01), haploidentical transplants (46% vs. 14%, p = 0.004), and posttransplant cyclophosphamide exposure (46% vs. 14%, p = 0.003) than did the FQ cohort. Despite this, the incidence of GNB bacteremia was not significantly different between the two cohorts (37% vs. 34%, p = 0.6). There were no differences in parenteral antibiotic use or hospitalization duration, as well as the incidence of acute GVHD (53% vs. 53%, p = 0.3). The 1-year OS was similar between the two cohorts (66% vs. 67%, p = 0.6). This study shows that FQ prophylaxis did not affect the incidence of GNB bacteremia, parenteral antibiotic use, hospitalization duration, acute GVHD, and OS post-allo-HCT.


Fate of HIV-1 cDNA intermediates during reverse transcription is dictated by transcription initiation site of virus genomic RNA.
Retroviral reverse transcription is accomplished by sequential strand-transfers of partial cDNA intermediates copied from viral genomic RNA. Here, we revealed an unprecedented role of 5'-end guanosine (G) of HIV-1 genomic RNA for reverse transcription. Based on current consensus for HIV-1 transcription initiation site, HIV-1 transcripts possess a single G at 5'-ends (G1-form). However, we found that HIV-1 transcripts with additional Gs at 5'-ends (G2- and G3-forms) were abundantly expressed in infected cells by using alternative transcription initiation sites. The G2- and G3-forms were also detected in the virus particle, although the G1-form predominated. To address biological impact of the 5'-G number, we generated HIV clone DNA to express the G1-form exclusively by deleting the alternative initiation sites. Virus produced from the clone showed significantly higher strand-transfer of minus strong-stop cDNA (-sscDNA). The in vitro assay using synthetic HIV-1 RNAs revealed that the abortive forms of -sscDNA were abundantly generated from the G3-form RNA, but dramatically reduced from the G1-form. Moreover, the strand-transfer of -sscDNA from the G1-form was prominently stimulated by HIV-1 nucleocapsid. Taken together, our results demonstrated that the 5'-G number that corresponds to HIV-1 transcription initiation site was critical for successful strand-transfer of -sscDNA during reverse transcription.


A comparison of nutritionally-related blood metabolites among Nguni, Bonsmara and Angus steers raised on sweetveld.
The objective of the study was to determine monthly variations in serum glucose, cholesterol, total protein (TP), urea, albumin, globulin, albumin/globulin ratio, creatinine, aspartate aminotransferase (AST), creatinine kinase (CK), alkaline phosphatase (ALP), calcium, phosphorus and magnesium in Nguni, Bonsmara and Angus beef steers raised on sweetveld. Twenty-five Nguni, 15 Aberdeen Angus and 15 Bonsmara 8-month old steers were studied from June 2006 until March 2007. Across the 9 months, Nguni had higher concentrations of glucose (P =0.019) and cholesterol (P =0.001) than the other two breeds. The overall glucose and cholesterol concentrations in the Nguni were 4 and 2.86mmol/L, respectively. There was a breedxmonth interaction on glucose, cholesterol, creatinine, calcium, albumin and phosphorus concentrations. Breed had no effect on TP, urea, globulin and AST concentrations. Breed and month differences obtained could be attributed to changes in environment temperature and nutrient content of the forage.


Development of an ELISA for detection of an organophosphorus compound using monoclonal antibodies.
This paper describes a specific and highly sensitive ELISA system using monoclonal antibodies in order to assay an organophosphorus compound. The soman derivative methyl phosphonic acid, p-aminophenyl 1,2,2,-trimethyl-propyl diester (MATP) served as model substance. In order to obtain antibody-producing hybridomas BALB/c mice were immunized with MATP linked onto human serum albumin (HSA). The spleen cells of immunized mice were fused with syngenic plasmacytomas of the non-producer-line X63Ag8.653 with the aid of polyethylene glycol. To eliminate undesirable cross-reaction, common screening procedures were modified by directly coating the ELISA plates with hapten. Five out of 15 positive cell-lines were cloned by limiting dilution and further propagated. The respective immunoglobulin class and subclass of the obtained monoclonal antibodies was determined. Four of which were identified as IgG1, the other as IgG2a. After enrichment of antibodies in ascites and their isolation by protein A-sepharose, the affinity of various monoclonal antibodies was estimated in competitive inhibition enzyme immunoassay (CIEIA) by measuring the IC50 rates of free MATP. The rates were found to lie between 2.5 x 10(-6) mol/l and 4.3 x 10(-4) mol/l MATP. The IC10 rate for detectable MATP concentration was 5.4 x 10(-7) mol/l MATP. Test duration was 280 min. The reactivity of the monoclonal antibodies with structurally related substances was used to check their specificity. Cross-reaction turned out to be negative. In order to develop a direct competitive ELISA, MATP was linked to horse radish peroxidase (HRPO) by adding a spacer. This helped to reduce total duration to 40 min.(ABSTRACT TRUNCATED AT 250 WORDS)


Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus-induced keratinocyte carcinomas.
Infection with certain cutaneous human papillomaviruses (HPV), in conjunction with chronic ultraviolet (UV) exposure, are the major cofactors of non-melanoma skin cancer (NMSC), the most frequent cancer type worldwide. Cutaneous squamous cell carcinomas (SCCs) as well as tumors in general represent three-dimensional entities determined by both temporal and spatial constraints. Whole tissue proteomics is a straightforward approach to understand tumorigenesis in better detail, but studies focusing on different progression states toward a dedifferentiated SCC phenotype on a spatial level are rare. Here, we applied an innovative proteomic workflow on formalin-fixed, paraffin-embedded (FFPE) epithelial tumors derived from the preclinical animal model Mastomys coucha. This rodent is naturally infected with its genuine cutaneous papillomavirus and closely mimics skin carcinogenesis in the context of cutaneous HPV infections in humans. We deciphered cellular networks by comparing diverse epithelial tissues with respect to their differentiation level and infection status. Our study reveals novel regulatory proteins and pathways associated with virus-induced tumor initiation and progression of SCCs. This approach provides the basis to better comprehend the multistep process of skin carcinogenesis.


FT-IR spectroscopic analyses of 3-Methyl-5-Pyrazolone (MP).
In the present work both experimental and computational FT-IR spectroscopic studies on 3-Methyl-5-Pyrazolone (MP) were reported. Experimental FT-IR spectrum for MP compound is recorded in powder form. Important physical parameters were reported such as structural parameters, vibrational frequencies, entropy, total energy, total dipole moment and HOMO-LUMO energy gap using DFT/B3LYP/6-311G(d,p) basis set. MP molecule has a total dipole moment of 2.83 Debye and HOMO-LUMO energy gap of 5.80 eV. Results indicate also that exposure to UV changes the spin from singlet to doublet state; one can conclude that MP compound may undergo anomalous Zeeman like effect.


Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of rRNA genes.
The tandem Tudor-like domain-containing protein Spindlin1 has been reported to be a meiotic spindle-associated protein. Here we report that Spindlin1 is not associated with the spindle in mouse embryonic fibroblast cells during mitotic divisions. In interphase cells, Spindlin1 specifically localizes to the nucleoli. Moreover, Spindlin1 is a histone methylation effector protein that specifically recognizes H3K4 methylation. Finally, Spindlin1 localizes to the active ribosomal DNA (rDNA) repeats, and Spindlin1 facilitates the expression of rRNA genes.


GM-CSF-induced acute eosinophilic pneumonia.
There is increasing evidence that haemopoietic growth factors are effective in reversal of neutropenia associated with large granular lymphocytes (LGLs) proliferation. A 19-year-old woman with CD3+/TCR gamma delta+, CD4-, CD8- LGL proliferation and severe neutropenia repeatedly developed blood eosinophilia, fever and dyspnoea after administration of GM-CSF. Acute eosinophilic pneumonia with a lobar lung infiltrate pleural effusion, and marked bronchoalveolar lavage fluid eosinophilia was diagnosed. Treatment with corticosteroids and discontinuation of GM-CSF lead to rapid improvement. In addition, haematological analysis revealed that H*1 Technicon, a widely-used automated cell counter, may misinterpret eosinophils erroneously as neutrophils, therefore examination of blood smears to prevent eosinophil-mediated toxicity during GM-CSF treatment is recommended.


Hysterosalpingography in the evaluation of infertility: a six-year review.
A series of 505 consecutive hysterosalpingograms (HSG) for the evaluation of infertility is reviewed. Two hundred and seventy-five (54.3%) were interpreted as normal. A tubal abnormality was found in 188 (37.2%) and a uterine abnormality in 42 (8.5%). The literature is reviewed. Hysterosalpingographic abnormalities in the present series are compared with those reported in studies previously published. Complications and advantages of the procedure are outlined. Analysis of the results shows a low morbidity and high return (45.7% abnormal), making HSG one of the most valuable tools in the initial evaluation of the infertile couple.


Impact of Motivation on Selected Aspects of Attention in Children with ADHD.
Earlier reports showed the co-occurrence of a motivation deficit in children with ADHD. The purpose of this study was to assess the impact of extrinsic motivation on selected aspects of attention in children with ADHD, as well as to measure cortical activity and dimensions of motivation as per the self-determination theory. The study included 30 children with ADHD and 30 typically developing (TD) children aged 9-13 years. Children with ADHD exhibited a higher theta/beta power ratio (TBR) in the midline and a lower regional cerebral blood oxygenation (rCBO2) level in prefrontal areas measured using the HEG ratio compared to TD children. Children with ADHD were more likely to undertake activity under the pressure of external stimuli and exhibited attention deficits regarding vigilance, visual search and divided attention. Differences between groups regarding attention decreased in conditions of increased motivation, indicating that motivation can reduce cognitive deficits in children with ADHD.


Integration of chemical and biological methods: A case study of polycyclic aromatic hydrocarbons pollution monitoring in Shandong Peninsula, China.
Polycyclic aromatic hydrocarbons (PAHs), as persistent toxic substances (PTS), have been widely monitored in coastal environment, including seawater and sediment. However, scientific monitoring methods, like ecological risk assessment and integrated biomarker response, still need massive researches to verify their availabilities. This study was performed in March, May, August and October of 2018 at eight sites, Yellow River estuary (S1), Guangli Port (S2), Xiaying (S3), Laizhou (S4), Inner Bay (S5), Outer Bay (S6), Hongdao (S7) and Hongshiya (S8) of Shandong Peninsula, China. The contents of 16 priority PAHs in local seawater and sediment were determined, by which ecological risk assessment risk quotient (RQ) for seawater and sediment quality guidelines (SQGs) were calculated to characterize the PAHs pollution. Meanwhile, multiple biomarkers in the digestive gland of clam Ruditapes philippinarum were measured to represent different biological endpoints, including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), sulfotransferase (SULT), superoxide dismutase (SOD) and lipid peroxidation (LPO), by which integrated biomarker response (IBR) was calculated to provide a comprehensive assessment of environmental quality. Taken together, these results revealed the heaviest pollution at S2 as both PAHs concentrations and biomarkers responses reflected, and supported the integrated biomarker response as a useful tool for marine environmental monitoring, through its integration with SQGs.


Maternal Decision-making During Pregnancy: Parental Obligations and Cultural Differences.
Decision-making during pregnancy can be ethically complex. This paper offers a framework for maternal decision-making and clinical counseling that can be used to approach such decisions in a systematic way. Three fundamental questions are addressed: (1) Who should make decisions? (2) How should decisions be made? and (3) What is the role of the clinician? The proposed framework emphasizes the decisional authority of the pregnant woman. It draws ethical support from the concept of a good parent and the requirements of parental obligations. It also describes appropriate counseling methods for clinicians in light of those parental obligations. Finally, the paper addresses how cultural differences may shape the framework's guidance of maternal decision-making during pregnancy.


Psychiatric Disorders and Montelukast in Children: A Disproportionality Analysis of the VigiBase(®).
In 2008, the US FDA issued an alert about an increased risk of psychiatric events associated with montelukast. Recent national pharmacovigilance analyses in Sweden, France and Spain detected a potential increase in reporting risk of the association. Our objective was to analyse spontaneous reports of psychiatric events in children and adolescents worldwide treated with montelukast. We conducted a retrospective analysis of Individual Case Safety Reports (ICSRs) recorded up to 1 January 2015 in the World Health Organization (WHO) database (VigiBase(®)), in which montelukast was associated with 'psychiatric disorders'. We used the Bayesian Confidence Propagation Neural Network (BCPNN) approach for signal generation. A total of 14,670 ICSRs for montelukast were recorded, of which 2630 corresponded to psychiatric disorders in people aged <18 years. The main symptoms reported for infants (aged <2 years) were sleep disorders, for children (aged 2-11 years) the main symptoms were depression/anxiety, and for adolescents (aged 12-17 years) they were suicidal behaviour and depression/anxiety. Suicidal behaviour was over-represented in all age groups with information component (IC) values that reached 5.01 in children and 3.85 in adolescents. Unexpectedly, completed suicides were reported more frequently for children (IC: 3.15; IC025: 1.98) than for adolescents (IC: 3.11; IC025: 2.61) or the total population (IC 1.95; IC025: 1.73). Neuropsychiatric disorders as side effects of montelukast were more frequently reported for children than for adults. Infants and children seem to be more prone to sleep disturbances, whereas adolescents present symptoms of depression/anxiety and psychotic reactions more often. Suicidal behaviour and completed suicide appear to be more frequently reported than previously thought in practice. Risk management plans and epidemiological studies are needed to quantify the risk. Practitioners should be aware of the risk of neuropsychiatric events associated with montelukast use, and should advise the patient and report new cases.


Computational reconstruction of pacemaking and intrinsic electroresponsiveness in cerebellar Golgi cells.
The Golgi cells have been recently shown to beat regularly in vitro (Forti et al., 2006. J. Physiol. 574, 711-729). Four main currents were shown to be involved, namely a persistent sodium current (I(Na-p)), an h current (I(h)), an SK-type calcium-dependent potassium current (I(K-AHP)), and a slow M-like potassium current (I(K-slow)). These ionic currents could take part, together with others, also to different aspects of neuronal excitability like responses to depolarizing and hyperpolarizing current injection. However, the ionic mechanisms and their interactions remained largely hypothetical. In this work, we have investigated the mechanisms of Golgi cell excitability by developing a computational model. The model predicts that pacemaking is sustained by subthreshold oscillations tightly coupled to spikes. I(Na-p) and I(K-slow) emerged as the critical determinants of oscillations. I(h) also played a role by setting the oscillatory mechanism into the appropriate membrane potential range. I(K-AHP), though taking part to the oscillation, appeared primarily involved in regulating the ISI following spikes. The combination with other currents, in particular a resurgent sodium current (I(Na-r)) and an A-current (I(K-A)), allowed a precise regulation of response frequency and delay. These results provide a coherent reconstruction of the ionic mechanisms determining Golgi cell intrinsic electroresponsiveness and suggests important implications for cerebellar signal processing, which will be fully developed in a companion paper (Solinas et al., 2008. Front. Neurosci. 2:4).


Polymyxin use as a risk factor for colonization or infection with polymyxin-resistant Acinetobacter baumannii after liver transplantation.
Acinetobacter baumannii is a leading agent of healthcare-associated infection. The objective of this study was to evaluate cases of colonization or infection with polymyxin-resistant A. baumannii (PRAB) in liver transplant recipients and to identify the risk factors for the acquisition of PRAB. We evaluated all patients undergoing liver transplantation (LT) between January and November of 2011. The exclusion criterion was death within the first 72 h after transplant. Patients were screened for PRAB through weekly rectal and inguinal swabs during their stay in the intensive care unit (ICU) and at ICU discharge. Patients who came from other hospitals or had been treated in the emergency room for >72 h were screened at ICU admission. The minimum inhibitory concentrations (MICs) for polymyxins were determined by broth microdilution, and clonality was determined by pulsed-field gel electrophoresis. The stepwise logistic regression was used to identify risk factors related to acquisition of PRAB, and Cox forward regression used to identify risk factors for 60-day mortality. We evaluated 65 patients submitted to LT, among whom PRAB was isolated in 7, 4 of whom developed infection. The MICs for polymyxin E ranged from 16 to 128 mg/mL. All patients with PRAB required dialysis. The median time of polymyxin use before PRAB isolation was 21 days. These 4 included 1 case of primary bloodstream infection (BSI), which was treated with the carbapenem-polymyxin combination; 1 case of surgical site infection, which was treated with gentamicin, polymyxin, ampicillin-sulbactam, and tigecycline; and 2 cases of pneumonia, treated with the combination of carbapenem-polymyxin. In the case of BSI and in 1 of the cases of pneumonia, the treatment was considered successful. Mortality was 71% among the cases, compared with 33% among the non-cases. In the final model of the survival analysis, PRAB colonization or infection after LT was independently associated with mortality. One predominant clone was identified. The only risk factor identified in the multivariate analysis was polymyxin use. PRAB was an agent with high mortality, and the most important risk factor associated with colonization or infection for such bacterium was polymyxin use.


Self-esteem, confidence, and relationships in men treated with sildenafil citrate for erectile dysfunction: results of two double-blind, placebo-controlled trials.
Men with erectile dysfunction (ED) often have low self-esteem, confidence, and sexual relationship satisfaction. We evaluated the impact of sildenafil citrate and its generalizability across cultures on self-esteem, confidence, and sexual relationship satisfaction in men with ED using the Self-Esteem And Relationship (SEAR) questionnaire. Pooled analysis of 2 double-blind, placebo-controlled, flexible-dose trials of sildenafil with identical protocols: 1 was conducted in the United States and the other in Mexico, Brazil, Australia, and Japan. Men > or = 18 years old with ED. The impact of treatment on psychosocial factors associated with ED was determined by patient responses to the SEAR questionnaire. Erectile function was determined using the International Index of Erectile Function (IIEF) and a global efficacy question. Successful sexual intercourse attempts were derived from event logs of sexual activity. Treatment effect sizes were calculated for all study outcomes. Compared with patients who received placebo (n = 274), patients who received sildenafil (n = 279) reported significantly greater improvements (P < .0001) in self-esteem, confidence, sexual relationship satisfaction, and in all sexual function domains of the IIEF. Treatment effect sizes were large (range, 0.7 to 1.2) for all SEAR components, and improvement in psychosocial measures showed moderate to high correlations (range, 0.50 to 0.83, P < .0001) with improvement in erectile function, percentage of successful intercourse attempts, and global efficacy. In men with ED from 5 different nations, sildenafil produced substantial improvements in self-esteem, confidence, and sexual relationship satisfaction. Improvements in these psychosocial factors were observed crossculturally and correlated significantly and tangibly with improvements in erectile function.


Variations in T(2)* and fat content of murine brown and white adipose tissues by chemical-shift MRI.
The purpose was to compare T(2)* relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T(2)*-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T(2)* and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T(2)* and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. Significant differences (P<.01) in BAT T(2)* and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T(2)* and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T(2)* and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. T(2)* and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter.


Drowning and near-drowning in Northern Territory children.
To compare incidences of drowing for children in the Northern Territory (NT) with those in Queensland and the rest of Australia. Descriptive, retrospective, population-based analysis of death and hospitalisation data for drowning and near-drowning. Children aged 0-14 years resident in Australia from 1983 to 1998. Age-standardised average annual incidence of drowning (1983-1998) and near-drowning (1994-1997) in children aged 0-4 and 5-14 years in the NT, Queensland and the rest of Australia. The average annual incidence of drowning and near-drowning from 1994 to 1997 for children aged 0-4 years in the NT (67.82 per 100,000) was significantly higher than for Australia (24.45 per 100,000) (incident rate ratio [IRR], 2.77; 95% CI, 1.40-4.91) and for Queensland (32.55 per 100,000) (IRR, 2.13; 95% CI, 1.05-3.94). The proportion of children aged 0-4 years drowning or near-drowning in swimming pools from 1994 to 1997 was also significantly higher in the NT (83%) than Australia (64%) (difference, 0.19; 95% CI, 0.086-0.30) and Queensland (65%) (difference, 0.18; 95% Cl, 0.069-0.29). From 1983 to 1998, the incidence of drowning in NT children aged 0-4 years increased by 0.4% per year (IRR, 1.004; 95% Cl, 0.994-1.070), compared with a 5.0% reduction per year (IRR, 0.950; 95% Cl, 0.937-0.963) in Australian children. The incidences of drowning and near-drowning in the NT are higher than in the rest of Australia and show no significant decrease. The NT should improve its measures for prevention of childhood drowning.


Enhancing the protective efficacy of Mycobacterium bovis BCG vaccination against tuberculosis by boosting with the Mycobacterium tuberculosis major secretory protein.
Tuberculosis continues to ravage humanity, killing 2 million people yearly. Most cases occur in areas of the world to which the disease is endemic, where almost everyone is vaccinated early in life with Mycobacterium bovis BCG, the currently available vaccine against tuberculosis. Thus, while more-potent vaccines are needed to replace BCG, new vaccines are also needed to boost the immune protection of the 4 billion people already vaccinated with BCG. Until now, no booster vaccine has been shown capable of significantly enhancing the level of protective immunity induced by BCG in the stringent guinea pig model of pulmonary tuberculosis, the "gold standard" for testing tuberculosis vaccines. In this paper, we describe a booster vaccine for BCG comprising the purified recombinant Mycobacterium tuberculosis 30-kDa protein, the major secreted protein of this pathogen. In the guinea pig model of pulmonary tuberculosis, boosting BCG-immunized animals once with the 30-kDa protein greatly increased cell-mediated and humoral immune responses to the protein in three consecutive experiments. Most importantly, boosting BCG-immunized animals once with the 30-kDa protein significantly enhanced protective immunity against aerosol challenge with highly virulent M. tuberculosis, as evidenced by a significantly reduced lung and spleen burden of M. tuberculosis compared with those for nonboosted BCG-immunized animals (mean additional reduction in CFU of 0.4 +/- 0.1 log in the lung [P = 0.03] and 0.6 +/- 0.1 log in the spleen [P = 0.002]). This study suggests that administering BCG-immunized people a booster vaccine comprising the 30-kDa protein may enhance their level of immunoprotection against tuberculosis.


Nickel carbonate Hydroxide-based Core-Triple-Shelled nanofibers with ultrahigh specific capacity for flexible hybrid supercapacitors.
Designing novel efficient electrode materials with controlled hierarchical structure and composition for advanced supercapacitors remains a great challenge. Herein, a core-triple-shelled hierarchical GCNF/PANI/NCO nanostructure has been designed and fabricated by sequential growth of the conductive polyaniline (PANI) layers and nickel carbonate hydroxide (Ni2(CO3)(OH)2) nanosheets on the graphene-coated electrospun carbon nanofibers (GCNF) via a facile wet-chemical strategy. Taking full advantage of the free-standing architecture of graphene-coated electrospun carbon nanofibers, high conductivity and flexibility of the PANI layers, and abundant active sites of Ni2(CO3)(OH)2 nanosheets, the optimal GCNF/PANI/NCO (2 h) electrode exhibits a high specific capacitance of 1565F g-1 at 1 A/g and enhanced rate capability, which are higher than those of the GCNF, GCNF/PANI, and GCNF/NCO (2 h) electrodes at the same situation, and also exceeds most of the reported nickel carbonate hydroxide-based electrodes in literature. The superior performance should be mainly ascribed to the collaborative contribution of each component. Moreover, a self-assembled GCNF/PANI/NCO//AC hybrid supercapacitor delivers a high energy density of 35.4 Wh kg-1@750 W kg-1 and a long cycle lifespan. This strategy enables the controllable synthesis of core-triple-shelled hierarchical materials applicable to advanced electrochemical applications.


[Carcinosarcoma of the renal pelvis in a horseshoe kidney: about a case].
Carcinosarcoma of the renal pelvis is a rare tumor, and its development in a horseshoe kidney makes it even more special. This is the first case reported in the literature of a renal pelvis carcinosarcoma developed in a horseshoe kidney and diagnosed on macroscopic hematuria.


Heterogeneity in resistant fecal Bacteroides fragilis group collected from healthy people.
Normal nonpathogenic flora would represent a constant lake of resistance genes potentially transferable to human pathogens. To assess the prevalence of resistance genes and genetic variability of Bacteroides fragilis group (BFG) from normal flora, 177 Bacteroides isolates obtained from the fecal samples of healthy individuals. These isolates were subjected to antibiotic susceptibility testing and pulsed field gel electrophoresis (PFGE). The isolates were further tested for the presence of ermF, tetQ and bft genes by PCR. Our results indicated the presence of different clonal strains (1 common type and 57 single types) among the resistant isolates. The resistance rate for the six antibiotics in this study was between 1% and 95%. Most of the isolates (99%) were susceptible to metronidazole. ermF and tetQ were detected in all erythromycin and tetracycline resistant isolates. None of the isolates were carried bft gene. These data suggest dissemination of heterogenic clonal groups in healthy persons and resistance to 5 high commonly used antibiotics.


Simultaneous achievement of efficient hemicellulose separation and inhibition of lignin repolymerization using pyruvic acid treatment.
The efficiency of organic acid treatment in the conversion of lignocellulosic biomass fractions has been widely recognized. In this study, a novel green pyruvic acid (PA) treatment is proposed. The higher separation efficiency of eucalyptus hemicellulose was obtained at 4.0% PA and 150 °C. The hemicellulose separation yield was increased from 71.71 to 88.09% compared to glycolic acid (GA) treatment. In addition, the treatment time was significantly reduced from 180 to 40 min. The proportion of cellulose in the solid increased after PA treatment. However, the accompanying separation of lignin was not effectively controlled. Fortunately, a six-membered ring structure was formed on the diol structure of the lignin β-O-4 side chain. Fewer lignin-condensed structures were observed. High-value lignin rich in phenol hydroxyl groups were obtained. It provides a green path for the simultaneous achievement of efficient hemicellulose separation and inhibition of lignin repolymerization using organic acid treatment.


Hyperinsulinaemia in thyrotoxic hypokalaemic periodic paralysis.
To test the hypothesis that there is an abnormal serum insulin response to a carbohydrate load in thyrotoxic hypokalaemic periodic paralysis (THPP), 18 men with THPP and 15 with uncomplicated thyrotoxicosis were studied during an oral glucose tolerance test. The THPP group had significantly higher fasting insulin concentrations (27.6 [3.6] vs 13.4 [1.8] mU/l; p less than 0.005) and a higher overall insulin response to oral glucose (p less than 0.001 by ANOVA) than the thyrotoxicosis group. There were no significant differences in fasting or stimulated glucose. Hyperinsulinaemia may be an important factor in the precipitation of acute paralysis in THPP.


Pain coping strategies and their association with quality of life in people with Parkinson's disease: A cross-sectional study.
To develop multidimensional approaches for pain management, this study aimed to understand how PD patients cope with pain. Cross-sectional, cohort study. Monocentric, inpatient, university hospital. 52 patients with Parkinson's disease (without dementia) analysed. Motor function, nonmotor symptoms, health-related quality of life (QoL), and the Coping Strategies Questionnaire were assessed. Elastic net regularization and multivariate analysis of variance (MANOVA) were used to study the association among coping, clinical parameters, and QoL. Most patients cope with pain through active cognitive (coping self-statements) and active behavioral strategies (increasing pain behaviors and increasing activity level). Active coping was associated with lower pain rating. Regarding QoL domains, active coping was associated with better physical functioning and better energy, whereas passive coping was associated with poorer emotional well-being. However, as demonstrated by MANOVA, the impact of coping factors (active and passive) on the Short Form 36 domains was negligible after correction for age, motor function, and depression. Passive coping strategies are the most likely coping response of those with depressive symptoms, whereas active coping strategies are the most likely coping response to influence physical function. Although coping is associated with pain rating, the extent that pain coping responses can impact on QoL seems to be low.


[Blood conservation effect and safety of shed mediastinal blood autotransfusion after cardiac surgery].
Autotransfusion of shed mediastinal blood after cardiac surgery has been used to reduce risks related to homologous blood transfusions. To document the efficacy and safety of autotransfusion, we compared clinical findings of 80 patients receiving shed mediastinal blood (autotransfusion group) with those of the control group of 52 patients. The amount of the autotransfusion was limited to 800 ml, given the potentially harmful effects of shed blood transfusion. The mean transfused shed volume was 314 +/- 236 ml (S.D.). The serum levels of FDP-E, D-dimer and TAT after autotransfusion were higher in the autotransfusion group than in the control group (p = 0.01, p = 0.0004, p = 0.001, respectively). However, postoperative blood loss and the rate of reexploration for bleeding were similar in the two groups. The patients receiving blood products were fewer in the autotransfusion group than those in the control group (21% vs 44%; p = 0.005). Autotransfusion did not increase postoperative complications, including infection. Thus, although autotransfusion of mediastinal shed blood has the potential to affect hemostasis, unless the amount of autotransfusion exceeds 800 ml, it appears that this method is clinically safe and effective as a mean of blood conservation.


Clinicopathological features and prognostic factors analysis of multiple synchronous distinct subtypes of primary thyroid carcinoma.
To investigate the clinicopathological features, diagnosis, treatment, and prognosis of multiple synchronous distinct subtypes of primary thyroid carcinomas. The clinical data of 68 cases of synchronous carcinomas of the thyroid (STC) admitted to the Department of Thyroid Surgery in our hospital from January 2013 to December 2021 were reviewed. According to the pathological type, they were divided into the Synchronous differentiated and differentiated thyroid Carcinoma (SDDTC) group (42 cases), the Synchronous medullary and differentiated thyroid Carcinoma (SMDTC) group (18 cases), and the Synchronous Anaplastic and differentiated thyroid Carcinoma (SADTC)group (8 cases). The diagnosis, treatment, and survival of patients in each group were analyzed. Women with coexisting thyroid cancer were predominant (59 cases). Most of the symptoms were found on physical examination (47.1%) and neck mass (45.6%). The median age of patients in the SDDTC group, SADTC group, and SMDTC group was 47.5 (28-74) years old, 68.5 (26-75) years old, and 56.5 (39-74) years old. The age of the SADTC group and SMDTC group was older than that of the SDDTC group (P = 0.04, P = 0.03), and the rate of lymph node metastasis in groups SADTC (62.5%) and SMDTC (55.6%) was higher than in group SDDTC (21.4%). The disease course time, tumor location, clinical stage, and mortality of the SADTC group were significantly different from those of the SDDTC group and SMDTC group (P < 0.05). The overall survival of patients with synchronous carcinomas of the thyroid was 6-105 months, and the median overall survival was 38.5 months. The tumor-free survival was 0-90 months, 19.1% of patients developed distant metastasis, 11.8% of patients had postoperative recurrence, as well as the survival rate was estimated 91.18%. Cox model multivariate analysis showed that cervical lateral lymph node metastasis and tumor stage III/IV were independent risk factors for progression-free survival(PFS). The comparison results of the survival curves showed that the overall survival (OS)of the patients in the SADTC group was significantly worse (P < 0.01), while there was no significant difference in the PFS of different pathological types (χ2 = 5.024, P = 0.081).The OS of different treatment methods was significantly different (P = 0.002), but there was no significant difference in OS between local recurrence and distant metastases with or without surgery (χ2 = 0.954, P = 0.329). The STC has relatively unique clinical characteristics, and most patients can get a better prognosis after radical surgery. Pathological type, lateral cervical lymph node metastasis, tumor stage, and treatment are important factors which affect the prognosis of the disease. Since there are two distinct tumors with different aggressiveness, treatment options, and prognosis, individualized management is required.


Serological surveillance of H5 and H9 avian influenza A viral infections among pigs in Southern China.
Pigs are susceptible to both human and avian influenza viruses (AIV). Moreover, they are suspected of being the intermediate hosts or mixing vessels of pandemic influenza viruses. Researchers suspect that the influenza viruses are able to undergo reassortment or to adapt to various mammalian hosts while they incubate in pigs. For the present report, we conducted a serological surveillance of pigs in southern China from 2008 to 2012 to establish the prevalence of antibodies against H5N1 and H9N2 AIV. A total of one hundred pig farms from the Guangdong, Zhejiang, Fujian, and Yunnan Provinces were sampled, yielding a total of 3960 serum specimens. The haemagglutination inhibition (HI) tests revealed no evidence of H5 infection when the Clade 2.3.2 virus was used as the antigen, but a 4.6% positive rate of H9 infection was observed when using the Beijing/1/94-like virus as the antigen. The positive sera for H9 infection were further verified with neutralization tests, which confirmed a 3.7% rate of positive sera of H9 infection. In summary, the results imply that the swine populations in southern China had not been affected greatly by the H5N1 avian influenza virus. Nevertheless, these swine H9N2 influenza viruses might pose a threat to human health, and so researchers should continue to carry out swine influenza virus surveillance in China.


Effects of micro(nano)plastics on soil nutrient cycling: State of the knowledge.
The ecological impacts of micro(nano)plastics (MNPs) have attracted attention worldwide because of their global occurrence, persistence, and environmental risks. Increasing evidence shows that MNPs can affect soil nutrient cycling, but the latest advances on this topic have not systematically reviewed. Here, we aim to present the state of knowledge about the effects of MNPs on soil nutrient cycling, particularly of C, N, and P. Using the latest data, the present review mainly focuses on three aspects, including (1) the effects and underlying mechanisms of MNPs on soil nutrient cycling, particularly of C, N and P, (2) the factors influencing the effects of MNPs on soil nutrient cycling, and (3) the knowledge gaps and future directions. We conclude that MNPs can alter soil nutrient cycling via mediating soil nutrient availability, soil enzyme activities, functional microbial communities, and their potential ecological functions. Furthermore, the effects of MNPs vary with MNPs characteristics (i.e., polymeric type, size, dosage, and shape), chemical additives, soil physicochemical conditions, and soil biota. Considering the complexity of MNP-soil interactions, multi-scale experiments using environmental relevant MNPs are required to shed light on the effects of MNPs on soil nutrients. By learning how MNPs influence soil nutrients cycles, this review can guide policy and management decisions to safeguard soil health and ensure sustainable agriculture and land use practices.


Microsecond rotational motions of eosin-labeled myosin measured by time-resolved anisotropy of absorption and phosphorescence.
We have studied submicrosecond and microsecond rotational motions within the contractile protein myosin by observing the time-resolved anisotropy of both absorption and emission from the long-lived triplet state of eosin-5-iodoacetamide covalently bound to a specific site on the myosin head. These results, reporting anisotropy data up to 50 microseconds after excitation, extend by two orders of magnitude the time range of data on time-resolved site-specific probe motion in myosin. Optical and enzymatic analyses of the labeled myosin and its chymotryptic digests show that more than 95% of the probe is specifically attached to sulfhydryl-1 (SH1) on the myosin head. In a solution of labeled subfragment-1 (S-1) at 4 degrees C, absorption anisotropy at 0.1 microseconds after a laser pulse is about 0.27. This anisotropy decays exponentially with a rotational correlation time of 210 ns, in good agreement with the theoretical prediction for end-over-end tumbling of S-1, and with times determined previously by fluorescence and electron paramagnetic resonance. In aqueous glycerol solutions, this correlation time is proportional to viscosity/temperature in the microsecond time range. Furthermore, binding to actin greatly restricts probe motion. Thus the bound eosin is a reliable probe of myosin-head rotational motion in the submicrosecond and microsecond time ranges. Our submicrosecond data for myosin monomers (correlation time 400 ns) also agree with previous results using other techniques, but we also detect a previously unresolvable slower decay component (correlation time 2.6 microseconds), indicating that the faster motions are restricted in amplitude. This restriction is not consistent with the commonly accepted free-swivel model of S-1 attachment in myosin. In synthetic thick filaments of myosin, both fast (700 ns) and slow (5 microseconds) components of anisotropy decay are observed. In contrast to the data for monomers, the anisotropy of filaments has a substantial residual component (26% of the initial anisotropy) that does not decay to zero even at times as long as 50 microseconds, implying significant restriction in overall rotational amplitude. This result is consistent with motion restricted to a cone half-angle of about 50 degrees. The combined results are consistent with a model in which myosin has two principal sites of segmental flexibility, one giving rise to submicrosecond motions (possibly corresponding to the junction between S-1 and S-2) and the other giving rise to microsecond motions (possibly corresponding to the junction between S-2 and light meromyosin).(ABSTRACT TRUNCATED AT 400 WORDS)


Expedited MitraClip: Rapid Evaluation, Treatment, and Discharge in the COVID-19 Era.
Undertreatment of patients with severe mitral regurgitation (MR) has been exaggerated during the coronavirus disease of 2019 (COVID-19) pandemic. Expedited workup and shortened post-procedural hospital stay after percutaneous mitral valve repair (PMVR) would be incredibly helpful to relieve the constrain in the era of the COVID-19 pandemic and immediately afterward. We report a patient who underwent PMVR with a simplified pre-operative workup, a shortened hospital stay, and expedited discharge.


Crosstalk between ABA and ethylene in regulating stomatal behavior in tomato under high CO2 and progressive soil drying.
Increasing atmospheric CO2 concentrations accompanied by intensifying drought markedly impact plant growth and physiology. This study aimed to explore the role of abscisic acid (ABA) in mediating the response of stomata to elevated CO2 (e[CO2]) and drought. Tomato plants with different endogenous ABA concentrations [Ailsa Craig (AC), the ABA-deficient mutant flacca, and ABA-overproducing transgenic tomato SP5] were grown in ambient (a[CO2], 400 μmol mol-1) and elevated (e[CO2],800 μmol mol-1) CO2 environments and subjected to progressive soil drying. Compared with a[CO2] plants, e[CO2] plants had significantly lower stomatal conductance in AC and SP5 but not in flacca. Under drought, e[CO2] plants had better water status and higher water use efficiency. e[CO2] promoted the accumulation of ABA in leaves of plants subjected to drought, which coincided with the up-regulation of ABA biosynthetic genes and down-regulation of ABA metabolic genes. Although the increase of ABA induced by drought in flacca was much less than in AC and SP5, flacca accumulated large amounts of ethylene, suggesting that in plants with ABA deficiency, ethylene might play a compensatory role in inducing stomatal closure during soil drying. Collectively, these findings improve our understanding of plant performance in a future drier and higher-CO2 environment.


Crown repair with a cast post and core.
A technique to make a post and core pattern that can be used to save an existing crown has been presented. The technique should become an additional tool in the treatment armamentarium.


Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression.
The study was aimed at detecting the expression of a newly found oncogene, astrocyte elevated gene-1 (AEG-1), in renal cell carcinoma (RCC) and its correlation with histopathologic features and the survival of patients. Real-time reverse transcription-PCR and Western blot showed markedly higher expression of AEG-1 in 8 cases of RCC tissue compared with the paired normal tissue from the same patient. The expression level of AEG-1 was also increased in four RCC cell lines in contrast with normal tubular epithelial human kidney cells 2 (HK-2) at both mRNA and protein levels. Furthermore, immunohistochemistry analysis showed highly expressed AEG-1 in 96 of 102 (94.1%) cases of paraffin-embedded archival RCC tissue. Statistical analysis showed a significant correlation of AEG-1 expression with tumor grade (P <0.001), clinical staging (P = 0.003), T classification (P = 0.003) as well as metastasis classification (P=0.032). The means for survival time of low AEG-1 expression group was 76.98m
while high AEG-1expression group was 60.94m. Our results suggest that AEG-1 protein is overexpressed in RCC and plays an important role in tumor differentiation and progression.
High AEG-1 expression is closely associated with poor prognosis. Astrocyte elevated gene-1, AEG-1, renal cell carcinoma, prognosis.


Compensatory hyperhidrosis: a consequence of truncal sympathectomy treated by video assisted application of botulinum toxin and reoperation.
Hyperhidrosis is a debilitating condition characterised by sweating that exceeds the need of normal thermoregulation. Surgical management of primary hyperhidrosis by upper dorsal sympathectomy is the treatment of choice for intractable hyperhidrosis, however, paradoxically it may be followed by troublesome compensatory hyperhidrosis in a significant number of patients. The frequency of compensatory hyperhidrosis often reflects the extensiveness of the denervation. We report for the first time the successful treatment of a patient who developed compensatory hyperhidrosis following sympathectomy using video assisted extension of the sympathectomy by application of botulinum toxin (BTX-A). In addition, this case highlights the use of botulinum toxin as a guide for the potential successful management of compensatory hyperhidrosis prior to definitive extension of a sympathectomy.


Limited utilization options for secondary plastics may restrict their circularity.
Plastic recycling can provide environmental benefits by avoiding the detrimental impacts of alternative disposal pathways and enabling the substitution of primary materials. However, most studies aiming at increasing recycling rates have not investigated how the resulting secondary materials can be utilized in product manufacturing. This study assesses the future substitution potential of primary with secondary plastics, building on a material flow system of 11 plastic types in 54 product subsegments in Switzerland in 2017 with a recycling rate of 9%. In a prospective material flow analysis of a scenario for 2025, the collection rate of the plastic fractions collected in 2017 is increased to 80%. The secondary material flows are allocated to suitable uptaking product subsegments using a linear optimization. The maximum share of secondary materials utilizable in each product subsegment is estimated, whereby three sub-scenarios involving high, moderate and low allowed secondary material shares are modelled. Depending on plastic type and scenario, 21% to 100% of the secondary material gained can substitute for primary material, covering 11% to 17% of the total material demand. While the overall recycling rate could reach 23%, taking into account only the uptaken secondary materials a true recycling rate of only 17% results in the moderate applicability sub-scenario. Based on these results, the secondary material uptake can be said to constitute a limiting factor for increased future recycling. Therefore, thorough consideration of the possible secondary material application is a prerequisite for designing and assessing future recycling systems or for setting recycling rate targets.


Seasonal variation in leaf chemistry of the coast live oak Quercus agrifolia and implications for the California oak moth Phryganidia californica.
The perennial foliage of the California coast live oak (Quercus agrifolia Nee) permits herbivores to feed on this oak species throughout the year. Patterns of herbivory for a two-year period on Q. agrifolia were observed in relation to seasonal and age-related changes in the nutritional and defensive characteristics of leaves. Nitrogen and phosphorus contents were higher in new leaves compared to mature foliage. Structural compounds (e.g., cellulose) in leaves rapidly increased with age. Concentrations of tatal phenolics (Folin-Denis) and astringency were higher in new foliage, and concentrations of condensed tannins gradually increased as the leaves matured. Peaks of herbivore damage were observed in June and in September-October, and were caused by outbreaks of the California oak moth (Phryganidia californica). P. californica, a bivoltine oak specialist, exhibited feeding preferences in June for old leaves over emerging leaves, and showed no preferences for leaf classes in September. These results suggest that P. californica is adapted to survive on nutritionally poor foliage and to circumvent "quantitative defenses" such as condensed tannins.


Ependymoma with "granular cell" features: report of two cases.
We report two cases of ependymoma which showed prominent "granular cell" changes of the cytoplasm. The patients were a 7-year-old boy with a tumor in the cerebellum (case 1) and a 70-year-old man with a tumor in the frontal lobe (case 2). The tumor of case 1 showed a histopathological appearance of ependymoma containing many focal aggregates of large polygonal cells in which the cytoplasm was stuffed with numerous eosinophilic granules. The tumor of case 2 predominantly showed the features of papillary ependymoma, and some tumor cells were swollen and contained similar eosinophilic granules. Intracytoplasmic granules in both tumors were immunoreactive for GFAP and ubiquitin, but not for epithelial membrane antigen, CD68 or mitochondria. Ultrastructurally, they were found as aggregates of membrane-bound, electron-dense, globular structures. Karyotypic analysis of the tumor in case 1 demonstrated 2, 11 and 12 trisomies. Intracytoplasmic eosinophilic granules occasionally occur in astrocytic and oligodendroglial neoplasms, but an appearance of similar granules is very rare in ependymoma. The two cases presented here may represent a new histopathological variant of ependymoma, and the term "granular cell ependymoma" is appropriate for them.


Incidence and outcome of transplantation of fungal-culture-positive donor corneoscleral tissue in optical keratoplasty.
This study aims to determine the incidence of fungal-culture-positive corneoscleral donor rim in patients undergoing keratoplasty and evaluate clinical outcomes of eyes that received these contaminated donor tissues. Patients who had optical keratoplasty between 2006 and 2016 and were found to have fungal-culture-positive donor rim were included. Microbiological and eye bank records were reviewed to determine the incidence of positive fungal rim cultures. Data were collected on visual and clinical outcomes. The main outcome measures were fungal-culture-positive donor rim and development of fungal keratitis or endophthalmitis post keratoplasty. Long-term clinical outcome and associated complications were the secondary outcome measures. Out of 9620 cases of corneal transplants, 145 (1.5%) had fungal-culture-positive donor rim. Candida was the most common organism, cultured in 127 (87.6%) cases. There were no cases of postoperative fungal keratitis or endophthalmitis. Median follow-up was 4.8 years (interquartile range 3.8-7.2 years). Only eight cases (5.5%) received prophylactic antifungal treatment. There were 34 (23.4%) cases of rejection, 13 (8.9%) developed glaucoma, and 7 (4.8%) developed late bacterial keratitis. At last follow-up, best corrected visual acuity was 20/60 or better in 88 cases (60.7%) and 115 eyes (79.3%) had a clear graft. The incidence of fungal-culture-positive donor rim is extremely low. The risk of developing fungal keratitis or endophthalmitis in patients who received contaminated donor tissue was almost negligible. Further studies are warranted to prove whether prophylaxis or adding amphotericin B in Optisol-GS confers any added benefit.


Polymorphism of Sex Determination Amongst Wild Populations Suggests its Rapid Turnover Within the Nile Tilapia Species.
Sex-determining regions have been identified in the Nile tilapia on linkage groups (LG) 1, 20 and 23, depending on the domesticated strains used. Sex determining studies on wild populations of this species are scarce. Previous work on two wild populations, from Lake Volta (Ghana) and from Lake Koka (Ethiopia), found the sex-determining region on LG23. These populations have a Y-specific tandem duplication containing two copies of the Anti-Müllerian Hormone amh gene (named amhY and amhΔY). Here, we performed a whole-genome short-reads analysis using male and female pools on a third wild population from Lake Hora (Ethiopia). We found no association of sex with LG23, and no duplication of the amh gene. Furthermore, we found no evidence of sex linkage on LG1 or on any other LGs. Long read whole genome sequencing of a male from each population confirmed the absence of a duplicated region on LG23 in the Lake Hora male. In contrast, long reads established the structure of the Y haplotype in Koka and Kpandu males and the order of the genes in the duplicated region. Phylogenies constructed on the nuclear and mitochondrial genomes, showed a closer relationship between the two Ethiopian populations compared to the Ghanaian population, implying an absence of the LG23Y sex-determination region in Lake Hora males. Our study supports the hypothesis that the amh region is not the sex-determining region in Hora males. The absence of the Y amh duplication in the Lake Hora population reflects a rapid change in sex determination within Nile tilapia populations. The genetic basis of sex determination in the Lake Hora population remains unknown.


Comparison of safety between 1-stage and 2-stage surgery: from laparoscopic adjustable gastric banding to laparoscopic sleeve gastrectomy.
Laparoscopic sleeve gastrectomy (LSG) is becoming increasingly popular. With significant failure rates for laparoscopic adjustable gastric banding (LAGB), conversion to LSG is an attractive consideration for maintenance of target percentage excess weight loss (%EWL). Conversions can be successfully achieved in either 1-stage (OS) or 2-stage (TS) surgery. We intend to examine safety between OS and TS surgery and determine features indicative for OS surgery. Records were audited from the database of a private surgical practice located in Perth, Western Australia. We analyzed 86 patients in a prospective observational study over a 3-year time frame (38 OS, 48 TS). The primary outcome was perioperative events, graded using the Clavien-Dindo classification system. Secondary outcomes included any preoperative, intraoperative, and postoperative events. Surgical complications were similar between OS and TS groups. Grades of complications were not significantly different. No difference was found in procedural normality between cohorts (P = .95). More adhesions were present in the TS group compared with the OS group after accounting for adjustments (P = .05). Patient demographic characteristics were not different between groups, with the exception of body mass index (BMI). There were no staple line leaks within the OS group; 2 leaks occurred in the TS group. OS surgery appears as safe as TS surgery provided surgeons carefully assess patient eligibility. We recommend the following features for ideal OS candidacy: no previous band complications, minimal peritoneal adhesions under laparoscopy, minimal co-morbidities, and a lower BMI at entry into conversion.


Obtention of Dengue Virus Membrane Proteins and Role for Virus Assembly.
The four serotypes of dengue virus (DENV), belonging to the genus Flavivirus in the family Flaviviridae, are the leading cause of arboviral diseases in humans. The clinical presentations range from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Despite decades of efforts on developing intervention strategies against DENV, there is no licensed antiviral, and safe and effective vaccines remain challenging. Similar to other flaviviruses, the assembly of DENV particles occurs in the membranes derived from endoplasmic reticulum; immature virions bud into the lumen followed by maturation in the trans-Golgi and transport through the secretary pathway. A unique feature of flavivirus replication is the production of small and slowly sedimenting subviral particles, known as virus-like particles (VLPs). Co-expression of premembrane (prM) and envelope (E) proteins can generate recombinant VLPs, which are biophysically and antigenically similar to infectious virions and have been employed to study the function of prM and E proteins, assembly, serodiagnostic antigens, and vaccine candidates. Previously, we have developed several assays including sucrose cushion ultracentrifugation, sucrose gradient ultracentrifugation, membrane flotation, subcellular fractionation, and glycosidase digestion assay to exploit the interaction between DENV prM and E proteins, membrane association, subcellular localization, glycosylation pattern, and assembly of VLPs and replicon particles. The information derived from these assays have implications to further our understanding of DENV assembly, replication cycle, intervention strategies, and pathogenesis.


Sustained elevation of circulating growth and differentiation factor-15 and a dynamic imbalance in mediators of muscle homeostasis are associated with the development of acute muscle wasting following cardiac surgery.
Acute muscle wasting in the critically ill is common and causes significant morbidity. In a novel human model of acute muscle wasting following cardiac surgery, known or potential circulating modulators of muscle mass--insulin-like growth factor-1, myostatin, and growth and differentiation factor-15--were measured over a week. It was hypothesized that patients who developed acute muscle wasting would show distinct patterns of change in these mediators. A prospective longitudinal observational study of high-risk elective cardiac surgical patients identifying, by ultrasound, those developing muscle wasting. Tertiary cardiothoracic referral center: Royal Brompton Hospital, London, UK. Forty-two patients undergoing elective high-risk cardiothoracic surgery. Circulating insulin-like growth factor-1, myostatin, and growth and differentiation factor-15 were assayed preoperatively and over the first week postoperatively. The ability of growth and differentiation factor-15 to cause muscle wasting in vitro was determined in C2C12 myotubes. Of the 42 patients, 23 (55%) developed quadriceps atrophy. There was an acute decrease in insulin-like growth factor-1 and unexpectedly myostatin, known mediators of muscle hypertrophy and atrophy, respectively. By contrast, plasma growth and differentiation factor-15 concentrations increased in all patients. This increase in growth and differentiation factor-15 was sustained at day 7 in those who developed muscle wasting (day 7 compared with baseline, p<0.01), but recovered in the nonwasting group (p>0.05). Insulin-like growth factor-1 did not recover in those who developed muscle wasting (day 7 compared with baseline, p<0.01) but did in the nonwasting group (p>0.05). Finally, we demonstrated that growth and differentiation factor-15 caused atrophy of myotubes in vitro. These data support the hypothesis that acute muscle loss occurs as a result of an imbalance between drivers of muscle atrophy and hypertrophy. Growth and differentiation factor-15 is a potential novel factor associated with muscle atrophy, which may become a therapeutic target in patients with ICU acquired paresis and other forms of acute muscle wasting.


Local perceptions do not follow rainfall trends: A case study in traditional Marajo island communities (eastern para state, BR).
The great current challenge for the conservation and use of natural resources refers to global climate change, because of its impacts felt in different intensities at global, regional, and local spatial scales. Within the system of environmental protection areas in Brazil, the extractive reserves ensure the sustainable use of natural resources by traditional populations, thus maintaining the cultural and biological aspects of a region. Such populations, being in close management of the surrounding environments, tend to perceive changes in ecological processes that many need for their livelihoods. The use of this perception of local populations in conjunction with academic research evidence has a high potential to allow a whole and systemic view of possible changes in natural phenomena. This study developed an integrated analysis of scientific evidence and local perceptions to understand the variation of precipitation in a community inserted in an extractive reserve in the eastern Amazon. We used 30 years of precipitation data from the Brazilian National Institute of Meteorology - INMET, the Southern Oscillation Index - SOI, and the Atlantic Meridional Mode Index - AMM. Furthermore, we applied a form to measure the population's perception of possible changes in rainfall cycles in the region. The meteorological data indicate that the region of the community has been presenting a rainfall reduction; however, people in the community do not perceive this trend. Although it is public knowledge that the global climate is undergoing changes, a fact noted after the integrating analysis of scientific evidence with local knowledge in Resexmar Soure is that the perceptions of traditional populations often focus on smaller temporal and spatial scale visions.


Association between polymorphisms of folate-metabolizing enzymes and risk of prostate cancer.
Polymorphisms of the genes 5'-10'-methylenetetrahydrofolate reductase (MTHFR, 677CT and 1298AC), methionine synthase (MTR, 2756AC) and methionine synthase reductase (MTRR, 66AC) provoke variations in enzyme activity, which can lead to alterations in the metabolism of folates and in the synthesis of S-adenosyl-methionine (SAM), the most active methyl donor in the body. This could play an important role in carcinogenesis through the degree of DNA methylation and of nucleotide synthesis. In the present study, four polymorphisms were studied, two of the methylenetetrahydrofolate reductase gene, and the other two of methionine synthase and methionine synthase reductase. Our aim was to study the association between prostate carcinoma susceptibility and these polymorphisms. A hospital-based case-control study was conducted in 182 patients (mean age: 70.7+/-7.29 years) with histologically confirmed prostate carcinoma and in 205 control subjects (mean age: 70.3+/-7.82 years) diagnosed with benign prostatic hyperplasia (BPH). Genomic DNA was extracted from peripheral leukocytes. Comparison of the MTHFR CT and TT genotypes in patients and the controls revealed significant differences (0.57 vs 0.38) (OR: 2.19, 95% CI: 1.46-3.30) and (0.06 vs 0.15) (OR: 0.36, 95% CI: 0.17-0.73), respectively. No statistically significant differences were found between patients and controls with respect to the MTHFR 1298AC, the MTR 2756AC and the MTRR 66AC polymorphisms. However, among the patients, the MTR 2756 allele C was related to a high Gleason score. We conclude that the polymorphism MTHFR C677T is clearly related to prostatic carcinogenesis, on the contrary to the other polymorphisms studied, although the MTR 2756 allele C acts as a factor of tumor aggressiveness, this being found in tumors with high carcinogenic potential.


Sinus augmentation with poly(ε)caprolactone-β tricalcium phosphate scaffolds, mesenchymal stem cells and platelet rich plasma for one-stage dental implantation in minipigs.
This study evaluated the efficacy of a tube-shaped poly(ε) caprolactone - β tricalcium phosphate (PCL-TCP) scaffold with the incorporation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and platelet-rich plasma (PRP) for bone regeneration in the procedure of single-stage sinus augmentation and dental implantation in minipigs. Implants were placed in the bilateral sides of the maxillary sinuses of 5 minipigs and allocated to a PCL-TCP+hUCMSCs+PRP group (n=5), a PCL-TCP+PRP group (n=5), and a PCL-TCP-only group (n=6). After 12 weeks, bone regeneration was evaluated with soft X-rays, micro-computed tomography, fluorescence microscopy, and histomorphometric analysis. Four implants failed (2 each in the PCL-TCP+hUCMSCs+PRP and PCL-TCP+hUCMSC groups). An analysis of the grayscale levels and bone-implant contact ratio showed significantly higher mean values in the PCL-TCP+hUCMSCs+PRP than in the PCL-TCP group (P=0.045 and P=0.016, respectively). In fluoromicroscopic images, new bone formation around the outer surfaces of the scaffolds was observed in the PCL-TCP+hUCMSCs+PRP group, suggesting a tenting effect of the specially designed scaffolds. Bone regeneration at the scaffold-implant interfaces was observed in all 3 groups. Using a tube-shaped, honeycombed PCL-TCP scaffold with hUCMSCs and PRP may serve to enhance bone formation and dental implants' osseointegration in the procedure of simultaneous sinus lifting and dental implantation.


Hepatic estrogen and androgen receptors and binding proteins in streptozotocin-diabetic male Wistar rats.
We have previously shown that there are decreases in the sex differences seen in certain hepatic drug and steroid metabolising enzymes in rats with early (4 day) streptozotocin-induced diabetes. We postulated that hepatic sex hormone receptors or binding proteins might be involved in modulation of the sex differences noted in metabolism. In the present study, we measured the binding kinetics of the hepatic cytosolic estrogen receptor and androgen receptor, along with the high capacity-low affinity estrogen binding protein. At 4 or 10 days post-streptozotocin (60 mg/kg intravenously), there was no change in the maximum binding capacity of the estrogen receptor, nor in the hormone affinity of any of the three proteins. However, the binding capacity of the androgen receptor and estrogen binding protein in the diabetic animals was decreased to less than half of control levels. This effect could not be reversed by hormone replacement with any of the following regimens: protamine zinc insulin, 10 U/kg subcutaneously once a day; Toronto insulin, 15 U/kg subcutaneously twice a day; testosterone enanthate, 1 mg/kg s.c. once a day; triiodothyronine, 30 micrograms/kg s.c. daily; ovine growth hormone: 0.02 U/h s.c., 30 micrograms s.c. 7 times daily, 30 micrograms i.v. 4 times daily; or various combinations of these hormones. Stress, such as 4 intravenous injections of saline per day, was noted to decrease the binding capacity of the estrogen binding protein. Therefore, we measured the basal serum corticosterone levels, which were not significantly different from control values in untreated or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical Effectiveness of Tetracycline-Class Agents Based Regimens in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia: A Single-Center Retrospective Cohort Study.
This study evaluated the clinical outcome of carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia and the clinical effectiveness of tetracyclines-based therapy. In a retrospective cohort study over 5 years period, 108 patients were included in the study. The overall 30-day mortality rate was 71.4%. Pitt's bacteremia score (PBS) (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 1.22-1.42 per 1-point), colistin-single regimens (aHR, 0.34; 95% CI, 0.17-0.69), and tetracyclines single/tetracyclines-colistin combination regimens (aHR, 0.18; 95% CI, 0.07-0.48) were independently associated with 30-day mortality. Among patients with a PBS < 6, only tetracycline-containing regimens were associated with decreased mortality. Among patients receiving appropriate definite antimicrobials, the tetracyclines-colistin combination (7 of 7, 100%) tended to a higher 30-day survival rate compared to a tetracycline (7 of 12, 57.1%) or colistin single regimen (10 of 22, 41.6%, P = 0.073). Our findings suggest tetracyclines might be effective for treating CRAB infections when combined with colistin.


Business continuity and pandemic preparedness: US health care versus non-health care agencies.
Only limited data are available on US business continuity activities related to biologic events. A questionnaire was administered to human resource professionals during May-July 2011 to assess business continuity related to biologic events, incentives businesses are providing to maximize worker surge capacity, and seasonal influenza vaccination policy. Linear regressions were used to describe factors associated with higher business continuity and pandemic preparedness scores. The χ(2) and Fisher exact tests compared health care versus non-health care businesses on preparedness indicators. Possible business continuity and pandemic preparedness scores ranged from 0.5 to 27 and 0 to 15, with average resulting scores among participants at 13.2 and 7.3, respectively. Determinants of business continuity and pandemic preparedness were (1) business size (larger businesses were more prepared), (2) type of business (health care more prepared), (3) having human resource professional as company disaster planning committee member, and (4) risk perception of a pandemic in the next year. Most businesses (63.3%, n = 298) encourage staff influenza vaccination; 2.1% (n = 10) mandate it. Only 10% of businesses (11.0%, n = 52) provide employee incentives, and fewer than half (41.0%, n = 193) stockpile personal protective equipment. Despite the recent H1N1 pandemic, many US businesses lack adequate pandemic plans. It is critical that businesses of all sizes and types become better prepared for a biologic event.


Ovarian Lipid Metabolism Modulates Circulating Lipids in Premenopausal Women.
The premenopausal circulating lipid profile may be linked to the hormonal profile and ovarian lipid metabolism. Assess how estradiol, progesterone, and ovarian lipid metabolism contributes to the premenopausal lipid profile; and evaluate the acute effects of a common hormonal oral contraceptive (OC) on circulating lipids. Experimental crossover with repeated measures. Academic hospitals. Eight healthy, regularly menstruating women. Participants underwent periodic serum sampling during a normal menstrual cycle; a standard 21-day, monophasic combined hormonal OC cycle (30 µg of ethinyl estradiol and 150 µg of levonorgestrel per day); menopause simulated by leuprolide acetate (22.5-mg depot); and an artificial menstrual cycle achieved via transdermal estradiol (50 to 300 µg/d) and vaginal micronized progesterone (100 to 300 mg/d). Primary outcomes included evaluation of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, and the total cholesterol to HDL cholesterol ratio. To estimate the effect of estradiol, progesterone, and ovarian lipid metabolism, all specimens except those from the OC cycle were analyzed. Subgroup analysis was conducted on the follicular and luteal phases. In a separate analysis, the effect of the OC was evaluated relative to the normal menstrual cycle. Estradiol was significantly associated with increased levels of HDL cholesterol throughout the menstrual cycle and in the follicular phase. Ovarian effects were associated with reduced lipid levels, especially during the luteal phase. The OC was associated with an increased total cholesterol to HDL cholesterol ratio and triglycerides. Previously unappreciated factors including ovarian lipid metabolism may contribute to the premenopausal lipid profile.


Differential antagonism of platelet activating factor-induced neutrophilia and gastric hemorrhage in the rat.
Intravenous injection of platelet activating factor (PAF) in rats produced hypotension, neutrophilia, gastric congestion, and sloughing of the gastric epithelium. The congestion was quantified by measuring hemoglobin in the gastric mucosa. Other lesions were quantified by scores of gross pathology and histopathology. PAF-induced changes in neutrophil levels were prevented by pretreatment with the PAF-antagonist Ro24-4736, but not by the PAF-antagonist CV-3988. Both PAF antagonists reduced the hypotension, the amount of hemoglobin in the gastric mucosa, and the PAF-induced gastric pathology. These results suggest that PAF receptors involved in PAF-induced neutrophil mobilization respond differently from PAF receptors in the gastrointestinal and cardiovascular systems.


The emergence of drug resistance to targeted cancer therapies: Clinical evidence.
For many decades classical anti-tumor therapies included chemotherapy, radiation and surgery; however, in the last two decades, following the identification of the genomic drivers and main hallmarks of cancer, the introduction of therapies that target specific tumor-promoting oncogenic or non-oncogenic pathways, has revolutionized cancer therapeutics. Despite the significant progress in cancer therapy, clinical oncologists are often facing the primary impediment of anticancer drug resistance, as many cancer patients display either intrinsic chemoresistance from the very beginning of the therapy or after initial responses and upon repeated drug treatment cycles, acquired drug resistance develops and thus relapse emerges, resulting in increased mortality. Our attempts to understand the molecular basis underlying these drug resistance phenotypes in pre-clinical models and patient specimens revealed the extreme plasticity and adaptive pathways employed by tumor cells, being under sustained stress and extensive genomic/proteomic instability due to the applied therapeutic regimens. Subsequent efforts have yielded more effective inhibitors and combinatorial approaches (e.g. the use of specific pharmacologic inhibitors with immunotherapy) that exhibit synergistic effects against tumor cells, hence enhancing therapeutic indices. Furthermore, new advanced methodologies that allow for the early detection of genetic/epigenetic alterations that lead to drug chemoresistance and prospective validation of biomarkers which identify patients that will benefit from certain drug classes, have started to improve the clinical outcome. This review discusses emerging principles of drug resistance to cancer therapies targeting a wide array of oncogenic kinases, along with hedgehog pathway and the proteasome and apoptotic inducers, as well as epigenetic and metabolic modulators. We further discuss mechanisms of resistance to monoclonal antibodies, immunomodulators and immune checkpoint inhibitors, potential biomarkers of drug response/drug resistance, along with possible new therapeutic avenues for the clinicians to combat devastating drug resistant malignancies. It is foreseen that these topics will be major areas of focused multidisciplinary translational research in the years to come.


Association study of the DISC1/TRAX locus with schizophrenia in a Japanese population.
Disrupted-in-Schizophrenia-1 (DISC1), identified by cytogenetic approaches in a pedigree with familial psychosis, is considered a candidate susceptibility gene for schizophrenia in some populations. In the pedigree, the TRAX gene, located adjacent to DISC1 on the disrupted chromosome 1, may also contribute to the pathophysiology of the familial schizophrenia. We studied association of the DISC1 and TRAX genes with schizophrenia in 338 Japanese by analyzing 15 single nucleotide polymorphisms (SNPs), including 12 SNPs in DISC1 and three in TRAX, respectively. No significant difference was observed between the patients and controls in allelic frequencies or genotypic distributions of 15 SNPs. A weak trend for the association in genotypic distribution of one SNP in TRAX (major homo/hetero/minor homo: 0.324/0.431/0.245 vs. 0.293/0.526/0.181 for patients vs controls, p = 0.039 in the 2 x 3 comparison) turned out to be insignificant after Bonferroni correction. Haplotype analysis did not support the association between the patients and controls. The present study suggests that the DISC1/TRAX locus may not have a major role in Japanese schizophrenia.


Excessive compression of the human tibio-femoral joint causes ACL rupture.
The knee is one of the most frequently injured joints in the human body. A recent study suggests that axial compressive loads on the knee may play a role in injury to the anterior cruciate ligament (ACL) for the flexed knee, because of an approximate 10 degrees posterior tilt in the tibial plateau (J. Orthop. Res. 16 (1998) 122-127). The hypothesis of the current study was that excessive axial compressive loads in the human tibio-femoral (TF) joint would cause relative displacement and rotation of the tibia with respect to the femur, and result in isolated injury to the ACL when the knee is flexed to 60 degrees , 90 degrees or 120 degrees . Sixteen isolated knees from eleven fresh cadaver donors (74.3+/-10.5 yr) were exposed to repetitive TF compressive loads increasing in intensity until catastrophic injury. ACL rupture was documented in 14/16 cases. The maximum TF joint compressive force for ACL failure was 5.1+/-2.1 kN for all flexion angles combined. For the 90 degrees flexed knee, the injury occurred with a relative anterior displacement of 5.4+/-3.8mm, a lateral displacement of 4.1+/-1.4mm, and a 7.8+/-7.0 degrees internal rotation of the tibia with respect to the femur.


[Child behavior disorder : clinical reasoning in general practice].
in Belgium 70 % of the children aged 0 - 14 years have at least one annual contact with their family doctor, while for the same period, only 6 - 12 % of them will see a neuropaediatrician and/or a child psychiatrist, despite the fact that a diagnostic of Externalizing behavior before the age of 6 to 7 years, such as various ways of aggressiveness, of anger or of stealing will very often alert the family, the staff of creches or nursery as well as the teachers. Other children are showing signs of Internalizing behavior, very often together with depression or other forms of anxiety. considering the role and the skills of the family doctor, the target is to propose a clinical approach adapted to the first line practitioner having to face the majority of complaints about the behaviour of a child younger than 10 years. bibliographic research. The research equations were used on the data base TRIP DATA BASE, Cochrane Library, PUBMED and Google Scholar (EN/FR), searching, bare exception, the literature of the last five years. Moreover, the sites of the Haute Autorité Française (HAS), Société Scientifique de Médecine Générale (SSMG), Centre d'Expertise en Soins de Santé (KCE), Institut Scientifique en Santé Publique (ISSP) and of the DSM V (Diagnostic and Statistical Manual of Mental Disorders) were consulted too. the age of the child, his social and family environment will guide the family doctor and in the majority of cases, he will be able to reassure the family. Moreover, when in front of any problem within the family life it should be advisable to inquire about the health of the children in question, especially from a behavioural point of view. To the opposite, when a child is showing TEC or TIC, it is important to inquire about circumstances in his environment that might potentially be at the origin of (or contributing to) the troubles. the challenge the family doctor is facing is to be able in a consultation of 15-30 minutes to make the difference between serious and less serious behaviour troubles of the child. We are suggesting a first approach to a tool that would allow the front-line doctors to make an evaluation. More developed evaluation scales to be used by the family doctor will be the subject matter of future research work.


An NMR Spectroscopic Investigation of Aluminosilicate Gel in Alkali-Activated Fly Ash in a CO₂-Rich Environment.
The present study investigated aluminosilicate gel in alkali-activated fly ash exposed to a CO₂-rich environment by means of NMR spectroscopy. The alkali-activated fly ash was exposed to an atmospheric CO₂ concentration of 10% after curing at 80 °C initially for 24 h. Under high concentrations of CO₂, highly reactive components Na and Al, which completely reacted within the first few hours, were unaffected by carbonation, while Si, with relatively slower reactivity, behaved differently. Despite a lower degree of the reaction in the carbonated sample, the monomeric silicates rapidly became of higher polymerization, meaning that exposure to high concentrations of CO₂ caused Si to form a binding gel phase. Consequently, the carbonated sample possessed a higher amount of binding gel. The obtained results may be useful to understand the fundamental chemistry and behavior of aluminosilicate gel under high concentrations of CO₂.


The efficacy, safety, and tolerability of an estrogen-free oral contraceptive drospirenone 4 mg (24/4-day regimen) in obese users.
This study aimed to compare contraceptive efficacy and safety of drospirenone 4 mg in a 24/4-day regimen in nonobese and obese users and describe pharmacokinetics according to bodyweight. We analyzed data from three drospirenone 4 mg trials (2 European and 1 United States) to report outcomes in nonobese (body mass index <30 kg/m2) and obese (body mass index ≥30 kg/m2) users. We used data from the US trial to calculate the Pearl Index (pregnancies per 100 woman-years) in nonbreastfeeding participants aged ≤35 years at enrollment for confirmed pregnancies. We assessed safety outcomes from all trials based on reported treatment-emergent adverse events. We evaluated pharmacokinetics by bodyweight in the US trial. The three trials combined comprised 2152 nonobese and 425 obese participants, including 590 nonobese and 325 obese participants in the US trial. Eight nonobese and four obese participants had confirmed pregnancies in the US trial, resulting in Pearl Indices of 3.0 (95% CI: 1.3-5.8) and 2.9 (95% CI: 0.8-7.3), respectively. Two-hundred forty-four (11.3%) nonobese and 39 (9.2%) obese participants discontinued due to a treatment-emergent adverse event. The pharmacokinetic analysis included 814 participants with a median weight of 73 (interquartile range 61-89) kg and median plasma drospirenone exposure (AUC0-24ss) of 661.3 (interquartile range 522-828) ng∙h/mL. Changing bodyweight from the median to the fifth percentile (51 kg) or 95th percentile (118 kg) changed drospirenone exposure (AUC0-24,ss) by 22.2% and -23.6%, respectively. Drospirenone 4 mg demonstrated similar contraceptive efficacy for both nonobese and obese users despite a difference in exposure based on bodyweight. Our limited comparison between obese and nonobese users of drospirenone-only oral contraception demonstrated no evidence that efficacy or discontinuation for adverse events differs between groups. Serum drospirenone levels vary by bodyweight and may correlate with bleeding outcomes.


hecate, a zebrafish maternal effect gene, affects dorsal organizer induction and intracellular calcium transient frequency.
A zebrafish maternal effect mutation, in the gene hecate, results in embryos that have defects in the formation of dorsoanterior structures and altered calcium release. hecate mutant embryos lack nuclear accumulation of beta-catenin and have reduced expression of genes specific to the dorsal organizer. We found that hecate mutant embryos exhibit a nearly 10-fold increase in the frequency of intracellular Ca2+ transients normally present in the enveloping layer during the blastula stages. Inhibition of Ca2+ release leads to ectopic expression of dorsal genes in mutant embryos suggesting that Ca2+ transients are important in mediating dorsal gene expression. Inhibition of Ca2+ release also results in the expression of dorsal-specific genes in the enveloping layer in a beta-catenin-independent manner, which suggests an additional function for the Ca2+ transients in this cellular layer. The mutant phenotype can be reversed by the expression of factors that activate Wnt/beta-catenin signaling, suggesting that the Wnt/beta-catenin pathway, at least as activated by an exogenous Wnt ligand, is intact in hec mutant embryos. Our results are consistent with a role for the hecate gene in the regulation of Ca2+ release during the cleavage stages, which in turn influences dorsal gene expression in both marginal cells along the dorsoventral axis and in the enveloping layer.