Becoming a mother during the COVID-19 pandemic: The lived experience as told by birthing mothers: A qualitative study.
The aim of this study is to explore the lived experience of women who gave birth during the COVID-19 pandemic. Experiencing pregnancy during the Covid-19 pandemic exacerbates the risk of the onset of psychological problems. This is a descriptive, single-centre, qualitative study. The enrolment for data collection included childbearing mothers aged 18 years and over between November 2021 and April 2022. The researchers invited them to write about their personal experiences during the isolation period of the first pandemic wave. The descriptive phenomenological analysis of the data was carried out using the method described by Mortari. A total of 50 mothers were recruited, of whom 28 were primiparous (56.0%) and 22 multiparous (44.0%). From the analysis of the interviews, five main themes emerged that enclose the experience of both primiparous and multiparous mothers: 'The negative feeling: between loneliness, sadness and fear'; 'The comfort of being cared for: between humanity and competence'; 'Family proximity: between comfort and stress'; 'Symbiotic intimacy: bonding; Managing physical pain and consciousness of being resilient women'. The study showed that the discomfort associated with the absence of family support in the phase of labour and childbirth was compensated by the professionalism of the health staff and allowed new mothers to experience moments of great intimacy with the child. Such data could help create recommendations based on the assisted person's experiences to ensure that care is increasingly attentive and tailored to the needs of mothers and, thus, of children.


Optimizing the hospital discharge process to facilitate family-centered care for well newborns.
The perceptions of discharge readiness differ among caregivers and providers. An efficient planning process ensures timely attainment of discharge readiness. Our aim was to increase the percentage of discharge orders placed by 10 a.m. from 0.5% to 10% within 6 months thereby improving discharge readiness. We conducted a quality improvement initiative in the newborn nursery between March 2021 and June 2022 (n = 2307). We implemented a physician-led early discharge huddle and standardized the newborn screen (NBS) and circumcision process. By 10 a.m., our primary outcome measure, discharge orders, improved from 0.5 to 19%. Our process measures also increased. NBS specimens collected improved from 56 % to 98 % and circumcision rates increased from 66 to 88%. Balancing measure of postpartum hospital days remained stable. Optimizing family-centered discharge processes by addressing key drivers is essential and can be achieved without an increase in postpartum hospital days.


Dose- and time-dependent expression of transforming growth factor-beta 1 mRNA and protein in mouse epidermis and papillomas after repeated topical application of benzo[a]pyrene.
Topical weekly application of 64 micrograms of benzo[a]pyrene (BAP) for 4 wk induced transforming growth factor (TGF)-beta 1 mRNA in the epidermis of Swiss (ICR) mice, with a maximum at 6-12 h after the last treatment. The increase in TGF-beta 1 mRNA concentration was accompanied by an increase in immunohistochemically detectable intracellularly localized TGF-beta 1 protein in the suprabasal epidermis and by the appearance of extracellularly localized TGF-beta 1 in the basal layers. A dose rate of 16 micrograms/wk for 4 wk was unable to induce the same response. In contrast, after 20 weekly topical applications of 16 or 64 micrograms of BAP, an increase in TGF-beta 1 mRNA concentration and the appearance of extracellularly localized protein in the epidermis were observed. These changes in TGF-beta 1 expression were paralleled by changes in epidermal morphology. A similar group of animals treated with 4 micrograms of BAP/wk for 20 wk did not respond differently from untreated controls. Papillomas resulting from treatment with 16 or 64 micrograms of BAP/wk for 28 wk stained for intracellularly localized TGF-beta 1 predominantly in the differentiating and nondividing layers. Papillomas stained for extracellularly localized TGF-beta 1 solely in the less differentiated and dividing cells. These results suggest that tumorigenesis by BAP involves the induction of cumulative changes in epidermal TGF-beta 1 mRNA and protein concentrations as well as alterations in skin morphology associated with a tumor-promotion process.


Distinct modulation of group I ribozyme activity among stereoisomers of a synthetic pentamine with structural constraints.
Among cationic molecules that can modulate ribozyme activities, polyamines act as both activator and inhibitor of ribozyme reactions partly due to their structural flexibility. Restriction of structural flexibility of polyamines may allow them to emphasize particular modulation effects. We examined eight stereoisomers of a synthetic pentamine bearing three cyclopentane rings. In the reaction of a structurally unstable group I ribozyme, three stereoisomers exhibited distinct effects as inhibitor, an additive with a neutral effect, and also as an activator.


[The effect of the sperm count in the insemination dose and storage time on the fertilizing capability of the ejaculate of roosters].
Ejaculate of cooks was diluted by the Wishart and Davtjan diluents at a ratio of 1 : 1 and stored at a temperature of 4 degrees C during 2, 24, 48 and 72 hours before insemination of laying hens by the doses of 25, 50, 75, 100 and 150. 10(6) spermatozoa. With both diluents, egg fertility higher than 90 per cent was gained after 48 hours of keeping the ejaculate in sperm doses of 75 and 100 . 10(6) spermatozoa in the case of both diluents.


[Total hip prosthesis at or beforeSO years old - Personal series of 188 cases].
215 cases operated on by one surgeon have been studied. Several prosthesis types, cemented and cementless were used. 188 cases could be analyzed correctly for this study, and rewied after a variable period, from 3 to 25 years.The year 90 being considered as a turning point in the evolution of our ideas, we divided this study into two parts : before 1990 (156 cases), and after 1990 (32 cases).Before 1990: The loosening rate is rather high: 46 reoperations in 156 cases, with a few being examined with a first intention, which represents a 29% rate. For the primary implantation, the rate is close to 19%. The 8th year seems to be a decivise one with many reoperations. Another rise in the number of revisions appears near the 13th year -several reoperations before 5 years correspond to technical weaknesses. - The reoperation rate is higher for cemented prostheses (34% of two pole cementing). - It is lower for cementless prostheses, especially for the femoral component, but the use of screwed rings led to failures. - The group of metal-metal prosthesis (type Mc Kee - Farrar) shows a higher loosening rate (around 50%), but it's the oldest range (more than 15 years). One the other hand, excellent results have been underlined in these series of «Mc Kee-Farrar» prosthesis after more than 20 years (this analyzed later). - The number of reoperations for the bearing shows a clear improvement thanks to the use of 22 mm or 28 mm heads, and of ceramics (Alumina), for the femoral head. Our short experience of alumina-alumina bearings with cup cementing was not favorable at the beginning of the 80's. - The loosening risk appeared all the more marked when the person was young. - The oldest prostheses (more than 15 years), were reoperated in 50% of the cases. 10 years later, the rate is near 30%. For 50 cases, after a 5 to 10 year period following the first operation, it is still close to 10%. It concerns the latest prostheses, that are sometimes cementless. After 1990: The study period is not long but the results of a short series of 32 cases are extremely positive. Only one prosthesis was cemented: the 31 other cases were operated on without cement. Cups were impacted respecting the acetabulum's elasticity. The femoral components were customised prostheses (Computer Assited Design), or ESOP type prostheses, since the Modularity allows good adaptation to the femur. Two revisions were necessary, but were not related to the type of the prosthesis.Hence, our ideas changed in terms of hip prosthesis implantation under 50 years and we think today that we should use: - cementless prostheses, - which allow a good stress distribution, at the femoral and acetabular fixation, - with an improved bearing surface material and size, - particulary easy to implant and possibly easy to take out, since it may be necessary to change so young and active patient's prostheses some day.


The prognostic impact of pelvic lymph node metastasis and lymphovascular invasion on bladder cancer.
To present long-term results of a single-center series of patients undergoing bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer and to analyze the impact of pelvic lymph node metastasis and lymphovascular invasion on clinical outcome. Between 1986 and 2005 833 patients were treated with bilateral pelvic lymphadenectomy and radical cystectomy at our institution. 614 of them with valid clinical follow-up information and no neoadjuvant therapy could be evaluated. Disease-free and overall survival in the entire cohort was 56.7% and 49.5% at 5 years and 52.4% and 38.2% at 10 years, respectively. 28.1% of all patients had pelvic lymph node metastasis. We found organ-confined tumor stages (<or=pT2) in 43.8%. Patients with non-organ-confined tumor stages (>or=pT3) and positive pelvic lymph nodes had a significantly shorter overall survival than those without lymph node metastasis (P < 0.0001). In the subgroup of <or=pT2, the presence of pelvic lymph node metastasis did not show a statistically significant effect on overall survival (P = 0.618). The presence of lymphovascular invasion was associated with an impaired survival (P < 0.0001). In multivariate analysis, pathological tumor stage (P < 0.0001), lymph node stage (>or=pT3) (P = 0.004) and lymphovascular invasion (P = 0.001) were independent prognostic parameters. According to the present series, survival for patients with <or=pT2 does not depend on the lymph node stage. Lymphovascular invasion is an independent parameter of impaired survival and should be determined routinely in cystectomy specimens to identify patients, who may benefit from adjuvant systemic therapy.


Community-based Agency Delivery of Parent-Child Interaction Therapy: Comparing Outcomes for Children with and Without Autism Spectrum Disorder and/or Developmental Delays.
While externalizing behaviors are common among children with autism spectrum disorder (ASD), there is a shortage of specialist community-based clinicians to provide treatment. Parent-Child Interaction Therapy (PCIT), an intervention designed to reduce child disruptive behaviors, may be effective for families of children with ASD but has rarely been studied outside of university-based research settings. We examined the effectiveness of PCIT delivered for children with (N = 109) and without (N = 2,324) ASD/developmental delays (DD) across community-based agencies in Oregon. Findings revealed significant reductions in disruptive behavior and positive changes in the parent-child relationship in both groups. These findings support PCIT as an efficacious intervention for children with ASD/DD and demonstrate PCIT's promise in community-based agencies with non-specialized clinicians.


Absence of Chlamydia in trachomatous lacrimal sacs.
We performed lacrimal sac biopsies in 35 patients who underwent dacryocystohinostomies in Saudi Arabia. The nasolacrimal duct obstructions were presumably secondary to trachoma in 22 cases and unknown in the remaining 13 cases. Lacrimal sac specimens were submitted for routine histopathologic examination and the direct-smear fluorescent antibody test. All specimens were negative for chlamydia. Possible reasons for the low detection rate of chlamydia in the trachomatous group were the frequent finding of clinically inactive disease, common canalicular obstruction, and loss of the epithelial lining in the lacrimal sac.


The impact of nonmotor symptoms on quality of life in patients with Parkinson's disease in Taiwan.
The nonmotor symptoms (NMS) of Parkinson's disease (PD) are important factors for quality of life (QoL). Few studies on NMS have been conducted in Asian PD patients. Additionally, effects of anti-PD drugs on risk of NMS are still controversial. We therefore conducted this hospital-based cross-sectional study to examine the clinical factors, including concomitant anti-PD medication use, on the occurrence of NMS and QoL in Taiwanese PD patients. PD patients who received long-term follow-up in the movement disorders clinics were enrolled and received NMS questionnaire (NMSQuest) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). Spearman's rank correlation coefficient was checked for the correlation between clinical factors and NMSQT/PDQSI. Multiple linear regressions were applied to assess the influence of clinical factors on NMSQT/PDQSI. A total of 210 PD patients (mean age 66.1±9.86 years, Hoehn and Yahr stage 2.2±0.9) were included in this study. Up to 98% of patients reported at least one symptom of NMS. The most prevalent symptom was urinary complaints (56%), followed by memory/apathy (30%) and depression/anxiety (28%). The correlation between NMSQT and PDQSI was strong (r s=0.667), especially the item of depression/anxiety (r s=0.607). The regression model for NMSQT indicated that disease duration and severity, but not pharmacological therapy, were major predictors of NMS. Our data indicated a high prevalence rate of NMS in PD patients. Among symptoms of NMS, depression and anxiety had the greatest impact on QoL. Concomitant anti-PD medication use did not affect the occurrence of NMS and QoL.


Low-dose febuxostat exhibits a superior renal-protective effect and non-inferior safety profile compared to allopurinol in chronic kidney disease patients complicated with hyperuricemia: A double-centre, randomized, controlled study.
The present study compared the efficacy and safety of low-dose febuxostat versus allopurinol in chronic kidney disease (CKD) patients complicated with hyperuricemia (HUA). In this double-centre, randomized, controlled study, 120 CKD patients complicated with HUA were recruited and randomly assigned to low-dose febuxostat group (20 mg/day) or allopurinol group (200 mg/day) at 1:1 ratio. The serum creatinine (Scr), serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were measured at baseline (M0), month (M) 1, M3, and M6. Besides, the drug-related adverse events (AEs) were recorded. The primary outcome was the proportion of patients showing a > 10% decline in eGFR from M0 to M6. The eGFR level was increased at M6, but similar at M0, M1 and M3 in febuxostat group compared with allopurinol group. Notably, the proportion of patients with >10% decline in eGFR from M0 to M6 was decreased in febuxostat group compared with allopurinol group. However, there was no difference of Scr, SUA at M0, M1, M3 and M6 between febuxostat group and allopurinol group. Moreover, there was no difference of drug-related AEs between febuxostat group and allopurinol group. Further subgroup analysis exhibited that low-dose febuxostat presented superior effect on attenuating eGFR decline and lowering SUA level compared with allopurinol in CKD stage 3 subgroup, but not in CKD stage 2 subgroup. Low-dose febuxostat may exhibit a superior renal-protective effect, non-inferior SUA lowering ability and safety profile compared with allopurinol in CKD patients complicated with HUA.


Mutational analysis of the structure and function of GTP-binding proteins.
Structural, biochemical and molecular genetic studies of EF-Tu, p21ras and alpha s have begun to reveal the inner workings of the molecular machine used by these and other GTP-binding proteins. Further understanding of this molecular machine will ultimately come from crystal structures of the G protein alpha chains as well as from crystal structures of the GTP-bound forms of p21ras and EF-Tu. Mutational analysis will continue to add meaning to the static pictures provided by these crystal structures. Aside from their intrinsic biological interest, other reasons motivate our exploration of the GTP-dependent molecular machine used by GTP-binding proteins. Mutations or bacterial toxins cause disease by inhibiting the GTPase function of p21ras and alpha s. Other G protein alpha chains carry signals that regulate important cell functions, including proliferation. Malfunctions of these other G proteins are highly likely to cause disease. Applying our knowledge of p21ras and alpha s to these additional proteins may turn out to have significant practical consequences.


Rural diabetes prevalence quintuples over twenty-five years in low- and middle-income countries: a systematic review and meta-analysis.
To verify the assertions that diabetes pandemic may be spreading across rural parts of low- and middle-income countries (LMICs), we performed a systematic review of published studies reporting diabetes prevalence in rural parts of LMICs. Electronic databases (EMBASE and MEDLINE) were searched for papers published from 1990 to 2011. Two independent reviewers screened the articles using structured criteria for inclusion and performed full-text reviews. Pooled prevalence of diabetes was estimated using meta-analysis. Potential factors influencing the estimates were identified by meta-regression and used for sensitivity analyses. Rural prevalence of diabetes of LMICs was 5.6% (95% CI=4.6-6.6), and similar between men and women. This estimate remained robust in separate sensitivity analyses accounting for study quality, level of heterogeneity, age, and sex. In a multivariate meta-regression analysis, pooled prevalence varied by study year and region. Diabetes prevalence increased over time, from 1.8% (1.0-2.6) in 1985-1989, 5.0% (3.8-6.3) in 1990-1994, 5.2% (4.1-6.2) in 1995-1999, 6.4% (5.1-7.7) in 2000-2004, and to 8.6% (6.4-10.7) for 2005-2010 (p=0.001 for secular trend). Prevalence of diabetes in rural parts of LMICs has risen dramatically. As 55% of LMIC populations live in rural areas, this trend has enormous implications for the global burden of diabetes.


Could COVID-19 induce remission of acute leukemia?
COVID-19 viral pandemic caused many mortalities in cancer patients especially those with hematological malignancies. The immunological response to COVID-19 infection is responsible for the outcome of cases whether mild, severe or critical. Two cases presented with moderate COVID-19 viral infection, concomitant with acute myeloid leukemia and T acute lymphoblastic leukemia, respectively. Surprisingly, after the administration of COVID-19 supportive therapy, the cases showed disease remission after a follow-up period of 12 and 5 months, respectively. Additionally, the blast cells dropped to only 3% and 0% in the bone marrow aspirates of those two cases, respectively, after it was 30% in both cases at diagnosis. The immune response that emerged against COVID-19 infection could potentially produce anti-tumor immunity in some patients, or the virus may act as an oncolytic virus. However, further investigations are required to explain this phenomenon, which may help in finding a possible new targeted therapy for these cases.


Hepatic gene therapy for haemophilia B.
Early retroviral-mediated factor IX gene transfer into deficient dogs showed that constitutive expression of low levels of factor IX which has led to persistent improvement of clinically relevant parameters such as the WBCT and PTT. Conversely, in vivo adenoviral mediated delivery of the factor IX cDNA into hepatocytes of haemophilia B dogs has resulted in greater than wild-type plasma concentrations of clotting factor with complete, albeit transient normalization of haemostasis for a short time. An immune response directed against the vector transduced cells presented a big obstacle to clinical application. However, the future of gene therapy for factor IX deficiency appears bright with the development of fully adenoviral-gene deleted vectors, rAAV and lentiviral vectors which seem to offer safety, therapeutic levels of factor IX and relatively long-term persistence. We must proceed with cautious optimism as these vector systems undergo further scrutiny.


Topoisomerase II-associated protein PAT1H1 is involved in the root stem cell niche maintenance in Arabidopsis thaliana.
PAT1H1, one of the homologues of Topoisomerase II-associated protein, is involved in the maintenance of root stem cell niche through the interaction with NINJA. The root stem cell niche, which possesses four mitotically inactive quiescent cells (QC) and the surrounding mitotically active stem cells, is critical for root development in Arabidopsis thaliana. However, the molecular regulation of the maintenance of root stem cell niche identity is still not fully understood. Here we show that one of the homologues of Topoisomerase II-associated protein, here named as PAT1H1, could regulate root stem cell niche identity. The pat1h1 mutant showed higher frequency of QC cell division and root distal stem cell (DSC) differentiation. With a high expression in roots, PAT1H1 was found to interact with the jasmonic acid (JA) signalling negative regulator Novel Interactor of JAZ (NINJA) and thus regulate root DSC niche identity. Consistent with the active QC cell division, which rarely occurs in wild-type controls, the pat1h1 mutant displayed higher expression of CYCB1 in the root stem cell niche. Together our data reveals that PAT1H1 maintains root stem cell niche stability through the interaction with NINJA and the regulation of cell division.


Construction of MoS2 nanoarrays and MoO3 nanobelts: Two efficient adsorbents for removal of Pb(II), Au(III) and Methylene Blue.
Toxic heavy metal ions, valuable noble metal ions and organic dyes are significant concerns in wastewater treatment. In this work, MoO3 nanobelts (MoO3 NBs) prepared by solvothermal method and MoS2 nanoarrays (MoS2 NAs) constructed using MoO3 NBs precursor were proposed to effectively remove heavy/noble metal ions and organic dyes, such as Pb(II), Au(III) and Methylene Blue (MB). The two adsorbents exhibited the excellent adsorption capacity towards Pb(II), Au(III) and MB. The maximum removal capacity of Pb(II) and MB on MoO3 NBs was 684.93 mg/g and 1408 mg/g, respectively, whereas that of Au(III) and MB on MoS2 NAs was 1280.2 mg/g and 768 mg/g, respectively. Furthermore, the thermodynamic parameters were calculated from the temperature-dependent curves, suggesting that the removal of Pb(II) and Au(III) on both adsorbents was spontaneous and endothermic. The new adsorbents introduced here were high adsorption activity, ease of fabrication, high scalability, good chemical stability, great repeatability and abundant and cheap supply, which were highly attractive for wastewater treatment.


Analysis of the intensity of radio-frequency signals in intracranial ultrasonography of preterm infants.
The purpose of this study was to evaluate the usefulness of analysis of the intensity of radio-frequency (RF) signals in intracranial ultrasonography of preterm infants. Twenty neonatal infants admitted to the neonatal intensive care unit of our hospital were included in this study. Their gestational age was 33-35 weeks. The studies were performed with a System 5 ultrasound system with 3.0-and 5.0-MHz transducers. The transducer was placed on the anterior fontanel to obtain images. Regions of interest were determined based on B-mode images and were positioned at the thalamus, caudate nucleus, cerebral white matter, cerebellum, brain stem, and lateral ventricle. The software used for analysis of the RF signals was EchoMAT (Vingmed Ultrasound). The RF signals of the ventricle and the choroid plexus showed the lowest and the highest intensities, respectively. The intensities of the brain stem and vermis signals were the same, and were higher than the intensity of the cerebellar hemisphere. The thalamus and caudate nucleus showed macroscopically identical brightness levels; however, the intensity of the thalamus was lower than that of the caudate nucleus. The intensity of subependymal hemorrhage was lower than that of the caudothalamic groove. The intensity of subependymal cyst was the same as that of the lateral ventricle. The RF signal frequencies and intensities were distinctive in each tissue. The results of this study suggest that measurement of RF signal intensity may be useful to differentiate macroscopically similar lesions.


Anterior approach lumbar fusions cause a marked increase in thromboembolic events: Causal inferences from a propensity-matched analysis of 1147 patients.
Anterior lumbar fusions are thought to be associated with elevated venous thromboembolic event (VTE) rates, but the magnitude of this increase in VTE is not well described. The objective of this study was to quantify any increase in VTE caused by anterior approach lumbar fusion. 1147 consecutive lumbar fusions performed at our institution over a six-year period were identified, and clinical and demographic data were collected. K-nearest neighbor propensity score matching and propensity score adjusted regression were performed. Patients undergoing anterior versus posterior approach lumbar fusions were matched according to age, body mass index, sex, VTE history, estimated blood loss, length of surgery, transfusion, selection for postoperative intensive care unit (ICU) admission, comorbid disease burden, and use of chemoprophylactic anticoagulation. Anterior approach surgery (OR=4.29, p < 0.001), a history of VTE (OR=8.67, p < 0.001), age (OR=1.53, p = 0.014), length of surgery (OR=1.16, p = 0.044), and selection for postoperative ICU admission (OR=4.60, p = 0.005) were independently associated with VTE on multivariable regression. 1058 anterior or posterior approach fusion patients were matched. After matching, overall bias was reduced by 71.0 %, no covariates remained significantly different between groups, and propensity scores were well balanced between populations (Rubin's B≤0.25, 0.5 ≤Rubin's R≤2.0). Significantly more patients in the anterior group underwent lower extremity duplex ultrasonography (LED) (36.9 % vs. 14.8 %, OR=3.36 [2.38, 4.76], p < 0.0001), and a statistically insignificantly higher proportion of LEDs were positive among patients in the anterior group (23.2 % vs. 13.2 %, OR=1.99 [0.92, 4.25], p = 0.108). After matching, the rate of VTE was 8.6 % for the anterior group and 1.3 % for the posterior group, with anterior approach surgery causing an increase in VTE by 7.2 % (95 % CI [2.28 %, 12.16 %], p = 0.004). Among patients undergoing lumbar fusions, anterior approach surgery causes an increase in VTE by 7.2%, which is a multifold increase in the proportion of patients with thromboembolic complications.


Use of small-caliber polytetrafluoroethylene (Gore-Tex) grafts in microsurgical training.
We present the use of polytetrafluoroethylene (PTFE) graft material as a microsurgical training model that better simulates live vessel repairs. PTFE grafts have mechanical advantages over polyethylene or silicone tubing in that they better mimic the "feel" of an arterial vessel wall, thus allowing the student to perfect counterpressor maneuvers before attempting live vessel repairs. Saving the PTFE "repairs" for later comparison and study provides the student with positive feedback that is not possible with living models. This cost-effective model has helped to shorten our directed teaching program and has reduced the use of laboratory animals.


Effect of Sequential Intravenous and Oral Tranexamic Acid on Hemoglobin Drop After Total Knee Arthroplasty: A Randomized Controlled Trial.
Tranexamic acid (TXA) is typically discontinued on the day of total knee arthroplasty (TKA). However, bleeding may persist for several days. We sought to determine whether sequential administration of intravenous (IV) and oral TXA could reduce hemoglobin (Hb) drop more than IV TXA alone. We also wanted to determine whether the use of additional oral TXA increased the rate of complications of deep vein thrombosis (DVT) or symptomatic pulmonary embolism (PE). This prospective, randomized controlled trial included 141 patients. We compared the Hb drop, estimated blood loss (EBL), and transfusion rate of patients receiving IV TXA alone (group IV, n = 48) to those of patients who received IV TXA followed by oral TXA for 2 days (group 2D, n = 46) or 5 days (group 5D, n = 47). IV TXA was administered 10 minutes prior to the tourniquet release and 3 hours after the first IV TXA administration. Computed tomography (CT) was performed on postoperative day 6 to identify radiographic evidence of DVT. We also assessed the prevalence of symptomatic DVT and PE. There were no differences in maximal Hb drop, Hb drops measured at each time point, EBL, or transfusion rate among the 3 groups. The mean maximal Hb drop was 3.5 g/dL in group IV, 3.2 g/dL in group 2D, and 3.4 g/dL in group 5D. The mean EBL was 999.9 mL in group IV, 886.4 mL in group 2D, and 972.5 mL in group 5D. One patient in each group required a transfusion. There were no differences in the prevalence of radiographic evidence of DVT or symptomatic DVT. Symptomatic DVT occurred in 3 patients in group IV and 2 patients in group 5D. One patient in group IV developed a symptomatic PE. Although there was no increase in the complication rate, the sequential administration of oral TXA for up to 5 days after IV TXA did not decrease Hb drop. Therefore, our findings suggest that sequential use of oral and IV TXA is not recommended. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Protection with a recombinant Hc of Clostridium Botulinum neurotoxin serotype A from Escherichia coli as an effective subunit vaccine.
A recombinant Hc of Clostridium botulinum neurotoxin serotype A (AHc) was successfully expressed in Escherichia coli for use as an antigen, and the purified AHc was used to vaccinate mice and evaluate their survival against challenge with active botulinum neurotoxin serotype A. The mice, given twice or third subcutaneous vaccinations with a dosage of 1 microg AHc mixed with Freund adjuvant, were completely protected against an intraperitoneal administration of 1,000,000 50% lethal doses (LD(50)) of neurotoxin serotype A. Following the administration of AHc using alhydrogel adjuvant via the intramuscular route, a strong protective immune response was also elicited in the vaccinated mice. A dose-response was observed in protective efficacy with increasing AHc dosage and number of vaccinations. Mice that received two injections of >or= 0.2 microg and three injections of >or= 0.04 microg were completely protected when challenged with 100,000 LD(50) of neurotoxin serotype A. These results clearly suggest that the recombinant AHc highly expressed in Escherichia coli is very efficacious in protecting against challenge with active botulinum neurotoxin serotype A in mouse model and a good subunit candidate vaccine against botulinum neurotoxin serotype A for human use.


The Evolutionary History of Breast Cancer and Related Clones Is Revealed.
Driver events occur early in breast cancer evolution followed by emergence of a common ancestor.


[A new Typhloceras from Tunisia (author's transl)].
Typhloceras favosus benrachidi ssp. nova, parasitic on Apodemus sylvaticus ssp., can be separated from all others Typhloceras, by the morphology of segments VIII and IX in the male. Synonymy with T. f. asunicus Jordan, described on female only, is discuted.


Effect of polyethylene glycol on the in vitro production of L-lactate by rat liver under near physiological conditions.
The effect of polyethylene glycol (PEG) on lactate production from glucose by rat liver postmitochondrial fraction has been examined, using physiological concentrations of substrate and effectors. Addition of 10% polyethylene glycol (Mw 6000) resulted in an increase in lactate production, while the inhibition of lactate production by citrate and ATP was decreased. These results in conjunction with analysis of glycolytic intermediates suggest that PEG exerts its major action on phosphofructokinase.


Comparative efficacy of three regimens (cyclosporine, tacrolimus, and cyclophosphamide) combined with steroids for the treatment of idiopathic membranous nephropathy.
To investigate the efficacy of combined immunosuppressive regimens of cyclosporine (CsA), tacrolimus (TAC), or cyclophosphamide (CTX) combined with steroids in the treatment of idiopathic membranous nephropathy (IMN). A total of 150 biopsy-proven IMN patients were divided into three groups: CTX, TAC, and CsA groups (50 cases each). Patients received a selected regimen for 48 weeks. The efficacy (remission rate, 24h urinary protein, and serum albumin and creatinine) and safety (adverse events) profiles of administered regimens were evaluated at 12, 24 and 48 weeks. At 12 weeks, the response rates for CsA, TAC, and CTX groups were 14%, 50%, and 22%, respectively. This increased to 74%, 84%, and 82%, respectively at 48 weeks. During follow-up, 24h urinary protein significantly reduced from baseline in all regimens (P<0.05), while serum albumin increased in TAC and CTX groups after 12 weeks (P<0.05), and CsA group at 48 weeks (P<0.05). No significant changes in serum creatinine levels were noted in all three regimens (P>0.05). Safety was comparable in all groups, with lower respiratory tract infection being the most frequent adverse event. The combined regimens (i.e., TAC, CsA, and CTX) are effective in the treatment of patients with IMN at 48 weeks, while TAC and CTX might be more beneficial in terms of shortened time to remission and increased complete response rate.


The effect of person-centred communication on parental stress in a NICU: a randomized clinical trial.
To investigate the effect of the Guided Family-Centred Care intervention, developed by the lead author, on parental stress in a neonatal intensive care unit (NICU). Parents (n = 134) of infants born ≤34 weeks gestational age were randomly assigned to a standard care group (n = 60) or intervention group (n = 74) between April 2011 and August 2012. Guided Family-Centred Care components used were as follows: scheduled nurse-parent dialogues, semi-structured reflection sheets and person-centred communication. Parental stress was assessed at discharge using parent-reported outcomes on the Nurse Parent Support Tool and the Parental Stressor Scale: Neonatal Intensive Care Unit. The total stress scores reported by parents did not vary significantly between the intervention and standard groups, with a mean (SD) of 2.70 (0.67) versus 2.84 (0.71), respectively. However, the confidence interval included the prespecified clinical significance level. Subscale and Nurse Parent Support Tool scores did not differ between the groups. Overall, mothers reported more stress than fathers (p < 0.001). Our study was unable to demonstrate the effect of person-centred communication using the Guided Family-Centred Care intervention. It may be necessary to replicate the design to address the risk of contamination and add instruments sensitive to human interaction.


Accuracy of detection of myocardial viability and residual infarct vessel stenoses with rest Tl-201 and adenosine Tc-99m sestamibi imaging after coronary reperfusion in dogs with experimental acute myocardial infarction.
We sought to determine whether a dual-isotope imaging strategy (rest thallium 201/stress technetium 99m sestamibi) might be useful for assessing myocardial viability and residual ischemia in the infarct zone very early after reperfusion. Fifteen open-chest dogs had left anterior descending coronary artery occlusion for 60 minutes, followed by full reperfusion (group 1, n = 8) or reperfusion through a residual critical stenosis (group 2, n = 7). Tl-201 was injected at rest 45 minutes after reperfusion, and initial and 2-hour redistribution images were acquired. Tc-99m sestamibi was then injected during vasodilator stress, followed by imaging. Infarct size was similar in both groups (risk area, 21% +/- 4% vs 22% +/- 3%). Rest Tl-201 defect count ratios (left anterior descending coronary artery/left circumflex artery) were comparable (0.71 +/- 0.03 vs 0.74 +/- 0.02) and reflected infarct size. With vasodilation, Tc-99m sestamibi defect count ratio in group 1 (0.71 +/- 0.02) was comparable to rest Tl-201 and was significantly greater than in group 2 (0.62 +/- 0.02) with residual stenoses (P <.01). Although vasodilator Tc-99m sestamibi imaging unmasked the presence of residual stenoses, Tc-99m sestamibi uptake underestimated their functional severity (flow ratio, 0.38 +/- 0.03). Dual-isotope imaging very early after reperfusion may have limited utility for detecting residual stenoses in the infarct zone. Underestimation of the flow disparity by Tc-99m sestamibi may make the detection of stenoses more difficult, and impaired flow reserve after ischemic insult may complicate the detection of fully reperfused segments.


Long-term follow-up (9 to 20 years) after surgical closure of atrial septal defect at a young age.
To assess the long-term cardiac status after surgical closure of an atrial septal defect (ASD) at a young age, 104 of 135 children who consecutively underwent surgery (aged 0 to 14 years) at 1 institution between 1968 and 1980 participated in a follow-up study and underwent a complete cardiologic examination. Mean follow-up was 14.5 +/- 2.8 years. Most patients (87%) believed their health to be good or very good. At physical examination, all patients were in good health. Ninety-three patients (89%) were in sinus rhythm. Echocardiography showed that right ventricular dilatation was present in 27 patients (26%), 2 of whom had a residual ASD. Bicycle ergometry revealed that 88 patients (88%) had a normal exercise capacity. Both supraventricular and ventricular arrhythmias were observed in 67% of patients by 24-hour ambulatory electrocardiography, but only 3 (3%) had received antiarrhythmic medication, and 4 (4%) had needed a pacemaker. In the group of patients with right ventricular dilatation, the exercise capacity and prevalence of arrhythmias did not differ significantly from those in the group with a normal sized right ventricule. The outcome in patients with a secundum-type ASD was not different from that of those with a sinus venosus-type ASD. The finding of anatomic, functional or electrophysiologic abnormalities was not associated with a longer duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


Hyperthermia and the heat-shock proteins of HeLa cells.
When HeLa cells are subject to hyperthermia, the synthesis of specific heat-shock proteins (HSP) is induced under a variety of thermal conditions. HSP synthesis does not occur at temperatures above 43 degrees C but requires return to a culture temperature of 37 degrees C. Maximal induction appears to be achieved if a brief hyperthermia treatment (10 min, 45 degrees -46 degrees C) is followed by 2 h "development" at 37 degrees C. The induction process requires transcription but not DNA replication, and general cell metabolism is probably also required, as induction does not occur if the heat-treated cells are returned to 4 degrees (rather than 37 degrees C) for development. A small proportion of the HSPs of 72-74 Kd are found in nuclei, but do not appear to bind to DNA. The bulk of these proteins, as well as those at 100 Kd, are cytoplasmic, but none are preferentially associated with mitochondria. Increased synthesis of the 100Kd and 72-74 Kd HSPs was also triggered by pretreatment of the cells with 5 x 10(-5) M sodium arsenite.


The Promise of Predictive Biomarkers for Antipsychotic Efficacy: A Review of Peripheral microRNAs to Evaluate Schizophrenia Treatment Response.
With the ongoing evolution in genetics, recent evidence highlights the role of circulatory microRNA (miRNA) for schizophrenia. The objective of this article is to explore the role of blood/serum miRNA expression in schizophrenia management and to review the expression of different miRNAs before and after treatment with antipsychotics. miRNAs can help increase the accuracy of diagnosis, identify patients at risk of developing schizophrenia, and possibly predict drug response. The collective evidence from this review showed that several miRNAs are promising candidates for schizophrenia diagnosis, management, and prognosis.


Hepatic and cardiac necrosis in a patient with prostatic carcinoma given 6-aminocaproic acid.
The pathological findings in a case of prostatic carcinoma with fibrinolysin, treated with epsilon-aminocaproic acid, included hepatic and cardiac necrosis. The possibility is discussed that the latter lesions may be a complication of epsilon-aminocaproic acid therapy or produced by the proteolytic action of the fibrinolysin.


Reliable quantitation of β-hydroxyethoxyacetic acid in human urine by an isotope-dilution GC-MS procedure.
An analytical method for the determination of β-hydroxyethoxyacetic acid (HEAA), the main urinary metabolite of 1,4-dioxane was developed and validated. The presented method involves liquid-liquid extraction of HEAA from the urine samples, followed by silylation and subsequent analytical separation and detection using GC-MS. The method is characterized by its simple and fast sample preparation in combination with a robust chromatography. The use of isotope dilution analysis enables an efficient compensation of matrix related effects and analyte losses due to sample workup. The excellent reliability and reproducibility of the method is demonstrated by the good accuracy and precision data. Within-day precision and day-to-day precision ranged from 0.6 to 1.2% and 1.5 to 2.6%, respectively. The mean relative recovery of the method was found to be 98-101%. The LOD and LOQ of HEAA were determined to be 0.2mg/L and 0.6mg/L, respectively. In summary, the presented analytical method is well suited to be used for routine biomonitoring of occupational exposure to 1,4-dioxane.


Automated external defibrillators: to what extent does the algorithm delay CPR?
Maximizing cardiopulmonary resuscitation (CPR) during resuscitation may improve survival. Resuscitation protocols stack up to 3 shocks to achieve defibrillation, followed by an immediate postdefibrillation pulse check. The purpose of this study is to evaluate outcomes of rhythm reanalyses immediately after shock, stacked shocks, and initial postshock pulse checks in relation to achieving a pulse and initiating CPR. We conducted an observational study of patients with ventricular fibrillation treated by first-tier emergency medical services (EMS). We collected data from EMS, dispatch, and hospital records. Additionally, we analyzed automatic external defibrillator recordings to determine the proportion of cardiac arrest victims who were defibrillated and achieved a pulse according to shock number (single versus stacked shock), proportion of victims with a pulse during the initial postdefibrillation pulse check, and interval from initial shock to CPR. The study included 481 cardiac arrest subjects. Automatic external defibrillators terminated ventricular fibrillation with the initial shock in 83.6% (n=402) of cases. A second shock terminated ventricular fibrillation in an additional 7.5% (n=36) of cases, and a third shock terminated ventricular fibrillation in 4.8% (n=23) of cases. The initial sequence of 3 shocks failed to terminate ventricular fibrillation in 4.1% (n=20) of cases. In total, automatic external defibrillators performed 560 rhythm reanalyses during the initial shock sequence and delivered 122 "stacked" shocks. Termination of ventricular fibrillation was not synonymous with return of a pulse. The initial shock produced a pulse that was eventually detected in 21.8% (105/481) of cases. Stacked shocks produced a pulse in 10.7% (13/122) of cases. For the 24.5 % (n=118) of cases in which a pulse returned, the pulse was detected during the initial postshock pulse check only 12 times, or 2.5% of all cases. The median interval from initial shock until CPR was 29 (23,41) seconds. Rhythm reanalyses, stacked shocks, and postshock pulse checks had low yield for achieving or detecting return of a pulse. CPR was not initiated until 29 seconds after the initial shock.


Editorial Commentary: Posterior Cruciate Ligament Remnant Preservation Has Hypothetical Advantages.
Posterior cruciate ligament (PCL) remnant preservation has hypothetical advantages, but studies directly comparing PCL reconstruction with or without remnant preservation are not identified.


Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system.
Centralized outcome adjudication has been used widely in multicenter clinical trials in order to prevent potential biases and to reduce variations in important safety and efficacy outcome assessments. Adjudication procedures could vary significantly among different studies. In practice, the coordination of outcome adjudication procedures in many multicenter clinical trials remains as a manual process with low efficiency and high risk of delay. Motivated by the demands from two large clinical trial networks, a generic outcome adjudication module has been developed by the network's data management center within a homegrown clinical trial management system. In this article, the system design strategy and database structure are presented. A generic database model was created to transfer different adjudication procedures into a unified set of sequential adjudication steps. Each adjudication step was defined by one activate condition, one lock condition, one to five categorical data items to capture adjudication results, and one free text field for general comments. Based on this model, a generic outcome adjudication user interface and a generic data processing program were developed within a homegrown clinical trial management system to provide automated coordination of outcome adjudication. By the end of 2014, this generic outcome adjudication module had been implemented in 10 multicenter trials. A total of 29 adjudication procedures were defined with the number of adjudication steps varying from 1 to 7. The implementation of a new adjudication procedure in this generic module took an experienced programmer 1 or 2 days. A total of 7336 outcome events had been adjudicated and 16,235 adjudication step activities had been recorded. In a multicenter trial, 1144 safety outcome event submissions went through a three-step adjudication procedure and reported a median of 3.95 days from safety event case report form submission to adjudication completion. In another trial, 277 clinical outcome events were adjudicated by a six-step procedure and took a median of 23.84 days from outcome event case report form submission to adjudication procedure completion. A generic outcome adjudication module integrated in the clinical trial management system made the automated coordination of efficacy and safety outcome adjudication a reality.


Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase.
The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.46-12.09μM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered asa potential lead compound towards new drugs for the treatment of Alzheimer's disease.


Cerebral herniation from ventricular dilatation after craniectomy: a method of treatment.
Local cerebral herniation due to ventricular dilatation was observed in a patient who had had removal of a bone flap and whose dura had previously been left open. The explanation of this problem was suggested by experimental and clinical evidence relating the development of ventricular enlargement to loss of support of the brain. Such an explanation also suggested that head wrapping to buttress the brain and promote transependymal absorption of cerebrospinal fluid could reverse the condition. This treatment was employed with apparent success.


The volatiles of Chaerophyllum bulbosum L. ssp. bulbosum growing wild in Greece.
The analysis of the volatile fraction of Chaerophyllum bulbosum L. ssp. bulbosum (Apiaceae) growing wild in Greece, by capillary GC and GC-MS, demonstrated the presence of at least 34 constituents; 29 of which were identified, corresponding to 95% of the total. The following major components were found: apiol (37%), trimethyl-3,7,11-dodecatrien-1,6,10-ol-3 (8.5%), linalool (7.7%), myristicine (6.9%) and eugenol (5.8%).


Electrochemical investigations of immunologically reactive procainamide metabolites.
As a result of the implication of N-oxidized procainamide metabolites in drug-related lupus (DRL), the electrochemical behaviour of these compounds was investigated and a coulometric synthesis of the nitroso derivative developed using a previously described carbon packed bed bulk electrolysis flow cell. The electrochemical characterization of the parent p-substituted aromatic amine and the N-oxidized derivatives was achieved through systematic comparison with previously well described aromatic amine and nitro systems using cyclic voltammetry and liquid chromatography with electrochemical detection (LC-EC). Chromatographically assisted hydrodynamic voltammetry indicated current limiting plateau potentials of 0.45 and -0.2 V versus Ag/AgCl, respectively, for synthetically prepared procainamide hydroxylamine and electrolytically prepared nitrosoprocainamide. Reaction characterization and binding behaviour is described for each of the procainamide metabolites following in vitro incubations with cysteine, glutathione, ascorbic acid and mouse haemoglobin.


Oxidation Effects in Rare Earth Doped Topological Insulator Thin Films.
The breaking of time-reversal symmetry (TRS) in topological insulators is a prerequisite for unlocking their exotic properties and for observing the quantum anomalous Hall effect (QAHE). The incorporation of dopants which exhibit magnetic long-range order is the most promising approach for TRS-breaking. REBiTe3, wherein 50% of the Bi is substitutionally replaced by a RE atom (RE = Gd, Dy, and Ho), is a predicted QAHE system. Despite the low solubility of REs in bulk crystals of a few %, highly doped thin films have been demonstrated, which are free of secondary phases and of high crystalline quality. Here we study the effects of exposure to atmosphere of rare earth-doped Bi2(Se, Te)3 thin films using x-ray absorption spectroscopy. We demonstrate that these RE dopants are all trivalent and effectively substitute for Bi(3+) in the Bi2(Se, Te)3 matrix. We find an unexpected high degree of sample oxidation for the most highly doped samples, which is not restricted to the surface of the films. In the low-doping limit, the RE-doped films mostly show surface oxidation, which can be prevented by surface passivation, encapsulation, or in-situ cleaving to recover the topological surface state.


Intra-dorsolateral striatal AMPA receptor antagonism reduces binge-like alcohol drinking in male and female C57BL/6J mice.
The dorsolateral striatum (DLS) is involved in addiction, reward, and alcohol related behaviors. The DLS primarily receives excitatory inputs which are gated by post-synaptic AMPA receptors. We antagonized AMPA receptors in the DLS to investigate how such modulation affects binge-like alcohol drinking in male and female C57BL/6J mice and whether an associated alcohol drinking history alters dorsomedial striatum (DMS) and DLS AMPA receptor expression. We also investigated the effect of intra-DLS NBQX on locomotor activity and saccharin drinking in mice. Mice were allowed free access to 20% alcohol for two hours each day for a total of seven days. Mice received an intra-DLS infusion of one of four concentrations of NBQX (saline, 0.15, 0.5, or 1.5 μg/side), an AMPA receptor antagonist, immediately prior to alcohol access on day 7. Two-hour binge alcohol intakes, locomotor activity, and blood alcohol concentrations were determined. Intra-DLS NBQX reduced binge-like alcohol drinking in a U-shaped manner in male and female mice. Intake predicted blood alcohol concentration, and locomotor activity was not affected. In a follow up experiment, we assessed whether the most effective NBQX concentration for reducing alcohol consumption also reduced saccharin drinking, finding intra-DLS NBQX did not alter saccharin drinking in male and female mice. These data suggest that AMPA receptors in the DLS play a role in the modulation of binge-like alcohol drinking. These findings further validate the importance of the DLS for alcohol related behaviors and alcohol use disorder.


Sonic Hedgehog Signaling Affected by Promoter Hypermethylation Induces Aberrant Gli2 Expression in Spina Bifida.
GLI2 is a key mediator of the sonic hedgehog (Shh) signaling pathway and plays an important role in neural tube development during vertebrate embryogenesis; however, the role of gli2 in human folate-related neural tube defects remains unclear. In this study, we compared methylation status and polymorphisms of gli2 between spina bifida patients and a control group to explore the underlying mechanisms related to folate deficiency in spina bifida. No single nucleotide polymorphism was found to be significantly different between the two groups, although gli2 methylation levels were significantly increased in spina bifida samples, accompanied by aberrant GLI2 expression. Moreover, a prominent negative correlation was found between the folate level in brain tissue and the gli2 methylation status (r = -0.41, P = 0.014), and gli2 hypermethylation increased the risk of spina bifida with an odds ratio of 12.45 (95 % confidence interval: 2.71-57.22, P = 0.001). In addition, we established a cell model to illustrate the effect of gli2 expression and the accessibility of chromatin affected by methylation. High gli2 and gli1 mRNA expression was detected in 5-Aza-treated cells, while gli2 hypermethylation resulted in chromatin inaccessibility and a reduced association with nuclear proteins containing transcriptional factors. More meaningful to the pathway, the effect gene of the Shh pathway, gli1, was found to have a reduced level of expression along with a decreased expression of gli2 in our cell model. Aberrant high methylation resulted in the low expression of gli2 in spina bifida, which was affected by the change in chromatin status and the capacity of transcription factor binding.


Comparison of microdialysis with solid-phase microextraction for in vitro and in vivo studies.
Microdialysis (MD) and solid-phase microextraction (SPME) methods have been developed and compared through in vitro and in vivo studies. For in vitro study, both methods offered accurate and precise results for complex sample matrices by standard addition method. Compared to MD, the fully automated SPME procedure offered several advantages including high-throughput and more efficient sampling, less labor intensity, and capability for batch analysis. For in vivo study, although both techniques provided sampling with minimal perturbation to the system under study, SPME was more sensitive, precise and accurate, suitable for field sampling and had a wider application than MD. It demonstrated that SPME has the potential to replace MD for in vivo study.


Toxic effects of methyl methanesulfonate (MMS) on activated macrophages from chickens.
Adherent peritoneal exudate cells rich in macrophages were harvested from Cornell K-strain chickens 42 hr after i.p. stimulation with Sephadex G-50. Glass-adherent monolayers were obtained on coverslips and subjected to in vitro exposure to methyl methanesulfonate (MMS) at various doses for 1 hr. Solvent (0.17% ethanol final concentration) and sham (RPMI 1640 growth media) exposures were also performed. At selected times after exposure, the macrophages were analyzed for cell viability, adherence, DNA damage, and functional activity. Although MMS doses of 5 x 10(-3) M and 1 x 10(-3) M concentrations resulted in significant cytoxicity, 2 x 10(-4) M had no significant cytotoxic effect. However, this exposure resulted in DNA damage as measured by alkaline elution. Concomitant with the DNA damage was a significant decrease in the phagocytic activity of macrophages. Repair of MMS-induced DNA lesions in macrophages was indicated by a normal DNA alkaline elution profile 10 hr postrecovery. Functional activity of cells also returned to normal levels. In contrast, the incidence of Fc receptor-positive cells detected by rosetting increased immediately after MMS exposure, and phagocytosis of opsonized SRBCs was not affected by 2 x 10(-4) M MMS treatment. Similarly, MMS treatment did not alter the acid phosphatase activity of macrophages. However, bactericidal ability of MMS-treated macrophages for unopsonized Escherichia coli was significantly depressed. These results suggest that the avian macrophage is a useful target cell for examining possible relationships between genotoxic and immunotoxic effects of environmental mutagens.


Performance perception of Canadian dairy producers when transitioning to an automatic milking system.
Adoption of automated milking systems (AMS) has increased exponentially around the world in recent years. The objective of this observational study was to evaluate how producer perception of changes in cow-average milk yield and somatic cell count (SCC) compared with the actual changes in their herds after the introduction of AMS in Canadian commercial dairy herds. Data were collected (in 2014 and 2015) through a survey of 97 Canadian dairy herds that shifted to AMS from 2000 to 2014. Producers were asked their perception about milk yield and SCC changes (increase, decrease, or no change) after AMS introduction. Actual herd performance data were obtained from dairy herd improvement organizations. Differences between the 12-mo rolling herd-average milk yield (kg/cow per year) and SCC (cells/mL) at the closest test 2 yr after transitioning to AMS and at the last test before the transition were calculated and compared with the producer perception answers. After AMS adoption, milking herd size, milk yield, SCC, and number of AMS units per herd averaged (± standard deviation) 99.8 ± 54.4 cows, 9,619 ± 1,354 kg/cow per year, 248,825 ± 97,286 cells/mL, and 1.9 ± 1.1 units, respectively. On average, after AMS introduction, herd size, milk yield, and culling rate increased by 11.3 cows, 441 kg/cow per year, and 1.3%, respectively, and calving interval decreased by 7 d. For producers who perceived an increase, actual milk yield and SCC increases averaged (mean ± standard deviation) +534 ± 1,003 kg/cow per year and +56,679 ± 66,662 cells/mL, respectively. Alternatively, for producers who perceived a decrease, actual milk yield and SCC decreases averaged -984 ± 658 kg/cow per year and -26,976 ± 94,099 cells/mL, respectively. An actual milk yield change of +83.1 ± 1,113.3 kg/cow per year and an SCC change of +6,135 ± 72,609 cells/mL were observed in the herds in which the dairy producers perceived no change with the AMS introduction. Hence, dairy producers were, on average, able to discern their actual milk yield and SCC changes after AMS adoption. However, the proportions of dairy producers who accurately perceived their actual milk yield and SCC changes after AMS introduction were 39.4% for milk yield (increase: 36.3%; decrease: 100.0%; and no change: 45.5%) and 46.7% for SCC (increase: 50.0%; decrease: 39.0%; and no change: 54.1%). From these results, we concluded that several dairy producers distorted their actual milk yield and SCC changes or were not fully aware of those changes.


Cutting edge: invariant V alpha 14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model.
Airway hyperreactivity (AHR), eosinophilic inflammation with a Th2-type cytokine profile, and specific Th2-mediated IgE production characterize allergic asthma. In this paper, we show that OVA-immunized Jalpha18(-/-) mice, which are exclusively deficient in the invariant Valpha14(+) (iValpha14), CD1d-restricted NKT cells, exhibit impaired AHR and airway eosinophilia, decreased IL-4 and IL-5 production in bronchoalveolar lavage fluid, and reduced OVA-specific IgE compared with wild-type (WT) littermates. Adoptive transfer of WT iValpha14 NKT cells fully reconstitutes the capacity of Jalpha18(-/-) mice to develop allergic asthma. Also, specific tetramer staining shows that OVA-immunized WT mice have activated (CD69(+)) iValpha14 NKT cells. Importantly, anti-CD1d mAb treatment blocked the ability of iValpha14 T cells to amplify eosinophil recruitment to airways, and both Th2 cytokine and IgE production following OVA challenge. In conclusion, these findings clearly demonstrate that iValpha14 NKT cells are required to participate in allergen-induced Th2 airway inflammation through a CD1d-dependent mechanism.


Renal cell carcinoma: surgical management of regional lymph nodes and inferior vena-caval tumor thrombus.
Aggressive surgical management is the primary effective treatment of renal cell carcinoma, even with regional spread to lymph nodes or the vena cava. The extent of regional lymphadenectomy with radical nephrectomy and excision of vena-caval tumor thrombi are defined. In the future, with increasingly effective adjuvant therapy, these adjuncts to radical nephrectomy will continue to be important in the treatment of renal cell carcinoma.


Assessment of wing geometric morphometrics of urban Culex quinquefasciatus (Diptera: Culicidae) populations.
Culex quinquefasciatus is a cosmopolitan species distributed throughout tropical and subtropical areas of the world. The species is of great epidemiological importance as it is responsible for vectoring the causative agent of lymphatic filariasis and several arboviruses, including West Nile virus. Wing geometric morphometrics has been widely used to assess phenotypic variations in mosquito species. Here, we hypothesize that Cx. quinquefasciatus populations in urban parks in the city of São Paulo, Brazil, have been subjected to anthropogenic selective pressures that are responsible for driving their ecology and behavior. Mosquitoes were collected by CDC traps in five municipal parks in the city of São Paulo. Eighteen anatomical landmark coordinates on each female right wing were digitized. Canonical variate analysis, wireframe graphs, cross-validated reclassification tests and the neighbor-joining method were used to assess phenotypical dissimilarity in wing shape between populations. Centroid size was calculated to assess differences in wing size between populations, which can result from different environmental conditions during immature mosquito development. Moderately heterogeneous wing shape and wing size patterns were found in the populations analyzed, indicating that selective pressures in the urban environment are affecting the wing patterns of Cx. quinquefasciatus populations in the city of São Paulo, Brazil.


A new species of Isospora Schneider, 1881 (Apicomplexa: Eimeiriidae) from the grey-hooded attila Attila rufus Vieillot, 1819 (Passeriformes: Tyrannidae) on the Marambaia island, Brazil.
The New World tyrant-flycatcher (Tyrannidae) Attila rufus (Vieillot, 1819) is commonly known as grey-hooded attila or 'capitão-de-saíra' in Brazil (Sick 1997; CBRO 2014). This species has a wide distribution and their population trends appear to be stable; therefore, it is least concern according to IUCN (2015) criteria.


The role of fibroblast activation protein in progression and development of osteosarcoma cells.
To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.


A Prospective Study of the Size, Number and Histopathology of New and Recurrent Bladder Tumors.
We prospectively registered the grade, stage, number and size of bladder tumor recurrences as to our knowledge this has not yet been done. New tumors were included in the study for comparative purposes. All 581 transurethral resections, random biopsies and fulgurations for a suspected bladder tumor were prospectively registered during a 15-month period at a single institution. Tumor size was determined using the size of the resection loop or biopsy forceps as a reference. Of all suspected new and recurrent bladder tumors 22% were benign or inflammatory lesions. A total of 167 patients with a new urothelial tumor and 214 recurrences in 166 patients were registered during the study period. Compared to new tumors, recurrences were more often noninvasive (88% vs 67%, p <0.001), more often 10 mm or less in diameter (63% vs 18%, p <0.001) and more often multifocal (55% vs 38%, p <0.01). New and recurrent tumors had a median size of 20 and 8 mm, respectively. The absolute majority of suspected bladder tumor recurrences are benign or low grade noninvasive malignant tumors and are less than 10 mm in diameter. This finding suggests that there is great potential for cost reductions when a significant proportion of patients with suspected recurrences after treatment of low grade tumors could undergo biopsy and fulguration using local anesthesia in the office instead of general anesthesia.


Topical anesthesia versus regional anesthesia for cataract surgery: a meta-analysis of randomized controlled trials.
To examine possible differences in the clinical outcomes of topical anesthesia (TA) and regional anesthesia including retrobulbar anesthesia (RBA) and peribulbar anesthesia (PBA) in phacoemulsification. Systematic review and meta-analysis. Patients from previously published randomized controlled trials (RCTs) of phacoemulsification under TA and RBA/PBA reporting clinical outcomes. A comprehensive literature search was performed according to the Cochrane Collaboration method to identify RCTs that compare TA and RBA/PBA in phacoemulsification. Primary outcome parameters investigated were pain score during and after surgery, intraoperative difficulties and inadvertent ocular movement, intraoperative necessity to administer additional anesthesia, and patient preference. Secondary outcome parameters investigated were postoperative visual acuity, anesthesia-related complications, intraoperative complications, and severe local or systemic complications. Fifteen studies were identified and analyzed to compare TA (1084 eyes) with RBA/PBA (1121 eyes) in phacoemulsification. Data synthesis showed that intraoperative and postoperative pain perception was significantly higher in the TA group (P < 0.05). The TA group showed more frequent inadvertent ocular movement (P < 0.05) and a greater intraoperative need for supplementary anesthesia (P = 0.03). There was no statistically significant difference between the 2 groups in intraoperative difficulties as assessed by the surgeons (P > 0.05). Patients significantly preferred TA (P < 0.00001). The RBA/PBA group had more frequent anesthesia-related complications, such as chemosis, periorbital hematoma, and subconjunctival hemorrhage (P < 0.05). There was no statistically significant difference in surgery-related complications (P > 0.05). Compared with RBA/PBA, TA does not provide the same excellent pain relief in cataract surgery; however, it achieves similar surgical outcomes. Topical anesthesia reduces injection-related complications and alleviates patients' fear of injection. The choice of TA is not suitable for patients with a higher initial blood pressure or greater pain perception.


[Clinical study of sudden deafness treated with method of integrated traditional Chinese and Western medicine].
To explore the mechanisms of sudden deafness treated with integrated traditional Chinese and Western medicine (TCM-WM). One hundred and forty-six patients suffering from sudden deafness were divided into two groups, 64 cases of treated group treated with the method of integrated TCM-WM and the other 82 cases treated with Western medicine alone for control. The total effective rate of the treated group was 92.19%, that of the control group was 75.61%. The difference between two groups was significant, P < 0.01. The integrated method is very effective in treating sudden deafness. Its mechanism might be: (1) Decrease the blood viscosity and increase the red blood cell's tenacity, so that the blood stream is passing through unimpeded. (2) Decrease the plasma TXA2 level and increase the PGI2 level, keep the blood supply for inner ear. (3) Increase the activity of SOD and clear away the free radicals so as to reduce the damage of inner ear.


Fascicular conduction disturbances after coronary artery bypass surgery: a review with a meta-analysis of their long-term significance.
Fascicular conduction abnormalities are frequently reported following adult cardiac surgery, but their pathogenesis and long-term outcomes remain unclear. In this article, we review the epidemiological features, pathogenesis, diagnosis, and management, and the short-term and long-term significance of fascicular conduction abnormalities following coronary artery bypass graft (CABG) surgery, based on data from 30 studies. Conduction disturbances have an incidence of 3.4% to 55.8% after CABG surgery, the most common being right bundle branch block (RBBB). RBBB is usually transient and benign. Although a slew of factors have been implicated in the pathogenesis of fascicular conduction disturbances, the two most important factors are myocardial ischemia and type of cardioplegia. While a 12-lead electrocardiogram is the gold standard for diagnosis, additional tests such as myocardial enzymes or echocardiography may have additional diagnostic and prognostic value. Short-term prognosis after RBBB is good, but its impact on long-term survival is unclear. We conducted a meta-analysis, the first of its kind in this area, using long-term survival data from five studies. There was no difference in long-term survival between patients who developed conduction disturbances after CABG surgery, and those who did not, indicating a benign influence of conduction disturbances on long-term survival, and the lack of the necessity for monitoring or pacing. While the older literature reported an adverse impact of fascicular conduction disturbances on long-term survival, the more recent studies report a substantially reduced mortality after CABG surgery, despite a higher incidence of conduction disturbances, pointing to the effect of improved surgical techniques.


Prefrontal cortex activity related to abstract response strategies.
Many monkeys adopt abstract response strategies as they learn to map visual symbols to responses by trial and error. According to the repeat-stay strategy, if a symbol repeats from a previous, successful trial, the monkeys should stay with their most recent response choice. According to the change-shift strategy, if the symbol changes, the monkeys should shift to a different choice. We recorded the activity of prefrontal cortex neurons while monkeys chose responses according to these two strategies. Many neurons had activity selective for the strategy used. In a subsequent block of trials, the monkeys learned fixed stimulus-response mappings with the same stimuli. Some neurons had activity selective for choosing responses based on fixed mappings, others for choosing based on abstract strategies. These findings indicate that the prefrontal cortex contributes to the implementation of the abstract response strategies that monkeys use during trial-and-error learning.


Ecophysiological studies of Sonoran Desert plants : III. The daily course of photosynthesis for Acacia greggii and Cercidium microphyllum.
The gas exchange and water relations of two Sonoran Desert plants are compared during contrasting periods of water and heat stress. Photosynthesis of Acacia greggii, a winter deciduous shrub, and Cercidium microphyllum, a chlorophyllous stemmed tree, show a moderate correlation with dawn plant water potential. For both species a relationship between stomatal conductance and dawn plant water potential was not apparent, although A. greggii demonstrated a greater overall stomatal conductance. This affected a greater daytime decrease in plant water potential at all levels of water stress and suggests A. greggii is less sensitive to water stress. Our results suggest the lower limit for gross photosynthesis occurs when dawn plant water potentials are less than -44 and -31 bars for the shrub and tree species, respectively. During periods of extreme water and heat stress the photosynthetic capacity of both species is regulated more by mesophyll than stomatal conductance. However, partial stomatal closure causes plant water potential to increase during the day and exceed dawn values. During periods of minimal water and heat stress the daily course of photosynthesis parallels the change in stomatal conductance and irradiance. Maximum gross photosynthesis rates are nearly three-fold higher than the rates observed during periods of stress, with those of A. greggii generally greater than the rates observed in plants of C. microphyllum.


Monosomy for 21pter-q21: case report and assignment of a DNA clone (Fr8-77) to the deleted segment.
A 4-month-old Japanese girl with partial monosomy 21 was described. The patient has craniofacial anomalies, a short neck, wide-set nipples, anal atresia, deformed feet, hypertonia, intrauterine growth retardation, and mental deficiency. RFA- and high-resolution GTG-banding chromosome analyses, and Southern- and slot-blot analyses interpreted her karyotype as 45,XX,-2,-21, + der(2)t(2:21)(q37.3;q22.1). The origin of this de novo translocation ascertained by analyses with both QFQ-heteromorphisms and a Fr8-77/BamHI RFLP was paternal. Comparison of the patient with previously reported patients confirmed that her manifestations are consistent with those of monosomy for 21pter-q21. Based on the results of molecular analyses on the present patient, a DNA clone, Fr8-77 (D21S82), was assigned to pter-q21.


Activation-induced cytidine deaminase expression in follicular lymphoma: association between AID expression and ongoing mutation in FL.
Activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) gene. AID has been reported to be specifically expressed in the germinal center (GC). Follicular lymphoma (FL) cells are known to be exposed to GC reaction, as characterized by a high degree of SHM with some heterogeneity in terms of intraclonal microheterogeneity and antigen selection. The heterogeneity of SHM pattern in FL intrigued us to investigate the AID expression. AID expression was investigated in 19 FL materials consisting of 15 cases of FL fresh cells and four cell lines. In all, 10 fresh cells and three cell lines expressed AID, but the others did not. SHM was investigated in 12 fresh cells and four cell lines. The ongoing mutation was significantly different between AID-positive and AID-negative FL fresh cells (unpaired Student's t-test, P=0.047). Ongoing mutation was not seen in any of the cell lines. AID expression was associated with the ongoing mutation in FL fresh cells (two-tailed Pearson's coefficient correlation, r=0.899, P=0.01). The switch off of AID expression may start in the B-lineage differentiation stage counterpart of FL after optimizing SHM, indicated by the cessation of the ongoing mutation in AID-negative FL fresh cells.


Putative type VI secretion systems of Vibrio parahaemolyticus contribute to adhesion to cultured cell monolayers.
Analysis of the genome sequence of Vibrio parahaemolyticus reveals two IcmF family genes in putative type VI secretion system (vpT6SS) clusters in chromosomes 1 (icmF1) and 2 (icmF2). The icmF1 gene is present in majority of clinical isolates (87.5 %), but has a low fraction (25.0 %) in environmental isolates. However, icmF2 is contained in all strains of both clinical and environmental sources. Deletion of either icmF1 or hcp1 significantly reduced bacterial adhesion to Caco-2 cells or HeLa monolayers. However, the ΔicmF2 and Δhcp2 mutants showed decreased adhesion only to HeLa monolayers. Western blot analysis showed that Hcp2 was present both in the supernatant and pellet samples in the wild-type strain, but only in the pellet of the ΔicmF2 mutant, indicating that Hcp2 is a translocon of T6SS2. Although vpT6SS1 might be functional in cellular adhesion, the putative translocon Hcp1 was not detectable. Quantitative PCR revealed 10-fold and 17-fold less transcripts of hcp1 and icmF1 mRNA than those of hcp2 and icmF2 accordingly. Thus, we postulate that the putative vpT6SS systems contribute to adhesion of V. parahaemolyticus to host cells.


A comparison of the carrageenan edema test and ultraviolet light-induced erythema test as predictors of the clinical dose in rheumatoid arthritis.
Twelve non-steroidal anti-inflammatory agents (NSAI's) and one steroidal anti-inflammatory agent, dexamethasone, were examined in the carrageenan edema test (CET) in the rat and in the ultraviolet light-induced erythema test (UVE) in the guinea pig to evaluate the correlation between those models of inflammation and the clinical dose of the NSAI's in the treatment of rheumatoid arthritis. The regression of the logarithm of the clinical dose with the logarithm of the ED50 for UVE gave a slope of 0.54 implying a non-parallelism of assays and a difference in mechanism. Dexamethasone failed to inhibit the UVE thereby corroborating this point. The parallelism of the logarithm of the clinical dose with the logarithm of the ED50 for the CET was substantially better (slope = 0.86). Dexamethasone was active in CET and its dose would be predicted by the CET regression. When only one variable was used for a prediction, log(CET) was a better predictor of log (clinical dose) than log(UVE). Standard methods for best regression selection indicated that even when both predictor variables were considered, log(CET) alone gave the best regression equation for predicting clinical dose. The view that inhibition of prostaglandin biosynthesis is the primary anti-inflammatory mechanism of NSAI's in rheumatoid arthritis is discussed in terms of these findings.


Left ventricular function in mild hypertension after adrenergic blockade.
We previously used the Doppler transmitral flow velocity ratio A/E (A = late ventricular filling peak velocity; E = early ventricular filling peak velocity) and the age-adjusted ratio A/E/Age to detect left ventricular filling abnormalities in untreated mild hypertension. This study is a double-blind assessment of the effect of combined alpha- and beta-blockade (labetalol) and beta-blockade alone (atenolol) on left ventricular filling in mild hypertension. Twenty-seven patients blindly randomized to labetalol (12 patients) and atenolol (15 patients) treatment completed the echocardiographic and Doppler studies. Clinical and echo-Doppler data obtained at baseline and 6 weeks after initiation of therapy showed no difference between the two groups for age (49 +/- 10 vs 46 +/- 10 years), mean blood pressure (before therapy, 118 +/- 9 vs 117 +/- 8 mm Hg; after therapy, 108 +/- 12 mm Hg), left ventricular dimensions, wall thickness, systolic function, and mean late filling velocity A. There was no significant change in left ventricular mass and mass index with labetalol (left ventricular mass, 211 +/- 36 vs 216 +/- 38; mass index, 110 +/- 17 vs 112 +/- 16) or atenolol (245 +/- 41 vs 271 +/- 65; 120 +/- 18 vs 130 +/- 35). The mean velocity E, A/E, and A/E/Age ratios significantly improved with labetalol (p less than 0.05) but did not change significantly with atenolol. The improvement in A/E and A/E/Age ratios was primarily due to an increase in early filling velocity E.(ABSTRACT TRUNCATED AT 250 WORDS)


Postabortal insertion of IUD.
During 1983, 823 first trimester therapeutic abortions were performed at the University Hospital of Trondheim, Norway. Of these patients, 229 had an IUD inserted at the end of the operative procedure. The remaining 594 patients served as controls. Microbiological samples were taken from the cervix and the urethra. No prophylactic antibiotic treatment was given. Compared to the group of patients not selecting an IUD as contraception, there was no increase in readmission frequency due to immediate postabortal IUD insertion. There were no positive cultures for N. gonorrhoeae, and the relative number of positive chlamydia cultures was the same in both groups. In the IUD group we did not find any increase in complications such as bleeding, pain, perforations or infections. During the first year of observation, 3 pregnancies occurred in the IUD group, giving a Pearl index of 1.3 pregnancies per year. Continuation rate after one year was 72.8%. We recommend immediate postabortal insertion of an IUD after first trimester abortion as a practical and safe procedure.


A study of the distribution patterns and levels of Salmonella enteritidis in the immune organs of ducklings after oral challenge by serovar-specific real-time PCR.
The objective of this study was to understand the distribution patterns and levels of Salmonella Enteritidis (SE) in the immune organs of ducklings after oral challenge. We conducted serovar-specific real-time polymerase chain reaction (PCR) for SE to detect the genomic DNA of SE in the blood and immune organs, including the bursa of Fabricius, thymus, spleen, and Harderian gland, from ducklings after oral challenge at different time points. The results showed that SE was consistently detected in all the samples. The Harderian gland and spleen tested positive at 8 hr postinoculation (PI). The organism was detected in the blood, bursa of Fabricius, and thymus at 10 hr PI. The copy number of SE DNA in each tissue reached a peak at 24-36 hr PI. The spleen, blood, and Harderian gland contained high concentrations of SE, whereas the thymus and bursa of Fabricius had low concentrations. SE populations began to decrease and were not detectable at 2 days PI, but they were still present up to 9 days PI in the spleen, without producing any apparent symptoms. To validate these results, the indirect immunofluorescent antibody (IFA) technique was used, and the IFA results were similar to those of the fluorescent quantitative-PCR. In conclusion, the results provided insight into the SE life cycle in the immune organs; furthermore, the Harderian gland and spleen were determined to be the primary sites of invasion among the immune organs of normal ducklings after oral SE challenge. This study will help in understanding the pathogenesis of SE infection in vivo and may help in the development of a live Salmonella vaccine in the future.


Antigenic structure and variation of canine parvovirus type-2, feline panleukopenia virus, and mink enteritis virus.
The antigenic structure and variation of canine parvovirus type-2 (CPV), feline panleukopenia virus (FPV), mink enteritis virus (MEV), and a closely related virus of raccoons (RPV) was investigated using a panel of 13 monoclonal antibodies (mAb) formed against CPV and 8 mAb formed against FPV. Each mAb both neutralized and inhibited the hemagglutination of the homologous virus. All mAb tested immunoprecipitated the two capsid proteins. Five mAb were specific for the CPV isolates and one reacted with the FPV, MEV, and RV isolates, but not the CPV. Another mAb reacted only with certain FPV and MEV isolates. The remaining 14 mAb reacted with most parvoviral isolates from the four animal species. Antigenic variation was observed both within and between the parvovirus isolates from each species. The 12 MEV isolates could be grouped into three antigenic types based on their reactivity with the panel of mAb. Antigenic variants of either CPV or FPV were readily selected with several mAb. Analysis of these variant viruses by direct serological tests and competition radioimmune assays between different mAb revealed that the capsid surface contained at least two determinants, each being comprised of many different but overlapping epitopes.


Human intestinal organoid models for celiac disease research.
Celiac disease pathogenesis, in addition to immune cell component, encompasses pathogenic events also in the duodenal epithelium. In celiac disease patients, exposure to dietary gluten induces drastic changes in epithelial differentiation and elicit cellular response to inflammatory cytokines. The autoantigen in celiac disease, transglutaminase 2 (TG2) enzyme, has been also suggested to play its pathogenic gliadin deamidation event in the intestinal epithelium. Therefore in vitro epithelial cell-line models have been exploited in the past to study these pathogenic mechanisms, but they are hampered by their simplistic nature lacking proper cell-type composition and intestinal environ. Moreover, these cell models harbor many cancer-related mutations in tumor suppressor genes making them unsuitable for studying cell differentiation. Intestinal organoids provide a near-native epithelial cell model to study pathogenic agents and mechanisms related to celiac disease. Here we describe protocols to initiate and maintain celiac patient-derived organoid cultures and how to grow them in alternative ways allowing their exploitation in different kind of experiments.


Uncertainties in CT-based radiation therapy treatment planning associated with patient breathing.
To evaluate uncertainties associated with treatment-planning computed tomography (CT) data obtained with the patient breathing freely. Patients with thoracic or abdominal tumors underwent a standard treatment-planning CT study while breathing quietly and freely, followed by CT scans while holding their breath at normal inhalation and normal exhalation. Identical treatment plans on all three CT data sets for each patient pointed out differences in: (a) radiation path lengths; (b) positions of the organs; (c) physical volumes of the lung, liver, and kidneys; (d) the interpretation of plan evaluation tools such as dose-volume histograms and normal tissue complication probability (NTCP) models; and (e) how well the planning CT data set represented the average of the inhalation and exhalation studies. Inhalation and exhalation data differ in terms of radiation path length (nearly one quarter of the cases had path-length differences > 1 cm), although the free breathing and average path lengths do not exhibit large differences (0-9 mm). Liver and kidney movements averaged 2 cm, whereas differences between the free breathing and average positions averaged 0.6 cm. The physical volume of the liver between the free breathing and static studies varied by as much as 12%. The NTCP calculations on exhale and inhale studies varied from 3 to 43% for doses that resulted in a 15% NTCP on the free-breathing studies. Free-breathing CT studies may improperly estimate the position and volume of critical structures, and thus may mislead evaluation of plans based on such volume dependent criteria such as dose-volume histograms and NTCP calculations.


Afferent fibers to rat cingulate cortex.
Afferent fibers to the rat cingulate cortex were studied by the retrograde labeling technique using horseradish peroxidase-wheat germ agglutinin conjugate as the tracer. The results showed that the posterior cingulate cortex, but not the anterior, received input from the anterior dorsal and anterior ventral nuclei of the anterior thalamic group of nuclei (part of the so-called limbic thalamus), and from the subicular complex. The anterior cingulate cortex, but not the posterior, received input from the mediodorsal and ventral thalamic nuclei. Both posterior and anterior cingulate cortex received input from the hippocampus pars anterior; claustrum; globus pallidus; nucleus of the diagonal band of Broca (a particularly reliable source of afferent fibers); anterior medial, lateral, rhomboid, and reuniens nuclei of the thalamus; region of the medial forebrain bundle; periventricular nucleus of the hypothalamus; the dorsal and median raphe; and the locus ceruleus. Corticocortical projections were seen anterior, posterior, and lateral to the injection site, and in the homologous contralateral cingulate cortex. The results demonstrate a prominent source of cingulate afferent fibers from the subicular complex, provide evidence for a functional division of anterior and posterior cingulate cortices in the rat, and provide information about the relative anatomic importance of cingulate afferent fibers from those different regions.


Distribution of vitamin B12 R-binder in lung tumors. Implications for cell differentiation.
Expression of vitamin B12 R-binder, a specific binding protein for vitamin B12, was studied immunohistochemically in normal lung tissues and 107 lung tumors of various types. In normal tissues, vitamin B12 R-binder (R-binder) expression was restricted to the mucous cells of bronchial or bronchiolar epithelium and submucosal glands as well as to nonciliated bronchiolar (Clara) cells. Among lung carcinomas, 38% of squamous cell carcinomas, 42% of adenocarcinomas and 23% of large cell carcinomas showed positive staining for R-binder whereas small cell carcinomas did not. These findings offer the possibility that a majority of the histologic types of lung carcinoma have common histogenetical characteristics with mucous or Clara cells. Of the bronchial gland tumors, R-binder could be detected in a mucoepidermoid carcinoma but not in adenoid cystic carcinomas. Epithelial components in both pulmonary blastomas and hamartomas showed a reactivity for R-binder, suggesting that these tumors contained components composed of cells with bronchiolar cell differentiation. The immunohistochemical examination of lung tumors, using anti-R-binder antibody, may have some implications in the cell differentiation of lung tumors.


Influence of load of hepatitis A virus on disease severity and its relationship with clinical manifestations in patients with hepatitis A.
The purpose of the present study was to investigate the influence of viral load on disease severity and analyze the possible relationship of the load of hepatitis A virus (HAV) with disease severity and laboratory findings. Fifty-eight patients diagnosed with acute hepatitis A were used in the current study, of whom 12 patients progressed to severe acute hepatitis (s-AH) defined on the basis of a prothrombin time (PT) of <40% and 46 patients were diagnosed as having mild acute hepatitis (m-AH). The load of HAV was measured with real-time polymerase chain reaction. Peak viral load showed a significant correlation with alanine aminotransferase (ALT) (r = 0.363, P = 0.0048) and PT levels (r = -0.330, P = 0.0110). In terms of disease severity, there was a significant correlation with ALT (r = 0.462, P = 0.0012) and PT levels (r = 0.400, P = 0.0059) in the m-AH group, but not in the s-AH group. A significant positive correlation of peak viral load with the C-reactive protein level (r = 0.270, P = 0.0400) and a significant negative correlation of peak viral load with the platelet count (r = -0.313, P = 0.0015) was also found. The load of HAV was closely correlated with liver damage and disease severity in m-AH, but not in s-AH. The load of HAV was also closely associated with the increase in C-reactive protein level and enhancement of thrombocytopenia.


Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model.
The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar(®) (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar(®) at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar(®) were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes.


Examining emergency department inequities: Descriptive analysis of national data (2006-2012).
Internationally, Indigenous and minoritised ethnic groups experience longer wait times, differential pain management and less evaluation and treatment for acute conditions within emergency medicine care. Examining ED Inequities (EEDI) aims to investigate whether inequities between Māori and non-Māori exist within EDs in Aotearoa New Zealand (NZ). This article presents the descriptive findings for the present study. A retrospective observational study framed from a Kaupapa Māori positioning, EEDI uses secondary data from emergency medicine admissions into 18/20 District Health Boards in NZ between 2006 and 2012. Data sources include variables from the Shorter Stays in ED National Research Project database and comorbidity data from NZ's National Minimum Dataset. The key predictor of interest is patient ethnicity with descriptive variables, including sex, age group, area deprivation, mode of presentation, referral method, Australasian Triage Scale and trauma status. There were a total of 5 972 102 ED events (1 168 944 Māori, 4 803 158 non-Māori). We found an increasing proportion of ED events per year, with a higher proportion of Māori from younger age groups and areas of high deprivation compared to non-Māori events. Māori also had a higher proportion of self-referral and were triaged to be seen within a longer time frame compared to non-Māori. Our findings show that there are different patterns of ED usage when comparing Māori and non-Māori events. The next level of analysis of the EEDI dataset will be to examine whether there are any associations between ethnicity and ED outcomes for Māori and non-Māori patients.


Rethinking Medicare Payment Adjustments for Quality.
Payment reforms aimed at linking payment and quality have largely been based on the adherence to process measures. As a result, the attempt to pay for value is getting lost in an overly complex attempt to measure value. The "Incentivizing Health Care Quality Outcomes Act of 2014" (HR 5823) proposes to replace the existing patchwork of process and outcomes quality measures with a uniform, coordinated, and comprehensive outcomes-based quality measurement system. The Outcomes Act represents a shift in payment policy toward getting value instead of an increasingly complex attempt to measure value.


Control of Multiferroic properties in BiFeO3 nanoparticles.
BiFeO3 (BFO) nanoparticles (NPs) were synthesized using the sol-gel method at different calcination temperatures from 400 °C to 600 °C. XRD studies have confirmed that all BFO NPs show distorted rhombohedral crystals that match the R3c space group. We found evidence of local structural strain that develops with increasing particle size as suggested by TEM and Raman spectroscopy measurements. Magnetic measurements suggest that NPs have two distinct regimes: a ferromagnetic-like one at low temperatures and a superparamagnetic-like one at room temperature. The crossover temperature increases with NPs size, suggesting a size-dependent blocking magnetic regime. Similarly, local piezoelectric measurements at room temperature in single NP have confirmed a ferroelectric order with a NP size-dependent d33 coefficient. An analysis of both the ferroelectric and the magnetic results suggest that ferromagnetism and ferroelectricity coexist at room temperature in NPs. Our results lead to the possibility of tailoring the ferroic order in multifunctional materials by means of NP size.