Effect of lifetime antiepileptic drug treatment history on efficacy and tolerability of adjunctive brivaracetam in adults with focal seizures: Post-hoc analysis of a randomized, placebo-controlled trial.
To evaluate the efficacy and tolerability of adjunctive brivaracetam (BRV) in adults with focal seizures by the number of lifetime (previous and concomitant) antiepileptic drugs (AEDs). Post-hoc analysis of data from N01358 (NCT01261325), a randomized, double-blind, placebo (PBO)-controlled Phase III trial evaluating BRV 100 and 200 mg/day in patients ≥16 years of age with uncontrolled focal seizures. Efficacy and tolerability outcomes were assessed for the 12-week Treatment Period in subgroups of patients with 1-2, 3-4, 5-6, or ≥7 lifetime AEDs. 764 patients received at least one dose of trial medication (BRV: 503; PBO: 261; Safety Set), of whom 14.3% had 1-2, 20.8% had 3-4, 21.3% had 5-6, and 43.6% had ≥7 lifetime AEDs. In all lifetime AED subgroups, >85% of patients completed the trial. Patients with a higher number of lifetime AEDs had a younger age at epilepsy onset, longer epilepsy duration, and higher baseline seizure frequency. In patients on BRV, 50% responder rates were 49.3%, 44.4%, 47.2% and 27.4% in patients with 1-2 (n = 75), 3-4 (n = 99), 5-6 (n = 108) and ≥7 (n = 219) lifetime AEDs; 75% responder rates were 36.0%, 21.2%, 22.2% and 12.3%. In patients on PBO, 50% responder rates were 35.3%, 25.9%, 20.4% and 15.9% in patients with 1-2 (n = 34), 3-4 (n = 58), 5-6 (n = 54) and ≥7 (n = 113) lifetime AEDs; 75% responder rates were 26.5%, 6.9%, 3.7% and 4.4%. The Kaplan-Meier estimated probability of patients achieving a sustained 50% or 75% response from the first day of treatment was generally higher in patients with a lower number of lifetime AEDs (both in patients on BRV and PBO). In patients on adjunctive BRV, the incidence of drug related treatment-emergent adverse events (TEAEs) was 34.7%, 26.0%, 44.4% and 47.7% in patients with 1-2 (n = 75), 3-4 (n = 100), 5-6 (n = 108) and ≥7 (n = 220) lifetime AEDs; the incidence of discontinuations due to TEAEs was 1.3%, 3.0%, 8.3% and 10.5%. This post-hoc analysis suggests a numerically higher response to adjunctive BRV in patients with fewer lifetime AEDs. The lowest response was observed in patients with ≥7 lifetime AEDs, although these patients could also benefit from adjunctive BRV treatment. Patients with fewer lifetime AEDs had lower discontinuation of BRV due to TEAEs.


Heterotopia associated with hippocampal sclerosis: an under-recognized cause of early onset epilepsy in children operated on for temporal lobe epilepsy.
The aim of this study is to report on 52 children operated on for pharmacoresistant temporal lobe epilepsy, with special emphasis on histopathology and correlation with clinical features. Charts were retrospectively analyzed. All children underwent comprehensive clinical, electrophysiological and radiological investigations before surgery. Surgical procedures were tailored according to scalp, foramen ovale and eventually depth electrode recordings. Histopathology was compared with clinical variables (χ (2) and Fisher's exact tests). Outcome was evaluated using the Engel scale. Developmental tumor was found in 14 cases, malformation of cortical development (MCD) in 26, isolated hippocampal sclerosis (HS) in 5 and gliosis in 7. Dual pathology (DP) affected 18 patients and the main extrahippocampal lesion consisted of microscopic sub-cortical heterotopias (HS-HT) for 15 patients who shared a particular clinical pattern: a history of febrile seizures (FS) and/or brain injury, early onset of epilepsy without latent period from FS to the first temporal seizure, and a particularly good outcome following surgery. In our pediatric temporal lobe surgery series, the prevalence for MCD and for DP was higher than in adult series. Age at seizure onset depends on pathology, and is earlier when involving the neocortex rather than only the hippocampus. We identify the association HS-HT (the most frequent DP in this series), with particular clinical features.


Drotrecogin alfa (activated) may attenuate severe sepsis-associated encephalopathy in clinical septic shock.
Sepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction induced by the immuno-inflammatory response to infection. Elevated levels of the brain-specific S100B protein are present in many septic patients and reflect the severity of SAE. Adjunctive treatment with drotrecogin alfa (activated) (DrotAA), the human recombinant form of activated protein C, has been shown to improve mortality in patients with severe sepsis-induced organ failure. We studied the effect of DrotAA on S100B levels in patients with acute septic shock who presented with increased baseline values of this biomarker. All patients received standard goal-directed resuscitation treatment. Patients with pre-existing or acute neurological disorders were excluded. Based on the Glasgow coma scale (GCS), patients were classified into two groups: GCS >or= 13 and GCS <13. DrotAA was given as a continuous infusion of 24 microg/kg/h for 96 h. S100B was measured before sedation and the start of DrotAA (0 h) and at 32 h, 64 h and 96 h and at corresponding time points in patients not treated with DrotAA. The lower limit of normal was < 0.5 microg/L. Fifty-four patients completed the study. S100B was increased in 29 (54%) patients. Twenty-four patients (9 with GCS >or= 13 and 15 with GCS <13) received DrotAA. S100B levels in DrotAA-treated patients with a GCS <13, though higher at baseline than in untreated subjects (1.21 +/- 0.22 microg/L vs. 0.95 +/- 0.12 microg/L; P = 0.07), progressively and significantly decreased during infusion (0.96 +/- 0.22 microg/L at 32 h, P = 0.3; 0.73 +/- 0.12 microg/L at 64 h, P < 0.05; and 0.70 +/- 0.13 microg/L at 96 h, P < 0.05 vs. baseline). This patient group had also significantly lower S100B values at 64 h and at 96 h than their untreated counterparts. In the patients with a GCS >or= 13, S100B levels were not influenced by DrotAA treatment. S100B-positivity is present in more than half of the patients with septic shock. When increased S100B levels are used as a surrogate for SAE, adjunctive DrotAA treatment seems to beneficially affect the evolution of severe SAE as discriminated by an admission GCS <13.


Genotoxicity of two heavy metal compounds: lead nitrate and cobalt chloride in Polychaete Perinereis cultrifera.
The present study explores the in vivo and in vitro genotoxic effects of lead nitrate, [Pb(NO3)2] a recognized environmental pollutant and cobalt chloride (CoCl2), an emerging environmental pollutant in polychaete Perinereis cultrifera using comet assay. Despite widespread occurrence and extensive industrial applications, no previous published reports on genotoxicity of these compounds are available in polychaete as detected by comet assay. Polychaetes were exposed in vivo to Pb(NO3)2 (0, 100, 500, and 1000 μg/l) and CoCl2 (0, 100, 300, and 500 μg/l) for 5 days. At 100 μg/l Pb(NO3)2 concentration, tail DNA (TDNA) values in coelomocytes were increase by 1.16, 1.43, and 1.55-fold after day 1, day 3, and day 5, whereas, OTM showed 1.12, 2.33, and 2.10-fold increase in in vivo. Pb(NO3)2 showed a concentration and time-dependent genotoxicity whereas CoCl2 showed a concentration-dependent genotoxicity in in vivo. A concentration-dependent increase in DNA damage was observed in in vitro studies for Pb(NO3)2 and CoCl2. DNA damage at 500 μg/L showed almost threefold increase in TDNA and approximately fourfold increase in OTM as compared to control in in vitro. Our studies suggest that Pb(NO3)2 and CoCl2 have potential to cause genotoxic damage, with Pb(NO3)2 being more genotoxic in polychaete and should be used more carefully in industrial and other activities. Graphical abstract.


Transanal endoscopic microsurgery for the treatment of rectal cancer: comparison of wound complication rates with and without neoadjuvant radiation therapy.
Neoadjuvant therapy for rectal cancer has led to improved tumor downstaging and higher complete pathologic response rates. At the same time, the introduction of transanal endoscopic microsurgery (TEM) technique has renewed interest in local excision of rectal cancer. There has been concern that radiation may make the more radical local excision with TEM unsuitable. Our study compared morbidity rates and wound complication rates for patients undergoing TEM and local excision with and without neoadjuvant radiation to determine whether this could be accomplished safely. Data for all patients undergoing TEM are prospectively entered into a database. This database was queried for patients with rectal cancer undergoing TEM from November 1997 to June 2007. Of 64 patients identified, 2 were excluded because of previous radiation to the pelvis. The study enrolled 62 patients with a final pathologic diagnosis of rectal cancer: 43 treated using neoadjuvant therapy with radiation (XRT) and 19 patients treated with TEM alone. The patients in the XRT group were 67 years of age (range, 29-86 years) and included 13 women. The patients in the non-XRT group were 66 years of age (range, 40-89 years) and included 8 women. Neither group had any mortalities. The overall morbidity rate was 33% for the XRT group and 5.3% for the non-XRT group, and this difference was statistically significant (p < 0.05). The wound complication rates were 25.6% for the XRT group (11 patients) and 0% for the non-XRT group (p = 0.015). Nine patients in the XRT group (82%) had minor wound separations, and two patients (18%) had major wound separation. Ten patients with wound separations were treated as outpatients and administered long-term oral antibiotics. One patient required additional surgery (diverting stoma). Not unexpectedly, the wound complication rate was higher in the XRT group. However, 82% of those wounds were minor, and 91% were treated without any additional surgery or intervention. Although a significant concern, wound complications do not prohibit TEM treatment after neoadjuvant treatment.


Genome-wide association study and premature ovarian failure.
Premature ovarian failure (POF) is defined as an amenorrhea for more than 4months, associated with elevated gonadotropins, usually higher than 20mIU/ml, occurring in a woman before the age of 40. Some candidate genes have been identified in the past 15years, such as FOXL2, FSHR, BMP15, GDF9, Xfra premutation. However, POF etiology remains unknown in more than 90% of cases. The first strategy to identify candidate gene, apart from studying genes involved in ovarian failure in animal models, relies on the study of X chromosome deletions and X;autosome translocations in patients. The second strategy is based on linkage analysis, the third one on Comparative Genomic Hybridization (CGH) array. The latest strategy relies on Genome-Wide Association Studies (GWAS). This technique consists in screening single nucleotide polymorphisms (SNPs) in patients and controls. So far, three studies have been performed and have identified different loci potentially linked to POF, such as PTHB1 and ADAMTS19. However, replications in independent cohorts need to be performed. GWAS studies on large cohorts of women with POF should find new candidate genes in the near future.


Altered expression of a new antigen of the dermal-epidermal junction (NU-T2 DEJ Ag) in junctional epidermolysis bullosa.
NU-T2 antigen (Ag) is a new and recently described antigen of the dermal-epidermal junction, recognized by an anti-CD1b monoclonal antibody denominated NU-T2. We studied NU-T2 Ag expression in junctional epidermolysis bullosa (13 patients) and in other forms of hereditary epidermolysis bullosa (23 patients), comparing the results with nicein expression. In junctional epidermolysis bullosa gravis type no differences were found between the expression of NU-T2 and nicein, both being negative in bullous as well as in non-bullous skin. Interestingly, in mitis type junctional epidermolysis bullosa, NU-T2 Ag was found to be absent or reduced in five of six patients both in lesional and in uncleaved skin. When compared with nicein expression, clearcut differences were found, further suggesting that these two antigens are different. These data confirm that NU-T2 Ag is a novel epitope of the dermal-epidermal junction, probably relevant in dermal-epidermal cohesion, and it could be responsible, together with nicein, 19-DEJ-1 and other adhesion molecules, for the different subtypes of junctional epidermolysis bullosa. Finally, NU-T2 monoclonal antibody is a new relevant tool for the diagnosis, classification, and prenatal diagnosis of junctional epidermolysis bullosa.


Robust linear and non-linear models of NIR spectroscopy for detection and quantification of adulterants in fresh and frozen-thawed minced beef.
This study aimed to evaluate the potential of near infrared spectroscopy (NIRS) as a fast and non-destructive tool for detecting and quantifying different adulterants in fresh and frozen-thawed minced beef. Partial least squares regression (PLSR) models were built under cross validation and tested with different independent data sets, yielding determination coefficients (R(P)(2)) of 0.96, 0.94 and 0.95 with standard error of prediction (SEP) of 5.39, 5.12 and 2.08% (w/w) for minced beef adulterated by pork, fat trimming and offal, respectively. The performance of the developed models declined when the samples were in a frozen-thawed condition, yielding R(P)(2) of 0.93, 0.82 and 0.95 with simultaneous augments in the SEP of 7.11, 9.10 and 2.38% (w/w), respectively. Linear discriminant analysis (LDA), partial least squares-discriminant analysis (PLS-DA) and non-linear regression models (logistic, probit and exponential regression) were developed at the most relevant wavelengths to discriminate between the pure (unadulterated) and adulterated minced beef. The classification accuracy resulting from both types of models was quite high, especially the LDA, PLS-DA and exponential regression models which yielded 100% accuracy. The current study demonstrated that the VIS-NIR spectroscopy can be utilized securely to detect and quantify the amount of adulterants added to the minced beef with acceptable precision and accuracy.


An intriguing tetranuclear Rh-based polyoxometalate for the reduction of nitroarene and oxidation of aniline.
An organic-inorganic hybrid polyoxometalate Na5H5.68 [Na0.17Rh0.83III(C6H8N2)2Cl2]2(C8H8N2)2[As4W40O140Rh4IV(C6H4N2S)2]·nH2O (1) containing 5.66 Rh atoms is prepared; to our knowledge, it owns the largest number of Rh atoms in the Rh-POM family. Compound 1 demonstrates good catalytic performance in the reduction of nitrobenzene to aniline and the oxidation of aniline to azobenzene under mild conditions. Moreover, catalyst 1 exhibits high activity, excellent stability and recyclability.


Increased Skin Clearance and Quality of Life Improvement with Brodalumab Compared with Ustekinumab in Psoriasis Patients with Aggravating Lifestyle Factors.
Obesity, smoking, and alcohol consumption are prevalent in psoriasis patients and have been associated with increased disease severity and reduced treatment adherence and response. This post hoc analysis of pooled data from the phase 3 AMAGINE-2 and -3 trials compared the efficacy of brodalumab versus ustekinumab in psoriasis patients with aggravating and potentially treatment-confounding lifestyle risk factors. This post hoc analysis evaluated complete skin clearance, as measured by a 100% reduction of Psoriasis Area and Severity Index (PASI100) and quality of life (QoL), as measured by a Dermatology Life Quality Index (DLQI) score of 0/1, by the presence of risk factors (obesity, tobacco or alcohol use). A competing risk model assessed cumulative incidence over 52 weeks with outcomes of PASI100 or inadequate response. This analysis included 929 patients (brodalumab 210 mg, n = 339; ustekinumab, n = 590) with moderate-to-severe psoriasis. At week 52, odds ratios (95% confidence intervals [CIs]) for complete clearance with brodalumab versus ustekinumab were 2.50 (1.14-5.46, P = 0.0186), 4.64 (2.80-7.69, P < 0.0001), 2.06 (1.25-3.40, P = 0.0045), and 2.55 (0.55-11.91, P = 0.2117) in patients with no, one, two, or three risk factors, respectively. Corresponding odds ratios (ORs) (95% CIs) for DLQI 0/1 with brodalumab versus ustekinumab were 1.72 (0.78-3.79, P = 0.1883), 2.49 (1.54-4.02, P < 0.0002), 1.57 (0.97-2.54, P = 0.0666), and 2.07 (0.45-9.57, P = 0.3438). The 52-week cumulative incidence of patients achieving PASI100 was consistently higher for brodalumab versus ustekinumab, regardless of number of risk factors (P < 0.0001 for one or two risk factors and P = 0.0029 for three risk factors). Higher levels of complete skin clearance and QoL were achieved and maintained with brodalumab versus ustekinumab in patients with moderate-to-severe psoriasis, regardless of the presence of lifestyle risk factors. AMAGINE-2 (NCT01708603); AMAGINE-3 (NCT01708629).


Quality of life and falls in elderly people: a mixed methods study.
to assess elderly people's quality of life, understanding the social representations of falls. a convergent mixed methods research carried out at homes, with a sample of 134 elderly people. A structured questionnaire was used, covering sociodemographic variables and factors that indicated frailty and risk of falling. For quality of life assessment, Medical Outcomes Study Short-Form 36 and Theory of Social Representations, Abric's structural approach were used, with data treated by dictionary of equivalent terms, processed in Evoc 2000, converging analytically according to Neuman. quality of life impairment was identified in terms of physical, emotional and functional capacity. The elements of the possible central nucleus were fall, fear, and bruised-broken-bone. quality of life impairment can contribute to increase the number of falls, which has been shown to be an event present in elderly people's lives through evocations. Understanding elderly people's individual demands allows planning actions.


Base-selective adsorption of nucleosides to pore-engineered nanocarbon, carbon nanocage.
Selective molecular recognition is an important subject in supramolecular science as well as in practical applications such as sensing, drug delivery, and biomedical processes. In this research we have investigated adsorption behavior of nucleosides (adenosine, guanosine, and thymidine) onto various porous supports. When compared with mesoporous silica, porous carbons exhibit superior adsorptive performance. We serendipitously observed a pronounced selectivity between purine-base and pyrimidine-base nucleosides by carbon naonocage. These findings are useful for design of materials for applications in adsorption-based separations and as column stationary phases for separation of costly and important biomolecules.


Do Bedsider Family Planning Mobile Text Message and E-mail Reminders Increase Kept Appointments and Contraceptive Coverage?
To determine whether Bedsider text message and e-mail reminders increase family planning contraceptive continuation and appointment rates. We trained staff at three high-volume Family Planning, Access, Care, and Treatment (Family PACT) clinics to enroll women through a special portal to receive text message or e-mail reminders for contraceptive refills and clinic appointments. Women were matched by contraceptive method, time frame of index visit, age group, and language preference to Family PACT clients at comparison sites that did not use the Bedsider program. Family PACT claims data was used to assess the contraceptive coverage of Bedsider and comparison women over 12 months. We assessed differences in contraceptive coverage between the two groups using McNemar's test of matched comparisons. Clinic records from one clinic were available to assess impact on kept appointment rates. Of the 488 women enrolled, 370 had a claim for a hormonal method (oral contraceptive, patch, ring, contraceptive injection) in the Family PACT database. Matching resulted in 365 matched pairs. The median length of enrollment in the reminder system was 115 days (16 weeks). A greater percentage of Bedsider women returned on time for contraceptive injections than women in the comparison group. However, McNemar's test showed no differences in contraceptive coverage between the intervention and comparison groups. Kept appointment rates showed a statistically significant increase after the intervention at the clinic providing data. Contraceptive injection users showed a positive impact from receiving reminders, but overall there was no impact of the Bedsider reminders on return on time for contraceptive refills and injections. We were able to measure a significant increase in kept appointment rates at one clinic using the Bedsider text message and e-mail reminder system.


Profiles of caregivers most at risk of having unmet supportive care needs: Recommendations for healthcare professionals in oncology.
This study aimed to identify profiles of caregivers to cancer patients at higher risk of having at least one moderately or highly unmet supportive care need based on 1) relevant socio-demographic (e.g. age, gender) and clinical (e.g. type of cancer, phase of the cancer pathway) variables highlighted in the literature and easily identifiable in routine, and 2) caregivers' anxiety and depression symptoms. Three hundred and sixty-four main caregivers completed a questionnaire assessing their supportive care needs (SCNS-P&C-F) and anxiety and depression symptoms (HADS) during the treatment or follow-up stage of patients with digestive, breast, or lung cancer. Decision trees were used to identify profiles of caregivers with the Conditional inference Tree (CTree) technique. In our study, only the combination of three main variables was important to predict the risk of unmet supportive care needs of caregivers: anxiety and/or depression symptoms, the age of caregivers or patients, and the presence/absence of metastases. Emotional distress has the greatest impact, exceeding that of the socio-demographic and clinical variables considered in this study. This study shows the importance of considering a set of variables and their combinations rather than evaluating their effects separately. Routinely assessing the anxiety and depression symptoms of caregivers using the HADS could improve the screening of caregivers at higher risk of unmet supportive care needs based on socio-demographic and clinical variables only. This study provides recommendations on how to identify caregivers at risk of unmet needs, in the context of an inability to support all caregivers.


Ribosome biogenesis factor Bms1-like is essential for liver development in zebrafish.
Ribosome biogenesis in the nucleolus requires numerous nucleolar proteins and small non-coding RNAs. Among them is ribosome biogenesis factor Bms1, which is highly conserved from yeast to human. In yeast, Bms1 initiates ribosome biogenesis through recruiting Rcl1 to pre-ribosomes. However, little is known about the biological function of Bms1 in vertebrates. Here we report that Bms1 plays an essential role in zebrafish liver development. We identified a zebrafish bms1l(sq163) mutant which carries a T to A mutation in the gene bms1-like (bms1l). This mutation results in L(152) to Q(152) substitution in a GTPase motif in Bms1l. Surprisingly, bms1l(sq163) mutation confers hypoplasia specifically in the liver, exocrine pancreas and intestine after 3 days post-fertilization (dpf). Consistent with the bms1l(sq163) mutant phenotypes, whole-mount in situ hybridization (WISH) on wild type embryos showed that bms1l transcripts are abundant in the entire digestive tract and its accessory organs. Immunostaining for phospho-Histone 3 (P-H3) and TUNEL assay revealed that impairment of hepatoblast proliferation rather than cell apoptosis is one of the consequences of bms1l(sq163) giving rise to an under-developed liver. Therefore, our findings demonstrate that Bms1l is necessary for zebrafish liver development.


Epileptic-network-based prediction and control of seizures in humans.
Epilepsy is now conceptualized as a network disease. The epileptic brain network comprises structurally and functionally connected cortical and subcortical brain regions - spanning lobes and hemispheres -, whose connections and dynamics evolve in time. With this concept, focal and generalized seizures as well as other related pathophysiological phenomena are thought to emerge from, spread via, and be terminated by network vertices and edges that also generate and sustain normal, physiological brain dynamics. Research over the last years has advanced concepts and techniques to identify and characterize the evolving epileptic brain network and its constituents on various spatial and temporal scales. Network-based approaches further our understanding of how seizures emerge from the evolving epileptic brain network, and they provide both novel insights into pre-seizure dynamics and important clues for success or failure of measures for network-based seizure control and prevention. In this review, we summarize the current state of knowledge and address several important challenges that would need to be addressed to move network-based prediction and control of seizures closer to clinical translation.


Tuberculosis with Evans syndrome: A case report.
Evans syndrome and tuberculosis could be predisposing factors for one another, or there may be a common pathophysiological denominator for the co-occurrence. Further research is needed for a better understanding of pathophysiology and treatment.


Chimeric profunda artery perforator - gracilis flap: A computed tomographic angiography study and case report.
The possibility of harvesting the profunda artery perforator (PAP) flap in a chimeric configuration together with the innervated gracilis muscle may be a good option for dynamic reconstruction following total glossectomies. In this paper, we present a retrospective radiological study, which evaluates the presence and characteristics of the anatomical variation of the chimeric PAP - gracilis flap. The study sample comprised 66 patients (132 legs), 38 men, and 28 women with an average age of 56 ± 2 years old, who underwent head and neck reconstruction with a free flap. Preoperative computed tomographic angiography (CTA) was used for morphologic analysis. We present a case report of a patient with a total glossectomy reconstructed with this flap. A perforator in the PAP area joining with the main pedicle of the gracilis muscle was found in 38 legs (28.8%). Mean length of the pedicle from the profunda femoral artery to the point where the perforator in the PAP area and the pedicle of the gracilis joined was 3.0 ± 0.3 cm. Differences in the existence of this vascular configuration were not significant comparing groups by sex, BMI, height, side or source vessel. Motion of the new tongue was documented clinically and with electromyography. The patient achieved an intelligible speech and normal diet. Preoperative evaluation is necessary to assess the existence of a perforator in the PAP area joining with the main pedicle of the gracilis muscle. This chimeric flap has been demonstrated useful for dynamic reconstruction of a patient with a total glossectomy.


Vanillin-crosslinked chitosan/ZnO nanocomposites as a drug delivery system for 5-fluorouracil: study on the release behavior via mesoporous ZrO2-Co3O4 nanoparticles modified sensor and antitumor activity.
Herein, a series of vanillin-crosslinked chitosan (Vn-CS) nanocomposites (NCs) containing various contents of ZnO nanoparticles (NPs) was prepared and characterized via FTIR spectroscopy, XRD, TGA, SEM and TEM. Changing the weight% of ZnO NPs in the prepared NCs resulted in an improvement in their antibacterial activity against Gram-negative and Gram-positive bacteria strains compared with the unmodified CS, and the encapsulation efficiency of 5-fluorouracil (5-FU) was found to be in the range of 61.4-69.2%. Subsequently, the release of 5-FU was monitored utilizing the mesoporous ZrO2-Co3O4 NPs modified carbon paste sensor via the square-wave adsorptive anodic stripping voltammetry (SW-AdASV) technique. Also, the release mechanism of 5-FU from each NC was studied by applying the zero-order, first-order, Hixson-Crowell and Higuchi models to the experimental results. The cytotoxicity of prepared NCs and 5-FU-encapsulated NCs was evaluated against the HePG-2, MCF-7 and HCT-116 cancer cell lines, in addition to the WI-38 and WISH normal cell lines using the MTT assay. Notably, 5-FU/CV10 NC exhibited the highest antitumor activity towards all tested cancer cell lines and a moderate activity against WI-38 and WISH normal cell lines with IC50 values of 28.02 ± 2.5 and 31.65 ± 2.7 μg mL-1, respectively. The obtained nanocomposites exhibited suitable selectivity with minimum toxicity against normal cells.


Immunobiology of paediatric intracranial tumours. A preliminary report.
Preliminary findings in the evaluation of the immune response of children with primary neoplasms of the CNS, mainly medulloblastomas, are reported and discussed. A broad scheme for the monitoring of B- and T-cell-dependent immunity and of delayed hypersensitivity reactions in this type of patient is presented. The most important immunobiological findings are discussed. Special attention is given to the striking failure of the T-cell-dependent pool (currently identified by "active" RFC and blastigenesis tests) and to the remarkable decrease of hypersensitivity reactions (depressed skin-test response), both of which seem to be related to the degree of malignancy of the tumour. A very peculiar feature, i.e., the appearance of cells with natural cytotoxic activity, is dealt with in some detail. Our present knowledge concerning the immunobiology of primary CNS neoplasms is still very incomplete, but seems to suggest a possible role for immunotherapy in paediatric neurosurgery.


Factors affecting predictability of radial keratotomy.
A major criticism of radial keratotomy (RK) has been its lack of predictability, a lack due in large measure to the use of simple correlational statistics assessing the relationship between refractive result and each predictor-variable being evaluated separately. This report utilizes multivariate analysis in an attempt to account for the effects of a number of predictor-variables simultaneously. Variables studied are patient age, optical zone size, number of incisions, mean incision depth, preoperative average keratometry, preoperative average applanation tension, patient sex, and age-sex interrelationship. The area of the optical clear zone selected by the surgeon was found to be the most important factor determining refractive change as a result of RK, explaining one-quarter to one-half of the variability of the procedure. The effects of the other factors and the limitations of the method are discussed. Although this method cannot produce a fully predictive equation, we believe this analysis can serve as a good starting point for beginning RK surgeons and a method by which experienced RK surgeons can improve their techniques.


Detection of mammographically occult architectural distortion on digital breast tomosynthesis screening: initial clinical experience.
Digital breast tomosynthesis (DBT) has been shown to improve the sensitivity of screening mammography. DBT may have the most potential impact in cases of subtle mammographic findings such as architectural distortion (AD). The objective of our study was to determine whether DBT provides better visualization of AD than digital mammography (DM) and whether sensitivity for cancer detection is increased by the addition of DBT as it relates to cases of mammographically occult AD. Retrospective review of BI-RADS category 0 reports from 9982 screening DM examinations with adjunct DBT were searched for the term "architectural distortion" and were reviewed in consensus by three radiologists. ADs were classified by whether they were seen better on DM or DBT, were seen equally well on both, or were occult on either modality. The electronic medical record was reviewed to identify additional imaging studies, biopsy results, and surgical excision pathology results. Review identified 26 cases of AD, 19 (73%) of which were seen only on the DBT images. Of the remaining seven ADs, six were seen better on DBT than DM. On diagnostic workup, nine lesions were assigned to BI-RADS category 4 or 5. Surgical pathology revealed two invasive carcinomas, two ductal carcinoma in situ lesions, three radial scars, and two lesions showing atypia. The cancer detection rate of DBT in mammographically occult AD was 21% (4/19). The positive predictive value of biopsy was 44%. DBT provides better visualization of AD than DM and identifies a subset of ADs that are occult on DM. Identification of additional ADs on DBT increases the cancer detection rate.


Influence of cation structure on binary liquid-liquid equilibria for systems containing ionic liquids based on trifluoromethanesulfonate anion with hydrocarbons.
Binary liquid-liquid equilibria for 15 systems containing an ionic liquid (1-butyl-3-methylimidazolium trifluoromethanesulfonate, 1-butyl-3-methylpyridinium trifluoromethanesulfonate, 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate) with a hydrocarbon (n-hexane, n-heptane, cyclohexane, benzene, toluene) were measured by the dynamic method. The influence of cation structure of trifluoromethanesulfonate anion based ionic liquids on solubility of aliphatic and aromatic hydrocarbons is discussed.


Maintenance chemotherapy for anaplastic small cell carcinoma of the bronchus: a randomised, controlled trial.
Since March 1980, 309 patients with anaplastic small cell carcinoma of the bronchus (ASCB) have received remission induction therapy prior to randomisation to maintenance (M) or no maintenance (NM) chemotherapy. Induction therapy consisted of six courses of vincristine, doxorubicin and cyclophosphamide (VAC) given IV every 3 weeks. Those with limited disease also received mediastinal irradiation. Consenting patients with no unequivocal residual disease were randomised to have no further treatment until relapse or a further eight courses of VAC, at a lower dosage, every 4 weeks. Patients failing to achieve randomisation status received palliative treatment only. The median survival for all patients with limited disease (LD) is 363 days and that for patients with extensive disease (ED) is 272 days (P less than 0.00001). Sixty-one patients with ED were randomised. Those having maintenance chemotherapy lived significantly longer (median 372 days) than those who did not continue therapy (median 259 days) (P = 0.006). An imbalance in the proportion of 'complete remitters' randomised to maintenance therapy does not account for this difference. There is no significant difference between the M and NM groups in the 32 randomised LD patients. Continuing treatment during remission with agents used to induce the remission can prolong survival in patients with extensive stage ASCB.


In vivo transport of three radioactive [18F]-fluorinated deoxysucrose analogs by the maize sucrose transporter ZmSUT1.
Sucrose transporter (SUT) proteins translocate sucrose across cell membranes; however, mechanistic aspects of sucrose binding by SUTs are not well resolved. Specific hydroxyl groups in sucrose participate in hydrogen bonding with SUT proteins. We previously reported that substituting a radioactive fluorine-18 [18F] at the C-6' position within the fructosyl moiety of sucrose did not affect sucrose transport by the maize (Zea mays) ZmSUT1 protein. To determine how 18F substitution of hydroxyl groups at two other positions within sucrose, the C-1' in the fructosyl moiety or the C-6 in the glucosyl moiety, impact sucrose transport, we synthesized 1'-[F18]fluoro-1'-deoxysucrose and 6-[F18]fluoro-6-deoxysucrose ([18F]FDS) analogs. Each [18F]FDS derivative was independently introduced into wild-type or sut1 mutant plants, which are defective in sucrose phloem loading. All three (1'-, 6'-, and 6-) [18F]FDS derivatives were efficiently and equally translocated, similarly to carbon-14 [14C]-labeled sucrose. Hence, individually replacing the hydroxyl groups at these positions within sucrose does not interfere with substrate recognition, binding, or membrane transport processes, and hydroxyl groups at these three positions are not essential for hydrogen bonding between sucrose and ZmSUT1. [18F]FDS imaging afforded several advantages compared to [14C]-sucrose detection. We calculated that 1'-[18F]FDS was transported at approximately a rate of 0.90 ± 0.15 m.h-1 in wild-type leaves, and at 0.68 ± 0.25 m.h-1 in sut1 mutant leaves. Collectively, our data indicated that [18F]FDS analogs are valuable tools to probe sucrose-SUT interactions and to monitor sucrose transport in plants.


Microbial communities and their enzymes facilitate degradation of recalcitrant polymers in anaerobic digestion.
Microbial consortia efficiently degrade complex biopolymers found in the organic fraction of municipal solid waste (OFMSW). Through enzyme production and division of labor during anaerobic digestion, microbial communities break down recalcitrant polymers and make fermentation products, including methane. However, microbial communities remain underutilized for waste degradation as it remains difficult to characterize and predict microbial interactions during waste breakdown, especially as cultivation conditions change drastically throughout anaerobic digestion. This review discusses recent progress and opportunities in cultivating natural and engineered consortia for OFMSW hydrolysis, including how recalcitrant substrates are degraded by enzymes as well as the critical factors that govern microbial interactions and culture stability. Methods to measure substrate degradation are also reviewed, and we demonstrate the need for increased standardization to enable comparisons across different environments.


Taurine for EPR dosimetry.
EPR dosimetry is characterized by its non-destructive read-out and the possibility of dose archival. Here, taurine is proposed as a radiation dosimeter using EPR spectroscopy. The EPR spectrum of taurine was studied and assigned, and changes in the taurine EPR spectrum as a result of the change in both modulation amplitude and microwave power were quantified. For gamma radiation, the energy absorption coefficient and the collision mass stopping power of taurine were compared to the corresponding values of soft tissue and alanine, in addition to calculation of effective atomic numbers. The response of taurine to gamma radiation doses in the range from 0.1 to 50 kGy was investigated, as well as that in the range from 1.0 to 20.0 Gy using numerically enhanced EPR taurine spectra. Both response curves showed a linear behavior. In addition, the time dependence of radiation-induced radicals was studied for short (during the first 6 h after irradiation) and long (during about 3 months after irradiation) time periods, and a reasonable degree of stability of the taurine radicals was observed. It is concluded that taurine is a promising dosimeter, which is characterized by its simple spectrum, radical stability, and wide range of linear response to gamma radiation.


Fetal development and growth of the human erector spinae with special reference to attachments on the surface aponeurosis.
The longissimus (LO) and iliocostalis (IC) of adults consist of myofibers extending from the superolateral to the inferomedial side of the back and, because of the same course, they are fused in the thoracolumbar region. The LO also has a medial attachment to the long myofibers of the transversospinalis (TS) showing a course from the superomedial to the inferolateral side. However, there is apparently no information regarding when and how these similar longitudinal muscles differentiate from a cluster of dorsomedial myotome cells. We examined sagittal and horizontal sections of the trunks of 39 human embryos and fetuses (18-330 mm crown-rump length). At 6-7 weeks gestational age (GA), the surface aponeurosis appeared prior to and independent of the thoracolumbar fascia. At 6-9 weeks GA, the LO myofibers had a postero-inferior course, from the transverse process to the initial aponeurosis, whereas the TS myofibers had a postero-superior course, from a lateral extension of the intertransverse ligament to the aponeurosis. However, the IC consisted of supracostal longitudinal myofibers and was distant from the LO until 12 weeks GA. Because of the lack of ligamentous attachments and ribs, myofibers of the TS, LO, and IC took a similar inferior course in the lumbar region. When the early TS was represented by the transverso-aponeurotic muscle, consequently, the LO corresponded to the aponeuro-transversal muscle and was independent from the IC. The classical model of TS and LO development does not recognize the essential role of the aponeurosis identified here.


More than just accent? The role of dialect words in children's language-based social judgments.
Recent research suggests that young children are capable of distinguishing between phonetically dissimilar spoken accents yet have difficulty in distinguishing between phonetically similar accents. The current studies aimed to determine whether the presence of dialect-specific vocabulary enhances young children's ability to categorize speakers. In Study 1, 4- to 7-year-old children performed tasks in which they matched speakers based on the dialect-specific vocabulary the speakers used. Participants were successful in matching speakers based on vocabulary at a rate significantly greater than chance. In Study 2, participants performed a task in which they inferred a speaker's future dialect-specific vocabulary use based on the speaker's previous vocabulary use. Participants were able to infer a speaker's vocabulary use at a rate significantly greater than chance, and participants also showed social preference for and selective trust of speakers who used the participants' native dialect vocabulary over those who used a non-native dialect vocabulary. These interesting results suggest that when accent differences are too subtle for children to categorize speakers, dialect-specific vocabulary may enhance young children's ability to categorize a speaker. The results of preference and selective trust questions also suggest that children as young as 4 years use their knowledge of a speaker's vocabulary to guide their preferred social interactions, choosing to interact with others who speak similarly to them.


Modifying the Nonradiative Decay Dynamics through Conical Intersections via Collective Coupling to a Cavity Mode.
The coupling of a molecular ensemble to the confined electromagnetic modes of a microcavity can strongly modify the photophysics and photochemistry of the molecules upon photoexcitation. We investigate here how collective coupling effects lead to modifications of the mechanisms and rates of photochemical processes, in particular, photodissociation and nonradiative decay in NaI and pyrazine, respectively. We show that, after direct excitation into the lower polaritonic states, the lower-energy light-matter hybrid states, the dynamics of the molecular ensemble coupled to light is very similar to the dynamics of the corresponding isolated molecules. Conversely, excitation into the upper polaritonic states results in more complex dynamics that involve as a first step the population transfer toward the manifold of intermediate dark states. These dynamics differ substantially from those of the isolated molecules and may result in measurable time delays for nonradiative decay or excited-state reaction mechanisms. Similarly, we describe how addition of a buffer of nonreactive molecules coupled to the cavity mode can be used to delay the onset of the photochemical processes of the reactive part of the ensemble, where the buffer medium is more effective in inhibiting the reactive process than only reactive molecules in the cavity.


Chitosan/fucoidan multilayer nanocapsules as a vehicle for controlled release of bioactive compounds.
Hollow multilayer nanocapsules were successfully prepared through layer-by-layer assembly of two bioactive polysaccharides, chitosan and fucoidan. The stepwise adsorption of 10 chitosan/fucoidan layers and the consequent formation of a multilayer film on polystyrene nanoparticles (used as templates) were followed through ζ-potential measurement and the removal of the polystyrene core was confirmed by FTIR analysis. The chitosan/fucoidan nanocapsules morphology and size were evaluated by SEM and TEM, which showed that after the core removal, the nanocapsules maintained their spherical shape and a decrease of size occurred. A cationic bioactive compound, poly-L-lysine (PLL), was chosen to evaluate the loading and release behaviour of the nanocapsules. The chitosan/fucoidan nanocapsules showed a good capacity for the encapsulation and loading of PLL, which shows to be influenced by the initial PLL concentration and the method of encapsulation used. The results of fitting the linear superimposition model to the experimental data of PLL release suggest an anomalous behaviour, with one main polymer relaxation. The PLL release was found to be pH-dependent: at pH 2 relaxation is the governing phenomenon and at pH 7 Fick's diffusion is the main mechanism of PLL release. Chitosan/fucoidan nanocapsules is a promising delivery system for water soluble bioactive compounds, such as PLL, showing a great potential of application in food and pharmaceutical industries.


Treatment Bed Utilization Following Placement in a Foster Care Program for Veterans with Serious Mental Illness.
Hospital and residential treatment bed utilization rates were measured before and after foster home placement in individuals with serious mental illness. Medical records of all Veterans consecutively enrolled in a Department of Veterans Affairs Community Residential Care (CRC) program during a 6 year period (N = 140) were reviewed retrospectively. Treatment bed days were tabulated by bed type (psychiatric hospital, inpatient detoxification, medical hospital, physical rehabilitation, and psychosocial residential treatment) for each patient during symmetric pre- and post-placement time intervals. Pre- and post-placement bed days were compared using the paired-sample t test in a naturalistic one-group pretest-posttest analytic design. Psychiatric hospital and residential treatment bed days were significantly reduced post-placement (-77.5% and -99.8%, respectively). Most patients (89.0%) had fewer psychiatric hospital bed days post-placement, and all patients with pre-placement residential treatment program bed days had fewer of those days post-placement. Longer CRC placements were associated with greater reductions in bed utilization.


Relational autonomy: lessons from COVID-19 and twentieth-century philosophy.
COVID-19 has turned many ethical principles and presuppositions upside down. More precisely, the principle of respect for autonomy has been shown to be ill suited to face the ethical challenges posed by the current health crisis. Individual wishes and choices have been subordinated to public interests. Patients have received trial therapies under extraordinary procedures of informed consent. The principle of respect for autonomy, at least in its mainstream interpretation, has been particularly questioned during this pandemic. Further reflection on the nature and value of autonomy is urgently needed. Relational autonomy has been proposed as an alternative account of autonomy that can more adequately respond to contemporary ethical issues in general and to a pandemic such as the one we are currently facing in particular. As relational autonomy is an emerging notion in current bioethics, it requires further consideration and development to be properly operationalized. This paper aims to show how six different philosophical branches--namely, philosophy of nature, philosophical anthropology, existential phenomenology, discourse ethics, hermeneutics, and cultural anthropology--have incorporated the category of relation throughout the twentieth century. We first delve into primary philosophical sources and then apply their insights to the specific field of medical ethics. Learning from the historical developments of other philosophical fields may provide illumination that will enable bioethics to experience a successful "relational turn", which has been partially initiated in contemporary bioethics but not yet achieved.


Isolation and characterisation of promoters from mouse genome to drive post-meiotic germ cell-specific robust gene expression for functional genomics studies.
The generation of spermatozoa from developing germ cells through mitotic and meiotic divisions is a highly regulated and complex process. Any defect in this process, may lead to subfertility/infertility. The role of different transcripts (mRNA/miRNA/lncRNA) in regulation of the pre-meiotic, meiotic, and post-meiotic stages of spermatogenesis are being proposed based on various multiomics based approaches. Such differential gene-expression is regulated by promoter elements that are activated in a stage specific manner. To determine the role of these differentially expressed transcripts in the process of meiosis, a robust post-meiotic germ cell specific promoter is required. In the present study, we have isolated and characterized the expression of the mouse Proacrosin, SP10, and ELP promoters for driving post-meiotic germ cell specific gene-expression. Promoter regions of all these 3 genes were isolated and cloned to generate mammalian expression vector. The transgene expression in post-meiotic germ cells was assessed in mice using the testicular electroporation method in vitro as well as in vivo, using above promoters. It was also validated in goat seminiferous tubules, in vitro. We have also carried out a comparative analysis of the strength of these promoters to confirm their robustness that indicated Proacrosin to be the most robust promoter that can be useful for diving post-meiotic germ cells specific gene-expression. These promoters can be used to alter gene-expression specifically in post-meiotic germ cells for deciphering the role(s) of germ cell genes in spermatogenic progression or for expressing various genome editing tools for engineering the germ cell genome to understand basis of subfertility/infertility.


[The solid pseudopapillary tumor of pancreas: two cases and literature review].
Solid pseudopapillary tumor (SPT) of the pancreas is a rare exocrine pancreatic tumor behaving in a low-grade fashion, with limited local invasion risk and a rare metastatic evolution. We report SPT in two young females, revealed by abdominal pain and an epigastric mass. The diagnosis of a cystic tumor was based on abdominal ultrasound and CT data in the first case and on MRI in the second. A distal pancreatectomy and splenectomy were successfully performed in the first case and a central pancreatectomy in the second. Histological study confirmed the diagnosis of SPT of the pancreas.


Expression of mdr1 and mrp in the normal B-cell homologue of B-cell chronic lymphocytic leukaemia.
B-cell chronic lymphocytic leukaemia (CLL) cells commonly express the multidrug resistance phenotype. The aim of this study was to establish whether the normal homologue in B-cell ontogeny of B-CLL also expressed the multidrug resistance (mdr) phenotype. Human tonsillar lymphocytes were sorted to yield two B-cell subsets based on the expression of CD19, CD5 and CD10. The normal homologue was represented by a population of B cells that was CD19 positive, CD10 negative and weakly expressed CD5. Based upon functional analysis and the detection of mdr1 mRNA by semi-quantitative PCR, these cells expressed the mdr phenotype. In contrast, functional multidrug resistance could not be demonstrated in CD19-positive CD10-positive cells with strong expression of CD5, nor could mdr1 mRNA be found in these cells. MRP was variably expressed in both B-cell subsets with no discernable differences in the pattern of expression. We conclude that normal B cells with a phenotype resembling that of B-CLL cells express the multidrug resistance phenotype.


Development of alternative gene transfer techniques for ex vivo and in vivo gene therapy in a canine model.
Gene therapy have recently attracted much attention as a curative therapeutic option for inherited single gene disorders such as hemophilia. Hemophilia is a hereditary bleeding disorder caused by the deficiency of clotting activity of factor VIII (FVIII) or factor IX (FIX), and gene therapy for hemophilia using viral vector have been vigorously investigated worldwide. Toward further advancement of gene therapy for hemophilia, we have previously developed and validated the efficacy of novel two types of gene transfer technologies using a mouse model of hemophilia A. Here we investigated the efficacy and safety of the technologies in canine model. Especially, validations of technical procedures of the gene transfers for dogs were focused. Green fluorescence protein (GFP) gene were transduced into normal beagle dogs by ex vivo and in vivo gene transfer techniques. For ex vivo gene transfer, blood outgrowth endothelial cells (BOECs) derived from peripheral blood of normal dogs were transduced with GFP gene using lentivirus vector, propagated, fabricated as cell sheets, then implanted onto the omentum of the same dogs. For in vivo gene transfer, normal dogs were subjected to GFP gene transduction with non-viral piggyBac vector by liver-targeted hydrodynamic injections. No major adverse events were observed during the gene transfers in both gene transfer systems. As for ex vivo gene transfer, histological findings from the omental biopsy performed 4 weeks after implantation revealed the tube formation by implanted GFP-positive BOECs in the sub-adipose tissue layer without any inflammatory findings, and the detected GFP signals were maintained over 6 months. Regarding in vivo gene transfer, analyses of liver biopsy samples revealed more than 90% of liver cells were positive for GFP signals in the injected liver lobes 1 week after gene transfers, then the signals gradually declined overtime. Two types of gene transfer techniques were successfully applied to a canine model, and the transduced gene expressions persisted for a long term. Toward clinical application for hemophilia patients, practical assessments of therapeutic efficacy of these techniques will need to be performed using a dog model of hemophilia and FVIII (or FIX) gene.


Functional Impairments and Quality of Life in Older Adults With Upper Gastrointestinal Cancers.
Functional impairments (measured by activities of daily living [ADLs]) and health-related quality of life (HRQOL) may complicate outcomes in older adults diagnosed with cancer. In this retrospective cohort analysis, we characterized ADLs and HRQOL in adults older than 65 y with upper gastrointestinal (UGI) cancers and evaluated for an association to cancer-specific survival. Patients with UGI cancers aged 65 y or older were selected from the Surveillance, Epidemiology and End Results and the Medicare Health Outcomes Survey-linked database. Demographics, comorbidities, stage, ADLs, and HRQOL were summarized by patients managed with and without surgery. Because of the wide variety of cancers, we subdivided patients into cohorts of esophagogastric [EG; n = 88] or hepatobiliary/pancreatic [n = 68]. Cancer-specific survival curves were modeled for changes in ADL and HRQOL scores after diagnosis. Risk factors for cancer-specific survival were assessed with hazard ratios (HRs) and adjusted for demographics, stage, comorbidities, and disease cohorts. HRQOL scores declined after diagnosis, with a sharper decline in nonsurgery patients. On multivariate analysis, inability to perform specific ADLs was associated with worse survival in multiple cohorts: hepatobiliary/pancreatic nonsurgery patients unable to eat (HR 3.3 95% confidence interval (CI) 1.7-6.5); all patients with EG unable to use the toilet (HR 3.3 95% CI 1.5-7.9); EG nonsurgery cohort unable to dress or use the toilet (dress HR 14.1 95% CI 4.0-49.0; toilet HR 4.7 95% CI 1.8-12.3). Older survivors with UGI cancers report declines in HRQOL, especially those not undergoing surgery. The ability to perform ADLs may be linked to survival in this population.


Assays for the fidelity of DNA polymerases in cell-free extracts of Escherichia coli are complicated by contaminating nucleoside triphosphatases.
In the presence of DNA and a divalent cation, an enzyme activity in cell-free extracts of Escherichia coli readily hydrolyses dATP to dADP. dGTP is degraded to a smaller extent, dCTP and dTTP being hardly affected. The artificial template primers poly(dC) . oligo(dG) and poly(dT) . oligo(dA) are also effective cofactors for this triphosphatase activity. As a consequence, assays measuring the misincorporation, by cell-free extracts, of dATP and dGTP into these defined templates are difficult to interpret, since the triphosphate substrate is being rapidly degraded during the polymerase reaction. A partial characterization of the dATPase activity was performed, demonstrating that the optimal conditions for its activity resemble those commonly used for assaying polymerase activity. Thus in crude extracts both polymerase and dATPase compete for the same substrate. The inclusion of an ATP-generating system in the reaction mixture maintains the levels of deoxynucleoside triphosphates and changes the kinetics of misincorporation of dAMP into poly(dC) . oligo(dG). No reproducible difference in such misincorporation has been found between lysates prepared from tif-1 cells grown at either permissive or restrictive temperature.


Kinetics of the inhibition of tissue factor-factor VIIa by tissue factor pathway inhibitor.
Tissue factor-factor VIIa catalysed activation of factor IX is inhibited by the complex of tissue factor pathway inhibitor (TFPI) and factor Xa. At present, no information is available as to what extent the kinetics of complex formation between TFPI and factor Xa during factor X activation contribute to the overall rate of inactivation of the factor X converting complex. We have determined the kinetic parameters of the individual reactions, i.e. factor X activation, formation of the TFPI-factor Xa complex, and inactivation of tissue factor-factor VIIa by the TFPI-factor Xa complex. We modelled the overall reaction by assuming a two-step reaction: factor Xa generated by tissue factor-factor VIIa forms a reversible complex with TFPI and in the second step this complex forms a reversible quaternary complex with tissue factor-factor VIIa. The validity of the model was demonstrated by analysis of factor Xa generation curves in the presence of TFPI. Independently determined constants for factor X activation (kcat = 12 s-1, Km = 70 nM) and inhibition of tissue factor-factor VIIa by TFPI-factor Xa complex (rate constant of inhibition of 1.1 x 10(8) M-1S-1) were used. The association rate constant of the formation of the TFPI-factor Xa complex was estimated by fitting the model to the data.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects and duration of resistance acquired by rabbits on feeding and egg laying in Ixodes ricinus L.
Rabbits gradually developed a resistance against Ixodes ricinus ticks as a result of sequential experimental infestations. The resistance was characterized by an increase duration of feeding, by ticks engorging to a smaller extent and by reduced egg production. Once established, the immunity persisted for at least 9 months. Changes in the titre of circulating anti-I. ricinus antibodies was measured by indirect immunofluorescence.


Flow field around bubbles on formation of air embolism in small vessels.
An air embolism is induced by intravascular bubbles that block the blood flow in vessels, which causes a high risk of pulmonary hypertension and myocardial and cerebral infarction. However, it is still unclear how a moving bubble is stopped in the blood flow to form an air embolism in small vessels. In this work, microfluidic experiments, in vivo and in vitro, are performed in small vessels, where bubbles are seen to deform and stop gradually in the flow. A clot is always found to originate at the tail of a moving bubble, which is attributed to the special flow field around the bubble. As the clot grows, it breaks the lubrication film between the bubble and the channel wall; thus, the friction force is increased to stop the bubble. This study illustrates the stopping process of elongated bubbles in small vessels and brings insight into the formation of air embolism.


Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro.
The brain is the most cholesterol-rich organ in the body. Brain cholesterol is characterized by a very low turnover with very little exchange with lipoproteins in the circulation. Very recently we showed that there is a continuous age-dependent flux of 24(S)-hydroxycholesterol from the human brain into the circulation (Lütjohann, D., Breuer, O., Ahlborg, G., Nennesmo, I., Sidén, A., Diczfalusy, U., and Björkhem, I. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 9799-9804). Here we measured the rate of synthesis of cholesterol as well as the conversion of cholesterol into 24(S)-hydroxycholesterol in rat brain in vivo with use of an 18O2 inhalation technique and mass isotopomer distribution analysis. Cholesterol synthesis was found to correspond to 0.03 +/- 0.01% of the pool per h. Conversion of cholesterol into 24(S)-hydroxycholesterol was of a similar magnitude, about 0.02% of the pool per h. Brain microsomes converted endogenous cholesterol into 24(S)-hydroxycholesterol at a similar rate when incubated in the presence of NADPH. When incubated with whole homogenate and subcellular fractions of rat brain, there was no significant conversion of tritium-labeled 24-hydroxycholesterol into more polar products. Plasma from 18O2-exposed rats contained 24(S)-hydroxycholesterol with an enrichment of 18O similar to that in 24(S)-hydroxycholesterol in the brain. The results suggest that the present 24(S)-hydroxylase mediated mechanism is most important for elimination of cholesterol from the brain of rats. There is a slow conversion of brain cholesterol into 24(S)-hydroxycholesterol with a rapid turnover of the small pool of the latter oxysterol due to leakage to the circulation (half-life of brain 24(S)-hydroxycholesterol is about 0.5 days as compared with 2-4 months for brain cholesterol). It is evident that the 24(S)-hydroxylation greatly facilitates transfer of cholesterol over the blood-brain barrier and that this hydroxylation may be critical for cholesterol homeostasis in the brain.


Determining the psychometric properties of a novel questionnaire to measure "preparedness for the future" (Prep FQ).
People are living longer than ever before. However, with living longer comes increased problems that negatively impact on quality of life and the quality of death. Tools are needed to help individuals assess whether they are practicing the best attitudes and behaviors that are associated with a future long life, high quality of life, high quality of death and a satisfying post-death legacy. The purpose of paper is to describe the process we used to develop a novel questionnaire ("Preparedness for the Future Questionnaire™ or Prep FQ") and to define its psychometric properties. Using a multi-step development procedure, items were generated, for the new questionnaire after which the psychometric properties were tested with a heterogeneous sample of 502 Canadians. Using an online polling panel, respondents were asked to complete demographic questions as well as the Prep-FQ, Global Rating of Life Satisfaction, the Keyes Psychological Well-Being scale and the Short-Form 12. The final version of the questionnaire contains 34 items in 8 distinct domains ("Medico-legal", "Social", "Psychological Well-being", "Planning", "Enrichment", "Positive Health Behaviors", "Negative Health Behaviors", and "Late-life Planning"). We observed minimum missing data and good usage of all response options. The average overall Prep FQ score is 51.2 (SD = 13.3). The Cronbach alphas assessing internal reliability for the Prep FQ domains ranged from 0.33 to 0.88. The intra-class correlation coefficient (ICC) used to assess the test-retest reliability had an overall score of 0.87. For the purposes of establishing construct validity, all the pre-specified relationships between Prep FQ and the other questionnaires were met. Analyses of this novel measure offered support for its face validity, construct validity, test-retest reliability, and internal consistency. With the development of this useful and valid scale, future research can utilize this measure to engage people in the process of comprehensively assessing and improving their state of preparedness for the future, tracking their progress along the way. Ultimately, this program of research aims to improve the quality and quantity of peoples live by helping them 'think ahead' and 'plan ahead' on the aspects of their daily life that matter to their future.


Anterior cruciate ligament reconstruction using patellar tendon allograft: an age-dependent outcome evaluation.
To compare the outcomes of a consecutive series of nonrevision bone-patellar tendon-bone (BPTB) allograft anterior cruciate ligament (ACL) reconstructions in patients aged 40 years or older and patients aged younger than 40 years. Prospectively collected data from consecutive BPTB allograft ACL reconstructions fixed with biodegradable interference screws and performed by a single surgeon were analyzed by use of established outcome measures. Preoperative and postoperative outcome assessments included Cincinnati, Lysholm, and Tegner scores and International Knee Documentation Committee (IKDC) activity scores. Lachman test, pivot-shift test, and KT arthrometer (MEDmetric, San Diego, CA) measurements were obtained at a minimum of 24 months after surgery. In total, 32 patients met the inclusion criteria (21 men and 11 women). The mean follow-up was 35 months (range, 24 to 58 months). Of the patients, 21 were aged younger than 40 years (66%) and 11 were aged 40 years or older (34%). The mean age was 35 years (range, 18 to 55 years). In patients aged younger than 40 years, the mean postoperative Cincinnati score was 82.4 (39.1 preoperatively); Tegner score, 6.2 (3.9 preoperatively); Lysholm score, 89.5 (46.8 preoperatively); and IKDC activity score, 2.7 out of 4 (1.7 preoperatively). Five patients had a positive postoperative Lachman test, but none had a positive pivot-shift test. KT examinations showed a manual maximum difference of less than 3 mm in all but 1 patient (mean, 0.7 mm). In patients aged 40 years or older, the mean postoperative Cincinnati score was 83.8 (44.4 preoperatively); Tegner score, 6.6 (3.9 preoperatively); Lysholm score, 88.8 (50.1 preoperatively); and IKDC activity score, 2.7 out of 4 (2.1 preoperatively). One patient had a positive postoperative Lachman test, but none had a positive pivot-shift test. KT examinations showed a manual maximum difference of less than 3 mm in all but 1 patient (mean, 1.3 mm). The outcomes of BPTB allograft ACL reconstructions were not different both subjectively and objectively for patients aged 40 years or older and patients aged younger than 40 years. BPTB allograft ACL reconstruction provides consistent results for patients of all age groups. Level III, retrospective comparative study.


Isoprenaline and canine cardiac refractory periods.
Atrioventricular refractory periods and their modifications induced by variable doses of sioprenaline have been investigated in dogs. Premature atrial stimuli (St2) were applied at variable intervals following regular stimuli (St1) which ensured atrial pacing. Atrial (AERP), nodoventricular (NERP) and global (GERP) effective refractory periods, as well as the global functional refractory period (GFRP) were determined before, during and after infusion of the drug. In low doses, isoprenaline did not significantly alter these various parameters. This confirms its lack of dromotropic effect on the healthy heart. In contrast, high doses of the drug significantly reduced the refractory periods, probably by simple correction of the negative dromotropic effects resulting from overstimulation. Also when the infusion was stopped, marked but reversible conduction depression was observed. It would appear that this reflects 'exhaustion' of cell metabolism induced by the drug.


Thermography as a tool to assess training effects in military working dogs.
Military working dogs are exposed to high levels of physical load during their work, although this is not always evident from their behaviour. This workload causes various physiological changes, including variation in the temperature of the affected body parts. In this preliminary study, we investigated whether thermal changes following the daily work routine of military dogs are detectable by infrared thermography (IRT). The experiment was carried out on eight male German and Belgian shepherd patrol guard dogs performing two training activities, obedience and defence. The surface temperature (Ts) of 12 selected body parts on both body sides was measured with the IRT camera 5 min before, 5 min after and 30 min after training. As predicted, there was a greater increase in Ts (mean of all measured body parts) after defence than after obedience, 5 min (by 1.24 vs. 0.60 °C, P < 0.001) and 30 min after activity (by 0.90vs. 0.57 °C, P < 0.01) compared to pre-activity levels. These findings indicate that defence is more physically demanding than obedience activity. Considering the activities separately, obedience increased Ts 5 min after the activity only in the trunk (P < 0.001) but not in the limbs, whereas defence increased it in all measured body parts (P < 0.001). Ts 30 min after obedience decreased to the pre-activity level in parts at trunk, while in distal parts of the limbs Ts remained elevated. The prolonged elevation in Ts of the limbs after both activities indicates heat flow from the core to the periphery as a thermoregulatory mechanism. The current study suggests that IRT may be a useful tool for assessing physical workload in different body parts of dogs.


Transplantable pancreatic acinar carcinoma.
Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with [3H]-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with [3H]-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed.


Randomized trial of aloe vera gel vs triamcinolone acetonide ointment in the treatment of oral lichen planus.
To determine the effectiveness of aloe vera gel in the treatment of oral lichen planus when compared with triamcinolone acetonide. A randomized, double-blind, clinical trial was designed. The study sample constituted 40 patients (23 males and 17 females) who were randomly divided into two equal groups. Group A patients received aloe vera gel, while group B patients received triamcinolone acetonide. Forty patients were included in the study. Most of the sample presented with erosive (n = 18) and atrophic (n = 14) variants of oral lichen planus. When clinical signs and symptoms were observed after 8 weeks of therapy, it was determined that aloe vera gel was more effective than triamcinolone acetonide in the treatment of oral lichen planus. Aloe vera gel can be considered a safe alternative treatment for oral lichen planus.


Regular firing of a single output neuron reduces its own inhibition through endocannabinoids in substantia nigra pars reticulata of juvenile mice.
Depolarization-induced suppression of inhibition in substantia nigra pars reticulata suggests that burst-like activity but not regular firing suffices to activate presynaptic endocannabinoid CB1 receptors. To more closely determine the type of activity required, we applied gramicidin perforated patch recording under visual control to substantia nigra slices of juvenile mice. We found that evoked inhibitory postsynaptic currents (eIPSCs) were reduced in amplitude by the spontaneous firing of a neuron under study, whereas silencing this neuron enhanced inhibitory responses. Autonomous firing reduced eIPSCs to 78%+/-2% in a time- but not frequency-dependent manner. The phenomenon which we termed firing-induced suppression of inhibition was cannabinoid receptor subtype 1-dependent, whereas adenosine A1 receptors played only a minor role. Depletion of intracellular Ca(2+) stores abolished the firing-induced suppression of inhibition suggesting that Ca(2+) release from internal stores is necessary for the production of endocannabinoids during autonomous firing. We suggest that the Ca(2+) influx during autonomous activity of pars reticulata neurons suffices to selectively dampen incoming inhibition from striatal neurons because it is amplified by ryanodine receptor-mediated Ca(2+) release from intracellular stores.


ACSNI: An unsupervised machine-learning tool for prediction of tissue-specific pathway components using gene expression profiles.
Determining the tissue- and disease-specific circuit of biological pathways remains a fundamental goal of molecular biology. Many components of these biological pathways still remain unknown, hindering the full and accurate characterization of biological processes of interest. Here we describe ACSNI, an algorithm that combines prior knowledge of biological processes with a deep neural network to effectively decompose gene expression profiles (GEPs) into multi-variable pathway activities and identify unknown pathway components. Experiments on public GEP data show that ACSNI predicts cogent components of mTOR, ATF2, and HOTAIRM1 signaling that recapitulate regulatory information from genetic perturbation and transcription factor binding datasets. Our framework provides a fast and easy-to-use method to identify components of signaling pathways as a tool for molecular mechanism discovery and to prioritize genes for designing future targeted experiments (https://github.com/caanene1/ACSNI).


Associations between healthy lifestyle score and health-related quality of life among Chinese rural adults: variations in age, sex, education level, and income.
This study aimed to investigate the associations between overall lifestyles and HRQoL, as well as the variations in age, sex, education level, and income. A total of 23,402 participants from the Henan rural cohort were included. The healthy lifestyle score (HLS) consists of five lifestyle factors: smoking, alcohol drinking, physical activity, diet, and body mass index. HRQoL was assessed by the EQ-5D-5L questionnaire. The general linear model and Tobit regression model were utilized to assess the associations of HLS with visual analogue score (VAS) and utility index. Compared with participants with an HLS of 0-2, the corresponding regression coefficients (β) and 95% confidence intervals (CI) of participants with an HLS of 3, 4, and 5 for VAS score were 1.09 (0.59, 1.59), 1.92 (1.38, 2.46), and 2.60 (1.83, 3.37); the corresponding β and 95% CI for utility index were 0.02 (0.01, 0.03), 0.05 (0.03, 0.06), and 0.06 (0.04, 0.07). Notably, these positive associations were greater among the elderly, female, and those with lower education level and average monthly income (p for interaction < 0.05). For instance, the corresponding β and 95% CI of individuals with an HLS of 5 for utility index in average monthly income < 500 RMB, 500-999 RMB, and ≥ 1000 RMB groups were 0.08 (0.05, 0.11), 0.06 (0.03, 0.09), and 0.02 (- 0.00, 0.05). Engaging in healthier lifestyle habits was associated with a higher level of HRQoL, especially in the elderly, females, and those with low education level and average monthly income.


Complications after mandibular setback with intraoral vertical ramus osteotomies: a retrospective cohort analysis of 133 patients.
In the present study, we assessed the rate of complications and morbidity after mandibular setback with bilateral intraoral vertical ramus osteotomy (IVRO). In total, 133 patients were included. The prevalence of neurosensory disturbance (NSD), surgical site infection (SSI), and other complications were registered 2 months and 1 year after surgery. The correlations between complications and age, sex, American Society of Anesthesiologists classification, body mass index, blood loss, and operative time were evaluated. NSD was reported for 6.8% of the patients (9 of 133) 2 months after surgery (3.8% of the operated sites). The prevalence was significantly higher in female patients (P < .05). Two patients described persistent unilateral reduced sensibility after 1 year (1.5%). In total, 0.8% of the operated sites (2 of 266) had persistent NSD after 1 year. None of the patients required prolonged hospitalization, and 95.5% (127 of 133) were discharged the day after surgery. None of the patients experienced severe bleeding, and only 1 patient developed SSI. There were no significant correlations between patient-specific or intraoperative parameters evaluated and registered complications. This study shows that IVRO is a safe surgical technique associated with a low complication rate. IVRO can be an alternative technique for mandibular setback in patients who can tolerate postoperative maxillomandibular fixation.


Cancer screening in women by internal medicine resident physicians.
Research suggests that women may not have consistent cancer surveillance. We conducted a retrospective review of internal medicine resident physicians' screening methods for breast, cervical, and colorectal cancer of women aged 50 or older. Resident physicians did breast examinations in 39.1%, mammography in 37.3%, Pap smears in 32.7%, rectal examinations in 37.3%, fecal occult blood testing in 39.1%, and flexible sigmoidoscopy in 11.8% of the women. They instructed 3.6% to do breast self-examination. There was no statistically significant difference in the breast or cervical cancer screening based on patient race, insurance type, or sex of physician. Female physicians did more rectal examinations and fecal occult blood testing than male physicians. There was no statistically significant difference in colorectal cancer surveillance based on physician race or insurance status. We need to increase cancer screening in women. Assessment of the impact of the sex of the physician on cancer surveillance needs to be further evaluated.


Automatic quantitative evaluation of normal pancreas based on deep learning in a Chinese adult population.
To develop a 3D U-Net-based model for the automatic segmentation of the pancreas using the diameters, volume, and density of normal pancreases among Chinese adults. A total of 2778 pancreas images (dataset 1) were retrospectively collected and randomly divided into training (n = 2252), validation (n = 245), and test (n = 281) datasets. The segmentation model for the pancreas was constructed through cascaded application of two 3D U-Net networks. The segmentation efficiency for the pancreas was evaluated by the Dice similarity coefficient (DSC). Another dataset of 3189 normal pancreas CT images (dataset 2) was obtained for external validation, including 1063 non-contrast images, 1063 arterial phase images, and 1063 portal venous phase images. The pancreas segmentation in dataset 2 was assessed objectively and manually revised by two radiologists. Then, the pancreatic volume, diameters, and average CT value for each phase of pancreas images in dataset 2 were calculated. The relationships between pancreas volume and age, sex, height, and weight were analyzed. In dataset 1, a mean DSC of 0.94 for the test dataset was achieved. In dataset 2, the objective assessment yielded a 90% satisfaction rate for the automatic segmentation of the pancreas as external validation. The diameters of the pancreas were 43.71-44.28 mm, 67.40-68.15 mm, and 114.53-117.06 mm, respectively. The average pancreatic volume was 63,969.06-65,247.75 mm3, which was greatest at the age of 18-38 and then decreased to a minimum at the age of 69-85. The CT value of the pancreas also decreased with age, from a maximum value of 38.87 ± 9.70 HU to a minimum of 27.72 ± 10.85 HU. The pancreas segmentation tool based on deep learning can segment the pancreas on CT images and measure its normal diameter, volume, and CT value accurately and effectively.


Three-year clinical follow-up after strontium-90/yttrium-90 beta-irradiation for the treatment of in-stent coronary restenosis.
Because late vessel failure has been speculated as a possible limitation of vascular brachytherapy, we conducted a prospective clinical evaluation at 6, 12, 24, and 36 months of follow-up after irradiation with strontium-90/yttrium-90 for in-stent restenosis, regardless of the patient's symptomatic status. We report complete 3-year follow-up data for 106 consecutive patients. The cumulative rate of death at 6, 12, 24, and 36 months was 0.9%, 0.9%, 0.9%, and 1.9% respectively. The corresponding rates for acute ST-elevation myocardial infarction were 2.8%, 4.7%, 4.7%, and 4.7%, respectively. The cumulative rate of late thrombotic occlusion at 6, 12, 24, and 36 months was 3.8%, 4.7%, 4.7%, and 4.7%, respectively. The corresponding rates of target lesion revascularization and target vessel revascularization were 8.5% and 12.3% (p = 0.046), 14.2% (p = 0.157) and 18.0% (p = 0.046), 12.3% and 18.9% (p = 0.008), and 21.7% (p = 0.083) and 29.2% (p = 0.005), respectively. The cumulative rate of all major adverse cardiovascular events at 6, 12, 24, and 36 months was 16.1%, 24.5% (p = 0.003), 27.4% (p = 0.083), and 35.8% (p = 0.003), respectively. In conclusion, these results indicate a delayed and, even in the third year after the index procedure, continued restenotic process after beta irradiation of in-stent restenotic lesions.


Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia.
Recently, we and others could define the molecular cause of the rare disease congenital amegakaryocytic thrombocytopenia (CAMT) as mutations in the c-mpl gene (Blood 97: 139, 2001). We proposed that c-mpl mutations are the cause not only for the hypomegakaryocytic thrombocytopenia, but also for the development of an aplastic anemia (AA) in patients with CAMT. The effects of thrombopoietin (TPO) on early multipotent hematopoietic progenitors were elucidated by a recent series of in vitro and in vivo studies. Like CAMT patients, mice lacking the TPO receptor c-Mpl demonstrate a major reduction of early hematopoietic progenitor cells of all lineages. However, these mice achieve a normal marrow cellularity and composition, despite the lack of megakaryocytes. On the other hand, the incidence of development of aplastic anemia in CAMT is not clear owing to difficult and not consistent diagnosis of this disease.


The complete chloroplast genome of Vitis amurensis Rupr., an economic plant to China.
The chloroplast (cp) genome sequence of Vitis amurensis has been characterized from Illumina pair-end sequencing. The complete cp genome was 161,014 bp in length, containing a large single-copy region (LSC) of 89,239 bp and a small single-copy region (SSC) of 19,067 bp, which were separated by a pair of 26,354 bp inverted repeat regions (IRs). The genome contained 133 genes, including 88 protein coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content is 37.4%, while the corresponding values of the LSC, SSC, and IR regions are 35.3%, 31.7%, and 43.0%, respectively. Further, phylogenetic analysis suggested that the V. amurensis was sister to Vitis coignetiae.


Femtosecond laser writing of multifunctional optical waveguides in a Nd:YVO4 + KTP hybrid system.
We report on the fabrication of optical channel waveguides supporting both visible and IR TE and TM confinement in a hybrid system composed of a Nd:YVO4 laser gain medium glued to a potassium titanyl phosphate (KTP) nonlinear crystal. The microphotoluminescence and second harmonic confocal images of the fabricated waveguides have revealed that the laser and nonlinear properties of the constituent crystals have not been deteriorated because of the waveguide inscription. The resulting structures emerge as promising candidates for the development of multifrequency waveguide lasers.


Does pregnancy and/or shifting positions create more room in a woman's pelvis?
The purpose of this study was to assess the impact of different positions on pelvic diameters by comparing pregnant and nonpregnant women who assumed a dorsal supine and kneeling squat position. In this cohort study from a tertiary referral center in Germany, we enrolled 50 pregnant women and 50 nonpregnant women. Pelvic measurements were obtained with obstetric magnetic resonance imaging pelvimetry with the use of a 1.5-T scanner. We compared measurements of the depth (anteroposterior (AP) and width (transverse diameters) of the pelvis between the 2 positions. The most striking finding was a significant 0.9-1.9 cm increase (7-15%) in the average transverse diameters in the kneeling squat position in both pregnant and nonpregnant groups. The average bispinous diameter in the pregnant group increased from 12.6 cm ± 0.65 cm in the supine dorsal to 14.5 cm ± 0.64 cm (P < .0001) in the kneeling squat; in the nonpregnant group the increase was from 12 cm ± 0.76 cm to 13.9 cm ± 1.04 cm (P < .0001). The average bituberous diameter in the pregnant group increased from 13.6 cm ± 0.93 cm in the supine dorsal to 14.5 cm ± 0.83 cm (P < .0001) in the kneeling squat position; in the nonpregnant women the increase was from 12.6 cm ± 0.92 cm to 13.5 cm ± 0.88 cm (P < .0001). A kneeling squat position significantly increases the bony transverse and anteroposterior dimension in the mid pelvic plane and the pelvic outlet. Because this indicates that pelvic diameters change when women change positions, the potential for facilitation of delivery of the fetal head suggests further research that will compare maternal delivery positions is warranted.


Use of the redox-dependent intein system for enhancing production of the cyclic green fluorescent protein.
To expand the reported redox-dependent intein system application, in this work, we used the split intein variant with highly trans-splicing efficiency and minimal extein dependence to cyclize the green fluorescent protein variant reporter in vitro. The CPG residues were introduced adjacent to the intein's catalytic cysteine for reversible formation of a disulfide bond to retard the trans-splicing reaction under the oxidative environment. The cyclized reporter protein in Escherichia coli cells was easily prepared by organic extraction and identified by the exopeptidase digestion. The amounts of extracted cyclized protein reporter in BL21 (DE3) cells were higher than those in hyperoxic SHuffle T7 coexpression system for facilitating the disulfide bond formation. The double His6-tagged precursor was purified for in vitro cyclization of the protein for 3 h. Compared with the purified linear counterpart, the cyclic reporter showed about twofold increase in fluorescence intensity, exhibited thermal and hydrolytic stability, and displayed better folding efficiency in BL21 (DE3) cells at the elevated temperature. Taken together, the developed redox-dependent intein system will be used for producing other cyclic disulfide-free proteins. The cyclic reporter is a potential candidate applied in certain thermophilic aerobes.


Experimental and theoretical study of dyes adsorption process on chitosan-based cryogel.
In this research, the adsorption of three synthetic dyes dissolved in an aqueous solution on chitosan cryogel beads (Q-C-EGDE) was compared. The effect of the pH of the solution on the adsorption capacity of each dyes was analyzed. Furthermore, the kinetics and adsorption isotherms were compared, at temperatures of 283.15 K, 303.15 K and 323.15 K, and the kinetic and adsorption equilibrium data were fitted to three mathematical models, respectively. The biosorbent was characterized by scanning electron microscopy (SEM), the nitrogen physisorption BET method and Fourier transform infrared spectroscopy (FTIR). The characterization results show that the cryogel is composed of low-surface, macroporous, porous grooved walls. The functional groups that took part in the adsorption were mainly amino groups (NH3+). When comparing the adsorption capacities, it was found that the dyes adsorb in the following order Blue 1 > Red 2 > Yellow 5 reaching capacities from 1600 mg/L to 850 mg/L. The results of the adsorption and mathematical modelling suggest that the process is regulated mainly by physisorption and is largely limited by mass transfer mechanisms within the cryogel, where the electrostatic charges present affect adsorption. The latter was corroborated by the Monte Carlo simulation.


The effect of Mitoquinol (MitoQ) on heat stressed skeletal muscle from pigs, and a potential confounding effect of biological sex.
Heat stress (HS) poses a major threat to human health and agricultural production. Oxidative stress and mitochondrial dysfunction appear to play key roles in muscle injury caused by HS. We hypothesized that mitoquinol (MitoQ), would alleviate oxidative stress and cellular dysfunction in skeletal muscle during HS. To address this, crossbred barrows (male pigs) were treated with placebo or MitoQ (40 mg/d) and were then exposed to thermoneutral (TN; 20 °C) or HS (35 °C) conditions for 24 h. Pigs were euthanized following the environmental challenge and the red portion of the semitendinosus (STR) was collected for analysis. Unexpectedly, malondialdehyde concentration, an oxidative stress marker, was similar between environmental and supplement treatments. Heat stress decreased LC3A/B-I (p < 0.05) and increased the ratio of LC3A/B-II/I (p < 0.05), while p62 was similar among groups suggesting increased degradation of autophagosomes during HS. These outcomes were in disagreement with our previous results in muscle from gilts (female pigs). To probe the impact of biological sex on HS-mediated injury in skeletal muscle, we compared STR from these barrows to archived STR from gilts subjected to a similar environmental intervention. We confirmed our previous findings of HS-mediated dysfunction in muscle from gilts but not barrows. These data also raise the possibility that muscle from gilts is more susceptible to environment-induced hyperthermia than muscle from barrows.


Classical conditioning of the nictitating membrane response of the rabbit. I. Lesions of the cerebellar nuclei.
The classically conditioned nictitating membrane response (NMR) of the rabbit, a simple form of associative motor learning, is crucially dependent upon the cerebellum. Discrete unilateral lesions of the cerebellar nuclei were made in 20 rabbits. Lesions of the anterior interpositus nucleus (IA) abolished NMR conditioning to light and white noise stimuli on the side of the lesion without affecting unconditional responses. Lesions of the posterior interpositus nucleus, fastigial and dentate nuclei were without effect upon NMR conditioning.


Cranial MR-Guided Focused Ultrasound: Clinical Challenges and Future Directions.
Magnetic resonance-guided focused ultrasound is a powerful new technology that is enabling development of noninvasive applications for complex brain disorders. This is currently revolutionizing the treatment of tremor disorders, and a variety of experimental applications are under active investigation. To fully realize the potential of this disruptive technology, many challenges have been identified, some of which have been addressed and others remain to be solved. As an image-based technology, optimal intraoperative imaging can be difficult to achieve and several factors can influence the quality of these images. Technical issues with current devices can also limit the effective delivery of ultrasound technology to particular targets. While lesioning is the primary approved application of magnetic resonance-guided focused ultrasound at present, the ability to transient and precisely open the blood-brain barrier has the potential to clear brain pathologies and deliver restorative therapies, but this more experimental method presents unique difficulties to overcome. Finally, regulatory and reimbursement hurdles currently remain complex and continue to limit widespread application of even approved, effective applications. Here we review many of these challenges, discuss several solutions that have already been developed, and propose potential options for addressing some of these complexities in the future.


The Effect of E-Learning Program for COVID-19 Patient Care on the Knowledge of Nursing Students: A Quasi-Experimental Study.
As COVID-19 is an emerging disease, nursing students have little experience in caring for COVID-19 patients while they will be part of the country's health system and have the closest relationship with the treatment team. Therefore, considering the importance and challenges of nursing students' education during the COVID-19 pandemic, the present study aimed to investigate the effect of e-learning programs for COVID-19 patient care on nursing students' knowledge in Tehran, Iran 2021. The present quasi-experimental study was performed on 100 nursing students selected by a random sampling method. The demographic and knowledge assessment questionnaires were used to collect data before the intervention. Then, the e-learning program was implemented, in which students participated in three sessions for two weeks, the educational content was provided for the students in the form of text, audio, video, and image files, and questions were asked to them. Data were collected immediately after completing the e-learning program and four weeks later. The mean age value was 22 ± 1.25, and 61% of participants were female. The total mean score of knowledge immediately after training (22.95 ± 0.30) and one month after training (22.79 ± 0.30) significantly increased compared to baseline time (17.21 ± 0.48). The main effect of time was significant for the total score of knowledge from baseline to immediately after training (B = 5.79) and one-month follow-up (B = 5.63). The findings of the study showed that the total mean score of the knowledge of students increased significantly in all dimensions after the e-learning program for COVID-19 patient care. Considering the effectiveness of the e-learning program for COVID-19 patient care in increasing the knowledge of nursing students, it is necessary to provide more training programs focusing on new scientific findings because increasing nurses' and nursing students' knowledge plays a significant role in achieving more skills and promoting community health.


New developments in the analysis of fragrances and earthy-musty compounds in water by solid-phase microextraction (metal alloy fibre) coupled with gas chromatography-(tandem) mass spectrometry.
Fragrances are widespread aquatic contaminants due to their presence in many personal care products used daily in developed countries. Levels of galaxolide and tonalide are commonly found in surface waters, urban wastewaters and river sediments. On the other hand, earthy-musty compounds confer bad odour to drinking water at levels that challenge the analytical capabilities. The combined determination of earthy-musty compounds and fragrances in water would be a breakthrough to make the traditional organoleptic evaluation of the water quality stricter and safer for the analyst. Two approaches were attempted to improve the analytical capabilities: analyte pre-concentration with a newly developed PDMS-DVB solid-phase microextraction fibre on metal alloy core and sensitive detection by tandem mass spectrometry (MS/MS). The optimization of SPME parameters was carried out using a central composite design and desirability functions. The final optimum extraction conditions were: headspace extraction at 70°C during 40 min adding 200 g L(-1) of NaCl. The detection limits in tandem MS (0.02-20 ng L(-1)) were marginally lower compared to full scan except for geosmin and trichloroanisol which go down to 0.1 and 0.02 ng L(-1), respectively. The analysis of different water matrices revealed that fragrances and earthy-musty compounds were absent from ground- and drinking waters. Surface waters of river Leça contained levels of galaxolide around 250 ng L(-1) in the 4 terminal sampling stations, which are downstream of WWTPs and polluted tributaries. Geosmine was ubiquitously distributed in natural waters similarly in rivers Leça and Douro at concentrations <7 ng L(-1).