Crystal structure and electrostatic properties of prednisolone acetate studied using a transferred multipolar atom model.
Prednisolone acetate {systematic name: 2-[(8S,9S,10R,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate}, is an ophthalmic drug that belongs to the class of corticosteroids. Its crystal structure was refined using the classical independent atom model (IAM) and a transferred multipolar atom model using the ELMAM2 database. The results of both refinements have been compared. The ELMAM2 refinement was found to be superior in terms of the refinement statistics. It has been shown that certain electron-density-derived properties can be calculated on the basis of the transferred parameters for crystals which diffract to ordinary resolution. The procedure proves helpful in understanding the mode of action of the drug molecule.


Approach to the synthesis of indoline derivatives from diaryliodonium salts.
An effective method of constructing the indoline moiety via intramolecular nucleophilic ring closure of a diaryliodonium salt is described. Diacetoxyiodoarene compounds (1a-1e) were converted into intermediate Koser's reagent and coupled with arylstannanes (7-10) to form diaryliodonium salts (11a-14e). Indoline compounds with different N-protecting groups, 15, 16, 17, and 18, were synthesized in higher yields by treating salts (11a-14e) with Cs(2)CO(3) and TEMPO. Regardless of the electronic environment of five para-substituted iodoarenes and the natures of four N-protected arylstannane groups, the conversion proceeded well to afford corresponding indolines in yields of 72-84 and 70-84%, respectively.


Influence of electron donor and acceptor substituents on tuning the nonlinear optical properties of zinc phthalocyanine derivatives.
Four phthalocyanine derivatives with different electron donor and acceptor substituents (B1, B2, B3, and B4) were synthesized by a solid-phase melting method. The influence of substituent type on the nonlinear optical properties of the materials was investigated in detail. In the case of similar conjugated structures, B3, which has amino electron-donor groups, presents high intramolecular charge transfer, a low energy gap (2.05 eV), and good nonlinear optical properties. Compared with B3, B4 has a larger π-conjugated structure and its energy gap is 0.04 eV smaller. Moreover, B4 has stronger reverse saturation absorption (7 × 10-12 m/W) and optical limiting performance. The four phthalocyanine derivatives exhibit third harmonic generation (THG) characteristics. Furthermore, the third harmonic strengths of B1, B2, B3, and B4 are 4 times, 9 times, 11 times, and 21 times that of SiO2, respectively. So, B4 has the best application potential in laser protection and frequency conversion.


Chirp-driven vibrational distribution in transition metal carbonyl complexes.
In this theoretical study vibrational ladder climbing in transition metal carbonyl complexes, as a possible means to initialize chemical ground state reactions, and the resulting vibrational population distribution using chirped mid-infrared femtosecond laser pulses is investigated. Our model system is MnBr(CO)(5), a strong IR-absorber within an experimentally easily accessible wavelength region. Special emphasis is put on the perturbation due to additional vibrational modes, especially on one, which allows dissociation at low energies. The related potential energy surface for the three representative modes is calculated, whereon quantum dynamics calculations, including the laser-molecule interaction, are performed. No significant coupling could be detected, neither in the bound, nor in the dissociative region. Contrarily, we found a dynamical barrier even for energies high above the dissociation limit. Different vibrational population distributions after the laser excitation of the CO stretching mode could be generated in dependence of the chirp parameters. Based on these findings we simulated the laser excitation corresponding to an experiment by M. Joffre et al., Proc. Natl. Acad. Ssi. U. S. A., 2004, 101(36), 13216-13220, where coherent vibrational ladder climbing in carboxyhemoglobin was demonstrated and we could offer an explanation for an open question, concerning the interpretation of the spectroscopic data.


Preparing for adulthood--patterns of physical growth, sexual maturity and menarche of adolescent girls in selected urban slums and rural areas.
Adolescent girls are the future mothers. Height less than 145 cm and weight less than 45 kg are considered to be high obstetric risk factor for adverse maternal and perinatal outcome including low birth weight. Teenage pregnancy is another problem in our country. This study aimed to study height and weight of girls of vulnerable urban slums and rural areas. It also studied the pattern of onset of menarche and attainment of sexual maturity in relation to age. The longitudinal, multicentric, descriptive observational study was carried out by the Indian Council of Medical Research during the period of 1986 to 1991 in selected rural (Chandigarh, Hyderabad, Jabalpur, Varanasi, Vellore) and two urban slum areas (Vellore and Delhi) in different regions of India. Girls of ages 10-12 years were followed up till 16 years for their height and weight. Weight increased from 22.3 to 39.4 kg in rural and 23.4 to 41.9 kg in urban areas from 10 to 16 years. Height increased from 126.2 cm to 150.2 cm in rural and 128.2 to 153.0 cm in urban areas. Large variations from centre to centre were observed in ages for appearance of sexual characteristic and the order in which these appeared. Pubic hair was the first sexual characteristic to appear in majority of the girls in all the centres. The mean age at stages II, III and IV of breast development in girls varied between 11.3 to 12.3 years, 12.3 to 13.2 years and 13.3 to 14.1 years respectively. The percentage of girls who had attained menarche by the age of 15 years, ranged from 30 to 100 per cent between centres. Those children in whom the sexual characteristics had appeared earlier than others had higher mean body weight and height as compared to others at the same age points. The data on physical growth parameters during adolescence revealed that girls from rural areas, were shorter and weighed less compared to those from urban slums. Adolescent girls are undernourished in urban slums and rural areas.


Aripiprazole versus other atypical antipsychotics for schizophrenia.
In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first-line drug treatments for people with schizophrenia. In this review, we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. To review the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group Trials Register (November 2012), inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study and used GRADE approach to rate quality of evidence. We now have included 174 trials involving 17,244 participants. Aripiprazole was compared with clozapine, quetiapine, risperidone, ziprasidone and olanzapine. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with clozapine, there were no significant differences for global state (no clinically significant response, n = 2132, 29 RCTs, low quality evidence); mental state (BPRS, n = 426, 5 RCTs, very low quality evidence); or leaving the study early for any reason (n = 240, 3 RCTs, very low quality evidence). Quality of life score using the WHO-QOL-100 scale demonstrated significant difference, favouring aripiprazole (n = 132, 2 RCTs, RR 2.59 CI 1.43 to 3.74, very low quality evidence). General extrapyramidal symptoms (EPS) were no different between groups (n = 520, 8 RCTs,very low quality evidence). No study reported general functioning or service use.When compared with quetiapine, there were no significant differences for global state (n = 991, 12 RCTs, low quality evidence); mental state (PANSS positive symptoms, n = 583, 7 RCTs, very low quality evidence); leaving the study early for any reason (n = 168, 2 RCTs, very low quality evidence), or general EPS symptoms (n = 348, 4 RCTs, very low quality evidence). Results were significantly in favour of aripiprazole for quality of life (WHO-QOL-100 total score, n = 100, 1 RCT, MD 2.60 CI 1.31 to 3.89, very low quality evidence). No study reported general functioning or service use.When compared with risperidone, there were no significant differences for global state (n = 6381, 80 RCTs, low quality evidence); or leaving the study early for any reason (n = 1239, 12 RCTs, very low quality evidence). Data were significantly in favour of aripiprazole for improvement in mental state using the BPRS (n = 570, 5 RCTs, MD 1.33 CI 2.24 to 0.42, very low quality evidence); with higher adverse effects seen in participants receiving risperidone of general EPS symptoms (n = 2605, 31 RCTs, RR 0.39 CI 0.31 to 0.50, low quality evidence). No study reported general functioning, quality of life or service use.When compared with ziprasidone, there were no significant differences for global state (n = 442, 6 RCTs, very low quality evidence); mental state using the BPRS (n = 247, 1 RCT, very low quality evidence); or leaving the study early for any reason (n = 316, 2 RCTs, very low quality evidence). Weight gain was significantly greater in people receiving aripiprazole (n = 232, 3 RCTs, RR 4.01 CI 1.10 to 14.60, very low quality evidence). No study reported general functioning, quality of life or service use.When compared with olanzapine, there were no significant differences for global state (n = 1739, 11 RCTs, very low quality evidence); mental state using PANSS (n = 1500, 11 RCTs, very low quality evidence); or quality of life using the GQOLI-74 scale (n = 68, 1 RCT, very low quality of evidence). Significantly more people receiving aripiprazole left the study early due to any reason (n = 2331, 9 RCTs, RR 1.15 CI 1.05 to 1.25, low quality evidence) and significantly more people receiving olanzapine gained weight (n = 1538, 9 RCTs, RR 0.25 CI 0.15 to 0.43, very low quality evidence). None of the included studies provided outcome data for the comparisons of 'service use' or 'general functioning'. Information on all comparisons is of limited quality, is incomplete and problematic to apply clinically. The quality of the evidence is all low or very low. Aripiprazole is an antipsychotic drug with an important adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerge from ongoing larger, independent pragmatic trials.


Dopamine D2-like receptor agonist bromocriptine protects against ischemia/reperfusion injury in rat kidney.
Dopamine, via activation of D1-like and D2-like receptors, plays an important role in the regulation of renal sodium excretion. Recently, we demonstrated that dopamine D2-like receptor agonist (bromocriptine) stimulates p44/42 mitogen-activated protein kinases (MAPKs) and Na+,K(+)ATPase (NKA) activity in proximal tubular epithelial cells. Since both these parameters are compromised in ischemia/reperfusion (I/R) injury to the kidney, we investigated whether bromocriptine protects against the injury. In this study we used unilateral rat model of renal I/R injury. The Sprague-Dawley rats were divided into vehicle and bromocriptine groups. The vehicle and bromocriptine group was treated with vehicle and bromocriptine (500 microg/kg intravenously), respectively, 15 minutes before the induction of unilateral ischemia followed by 24- or 48-hour reperfusion. At the end of 24 or 48 hours the animals were sacrificed to collect control and ischemic kidney cortices, in which necrosis, apoptosis, NKA activity, NKA alpha1 subunit expression, and p44/42 MAPK phosphorylation were measured. We found extensive necrosis, apoptosis, and decreased NKA activity (with no change in alpha1 subunit) in the ischemic kidney cortex compared to the nonischemic cortex from the vehicle-treated rats as early as 24 hours post-reperfusion. In contrast, I/R injury-induced necrotic, apoptotic, and decrease in NKA activity were absent in the outer cortex of bromocriptine-treated rats after 24 or 48 hours. Interestingly, we detected significantly higher phosphorylation of p44/42 MAPKs in control and ischemic kidneys of bromocriptine-treated rats compared to those of vehicle-treated rats. Therefore, bromocriptine, a D1-like receptor agonist, may protect against I/R injury to proximal tubules of the kidney, via p44/42 MAPK activation.


Too sick or not too sick? The importance of stress and satisfaction with supervisor support on the prevalence of sickness presenteeism.
In a sample of 3274 full-time Belgian workers, this article found that 62% of workers went to work while being sick (sickness presenteeism) at least once over the past 12 months. Of all workers who did not show sickness presenteeism themselves, another 6 out of 10 saw or heard about sickness presenteeism in their own organization. Women were more likely to report sickness presenteeism than men and junior workers were more prone to sickness presenteeism than senior workers. Education did not explain the choice for sickness presenteeism. Satisfaction with the supervisor had a direct negative effect on sickness presenteeism. Finally, indirect effects were found between satisfaction with the supervisor and sickness presenteeism via the prevalence of stress. While previous studies showed that good supervisor support can make sick workers more productive when they show up at work, this study shows that good supervisor support makes sick workers stay at home.


Providing Crisis-oriented and Recovery-based Treatment in Partial Hospitalization Programs.
Partial hospitalization programs represent a midpoint along the treatment intensity continuum between an inpatient and an outpatient service. Partial hospitalization programs can be used in place of an inpatient unit for patients who need crisis stabilization and amelioration of their acute symptoms, but who are not imminently homicidal or suicidal. Partial hospitalization programs can also manage adjustments in pharmacotherapy, conduct skills classes, and engage patients in group psychotherapy. In this article, the authors describe the roles and functions of partial hospitalization programs in today's spectrum of psychiatric services and describe the process of transition from an acute inpatient unit to a partial hospitalization programs.


Anaerobacillus alkaliphilus sp. nov., a novel alkaliphilic and moderately halophilic bacterium.
Two alkaliphilic and moderately halophilic bacterial strains B16-10T and Z23-18 characterized by optimal growth at pH 9.0-10.0 and 5 % (w/v) NaCl, were isolated from the rhizosphere soil of the bayonet grass (Bolboschoenus maritimus) in the Kiskunság National Park, Hungary. Cells of both strains stained Gram-positive, were motile straight rods, and formed terminal, ellipsoidal endospores with swollen sporangia. The isolates were facultative anaerobic, catalase positive, oxidase negative. Both strains contained meso-diaminopimelic acid as diagnostic diaminoacid of the peptidoglycan. Menaquinone-7 (MK-7) was the predominant isoprenoid quinone. Anteiso-C15 : 0, C16 : 1ω11c and iso-C14 : 0 were the major cellular fatty acids. The DNA G+C content of both strains was 35.8 mol%. The 16S rRNA gene based phylogenetic analysis revealed that the facultative anaerobic strains B16-10T and Z23-18 showed the highest similarities to the type strains of anaerobic Anaerobacillus isosaccharinicus NB2006T (98.7 and 99.1 %), A. macyae JMM-4T (98.2 and 98.4 %), A. alkalidiazotrophicus MS 6T (97.7 and 98.4 %), A. alkalilacustris Z-0521T (97.5 and 98.3 %) and A. arseniciselenatis DSM 15340T (97.5 and 98.2 %). However, the distinctive phenotypic and genetic results of this study confirmed that strains B16-10T and Z23-18 represent a novel species, for which the name Anaerobacillus alkaliphilus sp. nov. is proposed. The type strain is B16-10T (=DSM 29790T=NCAIM B 02608T).


In situ experiments to reveal the role of surface feature sidewalls in the Cassie-Wenzel transition.
Waterproof and self-cleaning surfaces continue to attract much attention as they can be instrumental in various different technologies. Such surfaces are typically rough, allowing liquids to contact only the outermost tops of their asperities, with air being entrapped underneath. The formed solid-liquid-air interface is metastable and, hence, can be forced into a completely wetted solid surface. A detailed understanding of the wetting barrier and the dynamics of this transition is critically important for the practical use of the related surfaces. Toward this aim, wetting transitions were studied in situ at a set of patterned perfluoropolyether dimethacrylate (PFPEdma) polymer surfaces exhibiting surface features with different types of sidewall profiles. PFPEdma is intrinsically hydrophobic and exhibits a refractive index very similar to water. Upon immersion of the patterned surfaces into water, incident light was differently scattered at the solid-liquid-air and solid-liquid interface, which allows for distinguishing between both wetting states by dark-field microscopy. The wetting transition observed with this methodology was found to be determined by the sidewall profiles of the patterned structures. Partial recovery of the wetting was demonstrated to be induced by abrupt and continuous pressure reductions. A theoretical model based on Laplace's law was developed and applied, allowing for the analytical calculation of the transition barrier and the potential to revert the wetting upon pressure reduction.


Interrelationship between oral status and histopathological aspects of periodontitis in patients from Craiova, Romania.
The aim of the present study was to evaluate the oral status in a group of institutionalized individuals from Craiova, a city in South-Western Romania. Also, another objective of the study was to highlight the clinical, histological and immunohistochemical (IHC) aspects of periodontal disorders in the elderly. The study was performed on 48 institutionalized individuals examined in the Clinic of Dental Prosthetics, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, Romania, in 2013. The data were collected using medical records and intraoral clinical examination. The data were processed by descriptive statistical analysis. The gingival mucosa samples were harvested from subjects with teeth mobility. The gingival fragments collected were processed through the histological technique of paraffin inclusion. The serial sections were commonly stained with Hematoxylin-Eosin and processed by the IHC technique with anti-CD3, anti-CD45RO and anti-CD20 antibodies. Of the 48 study participants, 20 were males, 28 were females, aged over 56 years old. 66.6% of them had poor oral hygiene, with a mean simplified oral hygiene index (OHI-S) of 1.57, 16 had the generalized periodontitis, three experienced some form of gingival overgrowth at the remaining teeth caused by incorrect fixed prosthesis, and 25 participants presented a form of periodontitis with gingival retraction. Gingival mucosa samples were histologically diagnosed with papillomatosis with discrete parakeratosis and rich chronic inflammatory infiltrate. The IHC reactions for the studied antibodies were different for T- and B-cells, which had different disposition in lamina propria.


REPRODUCTIVE ISOLATION BETWEEN SYMPATRIC RACES OF PEA APHIDS. I. GENE FLOW RESTRICTION AND HABITAT CHOICE.
Determining the extent and causes of barriers to gene flow between genetically divergent populations or races of single species is an important complement to post facto analyses of the causes of reproductive isolation between recognized species. Sympatric populations of pea aphids (Acyrthosiphon pisum Harris, Homoptera: Aphididae) on alfalfa and red clover are highly genetically divergent and locally adapted. Here, hierarchical estimates of population structure based on Fst suggest that gene exchange between closely adjacent aphid populations on the two hosts is highly restricted relative to that among fields of the same host plant. Although these host-associated races are presently considered to be the same subspecies, they appear to be significantly reproductively isolated, suggesting incipient speciation. Habitat (host) choice was investigated as the first in a temporal series of factors that could reduce gene exchange between these sympatric populations. Field studies of winged colonists to newly planted fields of each host suggest pronounced habitat fidelity. This result was verified using replicated observations of the host choice behavior of different aphid genotypes for which the relative demographic performance on each host was known. These laboratory observations of behavior revealed a strong genetic correlation between habitat choice (or acceptance) and the relative performance in each habitat. Because mating occurs on the host plant, habitat choice in this system leads to assortative mating and is therefore a major cause of reproductive isolation between the sympatric pea aphid populations on alfalfa and clover. However, the extent of dispersal between hosts estimated from the field study of winged colonists (9-11%) is too great to be consistent with the genetic divergence estimated between the races. This suggests that barriers to gene flow other than host choice also exist, such as selection against migrants or hybrids in the parental environments, hybrid sterility, or hybrid breakdown.


The use of pharmacokinetic models in paediatric onco-haematology: effects on clinical outcome through the examples of busulfan and cyclosporine.
Overall survival after allogeneic haematopoietic stem cell transplantation (HSCT) is reduced by the high rate of transplantation-related mortality (TRM), especially because of liver veno-occlusive disease (VOD) or acute graft-vs.-host disease (GVHD) because of the toxicity or inefficacy of busulfan and cyclosporine (CsA), respectively. Results of clinical outcome of previous studies performed to optimize busulfan and CsA therapy by controlling their pharmacokinetic variability by means of maximum a posteriori (MAP) Bayesian individualization of both drugs are presented. The 90-day VOD-free survival was significantly higher in patients with individualized busulfan doses: 97% vs. 76%. Monitoring CsA trough blood concentrations allowed us to obtain a successful GVHD outcome (mild or moderate GVHD and graft vs. leukaemia effect (GVL) in malignant diseases and no GVHD (in non-malignant ones) in the majority of our patients. Severe GVHD occurred in <5% of patients. TRM in children can be significantly decreased by using population pharmacokinetic models and MAP Bayesian individualization of dose regimens for drugs such as CsA and busulfan.


Sexually dimorphic impact of preconceptional and gestational exposure to a real-life environmental chemical mixture (biosolids) on offspring growth dynamics and puberty in sheep.
Humans are ubiquitously exposed to complex mixtures of environmental chemicals (ECs). This study characterised changes in post-natal and peripubertal growth, and the activation of the reproductive axis, in male and female offspring of sheep exposed to a translationally relevant EC mixture (in biosolids), during pregnancy. Birthweight in both sexes was unaffected by gestational biosolids exposure. In contrast to females (unaffected), bodyweight in biosolids males was significantly lower than controls across the peripubertal period, however, they exhibited catch-up growth eventually surpassing controls. Despite weighing less, testosterone concentrations were elevated earlier, indicative of early puberty in the biosolids males. This contrasted with females in which the mean date of puberty (first progesterone cycle) was delayed. These results demonstrate that developmental EC-mixture exposure has sexually dimorphic effects on growth, puberty and the relationship between body size and puberty. Such programmed metabolic/reproductive effects could have significant impacts on human health and wellbeing.


Single-subject gray matter networks predict future cortical atrophy in preclinical Alzheimer's disease.
The development of preventive strategies in early-stage Alzheimer's disease (AD) requires measures that can predict future brain atrophy. Gray matter network measures are related to amyloid burden in cognitively normal older individuals and predict clinical progression in preclinical AD. Here, we show that within individuals with preclinical AD, gray matter network measures predict hippocampal atrophy rates, whereas other AD biomarkers (total gray matter volume, cerebrospinal fluid total tau, and Mini-Mental State Examination) do not. Furthermore, in brain areas where amyloid is known to start aggregating (i.e. anterior cingulate and precuneus), disrupted network measures predict faster atrophy in other distant areas, mostly involving temporal regions, which are associated with AD. When repeating analyses in age-matched, cognitively unimpaired individuals without amyloid or tau pathology, we did not find any associations between network measures and hippocampal atrophy, suggesting that the associations are specific for preclinical AD. Our findings suggest that disrupted gray matter networks may indicate a treatment opportunity in preclinical AD individuals but before the onset of irreversible atrophy and cognitive impairment.


Non-small cell lung cancer, version 1.2015.
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.


Arsenic trioxide induces apoptosis via the mitochondrial pathway by upregulating the expression of Bax and Bim in human B cells.
Arsenic trioxide (As2O3) has been approved for the treatment of acute promyelocytic leukemia (APML) and it is a promising candidate for the treatment of patients with lymphoproliferative disorders, such as relapsed or refractory multiple myeloma and myelodysplastic syndromes. The effects of As2O3 on B cells, specifically which do not express Bcl-2, have not been studied. In this study, we have demonstrated that As2O3, at clinically achievable therapeutic concentrations, induces apoptosis in Bcl-2 negative human B cell line Ramos. As2O3-induced apoptosis is associated with reduced mitochondrial transmembrane potential (delta psi), enhanced generation of intracellular reactive oxygen species (ROS), release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria into cytoplasm, activation of caspases, and upregulation of Bax and Bim expression. Exogenous glutathione (GSH) reverses the As2O3-induced apoptosis in a dose-dependent manner. Altogether, these data indicate that As2O3 induces apoptosis in B cells, regardless of Bcl-2 expression, via the mitochondrial pathway by enhancing oxidative stress.


Ultrasonographic characteristics of the portal venous system of 37 healthy, unsedated, student-owned cats: A prospective study.
The aim of this study was to determine portal vein and divisional branch diameters and portal vein velocities in healthy, unsedated cats, using B-mode and Doppler ultrasound. Thirty-seven healthy, adult cats, all owned by students. Enrollment of cats in the study was done prospectively. Ultrasonographic imaging in both the longitudinal and transverse planes was assessed, with all examinations and measurements done by the same person. The assessment included the following 3 sites: extra-hepatic portion of the portal vein, intra-hepatic branches of the portal vein, and the aorta at the level of the porta hepatis. The Shapiro-Wilk test was used for normality and P < 0.05 was used to define statistical significance. Both the extra-hepatic portion of the portal vein and the porta hepatis were identified in all 37 cats (100%), whereas the aorta was recorded in 31 (84%), and the left and right intra-hepatic branches of the portal vein were seen in 29 (78%). Pulsed-wave Doppler ultrasound of the portal vein was obtained in 32 cats (86%). In longitudinal view, average maximal diameter of the extra-hepatic portal vein was 3.6 mm (± 0.7 mm), and the mean portal flow velocity was 14.6 cm · s (± 4.3 cm · s). In transverse view, average maximal diameter was 4.8 mm (± 0.8 mm) for the extra-hepatic portal vein, and 3.1 mm (± 0.8 mm) and 2.6 mm (± 0.7 mm) for the left and right intra-hepatic branches, respectively. The portal-vein-to-aorta ratio averaged 1.2 (± 0.2). This study produced sonographic data of the portal venous system in healthy, conscious adult cats, which may be useful during investigation of liver diseases, including congenital and acquired liver diseases.


Recruiting an Acute Coronary Team to Perform Emergent Mechanical Thrombectomy in Acute Ischemic Stroke Patients: A Successful Case and Team Model in a Local Hospital.
Stroke treatment has entered a new era after the publication of multiple randomized trials involving the use of a stent retriever since 2015. In Taiwan, the demand for interventional neuroradiologists to perform mechanical thrombectomy is high. For this reason, providing this standard care requires reshaping of the care model. Here, we report our experience in recruiting an acute coronary care team to perform emergent mechanical thrombectomy, which is essential in a patient with acute ischemic stroke.


Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells.
While recent insights indicate that the transcription factor Krüppel-like factor 4 (KLF4) is indispensable for vascular homeostasis, its exact role in proliferation and angiogenesis and how it functions remain unresolved. Thus, the aim of the present study was to evaluate the role of KLF4 in the proliferations of endothelial and vascular smooth muscle cells, as well as the angiogenesis. The overexpression of KLF4 in endothelial cells significantly impaired tube formation. KLF4 inhibited the formation of a vascular network in implanted Matrigel plugs in nude mice. Importantly, we found that KLF4 significantly upregulated the miR-15a expression in endothelial cells and vascular smooth muscle cells, and conversely, KLF4 depletion reduced the amount of miR-15a. Furthermore, KLF4 blocked cell cycle progression and decreased cyclin D1 expression in endothelial cells and vascular smooth muscle cells through the induction of miR-15a. Intriguingly, the delivery of a miR-15a antagomir to nude mice resulted in marked attenuation of the anti-angiogenic effect of KLF4. Collectively, our present study provide the first evidence that miR-15a as a direct transcriptional target of KLF4 that mediates the anti-proliferative and anti-angiogenic actions of KLF4, which indicates that KLF4 upregulation of miR-15a may represent a therapeutic option to suppress proliferative vascular disorders.


Urosurgical management of urinary tract infection.
A wide range of abnormalities in the genito-urinary system predispose to infection and surgical solutions may be appropriate. This review considers the investigation of obstruction and the relationship between urinary infections and renal damage, chronic renal disease, renal abscesses, reflux, calculi, catheterization and instrumentation, the neuropathic bladder and prostatitis as well as the role of antibiotic prophylaxis in urological surgery. Recommendations for the urosurgical management of urinary infection are made.


Cephalometric and three-dimensional assessment of superior posterior airway space after maxillomandibular advancement.
The purpose of this study was to quantify cephalometric and three-dimensional alterations of the posterior airway space of patients who underwent maxillomandibular advancement surgery. 20 patients treated by maxillomandibular advancement were selected. The minimal postoperative period was 6 months. The treated patients underwent cone-beam computed tomography at 3 distinct time intervals, preoperative (T1), immediate postoperative period up to 15 days after surgery (T2), and late postoperative period at least 6 months after surgery. The results showed that the maxillomandibular advancement promoted an increase in the posterior airway space in each patient in all the analyses performed, with a statistically significant difference between T2 and T1, and between T3 and T1, p<0.05. There was a statistical difference between T2 and T3 in the analysis of area and volume, which means that the airway space became narrower after 6 months compared with the immediate postoperative period. The maxillomandibular advancement procedure allowed great linear area and volume increase in posterior airway space in the immediate and late postoperative periods, but there was partial loss of the increased space after 6 months. The linear analysis of airway space has limited results when compared with analysis of area and volume.


Predictors of Early Versus Late Recurrence in Invasive Lobular Carcinoma of the Breast: Impact of Local and Systemic Therapy.
Invasive lobular carcinoma (ILC) of the breast is known for high risk of late recurrence, yet some patients still recur within 5 years of diagnosis. Determining factors associated with early/late recurrence could help tailor treatment and surveillance strategies. Using an institutional database, we evaluated patients with ILC and ≥ 5 years of follow-up or recurrence within 5 years. We used multivariate logistic regression and the Kaplan-Meier method to evaluate which clinicopathologic features and treatment strategies were associated with recurrence < 5 years since diagnosis versus recurrence ≥ 5 years since diagnosis. Additionally, we explored the association between Clinical Treatment Score 5 (CTS5) with early versus late recurrence. Among 513 cases of stage I-III ILC, there were 75 early and 54 late recurrences during a median follow-up period of 9.4 years. Early recurrence was associated with larger tumors (mean 4.2 cm vs. 2.9 cm, p < 0.0001), higher incidence of > 3 positive nodes (32.4% vs. 9.11%, p > 0.0001), and more aggressive tumor biology (low/negative progesterone receptor expression, higher grade, and higher Ki67). Late recurrence was associated with younger age (mean 55.6 vs. 59.2 years, p = 0.037) and elevated body mass index (BMI > 25 kg/m2 in 60.1.0% vs. 45.4%, p = 0.021). Omission of adjuvant endocrine therapy or radiotherapy after lumpectomy conferred increased risk of early rather than late recurrence. Factors related to tumor aggressiveness and treatment were associated with early recurrence, whereas patient related factors were related to late recurrence. These data may help guide treatment strategies and surveillance approaches for patients with ILC.


[Diffusion tensor analysis: principles and applications].
Diffusion tensor analysis represents a versatile yet powerful application of magnetic resonance imaging (MRI). Early applications of diffusion weighted imaging(DWI), especially those related to ischemic brain disease were quickly overshadowed by more advanced applications of DTA, namely, those dealing with anisotropy analysis. Considering the array of possibilities, from neuronal tract tracing to neuronal density imaging, DTA is rapidly becoming an indispensable tool not only in neuroscience but also in clinical investigations of the brain.


Cold signalling associated with vernalization in Arabidopsis thaliana does not involve CBF1 or abscisic acid.
In genotypes of Arabidopsis that exhibit a winter-annual flowering habit, floral induction in response to extended cold exposure (vernalization) is mediated by repression of the flowering-inhibitor gene FLC. We are interested in identifying components of the cold signal transduction pathway leading to FLC repression. We examined the potential involvement of two factors that are known to play roles in plant cold responses: (1) CBF1, a cold-responsive transcription factor that is involved in activating the cold acclimation response, and (2) the phytohormone abscisic acid (ABA), which has traditionally been associated with plant cold responses. We introduced a transgene driving constitutive expression of CBF1 into a winter-annual genotype of Arabidopsis. In transgenic lines expressing CBF1 mRNA to high levels, FLC mRNA expression was not repressed, and flowering was not accelerated relative to control plants. We also introduced mutations that compromise ABA biosynthesis or sensitivity into a winter-annual genotype and found that the vernalization response was not affected. Finally, we found that presumed increases in ABA levels, as a result of direct application of the hormone or severe water stress, were insufficient to substitute for cold to induce flowering. Taken together, these findings indicate that vernalization involves a pathway that is distinct from cold-response mechanisms involving CBF1, cold-regulated genes under CBF1 control, and ABA.


The impact of paclitaxel or cisplatin-based chemotherapy on sympathetic skin response: a prospective study.
The current study aimed to assess the viability of sympathetic sudomotor fibers in cancer patients treated with cisplatin or paclitaxel-based chemotherapy and to ascertain whether this method could contribute to the diagnostic sensitivity of conventional techniques. Sympathetic skin response (SSR) from the hand and sole of 23 cancer patients (nine females and 14 males, mean age 62.4 +/- 10.5 years) was recorded unilaterally before and after chemotherapy with six courses of cumulative cisplatin or paclitaxel containing regimens. Clinical and electrophysiological data were also collected and correlated with the SSR results. Twenty-three healthy subjects served as controls. SSR abnormalities were only present in patients with evidence of peripheral neuropathy assessed by conventional nerve conduction techniques. Three patients had absent SSR in the upper limb whilst six patients had absent SSR both in the upper and lower limbs. In the upper limb, the mean SSR latency was not significantly altered through time (P = 0.086). In the lower limb the mean delay from baseline to follow-up was significantly changed (P = 0.029). In patients, the mean SSR latency was significantly prolonged compared with controls in both upper limb (P = 0.001) and lower limb (P = 0.000). SSR abnormalities were strongly related to sensory conduction abnormalities as detected by conventional techniques (r = 0.39, P = 0.004). Our results showed that SSR does not seem to add to the diagnostic sensitivity of conventional techniques in chemotherapy-induced neuropathy. However, its role in the disclosure of small fibers neuropathy abnormalities is worth considering. Further studies are warranted to address this important issue.


The Relationship Between Surface Area and Volume of Common Blow Fly (Diptera: Calliphoridae) Oviposition Sites and Carrion Body Mass.
Female blow flies (Diptera: Calliphoridae) demonstrate site preferences when ovipositing on carrion. Preference for oviposition sites is believed to reflect the suitability of the site such that the most preferred locations provide offspring with the greatest chance of survival. A number of factors might influence female choice, including area available for oviposition. For species known to aggregate during oviposition, the surface area of oviposition sites may be a key factor in the decision-making process. Using ImageJ, the surface area or volume of eight common oviposition sites on 13 fetal pig (Sus scrofa domesticus L.) carcasses was measured. Regression analysis was used to determine if body mass could predict the area or volume available for oviposition. We observed significant positive relationships between size of oviposition sites and body mass for all eight oviposition sites. The strongest relationships were observed for the face (R2 = 0.86) and legs (R2 = 0.84). To test the predictive capacity of this relationship, a blind validation study was performed. Five pigs of various body masses were randomly selected, and the available space of the eight sites was estimated using the regression equations. The validation study confirmed that the regression equations for most oviposition sites demonstrated their predictive capacity based on 95% prediction intervals. This research provides a tool that can be used to correct for differences in oviposition site area or volume between carcasses of varying mass so that researchers may gain a greater understanding of the oviposition preferences and aggregation behaviors in future studies.


[Safety and effectiveness of photoselective vaporization of the prostate (PVP) in patients with oral anticoagulant therapy].
We investigated the safety and efficacy of photoselective vaporization of the prostate (PVP) in 318 men who had lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia with or without oral anticoagulant therapy (OAT). PVP was done using an 80 W potassium titanyl phosphate (KTP) laser under general or spinal anesthesia. We evaluated perioperative parameters, functional outcome (international prostate symptom score, quality of life score, maximum flow rate, postvoid residual urine volume), and adverse events up to 3 months postoperatively. The results in 51 patients under OAT (the group includes 6 men ongoing oral anticoagulants during the procedure) were compared with those obtained in 267 men who underwent PVP for the same indication but who were not under OAT (control). KTP laser vaporization was successfully performed on all patients. There was minimal blood loss, thus none of the patients needed a blood transfusion. No major complications occurred intraoperatively or postoperatively. In patients under OAT, the international prostate symptom score, quality of life score, maximum flow rate and postvoid residual urine volume were significantly improved from preoperative data (p < 0.05), and were comparable with the control. Although postoperative gross hematuria increased with resumption of OAT, PVP using 80 W KTP laser proved to be safe and effective for men who were taking oral anticoagulant medication.


Programmed death ligand-1 and CD8 tumor-infiltrating lymphocytes (TILs) as prognostic predictors in ovarian high-grade serous carcinoma (HGSC).
P D-L1 is expressed in tumor cells and plays a crucial role in tumor immune escape. Tumor-infiltrating lymphocytes (TILs) as CD8 T cells contribute to reduced tumor growth. Few studies investigated the prognostic effect of PD-L1 and CD8 TILs in ovarian high-grade serous carcinoma (HGSC). In the present study, we analyzed the expression of PD-L1 and CD8 TILs in HGSC by immunohistochemistry, and results were correlated to prognosis. It was carried on 54 cases of ovarian HGSC who attended the Oncology Centre, Mansoura University, Egypt, from 2012 till 2019. Nearly 60% of cases showed positive PD-L1 expression in tumor cells. Regarding the clinicopathological characteristics, higher PD-L1 expression was found among patients with residual tumor (82.4%) compared to patients with no residual tumor (54.5%), with marginal statistical significance (p 0.07). PD-L1 was significantly associated with CD8 TILs expression. Higher PD-L1 expression was found among tumors with low expression of CD8 TILs with statistically significant difference (p≤0.001). Disease-free survival (DFS) was significantly lower among the group with positive expression of PD-L1 compared to the group with negative expression of PD-L1 (p 0.01), while overall survival (OS) was not associated with PD-L1 expression. On the other hand, the overall survival (OS) in patients with high CD8 expression was significantly higher than patients with low CD8 expression (p 0.043), while DFS was not significantly different among both CD8 TILS groups. PD-L1 and CD8 TILs may become a promising therapeutic target for patients with ovarian HGSC. More studies are needed to further validate their prognostic effect. Precise identification of patients who will benefit from PD-L1 checkpoint blockade and TILs adaptive immunotherapy is mandatory.


Occupation and lung cancer risk among women in northern China.
Lifetime occupational histories were obtained in a case-control study of 965 female lung cancer patients and 959 controls selected from the general population in Shenyang and Harbin, People's Republic of China, where most women have worked outside the home. After adjusting for smoking, we found a significantly increased risk of lung cancer associated with employment involving the manufacture of transportation equipment (OR = 1.6, 95% CI = 1.0, 2.6), in particular the manufacturing of automobiles (OR = 3.0, 95% CI = 1.4, 6.4). Metal smelting and treatment workers were at an increased risk of lung cancer (OR = 1.5, 95% CI = 1.0, 2.1); the highest risks were observed among metal surfacers (OR = 3.1, 95% CI = 1.1, 9.0) and currently employed foundry workers (OR = 13.0, 95% CI = 1.7, 99.4). On the other hand, about a 50% decreased risk of lung cancer was observed among those employed in textile industries or as leaders of state and party organizations. Based on self-reports, exposures to coal dust and smoke from burning fuel at the workplace were also significant risk factors. The findings were similar when the analyses were confined to nonsmokers and were comparable across the major cell types of lung cancer.


KCNN4 and S100A14 act as predictors of recurrence in optimally debulked patients with serous ovarian cancer.
Approximately 50-75% of patients with serous ovarian carcinoma (SOC) experience recurrence within 18 months after first-line treatment. Current clinical indicators are inadequate for predicting the risk of recurrence. In this study, we used 7 publicly available microarray datasets to identify gene signatures related to recurrence in optimally debulked SOC patients, and validated their expressions in an independent clinic cohort of 127 patients using immunohistochemistry (IHC). We identified a two-gene signature including KCNN4 and S100A14 which was related to recurrence in optimally debulked SOC patients. Their mRNA expression levels were positively correlated and regulated by DNA copy number alterations (CNA) (KCNN4: p=1.918e-05) and DNA promotermethylation (KCNN4: p=0.0179; S100A14: p=2.787e-13). Recurrence prediction models built in the TCGA dataset based on KCNN4 and S100A14 individually and in combination showed good prediction performance in the other 6 datasets (AUC:0.5442-0.9524). The independent cohort supported the expression difference between SOC recurrences. Also, a KCNN4 and S100A14-centered protein interaction subnetwork was built from the STRING database, and the shortest regulation path between them, called the KCNN4-UBA52-KLF4-S100A14 axis, was identified. This discovery might facilitate individualized treatment of SOC.


Will Multi-Parametric Magnetic Resonance Imaging be the Future Tool to Detect Clinically Significant Prostate Cancer?
Multi-parametric magnetic resonance imaging is an emerging imaging modality for diagnosis, staging, characterization, and treatment planning of prostate cancer. In this report, we reviewed the literature for studies assessing the accuracy of multi-parametric magnetic resonance imaging in detecting clinically significant prostate cancer, and we critically examined the future role of this imaging tool in various clinical diagnostic settings. There is accumulating evidence suggesting a high accuracy of multi-parametric magnetic resonance imaging in ruling out clinically significant disease. Although definition for clinically significant disease widely varies, the negative predictive value is very high at up to 98%. Multi-parametric magnetic resonance imaging should, thus, be further evaluated for application in different clinical scenarios in which it is desirable to reduce the proportion of unnecessary prostate biopsies and to limit the detection of indolent disease, such as opportunistic screening, persistent prostate cancer suspicion in men with previous negative prostate biopsies, and eligibility for active surveillance. Continued improvement in standardization of technical parameters, functional sequences, and image reporting systems is a pre-requisite for a rapid and successful dissemination of this imaging modality.


Does the conformation of Mg-ATPase (spectrin-dependent ATPase) influence the passive permeability to K+?
The processing of human erythrocytes disclosed changes in Mg-ATPase activity following action of Pb2+ and Nile blue, and changes of permeability of K+ after treatment with Nile blue. The obtained results and those from previous papers can be summarized as follows : Substances decreasing the activity of stimulated membrane Mg-ATPase (spectrin-dependent ATPase) in red blood cells increase the passive permeability to K+, and substances increasing the stimulated Mg-ATPase activity decrease the passive permeability to K+. A hypothesis is proposed that the conformation of Mg-ATPase is secondarily reflected in the state of the proper path for K+ transport through the membrane; thus the rate of passive permeability to K+ is influenced.


The US radon problem, policy, program and industry: achievements, challenges and strategies.
US radon research, policy and programs have stalled since their start in the late 1980s and early 1990s. In 2005, more homes had radon above the US Environmental Protection Agency (EPA) Reference Level than anytime in history since more homes were added to the housing stock that had indoor radon concentrations exceeding 150 Bq m(-3) than had been mitigated. Funding for the US radon program has declined two-thirds from 1997 to 2007. Despite impressive goals for radon reduction, EPA lacks sound progress indicators especially in new construction radon control systems. School radon reduction has been at a standstill since the early 1990s. There has been no significant radon risk reduction in low-income sectors of the population. There is need for effective partnerships between the public and private sectors of the US radon professional communities as well as with the international programs and professionals.


[Prevalence and severity of the dementia syndrome in homes for the aged and nursing homes. A study in elderly from a rural area near Zwolle].
In the Netherlands both nursing homes and homes for the aged serve as a residence for demented elderly. Although these institutions differ considerably regarding financing and care facilities, specific functions of each institute concerning demented elderly have not been clearly defined. In order to know to what extent residential facilities serve demented elderly, the prevalence and severity of dementia among residents aged 65 and over was studied as part of a prevalence study among elderly people in a rural area of the Netherlands. The target population existed of all persons aged 65 and over who were registered in eight general practices. Patients who had to leave the practice on account of ill-health and were admitted to nursing homes were included in the study. In a two stage study the MMSE was applied as a screening instrument. Based on MMSE-score a non-proportional stratified random sample was drawn for the second, diagnostic stage, which existed of the CAMDEX. Prevalence estimates for DSM-III-R-dementia were 21% among residents of homes for the aged, 48% among residents of somatic wards of nursing homes and 100% among those admitted to psychogeriatric wards of nursing homes. Severity of dementia was highest among residents of psychogeriatric wards of nursing homes and lowest among those living in homes for the aged. Prevalence of dementia among residents of homes for the aged can be fully attributed to the age-distribution. The high frequency of dementia among residents of somatic nursing home wards can be explained in several ways: First, admission can be necessary due to a combination of dementia and somatic illness.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis.
Considering that adipose tissue (AT) is an endocrine organ, it can influence whole body metabolism. Excessive energy storage leads to the dysregulation of adipocytes, which in turn induces abnormal secretion of adipokines, triggering metabolic syndromes such as obesity, dyslipidemia, hyperglycemia, hyperinsulinemia, insulin resistance and type 2 diabetes. Therefore, investigating the molecular mechanisms behind adipocyte dysregulation could help to develop novel therapeutic strategies. Our protocol describes methods for evaluating the molecular mechanism affected by hypoxic conditions of the AT, which correlates with adipocyte apoptosis in adult mice. This protocol describes how to analyze AT in vivo through gene expression profiling as well as histological analysis of adipocyte differentiation, proliferation and apoptosis during hypoxia exposure, ascertained through staining of hypoxic cells or HIF-1α protein. Furthermore, in vitro analysis of adipocyte differentiation and its responses to various stimuli completes the characterization of the molecular pathways behind possible adipocyte dysfunction leading to metabolic syndromes.


Reconstitution, characterisation and mass analysis of the pentacylindrical allophycocyanin core complex from the cyanobacterium Anabaena sp. PCC 7120.
The phycobilisome (PBS) of Anabaena sp. PCC 7120 was allowed to dissociate into its constituents and the resulting allophycocyanin (AP) fraction was purified. Its reconstitution yielded a complex which according to negative stain electron microscopy and spectral analysis was identical to the native pentacylindrical PBS core domain. Each cylinder of the central tricylindric unit was comprised of four AP (alphabeta)3 disks. Mass analysis using the scanning transmission electron microscope (STEM) showed the presence of 16 AP trimers in the intact reconstitute, which had a total mass of 1966(+/-66) kDa. Composition analysis indicated an AP trimer distribution of (AP-II):(AP-LCM):(AP-B):(AP-I)=6:2:2:6, i.e. an addition of two AP-I and two AP-II complexes compared to a tricylindrical PBS core domain. Therefore, we suggest that each supplementary half-core cylinder found in pentacylindrical AP core domains is comprised of one AP-I and one AP-II trimer, in agreement with the current model. The structural significance of the 127 kDa core membrane linker polypeptide was further investigated by subjecting the AP core reconstitute to mild chymotryptic degradation. After isolation, the digested complex exhibited a tricylindrical appearance while STEM mass analysis confirmed the presence of only 12 AP complexes. Polypeptide analysis by SDS-PAGE and Edman degradation related the half-cylinder loss to cleavage of the Rep4 domain of the core membrane linker polypeptide. On the basis of these data, a general model for the assembly of the three hemidiscoidal PBS types known to date is discussed.


Isolation and characterization of an algicidal bacterium indigenous to lake Taihu with a red pigment able to lyse microcystis aeruginosa.
To isolate and characterize indigenous algicidal bacteria and their algae-lysing compounds active against Microcystis aeruginosa, strains TH1, TH2, and FACHB 905. The bacteria were identified using the Biolog automated microbial identification system and 16S rDNA sequence analysis. The algae-lysing compounds were isolated and purified by silica gel column chromatography and reverse-phase high performance liquid chromatography. Their structures were confirmed by Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FT-IR) spectroscopy. Algae-lysing activity was observed using microscopy. The algae-lysing bacterium LTH-2 isolated from Lake Taihu was identified as Serratia marcescens. Strain LTH-2 secreted a red pigment identified as prodigiosin (C20H25N3O), which showed strong lytic activity with algal strains M. aeruginosa TH1, TH2, and FACHB 905 in a concentration-dependent manner. The 50% inhibitory concentration (IC50) of prodigiosin with the algal strains was 4.8 (± 0.4)× 10⁻² μg/mL, 8.9 (± 1.1)× 10⁻² μg/mL, and 1.7 (± 0.1)× 10⁻¹ μg/mL in 24 h, respectively. The bacterium LTH-2 and its pigment had strong Microcystis-lysing activity probably related to damage of cell membranes. The bacterium LTH-2 and its red pigment are potentially useful for regulating blooms of harmful M. aeruginosa.


Factors associated with the homicides of women who are victims of violence.
to identify factors associated with homicides in women who had prior notification of violence in the state of Pernambuco, 2011 to 2016. a transversal, quantitative and observational study, guided by the STROBE tool, with data of homicides of women obtained from the Mortality Information System; and of violence against women, from the Grievance Notification Information System. The logistic regression model was used to verify the factors associated with the homicides. there were 32,308 cases of violence against women and 1,162 homicides. The chances of homicide were higher for women: victims of physical violence (2.39 times more), aggression by object of court (2.32 times more), aggression by firearm (6 times more), and when there was a recurrence of violence (3.82 times more). association of physical violence, agression by object of court, aggression by firearm, recurrence of violence with homicides of women in the state of Pernambuco was found.


Self-assembly of monolayer-thick alumina particle-epoxy composite films.
Monolayer-thick composite films composed of alpha-alumina and Spurr's epoxy were prepared via a self-assembly process known as fluid forming. The process makes use of a high-spreading-tension fluid composed of volatile and nonvolatile components to propel particles across the air-water interface within a water bath. Continuous addition of the particle suspension builds a 2D particle film at the air-water interface. The spreading fluid compresses the film into a densely packed array against a submerged substrate. The assembled monolayer is deposited onto the substrate by removing the substrate from the bath. A dispersion containing a narrow size distribution, 10 microm alpha-alumina particles, light mineral oil, and 2-propanol was spread at the air-water interface and the alumina particles were assembled into densely packed arrays with an aerial packing fraction (APF) of 0.88. However, when mineral oil was replaced by Spurr's epoxy nonuniform films with low packing density resulted. It was found that replacing 2-propanol with a mixture of 2-propanol and 1-butanol with a volume ratio of 4:1 produced uniform, densely packed alumina/epoxy composite films. The role of the solvent mixture will be discussed.


Insulin involvement in intestinal macromolecular transmission and closure in neonatal pigs.
The involvement of insulin in the intestinal transmission of macromolecules to blood and the cessation of this transport (intestinal closure) was studied in neonatal pigs by measuring the serum levels of the markers bovine serum albumin and fluorescein isothiocyanate labelled dextran 70,000 (FITC-D) at 4 h after gavage feeding. In naturally suckled pigs, intestinal closure at 18 h was shown to be associated with an increase in serum immunoreactive insulin (IRI) levels. Similarly, intestinal closure obtained at 18 h, by gavage feeding unsuckled pigs a total of 48 g lactose/kg, was accompanied by an increase in serum IRI levels. Neither high serum IRI levels nor closure were observed in fasted pigs or in pigs gavage fed a total of 12 g lactose/kg. The effect of exogenous insulin on intestinal macromolecular transmission was studied by injecting 5 IU insulin/kg subcutaneously at 3 and 6 h, respectively, in newborn pigs gavage fed 10 ml sow colostrum/kg at 3 h intervals. This resulted in a reduction in the transmission of the markers when tested at 12 h, in comparison to littermates receiving the same amount of colostrum and littermates suckling the sow. It appears as if insulin, reflected as high serum levels over an extended period of time, is involved in the regulation of macromolecular transmission and intestinal closure in neonatal pigs. It was speculated that insulin may be involved in these processes by initiating the synthesis of membrane structural proteins in the enterocytes.


Endoplasmic reticulum-associated degradation and disposal of misfolded GPI-anchored proteins in Trypanosoma brucei.
Misfolded secretory proteins are retained by endoplasmic reticulum quality control (ERQC) and degraded in the proteasome by ER-associated degradation (ERAD). However, in yeast and mammals, misfolded glycosylphosphatidylinositol (GPI)-anchored proteins are preferentially degraded in the vacuole/lysosome. We investigate this process in the divergent eukaryotic pathogen Trypanosoma brucei using a misfolded GPI-anchored subunit (HA:E6) of the trypanosome transferrin receptor. HA:E6 is N-glycosylated and GPI-anchored and accumulates in the ER as aggregates. Treatment with MG132, a proteasome inhibitor, generates a smaller protected polypeptide (HA:E6*), consistent with turnover in the proteasome. HA:E6* partitions between membrane and cytosol fractions, and both pools are proteinase K-sensitive, indicating cytosolic disposition of membrane-associated HA:E6*. HA:E6* is de-N-glycosylated and has a full GPI-glycan structure from which dimyristoylglycerol has been removed, indicating that complete GPI removal is not a prerequisite for proteasomal degradation. However, HA:E6* is apparently not ubiquitin-modified. The trypanosome GPI anchor is a forward trafficking signal; thus the dynamic tension between ERQC and ER exit favors degradation by ERAD. These results differ markedly from the standard eukaryotic model systems and may indicate an evolutionary advantage related to pathogenesis.


Prospective, open, multicentre Phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and cisplatin for esophageal carcinoma.
Esophageal squamous cell carcinoma is increasingly treated with trimodality therapy. The objective of this Phase I/II clinical study is to assess the efficacy and safety of neoadjuvant radiochemotherapy with docetaxel and cisplatin and radiotherapy in patients with esophagectomy for locally advanced squamous cell carcinoma of the esophagus with neoadjuvant chemoradiotherapy. Patients with esophageal squamous cell carcinoma received radiochemotherapy (50 Gy/25 fractions during Weeks 1-5) using a three-dimensional conformal radiation therapy or intensity-modulated radiation therapy technique together with weekly docetaxel (20 mg/m(2) at dose levels 1 and 2, 25 mg/m(2) at dose level 3 on Weeks 1-5) and cisplatin (30 mg/m(2) at dose level 1, 40 mg/m(2) at dose levels 2 and 3 on Weeks 1-5) from January 2009 to December 2011. The dose-limiting toxicities and maximum tolerated dose were the primary endpoints and overall response rate and progression-free survival were the secondary endpoints. Over this timeframe, a total of 49 patients completed trimodality therapy. Thirteen patients were treated at dose level 1, 21 patients at dose level 2 and 15 patients at dose level 3.The maximum tolerated dose for docetaxel was 20 mg/m(2) and cisplatin 40 mg/m(2). The complete response or partial response was observed in 26.5% (13/49) of patients. Thirty-four patients (69.4%) were treated with neoadjuvant radiochemotherapy followed by surgical resection. The median progression-free survival and median overall survival for all patients (n = 49) were 8 and 17.2 months, respectively. The median overall survival was 27.5 months for patients treated at dose level 2. Neoadjuvant radiochemotherapy with docetaxel 20 mg/m(2) and cisplatin 40 mg/m(2) was effective and tolerable induction regimen in patients with esophageal tumors.


[Vinegar-processed Euphorbiae Pekinensis Radix improves intestinal flora disorder and reduces colon toxicity].
The present study investigated the effect of Euphorbiae Pekinensis Radix(EPR) on intestinal flora structure before and after vinegar processing and explored the detoxification mechanism of vinegar-processed EPR. In this study, the extraction efficiency of casbane diterpenes from EPR with different solvents was investigated, and the optimal solvent was selected to enrich these components. After 14 days of intragastric administration of total diterpene extract of EPR and vinegar-processed EPR, 16 S rDNA sequencing technology was used to detect the structural changes of intestinal flora. The flora related to the intestinal toxicity of EPR was screened out based on the results of intestinal pathological damage by correlation analysis. The results showed that Soxhlet extraction with chloroform as extraction solvent could enrich Casbane diterpenes in EPR. As revealed by 16 S rDNA sequencing results, EPR could significantly change the structure of intestinal flora, which could be reversed by vinegar-processing EPR. Some intestinal flora candidates might be related to detoxification of vinegar processing. The correlation analysis of intestinal flora candidates and indexes related to intestinal mucosal injury showed that compared with EPR, vinegar-processed EPR could down-regulate the abundance of some pathogenic bacteria such as Mucispirillum, Bilophila, and Ruminiclostridium, and up-regulated some probiotics such as Enterorhabdus, Ruminococcaceae_UCG-014, Barnesiella, and Candidatus. The intestinal toxicity caused by EPR may be related to the disturbance of intestinal flora, and vinegar-processed EPR can improve intestinal flora disorder by up-regulating the abundance of probiotics and down-regulating the abundance of pathogenic bacteria to remodel the intestinal mucosal barrier and reduce toxicity.


Adhesion of Cryptosporidium parvum and Giardia lamblia to solid surfaces: the role of surface charge and hydrophobicity.
Adhesion of Cryptosporidium parvum and Giardia lamblia to four materials of different surface charge and hydrophobicity was investigated. Glass beads were used with and without three polymer coatings: aminosilines (A0750), fluorosilines (T2494), an amino cationic polymer. Surface charge density and hydrophobicity of the beads were characterized by measuring the zeta potential (ZP) and the contact angle, respectively. Adhesion was derived from batch experiments where negatively charged (oo)cysts were mixed with the beads and recovery was determined by counting (oo)cysts remaining in suspension using a flow cytometer. Experimental results clearly show that adhesion to solid surfaces of C. parvum is different from G. lamblia. Adhesion of C. parvum to positively charged, hydrophilic beads (82% recovery relative to control) indicated that surface charge was the more important factor for C. parvum, dominating any hydrophobic effects. Adhesion of G. lamblia cysts to negatively charged, hydrophobic beads (0% recovery relative to control) indicated that although hydrophobicity and surface charge both played a role in the adhesion of G. lamblia to solid surfaces, hydrophobicity was more important than surface charge.


[Smallpox vaccination with protection by interferon and an interferon inducer].
The vaccinal process was studied in monkeys vaccinated with smallpox vaccine under the protection of fibroblastic or leukocytic interferons and modified poly(I) . poly(C). Simultaneous vaccination and administration of one of the studied preparations induced intense immunity and at the same time prevented viremia and alleviated local inflammatory reactions caused by the vaccination. The protective effect of the fibroblastic interferon was more marked than that of the leukocytic one in the vaccinal process. When the monkeys received the preparations intramuscularly the leukocytic but not the fibroblastic interferon was detected in the blood.


Reaction of nerve agents with phosphate buffer at pH 7.
Chemical weapon nerve agents, including isopropyl methylphosphonofluoridate (GB or Sarin), pinacolyl methylphosphonofluoridate (GD or Soman), and S-(2-diisopropylaminoethyl) O-ethyl methylphosphonothioate (VX), are slow to react in aqueous solutions at midrange pH levels. The nerve agent reactivity increases in phosphate buffer at pH 7, relative to distilled water or acetate buffer. Reactions were studied using (31)P NMR. Phosphate causes faster reaction to the corresponding alkyl methylphosphonic acids, and produces a mixed phosphate/phosphonate compound as an intermediate reaction product. GB has the fastest reaction rate, with a bimolecular rate constant of 4.6 × 10(-3) M(-1)s(-1)[PO(4)(3-)]. The molar product branching ratio of GB acid to the pyro product (isopropyl methylphosphonate phosphate anhydride) is 1:1.4, independent of phosphate concentration, and the pyro product continues to react much slower to form GB acid. The pyro product has two doublets in the (31)P NMR spectrum. The rate of reaction for GD is slower than GB, with a rate constant of 1.26 × 10(-3) M(-1)s(-1) [PO(4)(3-)]. The rate for VX is considerably slower, with a rate constant of 1.39 × 10(-5) M(-1)s(-1) [PO(4)(3-)], about 2 orders of magnitude slower than the rate for GD. The rate constant of the reaction of GD with pyrophosphate at pH 8 is 2.04 × 10(-3) min(-1) at a concentration of 0.0145 M. The rate of reaction for diisopropyl fluorophosphate is 2.84 × 10(-3) min(-1) at a concentration of 0.153 M phosphate, a factor of 4 slower than GD and a factor of 15 slower than GB, and there is no detectable pyro product. The half-lives of secondary reaction of the GB pyro product in 0.153 and 0.046 M solution of phosphate are 23.8 and 28.0 h, respectively, which indicates little or no dependence on phosphate.


The frequency of hepatitis B surface antigen in membranous nephropathy in black and white South Africans.
A series of 244 renal biopsy specimens obtained from patients with glomerulonephritis included 21 from patients with membranous nephropathy (MN). Of these patients 14 (10,7%) were Black, 1 was Indian and 6 were White (5,5%). It is suggested that the high frequency of MN in Black patients may be associated with the high carrier rate (7 - 10%) of hepatitis B virus (HBV) in the Black population. Twenty of the 21 renal specimens were investigated for deposits of hepatitis B surface antigen (HBsAg) using the peroxidase-antiperoxidase method. HBsAg deposits were found in 13 of the specimens obtained from Black patients, in the specimen obtained from the Indian patient and in 1 of the 6 specimens obtained from White patients. HBV appears to be an important aetiological factor in MN in Black South African patients.


Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer.
Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) has been successful in treating a considerable proportion of patients with metastatic melanoma. In addition, some patients with several other solid tumors were recently reported to have benefited clinically from such ACT. However, it remains unclear whether ACT using TILs is broadly applicable in breast cancer, the most common cancer in women. In this study, the utility of TILs as an ACT source in breast cancers was explored by deriving TILs from a large number of breast cancer samples and assessing their biological potentials. We successfully expanded TILs ex vivo under a standard TIL culture condition from over 100 breast cancer samples, including all breast cancer subtypes. We also found that the information about the percentage of TIL and presence of tertiary lymphoid structure in the tumor tissues could be useful for estimating the number of obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a considerable level of central memory phenotype T cells (about 20%), and a large proportion of TIL samples were reactive to autologous tumor cells in vitro. Furthermore, the in vitro tumor-reactive autologous TILs could also function in vivo in a xenograft mouse model implanted with the primary tumor tissue. Collectively, these results strongly indicate that ACT using ex vivo expanded autologous TILs is a feasible option in treating patients with breast cancer.


Ethanol consumption produces changes in behavior and on hippocampal alpha7 and alpha4beta2 nicotinic receptors.
Ethanol consumption produces a wide range of effects on the central nervous system, most of them related to changes in neural receptors. In vitro studies have demonstrated that ethanol increases neural nicotinic acetylcholine receptor (nnAChR) affinity for ACh (Narahashi et al., 1991) and have also reported differences in sensitivity of nnAChRs for ethanol, depending on the subunit composition of the receptor (Cardoso et al., 1999). There is evidence that ethanol induces changes in density of nnAChRs in cellular cultures (Gorbounova et al., 1998). However, there are no clear results concerning the effects of chronic ethanol on nicotinic receptors and on behavior in rats nonselected by their preference to ethanol. A number of studies demonstrate that nnAChRs participate in a variety of functions, including memory and learning processes, neurodegeneration, and neuroprotection (Picciotto et al., 2000). In the present work, we found significant alterations in the Fixed-Interval Behavioral Test, as well as in density and affinity parameters of hippocampal main subtypes of nnAChRs: alpha7 homopentamers and alpha4beta2 heteropentamers of ethanol-drinking rats nonselected by their preference to ethanol.


A simple and robust method for simultaneous dual-omics profiling with limited numbers of cells.
Deciphering epigenetic regulation of gene expression requires measuring the epigenome and transcriptome jointly. Single-cell multi-omics technologies have been developed for concurrent profiling of chromatin accessibility and gene expression. However, multi-omics profiling of low-input bulk samples remains challenging. Therefore, we developed low-input ATAC&mRNA-seq, a simple and robust method for studying the role of chromatin structure in gene regulation in a single experiment with thousands of cells, to maximize insights from limited input material by obtaining ATAC-seq and mRNA-seq data simultaneously from the same cells with data quality comparable to that of conventional mono-omics assays. Integrative data analysis revealed similar strong association between promoter accessibility and gene expression when using the data of low-input ATAC&mRNA-seq as when using single-assay data, underscoring the accuracy and reliability of our dual-omics assay to generate both datum types simultaneously with just thousands of cells. We envision our method to be widely applied in many biological disciplines with limited materials.


Prognostic influence of histopathological regression patterns in rectal adenocarcinoma receiving neoadjuvant therapy.
Neoadjuvant chemoradiation therapy (CRT) is an important management strategy in rectal carcinoma. Different systems grading response have shown varying prognostic influence. To analyze the prognostic influence of pathological response in a series of 183 patients with rectal carcinoma receiving neoadjuvant therapy. To determine the prognostic significance of the histopathological patterns of response. A total of 183 patients from two hospitals. The concordance rate between pathologists was good. In total, 18% of the patients showed grade 0 (complete response), 31.7% grade 1, 19.2% grade 2 and 31.1% grade 3 regression. T down-staging was found in 51.9% of the cases. 46 patients recurred and 18 died of disease (median follow-up time: 39 months). We found a statistically significant association between pathological response and pT stage and down-staging. Inflammatory reaction in the tumor bed was significantly associated to regression and prognosis. Cox's multivariate analysis of survival revealed that down-staging and presence of mucin pools in the tumor bed behaved as significant predictors of recurrence and regression grade and mucin pools as significant predictors of survival. Pathological response is an important surrogate marker of prognosis in some large series, but results are varying. There are many systems to grade regression and this makes it difficult to compare the results by different groups. It is important to report the specific pattern of response, for some of them may have prognostic relevance. We feel there is an urgent need to develop standarized protocols and employ a universal regression scheme if we intend to use this factor to guide therapy.


Target genes of neuron-restrictive silencer factor are abnormally up-regulated in human myotilinopathy.
Myotilinopathy is a subgroup of myofibrillar myopathies caused by mutations in the myotilin gene in which there is aggregation of abnormal cytoskeletal proteins and ubiquitin. We report here on the accumulation of neuron-related proteins such as ubiquitin carboxy-terminal hydrolase L1 (UCHL1), synaptosomal-associated protein 25, synaptophysin, and alpha-internexin in aberrant protein aggregates in myotilinopathy. We have determined that the neuron-restrictive silencer factor (NRSF)/RE1 silencing transcription factor (REST), a transcription factor expressed in non-neuronal tissues repressing the expression of several neuronal genes, is reduced in myotilinopathies. Moreover, NRSF transfection reduces UCHL1, synaptosomal-associated protein 25, synaptophysin, and alpha-internexin mRNA levels in DMS53 cells, whereas short interferring NRSF transfection increases UCHL1 and synaptophysin mRNA levels in U87-MG cells. Chromatin immunoprecipitation assays have shown that NRSF interacts with the UCHL1 promoter in U87-MG and HeLa cells. In silico analysis of the UCHL1 gene promoter sequence using the MatInspector software has predicted three potential neuron-restrictive silencer elements (NRSEs): NRSE1 located in the complementary DNA chain and NRSE2 and NRSE3 in intron 1, in the coding and complementary chains, respectively. Together, these findings show, for the first time, abnormal regulation of NRSF/REST as a mechanism associated with the aberrant expression of selected neuron-related proteins, which in turn accumulate in abnormal protein aggregates, in myotilinopathy.


Does minimally invasive surgery for radical cystectomy provide similar long-term cancer control as open radical surgery?
Open radical cystectomy (ORC) and pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive and high-risk nonmuscle-invasive bladder cancer (BCa), but is associated with significant morbidity. In the hope of decreasing the complications and improving the surgical tolerance, minimally invasive techniques to perform radical cystectomy and PLND have been adopted. This review focuses on the present state of the literature regarding the oncological efficacy of minimally invasive radical cystectomy (MIRC) and PLND. Most studies are retrospective, single surgeon or institution, and are subjected to significant selection bias. There is scarce data regarding intermediate and long term oncological outcomes following MIRC, and most reported series contain a lower proportion of patients with locally advanced disease compared with ORC series. Positive surgical margin rates are similar between the approaches in localized disease, but may be significantly higher in MIRC in patients with more advanced tumors. The current review of the literature demonstrates insufficient evidence regarding the long-term oncological outcomes of MIRC. There is a need for well controlled, prospective, randomized trials with sufficient follow-up to compare MIRC to ORC for the treatment of invasive BCa before the oncologic efficacy of these techniques can be adequately compared to the standards established by ORC.


Unifying Speed-Accuracy Trade-Off and Cost-Benefit Trade-Off in Human Reaching Movements.
Two basic trade-offs interact while our brain decides how to move our body. First, with the cost-benefit trade-off, the brain trades between the importance of moving faster toward a target that is more rewarding and the increased muscular cost resulting from a faster movement. Second, with the speed-accuracy trade-off, the brain trades between how accurate the movement needs to be and the time it takes to achieve such accuracy. So far, these two trade-offs have been well studied in isolation, despite their obvious interdependence. To overcome this limitation, we propose a new model that is able to simultaneously account for both trade-offs. The model assumes that the central nervous system maximizes the expected utility resulting from the potential reward and the cost over the repetition of many movements, taking into account the probability to miss the target. The resulting model is able to account for both the speed-accuracy and the cost-benefit trade-offs. To validate the proposed hypothesis, we confront the properties of the computational model to data from an experimental study where subjects have to reach for targets by performing arm movements in a horizontal plane. The results qualitatively show that the proposed model successfully accounts for both cost-benefit and speed-accuracy trade-offs.


Soil Acidobacteria Strain AB23 Resistance to Oxidative Stress Through Production of Carotenoids.
Metagenomic studies revealed the prevalence of Acidobacteria in soils, but the physiological and ecological reasons for their success are not well understood. Many Acidobacteria exhibit carotenoid-related pigments, which may be involved in their tolerance of environmental stress. The aim of this work was to investigate the role of the orange pigments produced by Acidobacteria strain AB23 isolated from a savannah-like soil and to identify putative carotenoid genes in Acidobacteria genomes. Phylogenetic analysis revealed that strain AB23 belongs to the Occallatibacter genus from the class Acidobacteriia (subdivision 1). Strain AB23 produced carotenoids in the presence of light and vitamins; however, the growth rate and biomass decreased when cells were exposed to light. The presence of carotenoids resulted in tolerance to hydrogen peroxide. Comparative genomics revealed that all members of Acidobacteriia with available genomes possess the complete gene cluster for phytoene production. Some Acidobacteriia members have an additional gene cluster that may be involved in the production of colored carotenoids. Both colored and colorless carotenoids are involved in tolerance to oxidative stress. These results show that the presence of carotenoid genes is widespread among Acidobacteriia. Light and atmospheric oxygen stimulate carotenoid synthesis, but there are other natural sources of oxidative stress in soils. Tolerance to environmental oxidative stress provided by carotenoids may offer a competitive advantage for Acidobacteria in soils.


Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens.
To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT). Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up. Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059). HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc.


Experiences of healthcare providers with eligible patients' loss of decision-making capacity while awaiting medical assistance in dying.
In Canada, under Bill C-14, patients who met all eligibility requirements were prevented from accessing medical assistance in dying (MAiD) following their loss of decision-making capacity while awaiting MAiD. The changes introduced with Bill C-7 continue to limit access to patients who did not enter a waiver of final consent agreement with their healthcare providers. Little is known about the experiences with patients' loss of capacity to consent and subsequent ineligibility for MAiD. Understanding healthcare providers' experiences has important implications for improving end-of-life care for those with capacity-limiting conditions. To explore Canadian healthcare providers' experiences with end-of-life of eligible patients who became ineligible for MAiD due to their loss of decision-making capacity to consent and the relational influences on their experiences prior to the implementation of Bill C-7 in Canada. A critical qualitative methodology and a feminist ethics theoretical lens guided this study. A voice-centred relational approach that allowed an in-depth exploration of how power, relationality and moral agency influenced participants' experiences was used for data analysis. Data consisted of semi-structured interviews with 30 healthcare providers. The analysis resulted in the following four main themes and corresponding subthemes: (1) identifying factors that may result in ineligibility for MAiD due to capacity loss; (2) maintaining eligibility required to access MAiD; (3) preparing for an alternative end-of-life; (4) experiencing patients' capacity loss. This study highlights that while MAiD is legally available to eligible Canadians, access to MAiD and care for eligible patients who were unable to access MAiD due to their loss of decision-making varied based on the geographical locations and access to willing MAiD and end-of-life care providers. The availability of high-quality palliative care for patients throughout the MAiD process, including following the loss of capacity to consent and subsequent ineligibility, would improve the end-of-life experience for all those involved. The need to establish a systematic approach to prepare and care for patients and their families following the patients' loss of capacity and subsequent ineligibility for MAiD is also identified.


[Application study of periarticular multimodal drug injection in total knee arthroplasty].
To investigate and compare the analgesic effect of a periarticular multimodal drug injection and patient-controlled epidural analgesia (PCEA) in total knee arthroplasty (TKA). Thirty-six patients undergoing unilateral TKA were randomly divided into two groups (A and B). Group A received a periarticular injection of ropivacaine, morphine and epinephrine at operation and Group B did not. All patients received postoperative patient-controlled epidural analgesia (PCEA). Preoperative baseline data, surgery-related conditions, postoperative VAS (visual analog score), range of motion (ROM), time of opening PCEA, drug dosage in PCEA and side effects were recorded respectively. At 6, 12 hour VAS in Group A was lower than Group B (P < 0.05). The time of opening PCEA in Group A was longer than Group B (P < 0.05). The drug dosage in PCEA in Group A was less than Group B (P < 0.05). There was no difference of surgical conditions, ROM, 24/48 hour VAS and side effects between two groups (P > 0.05). Periarticular drug injection during TKA can relieve pain early after TKA, prolong the time of opening PCEA and reduce the drug dosage in PCEA.


Cardiopulmonary bypass (CPB) for lung transplantation.
Surgeons have often been reluctant to use cardiopulmonary bypass (CPB) during single (SLTx) and double lung (DLTx) transplantation surgery because of the potential adverse sequelae of CPB including haemorrhage and activation of complement leading to sequestration of neutrophils and platelets in the pulmonary capillary bed, endothelial damage, increased capillary permeability and pulmonary oedema. To clarify the effect of CPB on lung transplant recipients, we reviewed our last four years' experience in 74 patients of whom 30 required CPB support. Indications for CPB were mean pulmonary artery pressure of greater than 50 mmHg, haemodynamic instability, hypoxia or hypercarbia. Patients undergoing SLTx were placed on CPB via the femoral artery and vein, while those undergoing DLTx were cannulated in the standard fashion using the ascending aorta and right atrium. All patients were administered aprotinin prior to CPB. Intraoperatively and postoperatively, haemorrhage was not a major problem. The 30-day mortality in the CPB group and the non-CPB group were 20% and 4.6%, respectively which was not statistically significant (p = 0.06). We conclude that CPB during lung transplantation is a safe, effective method to support these severely ill patients and should not be avoided because of concerns over adverse sequelae of CPB on postoperative graft function.


Microfabricated devices in microbial bioenergy sciences.
Microbes provide a platform for the synthesis of clean energy from renewable resources. Significant investments in discovering new microbial systems and capabilities, discerning the molecular mechanisms that mediate microbial bioenergy production, and optimizing existing microbial bioenergy systems have been made. However, further development is needed to achieve the economically feasible large-scale production of value-added energy products. Microfabricated lab-on-a-chip systems provide cost- and time-efficient opportunities for analyzing microbe-mediated bioenergy synthesis. Here, we review developments in the application of lab-on-a-chip systems to the bioenergy sciences. We focus on systems that support the analysis of microbial generation of bioelectricity, biogas, and liquid transportation fuels. We conclude by suggesting possible future directions.


Effectiveness of aroma massage on advanced cancer patients with constipation: a pilot study.
The purpose of this study was to verify the effect of aroma massage on constipation in advanced cancer patients. This study employed a randomized control group pre- and post test design and included an aroma massage group, plain massage group, and control group. To evaluate the effect of aromatherapy, the degree of constipation was measured using a constipation assessment scale, severity level of constipation and the frequency of bowel movements. Data was analyzed by repeated measures of Mann-Whitney U test, Wilcoxon signed ranks test, Spearman's rho and ANOVA using SPSS program. The score of the constipation assessment scale of the aroma massage group was significantly lower than the control group. Apart from the improvement in bowel movements, the results showed significantly improved quality of life in physical and support domains of the aroma massage group. The findings of this study suggest aroma massage can help to relieve constipation in patients with advanced cancer.


Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference.
On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame.


[Nutritional screening in hospitalized pediatric patients: systematic review].
malnutrition in the pediatric population has been associated with a great number of physiological problems and complications, which lead to a longer period of hospitalization, a higher risk of infections, a rise in mortality rate, and hence, a rise in assistance expenses. to collect available evidence on tools of nutritional screening frequently used in pediatrics that allow identifying, preventing and intervening hospital malnutrition, as well as providing guidelines regarding the appropriate application instant. a systematic review of literature was carried out in accordance with the PRISMA Declaration (Preferred Reporting Items in Systematic Reviews and Meta-Analyses) and in the main databases, search in ClinicalTrials and gray literature in Open Gray and TRIP Database. Then, the articles were selected and classified depending on the type of study. The quality assessment was done in accordance with the Scottish Intercollegiate Guidelines Network (SIGN) checklists. one hundred and ten articles were identified, following the parameters of the PRISMA declaration. Twenty-one articles were analyzed and evaluated through the SIGN methodology; 19 met the high quality criteria and were included in the present review. Six nutritional screening tools in pediatrics were identified, STRONGkids being the tool referred by 63% of the studies for the detection of malnutrition risk. the present systematic review allowed us to conclude that STRONGkids is the best screening tool for hospitalized children since it is practical, quick, easy to use and it reliably predicts the risk of malnutrition. However, further studies are required to validate the use of this in the Colombian context.


Transcranial Ultrasound Stimulation Improves Long-Term Functional Outcomes and Protects Against Brain Damage in Traumatic Brain Injury.
The purpose of this study was to assess the long-term treatment efficacy of low-intensity pulsed ultrasound (LIPUS) on functional outcomes, brain edema, and the possible involvement of reactions in mice following traumatic brain injury (TBI). Mice subjected to controlled cortical impact injury received LIPUS treatment daily for a period of 4 weeks. The effects of LIPUS on edema were detected by MR imaging in the mouse brain at 148 days following TBI. Long-term functional outcomes of LIPUS stimulation were evaluated by behavioral analyses. One-way or two-way analysis of variance and Student's t test were used for statistical analyses, with a significant level of .05. Up to post-injury day 148, treatment with LIPUS significantly improved functional outcomes (all p < 0.05). LIPUS also significantly attenuated brain edema and neuronal death at day 148 after TBI (all p < 0.05). Furthermore, LIPUS reduced MMP9 activity, neutrophil infiltration, and microglial activation at day 1 or day 4 following TBI (all p < 0.05). Meanwhile, LIPUS increased the Bcl-2/Bax ratio and enhanced the phosphorylation of Bad and FOXO-1 at day 1 or day 4 following TBI (all p < 0.05). Almost 5 months of follow-up showed that the treatment efficacy of post-injury LIPUS stimulation on reduced brain edema and improved functional outcomes persisted over time after TBI. The neuroprotective effects of LIPUS are associated with a reduction of early inflammatory events and inhibition of apoptotic progression.


Pain--from periphery to brain.
Pain is not simply due to the activation of peripheral nociceptors but to multiple factors. Part of the article is a review of scientific work on such factors at the different levels of the peripheral and central nervous system, with particular reference to possible new therapy strategies. A second part describes some aspects of clinical assessment of persistent pain conditions, such as differential diagnostics between musculoskeletal nociceptive and neurogenic pain, between referred pain from a musculoskeletal focus and projected neurogenic pain, and between psychogenic pain and pain with a somatic cause.