High-Throughput Measurement of Mitochondrial RNA Turnover in Human Cultured Cells.
RNA turnover is an essential part of the gene expression pathway, and there are several experimental approaches for its determination. High-throughput measurement of global RNA turnover rates can provide valuable information about conditions or proteins that impact gene expression. Here, we present a protocol for mitochondrial RNA turnover analysis which involves metabolic labeling of RNA coupled with quantitative high-throughput fluorescent microscopy. This approach gives an excellent opportunity to discover new factors involved in mitochondrial gene regulation when combined with loss-of-function screening strategy.


Prevalence of obesity and hypertension in children and determination of associated factors by CHAID analysis.
The prevalence of obesity and hypertension in children is associated with an increased risk of cardiovascular disease and increases the prevalence of heart failure and associated morbidity and mortality. This study aimed to determine the prevalence of obesity and hypertension, as well as the associated risk factors, in school-age children. This cross-sectional study was conducted in 21 schools in Antalya, Turkey. A total of 5160 students between the ages of 5 and 15 years participated in the study. The data were collected using a questionnaire, and students' height, weight, and blood pressure were measured. The data were evaluated using numbers, percentages, mean, and chi-squared automatic interaction detector (CHAID) analysis. In all, 11.4% of children were overweight, 11.8% were obese, 6.8% had prehypertension, and 5.7% had hypertension. School level, school location, and father's educational status were determined as factors associated with overweight and obesity; BMI, school level, school location, and mother's working status were determined as factors related to hypertension in the children. The prevalence of hypertension, overweight, and obesity was found to be significantly high in the children, especially those living in rural areas. Therefore, it is recommended that these health issues be monitored in children and that necessary measures be taken by considering regional differences.


Sampling rates for passive samplers exposed to a field-relevant peak of 42 organic pesticides.
Pesticide concentrations in agricultural streams are often characterised by a low level of baseline exposure and episodic peak concentrations associated with heavy rainfall events. Traditional sampling methods such as grab sampling, which are still largely used in governmental monitoring, typically miss peak concentrations. Passive sampling represents a cost-efficient alternative but requires the additional determination of sampling rates to calculate time-weighted average (TWA) water concentrations from the accumulated pesticide mass in the sampler. To date, sampling rates have largely been determined in experiments with constant exposure, which does not necessarily reflect field situations. Using Empore styrene-divinylbenzene (SDB) passive sampler disks mounted in metal holders, we determined sampling rates for 42 organic pesticides, of which 27 sampling rates were lacking before. The SDB disks were in an artificial channel system exposed to a field-relevant pesticide peak. We used an open-source algorithm to estimate coefficients of equations for the accumulated pesticide mass in disks and to determine exposure time-dependent sampling rates. These sampling rates ranged from 0.02 to 0.98 L d-1 and corresponded to those from previous studies determined with constant exposure. The prediction of sampling rates using compound properties was unreliable. Hence, experiments are required to determine reliable sampling rates. We discuss the use of passive sampling to estimate peak concentrations. Overall, our study provides sampling rates and computer code to determine these under peak exposure designs and suggests that passive sampling is suitable to estimate peak pesticide concentrations in field studies.


Presence of radial glia in foetal mouse cerebellum.
The ventricular layer (VL) of foetal mouse cerebellum at days 13--15 of gestation was studied by light and electron microscopy. In Golgi-stained material, round or ovoid cells are located in the VL. These cells have ascending processes, which extend to the pial surface. Ultrastructurally, the ascending processes are electron-lucent, contain microfilaments, some smooth endoplasmic reticulum and scant free ribosomes. They appear to be immature glial processes, oriented radially away from the ventricle. The perikarya of these glial cells lie either in the ventricular or subventricular zones. Juxtaposed along the length of these radially oriented glial processes are unidentified cells, some of which are attached to the immature glial fibres by puncta adhaerentia. These cells are elongated or ovoid with a thin rim of cytoplasm containing few organelles. These unidentified cells may represent neuroblasts (Purkinje cells, Golgi cells, cells of the deep cerebellar nuclei) or glioblasts, (precursors of astrocytes and/or oligodendrocytes) at very early stages of development.


The INDEHISCENT protein regulates unequal cell divisions in Arabidopsis fruit.
INDEHISCENT (IND) is one of the major factors of a transcriptional network regulating fruit dehiscence in Arabidopsis thaliana. However, partially owing to the lack of knowledge on the morphogenic process at the junction between the valve margin and the replum, the cellular processes regulated by IND have not been elucidated. Here we report the identification of a zone of seven layers of cells relevant to silique dehiscence, and the isolation and characterization of a transposon-enhancer-trap-generated null allele of IND, ind-6. Light microscopy analysis revealed that the beta-glucuronidase from the enhancer trap was expressed in a seven-layer zone, encompassing the valve margin and the replum border. Electron and light microscopy analyses also revealed that unequal cell divisions actively occurred at stage 15 in the seven-layer zone in wild type (WT), which apparently produced the distinct cell types in the WT seven-layer zone. In contrast, siliques of ind-6 at stage 15 did not exhibit such cell divisions but fewer cells and defective cytokinesis, hence lacking the distinct cell types in the seven-layer zone. These results demonstrate a cellular mechanism for establishing the distinct cell types and a role for IND in regulating the unequal cell divisions in the seven-layer zone.


Activity of suprachiasmatic and hypothalamic neurons during sleep and wakefulness in the rat.
Single unit activity was recorded from the suprachiasmatic nucleus (SCN) and preoptic/anterior hypothalamus (POAH) of unrestrained Wistar rats during sleep and wakefulness. Regularly firing cells, which are abundant in in vitro SCN preparations and have been considered the basis of a central neuronal oscillator, were conspicuously absent in this preparation and in other in vivo studies. Most of the 55 cells recorded in the SCN and POAH were characterized by spontaneous firing rates below 12 Hz and with heterogeneous patterns of changes in frequency with arousal states. In vivo neurophysiological studies of the SCN in which the anesthetic agent urethane is used should consider the effect of different levels of arousal, as indicated by the cortical EEG, in evaluating the relationship between sensory stimulation and single unit activity.


Monoclonal antibody therapy of chronic lymphocytic leukemia.
Cure of patients with chronic lymphocytic leukemia (CLL) has been an elusive goal. The recent availability of active monoclonal antibodies has rekindled enthusiasm for new and innovative therapeutic approaches. Alemtuzumab, induces responses in about a third of patients with relapsed or refractory CLL following therapy with fludarabine and an alkylating agent. Whereas, rituximab has limited activity in previously treated patients, response rates of 50-70% have been reported in those without prior therapy. Recent data on combinations with rituximab and chemotherapy have shown promise for improving patient outcome. Newer antibodies in development include the primatized monoclonal antibody lumiliximab (IDEC-152), directed against CD23. Other biological approaches include the use of antisense oligonucleotides, proapoptic small molecules, and vaccines directed against the malignant B cells. The rational development of combinations of these promising approaches may eliminate the need for chemotherapy, leading to safer and more effective approaches for patients with CLL.


Strong coupling and vortexes assisted slow light in plasmonic chain-SOI waveguide systems.
A strong coupling regime is demonstrated at near infrared between metallic nanoparticle chains (MNP), supporting localized surface plasmons (LSP), and dielectric waveguides (DWGs) having different core materials. MNP chains are deposited on the top of these waveguides in such a way that the two guiding structures are in direct contact with each other. The strong coupling regime implies (i) a strong interpenetration of the bare modes forming two distinct supermodes and (ii) a large power overlap up to the impossibility to distinguish the power quota inside each bare structure. Additionally, since the system involves LSPs, (i) such a strong coupling occurs on a broad band and (ii) the peculiar vortex-like propagation mechanism of the optical power, supported by the MNP chain, leads to a regime where the light is slowed down over a wide wavelength range. Finally, the strong coupling allows the formation of guided supermodes in regions where the bare modes cannot be both guided at the same time. In other words, very high k modes can then be propagated in a dielectric photonic circuit thanks to hybridisation, leading to extremely concentrated propagating wave. Experimental work gives indirect proof of strong coupling regime whatever the waveguide core indexes.


Micro-edaphic factors affect intra-specific variations in trace element profiles of Noccaea praecox on ultramafic soils.
The aim of this study was to compare trace element profiles of Noccaea praecox (Wulfen) F. K. Mey. growing on ultramafic soils in different habitat types and to observe differences in uptake and translocation of trace elements. Physico-chemical characteristics of the soil and concentrations of P2O5, K2O, Ca, Fe, Mn, Zn, Cu, Ni, Cr, Pb, Cd, and Co in plant samples were presented. Biological concentration, accumulation, and translocation factors were calculated to estimate accumulation potential of different N. praecox accessions. All of the studied accessions were Ni hyperaccumulators (with shoot concentrations up to 14,593 mg kg-1), but with notable differences in accumulation and translocation rates. Significant differences in accumulation and translocation patterns of trace elements were observed among accessions from habitats characterized as serpentine steppes on dry, shallow soils in contrast to the accessions from habitats with higher soil moisture, and higher content of organic matter.


[No increase in chemotherapeutic effectiveness of cyclophosphamide (CPA) in rat leukemia L 5222 by 5-ethyl-2'-deoxyuridine (EDU) (author's transl)].
Monotherapy of early rat leukemia L 5222 with 5 X 100 mg/kg EDU over 48 h yielded no increase in lifespan as compared to untreated controls. Combination therapy of advanced L 5222 with EDU and CPA in four different schedules results in no increase in life-span as compared to treatment with CPA only. DNA histogrms of preterminal L 5222 revealed no synchronizing effect of EDU.


Effects of DNA methylation on cardiometabolic risk factors: a systematic review and meta-analysis.
Epigenetic changes, especially DNA methylation have a main role in regulating cardiometabolic disorders and their risk factors. This study provides a review of the current evidence on the association between methylation of some genes (LINE1, ABCG1, SREBF1, PHOSPHO1, ADRB3, and LEP) and cardiometabolic risk factors. A systematic literature search was conducted in electronic databases including Web of Science, PubMed, EMBASE, Google Scholar and Scopus up to end of 2020. All observational human studies (cross-sectional, case-control, and cohort) were included. Studies that assessed the effect of DNA methylation on cardiometabolic risk factors were selected. Among 1398 articles, eight studies and twenty-one studies were included in the meta-analysis and the systematic review, respectively. Our study showed ABCG1 and LINE1 methylation were positively associated with blood pressure (Fisher's zr = 0.07 (0.06, 0.09), 95% CI: 0.05 to 0.08). Methylation in LINE1, ABCG1, SREBF1, PHOSPHO1 and ADRB3 had no significant association with HDL levels (Fisher's zr = - 0.05 (- 0.13, 0.03), 95% CI:-0.12 to 0.02). Positive association was existed between LINE1, ABCG1 and LEP methylation and LDL levels (Fisher's zr = 0.13 (0.04, 0.23), 95% CI: 0.03 to 0.23). Moreover, positive association was found between HbA1C and ABCG1 methylation (Fisher's zr = 0.11 (0.09, 0.13), 95% CI: 0.09 to 0.12). DNA methylation of LINE1, ABCG1 and SREBF1 genes had no significant association with glucose levels (Fisher's zr = 0.01 (- 0.12, 0.14), 95% CI:-0.12 to 0.14). This meta-analysis showed that DNA methylation was associated with some cardiometabolic risk factors including LDL-C, HbA1C, and blood pressure. Registration ID of the protocol on PROSPERO is CRD42020207677 .


Identification of the naturally processed form of hen egg white lysozyme bound to the murine major histocompatibility complex class II molecule I-Ak.
A murine B-cell lymphoma bearing the class II major histocompatibility complex molecule I-Ak was cultured with the protein antigen hen egg white lysozyme (HEL). The I-Ak molecules were purified, and their associated peptides were extracted for characterization. Five HEL peptides were identified. Four contained the 10 amino acid residues HEL 52-61 (DYGILQINSR) but were heterogeneous in length and flanking residues. This core sequence is known to confer a high binding affinity for I-Ak. One additional peptide contained the amino acid residues HEL 48-60. These data demonstrate that the HEL epitope containing residues 52-61 is the most abundant HEL epitope presented on the major histocompatibility complex of the antigen-presenting cells and consequently explains its immunodominance.


Importance of families in nursing care for people with mental disorders: attitudes of Portuguese and Brazilian nurses.
To characterize and compare the attitudes of nurses working in primary healthcare on the importance of involving the families of people with mental disorders in nursing care. A cross-sectional study carried out in the cities of Porto (Portugal) and São Paulo (Brazil). Data was collected in 2018 using the "The Importance of Families in Nursing Care - Nurses' Attitudes" scale. There were 250 Portuguese and 250 Brazilian nurses who participated. The total average score on the scale was 86.0 in Portugal and 82.1 in Brazil (with a maximum possible of 104). The variables which influence a more favorable attitude towards the involvement of families in nursing care in the Portuguese context are academic qualifications and age, while in Brazil they are training on Family Nursing and the weekly workload. Participants in both countries have a positive attitude towards families, which constitutes a first step towards their integration in nursing care and also enables advances in mental health politics.


1,4-Reductive addition of glutathione to quinone epoxides. Mechanistic studies with h.p.l.c. with electrochemical detection under anaerobic and aerobic conditions. Evaluation of chemical reactivity in terms of autoxidation reactions.
The nucleophilic addition of GSH to quinonoid compounds, characterized as a 1,4-reductive addition of the Michael type, was studied with p-benzoquinone- and 1,4-naphthoquinone epoxides with different degree of methyl substitution. Identification and evaluation of molecular products from the above reaction were assessed by h.p.l.c. with either reductive or oxidative electrochemical detection, based on the redox properties retained in the molecular products formed. It was found that the degree of methyl substitution of the quinone epoxide, from either the 1,4-naphthoquinone- or p-benzoquinone epoxide series, determined their rate of reaction with GSH. The reductive addition implied the rearrangement of the quinone structure with opening of the epoxide ring yielding as the primary product a hydroxy-glutathionyl substituted adduct of either p-benzohydroquinone or 1,4-naphthohydroquinone. The primary product undergoes elimination reactions and redox transitions which bring about a number of secondary molecular products. The distribution pattern of the latter depends on the degree of methyl substitution of the quinone epoxide studied and on the concentration of O2 in the solution. The occurrence of the hydroxy-substituent in position alpha, adjacent to the carbonyl group, enhances the autoxidation properties of the compound resulting in an augmented O2 consumption and H2O2 production. Therefore, it could be expected that the chemical reactivity of the products originating from the thiol-mediated nucleophilic addition to quinone epoxides would be of toxicological interest.


Utilization of multiple "omics" studies in microbial pathogeny for microbiology insights.
In the present day, bioinformatics becomes the modern science with several advantages. Several new "omics" sciences have been introduced for a few years and those sciences can be applied in biomedical work. Here, the author will summarize and discuss on important applications of omics studies in microbiology focusing on microbial pathogeny. It can be seen that genomics and proteinomics can be well used in this area of biomedical studies.


MR urography (MRU) of non-dilated ureter with diuretic administration: Static fluid 2D FSE T2-weighted versus 3D gadolinium T1-weighted GE excretory MR.
The goal of this prospective study was to compare the efficiency of two types of MRU after diuretic administration to identify the non-dilated ureter. MR pelvic examinations were performed in 126 patients after receiving furosemide. Each patient underwent in addition to their protocol for context, two types of MRU: 2D T2-weighted FSE (T2w-MRU) and 3D Gd T1-weighted GE (CE-MRU). Four segments were checked for each ureter. For the first part of the analysis, readers evaluated the whole image quality using a four points subjective scale and for the second part, they were asked to score separately each ureteral segment as present or absent. 1008 ureteral segments were checked. For the image quality, readers did not find any significant difference (3.8 ± 0.5 vs 3.6 ± 0.7, p value: 0.13) between MRU methods. The interobserver agreement was excellent with a κ correlation coefficient as high as 0.89 for T2w-MRU and 0.92 for CE-MRU, respectively. For the detection of the segments and considering the 9 rotations for the T2W MRU, there were no statistically significant differences between the two groups. T2-weighted MRU with multiple orientations and diuretic is sufficient to identify the non-dilated ureter. It offers information on ureteral peristaltism. It can be suggested that this sequence is able to detect an initial obstruction before hydronephrosis occurs.


Red cell ghost-mediated microinjection of RNA into HeLa cells. I. A comparison of two techniques for the entrapment and microinjection of tRNA and mRNA.
We have compared two techniques for introducing RNA into red blood cell ghosts. In the pre-swell technique, RNA is introduced into red cells without prior removal of endogenous contents. In the multiple lysis technique, the red cells are subjected to two or three cycles of of reversible lysis, prior to introducing the RNA, in order to first remove the normal red cell constituents. The pre-swell technique offers much greater entrapment of both tRNA and protamine messenger RNA (mRNA), but the RNA appears to be degraded during the procedure. This may be due either to nucleolytic degradation or oxidation by the high concentration of endogenous hemoglobin. The multiple lysis technique offers much lower entrapment but also results in diminished degradation of the entrapped RNA. Although some degradation is apparent, a significant portion of the biological activity of the entrapped protamine mRNA is retained. We have also fused red cells loaded with protamine mRNA by the multiple lysis technique to HeLa cells using polyethylene glycol 6000. The recipient HeLa cells are capable of translating this heterologous message into protamine, a trout testis chromosomal protein.


Aplysillin A, a thrombin receptor antagonist from the marine sponge Aplysina fistularis fulva.
Aplysillin A [1], an unusual disulfate ester of a 1,4-diphenyl-1,3-butadiene, was isolated from a deep water specimen of a sponge of the genus Aplysina. Its structure was determined through spectroscopic methods. The compound weakly inhibited binding to the thrombin receptor with an IC50 value of 20 microM.


Uric acid and cardiovascular risk.
Uric acid has long been associated with cardiovascular disease. Most epidemiological evidence suggests a significant, graded, independent and specific association between the level of serum uric acid and cardiovascular morbidity and mortality. This is particularly robust among persons at high cardiovascular risk, including those with hypertension, diabetes and congestive heart failure. Although several potential mechanisms have been identified to explain this association, as yet there is no evidence that uric acid bears a causal or reversible relationship to vascular disease.


Survey of threats and assaults by patients on psychiatry residents.
The authors sought to determine the prevalence of threats and assaults by patients on psychiatry residents, their consequences, and the perceived adequacy of supports and institutional responses. Authors conducted an anonymous survey of 519 psychiatry residents in 13 psychiatry programs across the United States. The survey questionnaire inquired about residents' experiences of threats and assaults by patients during their residency training. The response rate for this survey was 39% (N=204). Residents were most commonly threatened (N=175; 86%), physically intimidated (N=145; 71%) or received unwanted advances (N=118; 58%). One-quarter (N=51; 25%) were physically assaulted. Most of the incidents occurred in inpatient settings (N=92; 45%). This study, like previous studies on this topic, calls attention to the high number of residents that are affected by violence during their training, and it underscores the need to protect the safety of psychiatry residents and to support those who have been victimized.


Ketogenic diet increases calbindin-D28k in the hippocampi of male ICR mice with kainic acid seizures.
The ketogenic diet (KD) increased the expression of calbindin-D(28k) (CB) in the interneurons of the hippocampus compared with the normal diet (ND)-fed mice. Also, 2 days after kainic acid (KA) administration, numerous CB-expressing astrocytes were found in the KD-fed mice compared with those of the ND-fed mice. These results suggest that the neuroprotective effect of the KD on the KA-induced toxicity may be, in part, mediated via an increased expression of CB.


Removing uranium (VI) from aqueous solution with insoluble humic acid derived from leonardite.
The occurrence of uranium (U) and depleted uranium (DU)-contaminated wastes from anthropogenic activities is an important environmental problem. Insoluble humic acid derived from leonardite (L-HA) was investigated as a potential adsorbent for immobilizing U in the environment. The effect of initial pH, contact time, U concentration, and temperature on U(VI) adsorption onto L-HA was assessed. The U(VI) adsorption was pH-dependent and achieved equilibrium in 2 h. It could be well described with pseudo-second-order model, indicating that U(VI) adsorption onto L-HA involved chemisorption. The U(VI) adsorption mass increased with increasing temperature with maximum adsorption capacities of 91, 112 and 120 mg g-1 at 298, 308 and 318 K, respectively. The adsorption reaction was spontaneous and endothermic. We explored the processes of U(VI) desorption from the L-HA-U complex through batch desorption experiments in 1 mM NaNO3 and in artificial seawater. The desorption process could be well described by pseudo-first-order model and reached equilibrium in 3 h. L-HA possessed a high propensity to adsorb U(VI). Once adsorbed, the release of U(VI) from L-HA-U complex was minimal in both 1 mM NaNO3and artificial seawater (0.06% and 0.40%, respectively). Being abundant, inexpensive, and safe, L-HA has good potential for use as a U adsorbent from aqueous solution or immobilizing U in soils.


Refractory Epilepsy as a Late Effect of Chemoradiation in Childhood Cancer: A Case Series.
Seizures are a common complication of both primary central nervous system (CNS) tumors and other oncologic processes with CNS involvement. They occur most frequently during induction or consolidation therapy, but there is a growing body of evidence that they can also develop later in life. Refractory epilepsy can develop as a late complication for survivors of pediatric cancer with CNS involvement who undergo chemoradiation therapy. We report three patients who presented with atypical nonconvulsive seizures (behavioral arrest, falls, nonsensical speech) up to 14 years after cancer diagnosis. All underwent whole-brain radiation in addition to chemotherapy. None had a prior epilepsy diagnosis or known prior seizures. One patient suddenly passed away of unclear causes five months after diagnosis, and the other two continued to have EEG findings consistent with cerebral dysfunction and epileptogenicity years after diagnosis. We hypothesize that the development of refractory epilepsy may be a late effect of radiation treatment. Given the high morbidity and mortality associated with epilepsy, early identification is crucial to improve outcomes and quality of life for this vulnerable population. This is especially true for patients with medication-refractory epilepsy as there is an increasing breadth of effective surgical options.


Invasive carcinoma after endoscopic ablative therapy for high-grade dysplasia in Barrett's oesophagus.
Patients with high-grade dysplasia (HGD) in Barrett's oesophagus carry a significant risk of developing adenocarcinoma. Endoscopic mucosal resection (EMR) and photodynamic therapy (PDT) aim at the radical ablation of the dysplastic area. We used EMR to resect the macroscopic area of dysplastic mucosa followed by PDT to eliminate residual disease. PDT was performed after oral administration of 5-aminolevulinic acid (ALA, 40 mg/kg), using fractionated illumination 3 and 6 h later with 630 nm light at 100 J/cm(2) through an endoscopic balloon diffuser. We report 2 patients who developed adenocarcinoma shortly after incomplete endoscopic ablation of Barrett's epithelium. In a 61-year-old man with HGD in 8-cm Barrett's segment, HGD persisted 3 months after treatment. The oesophagectomy specimen showed a 2.3-cm pT2N0M0 adenocarcinoma in Barrett's. In a 69-year-old woman with extensive HGD in 5-cm Barrett's, HGD persisted after 3 PDT sessions in 1 year. Adenocarcinoma occurred 6 months after treatment. The oesophagectomy showed a pT1bN0M0 adenocarcinoma and extensive multifocal HGD in Barrett's. The combination of EMR and PDT may be a promising option for local treatment of patients with HGD in Barrett's oesophagus, provided all dysplastic tissue can be removed. Currently it should be offered only to patients who are willing to participate in a clinical trial with an intensive endoscopic follow-up programme.


Role of Vitamin D in Infliximab-induced Remission in Adult Patients with Crohn's Disease.
Vitamin D is a key immunomodulator and its deficiency is prevalent among Crohn's patients. The interaction between vitamin D and the response to infliximab induction therapy has not been previously described. Patients with moderate-severe Crohn's disease, defined as having a modified Harvey Bradshaw index ≥8, who were being induced with infliximab were recruited. Patients were divided into low and normal vitamin D groups. Patients were followed prospectively for 14 weeks for achievement of clinical remission (Harvey Bradshaw index <5). At week 14, vitamin D deficient patients were supplemented with intramuscular cholecalciferol; all patients were re-assessed at week 22. Serum cytokine levels were measured at weeks 0, 14, and 22. Twenty-eight patients initiating infliximab were included, with 54% of patients in the low vitamin D group. The proportion of patients in clinical remission was greater in the low vitamin D group compared with the normal vitamin D group at both week 14 (80% versus 23%, P = 0.007) and week 22 (79% versus 17%, P = 0.005). The low vitamin D group had higher baseline IL-6 levels (median, 4.4 [interquartile range, 2.0-5.7] versus 1.1 [0.8-1.7] pg/mL, P = 0.004) and lower interleukin-12 levels (0.3 [0.1-0.4] versus 0.5 [0.5-0.6] pg/mL, P = 0.006) compared with the normal vitamin D group. At week 14, IL-8 levels were significantly lower in the low vitamin D group compared with the normal vitamin D group (11.2 [9.1-13.8] versus 20.5 [17.9-37.2] pg/mL, P = 0.005). Crohn's patients initiating infliximab with a low vitamin D level are more likely to achieve infliximab-induced clinical remission at week 14.


Flexible, sticky, and biodegradable wireless device for drug delivery to brain tumors.
Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.


Growth Velocities Across Distinct Early Life Windows and Child Cognition: Insights from a Contemporary US Cohort.
To evaluate the relative importance of overall and period-specific postnatal growth and their interaction with fetal growth on cognition in a generally well-nourished population. We included 1052 children from Project Viva, a prospective cohort in Boston, Massachusetts. Using linear spline mixed-effects models, we modeled length/height and body mass index (BMI) trajectories from birth to 7 years and estimated standardized overall (0-7 years) and period-specific growth velocities ie, early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (37-84 months). We investigated associations of growth velocities as well as their interactions with birthweight-for-gestational age on mid-childhood (mean age: 7.9 years) IQ, visual memory and learning, and visual motor ability. Greater overall height velocity was associated with modestly higher design memory score, (adjusted β [95% CI] 0.19 [-0.01,0.38] P = .057])points per SD increase but lower verbal IQ (-0.88 [-1.76,0.00] P = .051). Greater early infancy height velocity was associated with higher visual motor score (1.92 [0.67,3.18]). Greater overall BMI velocity was associated with lower verbal IQ (-0.71 [-1.52,0.11] P = .090). Greater late infancy BMI velocity was associated with lower verbal IQ (-1.21 [-2.07,-0.34]), design memory score (-0.22 [-0.42,-0.03)], but higher picture memory score (0.22 [0.01,0.43]). Greater early infancy height velocity (-1.5 SD vs 1.5 SD) was associated with higher nonverbal IQ (margins [95% CI] 102.6 [98.9106.3] vs 108.2 [104.9111.6]) among small-for-gestational age infants (P-interaction = 0.04). Among generally well-nourished children, there might not be clear cognitive gains with faster linear growth except for those with lower birthweight-for-gestational age, revealing the potential importance of early infancy compensatory growth.


Erratum: What Does the Informal Caregiver of a Terminally Ill Cancer Patient Need? A Study from a Cancer Centre.
[This corrects the article on p. 191 in vol. 17, PMID: 22346043.].


Natriuretic action of central angiotensin II in conscious rats.
The effects of intracerebroventricular (i.c.v.) injections of angiotensin II (ANG II, 10 pg, 100 pg and 10 ng) on renal sodium excretion were investigated in conscious rats instrumented with a chronic urethral catheter. ANG II increased renal sodium excretion dose-dependently with a threshold i.c.v. dose of 10 pg. Only after the highest dose was a concomitant increase in arterial blood pressure and urinary flow observed. The ANG II-induced natriuresis began within 5 min of the i.c.v. injection and lasted for more than 1 h. The angiotensin receptor antagonist saralasin (1 ng, i.c.v.) largely prevented the natriuretic effect of i.c.v. injected ANG II (100 pg). Our results lend further support to the hypothesis that brain ANG II by its potent natriuretic actions may be instrumental in central osmotic control.


Prenatal diagnosis of severe tricuspid insufficiency in Ebstein's anomaly with pulmonary atresia and intact ventricular septum: a case report.
Pulmonary atresia with intact ventricular septum is an uncommon congenital cardiac anomaly which very often present varying degrees of downward displacement and dysplasia of the tricuspid valve. A 23-year-old woman was referred at 23 weeks' gestation because of fetal cardiomegaly detected by routine ultrasonography. Ebstein's anomaly with pulmonary atresia was diagnosed by fetal echocardiography. On pulsed Doppler examination, a severe tricuspid regurgitation was detected. Pulmonary atresia was suspected, as forward flow was not detected into pulmonary artery. The fetus was terminated at 25 weeks. At the postmorterm examination Ebstein's anomaly with pulmonary atresia and intact ventricular septum were confirmed. The finding of right atrial enlargement on an early sonogram should prompt the search for tricuspid valve abnormalities with tricuspid regurgitation and the presence or development of pulmonary atresia or stenosis. With the information provided, early detection of tricuspid valve disease should be possible so that the option of therapeutic abortion can be offered.


Mandibular infected buccal cyst: report of two cases.
Two cases of mandibular infected buccal cyst are presented. A thorough review of the literature reveals that this is a fairly new entity with the first cases reported by Stoneman and Worth in 1983.


Heme-hemopexin: a 'chronosteric' heme-protein.
Hemopexin (HPX) serves as scavenger and transporter of toxic plasma heme to the liver. HPX is formed by two four-bladed beta-propeller domains, resembling two thick disks that lock together at a 90 degrees angle. The heme is bound between the two beta-propeller domains in a pocket formed by the interdomain linker peptide. Residues His213 and His266 coordinate the heme iron atom giving a stable bis-histidyl complex. The HPX-heme geometry is reminiscent of heme-proteins endowed with ligand binding and (pseudo-)enzymatic properties. HPX-heme binds reversibly CO, (*)NO, and cyanide by detaching His213; however, O(2) induces HPX-heme(II) oxidation. Furthermore, HPX-heme(II) facilitates (*)NO/O(2) and (*)NO/peroxynitrite scavenging. Heme sequestering by HPX prevents heme-mediated activation of oxidants which induce the low-density lipoprotein oxidation. Here, ligand binding and (pseudo-)enzymatic properties of HPX-heme are reviewed. HPX, acting not only as a heme carrier but also displaying transient heme-based ligand binding and (pseudo-)enzymatic properties, could be considered a 'chronosteric' heme-protein.


Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis.
An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and action mechanisms of HOX proteins in GC. A comprehensive search of PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX protein expression on the prognosis and clinicopathological features of GC, respectively. Nineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2 = 90.5%, p = 0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36-0.59, I2 = 3.1%, p = 0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79-3.74, I2 = 73.5%, p = 0.000). The aberrant expression of HOX protein was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC. In addition, the molecular mechanisms by which HOX proteins regulate tumorigenesis and development of GC were also explored. HOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.


Inhibitory action of human serum on the isoprenaline-induced chronotropic effect in cultured rat heart cells. Influence of sex and pregnancy.
Cultures of beating rat myocardial cells brought into contact with various human sera during 24 hours were infused with isoprenaline. The isoprenaline-induced positive chronotropic effect (IIPCE) was not found with all sera. IIPCE was present in all the male sera, but was absent in the cases of clinically beta-blocked pindolol treated men. IIPCE was present only in about 50% of the female sera, menopaused or not. IIPCE was absent in 95% of the sera of pregnant women in the late phase of pregnancy. This suggests the presence in female sera, especially during pregnancy, of a circulating factor capable of "in vitro" inhibition of isoprenaline-induced positive chronotropic effect.


Topographical arrangement of thalamocortical neurons in the centrolateral nucleus (CL) of the cat, with special reference to a spino-thalamo-motor cortical path through the CL.
In the centrolateral nucleus of the thalamus (CL) in the cat, a topographical arrangement of the thalamocortical projection neurons was demonstrated by utilizing retrograde axonal transport of horseradish peroxidase (HRP). Following injections of HRP into the medial or lateral areas of the anterior sigmoid gyrus (ASG), HRP-labeled neurons were located medially or laterally in the caudal levels of the CL, respectively; neurons in the central areas of the CL were labeled after injections of HRP into the rostral areas of the middle suprasylvian or the lateral gyrus. It was also shown by means of the combined HRP and Fink-Heimer method (Blomqvist and Westman, 1975) that the spinothalamic fibers terminated around CL neurons which were labeled with HRP injected into the lateral areas of the ASG. Hence, the caudolateral aspects of the CL were considered to represent a relay of the spino-thalamo-motor cortical paths.


The small auxin-up RNA OsSAUR45 affects auxin synthesis and transport in rice.
This research is the first to demonstrate that OsSAUR45 is involved in plant growth though affecting auxin synthesis and transport by repressing OsYUCCA and OsPIN gene expression in rice. Small auxin-up RNAs (SAURs) comprise a large multigene family and are rapidly activated as part of the primary auxin response in plants. However, little is known about the role of SAURs in plant growth and development, especially in monocots. Here, we report the biological function of OsSAUR45 in the model plant rice (Oryza sativa). OsSAUR45 is expressed in a tissue-specific pattern and is localized to the cytoplasm. Rice lines overexpressing OsSAUR45 displayed pleiotropic developmental defects including reduced plant height and primary root length, fewer adventitious roots, narrower leaves, and reduced seed setting. Auxin levels and transport were reduced in the OsSAUR45 overexpression lines, potentially because of decreased expression of Flavin-binding monooxygenase family proteins (OsYUCCAs) and PIN-FORMED family proteins (OsPINs). Exogenous auxin application rapidly induced OsSAUR45 expression and partially restored the phenotype of rice lines overexpressing OsSAUR45. These results demonstrate that OsSAUR45 is involved in plant growth by affecting auxin synthesis and transport through the repression of OsYUCCA and OsPIN gene expression in rice.


The atomic-scale mechanism for the enhanced glass-forming-ability of a Cu-Zr based bulk metallic glass with minor element additions.
It is known that the glass forming-ability (GFA) of bulk metallic glasses (BMGs) can be greatly enhanced via minor element additions. However, direct evidence has been lacking to reveal its structural origin despite different theories hitherto proposed. Through the high-resolution transmission-electron-microscopy (HRTEM) analysis, here we show that the content of local crystal-like orders increases significantly in a Cu-Zr-Al BMG after a 2-at% Y addition. Contrasting the previous studies, our current results indicate that the formation of crystal-like order at the atomic scale plays an important role in enhancing the GFA of the Cu-Zr-Al base BMG.


Alterations of cytoskeletal morphologies and growth patterns in human fibroblasts treated with polyethylene glycol.
Non-transformed human fibroblasts, strain PA-2, were treated with polyethylene glycol (PEG) in monolayer culture to produce multinucleate fibroblast homokaryons. Antibodies to tubulin or actin were used to monitor cytoplasmic microtubule and actin filament patterns immediately after cytoplasmic fusion, as well as after the fused cells had been in culture for varying amounts of time. The cytoplasmic microtubule complex as increased for a short time after cell fusion and then decreased to resemble the complex seen in control cells. The actin stress fibers were similarly enhanced for a comparable period of time. However, this initial enhancement of the actin stress fibers gradually diminished for approximately one month in culture after which the fibers were greatly reduced in both size and number. Concurrent with the changes in cytoplasmic microtubule and actin fiber complexes, the PEG-treated cells began to show alterations in growth parameters which progressively resembled those characteristic of transformed cell populations. Fusion of normal cells may be an initial step in the transformation of such cells to malignancy.


[Effect of intratracheal gamma-globulin administration on the mitotic activity and proliferative pool of lymphoid cells of the respiratory tract].
After injection of gamma-globulin into respiratory tracts of rats a proliferative pool of lymphoid cells in the lungs increases and remains unchanged in the spleen. The increase in the proliferative pool was accompanied by a decrease in a mitotic cycle in the S-period. Immunization was followed by intensification of division processes in a group of medium lymphocytes and processes of blast cells differentiation.


Investigation of roe deer--criteria for use as a bioindicator in specimen banking.
Some results are given for a 5-year study to establish standard operation procedures for roe deer (Capreolus capreolus). The criteria for bioindication of roe deer are listed for three forestry districts in the east of Lower Saxony (Braunschweig, Fallersleben, Lappwald). The organs investigated for use are liver, kidney, kidney fat, brain and were collected from animals with an intact abdomen and were packed in Teflon bags after being shot. The fresh samples are kept at +4 degrees C and prepared in a laboratory within 24 h. The organs were investigated for 20 organic and 15 inorganic constituents. Twenty-two detectable contaminants from different collections are evaluated by using a personal computer (PC) with a Statistical Package of Social Science (SPSS) program. The results show that liver is a good accumulating organ; organ size and the regular distribution of the contaminants throughout the organ are an advantage. Significant variations in concentrations of contaminants are observed in May until August; levels stabilize in September to November. Animals < 18 months of age should be selected from rather narrow and uniform biotopes for specimen banking during the periods of autumn to winter or May. Pooling of the samples is not recommended.


The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity.
Western Equine Encephalitis (WEE) is a naturally acquired infection and potentially devastating bioweapon, with no specific human countermeasures. An experimental inactivated Western Equine Encephalitis Vaccine (WEEV; WEE TSI-GSD 210) has been used under an IND (investigational New Drug) protocol at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 1976. Over 24 years from 1987 to 2011, 876 subjects received 3 primary vaccine doses under 3 studies with 1,537 booster doses administered (FY87-8, phase 2, laboratory workers, vaccine lots 1-81-1, 1-81-2, and 2-1-91; FY99-12, phase 2 laboratory workers, lot 2-1-91; and FY09-02, phase 1 healthy volunteer, lot 3-1-92). Post-vaccination safety and immunogenicity [plaque reduction neutralization test 80% (PRNT80) > 1:40] were analyzed. Overall PRNT80 response to the primary series in FY87-8 was 42% (326/770) but dropped to 16% (14/87) in FY99-12, prompting study FY09-02, which achieved 89% (17/19). The first booster response rate was 68% (814/1194) in FY87-8, 53% (171/324) in FY99-12, and 100% (10/10) in FY09-02. The majority of definitely related adverse reactions (AEs) were mild and local with no definitely related serious AEs. No laboratory acquired WEE infection was documented during this period despite 4 reported exposures in vaccinated subjects. The TSI-GSD 210 WEE vaccine was immunogenic, safe and well tolerated. Use of this vaccine could be considered in an emergency setting. Despite decades of safe and effective use under IND, full licensure is not planned due to manufacturing constraints, and a strategic decision to develop alternatives. https://clinicaltrials.gov/, identifier NCT01159561.


DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice.
Maintaining DNA integrity is vital for all cells and organisms. Defective DNA repair may contribute to neurological disorders, including Alzheimer's disease (AD). We found reduced levels of BRCA1, but not of other DNA repair factors, in the brains of AD patients and human amyloid precursor protein (hAPP) transgenic mice. Amyloid-β oligomers reduced BRCA1 levels in primary neuronal cultures. In wild-type mice, knocking down neuronal BRCA1 in the dentate gyrus caused increased DNA double-strand breaks, neuronal shrinkage, synaptic plasticity impairments, and learning and memory deficits, but not apoptosis. Low levels of hAPP/Amyloid-β overexpression exacerbated these effects. Physiological neuronal activation increased BRCA1 levels, whereas stimulating predominantly extrasynaptic N-methyl-D-aspartate receptors promoted the proteasomal degradation of BRCA1. We conclude that BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.


Factors associated with personal recovery among psychiatric nursing home residents.
WHAT IS KNOWN ABOUT THE SUBJECT?: Poor recovery will cause harm to the quality of life and well-being of residents and that the scope of influence includes the self, family and society. No study to date has investigated empowerment and the other multiple factors associated with personal recovery among psychiatric nursing home residents. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: The factors associated with personal recovery are empowerment, social support and global functioning. This pioneer study contributes new evidence that personal recovery is mainly predicted by empowerment, social support and global function, with empowerment exhibiting the highest predictive value. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Strengthening empowerment in mental health nursing may contribute more to the personal recovery of psychiatric nursing home residents than improving global function or social support. Mental health professionals should shift to empowerment-oriented care to improve individuals' personal recovery, such as offering more opportunities to achieve autonomy, encouraging individuals' involvement in decision-making and promoting individuals' motivation for achieving their goals. ABSTRACT: Introduction Individuals diagnosed with mental illness have a need for recovery. No study to date has investigated empowerment and the other multiple factors associated with personal recovery among psychiatric nursing home residents. Aim The study aimed to identify the factors associated with personal recovery among psychiatric nursing home residents. Methods This was a cross-sectional study with convenience sampling. Participants were recruited from a psychiatric nursing home in Northern Taiwan between April and June 2018. Data were collected through self-reported, structured questionnaires with verified reliability and validity. Descriptive and hierarchical regression analyses were performed. The present study followed the STROBE guidelines. Results The study included 158 participants. The factors associated with recovery according to bivariate associations were religious belief, psychotic symptoms, global function, social support and empowerment. In the hierarchical regression, empowerment, social support and global function were the main predictive factors of recovery, with the explained variation reaching 40.8%. Empowerment exhibited the highest predictive value for the recovery. Implications for clinical practice Strengthening empowerment in mental health nursing may contribute more to the personal recovery of psychiatric nursing home residents than improving global function or social support.


Influence of livestock grazing on C sequestration in semi-arid mixed-grass and short-grass rangelands.
We evaluated the effects of livestock grazing on C content of the plant-soil system (to 60 cm) of two semi-arid grasslands: a mixed-grass prairie (grazed 12 years), and a short-grass steppe (grazed 56 years). Grazing treatments included season-long grazing at heavy and light stocking rates, and non-grazed exclosures. Significantly higher soil C (0-30cm) was measured in grazed pastures compared to non-grazed exclosures, although for the short-grass steppe higher soil C was observed with the heavy grazing treatment only. Excluding grazing caused an immobilization of C in excessive aboveground plant litter, and an increase in annual forbs and grasses which lack dense fibrous rooting systems conducive to soil organic matter formation and accumulation. Our data indicate that higher soil C with grazing was in part the result of more rapid annual shoot turnover, and redistribution of C within the plant-soil system as a result of changes in plant species composition.


Differentiated service delivery for people using second-line antiretroviral therapy: clinical outcomes from a retrospective cohort study in KwaZulu-Natal, South Africa.
Evidence is needed to guide the inclusion of broader groups of people living with HIV (PLHIV) in differentiated service delivery (DSD) programmes. We assessed treatment outcomes among PLHIV on second-line regimens in a community antiretroviral therapy (ART) delivery programme, compared to those who remained at clinics. Using data from 61 public clinics, we did a retrospective cohort study among PLHIV receiving second-line ART following rollout of the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme in KwaZulu-Natal, South Africa. We included PLHIV from the timepoint when they were first eligible, though not necessarily referred, for community ART within CCMDD and followed them for 18 months. We used multivariable logistic regression to compare 12-month attrition and viraemia between clients referred for community ART and those remaining in clinic care. Among 209,744 PLHIV aged ≥ 18 years who collected ART between October 2016 and December 2018, 7511 (3.6%) received second-line ART. Of these, 2575 (34.3%) were eligible for community ART. The median age was 39.0 years (interquartile range 34.0-45.0) and 1670 (64.9%) were women. Five hundred and eighty-four (22.7%) were referred for community ART within 6 months of meeting eligibility criteria. Overall, 4.5% [95% confidence interval (CI) 3.0-6.6%] in community ART and 4.4% (95% CI 3.5-5.4%) in clinic care experienced attrition at 12 months post eligibility for community ART. Two thousand one hundred and thirty-eight (83.0%) had a viral load recorded 6-18 months after becoming eligible, and of these, 10.3% (95% CI 7.7-13.3%) in community ART and 11.3% (95% CI 9.8-12.9%) in clinic care had viraemia > 200 copies/ml. In separate regressions adjusted for age, gender, district, time on second-line ART, nucleoside reverse transcriptase inhibitor backbone and year of eligibility, no differences in the odds of attrition [adjusted odds ratio (aOR) 1.02, 95% CI 0.71-1.47] or viraemia (aOR 0.91, 95% CI 0.64-1.29) were observed between those in community ART and those remaining in clinic care. We found good outcomes among PLHIV who were stable on second-line regimens and referred for community ART. Efforts to expand DSD access among this group should be prioritized.


Pain Neurophysiology Knowledge Enhances Attitudes toward Biopsychosocial Management of Low Back Pain among Japanese Physical Therapists.
The aim of the current study was to investigate whether a postgraduate academic degree, longer clinical experience, and pain neurophysiology knowledge influence attitudes toward the balance between biomedical and biopsychosocial management of low back pain (LBP). Ninety Japanese physical therapists completed the revised Neurophysiology of Pain Questionnaire (revised NPQ), the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT) questionnaire, and a survey on their degree qualifications and clinical experience. Their attitudes toward the balance between biomedical and biopsychosocial management of LBP were assessed using the mean biomedical scale scores divided by the mean biopsychosocial scale scores of the PABS-PT. Multiple regression modeling of the attitudes toward the balance between biomedical and biopsychosocial management of LBP was carried out using three independent variables: possession of an undergraduate or postgraduate academic degree, length of clinical experience, and the score on the revised NPQ. Of the 90 therapists, 72 had an undergraduate degree and 18 also had a postgraduate degree. Only the revised NPQ score (β=-0.364, P <0.001) was a statistically significant contributing factor to attitudes toward the balance between biomedical and biopsychosocial management of LBP (R 2=0.14). Neither having a postgraduate degree (β=0.017, P=0.871) nor the length of clinical experience (β=-0.107, P=0.303) had a significant effect. This study demonstrated that pain neurophysiology knowledge, but not the possession of a postgraduate academic degree or the length of clinical experience, promotes attitudes toward biopsychosocial management of LBP among Japanese physical therapists.


General practice and dementia. A national survey of Australian GPs.
To find out what difficulties general practitioners (GPs) experience with diagnosing and managing dementia. Postal questionnaire to a random stratified sample of one in seven active Australian GPs (2182 of 14,932). 1473 GPs (67.5%) responded to the questionnaire. The results indicated reasonable knowledge about diagnostic features of dementia and good insight into common issues facing family carers. Even so, GPs had difficulties with diagnosis and management of dementia and wanted assessment protocols and educational programs. A minority of GPs regularly screened elderly patients for cognitive impairment but the majority relied on passive means of diagnosing dementia. Although generally positive about Aged Care Assessment Teams (ACATs) and Aged Care Community Services (ACCS), GPs expressed some concerns about these services. Recommendations arising from the survey were: development of an assessment protocol and a screening instrument, regular cognitive check-ups for patients over 75 years, educational programs, improved coordination with Aged Care Assessment Teams and Community Services, inventories and registers of local community services and residential facilities, and appropriate Medicare rebates.


Impaired activity of thiol-dependent ATPases in rheumatoid mononuclear cell membranes.
Ion-motive ATPase play an essential role in many aspects of cell biology, including mononuclear cell (MNC) functions relevant to chronic inflammation. For example, ouabain, a specific inhibitor of Na+, K+ ATPase, suppresses both T and B cell proliferation but induces synthesis of IL-1. Using a cytochemical assay quantified by microdensitometry, total and ouabain-sensitive ATPase activities have been compared in MNC from rheumatoid and control subjects. The sensitivity of these enzymes to inactivation by thiol-blocking reagents has been studied by preincubation with an impermeant SH blocker p-hydroxymercuriphenylsulphonate (pHMPSA). The results show that rheumatoid MNC have significantly impaired ATPase activity compared to healthy cells and that both total and ouabain-sensitive ATPase activities are readily inhibited by pHMPSA. The depressed ATPase activity in rheumatoid MNC could thus be due to blockade/oxidation of a reactive surface thiol, and could contribute to perpetuation of the chronic inflammatory process in these patients.


Mycorrhizal diversity and community composition in co-occurring Cypripedium species.
Orchids commonly rely on mycorrhizal fungi to obtain the necessary resources for seed germination and growth. Whereas most photosynthetic orchids typically associate with so-called rhizoctonia fungi to complete their life cycle, there is increasing evidence that other fungi may be involved as well and that the mycorrhizal communities associated with orchids may be more diverse. Coexisting orchid species also tend to associate with different fungi to reduce competition for similar resources and to increase long-term population viability. However, few studies have related the mycorrhizal communities in the rhizosphere to communities found in the roots of closely related coexisting orchid species. In this study, we used high-throughput sequencing to investigate the diversity and community composition of orchid mycorrhizal fungi in the roots and the rhizosphere of four Cypripedium species growing in forests in Northeast China. The results showed that the investigated Cypripedium species associated with a wide variety of fungi including members of Tulasnellaceae, Psathyrellaceae, and Herpotrichiellaceae, whereas members of Russulaceae, Cortinariaceae, Thelephoraceae, and Herpotrichiellaceae showed high abundance in rhizosphere soils. The diversity of fungi detected in the rhizosphere soil was much higher than that in the roots. The observed variation in fungal communities in Cypripedium roots was not related to forest site or orchid species. On the other hand, variation in mycorrhizal communities of rhizosphere soil was significantly related to sampling site. These results indicate that orchid mycorrhizal communities in the rhizosphere display considerable variation among sites and that orchids use only a subset of the locally available fungi. Future studies focusing on the fine-scale spatial distribution of orchid mycorrhizal fungi and more detailed assessments of local environmental conditions will provide novel insights into the mechanisms explaining variation of fungal communities in both orchid roots and the rhizosphere.


Patient satisfaction with availability of general practice: an international comparison.
To identify associations between the characteristics of general practitioners and practices, and patients' evaluations of the availability of general practice. Written surveys completed by patients. General practice care in nine European countries: Denmark, Germany, The Netherlands, Norway, UK, Belgium (Flanders and Wallonia), Switzerland, Slovenia and Spain. 15996 adult patients consecutively visiting the general practitioner (response rates per country varied between 47 and 89%). The Europep instrument to assess patients' evaluations of five aspects of the availability of general practice care: (1) getting an appointment, (2) getting through on the phone, (3) being able to speak to the practitioner on the telephone, (4) waiting time in the waiting room, and (5) providing quick services for urgent health problems. Each general practitioner recorded age, sex, number of years in the practice, number of practitioners and other care providers in the practice, and urbanization level of the practice. Patients' more positive evaluations were associated with fewer general practitioners in the practice, except for quick services for urgent health problems (range of conditional overall odds ratios, 1.69-2.02). In addition, a number of significant unconditional overall odds ratios were found, particularly those related to the number of general practitioners' working hours and the number of care providers in the practice. None of the associations was found consistently in all countries. Patients favour small practices and full-time general practitioners, which contradicts developments in general practice in many countries. Policy makers should consider how the tensions between patients' views and organizational developments can be solved.


Model-driven insights into the effects of temperature on metabolism.
Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves the way to develop approaches for mitigating the effects of future climate scenarios. A systems view of the effects of temperature on cellular physiology can be obtained by focusing on metabolism since: (i) its functions depend on transcription and translation and (ii) its outcomes support organisms' development, growth, and reproduction. Here we provide a systematic review of modelling efforts directed at investigating temperature effects on properties of single biochemical reactions, system-level traits, metabolic subsystems, and whole-cell metabolism across different prokaryotes and eukaryotes. We compare and contrast computational approaches and theories that facilitate modelling of temperature effects on key properties of enzymes and their consideration in constraint-based as well as kinetic models of metabolism. In addition, we provide a summary of insights from computational approaches, facilitating integration of omics data from temperature-modulated experiments with models of metabolic networks, and review the resulting biotechnological applications. Lastly, we provide a perspective on how different types of metabolic modelling can profit from developments in machine learning and models of different cellular layers to improve model-driven insights into the effects of temperature relevant for biotechnological applications.


Adult vaccination as the cornerstone of successful ageing: the case of herpes zoster vaccination. A European Interdisciplinary Council on Ageing (EICA) expert focus group.
Herpes zoster (HZ) is a painful cutaneous rash with vesicular lesions, lasting up to 3 weeks, and caused by reactivation of the latent varicella zoster virus (VZV). It may be associated with complications, the most feared being post-herpetic neuralgia. Effective vaccines are available to prevent HZ, but uptake remains low. We report here the conclusions of an expert focus group convened by the European Interdisciplinary Council on Ageing (EICA). The group discussed how existing recommendations regarding HZ vaccination could be better implemented, and how compliance and coverage with HZ vaccination could be enhanced. This report proposes strategies to increase awareness of HZ and its vaccine, enhance vaccine uptake, and educate regarding the role of prevention, including immunization, as a means to "age well". A key strategy that could rapidly and easily be implemented at low cost is co-administration of HZ vaccine with other vaccines scheduled in the target age group. The scientific evidence surrounding the safety and efficacy of co-administration is discussed. Other strategies, such as active calls, publicity campaigns and national vaccine registries are also outlined. There is a compelling need for a full consensus document that carries weight across all the healthcare professions involved in vaccination, to issue simple and basic recommendations for all healthcare providers.


The predatory mite Neoseiulus paspalivorus (Phytoseiidae) in Brazil: taxonomic status, reproductive compatibility and morphological and molecular variability.
The predatory mite Neoseiulus paspalivorus (De Leon) is often found in association with the coconut mite, Aceria guerreronis Keifer. The identification of natural enemies is essential for the definition of biological control strategies. Therefore, the present study aimed to confirm whether the mite populations from different Northeastern Brazilian states identified as N. paspalivorus belong to the same species. This determination was accomplished through the study of morphometric variability in 33 anatomical characters and of molecular variability in two DNA fragments: Internal Transcribed Spacer (ITS) rDNA and cytochrome c oxidase subunit I (COI) mtDNA. This study also determined whether there is reproductive isolation between the two most morphologically distinct populations (Rio Grande do Norte and Paraíba). Intraspecific morphometric variability was observed among the five populations of N. paspalivorus. Despite this variability, the crosses and backcrosses of the most morphologically distinct populations did not show reproductive incompatibility. The molecular analysis indicated the absence of genetic differences among the N. paspalivorus populations for the ITS fragment. Three haplotypes were identified for the COI fragment, and the genetic distance ranged from 0 to 0.2 %. Despite the morphometric differences, the results of the molecular and biological analysis corroborate the previous identification of N. paspalivorus for all of the studied populations. The present study contributes to the systematics of Phytoseiidae predatory mites and to the biological control of A. guerreronis by the accurate identification and characterization of one of its main natural enemies along extensive areas in Brazil.


Repurposing pentosan polysulfate sodium as hyaluronic acid linked polyion complex nanoparticles for the management of osteoarthritis: A potential approach.
Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially weight-bearing joints like knee, hip, backbone, and phalanges. NSAIDs that are used for the management of inflammation associated with osteoarthritis have high side effects related to gastric upset, gastric ulcer, and long term treatment associated with liver and kidney damage. Nanotechnology has gained a huge scope for the management of arthritis as it can reach out to the deep inside the cell and alter cellular physiology as desired. The present study hypothesizes the use of polyion complex nanoparticles of hyaluronic acid linked Pentosan polysulfate sodium, a disease-modifying agent for the treatment of osteoarthritis administered through transdermal route. The hypothesis involves the use of drug repurposing as the drug was initially approved for interstitial cystitis, a condition of the urinary bladder associated with pain and swelling. Being very low oral bioavailability and gastric irritation profile, the transdermal route would be beneficial. To overcome the problem associated with the oral route, there is a need for the targeted approach that will particularly reach at inflammatory sites. Thereby transdermal delivery of hyaluronic acid linked Pentosan polysulfate sodium through polyion complex nanoparticle therapy will be a novel therapeutic approach to combat osteoarthritis.


Early sonographic evaluation of the transjugular intrahepatic portosystemic shunt (TIPS).
The purpose of this study was to evaluate duplex and color Doppler findings in patients before and within 24 h after transjugular intrahepatic portosystemic shunts (TIPS). Conventional duplex and color Doppler were used in the assessment of 19 patients who underwent TIPS as part of a prospective protocol. Patients were examined within 24 h before and after the procedure. Before TIPS, patency, flow direction, and peak flow velocity in the main portal vein and hepatic artery were studied, as well as patency and flow direction in hepatic veins, splenic vein, and inferior vena cava (IVC). Immediately after the procedure, sonographic identification of stent position, shunt patency, and flow dynamics were evaluated and patency and flow direction of hepatic veins, splenic vein, and IVC were determined. The portogram performed at the end of the procedure was compared with the 24-h sonographic studies after TIPS to determine sonographic/angiographic correlation. No intraparenchymal abnormalities or perihepatic fluid collections were detected after the procedure. The metallic stent was clearly seen in all patients. Mean peak shunt flow velocities were 139 +/- 50 cm/sec within 24 h after TIPS. Absence of flow through the shunt was correctly identified in one case and confirmed angiographically. Mean peak flow velocity in the portal vein before TIPS was 22 +/- 13.6 cm/sec and increased to 43.6 +/- 9.1 cm/sec after TIPS (p < 0.05). The hepatic artery peak systolic velocity increased from 77 +/- 51 cm/sec before TIPS to 119 +/- 53 cm/sec after the procedure (p = 0.029).(ABSTRACT TRUNCATED AT 250 WORDS)


Serum lipoproteins in the spiny lobster, Panulirus interruptus.
1. Most of the lipids in the hemolymph of the spiny lobster, Panulirus interruptus, were associated with a high density lipoprotein (HDL3). The lipid of this lipoprotein was composed of phospholipid (88%), sterol (4%) and triglyceride (3%). 2. In animals fed 14C-labeled triglyceride radioactivity was not seen in the serum until 12 hr after feeding. Most of this serum radioactivity was associated with phosphatidyl choline. 3. Electron micrographs showed that negatively stained high density lipoproteins of the lobster had a polymorphic appearance.


Stability of memories of parental rearing among psychiatric inpatients: a replication based on EMBU subscales.
With regard to information about parental rearing, retrospective data are exclusively available among adults. These data are vulnerable due to various biases. This study was performed in order to replicate the findings of overall stability of three perceived parental rearing factors of the EMBU (Swedish acronym for 'own memories of childhood upbringing') based on 14 rather detailed subscales. A consecutive sample of 220 depressive inpatients were investigated on admission and at discharge by means of the EMBU, the Beck Depression Inventory and the Dysfunctional Attitude Scale. Perceived parental rearing scores showed high stability despite clinically significant changes in the severity of depression, except for 'tolerance', 'guilt engendering', 'performance orientation' and 'shaming' parenting with probable gender-specific effects which were found to covary with dysfunctional attitudes. Recall of parenting should be taken as a subjective truth when it is assessed by standardised behaviour-oriented questionnaires like the EMBU.


Direct calculation of elementary flux modes satisfying several biological constraints in genome-scale metabolic networks.
The concept of Elementary Flux Mode (EFM) has been widely used for the past 20 years. However, its application to genome-scale metabolic networks (GSMNs) is still under development because of methodological limitations. Therefore, novel approaches are demanded to extend the application of EFMs. A novel family of methods based on optimization is emerging that provides us with a subset of EFMs. Because the calculation of the whole set of EFMs goes beyond our capacity, performing a selective search is a proper strategy. Here, we present a novel mathematical approach calculating EFMs fulfilling additional linear constraints. We validated our approach based on two metabolic networks in which all the EFMs can be obtained. Finally, we analyzed the performance of our methodology in the GSMN of the yeast Saccharomyces cerevisiae by calculating EFMs producing ethanol with a given minimum carbon yield. Overall, this new approach opens new avenues for the calculation of EFMs in GSMNs. Matlab code is provided in the supplementary online materials email@example.com. Supplementary data are available at Bioinformatics online.


Analyses of balance and flexibility of obese patients undergoing bariatric surgery.
To assess the postural control and flexibility of obese subjects before and both six and 12 months after bariatric surgery. To verify whether postural control is related to flexibility following weight reductions resulting from bariatric surgery. The sample consisted of 16 subjects who had undergone bariatric surgery. All assessments were performed before and six and 12 months after bariatric surgery. Postural balance was assessed using an Accusuway® portable force platform, and flexibility was assessed using a standard chair sit and reach test (Wells' chair). With the force platform, no differences were observed in the displacement area or velocity from the center of pressure in the mediolateral and anteroposterior directions. The displacement speed from the center of pressure was decreased at the six month after the surgery; however, unchanged from baseline at 12 months post-surgery. Flexibility increased over time according to the three measurements tested. Static postural balance did not change. The velocity of postural adjustment responses were increased at six months after surgery. Therefore, weight loss promotes increased flexibility. Yet, improvements in flexibility are not related to improvements in balance.


Irritable bowel syndrome symptom patterns: frequency, duration, and severity.
We examined symptom frequency, duration, and severity, as well as episode patterns, in 122 adult patients with irritable bowel syndrome in a 12-week study conducted in the United States, the United Kingdom, and The Netherlands. Patients used an interactive telephone data entry system daily to report symptoms. Data from 59 of the patients meeting inclusion criteria are presented, the remainder having been excluded for failing to complete at least 70 days of symptom reporting. The majority of patients experienced at least one symptom on over 50% of the reported days; however, individual symptoms were reported on less than 50% of the days, indicating that symptoms sometimes occurred sequentially rather than always simultaneously. On average, patients reported pain/discomfort on 33% of days, bloating on 28% of the days, altered stool form or stool passage on 25% and 18% of the days, respectively, and mucus on 7% of the days. The duration of symptoms was relatively short, with pain/discomfort and bloating lasting the longest, an average of five days each per episode. All symptoms but one (mucus) were moderately severe on the majority of reported days. Patients experienced an "episode" (defined as a period of days with symptoms bounded by one or more symptom-free days) on an average of 12.4 times during the study, but the duration of these episodes varied greatly among patients. These results further establish the chronic nature of irritable bowel syndrome and the burden that this condition imposes on patients.


Computed Tomography-Derived Three-Dimensional Printed Models versus Two-Dimensional Transesophageal Echocardiography for Left Atrial Appendage Occlusion Device Planning: A Systematic Review and Meta-Analysis.
This systematic review and meta-analysis compared computed tomography (CT)-derived three-dimensional (3D) modeling versus two-dimensional transesophageal echocardiography (TEE) for left atrial appendage occluder (LAAO) device planning. LAAO device planning is commonly performed with TEE. However, procedures often require multiple devices and deployments due to inaccurate sizing from TEE. The use of CT three-dimensional (3D) models for LAAO device planning may improve accuracy. Four clinical studies that reported procedural and clinical outcomes for CT-derived 3D modeling versus TEE for LAAO device planning were identified. End points were accurate device sizing, procedure failure, number of devices used per procedure, fluoroscopy time, and post-procedure leak. Risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI) were calculated by the Mantel-Haenszel and inverse variance methods. A total of 166 participants were included. When compared with conventional imaging, the use of 3D printed models was associated with less fluoroscopy time (MD -6.98 minutes, 95% CI -12.68 to -1.28, p=0.02) and lower risk of occluder device peri-prosthetic leak (RR 0.23, 95% CI 0.07-0.73, p=0.01) for LAAO. There were signals towards lower number of devices per procedure (MD -0.56 devices, 95% CI -1.16-0.05, p=0.07) and less total procedure time (MD -13.50 minutes, 95% CI -28.14-1.14, p=0.07) with printed modeling for LAAO. There was no difference between modalities in rates of procedure failure. CT-derived 3D printed models for LAAO device planning may offer the advantages of lower LAAO device peri-prosthetic leak and less fluoroscopy time when compared with conventional TEE guidance.


Cycloheximide treatment of cotton ovules alters the abundance of specific classes of mRNAs and generates novel ESTs for microarray expression profiling.
Fibres of cotton (Gossypium hirsutum L.) are single elongated epidermal cells that start to develop on the outer surface of cotton ovules on the day of anthesis. Little is known about the control of fibre initiation and development. As a first step towards discovering important genes involved in fibre initiation and development using a genomics approach, we report technical advances aimed at reducing redundancy and increasing coverage for anonymous cDNA microarrays in this study. Cotton ovule cDNA libraries (both normalised and un-normalised) from around the time of fibre initial formation have been prepared and partially characterised by sequencing. Re-association-based normalisation partially reduced library redundancy and increased representation of novel sequences. However, another library generated from in vitro cultured cotton ovules treated with the protein synthesis inhibitor, cycloheximide, showed a significantly altered gene representation including a greater proportion of protein phosphorylation genes, transport genes and transcription factors and a much reduced proportion of protein synthesis genes than were identified in the conventional types of libraries. Over 10,000 expressed sequence tag (EST) clones randomly selected from the three libraries were printed on microarray slides and used to assess gene expression in tissue cultured ovules with and without cycloheximide treatment. The microarray results showed that cycloheximide had a dramatic effect in modifying the pattern of the gene expression in cultured ovules, affecting the same types of genes identified in the preliminary analysis on relative EST abundance in the different ovule cDNA libraries. Cycloheximide clearly provided a simple and useful method for enriching novel gene sequences for genomic studies.


Immune responses in serum and respiratory secretions following vaccination with a live cold-recombinant (CR35) and inactivated A/USSR/77 (H1N1) influenza virus vaccine.
One hundred adult volunteers were administered inactivated vaccine (20 micrograms/0.5 cc) intramuscularly (IM) or intranasally (IN), or 10(4.7) TCID50 of a live cold-adapted vaccine (CR35) IN. Microneutralization (Nt) and radioimmunoprecipitation methods were employed to measure hemagglutinin antibody responses in sera, nasal washes, and in bronchopulmonary lavage fluids. In unprimed recipients, the relative frequency of serum antibody response and magnitude of rise was highest following the IM-inactivated vaccine (100%) and lowest after IN-live vaccine (29%). However, in individuals with pre-existing antibody, the three vaccines given were comparably immunogenic. Occurrences of secretory IgA hemagglutinin antibody in nasal washings were more frequently associated with topical administration of live or inactivated vaccine, whereas, IgG hemagglutinin antibody responses occurred with equal frequency in nasal washings in all three vaccine groups. Analysis of the hemagglutinin antibody responses in the lower respiratory tract showed that the IN-live vaccine favored the induction of secretory IgA hemagglutinin antibody and the IM-inactivated vaccine stimulated a more frequent IgG hemagglutinin antibody response.


Obesity as a Factor Contributing to Falls by Older Adults.
The growth of the worldwide population of older adults presents significant challenges, many inter-related, that range from the health of individuals to the health of national economies. In the US, more than one-third of older adults may be obese, a condition that may independently increase the risk for mobility impairment, fall-related injury and, possibly, costs of post-injury treatment and care. The effectiveness of conventional exercise-based fall prevention programs is significant but smaller than both the annual rate of falling of older adults and rate of growth of this population, who are at greatest risk for injurious falls. The anthropometric and functional consequences of obesity may impose limitations on the ability to perform compensatory stepping responses following large postural disturbances. The focus of this paper is the potential of task-specific training to improve compensatory stepping responses and reduce falls by obese people given the individual-specific anthropometric and functional consequences of obesity.


Spacer-free BODIPY fluorogens in antimicrobial peptides for direct imaging of fungal infection in human tissue.
Fluorescent antimicrobial peptides are promising structures for in situ, real-time imaging of fungal infection. Here we report a fluorogenic probe to image Aspergillus fumigatus directly in human pulmonary tissue. We have developed a fluorogenic Trp-BODIPY amino acid with a spacer-free C-C linkage between Trp and a BODIPY fluorogen, which shows remarkable fluorescence enhancement in hydrophobic microenvironments. The incorporation of our fluorogenic amino acid in short antimicrobial peptides does not impair their selectivity for fungal cells, and enables rapid and direct fungal imaging without any washing steps. We have optimized the stability of our probes in human samples to perform multi-photon imaging of A. fumigatus in ex vivo human tissue. The incorporation of our unique BODIPY fluorogen in biologically relevant peptides will accelerate the development of novel imaging probes with high sensitivity and specificity.


Basic concepts and directions in the radiation therapy quality assurance processes of clinical trials.
The radiation therapy quality assurance of clinical trials is internationally recognized as a key factor to control the quality of radiotherapy for its impact on clinical trial's goals. Quality assessment may be performed at different levels and by different means, which are now quite standardized. The optimal radiation therapy quality assurance of clinical trials trade-off to maintain accrual rates, radiotherapy quality and optimize clinical trial research processes is yet to be defined. This article addresses current definitions, processes, limitations and directions.


Sweet host revenge: Galectins and GBPs join forces at broken membranes.
Most bacterial pathogens enter and exit eukaryotic cells during their journey through the vertebrate host. In order to endure inside a eukaryotic cell, bacterial invaders commonly employ bacterial secretion systems to inject host cells with virulence factors that co-opt the host's membrane trafficking systems and thereby establish specialised pathogen-containing vacuoles (PVs) as intracellular niches permissive for microbial growth and survival. To defend against these microbial adversaries hiding inside PVs, host organisms including humans evolved an elaborate cell-intrinsic armoury of antimicrobial weapons that include noxious gases, antimicrobial peptides, degradative enzymes, and pore-forming proteins. This impressive defence machinery needs to be accurately delivered to PVs, in order to fight off vacuole-dwelling pathogens. Here, I discuss recent evidence that the presence of bacterial secretion systems at PVs and the associated destabilisation of PV membranes attract such antimicrobial delivery systems consisting of sugar-binding galectins as well as dynamin-like guanylate-binding proteins (GBPs). I will review recent advances in our understanding of intracellular immune recognition of PVs by galectins and GBPs, discuss how galectins and GBPs control host defence, and highlight important avenues of future research in this exciting area of cell-autonomous immunity.


Ileoanal Pouch Syndrome Is Common and Associated With Significant Disability in Patients With Ulcerative Colitis Undergoing IPAA.
Recently, ileoanal pouch syndrome (IPS) has been proposed and defined according to a series of patient-centered bowel symptoms and consequences after ileoanal pouch surgery. The purpose of this study was to investigate the prevalence of IPS and the related disability in UC patients undergoing IPAA. This was a cross-sectional study. This study was conducted in a tertiary center. Data of 128 UC-related IPAA from October 2014 to May 2021 were collected. Primary outcomes were prevalence of IPS. One hundred twenty-eight patients were enrolled with a median postoperative follow-up of 2.64 (IQR, 1.31-3.80) years. The prevalence of IPS and its constituent symptoms and consequences are lower for patients with longer follow-up after ileostomy reversal. Fecal incontinence and pad usage had the greatest impact on the quality of life affecting 29% and 31% of patients. IPS group had a significantly higher IBD-Disability Index score compared to the non-IPS group (27.25 vs 12.15, p < 0.001). Multivariate analysis showed that 4 symptoms (fecal incontinence, clustering, fragmentation and incomplete evacuation, and nocturnal symptoms) and 2 consequences (pad usage and negative mental alterations) were associated with increased IBD-Disability Index (p < 0.05). For patients followed-up for >2 years, multivariate analysis showed that male gender (OR, 4.485; 95% CI, 1.354-14.857; p = 0.014), preoperative duration of disease (OR, 1.013; 95% CI, 1.001-1.025; p = 0.031), and postoperative follow-up (OR, 0.462; 95% CI, 0.244-0.876; p = 0.049) were independently associated with IPS. This is a single-center cross-sectional study rather than a prospective multicenter large longitudinal study. IPS is a common situation negatively affecting the quality of life for patients with ulcerative colitis undergoing IPAA, and its rate decreased over time from ileal pouch surgery. See Video Abstract at http://links.lww.com/DCR/C41. ANTECEDENTES:Recientemente se propuso y definió el síndrome del reservorio ileoanal de acuerdo con una serie de síntomas intestinales centrados en el paciente y las consecuencias después de la cirugía del reservorio ileoanal.OBJETIVO:El propósito de este estudio fue investigar la prevalencia del síndrome del reservorio ileoanal y la discapacidad relacionada en pacientes con colitis ulcerosa con reservorio ileal y anastomosis reservorio-anal.DISEÑO:Este fue un estudio transversal.ESCENARIO:Este estudio se realizó en un centro terciario.PACIENTES:Se recopilaron datos de 128 pacientes con reservorio ileal por colitis ulcerosa desde octubre de 2014 hasta mayo de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la prevalencia del síndrome del reservorio ileoanal.RESULTADOS:Ciento veintiocho pacientes fueron reclutados con una mediana de seguimiento postoperatorio de 2,64 (IQR, 1,31-3,80) años. La prevalencia del síndrome del reservorio ileoanal y sus síntomas y consecuencias constituyentes es menor para los pacientes con un seguimiento más prolongado después de la reversión de la ileostomía. La incontinencia fecal y el uso de compresas tuvieron el mayor impacto en la calidad de vida, afectando al 29% y al 31% de los pacientes. El grupo con síndrome del reservorio ileoanal tuvo una puntuación del índice de discapacidad por enfermedad inflamatoria intestinal significativamente más alta en comparación con el grupo sin síndrome del reservorio ileoanal (27,25 frente a 12,15, p <0,001). El análisis multivariado mostró que 4 síntomas (incontinencia fecal, agrupamiento, fragmentación y evacuación incompleta y síntomas nocturnos) y 2 consecuencias (uso de toallas higiénicas y alteraciones mentales negativas) se asociaron con un aumento del índice de discapacidad por enfermedad inflamatoria intestinal (p <0,05). Para los pacientes seguidos durante más de dos años, el análisis multivariado mostró que el sexo masculino (OR, 4,485; IC 95%, 1,354-14,857; p = 0,014), la duración preoperatoria de la enfermedad (OR, 1,013; IC 95%, 1,001-1,025; p = 0,031) y el seguimiento postoperatorio (OR, 0,462; IC 95%, 0,244-0,876; p = 0,049) se asociaron de forma independiente con el síndrome del reservorio ileoanal.LIMITACIONES:Este es un estudio transversal de un solo centro en lugar de un gran estudio longitudinal prospectivo multicéntrico.CONCLUSIONES:El síndrome del reservorio ileoanal es una situación común que afecta negativamente la calidad de vida de los pacientes con colitis ulcerosa sometidos a anastomosis del reservorio ileal-anal, y su tasa disminuyó con el tiempo a partir de la cirugía del reservorio ileal. El sexo masculino y la mayor duración preoperatoria de la enfermedad son factores de riesgo importantes para el síndrome del reservorio ileoanal. Consulte Video Resumen en http://links.lww.com/DCR/C41. (Traducción-Dr. Felipe Bellolio).


Temperature and food quality influences feeding behavior, assimilation efficiency and growth rate of arctic woolly-bear caterpillars.
The energy budget for feeding activity and growth of larval Gynaephora groenlandica was investigated on the tundra and in the laboratory. Larvae fed only in June when the buds and young leaves of Salix arctica, its principal host plant, contained the highest concentrations of macro-nutrients and total nonstructural carbohydrates (TNC). The mid-summer hiatus in larval feeding was coincident with an abrupt decline in the TNC content of leaves and a buildup of plant secondary metabolites in the leaves of S. arctica. Following cessation of feeding, the larvae remained concealed from the sun within crevices and vegetation mats. Growth rates of larvae incubated at 15 and 30°C were similar (4.7-5.0 mg/larva/day), but the assimilation efficiency at 15°C was four times greater (40%) than at 30°C. Growth rates were lowest at 5°C (0.22mg/larva/day) as was the assimilation efficiency (6.6%), because of the extended residence time of food in the gut. The high rate of ingestion and excretion at 30°C was caused by elevated maintenance metabolism. Changes in metabolic state influenced oxygen consumption, which was highest for feeding larvae (0.29 ml/g/h) and significantly lower for each, digesting, moving, starved larvae, and lowest for inactive larvae (0.06 ml/g/h). An influence of temperature and leaf quality on digestion rate and maintenance metabolism is the most likely cause of the feeding behavior pattern in G. groenlandica. The larvae may undergo "voluntary hypothermia" in order to avoid an energy, deficit resulting from high maintenance metabolism during mid-season when the energy content and food quality declines. The restriction of growth and development to a very short period prior to mid-summer may have contributed, to the extended 14-year life cycle of this species.


'Smelling' the cerebrospinal fluid: olfactory signaling molecules are expressed in and mediate chemosensory signaling from the choroid plexus.
The olfactory-type signaling machinery has been known to be involved not only in odorant detection but also in other tissues with unsuspected sensory roles. As a barrier, the choroid plexus (CP) is an active participant in the monitoring of the cerebrospinal fluid (CSF), promptly responding to alterations in its composition. We hypothesized that olfactory signaling could be active in CP, contributing to the surveillance of the CSF composition. We determined the mRNA and protein expression of the major components of the olfactory transduction pathway in the rat CP, including odorant receptors, the olfactory G-protein (Gαolf), adenylate cyclase 3 and cyclic nucleotide-gated channel 2. The functionality of the transduction pathway and the intracellular mechanisms involved were analyzed by DC field potential recording electrophysiological analysis, in an ex vivo CP-brain setup, using polyamines as stimuli and blockers of the downstream signaling pathways. Concentration-dependent responses were obtained for the polyamines studied (cadaverine, putrescine, spermine and spermidine), all known to be present in the CSF. Transfection of a CP epithelial cell line with siRNA against Gαolf effectively knocked down protein expression and reduced the CP cells' response to spermine. Thus, the key components of the olfactory chemosensory apparatus are present and are functional in murine CP, and polyamines seem to trigger both the cAMP and the phospholipase C-inositol 1,4,5-trisphosphate pathways. Olfactory-like chemosensory signaling may be an essential component of the CP chemical surveillance apparatus to detect alterations in the CSF composition, and to elicit responses to modulate and maintain brain homeostasis.


Modeling dopamine system dysfunction in experimental animals.
Quite a substantial number of human disorders have been associated with a primary or a secondary impairment of one or several of the dopaminergic pathways. Among disorders associated with a primary impairment of dopaminergic transmission are Parkinson's disease, striatonigral degeneration, progressive supranuclear palsy, and possibly schizophrenia. Diseases of secondary dopamine dysfunction are chiefly represented by Huntington's disease in which dopaminergic transmission is being interrupted by progressive loss of the striatal neurons bearing the postsynaptic D1- and D2-dopamine receptors. Central dopaminergic systems have anatomical as well as organizational properties that render them unique by comparison to other neurotransmission systems, making them able to play a pivotal role in the modulation of various important brain functions such as locomotor activity, attention, and some cognitive abilities. These properties of dopamine neurons have obviously several implications in the clinical expression of human disorders involving dopamine neuron dysfunction. In addition, they can greatly influence the clinical/behavioral consequences of experimental lesions in animal models of dopamine dysfunctions.


Valvular Heart Disease in Pregnancy.
Valvular heart disease (VHD) is generally well tolerated during pregnancy; however, the dramatic changes in hemodynamics that occur during pregnancy can lead to clinical decompensation in high-risk women. Women with VHD considering pregnancy should undergo preconception counseling with a high-risk obstetrician and cardiologist to review the maternal, fetal, and obstetric risks of pregnancy and delivery. Vaginal delivery is recommended for most women with VHD. Given the complexity of managing VHD during pregnancy, women should be managed by a multidisciplinary Pregnancy Heart Team during pregnancy, consisting of a high-risk obstetrician, cardiologist, and cardiac anesthesiologist.


Biobutanol production from rice straw by a non acetone producing Clostridium sporogenes BE01.
Biobutanol from lignocellulosic biomass has gained much attention due to several advantages over bioethanol. Though microbial production of butanol through ABE fermentation is an established technology, the use of lignocellulosic biomass as feedstock presents several challenges. In the present study, biobutanol production from enzymatic hydrolysate of acid pretreated rice straw was evaluated using Clostridium sporogenes BE01. This strain gave a butanol yield of 3.43 g/l and a total solvent yield of 5.32 g/l in rice straw hydrolysate supplemented with calcium carbonate and yeast extract. Hydrolysate was analyzed for the level of inhibitors such as acetic acid, formic acid and furfurals which affect the growth of the organism and in turn ABE fermentation. Methods for preconditioning the hydrolysate to remove toxic end products were done so as to improve the fermentation efficiency. Conditions of ABE fermentation were fine tuned resulting in an enhanced biobutanol reaching 5.52 g/l.