In situ preparation of MOF-199 into the carrageenan-grafted-polyacrylamide@Fe3O4 matrix for enhanced adsorption of levofloxacin and cefixime antibiotics from water.
In this research study, a novel method, an in-situ growth approach, to incorporate metal-organic framework (MOF) into carrageenan-grafted- polyacrylamide-Fe3O4 substrate was introduced. Carrageenan-grafted-polyacrylamide-Fe3O4/MOF nanocomposite (kC-g-PAAm@Fe3O4-MOF-199) was fabricated utilizing three stages. In this way, the polyacrylamide (PAAm) was grafted onto the carrageenan (kC) backbone via free radical polymerization in the presence of methylene bisacrylamide (MBA) as cross-linker and Fe3O4 magnetic nanoparticles. Next, the kC-g-PAAm@Fe3O4 was modified by MOF-199 via an in-situ solvothermal approach. Several analyses such as Fourier transform infrared spectroscopy (FT-IR), X-Ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-Dispersive X-ray Spectroscopy (EDX), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), Brunauer-Emmett-Teller (BET) demonstrated the successful synthesis of kC-g-PAAm@Fe3O4-MOF-199 magnetic hydrogel nanocomposite. The XRD pattern of magnetic hydrogel nanocomposite illustrated characteristic peaks of Fe3O4, neat kC, and MOF-199 with enhanced crystallinity in comparison with kC-g-PAAm@Fe3O4. TGA showed it has a char yield of 24 wt% at 800 °C. VSM confirmed its superparamagnetic behavior (with Ms of 8.04 emu g-1), and the BET surface area of kC-g-PAAm@Fe3O4-MOF-199 was measured at 64.864 m2 g-1, which was higher than that of kC-g-PAAm@Fe3O4 due to the highly porous MOF-199 incorporation with a BET surface area of 905.12 m2 g-1). The adsorption effectiveness of kC-g-PAAm@Fe3O4-MOF-199 for eliminating cephalosporin and quinolones antibiotics, i.e., Cefixime (CFX) and Levofloxacin (LEV) from the aquatic area was considered. Several experimental setups were used to evaluate the efficacy of adsorption, such as solution pH, amount of adsorbent, contact duration, and initial concentration. The maximum adsorption capacity (Qmax) of the prepared magnetic hydrogel nanocomposite was found to be 2000 and 1666.667 mg-1 for LEV and CFX using employing 0.0025 g of adsorbent. The Freundlich isotherm model well described the experimental adsorption data with R2CFX = 0.9986, and R2LEV = 0.9939. And the adsorption kinetic data were successfully represented by the pseudo-second-order model with R2LEV = 0.9949 and R2CFX = 0.9906. Hydrogen bonding, π-π interaction, diffusion, and entrapment in the hydrogel network all contributed to the successful adsorption of both antibiotics onto the kC-g-PAAm@Fe3O4-MOF-199 adsorbent. Other notable physicochemical properties include the three-dimensional structure and availability of the reactive adsorption sites. Moreover, the adsorption/desorption efficacy of magnetic hydrogel nanocomposites was not significantly diminished after four cycles of recovery.


Interaction of C-reactive protein with artificial phosphatidylcholine bilayers.
C-Reactive protein (CRP), the most characteristic of the 'acute phase proteins' (ref. 1) is thought to participate in the mediation and/or modulation of acute inflammatory processes, but its exact function is unknown. CRP has a Ca2+-dependent binding specificity for phosphorylcholine, the polar head group of two widely distributed lipids, lecithin (phosphatidylcholine, PC) and sphingomyelin (SM). A number of observations suggest that at least some of the biological activities of CRP depend on its interaction with phospholipids of cell membranes. In addition, interaction of CRP with PC- and SM-containing lipid dispersions and with PC-containing liposomes can activate the complement system. We report here that binding of CRP to model membranes of PC requires the incorporation into the bilayer of lysophosphatidylcholine (LPC). Thus, a disturbance of the molecular organisation of the bilayer appears to be necessary for binding of CRP. These findings provide a possible biochemical explanation for binding of CRP to damaged but not intact cell membranes and might be relevant to its biological function.


Oral high-dose phenobarbital therapy for early infantile epileptic encephalopathy.
We report oral high-dose phenobarbital therapy for a patient with early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome). At 1 month of age, many series of tonic spasms, with raising limbs and crying lasting for a few minutes, developed and increased up to approximately 300 times per day. Initially intravenous midazolam (0.5 mg/kg/hour) slightly decreased the seizures, although oral vitamin B6, valproic acid, clonazepam, and zonisamide had little effect. Oral high-dose phenobarbital therapy was begun at a dosage of 15 mg/kg/day, and the seizures markedly decreased to 5-10 times per day and the epileptic discharges on electroencephalogram greatly decreased. Serum phenobarbital levels ranged between 60 and 100 mg/dL. High-dose phenobarbital therapy should be considered for the treatment of early infantile epileptic encephalopathy with suppression bursts.


Mononeuropathy multiplex as an uncommon presentation of intravascular lymphoma: A case report.
Although intravascular lymphoma rarely presents with peripheral neuropathy, learning about this presentation can lead to timely diagnosis and improved prognosis in patients with intravascular lymphoma. A 64-year-old man presented with asymmetric paresthesia and subsequent weakness of his feet and a 10 kg weight loss over 40 days. Electrodiagnostic studies revealed distal axonal sensory-motor polyneuropathy with ongoing axonal loss. A peroneal nerve biopsy showed intravascular proliferation of CD-20 positive lymphocytes, which suggested intravascular large B-cell lymphoma.


Leukocytoclastic vasculitis and infection. Report of a case.
Leukocytoclastic vasculitis is the most common cause of cutaneous vasculitis in clinical practice. Its causes are various, among which are certain infections. We report the case of a man (28 years old) who debuted with vasculitic lesions in inferior members compatibles leukocytoclastic vasculitis on pathology. The study of causation is the presence of a positive urethral discharge to Ureaplasma urealyticum, dramatically improving lesions after treatment thereof.


Examining adolescent daughters' and their parents' academic-gender stereotypes: Predicting academic attitudes, ability, and STEM intentions.
Women continue to be underrepresented in Science, Technology, Engineering, and Mathematics (STEM) and research suggests that academic-gender stereotypes can be a contributing factor. In the present research, we examined whether adolescent daughters' and their parents' gender stereotypes about math and liberal arts would predict the academic orientation of daughters at a critical time of career related decision-making. Participants included girls in late adolescence (N = 185, Mage = 17) and at least one parent (N = 230, Mage = 49), resulting in 147 mother-daughter dyads and 83 father-daughter dyads. Implicit academic-gender stereotypes were measured using an Implicit Association Test (IAT) and explicit stereotypes, academic attitudes, academic ability, and daughters' intentions to pursue a degree in STEM were measured using self-reports. Neither mothers' nor fathers' implicit or explicit academic-gender stereotypes predicted adolescent daughters' implicit stereotypes; however, fathers' explicit stereotypes predicted daughters' explicit stereotypes. In addition, daughters' academic orientation, a latent variable composed of adolescent girls' academic attitudes, academic ability, and intentions to pursue a degree in STEM, was predicted by daughters' own implicit and explicit stereotypes. This was the case for relative orientation toward math versus liberal arts, as well as math (but not liberal arts) orientation. These findings suggest the importance of challenging academic-gender stereotypes during adolescence and suggest that at this stage in development, mothers' and fathers' academic stereotypes might have limited relation to daughters' own implicit associations with academic domains.


Application of supercritical fluid chromatography in the quantitative analysis of minor components (carotenes, vitamin E, sterols, and squalene) from palm oil.
The application of supercritical fluid chromatography (SFC) coupled with a UV variable-wavelength detector to isolate the minor components (carotenes, vitamin E, sterols, and squalene) in crude palm oil (CPO) and the residual oil from palm-pressed fiber is reported. SFC is a good technique for the isolation and analysis of these compounds from the sources mentioned. The carotenes, vitamin E, sterols, and squalene were isolated in less than 20 min. The individual vitamin E isomers present in palm oil were also isolated into their respective components, alpha-tocopherol, alpha-tocotrienol, gamma-tocopherol, gamma-tocotrienol, and delta-tocotrienol. Calibration of all the minor components of palm as well as the individual components of palm vitamin E was carried out and was found to be comparable to those analyzed by other established analytical methods.


Substrate-induced modulation of ATP turnover in dog and rabbit proximal tubules.
In dog proximal tubules in suspension, the addition of glucose increased significantly the ouabain-sensitive fraction of respiration, a response suppressed by phlorizin. The addition of alpha-methyl-D-glucoside (alpha-MG) had a modest effect and 3-O-methyl-D-glucoside (3-O-MG) had no effect. The different stimulation of the Na+,K(+)-ATPase activity elicited for each hexose could be explained by a different increment of net transepithelial flux of sodium induced by the sodium: hexose cotransport. This flux is a direct function of the transport characteristics of both luminal and antiluminal membranes of proximal cells for these sugars: glucose is rapidly transported by both membranes (allowing a large transepithelial flux of glucose: sodium) while alpha-MG is poorly transported by the basolateral, and 3-O-MG by the luminal, membrane of the dog proximal tubule (allowing a small transepithelial flux of hexoses and sodium). However the overall tubular respiration of dog proximal tubules was not increased by glucose addition because the increment in the ouabain-sensitive fraction was accompanied by a reciprocal decrement in an ouabain-insensitive but oligomycin- or N',N' dicyclohexylcarbodiimide (DCCD)-sensitive (or in the bafilomycin-sensitive) component of respiration. This component reflects the activity of a large BBM-bound H(+)-ATPase found in this species. The intracellular pH of dog proximal tubules in suspension was measured using the proton-sensitive fluorescent probe 2',7'-bis-2-(carboxyethyl)-5, (and 6)-carboxyfluorescein. Glucose application significantly alkalinized the cells. In contrast, other substrates such as lactate or acetate simultaneously acidified the cells and increased the ouabain-insensitive phosphorylative respiration of dog tubules. These observations suggest that a modulation of the activities of both the sodium and most probably the proton pump is elicited by substrate availability in suspensions of proximal tubules.


Prevention and management of postoperative nausea and vomiting after cesarean section: A systematic literature review.
Post-operative nausea and vomiting (PONV) are a common post-operative problem in anesthesia. The incidence of PONV in patients undergoing cesarean sections is very high. Post-operative nausea and vomiting have many negative impacts on the patient, baby, family, and health care system. Therefore, appropriate evidence-based knowledge regarding the prevention and management of PONV for those high-risk patients is a timely and very important issue to address to decrease the associated complications. A comprehensive literature search was conducted in Pubmed/Medline, Cochrane reviews, and google scholar including those studies published in the English language from 2010 up to 2021. The methodological quality of the included studies was appraised by the Cochrane risk of a biased assessment tool for intervention and non-interventional studies. The search strategy identified a total of 10,540 articles from different electronic databases. 33 articles were selected for screening after duplicates were removed; finally, 17 articles were included for critical appraisal and 16 articles were excluded with reasons. The included articles consist of 15 RCT, 1 non-control prospective cohort, and 1 cross-sectional study. Pieces of evidence revealed that all obstetrics patients undergoing cesarean section should be given multimodal PONV prophylaxis. It is shown that a multimodal approach by a combination of different antiemetic agents should be preferred and most effective in preventing intraoperative and postoperative nausea and vomiting for patients undergoing cesarean section because of the complex pathophysiology of nausea and vomiting.


EstB from Burkholderia gladioli: a novel esterase with a beta-lactamase fold reveals steric factors to discriminate between esterolytic and beta-lactam cleaving activity.
Esterases form a diverse class of enzymes of largely unknown physiological role. Because many drugs and pesticides carry ester functions, the hydrolysis of such compounds forms at least one potential biological function. Carboxylesterases catalyze the hydrolysis of short chain aliphatic and aromatic carboxylic ester compounds. Esterases, D-alanyl-D-alanine-peptidases (DD-peptidases) and beta-lactamases can be grouped into two distinct classes of hydrolases with different folds and topologically unrelated catalytic residues, the one class comprising of esterases, the other one of beta-lactamases and DD-peptidases. The chemical reactivities of esters and beta-lactams towards hydrolysis are quite similar, which raises the question of which factors prevent esterases from displaying beta-lactamase activity and vice versa. Here we describe the crystal structure of EstB, an esterase isolated from Burkholderia gladioli. It shows the protein to belong to a novel class of esterases with homology to Penicillin binding proteins, notably DD-peptidase and class C beta-lactamases. Site-directed mutagenesis and the crystal structure of the complex with diisopropyl-fluorophosphate suggest Ser75 within the "beta-lactamase" Ser-x-x-Lys motif to act as catalytic nucleophile. Despite its structural homology to beta-lactamases, EstB shows no beta-lactamase activity. Although the nature and arrangement of active-site residues is very similar between EstB and homologous beta-lactamases, there are considerable differences in the shape of the active site tunnel. Modeling studies suggest steric factors to account for the enzyme's selectivity for ester hydrolysis versus beta-lactam cleavage.


Losartan reduces sympathetic nerve outflow from the brain of rats with chronic renal failure.
Sympathetic nervous system (SNS) activity, measured by norepinephrine (NE) turnover rate, was greater in the posterior hypothalamic (PH) nuclei, the paraventricular nuclei (PVN), and the locus coeruleus (LC) of 5/6 nephrectomised (CRF) rats than of control rats. NE secretion from the PH was also greater in CRF than in control rats. These findings demonstrate that SNS activity plays an important role in the genesis of hypertension associated with CRF. The increase in central SNS activity was mitigated by increased local expression of nitric oxide synthase (NOS)-mRNA and nitric oxide (NOx) production. Because angiotensin II may stimulate the central SNS, we tested the hypothesis that losartan, a specific angiotensin II AT(1)-receptor antagonist, may lower blood pressure (BP), at least in part, by central noradrenergic inhibition. To this end, we studied two groups of CRF rats. One group received losartan (10 mg/kg body weight) in drinking water between the 3rd and 4th week after nephrectomy, the second group received drinking water without losartan. SNS activity was measured by NE secretion from the PH using the microdialysis technique. NOS-mRNA gene expression was also measured by RT-PCR in the PH, PVN, and LC of CRF and control rats. Losartan reduced systolic BP from 184+/-3.7 to 152+/-3.1 mmHg and NE secretion from the PH from 340+/-9.7 to 247+/-4.8 pg/ml. CRF rats treated with losartan manifested a significant (p<0.01) increase in the expression of nNOS-mRNA in the PH (from 84+/-1.2 to 99+/-2.6), the PVN (from 44+/-1.5 to 63+/-2.1), and the LC (from 59+/-6.7 to 76+/-2.1). CRF rats also manifested a significant increase (p<0.01) in the expression of IL-1beta the PH (from 41.6+/-2.8 to 54.3+/-1.4), PVN (from 44+/-1.9 to 54+/-1.5), and LC (from 35.5+/-1.6 to 53.5+/-1.9). In conclusion, these studies suggest that the antihypertensive action of losartan in CRF rats may be mediated, at least in part, by inhibition of central SNS outflow. The studies also suggest that the inhibitory action of losartan on the SNS may be mediated by activation of IL-1beta, which, in turn, stimulates nNOS, an important modulator of central SNS activity.


Peri-partum cardiac failure.
The syndrome of peri-partum cardiac failure (PPCF) has been studied in 224 women seen in three years in Zaria, in northern Nigeria. A very high proportion were rural Hausa patients. There was a seasonal peak in July, and the incidence was about one per cent of deliveries. The risk increased with both age and parity. Symptoms began most commonly in the second week after delivery, and admission was commonest in the fourth. Typical signs of cardiac failure were found, and pulsus alternans, atrio-ventricular valvular incompetence, transient systemic hypertension and splenomegaly were common. The chest radiograph showed marked cardiomegaly, and extrasystoles and inverted T waves were often present in the electrocardiogram (ECG). Hypoalbuminaemia was common. Digoxin and diuretics were rapidly effective, causing a mean weight loss of 29 per cent in 15 days, resolution of hypertension, and a fall in the cardio-thoracic ratio (CTR) from 61 to 53 per cent. During the first year after diagnosis, the CTR became normal in 82 per cent of patients, and the ECG in 60 per cent. PPCF recurred, again with the same seasonal variation, after 19 per cent of subsequent pregnancies. During follow up for two to five years, 22 per cent of the women became hypertensive, and 11 per cent died. The prognosis was worst in those with an arrhythmia, hypertension, sustained cardiomegaly or aged 30 or more. Asymtomatic post-partum hypertension (PPHT) was found in 61 per cent of normal Hausa women, with a seasonal peak in May, especially in those with hypertension during pregnancy or labour, and twin pregnancies. Peri-partum cardiac failure may be due to the combined pressure load of PPHT, the volume load from eating the customary sodium-rich kanwa, and the cardiovascular demands of heat, both climatic and traditionally self-imposed.


Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group.
The aim of the present trial was to evaluate the effects of chemotherapy on the quality of life and survival of patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB or IV). In a controlled multicentre trial, patients were randomised to receive supportive care only or supportive care plus chemotherapy. Chemotherapy consisted of intravenous (i.v.) carboplatin 300 mg/m2 on day 1 and etoposide 120 mg/m2 orally on days 1-5 every 4 weeks for a maximum of eight courses. Quality of life was measured at randomisation and prior to each treatment course and at corresponding 4-week intervals in the control arm, using the EORTC QLQ-C30 + LC13 questionnaire. 48 patients were randomised (supportive care 26, chemotherapy 22), being eligible for comparative analyses. Another 102 patients, 97 of which received chemotherapy, were subsequently included in the study on an individual treatment preference basis. Data from these patients were used for confirmative purposes. Patients in the chemotherapy group reported better overall physical functioning and symptom control compared with the supportive care group. Group differences were smaller within the psychosocial domain, although trends were seen in favour of the chemotherapy group. No significant differences were seen in favour of the supportive care group, except for hair loss. Median survival times were 29 weeks in the chemotherapy group versus 11 weeks in the supportive care group, and 1-year survival rates were 28% versus 8%. Quality of life and survival outcomes were similar in the randomised and non-randomised patients receiving chemotherapy. No treatment-related deaths occurred. In conclusion, treatment with carboplatin and etoposide can improve both the quality of life and the survival of patients with advanced NSCLC.


Does capacity to produce androgens underlie variation in female ornamentation and territoriality in White-shouldered Fairywren (Malurus alboscapulatus)?
Historic bias toward study of sex hormones and sexual ornamentation in males currently constrains our perspective of hormone-behavior-phenotype relationships. Resolving how ornamented female phenotypes evolve is particularly important for understanding the diversity of social signals across taxa. Studies of both males and females in taxa with variable female phenotypes are needed to establish whether sexes share mechanisms underlying expression of signaling phenotypes and behavior. White-shouldered Fairywren (Malurus alboscapulatus) subspecies vary in female ornamentation, baseline circulating androgens, and response to territorial intrusion. The moretoni ornamented female subspecies is characterized by higher female, but lower male baseline androgens, and a stronger pair territorial response relative to pairs from the lorentzi unornamented female subspecies. Here we address whether subspecific differences in female ornamentation, baseline androgens, and pair territoriality are associated with ability to elevate androgens following gonadotropin releasing hormone (GnRH) challenge and in response to simulated territorial intrusion. We find that subspecies do not differ in their capacity to produce androgens in either sex following GnRH or simulated territorial intrusion (STI) challenges. STI-induced androgens were predictive of degree of response to territorial intrusions in females only, but the direction of the effect was mixed. GnRH-induced androgens did not correlate with response to simulated intruders, nor did females sampled during intrusion elevate androgens relative to flushed controls, suggesting that increased androgens are not necessary for the expression of territorial defense behaviors. Collectively, our results suggest that capacity to produce androgens does not underlie subspecific patterns of female ornamentation, territoriality, and baseline plasma androgens.


More persistent weather causes a pronounced soil microbial legacy but does not impact subsequent plant communities.
A soil history of exposure to extreme weather may impact future plant growth and microbial community assembly. Currently, little is known about whether and how previous precipitation regime (PR)-induced changes in soil microbial communities influence plant and soil microbial community responses to a subsequent PR. We exposed grassland mesocosms to either an ambient PR (1 day wet-dry alternation) or a persistent PR (30 days consecutive wet-dry alternation) for one year. This conditioned soil was then inoculated as a 10 % fraction into 90 % sterilized "native" soil, after which new plant communities were established and subjected to either the ambient or persistent PR for 60 days. We assessed whether past persistent weather-induced changes in soil microbial community composition affect soil microbial and plant community responses to subsequent weather persistence. The historical regimes caused enduring effects on fungal communities and only temporary effects on bacterial communities, but did not trigger soil microbial legacy effects on plant productivity when exposed to either current PR. This study provides experimental evidence for soil legacy of climate persistence on grassland ecosystems in response to subsequent climate persistence, helping to understand and predict the influences of future climate change on soil biota.


Short-term costs in patients with chronic kidney disease treated with dapagliflozin: a retrospective cohort study.
This real-world study evaluated the impact of dapagliflozin on short-term medical costs in patients with stage 3 chronic kidney disease (CKD). This retrospective, observational cohort study used medical and pharmacy claims data from IQVIA PharMetrics Plus. Patients aged ≥18 years with a filled dapagliflozin prescription after stage 3 CKD diagnosis between September 2020 and December 2021 were 1:1 propensity score matched with patients with stage 3 CKD who did not receive dapagliflozin. The primary endpoint was cardiorenal medical costs to payers over 6 months; all-cause medical and pharmacy costs were also analyzed. Within the overall population, there was a new-user subgroup of patients with no sodium-glucose co-transporter-2 use during baseline. The new-user subgroup included 503 matched patients per cohort. Mean per-patient cardiorenal medical costs were reduced by 49.0% in the dapagliflozin versus non-dapagliflozin cohort ($3172.15 vs $6219.50; P < 0.001). Mean all-cause medical costs were reduced ($8043.58 vs $12,194.87; P < 0.001) and mean all-cause pharmacy costs were increased ($9056.98 vs $7453.23; P = 0.22). Results were similar for the overall population. This study showed dapagliflozin was associated with reduced cardiorenal medical costs over 6 months compared with no dapagliflozin treatment in patients with stage 3 CKD, demonstrating real-world medical cost savings.


Enteric glial cells mediate gut immunity and repair.
In the gut, coordinated cell interactions regulate tissue repair and immunity. How enteric glial cells (EGCs) mediate these processes remained elusive. In a recent paper, Progatzky et al. demonstrate that EGCs interact with immune and mesothelial cells under homeostasis and helminth infection, revealing an indispensable role of an interferon-γ (IFNγ)-EGC-CXCL10 axis in tissue repair.


Radioimmunoassay for triiodothyronine: use of polyethylene glycol to precipitate immune complexes.
1. A rapid radioimmunoassay (RIA) for determining serum triiodothyronine (T3) concentration has been developed. The reaction of T3 with its antibody was performed at 37 degrees C for 3 hours; precipitation of antibody bound T3 by 15% polyethylene glycol (PEG) was done at ice-bath temperatures. 2. The effects of pH on the interaction of T3 with its antibody and on the precipitation of antibody gamman globulin by PEG are discussed. 3. PEG precipitates and supernatants were characterized by immunoelectrophoresis and polyacrylamide gel electrophoresis. 4. The RIA has a between run precision of 9.3% at a mean T3 concentration of 179 ng/dl. The recovery of 50 or 100 ng/dl T3 was 95-102% and the normal range estimate was 66-215 ng/dl (N equal to 49).


Life support system with autonomous control employing plant photosynthesis.
This research was aimed at obtaining a closed control system. This was achieved by placing all the technological processes providing for human vital activities within the hermetically sealed space, and by transferring the entire control and guidance of these processes to people inhabiting the system. In contrast to existing biological life support systems, man has been included not only as a participant of metabolism, but as an operator who is the central figure in collecting information, making decisions and controlling all technological processes. To tackle this problem, the "BIOS-3" experimental complex was created for performing long-term experiments using different structures of biological life-support system. The experiment lasted six months and consisted of three stages. During the first stage the system was comprised of two equivalent phytotrons with the culture of wheat and an assortment of vegetable plants, and the living compartment. At the second stage, one of the phytotrons was removed while a compartment of chlorella cultivators was introduced. The third stage differed from the second, the former using wheat phytotron and the latter employing phytotron with an assortment of vegetable cultures. Three men inhabited the system simultaneously. The experiment demonstrated that a biological life support system controlled autonomously from the inside is feasible within a small confined space. However, immunological and microbiological research shows, that the medium created by the system is not fully adequate for man. In conclusion, some prospects have been outlined for further studies of biological life support systems.


Generation of a human induced pluripotent stem cell line YCMi004-A from a patient with dilated cardiomyopathy carrying a protein-truncating mutation of the Titin gene and its differentiation towards cardiomyocytes.
Dilated cardiomyopathy (DCM) is a heart muscle disease that causes heart failure and is the leading cause for heart transplantation. It is a heart muscle disease resulted from a variety of genetics, toxic, metabolic, and infectious causes. One of the most prevalent genetic causes of DCM is a protein-truncating variant in the Titin gene (TTNtv). We have generated a human-induced pluripotent stem cell (hiPSC) line from patients who underwent heart transplantation due to DCM carrying a TTNtv mutation (c.70051C > T, p.Arg23351Ter) at the age of 20. The generated hiPSCs showed normal karyotype (46, XY) and expression of pluripotency markers, and were differentiated towards cardiomyocytes successfully.


Acetyl group assisted rapid intramolecular recognition of hydrogen peroxide: A novel promising approach for efficient hydrogen peroxide probe.
As a vital biomolecule, hydrogen peroxide (H2O2) is involved in many physiological and pathological processes. Therefore, it is important to detect H2O2 in vivo conveniently and efficiently. In this paper, we report a new method of nucleophilic addition of H2O2 to the acetyl group to promote the rapid intramolecular reaction, which can be used to develop an efficient H2O2 probe. Based on this unique auxiliary recognition part, a fluorescent probe for H2O2 detection was designed and synthesized. This probe has the advantages of high sensitivity (limits of detection 7.0 × 10-8 M or even lower.), fast response (within 3 min) and large Stokes shift (225 nm), which not only can monitor exogenous and endogenous H2O2 in cells but also successfully achieves the change of endogenous H2O2 level caused by drug sexual organ injury in zebrafish.


Splicing up pluripotency.
In this issue of Cell, Gabut and colleagues (2011) identify a new splice variant of FOXP1 that directly regulates the expression of pluripotency genes. It endows human embryonic stem cells with their pluripotent nature and is required for the reprogramming of somatic cells to induced pluripotent stem cells.


Pityriasis lichenoides et varioliformis acuta in pregnancy: a case report.
If pityriasis lichenoides et varioliformis acuta (PLAVA) exists in the vagina or cervical os of the uterus, it may cause premature labor and premature rupture of the membranes.


Effects of weight-shift training on walking ability, ambulation, and weight distribution in individuals with chronic stroke: a pilot study.
People with gait difficulties after a stroke usually have an asymmetrical gait and slower gait speed than age-matched controls. These difficulties restrict people with stroke in their daily life activities. This pilot study sought to evaluate the effects of weight-shift training on gait, weight distribution in standing, and ambulation in people with gait difficulties after a stroke. Ten subjects with chronic stroke (3-11 years since insult) and remaining gait difficulties participated in a 3-week weight-shift training program. Spatial and temporal gait parameters were assessed pre-, post-, and 3-month post-training with a motion analysis system. Weight distribution was assessed with force plates and ambulation with the Swedish version of the Clinical Outcome Variables Scale (S-COVS). Wilcoxon signed-rank tests were used to explore differences between test occasions. Significant changes were seen between pre-and post-tests in decreased stance time on the non-paretic leg (P = 0.005) and increased score on the S-COVS (P = 0.043). At the 3-month follow-up test, the subjects had also increased their gait speed significantly (P = 0.037). Standing weight distribution did not change between pre- and post-tests (P = 0.575), but between the pre-and follow-up tests it shifted from the paretic leg to the non-paretic (P = 0.007). Weight-shift training seems to improve gait and ambulation in subjects with chronic stroke, but not with standing weight distribution. However, this pilot study has several limitations and a larger sample size with a control group is necessary.


Increased susceptibility of CD4+ T cells from elderly individuals to HIV-1 infection and apoptosis is associated with reduced CD4 and enhanced CXCR4 and FAS surface expression levels.
Elderly HIV-1 infected individuals progress to AIDS more frequently and rapidly than people becoming infected at a young age. To identify possible reasons for these differences in clinical progression, we performed comprehensive phenotypic analyses of CD4+ T cells from uninfected young and elderly individuals, and examined their susceptibility to HIV-1 infection and programmed death. Peripheral blood mononuclear cells (PBMCs) from older people contain an increased percentage of central memory and Th17 CD4+ T cells that are main target cells of HIV-1 and strongly reduced proportions of naïve T cells that are poorly susceptible to HIV-1. Unstimulated T cells from elderly individuals expressed higher levels of activation markers, death receptors, and the viral CXCR4 co-receptor than those from young individuals but responded poorly to stimulation. CD4+ T cells from older individuals were highly susceptible to CXCR4- and CCR5-tropic HIV-1 infection but produced significantly lower quantities of infectious virus than cells from young individuals because they were highly prone to apoptosis and thus presumably had a very short life span. The increased susceptibility of T cells from the elderly to HIV-1 infection correlated directly with CXCR4 and inversely with CD4 expression. The levels of apoptosis correlated with the cell surface expression of FAS but not with the expression of programmed death receptor 1 (PD1) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Increased levels of activated and highly susceptible HIV-1 target cells, reduced CD4 and enhanced CXCR4 cell surface expression, together with the high susceptibility to FAS-induced programmed cell death may contribute to the rapid CD4+ T cell depletion and accelerated clinical course of infection in elderly HIV-1-infected individuals.


Neurocritical Care in the General Intensive Care Unit.
Neurologic conditions are often encountered in the general intensive care unit. This article will discuss some of the more common neurologic issues encountered and provide guidance in the assessment and management of these conditions.


Direct spectrophotometric determination of the two site binding of aluminum to transferrin.
Difference UV spectrophotometry is used to determine the conditional binding constants for aluminum to human transferrin in the presence of HCO3- of initial concentration 18 mM according to a two site model. The values obtained at 37 degrees C and pH 7.4 are: K1 = 3.0 (+/- 0.8) X 10(15) M-2, K2 = 2.9 (+/- 0.7) X 10(15) M-2 for the reactions: Tr + Al3+ + HCO3- = Tr-Al-HCO3 and Tr-Al-HCO3 + Al3+ + HCO3- = Tr-Al2-(HCO3)2 respectively. Possible consequences arising for the transport of aluminum in human serum are discussed.


Effect of sampling position in fresh, dry-aged and wet-aged beef from M. Longissimus dorsi of Simmental cattle analyzed by 1H NMR spectroscopy.
The aging of beef affects the metabolome and, thus, its quality, such as taste or tenderness. In addition to the aging method, intrinsic factors, such as breed, feed and muscle type, also have an effect on beef's metabolome. It is not known yet whether the position of the sampling in large muscles also has an influence on beef's metabolome and its aging outcome. The effect of the sampling position in M. longissimus dorsi as a large muscle was investigated in dry-aged and wet-aged beef over an aging period of 28 days. In this study, we analyzed 360 samples out of the entire length of M. longissimus dorsi of 18 'Simmental' young bulls by 1H NMR spectroscopy. The position in the muscle affected the polar fraction of metabolome of non-aged and aged beef significantly. However, sampling position did not overlay significant differences in the metabolome of dry-aged and wet-aged beef. The aging time of beef also had a significant effect on the metabolome. Marker metabolites, such as leucine, isoleucine, inosine 5'-monophosphate and hypoxanthine, were found to be indicative of the aging time applied. In addition, marker metabolites (lactic acid, anserine, O-acetyl-L-carnitine) were identified for the aging type applied.


Which is the best way for patients with ureteral obstruction? Percutaneous nephrostomy versus double J stenting.
Percutaneous nephrostomy (PCN) and Double J stenting (DJS) are the 2 main treatment options of ureteral obstruction. We evaluate which of these 2 methods is superior concerning the course of procedure, postoperative complication and quality of life. A detailed review of electronic databases including PubMed, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure up to February 21st, 2021 was searched. Continuous data were evaluated using mean difference (MD) with 95% confidence interval (CI), while nominal data were analyzed by risk ratio (RR) with 95% CI. Meanwhile, we performed the subgroup analysis based on study design, disease type, sample size, sepsis, DJ diameter, nephrostomy diameter, anesthesia type and guidance under X-ray or ultrasound. There were 18 previous studies included in current study. As a result, we found that there were significant differences in fluoroscopy time (MD = 0.31; 95% CI, 0.14-0.48, P < .001) and hospital stay (MD = 1.23; 95% CI, 0.60-1.85, P < .001). However, no statistic difference was detected in operative time (MD = 5.40; 95% CI, -1.78 to 12.58, P = .140) between the paired groups. Although DJS showed a higher rate of postoperative complications (25.19% vs 17.61%), there was no significant difference in the incidence of complications following DJS and PCN (RR = 0.92; 95% CI, 0.60-1.43; P = .720). Based on the EuroQol analysis, the 2 main treatment options had different impacts on quality of life. The pooled results showed that PCN patients reported more difficulties in self-care compared to DJS patients (RR = 3.07; 95% CI, 1.32-7.14; P = .009). DJS is a safe and better method of temporary urinary diversion than PCN for management of ureteral obstruction with shorter fluoroscopy time and hospital stay. As for quality of life, patients receiving PCN had a distinct difficulty in self-care compared to those receiving DJS. However, these 2 treatment options often depends on the individual situation.


An isolable germylyne radical with a one-coordinate germanium atom.
Carbynes (R-[Formula: see text]), species that bear a monovalent carbon atom with three non-bonding valence electrons, are important intermediates and potentially useful in organic synthetic chemistry. However, free species of the type R-[Formula: see text] of any group 14 element (E) have eluded isolation in the condensed phase due to their high reactivity. Here we report the isolation, characterization and reactivity of a crystalline germylyne radical by using a sterically hindered hydrindacene ligand. The germylyne radical bears an essentially one-coordinate germanium atom as shown by single-crystal X-ray diffraction analysis. Electron paramagnetic resonance spectroscopic studies and theoretical calculations show that the germylyne radical features a doublet ground state, and the three non-bonding valence electrons at the germanium atom contribute to the lone pair of electrons as the highest occupied molecular orbital-3 and one unpaired electron as the singly occupied molecular orbital.


Design and synthesis of bio-isosteres of thymidine triphosphate.
This paper describes the design and synthesis of potential isosteres of triphosphates which should show enhanced metabolic stability and lipophilicity compared to triphosphates. The triphosphate isosteres were then linked to nucleosides and evaluated for their inhibitory activity against HIV infection.


A comparison of combined modalities and single modality in the management of advanced head and neck tumors.
Advanced head and neck cancer patients can be managed by single modality or combined modalities. Between 1976 and 1979, three treatment groups were retrospectively identified. One group received induction chemotherapy, surgery, and postoperative radiation therapy. The second group received chemotherapy followed by radiotherapy. The third group was treated during the same time period with radiation alone. These groups were matched with respect to age, site of primary tumor, nodal status, absence of metastatic disease, and no prior cancer treatment. The combined modality groups were initially treated with two doses of cis-platinum and a bleomycin infusion. Evaluation of tumor response was done 2 weeks following chemotherapy; 24 patients had surgery and postoperative radiation, 23 had radiotherapy without surgery and 24 patients were treated with radiotherapy alone. Median survival was 22 and 13 months respectively for the 2 combined modality groups and 4.7 months for the radiotherapy group. Disease-free survival was a projected value of 40 and 35 months for the combined modality groups and an actual 3 months for the radiotherapy group. Combined modality treatment with chemotherapy and surgery and/or radiotherapy offers a higher response rate and prolonged survival than radiotherapy alone.


Artificial light at night, MRI-based measures of brain iron deposition and incidence of multiple mental disorders.
Epidemiologic evidence on whether iron accumulation in brain modified the association between artificial light at night (ALAN) and incident mental disorders is lacking. The authors aims to investigate modification of brain iron deposition on the associations of ALAN with multiple mental disorders in the middle-aged and older adults. This prospective study used data from the UK Biobank. ALAN was drawn from satellite datasets. Susceptibility-weighted magnetic resonance imaging was used to ascertain iron content of each brain region. T2* signal loss was used as indices of iron deposition. The main outcomes are impacts of ALAN exposure on onset of wide spectrum of physician-diagnosed mental disorders, which was estimated by time-varying Cox proportional hazard model. The authors further conducted stratified analyses by levels of iron brain deposition to examine the potential modifying effects. Among 298,283 participants followed for a median of 10.91 years, higher ALAN exposure was associated with increased risk of mental disorders. An IQR (11.37 nW/cm2/sr) increase in annual levels of ALAN was associated with an HR of 1.050 (95 % CI: 1.034,1.066) for any mental disorder, 1.076 (95 % CI: 1.053,1.099) for substance use disorder, and 1.036 (95 % CI: 1.004,1.069) for depression disorder in fully adjusted models. The exposure-response curves showed steeper trends at lower ALAN levels and a plateau at higher exposures. The associations were stronger in participants with high iron deposition in left hippocampus, left accumbens and left pallidum. ALAN was associated with multiple mental disorders in the middle-aged and older adults, and the findings indicated stricter standards of ALAN is needed and targeted preventive measures are warranted, especially with high brain iron deposition.


Safety of positive-pressure valve connectors in arterial catheters inserted into critically ill patients.
Needleless valve connectors were introduced to avoid needlestick injuries in healthcare workers but some concerns exist about their microbiological safety. A randomised controlled trial was performed to assess hub colonisation affecting positive-pressure valve connectors (PPVCs) compared to conventional caps used for radial arterial catheters inserted into critically ill patients. Patients were randomly assigned either to the PPVC (Smartsite Plus positive bolus valve) or to the conventional cap group. Only catheters inserted for >24h were analysed. Of 100 consecutive arterial lines, 80 were inserted for >24h (mean insertion duration 5.8 days), 41 in the PPVC group and 39 in the conventional cap group. Catheter hubs were colonised in eight cases in the control group (20.5%) and in one case in the PPVC group (2.4%). Hub colonisation was caused by coagulase-negative staphylococci in all cases. No attributable bacteraemia was observed. In multivariate analysis, PPVC (odds ratio: 0.09; 95% confidence interval: 0.1-0.79; P=0.03) and use of the line for continuous haemodynamic monitoring (0.16; 0.03-0.89; P=0.037) were independently associated with a lower incidence of hub colonisation.


Allele frequencies for 15 STR loci in Van-Ağri districts of the Eastern Anatolia region of Turkey.
Allele frequencies of 13 tetrameric short tandem repeat (STR) loci (D3S1358, TH01, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, CSF1PO, vWA, D8S1179, TPOX, FGA) and 2 pentameric short tandem repeat loci (Penta E and Penta D) included in the PowerPlex 16 kit were obtained from a sample of 116 unrelated individuals in Van-Ağri districts of the Eastern Anatolia region of Turkey. The expected performance of these loci for personal identification and paternity testing in this population was estimated.


Repeat infusion of autologous bone marrow cells in progressive multiple sclerosis - A phase I extension study (SIAMMS II).
During the safety and feasibility 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)', intravenous infusion of autologous marrow was well tolerated. The efficacy of the approach is being explored in a placebo-controlled randomised controlled trial (ACTiMuS, NCT01815632) but it is not known whether repeated infusions will be required to optimise benefit. The objective of the current study was to explore the safety and feasibility of repeat treatment with intravenous autologous bone marrow for patients with progressive multiple sclerosis (MS). 'SIAMMS II' was a prospective, single centre phase I extension study in which participants in the SIAMMS study were offered repeat bone marrow harvest and infusion of autologous, unfractionated bone marrow as a day-case procedure. The primary outcome measure was number of adverse events and secondary outcome measures included change in clinical rating scales of disability, global evoked potential and cranial magnetic resonance imaging (MRI). In total, 4 of the 6 participants in the SIAMMS study had repeat bone marrow harvest and infusion of filtered autologous marrow as a day case procedure which was well tolerated. There were no serious adverse effects. Additional outcome measures including clinical scales, global evoked potentials and cranial MRI were stable. SIAMMS II demonstrates the safety and feasibility of repeated, non-myeloablative autologous bone marrow-derived cell therapy in progressive MS.


A low-cost approach for soil moisture prediction using multi-sensor data and machine learning algorithm.
A high-resolution soil moisture prediction method has recently gained its importance in various fields such as forestry, agricultural and land management. However, accurate, robust and non- cost prohibitive spatially monitoring of soil moisture is challenging. In this research, a new approach involving the use of advance machine learning (ML) models, and multi-sensor data fusion including Sentinel-1(S1) C-band dual polarimetric synthetic aperture radar (SAR), Sentinel-2 (S2) multispectral data, and ALOS Global Digital Surface Model (ALOS DSM) to predict precisely soil moisture at 10 m spatial resolution across research areas in Australia. The total of 52 predictor variables generated from S1, S2 and ALOS DSM data fusion, including vegetation indices, soil indices, water index, SAR transformation indices, ALOS DSM derived indices like digital model elevation (DEM), slope, and topographic wetness index (TWI). The field soil data from Western Australia was employed. The performance capability of extreme gradient boosting regression (XGBR) together with the genetic algorithm (GA) optimizer for features selection and optimization for soil moisture prediction in bare lands was examined and compared with various scenarios and ML models. The proposed model (the XGBR-GA model) with 21 optimal features obtained from GA was yielded the highest performance (R2 = 0. 891; RMSE = 0.875%) compared to random forest regression (RFR), support vector machine (SVM), and CatBoost gradient boosting regression (CBR). Conclusively, the new approach using the XGBR-GA with features from combination of reliable free-of-charge remotely sensed data from Sentinel and ALOS imagery can effectively estimate the spatial variability of soil moisture. The described framework can further support precision agriculture and drought resilience programs via water use efficiency and smart irrigation management for crop production.


Deletion of Smad3 prevents renal fibrosis and inflammation in type 2 diabetic nephropathy.
Transforming growth factor (TGF)-β/Smad3 signaling is highly activated in kidneys of patients with type 2 diabetic nephropathy (T2DN), however, the precise role of Smad3 in the pathogenesis of diabetic nephropathy remains unclear. Smad3 knockout (KO)-db/db mice were generated by intercrossing of male and female double-heterozygous Smad3+/- db/m mice. Renal functions including urinary albumin excretion and serum creatinine were determined. Renal histological injury including renal fibrosis and inflammation were examined by periodic acid Schiff (PAS), periodic acid-silver methenamine (PASM), and immunohistochemistry (IHC) staining. Smad3 knockout (KO)-db/db mice were protected from the development of diabetic kidney injury, characterized by the normal levels of urinary albumin excretion and serum creatinine without any evidence for renal fibrosis and inflammation. In contrast, Smad3 wild-type (WT) db/db and Smad3+/- db/db mice developed progressively decline in renal function over the 12 to 32-week time course, including increased microalbuminuria and elevated levels of serum creatinine. Pathologically, Smad3 WT db/db and Smad3+/- db/db mice exhibited a marked deposition of collagen-I (colI), collagen-IV(col-IV), and an increased infiltration of F4/80+ macrophages in kidney. Mechanistically, Smad3 deficiency decreased the lncRNA Erbb4-IR transcription, while increased miR-29b transcription and therefore protected the kidney from progressive renal injury in db/db mice. Results from this study imply that Smad3 may represent as a novel and effective therapeutic target for T2DN.


Imaging GTP-bound tubulin: from cellular to in vitro assembled microtubules.
Microtubules display a very dynamic behavior, and the presence of the guanosine-triphosphate (GTP) cap at the plus ends of microtubules is essential to regulate microtubule dynamics. Dimitrov et al. (2008) showed that GTP-tubulin is present not only at the plus ends but also in discrete locations along the microtubule lattice. These GTP islands were proposed to contribute to rescue events. Studying the localization of GTP-tubulin in microtubules is essential to better comprehend some core aspects in the regulation of microtubule dynamics. In this chapter, we recapitulate essential tools to study the GTP-tubulin using the recombinant antibody MB11 from permeabilized cells to in vitro assays.


The effects of the aminopeptidase inhibitors amastatin and bestatin on angiotensin-evoked neuronal activity in rat brain.
During a recent comparison of iontophoretically applied angiotensin II (AII) and angiotensin III (AIII) in the paraventricular nucleus of the rat, we observed that the response latency for AIII was much shorter than that for AII. This suggested that AII may have to be converted to AIII before it becomes active. To test this hypothesis we performed 3 experiments. (1) We examined the effects of bestatin, an aminopeptidase B inhibitor, on the activity of applied AII and AIII. (2) Next, we monitored the effects of amastatin, a specific aminopeptidase A inhibitor, on the action of co-applied AII or AIII. (3) And, finally, we examined the response to the aminopeptidase-resistant analog Sar1-AII, both applied alone and in combination with AII or AIII. Bestatin, while having no activity of its own, dramatically enhanced the actions of both AII and AIII. Amastatin, on the other hand, had little effect on AII's action and diminished or totally blocked AII-dependent activity. Like bestatin, amastatin had no effect alone. Sar1-AII reduced spontaneous activity of angiotensin-sensitive neurons and inhibited the actions of AII and AIII in a reversible manner. The same cells were also blocked by the recognized angiotensin antagonist Sar1, Ile8-AII. In total these results strongly support the notion that AII must be converted to AIII in the brain before it is activated.


Preparation of an immunoadsorbent coupled with a recombinant antigen to remove anti-acetylcholine receptor antibodies in abnormal serum.
An immunoadsorbent that removes anti-acetylcholine receptor antibodies (AChRAb) in abnormal serum of myasthenia gravis (MG) patient was efficiently prepared by an expression product, the functional fragment of AChR(alpha205) fused with maltose binding protein (MBP). The ligand can then covalently bind to amylose resin through MBP fusion protein. It was shown from the result of this study with anti-AChR mice sera that the removal rate of AChRAb on this immunoadsorbent reached 87+/-10% (mean value of 10 mice) and the maximally binding capacity of AChRAb was approximately 260 microg/g immunoadsorbent (wet weight). Moreover, the immunoadsorption test of sera in two MG patients indicated that about 90% and 96% of abnormal AChRAb could be eliminated, while other serum components such as albumin, IgG, IgM and IgA only dropped 18%, 35%, 22%, 15% and 24%, 27%, 15%, 12%, respectively, for two MG patient sera. It is anticipated from this study that the immunoadsorbent reported here could, with further development, find its clinical application for removal of AChRAb from patient serum.


A numerical study of the nonsteady transport of gases in the pulmonary capillaries.
A mathematical model is formulated for simulating the unsteady transport of gases in the blood flowing through the pulmonary capillaries. The formulation takes into account the transport mechanisms of molecular diffusion, convection and facilitated diffusion of the species due to haemoglobin. A time dependent situation is created by allowing to vary suddenly the partial pressures of the gases either in the venous blood or in the alveolar air. A numerical technique is described to solve the resulting time-dependent system of nonlinear coupled partial differential equations with the physiologically relevant boundary, entrance and initial conditions. The time required by the gases to achieve equilibrium is computed. It is shown that the dissolved oxygen takes longest in reaching equilibration whereas the carbon dioxide is the fastest. The various physiologically relevant unsteady situations have been examined.


CCL5-28, CCL5-403, and CCR5 genetic polymorphisms and their synergic effect with alcohol and tobacco consumptions increase susceptibility to hepatocellular carcinoma.
The aim of this study was to estimate the relationship between gene polymorphisms of CCL5-28, CCL5-403, and CCR5 to the susceptibility of hepatocellular carcinoma (HCC). A total of 449 subjects, including 347 healthy controls and 102 patients with HCC, were recruited in this study and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to investigate the impact of these two polymorphic variants on HCC. A significant association between HCC susceptibility and genetic polymorphism, CG heterozygotes of CCL5-28 (AOR=2.35; 95% CI=1.27-4.33, p=0.006), AA homozygotes of CCL5-403 (AOR=5.18; 95% CI=2.25-11.91, p=0.0001), and AA homozygotes of CCR5 (AOR=2.47; 95% CI=1.24-4.90, p=0.009), was found compared with wild genotype after adjusting for other confounders. It was detected that synergistic effect between gene-to-gene polymorphisms increased the risk to have HCC among individuals with CG or GG of CCL5-28, and GA or AA of CCL-403, and GA or AA of CCR5 (AOR=3.42; 95% CI=1.39-8.38, p=0.007) compared to individuals with wild genotypes of CCL5-28, CCL-403, and CCR5. Also, alcohol or tobacco consumption increased the risk to have HCC among subjects with CG heterozygotes of CCL5-28 (alcohol: p=0.001; tobacco: p=0.006), AA homozygotes (alcohol: p=0.0004; tobacco: p≤0.0001) or GA heterozygotes (tobacco: p=0.03) of CCL5-403, and AA homozygotes of CCR5 (alcohol: p=0.02; tobacco: p=0.02), respectively. Gene polymorphisms of CCL5-28, CCL5-403, and CCR5 play an important factor for the susceptibility of HCC, respectively. The synergic effects of these two gene polymorphisms to tobacco or alcohol consumption significantly increase the risk to develop HCC.


Impact of the National Cervical Screening Programme in New Zealand by age: analysis of cervical cancer trends 1985-2013 in all women and in Māori women.
New Zealand is an example of a country with a well-established cytology-based screening program. New Zealand's National Cervical Screening Programme (NCSP) commenced in 1990, and recommends three-yearly cytology-based screening for women aged 20-69 years. In 2018, the NCSP will transition to five-yearly HPV-based screening for women aged 25-69 years. The aim of this study was to assess the impact of the program to date in different groups, to provide a benchmark for the new program. Analysis of cervical cancer trends in New Zealand by age and ethnicity over the period 1985-2013, and by morphology over the period 1997-2013, using data from the New Zealand Cancer Registry was conducted. The overall incidence of cervical cancer was 56% (95% CI 51-60%) lower in 2009-2013 than in 1985-1989, and significant reductions were observed in women aged 25-49, 50-69, and 70 + years. Relative reductions in cervical cancer were very similar for Māori and non-Māori women aged 25-49 (50% in Māori; 52% in non-Māori) and 50-69 years (65% in Māori; 69% in non-Māori). In contrast, incidence appeared to increase after around 1996 in women aged 20-24. The increasing trend was significant for women aged 20-24 overall and for non-Māori women (p < 0.01 in both cases). There have been substantial reductions in cervical cancer among women aged 25 + years in New Zealand since the inception of the NCSP, and these reductions are similar in Māori and non-Māori women. Cervical cancer incidence among women 20-24 years has not declined since the NCSP began, and appears to be increasing.


Biochemical markers in suicidal patients. Investigations with cerebrospinal fluid amine metabolites and neuroendocrine tests.
141 female psychiatric patients, suffering from major depression, schizophrenia, alcohol dependence or adjustment disorder, were investigated for their 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and cortisol level in the cerebrospinal fluid (CSF). Dexamethasone suppression tests were also performed in 111 cases, and TRH/TSH tests in 40 subjects. Fifty-two patients were hospitalized following a recent suicide attempt, 18 of which were made using a violent method. The other 34 attempters took tranquilizer or sedative overdoses. CSF 5-HIAA was significantly lower in violent attempters in all 4 diagnostic categories. CSF HVA was higher in those taking drug overdoses, but only in depression (and less markedly in schizophrenia). CSF cortisol did not differ among either diagnostic or suicidal subgroups. Dexamethasone suppression was more frequently abnormal in suicidal patients than in nonattempters, and this difference was more important where the overall nonsuppression rate was lower. Maximal TSH response to TRH showed an inverse correlation with CSF 5-HIAA, and it was lowest in the nonattempter group. The difference between violent suicide attempters and nonattempters in their TSH response was significant. Since these biochemical changes were more or less independent of clinical diagnoses, it seems relevant to explore further the biological background of human aggression and suicide as a separate research direction.


Dataset of concentrations of free terpenes at different phenological stages in Vitis vinifera L. Shiraz, Cabernet Sauvignon, Riesling, Chardonnay and Pinot Gris.
Five Vitis vinifera L. cultivars Shiraz, Cabernet Sauvignon, Riesling, Chardonnay and Pinot Gris at different E-L development stages were harvested in two experimental vintages. Temperature and rainfall data of the growing period were obtained from the Australian Government Bureau of Meteorology. Free terpene concentrations of all harvested grape samples were analysed using HS-SPME-GC-MS. One-way ANNOVA was performed to evaluate the significance of changes in terpene concentrations at different maturation stages. More analysis of the data is provided in "Free terpene evolution during the berry maturation of five Vitis vinifera L. cultivars" [1].


Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins.
Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive mutagenesis of expression plasmids and RNAi screening, we reveal that circularization of the Drosophila laccase2 gene is regulated by both intronic repeats and trans-acting splicing factors. Analogous to what has been observed in humans and mice, base-pairing between highly complementary transposable elements facilitates backsplicing. Long flanking repeats (∼ 400 nucleotides [nt]) promote circularization cotranscriptionally, whereas pre-mRNAs containing minimal repeats (<40 nt) generate circular RNAs predominately after 3' end processing. Unlike the previously characterized Muscleblind (Mbl) circular RNA, which requires the Mbl protein for its biogenesis, we found that Laccase2 circular RNA levels are not controlled by Mbl or the Laccase2 gene product but rather by multiple hnRNP (heterogeneous nuclear ribonucleoprotein) and SR (serine-arginine) proteins acting in a combinatorial manner. hnRNP and SR proteins also regulate the expression of other Drosophila circular RNAs, including Plexin A (PlexA), suggesting a common strategy for regulating backsplicing. Furthermore, the laccase2 flanking introns support efficient circularization of diverse exons in Drosophila and human cells, providing a new tool for exploring the functional consequences of circular RNA expression across eukaryotes.


Imaging in plague.
An 8-year-old boy presented with elevated temperature, malaise, hepatosplenomegaly, mesenteric adenitis, and septic shock. Cultures of biopsied abdominal lymph nodes as well as the blood grew Yersinia pestes. The boy's condition improved after two weeks of chloramphenicol and cefotaxime (Claforan). Two days after stopping intravenous antibiotic therapy, the patient again became febrile and complained of abdominal pain. Abdominal imaging with 111In-labeled leukocytes did not show any abnormalities, however, 67Ga-citrate scintigraphy demonstrated an abnormal focus of increased radiopharmaceutical uptake within a confluence of necrosed lymph nodes within the right upper quadrant of the abdomen. In addition, abnormal 67Ga-uptake was seen within the left hip region. Correlative imaging with computed tomography is also presented.


Potentiation of FMD vaccines with polycationic-nucleic acid complexes.
The effect of various polycations on the immune response potentiated with poly I:C was studied. It was found that low molecular weight polycations had no potentiating effect. Polylysine was ineffective whereas protamine was superior to lysozyme, poly-arginine, poly-histidine, DEAE-Dextran and histone. A foot-and-mouth disease trivalent vaccine composed of strains A24 Cruzeiro, O1 Caseros and C2 Resende elicited no immune response in swine when adjuvanted with aluminium hydroxide but was effective when emulsified in oil. In general, the immune response was potentiated ten-fold when the emulsion contained poly I:C. The antibody production was in most cases further potentiated by a factor of ten when the nucleic acid double-strand was complexed with 1 : 10 (w/w) DEAE-Dextran. Protamine was as effective, or perhaps even more, than DEAE-Dextran to this effect. Guinea pigs vaccinated with a water-in-oil emulsion type monovalent C3 vaccine showed an increase in antibody production when the vaccine contained poly I:C or poly I:C complexed with 1 : 10 (w/w) protamine.


Management of children with congenital nephrotic syndrome: challenging treatment paradigms.
Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.


Effect of food-grade surfactant on bioremediation of explosives-contaminated soil.
The use of native soil bacteria to biodegrade explosives-contaminated soil under co-metabolic conditions has been demonstrated. The addition of food-grade surfactants could improve the process by enhancing the rates of explosives desorption from soil, thereby increasing the bioavailability of explosives for microbial degradation. The objective of this study was to decrease residence time in the slurry reactor, thereby increasing output and reducing clean-up costs. In this study, Tween 80 (monooleate), served not only as a surfactant but also as the carbon substrate for the soil microorganisms. Four 2l soil slurry reactors were operated in batch mode with soil containing 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The results indicated that TNT and RDX were removed in all reactors except the control (no added carbon source). The reactor enriched with surfactant and molasses performed better than reactors with either molasses or surfactant alone. The TNT and its metabolite, 4-amino-2,6-dinitrotoluene were removed faster in the reactor with surfactant plus molasses (35 days) than in the reactor with molasses alone as carbon source (45 days). A radiolabeling study of the mass balance of TNT in the slurry reactors showed substantial mineralization of TNT to CO2.


Contribution of the gradient refractive index and shape to the crystalline lens spherical aberration and astigmatism.
The optical properties of the crystalline lens are determined by its shape and refractive index distribution. However, to date, those properties have not been measured together in the same lens, and therefore their relative contributions to optical aberrations are not fully understood. The shape, the optical path difference, and the focal length of ten porcine lenses (age around 6 months) were measured in vitro using Optical Coherence Tomography and laser ray tracing. The 3D Gradient Refractive Index distribution (GRIN) was reconstructed by means of an optimization method based on genetic algorithms. The optimization method searched for the parameters of a 4-variable GRIN model that best fits the distorted posterior surface of the lens in 18 different meridians. Spherical aberration and astigmatism of the lenses were estimated using computational ray tracing, with the reconstructed GRIN lens and an equivalent homogeneous refractive index. For all lenses the posterior radius of curvature was systematically steeper than the anterior one, and the conic constant of both the anterior and posterior positive surfaces was positive. In average, the measured focal length increased with increasing pupil diameter, consistent with a crystalline lens negative spherical aberration. The refractive index of nucleus and surface was reconstructed to an average value of 1.427 and 1.364, respectively, for 633 nm. The results of the GRIN reconstruction showed a wide distribution of the index in all lens samples. The GRIN shifted spherical aberration towards negative values when compared to a homogeneous index. A negative spherical aberration with GRIN was found in 8 of the 10 lenses. The presence of GRIN also produced a decrease in the total amount of lens astigmatism in most lenses, while the axis of astigmatism was only little influenced by the presence of GRIN. To our knowledge, this study is the first systematic experimental study of the relative contribution of geometry and GRIN to the aberrations in a mammal lens.


Linear dose response and quantitative attenuation by potassium of the inotropic action of acetylstrophanthidin.
To evaluate the nature of the inotropic dose response of digitalis and to determine the effects of potassium on this response, isometrically contracting isolated supported right ventricular cat papillary muscles were studied relative to their peak tension and peak dT/dt increases to physiologic cumulative doses of acetylstrophanthidin (ACS) in different extracellular potassium concentrations in the muscle bath. The inotropic dose response to ACS was observed to be linear in cumulative glycoside concentrations ranging from 0.40 to 4.23 X 10(-7) M ACS in 3.5 mM K+ medium and from 1.22 to 7.47 X 10(-7) M ACS in 7.0 mM K+ medium. The influence of potassium alterations in the muscle bath from the low to the high K+ concentrations prior to ACS resulted in marked attenuation of the positive inotropic property of ACS. From these data, it is concluded that the dose inotropic response of digitalis is linear, with small doses producing proportionally the same effects as larger doses, and that extracellular potassium markedly influences this linear dose response such that higher K+ concentrations considerably attenuate the positive inotropic response of digitalis.


Ventricular tachycardia in repaired double chambered right ventricle - identification of the substrate and successful ablation.
A 35 year old female presented with recurrent ventricular tachycardia 5 years after she had undergone surgical repair of double chambered right ventricle. Electroanatomical mapping showed a localised scar in the apex with double potentials and good pace map. Ablation here resulted in non-inducibility of ventricular tachycardia. We hypothesise that the scarring in the apex is the result of sustained pressure overload and becomes arrhythmogenic similar to the apical scar in patients with mid-ventricular hypertrophic cardiomyopathy.


[Secondary malignant lymphedema].
The diagnosis of a secondary malignant lymphoedema which is caused by tumor infiltration or tumor compression is a very important sign for an unknown primary, but also for a tumor relapse. It is a big challenge, because it is often associated with a long story of woe, severe pain and a big reduction in mobility. Only an early diagnosis and introduction of a tumor-specific therapy is able to prevent the progress of this disease. As the secondary lymphedema is a chronic progressive disease, the early beginning of the "Complex physical Oedematherapy" is necessary, which consists of a combination of manual lymph drainage, compression by the use of bandages and special stockings for compression, physical training to improve mobility, dermatological care and drug therapy. Lymphedema is a chronic incurable disease. Therefore the therapeutic goal is to reach a stable disease without symptoms, which means reducing the lymphedema to "Stadium 0, latent stage".


Retraction of: A Routine Electroencephalography Monitoring System for Automated Sports-Related Concussion Detection (DOI: 10.1089/neur.2021.0047).
[This retracts the article DOI: 10.1089/neur.2021.0047.].


Preanalytical venous blood sampling practices demand improvement--a survey of test-request management, test-tube labelling and information search procedures.
Most errors in laboratory medicine are preanalytical in nature. In the present study, we aimed to survey preanalytical steps in venous blood sampling, prior to actual sample collection. These steps included test-request management and test-tube labelling, as well as information search procedures. Venous blood sampling staff (n=314, response rate 94%) in hospital wards and laboratories completed a questionnaire related to clinical chemistry testing. Instructions for test-request management and test-tube labelling were not always followed. For example, only 66% of the ward staff reported always checking the test-request if someone else completed it, compared to 90% of the laboratory staff (p=0.003). As few as 16% of the ward staff reported desirable practices regarding test-tube labelling, compared to 100% of the laboratory staff (p<0.001). Furthermore, 18% of the ward staff reported always using online manuals (the only source of updated information), compared to 63% of the laboratory staff (p<0.001). Our results indicate a substantial risk of preanalytical error in test-request management, test-tube labelling, and information search practices, particularly in the wards. Our findings thus underscore the importance of quality control in venous blood sampling, in order to increase patient safety in modern health care.


Homocysteine oxidation and apoptosis: a potential cause of cleft palate.
Cleft palate is the most common craniofacial anomaly. Affected individuals require extensive medical and psychosocial support. Although cleft palate has a complex and poorly understood etiology, low maternal folate is known to be a risk factor for craniofacial anomalies. Folate deficiency results in elevated homocysteine levels, which may disturb palatogenesis by several mechanisms, including oxidative stress and perturbation of matrix metabolism. We examined the effect of homocysteine-induced oxidative stress on human embryonic palatal mesenchyme (HEPM) cells and demonstrated that biologically relevant levels of homocysteine (20-100 microM) with copper (10 microM) resulted in dose-dependent apoptosis, which was prevented by addition of catalase but not superoxide dismutase. Incubation of murine palates in organ culture with homocysteine (100 micro) and CuSO(4) (10 microM) resulted in a decrease in palate fusion, which was not significant. Gelatin gel zymograms of HEPM cell-conditioned media and extracts of cultured murine palates, however, showed no change in the expression or activation of pro-matrix metalloproteinase-2 with homocysteine (20 microM-1 mM) with or without CuSO(4) (10 microM). We have demonstrated that biologically relevant levels of homocysteine in combination with copper can result in apoptosis as a result of oxidative stress; therefore, homocysteine has the potential to disrupt normal palate development.


Deformation and Failure Properties of High-Ni Lithium-Ion Battery under Axial Loads.
To explore the failure modes of high-Ni batteries under different axial loads, quasi-static compression and dynamic impact tests were carried out. The characteristics of voltage, load, and temperature of a battery cell with different states of charge (SOCs) were investigated in quasi-static tests. The mechanical response and safety performance of lithium-ion batteries subjected to axial shock wave impact load were also investigated by using a split Hopkinson pressure bar (SHPB) system. Different failure modes of the battery were identified. Under quasi-static axial compression, the intensity of thermal runaway becomes more severe with the increase in SOC and loading speed, and the time for lithium-ion batteries to reach complete failure decreases with the increase in SOC. In comparison, under dynamic SHPB experiments, an internal short circuit occurred after impact, but no violent thermal runaway was observed.


Prevalence of current pregnancy among US women with and without chronic physical disabilities.
The number of US women of childbearing age who have chronic physical disabilities (CPD) is increasing. However, little is known about their reproductive experiences. Historically, women with physical disabilities have confronted stigmatized attitudes about becoming pregnant. To explore the national prevalence of current pregnancy among women with and without CPD; examine differences in current pregnancy prevalence between these 2 groups of women. Bivariable and multivariable analyses of cross-sectional, nationally representative National Health Interview Survey data from 2006 to 2011. Forty-seven thousand six hundred twenty-nine civilian, noninstitutionalized women aged 18-49 years. National Health Interview Survey asks women ages 18-49 if they are currently pregnant; it also asks about various movement difficulties. We used responses from 8 movement difficulty and other questions to identify women with CPD. Six thousand forty-three (12.7%) sampled women report CPD. Compared with other women, women with CPD are significantly: older; more likely to be black and less likely to be Asian or Hispanic; more likely to be divorced or separated; more likely to have less than a high school education; less likely to be employed; and have much lower incomes. Across all women, 3.5% report being currently pregnant: 3.8% of women without CPD and 2.0% with CPD. Controlling for sociodemographic factors, the adjusted odds ratio (95% confidence interval) of current pregnancy is 0.83 (95% confidence interval, 0.65-1.05; P=0.12) for women with CPD compared with nondisabled women. Women with CPD do become pregnant, and their numbers will likely grow. Obstetrical practitioners therefore require training about the special needs of these women.


Alteration of voltage-dependent calcium channels in canine brain during global ischemia and reperfusion.
Elevated intracellular calcium (iCa2+) plays an important role in the pathophysiology of ischemic brain damage. The mechanisms by which iCa2+ increases are uncertain. Recent evidence implicates the voltage-dependent calcium channel (VDCC) as a likely site for the alteration in Ca2+ homeostasis during ischemia. The purpose of this study was to determine whether VDCCs are altered by global ischemia and reperfusion in a canine cardiac arrest, resuscitation model. We employed the radioligand, [3H]PN200-110, to quantitate the equilibrium binding characteristics of the VDCCs in the cerebral cortex. Twenty-five adult beagles were separated into four experimental groups: (a) nonischemic controls, (b) those undergoing 10-min ventricular fibrillation and apnea, (c) those undergoing 10-min ventricular fibrillation and apnea followed by spontaneous circulation and controlled respiration for 2 and (d) 24 h. Brain cortex samples were taken prior to killing of the animal, frozen immediately in liquid nitrogen, and crude synaptosomal membranes isolated by differential centrifugation/filtration. After 10 min of ischemia the maximal binding (Bmax) of [3H]PN200-110 increased to greater than 250% of control values (control Bmax 11.16 +/- 0.98; ischemic 28.35 +/- 2.78 fmol/mg protein; p less than 0.05). Bmax returned to near control values after 2 h of reperfusion but remained significantly greater than the control at 24 h. Although the affinity constant (Kd) (control = 0.12 +/- 0.03 nM) appeared to increase with ischemia and normalize with reperfusion, the changes were not statistically significant. We conclude that the binding of [3H]PN200-110 to L-type VDCCs is increased after 10 min of global ischemia/anoxia produced by ventricular fibrillation and apnea in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)


Concurrent antiglomerular basement membrane antibody and immune complex mediated glomerulonephritis.
A teenage male, with Goodpasture's syndrome and serum antiglomerular basement membrane (anti-GBM) antibodies, had a focal proliferative glomerulonephritis with crescents. Immunofluorescence microscopy of his glomeruli using anti-IgG antibodies demonstrated both intense linear GBM staining, and granular subepithelial staining. Electron microscopy revealed numerous subepithelial electron-dense deposits. Identical IgG subclass restriction (dominance of IgG1 and IgG4) of both types of glomerular deposits in this patient supports, but does not prove, a postulate that the linear staining was due to anti-GBM antibodies bound to intact GBM, and that the granular staining was due to anti-GBM antibodies complexed with freed GBM antigens.


Full- versus partial-thickness sutures: experimental models of corneal injury repair.
To evaluate the performance of full-thickness (FT) versus partial-thickness (PT) sutures in a full-thickness corneal wound in an animal model. This is a prospective, experimental, comparative, longitudinal study. A 6-mm linear, full-thickness corneal incision was performed on the right eye of eight domestic pigs. Eyes were randomly assigned for repair with interrupted PT (80-90% depth) sutures or FT 10-0 nylon sutures. Anterior segment OCT, corneal pachymetry and clinical photographs were obtained 1, 4 and 8 weeks postoperatively. Corneal thickness, depth of suture placement, perilesional edema, coaptation of wound edges and complications were noted. Histopathologic examination was performed at 8 weeks. 100% of the eyes with FT sutures developed a linear, less opaque scar. 100% of the eyes with PT developed a dense, opaque stromal scar (p = 0.02). Vascularization of the cornea was present in 75% of PT group and 25% in the FT group (p = 0.50). As the corneas healed, there was a marked trend toward thicker corneas in the PT group versus FT group with a median difference of - 63 µm at week 1 [median 788 µm vs. 725 µm, (p = 0.11)], - 38 µm at week 4, (724 µm vs. 686 µm, (p = 0.63)) and - 47 µm median difference at week 8 with (670 µm vs. 623 µm, (p = 0.06)). Histopathology showed disorganization of the collagen fibers and the formation of a retrocorneal fibrous membrane in the PT group. The FT group presented less corneal edema at week 8 with a more linear and less opaque scar. Histopathology showed a better-organized scar and endothelialization without the formation of a fibrous membrane.


Study of the transcortin binding to human endometrium plasma membrane.
Transcortin complexed with progesterone was shown to bind specifically to the plasma membrane of human decidual endometrium. The binding reaction was characterized by a high affinity (an apparent Kd value was (1.0 +/- 0.2).10(-10) mol/l) and high selectivity: such human serum proteins as albumin, orosomucoid, transferrin, thyroxine-binding globulin and sex hormone-binding globulin did not compete with transcortin for the membrane binding sites. Transcortin binding to the membrane was steroid-dependent: transcortin-cortisol complex bound to the membranes substantially more weakly than transcortin-progesterone, and specific binding of transcortin devoid of steroid was not detected. Using a radioimmunoassay, we have measured the concentration of endogenous transcortin in highly purified membrane preparations solubilized with sodium cholate. It was found that an extensive washing of decidual strips with a physiological buffer prior to the membrane isolation resulted in a decrease of the endogenous transcortin level along with an increase of the specific membrane binding of exogenous 125I-labeled transcortin. Affinity chromatography on immobilized transcortin was used to isolate transcortin-binding components from 125I-labeled, cholate-solubilized plasma membrane of decidual endometrium. Along with lipid components, the structure of which was not investigated, a 125I-labeled transcortin-binding sialoglycoprotein with a minimal Mr of 20.0 +/- 1.5 kDa and a pI of approx. 3.3 was detected. In the presence of transcortin, this sialoglycoprotein could be precipitated with a monospecific antitranscortin antiserum. Using hydroxylapatite as a separating agent, the interaction of transcortin and the membrane sialoglycoprotein in model systems containing the two proteins and various steroid hormones was studied. It was found that the membrane sialoglycoprotein displayed a higher affinity for transcortin-progesterone than for transcortin-cortisol (the Kd values were, respectively, 2.10(-11) and 7.10(-11) mol/l) and it did not bind transcortin complexed with testosterone.


A network flow approach to predict drug targets from microarray data, disease genes and interactome network - case study on prostate cancer.
Systematic approach for drug discovery is an emerging discipline in systems biology research area. It aims at integrating interaction data and experimental data to elucidate diseases and also raises new issues in drug discovery for cancer treatment. However, drug target discovery is still at a trial-and-error experimental stage and it is a challenging task to develop a prediction model that can systematically detect possible drug targets to deal with complex diseases. We integrate gene expression, disease genes and interaction networks to identify the effective drug targets which have a strong influence on disease genes using network flow approach. In the experiments, we adopt the microarray dataset containing 62 prostate cancer samples and 41 normal samples, 108 known prostate cancer genes and 322 approved drug targets treated in human extracted from DrugBank database to be candidate proteins as our test data. Using our method, we prioritize the candidate proteins and validate them to the known prostate cancer drug targets. We successfully identify potential drug targets which are strongly related to the well known drugs for prostate cancer treatment and also discover more potential drug targets which raise the attention to biologists at present. We denote that it is hard to discover drug targets based only on differential expression changes due to the fact that those genes used to be drug targets may not always have significant expression changes. Comparing to previous methods that depend on the network topology attributes, they turn out that the genes having potential as drug targets are weakly correlated to critical points in a network. In comparison with previous methods, our results have highest mean average precision and also rank the position of the truly drug targets higher. It thereby verifies the effectiveness of our method. Our method does not know the real ideal routes in the disease network but it tries to find the feasible flow to give a strong influence to the disease genes through possible paths. We successfully formulate the identification of drug target prediction as a maximum flow problem on biological networks and discover potential drug targets in an accurate manner.


Reliability of stabilised commercial dynamometers for measuring hip abduction strength: a pilot study.
Reliable quantification of hip abductor strength in a clinical setting is challenging. To examine the intrarater and interrater reliability of three commonly used commercial dynamometers in the measurement of hip abduction. Supine gravity minimised measures of unilateral hip abduction strength were recorded in 10 women (mean (SD) age 23.5 (1.9) years) using three different commercially available dynameters. Measurements were repeated over a three day period with a different device used on each day. Intrarater reliability ranged from 0.880 to 0.958 across the three devices, and measures of interrater reliability ranged from 0.899 to 0.948. Commercially available dynamometers can be used to quantify hip abduction strength with good to excellent reliability. A previously undescribed method of quantifying hip abduction strength in a clinical setting using readily available instrumentation is presented.


A role for niches in the development of a multiplicity of dendritic cell subsets.
Although most studies on murine dendritic cell (DC) differentiation concentrate on the nature of the DC precursor population and the lineage relationship between DC and other hematopoietic cell types, very little research addresses the nature of the microenvironments necessary for DC hematopoiesis. Evidence supporting a major contribution of niches in DC differentiation within hematopoietic tissues is reviewed. A model is presented that identifies a potential role for multiple hematopoietic niches in DC differentiation. It is proposed that multiple DC subsets develop from one or a small number of DC progenitor types that lodge in various niches within different tissue sites. Implications of a niche-mediated model for differentiation of DC precursors are discussed in the context of both physiological and pathological situations.


Genetic evidence in tracking the origin of Ulva prolifera blooms in the Yellow Sea, China.
Recurrent green tides have been recorded in the Yellow Sea for 11 consecutive years. The origin of floating green algae in the Yellow Sea, however, remains a subject of debate. Previous studies suggest that the major bloom-forming green alga Ulva prolifera represent a unique ecotype different from other attached populations of U. prolifera in China. In this study, 97 green algal samples collected during the 2012 green-tide event and from other locations along the coastline of China were analyzed. Based on the sequences of nuclear ribosomal RNA gene (rDNA) internal transcribed spacer (ITS) region and 5S rDNA spacer region, the green alga U. prolifera in the samples were identified. The intraspecific genetic diversity within U. prolifera was then examined using sequences of 5S rDNA spacer and a marker of sequence characterized amplified region (SCAR) highly specific for bloom-forming U. prolifera in the Yellow Sea. The screening results for SCAR marker demonstrated that U. prolifera attached to aquaculture rafts in Subei Shoal belong to the same ecotype of the bloom-forming U. prolifera in the Yellow Sea. These findings offer genetic evidence that aquaculture rafts in Subei Shoal are a major source of floating green algae in the Yellow Sea.


Rho kinase is required to prevent retinal axons from entering the contralateral optic nerve.
To grow out to contact target neurons an axon uses its distal tip, the growth cone, as a sensor of molecular cues that help the axon make appropriate guidance decisions at a series of choice points along the journey. In the developing visual system, the axons of the output cells of the retina, the retinal ganglion cells (RGCs), cross the brain midline at the optic chiasm. Shortly after, they grow past the brain entry point of the optic nerve arising from the contralateral eye, and extend dorso-caudally through the diencephalon towards their optic tectum target. Using the developing visual system of the experimentally amenable model Xenopus laevis, we find that RGC axons are normally prevented from entering the contralateral optic nerve. This mechanism requires the activity of a Rho-associated kinase, Rock, known to function downstream of a number of receptors that recognize cues that guide axons. Pharmacological inhibition of Rock in an in vivo brain preparation causes mis-entry of many RGC axons into the contralateral optic nerve, and this defect is partially phenocopied by selective disruption of Rock signaling in RGC axons. These data implicate Rock downstream of a molecular mechanism that is critical for RGC axons to be able to ignore a domain, the optic nerve, which they previously found attractive.


Predicting metabolite-disease associations based on KATZ model.
Increasing numbers of evidences have illuminated that metabolites can respond to pathological changes. However, identifying the diseases-related metabolites is a magnificent challenge in the field of biology and medicine. Traditional medical equipment not only has the limitation of its accuracy but also is expensive and time-consuming. Therefore, it's necessary to take advantage of computational methods for predicting potential associations between metabolites and diseases. In this study, we develop a computational method based on KATZ algorithm to predict metabolite-disease associations (KATZMDA). Firstly, we extract data about metabolite-disease pairs from the latest version of HMDB database for the materials of prediction. Then we take advantage of disease semantic similarity and the improved disease Gaussian Interaction Profile (GIP) kernel similarity to obtain more reliable disease similarity and enhance the predictive performance of our proposed computational method. Simultaneously, KATZ algorithm is applied in the domains of metabolomics for the first time. According to three kinds of cross validations and case studies of three common diseases, KATZMDA is worth serving as an impactful measuring tool for predicting the potential associations between metabolites and diseases.


Prevalence of treatment, risk factors, and management of atrial septal defects in a pediatric Medicaid cohort.
Atrial septal defects (ASDs) vary greatly depending on their size, age at closure, and clinical management. This report characterizes the prevalence, complexity, and clinical management of these lesions in a statewide pediatric cohort and examines predictors for receiving closures. A 15-year Medicaid data set (1996-2010) from one state was analyzed. The selection criteria specified patients 17 years of age or younger with a diagnosis of ASD primum, secundum, or sinus venosus on one or more service visits to a pediatrician or pediatric cardiologist. During the 15-year period, ASDs represented a prevalence rate for treatment of 0.47/1000 CHDs identified, with 61 % presenting as complex lesions. Concomitant cardiac anomalies that might have a negative impact on prognosis were present including patent ductus arteriosus (26.1 %), pulmonary hypertension (3.8 %), and supraventricular tachycardia (2.4 %). Pharmacologic treatments, predominantly diuretics, were prescribed for 21 % of the cohort. Both surgical closures (6.3 %) and transcatheter closures (1.4 %) were used for ASD secundum cases, whereas surgical closures predominated for ASD primum (25.6 %) and sinus venosus (13.5 %) lesions. The postoperative follow-up period was two to three times longer for children with ASD primum or sinus venosus than for those with ASD secundum (average, ~1 year). Factors predicting the likelihood of having ASD closure were older age, having a concomitant patent ductus arteriosus (PDA) repair, treatment with ibuprofen, having two or more concomitant CHDs, and receiving diuretics or preload/afterload-reducing agents. Care of ASDs in routine practice settings involves more complications and appears to be more conservative than portrayed in previous investigations of isolated ASDs.


The influence of early parathyroidectomy on aluminum-induced rickets in growing uremic rats.
Rats were subjected to a two-stage 5/6 nephrectomy and treated with aluminum for 2 and 4 weeks with a cumulative dose of 4.2 and 8.4 mg of aluminum, respectively. Other animals were parathyroidectomized and loaded with 8.4 mg of aluminum for 4 weeks. Histomorphometry and electron microscopy (tibiae), aluminum tissue (bone, kidney, liver) determination, serum (Ca, Mg, Zn, P, urea, creatinine, alkaline phosphatase, 1,25(OH)2D3, PTH) and urine (creatinine, A1) revealed that: (a) a dose of 8.4 mg aluminum was sufficient to induce rickets within 4 weeks of treatment and was associated with decreased serum calcitriol values and high aluminum accumulation within organs (electron-dense material was found in osteoblasts only); (b) previous parathyroidectomy prevented the occurrence of any aluminum-induced alteration of bone. It was associated with higher calcitriol and phosphorus values than in corresponding non-parathyroidectomized rats and significantly reduced aluminum accumulation within organs. The results was influenced neither by a drop in serum calcium values nor by different degrees of renal failure. We suggest that aluminum-induced rickets in growing uremic rats is prevented or delayed when previous parathyroidectomy has been performed.