Leveraging electrophysiologic correlates of word encoding to map seizure onset zone in focal epilepsy: Task-dependent changes in epileptiform activity, spectral features, and functional connectivity.
Verbal memory dysfunction is common in focal, drug-resistant epilepsy (DRE). Unfortunately, surgical removal of seizure-generating brain tissue can be associated with further memory decline. Therefore, localization of both the circuits generating seizures and those underlying cognitive functions is critical in presurgical evaluations for patients who may be candidates for resective surgery. We used intracranial electroencephalographic (iEEG) recordings during a verbal memory task to investigate word encoding in focal epilepsy. We hypothesized that engagement in a memory task would exaggerate local iEEG feature differences between the seizure onset zone (SOZ) and neighboring tissue as compared to wakeful rest ("nontask"). Ten participants undergoing presurgical iEEG evaluation for DRE performed a free recall verbal memory task. We evaluated three iEEG features in SOZ and non-SOZ electrodes during successful word encoding and compared them with nontask recordings: interictal epileptiform spike (IES) rates, power in band (PIB), and relative entropy (REN; a functional connectivity measure). We found a complex pattern of PIB and REN changes in SOZ and non-SOZ electrodes during successful word encoding compared to nontask. Successful word encoding was associated with a reduction in local electrographic functional connectivity (increased REN), which was most exaggerated in temporal lobe SOZ. The IES rates were reduced during task, but only in the non-SOZ electrodes. Compared with nontask, REN features during task yielded marginal improvements in SOZ classification. Previous studies have supported REN as a biomarker for epileptic brain. We show that REN differences between SOZ and non-SOZ are enhanced during a verbal memory task. We also show that IESs are reduced during task in non-SOZ, but not in SOZ. These findings support the hypothesis that SOZ and non-SOZ respond differently to task and warrant further exploration into the use of cognitive tasks to identify functioning memory circuits and localize SOZ.


Blood-Based DNA Methylation Biomarkers for Type 2 Diabetes: Potential for Clinical Applications.
Type 2 diabetes (T2D) is a leading cause of death and disability worldwide. It is a chronic metabolic disorder that develops due to an interplay of genetic, lifestyle, and environmental factors. The biological onset of the disease occurs long before clinical symptoms develop, thus the search for early diagnostic and prognostic biomarkers, which could facilitate intervention strategies to prevent or delay disease progression, has increased considerably in recent years. Epigenetic modifications represent important links between genetic, environmental and lifestyle cues and increasing evidence implicate altered epigenetic marks such as DNA methylation, the most characterized and widely studied epigenetic mechanism, in the pathogenesis of T2D. This review provides an update of the current status of DNA methylation as a biomarker for T2D. Four databases, Scopus, Pubmed, Cochrane Central, and Google Scholar were searched for studies investigating DNA methylation in blood. Thirty-seven studies were identified, and are summarized with respect to population characteristics, biological source, and method of DNA methylation quantification (global, candidate gene or genome-wide). We highlight that differential methylation of the TCF7L2, KCNQ1, ABCG1, TXNIP, PHOSPHO1, SREBF1, SLC30A8, and FTO genes in blood are reproducibly associated with T2D in different population groups. These genes should be prioritized and replicated in longitudinal studies across more populations in future studies. Finally, we discuss the limitations faced by DNA methylation studies, which include including interpatient variability, cellular heterogeneity, and lack of accounting for study confounders. These limitations and challenges must be overcome before the implementation of blood-based DNA methylation biomarkers into a clinical setting. We emphasize the need for longitudinal prospective studies to support the robustness of the current findings of this review.


Indigenous community psychologies, decolonization, and radical imagination within ecologies of knowledges.
As the American Psychological Association Taskforce on Indigenous Psychology acknowledges, fidelity to the inalienable right to self-determination is the ethical foundation of Indigenous psychology. The task of decolonizing psychology is not only about divesting from Eurocentric paradigms that have controlled and limited Indigenous wellbeing, but producing new paradigms founded on Indigenous knowledges. The Indigenous paradigm of social and emotional wellbeing is both a new therapeutic practice and theory of wellbeing. As the exploration of the domains of SEWB has shown, findings from the National Empowerment Project indicate that strengthening a connection to culture is identified as of highest importance to the flourishing of Indigenous individuals, families, and communities. Wellbeing in Abya Yala (the Americas) is conceived as Sumak Kawsay or Buen Vivir and Māori constructs of wellbeing as Hauora. These transnational wellbeing conceptualizations can be situated within a larger global health movement, which is centered on strengthening Indigenous cultures of wellbeing, and sustainable planet-people relationships. Indigenous community psychologies are not anthropocentric and are centered on the sacredness of nature, the cultivation of spirituality, and accountability to maintain harmonious ecosystem relationships. Indigenous community psychologies from Australia, Aotearoa New Zealand, and Mexico are brought in plurilogue envisioning international solidarity networks that engage communities, activists, and committed student generations.


CD95 capping is ROCK-dependent and dispensable for apoptosis.
Upon engagement, the CD95 receptor is rapidly clustered into cellular 'caps'. This receptor capping is one of the first events to take place following activation and it has been proposed to be important for the initiation of apoptotic signaling. As the biological roles of CD95 capping are still elusive, we explored in detail the role of capping in induction of apoptosis in lymphocytes. CD95 capping was shown to be uncoupled from apoptosis, as apoptosis could occur in the absence of CD95 capping and, vice versa, capping could occur without inducing apoptosis. CD95 capping occurred concomitantly with reorganization of the actin cytoskeleton and aggregation of lipid rafts. While inhibition of actin polymerization and caspase-8 activity had cell type-specific effects on capping in type I and type II cells, the rapid CD95-mediated cellular polarization, as visualized by the orchestrated reorganization of CD95, F-actin and lipid rafts, was shown to be dependent on signaling by Rho kinase (ROCK) in both cell types, however, by distinct activation mechanisms in the respective cell type. CD95 activated RhoA exclusively in the type II cell, whereas ROCK activation was caspase-dependent in the type I cell. Taken together, our results imply that CD95 capping and the subsequent cellular polarization is a ROCK signaling-regulated process that does not correlate with the induction of apoptosis, but is more likely to be involved in the emerging non-apoptotic functions of CD95.


Short needles (8 mm) reduce the risk of intramuscular injections in children with type 1 diabetes.
To study whether 8-mm needles can reduce the frequency of intramuscular injections in diabetic children. We conducted a prospective crossover study in 50 children whose BMI was < or = 60th percentile to compare two lengths of needles (12.7 and 8 mm) regarding the occurrence of intramuscular injections as assessed by ultrasonography. The frequency of intramuscular injections was 86% with the 12.7-mm needles and 38% with the 8-mm needles. The frequency of intramuscular injections was significantly reduced when using the 8-mm needles in the arms (P < 0.01) and thighs (P < 0.001). The efficiency of 8-mm needles, as defined by an intramuscular injection with a 12.7-mm needle and a subcutaneous injection with an 8-mm needle, was found for half of the children who injected in the arm and for two-thirds of the children who injected in the thigh. The subcutaneous tissue (SQT) thickness measured by ultrasonography with a skinfold was significantly higher (9.8 +/- 2.2 mm) in the group in which the 8-mm needles were efficient than in the group in which they were not efficient (6.8 +/- 2.1 mm, P < 0.0001). The efficiency of the 8-mm needle was not related to age, sex, BMI, percentile of BMI, injection device, or injection site. The sensibility and specificity of SQT thickness in predicting the efficiency of the 8-mm needles were both 79%. Needles that are 8 mm long significantly reduce the risk of intramuscular insulin injection in slim or normal-weight (BMI < or = 60th percentile) diabetic children and adolescents.


Mixed Micellization of Dimeric (Gemini) Surfactants and Conventional Surfactants.
The aqueous solutions of mixtures of various conventional surfactants and dimeric anionic and cationic surfactants have been investigated by electrical conductivity, spectrofluorometry, and time-resolved fluorescence quenching to determine the critical micelle concentrations and the micelle aggregation numbers in these mixtures. The following systems have been investigated: 12-2-12/DTAB, 12-2-12/C(12)E(6), 12-2-12/C(12)E(8), 12-3-12/C(12)E(8), Dim3/C(12)E(8), and Dim4/C(12)E(8) (12-2-12 and 12-3-12=dimethylene-1,2- and trimethylene-1,3-bis(dodecyldimethylammonium bromide), respectively; C(12)E(6) and C(12)E(8)=hexa- and octaethyleneglycol monododecylethers, respectively; Dim3 and Dim4=anionic dimeric surfactants of the disodium sulfonate type, Scheme 1; DTAB=dodecyltrimethylammonium bromide). For the sake of comparison the conventional surfactant mixtures DTAB/C(12)E(8) and SDS/C(12)E(8) (SDS=sodium dodecylsulfate) have also been investigated (reference systems). Synergism in micelle formation (presence of a minimum in the cmc vs composition plot) has been observed for the Dim4/C(12)E(8) mixture but not for other dimeric surfactant/nonionic surfactant mixtures investigated. The aggregation numbers of the mixed reference systems DTAB/C(12)E(8) and SDS/C(12)E(8) vary monotonously with composition from the value of the aggregation number of the pure C(12)E(8) to that of the pure ionic component. In contrast, the aggregation number of the dimeric surfactant/C(12)E(8) mixtures goes through a minimum at a low value of the dimeric surfactant mole fraction. This minimum does not appear to be correlated to the existence of synergism in micelle formation. The initial decrease of the aggregation number of the nonionic surfactant upon addition of ionic surfactant, up to a mole fraction of ionic surfactant of about 0.2 (in equivalent per total equivalent), depends little on the nature the surfactant, whether conventional or dimeric. The results also show that the microviscosity of the systems containing dimeric surfactants is larger than that of the reference systems. Copyright 2001 Academic Press.


Perioperative management of a neurosurgical patient requiring antiplatelet therapy.
In patients who undergo neurovascular stent placement with postoperative dual antiplatelet therapy to prevent in-stent thrombosis, there is no protocol for balancing the risk of acute stent thrombosis and bleeding if urgent neurosurgical procedures are required. We detail perioperative management of dual antiplatelet therapy in a 66-year-old man with a dolichoectatic aneurysm of the basilar artery treated with a Pipeline stent. Postoperatively, the patient was placed on aspirin and clopidogrel to prevent in-stent thrombosis. One month after the procedure, his neurological status declined secondary to obstructive hydrocephalus. His condition necessitated urgent placement of a ventriculoperitoneal shunt, despite the dual antiplatelet therapy for the flow-diverting Pipeline stent. Aspirin and clopidogrel were discontinued seven days prior to the planned shunt placement. To minimize time off antiplatelet therapy, aspirin was immediately replaced with ibuprofen. Eptifibatide was then started three days prior to surgery. The ibuprofen/eptifibatide bridge was discontinued at midnight prior to surgery. Aspirin was restarted on the first postoperative day and clopidogrel was restarted on the second postoperative day. The patient tolerated shunt placement without excessive bleeding or hemorrhagic complications. During the remainder of his hospital course, no evidence of stent thrombosis or intracranial hemorrhage was noted. We conclude that management of antiplatelet prophylaxis for neurovascular stent thrombosis in patients requiring urgent neurosurgical procedures may be successfully achieved by bridging aspirin and clopidogrel with ibuprofen and eptifibatide in the preoperative period.


Iliopsoas hemophilic pseudotumor with bowel fistulization.
Haemophiliac pseudotumors are usually observed in the diaphysis of long bones. Pseudotumors due to psoas muscle hematoma are rare and surgical management is difficult. Surgical treatment of these lesions is usually associated with high morbidity and mortality rate. Here, we present a case with iliopsoas haemophiliac pseudotumors with bowel fistulization who underwent three abdominal operations and survived. Based on our experiences in this patient, we recommend to wait for the intraabdominal hematoma and adhesions to resolve and organise, so that the dissection can be kept to a minimum, which decreases the chances of iatrogenic injury and surgical bleeding (Fig. 3, Ref. 15). Full Text (Free, PDF) www.bmj.sk.


Breast milk lymphocyte response to K1 antigen of Escherichia coli.
Comparison milk and blood lymphocyte blastogenic responses to the K1 antigen of Escherichia coli and lipopolysaccharide (LPS) from E. coli O127,B8 were examined in 16 postpartum women by [3H]thymidine uptake. Rabbit hemolysincoated sheep erythrocyte monolayers were used to deplete macrophages from milk lymphocyte preparations and to enrich for T lymphocytes in order to make milk preparations more comparable to blood preparations. Response was defined as a stimulation index of greater than or equal to 2.0. There was no evidence of selective response to K1 antigen by milk lymphocytes, since both blood and milk lymphocytes responded in four women and neither blood nor milk lymphocytes responded in nine. Milk lymphocytes alone responded to K1 in one woman, whereas blood lymphocytes alone responded in two women. Additional nonpaired milk or blood cultures were available from three women. None of these responded to K1 antigen. Corresponding lymphocyte cultures were stimulated with LPS. A positive K1 response was always accompanied by an LPS response, and the LPS response correlated with the K1 response in 17 of 19 women. Stool cultures examined with an antiserum agar showed no correlation between the presence of K1 E. coli in the stool and milk or blood lymphocyte response to K1 antigen. In the system used here, no selectivity of response of breast milk lymphocytes to K1 antigen was noted.


[Selection and procurement of the bones for transplantation].
In 1971-1990 the laboratory of preservation of tissues procured 2970 bone segments of different localization (diaphysis of long bones--2535, vertebrae--222, ribs--53, articulation ends of the bones--53 ets.). Problems of selection and procurement of the bones under nonsterile conditions with the following treatment in the performic acid and cryopreservation are elucidated. Results of allotransplantation of bones were studied in 1517 patients: 412 patients with fractures and false joints, 50 patients with osteochondrosis of intervertebral disks, 68--with scoliosis, 602--with osseous tumors and tumor-like alterations, 35 patients with congenital dysplasia of the hip joint. Postoperative complications such as hematomas, suppurations of the wound, osteomyelitis, rejection of transplants took place in 1.7% of the cases which completely justifies bone alloplasty.


Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice.
Autosomal-dominant sensorineural hearing loss is genetically heterogeneous, with a phenotype closely resembling presbycusis, the most common sensory defect associated with aging in humans. We have identified SLC17A8, which encodes the vesicular glutamate transporter-3 (VGLUT3), as the gene responsible for DFNA25, an autosomal-dominant form of progressive, high-frequency nonsyndromic deafness. In two unrelated families, a heterozygous missense mutation, c.632C-->T (p.A211V), was found to segregate with DFNA25 deafness and was not present in 267 controls. Linkage-disequilibrium analysis suggested that the families have a distant common ancestor. The A211 residue is conserved in VGLUT3 across species and in all human VGLUT subtypes (VGLUT1-3), suggesting an important functional role. In the cochlea, VGLUT3 accumulates glutamate in the synaptic vesicles of the sensory inner hair cells (IHCs) before releasing it onto receptors of auditory-nerve terminals. Null mice with a targeted deletion of Slc17a8 exon 2 lacked auditory-nerve responses to acoustic stimuli, although auditory brainstem responses could be elicited by electrical stimuli, and robust otoacoustic emissions were recorded. Ca(2+)-triggered synaptic-vesicle turnover was normal in IHCs of Slc17a8 null mice when probed by membrane capacitance measurements at 2 weeks of age. Later, the number of afferent synapses, spiral ganglion neurons, and lateral efferent endings below sensory IHCs declined. Ribbon synapses remaining by 3 months of age had a normal ultrastructural appearance. We conclude that deafness in Slc17a8-deficient mice is due to a specific defect of vesicular glutamate uptake and release and that VGLUT3 is essential for auditory coding at the IHC synapse.


Rubicon-Dependent Lc3 Recruitment to Salmonella-Containing Phagosomes Is a Host Defense Mechanism Triggered Independently From Major Bacterial Virulence Factors.
Intracellular pathogens such as Salmonella depend on their molecular virulence factors to evade host defense responses like autophagy. Using a zebrafish systemic infection model, we have previously shown that phagocytes, predominantly macrophages, target Salmonella Typhimurium by an autophagy-related pathway known as Lc3-associated phagocytosis (LAP), which is dependent on the host protein Rubicon. Here, we explore the influence of Salmonella virulence factors on pathogenicity in the zebrafish model and induction of LAP as a defense response. We investigated five mutant strains that all could trigger GFP-Lc3 recruitment as puncta or rings around single bacteria or bacterial clusters, in a Rubicon-dependent manner. We found that S. Typhimurium strains carrying mutations in PhoP or PurA, responsible for adaptation to the intracellular environment and efficient metabolism of purines, respectively, are attenuated in the zebrafish model. However, both strains show increased virulence when LAP is inhibited by knockdown of Rubicon. Mutations in type III secretion systems 1 and 2, SipB and SsrB, which are important for invading and replicating in non-phagocytic cells, did not affect the ability to establish successful infection in the zebrafish model. This observation is in line with our previous characterization of this infection model revealing that macrophages actively phagocytose the majority of S. Typhimurium. In contrast to SipB mutants, SsrB mutants were unable to become more virulent in Rubicon-deficient hosts, suggesting that type III system 2 effectors are important for intracellular replication of Salmonella in the absence of LAP. Finally, we found that mutation of FlhD, required for production of flagella, renders S. Typhimurium hypervirulent both in wild type zebrafish embryos and in Rubicon-deficient hosts. FlhD mutation also led to lower levels of GFP-Lc3 recruitment compared with the wild type strain, indicating that recognition of flagellin by the host innate immune system promotes the LAP response. Together, our results provide new evidence that the Rubicon-dependent LAP process is an important defense mechanism against S. Typhimurium.


[Strains of human gastrointestinal and uterine tumors transplantable into athymic mice and rats].
The authors describe strains of human cancer of the stomach, colon, cervix and corpus uteri as well as uterine chorionepitheliomas transplanted into nude mice and rats. The histological appearance of these strains is in full accordance with that of primary tumors. Electrophoresis of lactate dehydrogenase isozymes indicates that the strains mainly consist of human cells. The strains are transplanted in nude animals at various time intervals. The strains of human gastric cancer are transplanted from animal to animal in a month and those of corpus uteri in a week.


Antioxidants in peripheral arterial disease.
Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis that is characterized by obstruction of the arteries in the lower limbs. Experimental and epidemiological studies suggested a key role for oxidative stress in initiation and progression of the atherosclerotic process. The results of these studies provided a good basis for interventional trials with antioxidants, particularly with vitamin E, but the findings were conflicting. In this paper we review the observational and interventional studies with antioxidants, and ask whether vitamins supplementation should or should be not be recommended for PAD patients.


Diagnostic Accuracy of Magnetic Resonance Cholangiopancreatography to Detect Benign and Malignant Biliary Strictures.
Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method to detect pancreaticobiliary strictures. In this study, we aimed to evaluate the diagnostic performance of MRCP and detect sensitive and specific radiologic features in distinguishing malignant and benign pathologies. In this study, 50 patients with biliary obstruction and a confirmed diagnosis using histopathology were included. The pathologies were evaluated using MRCP which were categorized into malignant and benign strictures. The etiology of strictures was detected using histopathology and endoscopic retrograde cholangiopancreatography. The diagnostic performance of MRCP was calculated using SPSS software. P < 0.05 was considered statistically significant. Of 50 patients, 23 patients (46%) had malignant strictures based on MRCP and histopathology. The sensitivity and specificity of MRCP to detect malignancy were 95.7% and 96.3%, respectively. The most sensitive MRCP features to detect malignancy were upstream biliary duct dilation, abrupt tapering, and the presence of a solid mass with sensitivity 100%, 95.7%, and 78.2%, respectively. The malignancy rate was significantly higher in the strictures with length >11.5 mm or wall thickness >2.75 mm (P < 0.05). MRCP is a sensitive method to differentiate malignant lesions from benign pathologies. A long and thick stricture with the presence of a solid mass, upstream biliary duct dilation, and abrupt tapering is highly suggestive of malignancy.


T2-weighted imaging of the prostate: Impact of the BLADE technique on image quality and tumor assessment.
To retrospectively compare standard and BLADE T2-weighted imaging (T2WI) sequences of the prostate in terms of image quality and tumor assessment. 49 prostate cancer patients (64 ± 6 years) who underwent 3 T phased-array coil MRI before prostatectomy were included. T2WI was acquired using standard rectilinear and BLADE techniques. Two readers (R1, R2) independently localized the dominant lesion using T2WI alone and using multi-parametric imaging; recorded presence of extraprostatic extension (EPE) in each lobe; and scored lesion conspicuity and absence of motion artifact (1-5 scale; 5 = highest quality). A third reader, unblinded to pathology, placed ROIs to record tumor-to-peripheral-zone contrast. Standard and BLADE T2WI were compared using paired Wilcoxon tests. BLADE showed a trend toward improved motion artifact for R1 (3.4 ± 1.3 vs. 2.9 ± 1.5; p = 0.054) but not R2 (4.0 ± 1.0 vs. 3.9 ± 1.1; p = 0.880). Dominant lesions showed significantly lower conspicuity using BLADE for R1 (2.8 ± 2.0 vs. 3.2 ± 2.0; p = 0.011) but not R2 (2.3 ± 1.6 vs. 2.4 ± 1.7; p = 0.353), and significantly lower tumor-to-peripheral-zone contrast using BLADE (0.35 ± 0.13 vs. 0.42 ± 0.15; p ≤ 0.001). R1 and R2 correctly localized four and three fewer dominant tumors, respectively, using BLADE than standard T2WI, although both correctly localized a similar fraction of dominant tumors using multi-parametric sequences. While R1 detected EPE in 10 of 11 patients using both sequences, R2 detected EPE in 3 more patients using BLADE. BLADE may help reduce motion artifact of prostate T2WI and assist EPE detection, although at expense of reduced image contrast. In practice, BLADE may be useful in patients in whom initial T2WI is degraded by motion.


In vitro antibacterial activities of antibiotics against Pseudomonas aeruginosa in peritoneal dialysis fluid.
Intraperitoneal antibiotics are used to treat Pseudomonas aeruginosa peritonitis, a serious complication of continuous ambulatory peritoneal dialysis. However, P. aeruginosa killing is often inefficient despite low MBCs. Broth dilution MIC/MBC and time kill curves of tobramycin, amikacin, netilmicin, azlocillin, piperacillin, ceftazidime, cefsulodin, and ciprofloxacin were determined in peritoneal dialysis fluid (PDF), buffered PDF, fluid recovered from patients on continuous ambulatory peritoneal dialysis (RPF), and cation-supplemented Mueller-Hinton broth. MBCs of all antibiotics were 8 to 16 times greater in PDF and RPF than in Mueller-Hinton broth or buffered PDF. Use of the time kill curve technique and Mueller-Hinton broth showed that aminoglycosides killed greater than or equal to 99.9% of P. aeruginosa at 1 h, ciprofloxacin killed greater than or equal to 99.9% at 2 h, and beta-lactams killed greater than or equal to 99.9% at 6 h. In contrast, killing was not demonstrated in PDF by any drug at 6 h and by aminoglycosides only at 24 h. Bactericidal activity was optimal in RPF for ciprofloxacin at 1 h and for aminoglycosides at 2 h; bactericidal activity was not demonstrated in RPF with any beta-lactam (no kill by penicillins; less than 99% kill by cephalosporins). Slow bacterial growth, increased protein binding, and glucose concentrations and other inhibitors may interfere with beta-lactam activity in RPF. These considerations and reported clinical failures and toxicity of aminoglycoside therapy warrant further study of quinolones and drug combinations in P. aeruginosa peritonitis.


[Basing approximate safe level of exposure to Triazavirin in air of workplace].
The authors present materials on experimental basis of approximate safe level of exposure to new anti-flu medication Triazavirin in air of workplace. The article covers acute toxicity parameters for various intake routes, results of irritating and sensitizing effects evaluation, determination of threshold concentration for single inhalation effect, value of recommended approximate safe level of exposure.


CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes.
Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of ATP, which acts as a neurotransmitter to activate afferent neural gustatory pathways. However, how ATP is released to fulfil this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel, is indispensable for taste-stimuli-evoked ATP release from sweet-, bitter- and umami-sensing taste bud cells. Calhm1 knockout mice have severely impaired perceptions of sweet, bitter and umami compounds, whereas their recognition of sour and salty tastes remains mostly normal. Calhm1 deficiency affects taste perception without interfering with taste cell development or integrity. CALHM1 is expressed specifically in sweet/bitter/umami-sensing type II taste bud cells. Its heterologous expression induces a novel ATP permeability that releases ATP from cells in response to manipulations that activate the CALHM1 ion channel. Knockout of Calhm1 strongly reduces voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Thus, CALHM1 is a voltage-gated ATP-release channel required for sweet, bitter and umami taste perception.


Ultrasonographic Investigation of Human Fetus Responses to Maternal Communicative and Non-communicative Stimuli.
During pregnancy fetuses are responsive to the external environment, specifically to maternal stimulation. During this period, brain circuits develop to prepare neonates to respond appropriately. The detailed behavioral analysis of fetus' mouth movements in response to mothers' speech may reveal important aspects of their sensorimotor and affective skills; however, to date, no studies have investigated this response. Given that newborns at birth are capable of responding with matched behaviors to the social signals emitted by the caregiver, we hypothesize that such precocious responses could emerge in the prenatal period by exploiting infants' sensitivity to their mother's voice. By means of a two-dimensional (2D) ultrasonography, we assessed whether fetuses at 25 weeks of gestation, showed a congruent mouthmotor response to maternal acoustic stimulation. Mothers were asked to provide different stimuli, each characterized by a different acoustic output (e.g., chewing, yawning, nursery rhymes, etc.) and we recorded the behavioral responses of 29 fetuses. We found that, when mothers sang the syllable LA in a nursery rhyme, fetuses significantly increased mouth openings. Other stimuli provided by the mother did not produce other significant changes in fetus' behavior. This finding suggests that fetuses are sensitive only to specific maternal vocalizations (LA) and that fetal matched responses are rudimentary signs of early mirroring behaviors that become functional in the postnatal period. In conclusion, fetuses seem to be predisposed to respond selectively to specific maternal stimuli. We propose that such responses may play a role in the development of behavioral and emotional attunement with their mothers long before birth.


Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L.
Due to its liver toxicity, the medicinal use of germander (Teucrium chamaedrys L.) was banned in some countries. Nevertheless, alcoholic extracts are still permitted as flavour ingredients since they are fundamental in providing a bitter aromatic taste. Teucrin A represents the substance of major concern regarding the potential toxicity of germander. Hence, teucrin A represents the best analytical and toxicological marker of alcoholic extracts of T. chamaedrys. A sensitive high-performance liquid chromatography method to detect teucrin A in beverages is reported. Teucrin A was prepared by isolation from the plant extract using column chromatography and crystallization. The identity and purity (99%) were established by melting point, nuclear magnetic resonance and liquid chromatography-mass spectrometry. The high-performance liquid chromatography procedure was validated and its intra- and interday performance was established (relative standard deviation < or = 13% and error < or = 10%). In-house validation was carried out by analysing samples of beverages not containing T. chamaedrys spiked with a range of concentrations of teucrin A. The limit of detection was 0.1 ppm and the limit of quantification was 0.3 ppm. Teucrin A accounted for about 70% of the neo-clerodane diterpenoids found in the total extract of a specimen of T. chamaedrys. The content (+/- standard deviation) in 18 batches of different geographical origin was 2338 +/- 740 ppm, per cent coefficient of variation = 32, minimum-maximum = 999 - 3445 ppm. The mean level of teucrin A in 10 bottles of the same brand was 6.1 +/- 0.8 ppm, per cent coefficient of variation = 12. In 10 different brands found on the Italian market, the content of teucrin A ranged from not detectable to 10 ppm.


Mode of action of natural inactivator proteins from corn and rice on a purified assimilatory nitrate reductase.
The molecular basis for the action of two natural inactivator proteins, isolated from rice and corn, on a purified assimilatory nitrate reductase has been examined by several physical techniques. Incubation of purified Chlorella nitrate reductase with either rice inactivator protein or corn inactivator protein results in a loss of NADH:nitrate reductase and the associated partial activity, NADH:cytochrome c reductase, but no loss in nitrate-reducing activity with reduced methyl viologen as the electron donor. The molecular weight of the reduced methyl viologen:nitrate reductase species, determined by sedimentation equilibrium in the Beckman airfuge after complete inactivation with rice inactivator protein or with corn inactivator protein, was 595,000 and 283,000, respectively, compared to a molecular weight of 376,000 for the untreated control determined under the same conditions. Two protein peaks were observed after molecular-sieve chromatography on Sephacryl S-300 of nitrate reductase inactivated by corn inactivator protein. The Stokes radii of these fragments were 68 and 24 A, compared to a value of 81 A for untreated nitrate reductase. The large fragment contained molybdenum and heme but no flavin, and had nitrate-reducing activity with reduced methyl viologen as electron donor. The small fragment contained FAD but had no NADH:cytochrome c reductase or nitrate-reducing activities. Molecular weights determined by sodium dodecyl sulfate-gel electrophoresis were 67,000 and 28,000 for the large and small fragments, respectively, compared to a subunit molecular weight of 99,000 determined for the untreated control. No change in subunit molecular weight of nitrate reductase after inactivation by rice inactivator protein was observed. These results indicate that rice inactivator protein acts by binding to nitrate reductase. The stoichiometry of binding is 1-2 molecules of rice inactivator protein to one tetrameric molecule of nitrate reductase. Corn inactivator protein, in contrast, acts by cleavage of a Mr 30,000 fragment from nitrate reductase which is associated with FAD. The remaining fragment is a tetramer of Mr 70,000 subunits which retains nitrate-reducing activity and contains molybdenum and heme but has no NADH:dehydrogenase activity. The action of rice inactivator protein was partially prevented by NADH and completely prevented by a combination of NADH and cyanide, while the action of corn inactivator protein was not significantly affected by these effectors.


How should we regulate risk in biomedical research? An ethical analysis of recent policy proposals and initiatives.
The existing regulatory framework for research is increasingly attacked for its "one-size-fits-all" approach. Many stakeholders contend that existing regulations formulate the same regulatory requirements for research involving very different levels of risk, and thereby unnecessarily stifle medical progress. To address this criticism, regulators are currently developing more risk-adapted approaches to regulating research. A key feature of these approaches is that they aim to calibrate subject protections, including ethical review and safety monitoring, to the risks that studies pose to participants. Risk-adapted systems of research oversight are ethically appealing because they have the potential to promote research within the constraints of adequate subject protection. However, this potential can only be realized if the complexities surrounding research risk can be addressed. The present paper offers the first systematic overview and ethical analysis of how European and U.S. regulators approach the development of more risk-adapted regulations. The analysis finds that so-called stratified approaches are ethically preferable because they specify risk categories with corresponding subject protections, and thereby reduce unwarranted variation in how research participants are protected in different studies. But the recent proposals for stratifying risk and subject protections raise various ethical concerns, for example regarding the accuracy of risk categories. Building on this analysis, the paper develops recommendations for future policy.


[Biotechnology of yogurt and kefir production, study of their effect on human health].
Biotechnological parameters of bioyogurt and biokefir production have been studied. The impact of the temperature on biological activity of lactic acid bacteria strains have been studied in the consortia of direct vat set (DVS). The phase of milk fermentation and increase of acid production comes within 6 hours at the temperature of 40 degrees C and pH in the limits of 4.7-5.1 for thermophilic strains and 30 degrees C and pH 5.4-5.7 for mezophilic strains. The concentration of alive cells counts 5 x 10(10) CFU per 1 ml of the product. The probiotic properties of bioyogurt and biokefir have been proved by clinical trials. Positive effect on the health of elder people has been shown. Bioproducts have been related by clinicists to the group of functional products.


Improved survival in critically injured combat casualties treated with fresh whole blood by forward surgical teams in Afghanistan.
The objective of this study was to assess transfusion strategies and outcomes, stratified by the combat mortality index, of casualties treated by small surgical teams in Afghanistan. Resuscitation that included warm fresh whole blood (FWB) was compared to blood component resuscitation. Casualties treated by a Role 2 surgical team in Afghanistan from 2008 to 2014 who received 1 or more units of red blood cells (RBCs) or FWB were included. Patients were excluded if they had incomplete data or length of stay less than 30 minutes. Patients were separated into two groups: 1) received FWB and 2) did not receive FWB; moreover, both groups potentially received plasma, RBCs, and platelets. The analysis was stratified by critically versus noncritically injured patients using the prehospital combat mortality index. Kaplan-Meier plot, log-rank test, and multivariable Cox regression were performed to compare survival. In FWB patients, median units of FWB and total blood product were 4.0 (interquartile range [IQR], 2.0-7.0) and 16.0 (IQR, 10.0-28.0), respectively. The Kaplan-Meier plot demonstrated that survival was similar between FWB (79.1%) and no-FWB (74.5%) groups (p = 0.46); after stratifying patients by the combat mortality index, the risk of mortality was increased in the no-FWB group (hazard ratio, 2.8; 95% confidence interval, 1.2-6.4) compared to the FWB cohort. In forward-deployed environments, where component products are limited, FWB has logistical advantages and was associated with reduced mortality in casualties with a critical combat mortality index. Additional analysis is needed to determine if these effects of FWB are appreciable in all trauma patients or just in those with severe physiologic derangement.


Glucocorticoid-associated blood glucose response and MS relapse recovery.
To determine the relationship between MS relapse recovery and blood glucose (BG) response to IV methylprednisolone (IVMP) treatment. We retrospectively identified 36 patients with MS admitted for IVMP treatment of acute relapse who had adequate data to characterize BG response, relapse severity, and recovery. The relationship between glucocorticoid-associated nonfasting BG (NFBG) and relapse recovery was assessed. Highest recorded nonfasting BG (maximum NFBG [maxNFBG]) values were significantly higher in patients with MS without relapse recovery compared with those with recovery (271 ± 68 vs 209 ± 48 mg/dL, respectively; p = 0.0045). After adjusting for relapse severity, MS patients with maxNFBG below the group median were 6 times (OR = 6.01; 95% CI, 1.08-33.40; p = 0.040) more likely to experience relapse recovery than those with maxNFBG above the group median. In a multiple regression model adjusting for age, sex, and relapse severity, a 1-mg/dL increase in the maxNFBG was associated with 4.5% decrease in the probability of recovery (OR = 0.955; 95% CI, 0.928-0.983; p = 0.002). These findings suggest that higher glucocorticoid-associated NFBG values in acutely relapsing patients with MS are associated with diminished probability of recovery. This relationship could reflect steroid-associated hyperglycemia and/or insulin resistance, defects in non-steroid-associated (e.g., prerelapse) glucose metabolism, or both. This study included only those admitted for an MS relapse, and it is this subset of patients for whom these findings may be most relevant. A prospective study to evaluate glucose regulation and MS relapse recovery in a broader outpatient MS population is under way.


Submersible Spectrofluorometer for Real-Time Sensing of Water Quality.
In this work, we present a newly developed submersible spectrofluorometer (patent pending) applied to real-time sensing of water quality, suitable for monitoring some important indicators of the ecological status of natural waters such as chlorophyll-a, oil and protein-like material. For the optomechanical realization of the apparatus, a novel conceptual design has been adopted in order to avoid filters and pumps while maintaining a high signal-to-noise ratio. The elimination of filters and pumps has the advantage of greater system simplicity and especially of avoiding the risk of sample degradation. The use of light-emitting diodes as an excitation source instead of Xe lamps or laser diodes helped save on size, weight, power consumption and costs. For sensor calibration we performed measurements on water samples with added chlorophyll prepared in the laboratory. The sensor functionality was tested during field campaigns conducted at Albano Lake in Latium Region of Italy as well as in the Herzliya Harbor, a few kilometers North East of Tel Aviv in Israel. The obtained results are reported in the paper. The sensitivity achieved for chlorophyll-a detection was found to be at least 0.2 µg/L.


Hepatitis B infection in patients with lymphomas.
This paper reviewed the clinical characteristics and treatment outcome of 484 lymphoma patients with known hepatitis B status. Comparisons were made between the hepatitis B surface antigen positive and negative patients. Also, the effect of treatment for lymphomas, including cytotoxic chemotherapy, in the hepatitis B antigen positive patients were analysed. The hepatitis B status was determined in 484 Chinese lymphoma patients at the time of initial diagnosis. Hepatic complications occurring during therapy for lymphomas were analysed. Although our lymphoma patients had a similar prevalence of hepatitis B markers of 42 per cent, they had a strikingly higher positive rate of 22 per cent for hepatitis B surface antigen and a relatively lower positive rate of 20 per cent for antibody, as compared to the respective figures of 9.5 per cent and 33 per cent in the control population. The hepatitis B surface antigen positive patients were younger than the negative patients but their treatment outcomes were similar despite the higher incidence of hepatic complications (21 per cent) in the hepatitis B surface antigen positive patients during therapy for lymphomas. None of the clinical parameters analysed appeared to be useful in predicting the development of these complications which included fatal liver failure (5.7 per cent), icteric hepatitis (5.7 per cent) and anicteric hepatitis (9.5 per cent). The high prevalence of hepatitis B surface antigen in our lymphoma patients may be related to the immunosuppressive effect of lymphomas. There is no definite evidence to suggest that hepatitis B infection has an aetiological or promoting role in the pathogenesis of lymphomas. Hepatitis B infection has contributed to the high incidence of hepatic complications during therapy for lymphomas and possible ways of prevention need to be investigated.


Determination of sulpiride by capillary electrophoresis with end-column electrogenerated chemiluminescence detection.
Capillary electrophoresis (CE) with tris(2,2'-bipyridyl)ruthenium(II) [Ru(bpy)3(2+)]-electrogenerated chemiluminescence (ECL) detection is a promising method for clinical analysis. In this study, a method combining CE with Ru(bpy)3(2+) ECL (CE-ECL) detection that can be applied to amine-containing clinical species was developed, and the performance of CE-ECL as a quantitative method for determination of sulpiride in human plasma or urine was evaluated. Sulpiride was separated by capillary zone electrophoresis in uncoated fused-silica capillaries [50 cm x 25 microm (i.d.)] filled with phosphate buffer (pH 8.0) and a driving voltage of +15 kV, with end-column Ru(bpy)3(2+) ECL detection. A platinum disc electrode was used as working electrode. Sulpiride in human plasma or urine samples (100 microL) was extracted by a double-step liquid-liquid extraction procedure, dried under nitrogen at 35 degrees C in a water bath, and reconstituted with 100 microL of filtered water. The extraction solvent was ethyl acetate-dichloromethane (5:1 by volume). Under optimum conditions (pH 8.0 phosphate buffer, injection for 6 s at 10 kV, and +1.2 V as detection potential), separation of sulpiride was accomplished within 4 min. The calibration curve was linear over a concentration range of 0.05-25.0 micromol/L, and the limit of detection was 2.9 x 10(-8) mol/L for sulpiride. Intra- and interday CVs for ECL intensities were <6%. Extraction recoveries of sulpiride were 95.6-101% with CVs of 2.9-6.0%. The method was clinically validated for patient plasma and urine samples. CE combined with Ru(bpy)3(2+) ECL is reproducible, precise, selective, and enables the analysis of sulpiride in human plasma and urine. It thus is of value for rapid and efficient analysis of amine-containing analytes of clinical interest.


ConsRM: collection and large-scale prediction of the evolutionarily conserved RNA methylation sites, with implications for the functional epitranscriptome.
Motivation N6-methyladenosine (m6A) is the most prevalent RNA modification on mRNAs and lncRNAs. Evidence increasingly demonstrates its crucial importance in essential molecular mechanisms and various diseases. With recent advances in sequencing techniques, tens of thousands of m6A sites are identified in a typical high-throughput experiment, posing a key challenge to distinguish the functional m6A sites from the remaining 'passenger' (or 'silent') sites. Results: We performed a comparative conservation analysis of the human and mouse m6A epitranscriptomes at single site resolution. A novel scoring framework, ConsRM, was devised to quantitatively measure the degree of conservation of individual m6A sites. ConsRM integrates multiple information sources and a positive-unlabeled learning framework, which integrated genomic and sequence features to trace subtle hints of epitranscriptome layer conservation. With a series validation experiments in mouse, fly and zebrafish, we showed that ConsRM outperformed well-adopted conservation scores (phastCons and phyloP) in distinguishing the conserved and unconserved m6A sites. Additionally, the m6A sites with a higher ConsRM score are more likely to be functionally important. An online database was developed containing the conservation metrics of 177 998 distinct human m6A sites to support conservation analysis and functional prioritization of individual m6A sites. And it is freely accessible at: https://www.xjtlu.edu.cn/biologicalsciences/con.


Reduced spillover transmission of Mycobacterium bovis to feral pigs (Sus scofa) following population control of brushtail possums (Trichosurus vulpecula).
In New Zealand, bovine tuberculosis (bTB) is present in domestic cattle and deer herds primarily as the result of on-going disease transmission from the primary wildlife host, the brushtail possum (Trichosurus vulpecula). However, bTB is also present in other introduced free-ranging mammalian species. Between 1996 and 2007, we conducted a series of studies to determine whether poison control of possum populations would have any effect on the prevalence of Mycobacterium bovis infection in sympatric feral pigs (Sus scrofa). We compared trends in the prevalence of bTB infection in feral pigs in six study areas: possum numbers were reduced in three areas, but not in the other three, effectively providing a thrice-replicated before-after-control-intervention design. Before possum control, the overall prevalence of culture-confirmed M. bovis infection in feral pigs was 16.7-94.4%, depending on area. Infection prevalence varied little between genders but did vary with age, increasing during the first 2-3 years of life but then declining in older pigs. In the areas in which possum control was applied, M. bovis prevalence in feral pigs fell to near zero within 2-3 years, provided control was applied successfully at the whole-landscape scale. In contrast, prevalence changed much less or not at all in the areas with no possum control. We conclude that feral pigs in New Zealand acquire M. bovis infection mainly by inter-species transmission from possums, but then rarely pass the disease on to other pigs and are end hosts. This is in contrast to the purported role of pigs as bTB maintenance hosts in other countries, and we suggest the difference in host status may reflect differences in the relative importance of the oral route of infection in different environments. Despite harbouring M. bovis infection for a number of years, pigs in New Zealand do not sustain bTB independently, but are good sentinels for disease prevalence in possum populations.


Phagocytic Receptors Activate Syk and Src Signaling during Borrelia burgdorferi Phagocytosis.
Phagocytosis of the Lyme disease-causing pathogen Borrelia burgdorferi has been shown to be important for generating an inflammatory response to the pathogen. As a result, understanding the mechanisms of phagocytosis has been an area of great interest in the field of Lyme disease. Several cell surface receptors that participate in B. burgdorferi phagocytosis have been reported, including the scavenger receptor MARCO and integrin α3β1. We sought to define the mechanisms by which these receptors mediate phagocytosis and to identify signaling pathways activated downstream of these receptors upon contact with B. burgdorferi We identified both Syk and Src signaling pathways as ones that participate in B. burgdorferi phagocytosis and the resulting cytokine activation. In our studies, we found that both MARCO and integrin β1 play a role in the activation of the Src kinase pathway. However, only integrin β1 participates in the activation of Syk. Interestingly, the integrin activates Syk without the help of the signaling adaptor Dap12 or FcRγ. Thus, we report that multiple pathways participate in B. burgdorferi internalization and that different cell surface receptors act simultaneously in cooperation and independently to mediate phagocytosis.


Concurrent evaluation of salivary and urinary α-amylase activity following prolonged exercise with or without carbohydrate solution in aerobically active men.
The purpose of this study was to determine the effects of 2-h moderately prolonged exercise with carbohydrate intake or water placebo on salivary and urinary α-amylase isoenzyme activity in trained men. Eleven aerobically fit men participated in this study. On two different occasions, participants performed 2-h cycling corresponding to a constant power output at 60% peak oxygen uptake. The study design involved a random order, placebo-controlled and cross-over assignment. Participants consumed either 6.2% carbohydrate solution or water placebo every twenty minutes thereafter (2 ml/kg body mass) over 2-h endurance exercise. Unstimulated whole salivary samples were collected using the passive drooling method at the 10-min period before and after exercise for the quantification of salivary α-amylase, immunoglobulin A (IgA) and total protein. Two-hour urinary samples were obtained at three time points before (-2-0h), immediately (0-2 h) after and 24-26 h after exercise for the analysis of α-amylase isoenzyme activity (pancreas- and saliva-derived types). The activity of α-amylase in saliva and urine was significantly increased in connect with salivary total protein concentration immediately after moderately long-lasting exercise, but salivary IgA concentration was not statistically significant with or without exogenous carbohydrate intake. These findings suggest that 2-h moderate exercise appears to lead to the enhanced α-amylase activity in saliva and urine regardless of exogenous carbohydrate availability, demonstrating enhanced mucosal immune defense.


The cardiovascular system.
This article, which forms part of the life science series, examines the cardiovascular system, focusing on the anatomy and physiology of the heart. The blood flow through the heart is described and the regulatory mechanisms of the heart are identified and discussed. The cardiac conduction system is examined, outlining the normal sequence of events in the cardiac cycle. In addition, a brief overview of some common cardiac disorders is provided.


Oscillations in cortico-basal ganglia circuits: implications for Parkinson's disease and other neurologic and psychiatric conditions.
Cortico-basal ganglia circuits are thought to play a crucial role in the selection and control of motor behaviors and have also been implicated in the processing of motivational content and in higher cognitive functions. During the last two decades, electrophysiological recordings in basal ganglia circuits have shown that several disease conditions are associated with specific changes in the temporal patterns of neuronal activity. In particular, synchronized oscillations have been a frequent finding suggesting that excessive synchronization of neuronal activity may be a pathophysiological mechanism involved in a wide range of neurologic and psychiatric conditions. We here review the experimental support for this hypothesis primarily in relation to Parkinson's disease but also in relation to dystonia, essential tremor, epilepsy, and psychosis/schizophrenia.


Replicated slanted gratings with a high refractive index material for in and outcoupling of light.
Diffractive slanted gratings are manufactured onto plastic light guides using a high refractive index material and UV replication technology. We show that the manufacturing of such components is possible in large quantities. The applications of the slanted gratings are a high efficiency light in- and outcoupling with plastic light guides. We also show that it is possible to control which outcoupling diffraction order, reflective or transmissive, is dominating and hence to maximize the light power to one direction.


Silencing the ap65 gene reduces adherence to vaginal epithelial cells by Trichomonas vaginalis.
Host parasitism by Trichomonas vaginalis is complex and in part mediated by adherence to vaginal epithelial cells (VECs). Four trichomonad surface proteins bind VECs as adhesins, and AP65 is a major adhesin with sequence identity to an enzyme of the hydrogenosome organelle that is involved in energy generation. In order to perform genetic analysis and assess the role of AP65 in T. vaginalis adherence, we silenced expression of ap65 using antisense RNA. The gene for ap65 was inserted into the vector pBS-neo in sense and antisense orientations to generate plasmids pBS-neoS (S) and pBS-neoAS (AS), respectively. Trichomonads were then transfected with S and AS plasmids for selection of stable transfectants using Geneticin, and the presence of plasmid in transfectants was confirmed by polymerase chain reaction of the neo gene. Reverse transcription polymerase chain reaction and Northern blot analysis showed decreased amounts of ap65 transcript in AS transfected parasites. Growth kinetics of the antisense-transfected and wild type organisms were similar, suggesting that silencing AP65 did not affect overall energy generation for growth. Immunoblot analysis using monoclonal antibody (mAb) to AP65 of AS transfectants showed decreased amounts of AP65 when compared to wild type or S transfectants. Not unexpectedly, this corresponded to decreased amounts of AP65 bound to VECs in a functional ligand assay. Reduction in parasite surface expression of AP65 was related to lower levels of adherence to VECs by AS-transfectants compared to control organisms. Antisense silencing of ap65 was not alleviated by growth of trichomonads in high iron, which up-regulates transcription of ap65. Our work reaffirms the role for AP65 as an adhesin, and in addition, we demonstrate antisense RNA gene silencing in T. vaginalis to study the contribution of specific genes in pathogenesis.


Arabidopsis accelerated cell death 11, ACD11, is a ceramide-1-phosphate transfer protein and intermediary regulator of phytoceramide levels.
The accelerated cell death 11 (acd11) mutant of Arabidopsis provides a genetic model for studying immune response activation and localized cellular suicide that halt pathogen spread during infection in plants. Here, we elucidate ACD11 structure and function and show that acd11 disruption dramatically alters the in vivo balance of sphingolipid mediators that regulate eukaryotic-programmed cell death. In acd11 mutants, normally low ceramide-1-phosphate (C1P) levels become elevated, but the relatively abundant cell death inducer phytoceramide rises acutely. ACD11 exhibits selective intermembrane transfer of C1P and phyto-C1P. Crystal structures establish C1P binding via a surface-localized, phosphate headgroup recognition center connected to an interior hydrophobic pocket that adaptively ensheaths lipid chains via a cleft-like gating mechanism. Point mutation mapping confirms functional involvement of binding site residues. A π helix (π bulge) near the lipid binding cleft distinguishes apo-ACD11 from other GLTP folds. The global two-layer, α-helically dominated, "sandwich" topology displaying C1P-selective binding identifies ACD11 as the plant prototype of a GLTP fold subfamily.


[Surgical treatment of lung cancer with brain metastasis].
Twelve cases of lung cancer with brain metastasis, which comprised 20% of all lung cancer patients complicated with brain metastasis in the same period in our hospital, underwent resection of both lung and brain lesions. There were 9 men and 3 women. The ages ranged from 29 to 65. The site of metastasis was supratentorial in 11 patients and on the right side in 8. The interval between thoracotomy and craniotomy was 18 days-5 years. There was no operative death. Six patients have survived for more than one year. Surgical approach to lung cancer with brain metastasis has proved to be better in comparison with other methods of treatment. Obviously, adjuvant therapy after surgery may play an important role in improving survival. Whether craniotomy or thoracotomy is first performed depends on the presence or absence of life-threatening neurological symptoms. If the patient's condition allows, the second operation should be performed as soon as possible. It is emphasized that in lung cancer patients, pre- and postoperative routine CT scan of the brain should be regularly done for early detection of brain metastasis. Meanwhile, a timely, planned, staged operation may improve survival.


Introduction of a leaky stop codon as molecular tool in Chlamydomonas reinhardtii.
Expression of proteins in the chloroplast or mitochondria of the model green alga Chlamydomonas reinhardtii can be achieved by directly inserting transgenes into organellar genomes, or through nuclear expression and post-translational import. A number of tools have been developed in the literature for achieving high expression levels from the nuclear genome despite messy genomic integration and widespread silencing of transgenes. Here, recent advances in the field are combined and two systems of bicistronic expression, based on ribosome reinitiation or ribosomal skip induced by a viral 2A sequence, are compared side-by-side. Further, the small subunit of Rubisco (RBCS) was developed as a functional nuclear reporter for successful chloroplast import and restoration of photosynthesis: To be able to combine RBCS with a Venus fluorescent reporter without compromising photosynthetic activity, a leaky stop codon is introduced as a novel molecular tool that allows the simultaneous expression of functional and fluorescently tagged versions of the protein from a single construct.


Grief and bereavement. Healing through hurt.
Based on the premise that understanding bereavement as a natural healing process provides a foundation for nursing assessment and intervention, this article focuses on adult reactions to grief. Suggestions for facilitation of healthy grieving in survivors including staff and for sensitive, caring, and empathetic responses are included. Nurses are challenged to use creative ways to help bereaved persons build bridges to health, not walls to loneliness.


Work-Recreation Balance, Health-Promoting Lifestyles and Suboptimal Health Status in Southern China: A Cross-Sectional Study.
Suboptimal health status (SHS)-an intermediate state between health and illness--refers to functional somatic symptoms that are medically undiagnosed. Although- SHS has become a great challenge for global public health, very little about its etiology and mechanisms are known. Work-recreation balance is a part of work-life balance, and is related to stress which greatly influences health status. We therefore carried out a cross-sectional investigation between 2012 and 2013 within a clustered sample of 24,475 individuals aged 15-60 years from a population in southern China. In so doing, we hoped to illuminate the associations between work-recreation balance conditions, healthy lifestyles, and SHS. Work-recreation balance conditions were categorically defined by frequency ("rarely, sometimes, or always"). Health-Promoting Lifestyle Profile (HPLP-II) was used to evaluate the level of healthy lifestyles, and the medical examination report and Sub-Health Measurement Scale V1.0 (SHMS V1.0) were both used to evaluate health status. The ratio of SHS (46.3%) is higher than health status (18.4%) or disease status (35.3%). Overall, 4.9% of respondents reported the lowest level of work-recreation balance, and they scored lower on both the HPLP-II and SHMS V1.0 compared with those who frequently maintained a work-recreation balance. Significant association was found between work-recreation balance behaviors and healthy lifestyles (p < 0.001) after demographic adjustment. In comparison with those reporting a frequent work-recreation balance, individuals whose work-recreation balance was categorically "rare" were 1.69 times as likely to develop SHS (odds ratio (OR): 1.69, 95% confidence interval (CI): 1.49-1.92), and those with infrequent work-recreation balance ("sometimes") were 1.71 times more likely to develop SHS (OR: 1.71, 95% CI: 1.62-1.81). These findings suggest that work-recreation balance conditions are significantly associated with, and seem to be accurate behavioral indicia of a healthy lifestyle. Poor work-recreation balance is associated with increased risk for SHS; thus, a healthier lifestyle that maintains a work-recreation balance should be promoted in order to reduce the development of SHS or disease in southern China.


Notch Signaling Pathway in Pancreatobiliary Tumors.
Background and objectives: The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival. Materials and Methods: We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, n = 14), intrahepatic cholangiocarcinoma (iCC, n = 24), and extrahepatic cholangiocarcinoma (eCC, n = 22) cholangiocarcinomas via immunohistochemistry and ImageJ software-assisted analysis. An Immunohistochemistry (IHC)-score was determined by the percentage and intensity of stained (positive) cells (scale 0-7) and normal and malignant tissue was compared. In the IHC results, patients' (gender, age) and tumor (TNM Classification of Malignant Tumors, Union Internationale contre le Cancer (UICC) stages, grading, and lymphangitic carcinomatosa) characteristics were correlated to patient survival. Results: For eCC, the expression of CD44 (p = 0.043, IHC-score 3.94 vs. 3.54) and for iCC, the expression of CD44 (p = 0.026, IHC-score 4.04 vs. 3.48) and Notch1 (p < 0.001, IHC-score 2.87 vs. 1.78) was significantly higher in the tumor compared to non-malignant tissue. For PDAC, the expression of ADAM17 (p = 0.008, IHC-score 3.43 vs. 1.73), CD44 (p = 0.012, IHC-score 3.64 vs. 2.27), Notch1 (p = 0.012, IHC-score 2.21 vs. 0.64), and Notch4 (p = 0.008, IHC-score 2.86 vs. 0.91) was significantly higher in the tumor tissue. However, none of the analyzed Notch-signaling related components showed an association to patient survival. Conclusion: A significant overexpression of almost all studied components of the Notch signaling pathway can be found in the tumor tissue, however, without a significant influence on patient survival. Therefore, further studies are warranted to draw conclusions on Notch pathway's relevance for patient survival.


Comparative study between endoscopic ultrasonography and positron emission tomography-computed tomography in staging patients with esophageal squamous cell carcinoma.
Treatment strategy of esophageal cancer mainly depends on accurate staging. At present, no single ideal staging modality is superior to another in preoperative tumor-node-metastasis (TNM) staging of patients with esophageal cancer. We aimed to investigate the efficacy of endoscopic ultrasonography (EUS) and positron emission tomography-computed tomography (PET-CT) for staging of esophageal cancer. We retrospectively studied 118 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy with or without neoadjuvant chemoradiotherapy (CRT) over a near 3-year period between January 2005 and November 2008 at a tertiary hospital in Taiwan. Patients were separated into two groups: without neoadjuvant CRT (group 1, n= 28) and with CRT (group 2, n= 90). Medical records of demographic data and reports of EUS and PET-CT of patients before surgery were reviewed. A database of clinical staging by EUS and PET-CT was compared with one of pathological staging. The accuracies of T staging by EUS in groups 1 and 2 were 85.2% and 34.9%. The accuracies of N staging by EUS in groups 1 and 2 were 55.6% and 39.8%. The accuracies of T and N staging by means of PET-CT scan were 100% and 54.5% in group 1, and were 69.4% and 86.1% in group 2, respectively. In group 2, 38 of 90 patients (42.2%) achieved pathologic complete remission. Among them, two of 34 (5.9%) and 12 of 17 (70.6%) patients were identified as tumor-free by post-CRT EUS and PET-CT, respectively. EUS is useful for initial staging of esophageal cancer. PET-CT is a more reliable modality for monitoring treatment response and restaging. Furthermore, the accuracy of PET-CT with regard to N staging is higher in patients who have undergone CRT than those who have not.


Interferon gamma (IFN-gamma) deficiency in generalized Epstein-Barr virus infection with interstitial lymphoid and granulomatous pneumonia, focal cerebral lesions, and genital ulcers: remission following IFN-gamma substitution therapy.
A 26-year-old previously healthy woman developed granulomatous pneumonitis, encephalitis, and genital ulceration during primary Epstein-Barr virus (EBV) infection. EBV DNA was demonstrated by polymerase chain reaction analysis of serum, lung tissue, and genital ulcer specimens. Serology verified primary EBV infection. The patient lacked lymphocytes cytotoxic to autologous EBV-transformed B lymphocytes. No spontaneous or in vitro EBV-induced interferon gamma (IFN-gamma) production was evident in peripheral blood. The cells had normal IFN-gamma production when stimulated with Staphylococcus aureus exotoxin A. In the bone marrow and peripheral blood, the number of large granular CD56+ lymphocytes (natural killer cells) increased 39%-55%, but no CD4 or CD8 cell lymphocytosis was initially found. A partial clinical response was achieved with treatment with acyclovir, corticosteroids, and intravenous gamma-globulin. Because of persistent granulomatous central nervous system and lung involvement, subcutaneous IFN-gamma therapy was started but was discontinued after 3 months because of development of fever, pancytopenia, and hepatitis. This therapy initiated a complete clinical recovery, which occurred parallel to development of EBV-specific cytotoxic CD8+ T lymphocytes and normalization of natural killer cell lymphocytosis. These findings provide evidence for an EBV-induced lymphoproliferative disorder due to a T lymphocyte dysfunction associated with a selective lack of IFN-gamma synthesis.


int-2 oncogene amplification and prognosis in node-negative breast carcinoma.
The role of int-2 oncogene amplification on the prognosis of breast cancer patients was investigated in 128 patients with node-negative primary breast cancers given first-line local-regional treatments until relapse and with a median follow-up of 65 months. Tumours had been previously characterised for oestrogen (ER) and progesterone receptor (PgR) status and proliferative activity (3H-thymidine labelling index). Amplification of the int-2 oncogene occurred in 18% of cases and was significantly related to the presence of hormone receptors and to menopausal status or age, but not to proliferative status. Patients with tumours exhibiting int-2 amplification had a lower probability of disease-free survival than patients with non-amplified tumours and frequently developed local-regional recurrence. Disease-free survival analysis, adjusted for the prognostic contribution provided by tumour size, steroid receptors and proliferative rate, indicated that the association between int-2 amplification and risk of relapse was maintained and remained constant even in the presence of the other co-variates. Interestingly, int-2 amplification was a further prognostic discriminant within subsets of patients with a putatively good (i.e., tumour size <20 mm, ER+ and PgR+) or poor prognosis (i.e., high labelling index). Our exploratory study suggests that within node-negative patients, int-2 amplification could be a valuable and independent prognosticator, useful to identify patients at high risk of local-regional recurrence.


IntSplice: prediction of the splicing consequences of intronic single-nucleotide variations in the human genome.
Precise spatiotemporal regulation of splicing is mediated by splicing cis-elements on pre-mRNA. Single-nucleotide variations (SNVs) affecting intronic cis-elements possibly compromise splicing, but no efficient tool has been available to identify them. Following an effect-size analysis of each intronic nucleotide on annotated alternative splicing, we extracted 105 parameters that could affect the strength of the splicing signals. However, we could not generate reliable support vector regression models to predict the percent-splice-in (PSI) scores for normal human tissues. Next, we generated support vector machine (SVM) models using 110 parameters to directly differentiate pathogenic SNVs in the Human Gene Mutation Database and normal SNVs in the dbSNP database, and we obtained models with a sensitivity of 0.800±0.041 (mean and s.d.) and a specificity of 0.849±0.021. Our IntSplice models were more discriminating than SVM models that we generated with Shapiro-Senapathy score and MaxEntScan::score3ss. We applied IntSplice to a naturally occurring and nine artificial intronic mutations in RAPSN causing congenital myasthenic syndrome. IntSplice correctly predicted the splicing consequences for nine of the ten mutants. We created a web service program, IntSplice (http://www.med.nagoya-u.ac.jp/neurogenetics/IntSplice) to predict splicing-affecting SNVs at intronic positions from -50 to -3.


Tachyarrhythmias and catheter ablation in adult congenital heart disease.
Advances in surgical technique have had an immense impact on longevity and quality of life in patients with congenital heart disease. However, an inevitable consequence of these surgical successes is the creation of a unique patient population whose anatomy, surgical history and haemodynamics result in the development of a challenging and complex arrhythmia substrate. Furthermore, this patient group remains susceptible to the arrhythmias seen in the general adult population. It is through a thorough appreciation of the cardiac structural defect, the surgical corrective approach, and haemodynamic impact that the most effective arrhythmia care can be delivered. Catheter ablation techniques offer a highly effective management option but require a meticulous attention to the real-time integration of anatomical and electrophysiological information to identify and eliminate the culprit arrhythmia substrate. This review describes the current approach to the interventional management of patients with tachyarrhythmias in the context of congenital heart disease.


Inner Nuclear Layer Microcyst Configuration, Distribution, and Visual Prognosis in Patients With Epiretinal Membrane After Vitrectomy and Membrane Peeling.
Inner nuclear layer(INL) microcysts at central macula are a common finding in patients with epiretinal membrane (ERM) after vitrectomy and membrane peeling. Using en face mode of optical coherence tomography (OCT) angiography, patients with ERM after surgery were retrospectively reviewed to understand the configuration and distribution of microcysts as well as their impact on visual acuity. Forty-six eligible patients were enrolled and their baseline best-corrected visual acuities improved from 20/67 to 20/29 (P < 0.01) after surgery. Twenty-eight (60.9%) patients had microcysts that appeared at a median of 5 months after the surgery and persisted for mean 16 months follow-up. The microcyst appeared as spheroidal shape with length ranged from 20 to 80 μm and widths of 80 μm in average. They tend to group in cluster with a density of 245 microcysts per mm2. The frequency of microcyst distribution was 86%, 54%, 32%, 25% and 18% at the nasal, superior, inferior, temporal quadrants and central 1 mm, respectively. Linear regression analysis showed that INL microcysts at central and temporal quadrants were associated with poorer visual acuity (P = 0.02 and P = 0.01, respectively). The presence of INL microcysts in center subfield and involved wider area is a poor prognostic factor for visual outcomes.


Hierarchically Compartmentalized Supramolecular Gels through Multilevel Self-Sorting.
Hierarchical compartmentalization through the bottom-up approach is ubiquitous in living cells but remains a formidable task in synthetic systems. Here we report on hierarchically compartmentalized supramolecular gels that are spontaneously formed by multilevel self-sorting. Two types of molecular gelators are formed in situ from nonassembling building blocks and self-assemble into distinct gel fibers through a kinetic self-sorting process; interestingly, these distinct fibers further self-sort into separated microdomains, leading to microscale compartmentalized gel networks. Such spontaneously multilevel self-sorting systems provide a "bottom-up" approach toward hierarchically structured functional materials and may play a role in intracellular organization.


Regulation of mature ADAM17 by redox agents for L-selectin shedding.
L-selectin is constitutively expressed by neutrophils and plays a key role in directing these cells to sites of inflammation. Upon neutrophil activation, L-selectin is rapidly and efficiently down-regulated from the cell surface by ectodomain shedding. We have directly shown that A disintegrin and metalloprotease 17 (ADAM17) is a primary and nonredundant sheddase of L-selection by activated neutrophils in vivo. Following cell activation, intracellular signals lead to the induction of ADAM17's enzymatic activity; however, the target of this inducer mechanism remains unclear. Our study provides evidence of an activation mechanism that involves the extracellular region of the mature form of cell surface ADAM17 and not its intracellular region. We demonstrate that the catalytic activity of purified ADAM17 lacking a prodomain and its intracellular region is diminished under mild reducing conditions by DTT and enhanced by H(2)O(2) oxidation. Moreover, H(2)O(2) reversed ADAM17 inhibition by DTT. The treatment of neutrophils with H(2)O(2) also induced L-selectin shedding in an ADAM17-dependent manner. These findings suggest that thiol-disulfide conversion occurring in the extracellular region of ADAM17 may be involved in its activation. An analysis of ADAM17 revealed that within its disintegrin/cysteine-rich region are two highly conserved, vicinal cysteine sulfhydryl motifs (cysteine-X-X-cysteine), which are well-characterized targets for thiol-disulfide exchange in various other proteins. Using a cell-based ADAM17 reconstitution assay, we demonstrate that the cysteine-X-X-cysteine motifs are critical for L-selectin cleavage. Taken together, our findings suggest that reduction-oxidation modifications of cysteinyl sulfhydryl groups in mature ADAM17 may serve as a mechanism for regulating the shedding of L-selectin following neutrophil stimulation.


Melatonin ameliorates testicular damages induced by nicotine in mice.
Nicotine as a toxic substance leads to impairment of the reproductive system function. The aim of this study was to evaluate effects of melatonin on testicular alterations, sperm nuclear integrity, and epididymal sperm parameters in mice treated with nicotine. Male mice were divided into four groups. Group A received the vehicle, group B received nicotine 0.1 mg/100 g BW, group C received melatonin 10 mg/kg, group D received nicotine plus melatonin. Evaluations were made by histology and Johnson's score for study of spermatogenesis, immunostaining for study of male germ cells apoptosis, sperm chromatin dispersion (SCD) test for assaying sperm chromatin integrity, enzyme-linked immunosorbent assay (ELISA) for assessment of serum levels of testosterone and luteinizing hormone (LH), and sperm parameters including morphology, motility, and count. Nicotine caused a significant decrease in spermatogenesis quantity and Johnson's score, sperm parameters, and sex hormones. Melatonin in group D, increased sperm chromatin integrity, improved spermatogenesis, Johnson's score, and sperm parameters (P<.01) and reduced apoptosis (P <0.01) in comparison with the nicotine group. Melatonin significantly increased testosterone and halo sperms. However, its effect on the LH level was insignificant. The serum testosterone and LH levels were negatively correlated with the DNA fragmentation index (DFI) (r= -0.86, P<0.001) and (r= -0.78, P<0.001), respectively. this study showed administration of melatonin in nicotine-treated mice increases both quality and quantity of spermatogenesis and integrity of sperm's chromatin through reducing apoptosis and modifying the testosterone level.


Infection control after and during natural disaster.
We encounter many natural disasters in Japan and various infectious diseases could occur during and after natural disasters. Two recent major natural disasters, the Great East Japan Earthquake and the Kumamoto Earthquake in 2011 and 2016, respectively, killed tremendous numbers of people and many were affected with infectious diseases in evacuation centers as well as shelters for long period. Infection control teams of medical facilities inside or outside of affected areas were dispatched, supported evacuees, and made great contributions to: (i) control epidemic infectious diseases such as influenza and norovirus infection, (ii) educate and encourage people, (iii) improve environments. According to the experiences and evidence accumulated from these two disasters, it is apparent that infection control activities will definitely reduce infection during and after disasters. However, unlike the Disaster Medical Assistance Team and Japan Medical Association Team, there is no organization specialized for infection control in disaster-affected areas. A disaster infection control team should be established by leads of either of government and/or societies related to infectious diseases and infection control.


Interactive crowdsourcing to fact-check politicians.
The discourse of political leaders often contains false information that can misguide the public. Fact-checking agencies around the world try to reduce the negative influence of politicians by verifying their words. However, these agencies face a problem of scalability and require innovative solutions to deal with their growing amount of work. While the previous studies have shown that crowdsourcing is a promising approach to fact-check news in a scalable manner, it remains unclear whether crowdsourced judgements are useful to verify the speech of politicians. This article fills that gap by studying the effect of social influence on the accuracy of collective judgements about the veracity of political speech. In this work, we performed two experiments (Study 1: N = 180; Study 2: N = 240) where participants judged the veracity of 20 politically balanced phrases. Then, they were exposed to social information from politically homogeneous or heterogeneous participants. Finally, they provided revised individual judgements. We found that only heterogeneous social influence increased the accuracy of participants compared to a control condition. Overall, our results uncover the effect of social influence on the accuracy of collective judgements about the veracity of political speech and show how interactive crowdsourcing strategies can help fact-checking agencies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Spread of virus and distribution of latent infection following ocular herpes simplex in the non-immune and immune mouse.
In both non-immune and immune mice infected with herpes simplex virus the incidence of latent infection of the trigeminal ganglion was related to the severity of ocular virus infection. During primary infection, virus was shown to travel via the ophthalmic part of the ganglion to reach the brainstem, from where centrifugal spread resulted in latent infection of neurones in the trigeminal ganglion which did not serve the site of inoculation. Primary infection also resulted in latent infection of the superior cervical ganglion. Shedding of virus occurred rarely in the tears of animals which had recovered from primary disease. In immune mice, spread of virus resulted in a much lower incidence of latent infection and that occurred only in ophthalmic neurones.


Optimal nutrition: vitamin A and the carotenoids.
There are two major dietary sources of vitamin A: easily absorbed retinyl palmitate in foods of animal origin, and poorly bioavailable carotenoids from plant foods. Plasma retinol is tightly controlled, probably by regulation of retinol-binding protein (RBP) formation in the liver, and only hormonal factors (e.g. oral contraceptives) and infection will alter the homeostasis. Delivery of retinol to the tissues is facilitated by the RBP-retinol complex; however, there is evidence that this mechanism can be bypassed when very high doses of vitamin A are given. Some retinyl ester may be released to tissues from chylomicrons when the latter bind to tissue lipoprotein receptors during their passage from the gut to the liver following a meal. High-dose vitamin A therapy is a means of rapidly improving vitamin A status in persons with sub-optimal vitamin A nutrition but there are dangers of toxic symptoms (e.g. teratogenicity) from excess vitamin A usage. Evidence is presented to suggest that the plasma retinol: RBP may be a guide to optimal vitamin A status, since values less than one frequently occur in less-developed countries and during infection. In contrast to plasma retinol, plasma carotenoids reflect the dietary intake of plant foods. However, absorption is limited by poor bioavailability and a saturable uptake mechanism in competition with other phytochemicals. Recent work on bioavailability suggests that the calculation of plant food vitamin A activity should be re-examined. Illness has little influence on plasma levels except by suppressing appetite. Carotenoids are generally regarded as non-toxic yet intervention studies with beta-carotene in smokers have been associated with increased lung cancer and heart disease. Some carotenoids are important as vitamin A precursors, but the physiological importance of their antioxidant properties is not known and consequently the amount needed for optimal nutrition is uncertain.


Colloidal PbS nanoplatelets synthesized via cation exchange for electronic applications.
In this work, we present a new synthetic approach to colloidal PbS nanoplatelets (NPLs) utilizing a cation exchange (CE) strategy starting from CuS NPLs synthesized via the hot-injection method. Whereas the thickness of the resulting CuS NPLs was fixed at approx. 5 nm, the lateral size could be tuned by varying the reaction conditions, such as time from 6 to 16 h, the reaction temperature (120 °C, 140 °C), and the amount of copper precursor. In a second step, Cu+ cations were replaced with Pb2+ ions within the crystal lattice via CE. While the shape and the size of parental CuS platelets were preserved, the crystal structure was rearranged from hexagonal covellite to PbS galena, accompanied by the fragmentation of the monocrystalline phase into polycrystalline one. Afterwards a halide mediated ligand exchange (LE) was carried out in order to remove insulating oleic acid residues from the PbS NPL surface and to form stable dispersions in polar organic solvents enabling thin-film fabrication. Both CE and LE processes were monitored by several characterization techniques. Furthermore, we measured the electrical conductivity of the resulting PbS NPL-based films before and after LE and compared the processing in ambient to inert atmosphere. Finally, we fabricated field-effect transistors with an on/off ratio of up to 60 and linear charge carrier mobility for holes of 0.02 cm2 V-1 s-1.


Understanding medulloblastoma.
Brain tumors are the most common solid tumor malignancies in childhood, and among them, medulloblastoma occurs with the greatest frequency. Because medulloblastomas occur in the posterior fossa, the presenting symptoms often are vague complaints and diagnosis may be delayed. Between 70% and 80% of patients who are diagnosed before metastatic dissemination survive, compared with 30% to 40% of those in higher risk groups. This article reviews the diagnosis, treatment, and prognosis for medulloblastoma.


Costs of medications used to treat inflammatory bowel disease.
Inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases causing a lifelong burden and often need sustained treatment throughout a patient's life. Both the incidence and prevalence of IBD has increased in the last decade. Evidence showing the drug costs to IBD patients in Finland is limited. No earlier study has evaluated the drug costs of IBD patients in Finland. Here, we thoroughly assessed these costs. A structured questionnaire, hospital records and national registers were combined to comprehensively assess the actual costs of drug purchases made by IBD patients. The study sample comprised 561 patients. Total annual mean drug costs were 1428€ per patient. CD patients had higher annual costs than UC patients at 2369€ and 902€, respectively. CD patients also had higher costs in the immunosuppressant, corticosteroid, and biologic subgroup analyses. In addition, C-reactive protein, serum albumin and fecal calprotectin levels had a correlation with costs if the patient had needed corticosteroids. In addition, women reported having a worse quality of life (QoL) but had lower total costs. Pharmaceutical drugs are major factors that affect the costs of IBD treatment, and the increased use of biologics has raised these costs.


Memorialization Practices Are Changing: An Industry Perspective on Improving Service Outcomes for the Bereaved.
Although considerable research efforts have focused on bereavement outcomes following loss, there are few studies which address the role of memorialization, particularly as it relates to formal service provision. Currently the funeral, cemetery, and crematorium industries are observing a steady decline in traditional and formal memorialization practices. This study aims to identify current memorialization practices and emerging trends, highlight key priorities for improving service outcomes for the bereaved, and understand the implications of changing consumer preferences for service provision. The study's qualitative research design incorporates two phases, a scoping literature review followed by in-depth interviews with eight service providers from the funeral, cemetery, and crematorium industries. A key finding is that the trend toward contemporary and informal memorialization practices blurs the lines between the role of consumers and service providers. There is a clear opportunity for service providers to engage in community education as a means of building supportive relationships with and improving service outcomes for the bereaved.


Assessment of the Factors Influencing the Recording Performance of Circumneural Electrodes.
The quality of recorded peripheral nerve signals is decisive for their application in therapies. The electroneurogram can be recorded via implantable circumeural electrodes that are wrapped around the peripheral nerve. The shape and amplitude of the signal recorded by the electrode are influenced by the design and contact configuration of the electrode. In this paper, the impact of the number of contacts, contact size and electrical insulation to the outside is investigated to predict the single fiber action potential based on the measured impedance data.


Fish scales and SNP chips: SNP genotyping and allele frequency estimation in individual and pooled DNA from historical samples of Atlantic salmon (Salmo salar).
DNA extracted from historical samples is an important resource for understanding genetic consequences of anthropogenic influences and long-term environmental change. However, such samples generally yield DNA of a lower amount and quality, and the extent to which DNA degradation affects SNP genotyping success and allele frequency estimation is not well understood. We conducted high density SNP genotyping and allele frequency estimation in both individual DNA samples and pooled DNA samples extracted from dried Atlantic salmon (Salmo salar) scales stored at room temperature for up to 35 years, and assessed genotyping success, repeatability and accuracy of allele frequency estimation using a high density SNP genotyping array. In individual DNA samples, genotyping success and repeatability was very high (> 0.973 and > 0.998, respectively) in samples stored for up to 35 years; both increased with the proportion of DNA of fragment size > 1000 bp. In pooled DNA samples, allele frequency estimation was highly repeatable (Repeatability = 0.986) and highly correlated with empirical allele frequency measures (Mean Adjusted R2 = 0.991); allele frequency could be accurately estimated in > 95% of pooled DNA samples with a reference group of at least 30 individuals. SNPs located in polyploid regions of the genome were more sensitive to DNA degradation: older samples had lower genotyping success at these loci, and a larger reference panel of individuals was required to accurately estimate allele frequencies. SNP genotyping was highly successful in degraded DNA samples, paving the way for the use of degraded samples in SNP genotyping projects. DNA pooling provides the potential for large scale population genetic studies with fewer assays, provided enough reference individuals are also genotyped and DNA quality is properly assessed beforehand. We provide recommendations for future studies intending to conduct high-throughput SNP genotyping and allele frequency estimation in historical samples.


Hydration assessment techniques.
Water in the human body is essential for metabolism, temperature regulation, and numerous other physiological processes that are consistent with good health. Accurate, precise, and reliable methods to assess body fluid compartments are needed. This review describes the hydration assessment techniques of isotope dilution, neutron activation analysis, bioelectrical impedance, body mass change, thirst, tracer appearance, hematologic indices, and urinary markers. It also provides guidance for selecting techniques that are appropriate for use with unique individuals and situations.


Task Partitioning in Insect Societies. II. Use of Queueing Delay Information in Recruitment.
The collection and handling of colony resources such as food, water, and nest-construction material is often divided into subtasks in which the material is passed from one worker to another. This is known as task partitioning. If tasks are partitioned with direct transfer of material between foragers and receivers, queueing delays can occur as individuals search or wait for a transfer partner. Changes in environmental conditions and relative number of foragers and receivers affect these delays as well as colony ergonomic efficiency. These delays are used in recruitment in both honeybees and Polybia wasps. This study investigates the distribution of queueing delays and the information content and quality of those delays using a stochastic-simulation model. Information quality increases with colony size. When the relative proportions of foragers and receivers are suboptimal, the group in excess has better information. Individuals can increase information quality of delays by two mechanisms: averaging over consecutive trips and averaging over multiple transfers within a trip where direct transfer occurs. We suggest that multiple transfer occurs in the honeybee in order to improve information quality.


Proteomic temporal profile of human brain endothelium after oxidative stress.
because brain endothelial cells exist at the neurovascular interface, they may serve as cellular reporters of brain dysfunction by releasing biomarkers into the circulation. we used proteomic techniques to screen conditioned media from human brain endothelial cultures subjected to oxidative stress induced by nitric oxide over 24 hours. Plasma samples from human stroke patients were analyzed by enzyme-linked immunosorbent assay. in healthy endothelial cells, interaction mapping demonstrated cross-talk involving secreted factors, membrane receptors, and matrix components. In oxidatively challenged endothelial cells, networks of interacting proteins failed to emerge. Instead, inflammatory markers increased, secreted factors oscillated over time, and endothelial injury repair was manifested as changes in factors related to matrix integrity. Elevated inflammatory markers included heat shock protein, chemokine ligand-1, serum amyloid-A1, annexin-A5, and thrombospondin-1. Neurotrophic factors (prosaposin, nucleobindin-1, and tachykinin precursors) peaked at 12 hours, then rapidly decreased by 24 hours. Basement membrane components (fibronectin, desomoglein, profiling-1) were decreased. Cytoskeletal markers (actin, vimentin, nidogen, and filamin B) increased over time. From this initial analysis, the high-ranking candidate thrombospondin-1 was further explored in human plasma. Acute ischemic stroke patients had significantly higher thrombospondin-1 levels within 8 hours of symptom onset compared to controls with similar clinical risk factors (659 ± 81 vs 1132 ± 98 ng/mL; P<0.05; n=20). screening of simplified cell culture systems may aid the discovery of novel biomarkers in clinical neurovascular injury. Further collaborative efforts are warranted to discover and validate more candidates of interest.


Loss of photosynthetic efficiency in the shade. An Achilles heel for the dense modern stands of our most productive C4 crops?
The wild progenitors of major C4 crops grew as individuals subjected to little shading. Today they are grown in dense stands where most leaves are shaded. Do they maintain photosynthetic efficiency in these low light conditions produced by modern cultivation? The apparent maximum quantum yield of CO2 assimilation (ΦCO2max,app), a key determinant of light-limited photosynthesis, has not been systematically studied in field stands of C4 crops. ΦCO2max,app was derived from the initial slope of the response of leaf CO2 uptake (A) to photon flux (Q). Leaf fractional light absorptance (α) was measured to determine the absolute maximum quantum yield of CO2 assimilation on an absorbed light basis (ΦCO2max,abs). Light response curves were determined on sun and shade leaves of 49 field plants of Miscanthus × giganteus and Zea mays following canopy closure. ΦCO2max,app and ΦCO2max,abs declined significantly by 15-27% (P<0.05) with canopy depth. Experimentally, leaf age was shown unlikely to cause this loss. Modeling canopy CO2 assimilation over diurnal courses suggested that the observed decline in ΦCO2max,app with canopy depth costs 10% of potential carbon gain. Overcoming this limitation could substantially increase the productivity of major C4 crops.