Receptive field size of human motion detection units.
Receptive field sizes of motion detector units in the human visual system were determined using a summation technique. Contrast sensitivity was measured for detecting the direction of motion of a drifting (8 Hz) sinewave grating (0.01-30.0 c/deg) multiplied by a stationary Gaussian envelope, for various widths of the Gaussian envelope. For each test spatial frequency, sensitivity increased linearly with aperture width up to a certain limit, and thereafter at a rate consistent with a model incorporating probability summation over space and between channels. The limit of linear summation designates the limit of the receptive field. Results show that the receptive field size varies with spatial frequency, from 2' arc at high spatial frequencies to as large as 7 deg at low frequencies. The change in field size was progressive. The smallest aperture width (delta W) for directional discrimination was also measured. Results show delta W to vary from 0.03 cycles at low spatial frequencies to 0.30 cycles at high frequencies.


Adsorption of catechin onto cellulose and its mechanism study: Kinetic models, characterization and molecular simulation.
Catechin, an important component of flavan-3-ol, and dietary fiber are both important ingredients with many associated health benefits. The adsorption of catechin onto various dietary fiber has been studied widely, most of the researches focus on the adsorption capacities of catechin under different fibers and the adsorption types by using adsorption models. However, little is known on the dynamic adsorption process and mechanism, including the adsorption sites, interaction types, and participant molecules. In this study, the adsorption behavior and mechanism of catechin onto cellulose were examined by the time function in combination with molecular simulation. The adsorption capacities of cellulose for catechin were 2.70 and 2.82 mg/g at pH 2.0 and 7.0, respectively. The adsorption process was fitted by three stage models (rapid adsorption, saturation, and equilibrium). The features of cellulose and catechin were characterized by FTIR to identify the functional groups in the adsorption. Molecular simulation revealed that the catechin was adsorbed onto the hydrophilic surface of cellulose rather than hydrophobic one, and that the total binding energy was -8.57 kcal/mol of the hydrophilic surface, which was due to Van der Waals' force and H-bond more than electrostatic force. Furthermore, the studies on isothermal adsorption combined with adsorption at various pH illustrated the main interaction between cellulose and catechin for the binding. This work assisted understanding of the adsorption of polyphenols on to insoluble dietary fiber and has the potential of applications in functional foods.


The National Poisons Information Service and hospital admissions for children--the experience in Wales of the Cardiff Centre.
When inquiries to the Cardiff Centre of the National Poisons Information Service were compared with hospital admissions in the eight health authorities in Wales the findings suggested fewer admissions in the area within which the centre is situated and showed a more extensive use in that area than elsewhere. High inquiry rates were associated with high hospital admission rates when the eight areas were compared. If the service were delegated to area level a more complete community use would result.


Dark current reduction in microjunction-based double electron barrier type-II InAs/InAsSb superlattice long-wavelength infrared photodetectors.
Microjunction InAs/InAs1-xSbx type-II superlattice-based long-wavelength infrared photodetectors with reduced dark current density were demonstrated. A double electron barrier design was employed to reduce both bulk and surface dark currents. The photodetectors exhibited low surface leakage after passivation with SiO2, allowing the use of very small size features without degradation of the dark current. Fabricating microjunction photodetectors (25 × 25 µm2 diodes with 10 × 10 µm2 microjunctions) in combination with the double electron barrier design results in a dark current density of 6.3 × 10-6 A/cm2 at 77 K. The device has an 8 µm cut-off wavelength at 77 K and exhibits a quantum efficiency of 31% for a 2 µm-thick absorption region, which results in a specific detectivity value of 1.2 × 1012 cm·Hz1/2/W.


Real-world efficacy and safety of eribulin in advanced and pretreated HER2-negative breast cancer in a Spanish comprehensive cancer center.
Eribulin improves survival in pre-treated HER2-negative advanced breast cancer (ABC). However, limited data exist on co-morbidities and central nervous system (CNS) efficacy. The purpose of this study was to review eribulin's efficacy and safety in everyday clinical practice with special focus on age, body mass index (BMI) and central nervous system (CNS) activity. An observational study was conducted in a series of HER2-negative ABC patients treated from January'14-December'17 outside a clinical trial. Objective Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS), and association of clinical and pathological variables with outcome were evaluated. Ninety-five women were treated with at least one cycle of eribulin. Median age was 57 (33-83), and 18% were obese. Median number of prior chemotherapies for ABC was 3 (2-5) and 76% of patients had visceral metastases, including 21% with CNS involvement. Most tumors were estrogen receptor-positive (79%). ORR and stable disease (SD) at 6 months were 26.2 and 37.5%, respectively. Remarkably, relevant CNS efficacy was observed with eribulin: 20% of patients obtained partial response and 25% SD. Treatment was generally well tolerated and manageable, with 29% grade 3 and 10.9% grade 4 toxicities. Median PFS and OS were 4.1 months (CI95% 3.2-4.9) and 11.1 months (CI95% 9.5-14.7), respectively. Triple-negative disease, > 2organs involved and being younger than 70 years old were independent prognosis factors for worse OS in multivariate analysis. Most patients (75%) progressed in pre-existing metastases sites. In everyday clinical practice, eribulin's efficacy seems similar to pivotal trials. CNS-efficacy was observed. TNBC, > 2 organs involved and being younger than 70 years old were independent prognosis factors for worse OS. Remarkably, less incidence of grade 4-toxicity compared to previous studies was found.


Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension.
Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity and cardiovascular parameters. A total of 21 consecutive patients with refractory hypertension (daytime ambulatory blood pressure (BP)≥150/100 mmHg despite the use of 3 or more antihypertensive drugs), no evidence for secondary hypertension and normal renovascular anatomy were included. RSD was performed with the Medtronic Symplicity renal denervation catheter with an average of 4.2 (range 3-6) ablations per renal artery. To assess cardiac sympathetic activity, 123I-mIBG cardiac scintigraphy was performed before and 6 weeks after. In addition, the effect of RSD on peripheral BP and cardiac hemodynamics were assessed non-invasively. 123I-mIBG uptake before and after RSD was 1.7±0.4% vs. 1.7±0.5% at 15 min. and 1.4±0.4% vs. 1.5±0.5% after 4 h. As a consequence, washout rate was similar before (33.7±11.7%) and after RSD (30.1±12.6%, p=0.27). In line with earlier RSD studies, a significant drop in systolic office BP (-12.2 mmHg, p=0.04) was detected, whereas the decrease in ambulatory BP was not significant. No changes were seen in heart rate, stroke volume or left ventricular contractility, both in supine position and after standing. In concert with previous reports, RSD leads to a significant drop in office BP. However, a reduction in sympathetic activity could not be demonstrated on a cardiac level.


Live attenuated Salmonella enterica serovar Choleraesuis vector delivering a conserved surface protein enolase induces high and broad protection against Streptococcus suis serotypes 2, 7, and 9 in mice.
Streptococcus suis, a major zoonotic pathogen in swine, can be classified into 35 serotypes. However, no universal vaccine against the multiple serotypes of S. suis is available, though some studies have shown homologous protection. Hence, developing an effective universal vaccine to protect pigs against multiple S. suis serotypes is necessary, or at the very least, to protect pigs against diseases caused by the dominant pathogenic serotypes. Enolase, a highly conserved surface protein, is present in all of the described S. suis serotypes. rSC0016 is an improved recombinant attenuated S. Choleraesuis vaccine vector, combining a sopB mutation with regulated delayed systems, achieving an adequate balance between host safety and immunogenicity. In order to develop a universal vaccine against the multiple serotypes of S. suis, a novel recombinant vaccine strain rSC0016 that carries a heterologous antigen enolase was developed in this study. According, it was found that the recombinant vaccine strain rSC0016(pS-Enolase) exhibited better colonization compared to the vaccine control strain rSC0018(pYA3493). In addition, a mouse model immunized with the strain rSC0016(pS-Enolase) elicited significant IgG antibody responses against both enolase and Salmonella antigens, while inducing good mucosal, humoral, and cellular immune responses against enolase. Finally, immunization with rSC0016(pS-Enolase) was shown to confer 100%, 80%, and 100% protection against the serotypes of SS2, SS7, and SS9, respectively, and significantly reduced histopathological lesions in mice. Overall, this study provides a promising universal vaccine candidate for use against the multiple serotypes of S. suis.


The effects of natural enemies, competition, and host plant water availability on an aphid population.
I used a factorial experiment repeated in two years to assess the relative effects of natural enemy attack, interspecific competition, and water availability to the host plant, and of interactions among these factors, on the population dynamics of the aphid Aphis varians feeding on fireweed (Epilobium angustifolium). The impact of a suite of coccinellid and syrphid predators emerged as the predominant factor affecting the success of aphid colonies: colonies protected from natural enemies grew in size at a rate of ten percent per day, were only one tenth as likely to go extinct, and produced over ten times more dispersing alates. In contrast, I found only minor effects of removing flea beetles, the most abundant herbivore with which A. varians colonies cohabit fireweed stems, and of supplementing water availability to fireweed host plants, in spite of a significant effect of watering frequency on aphid growth in the green-house. There was no evidence of significant two- or three-way interactions among factors. Hence, despite the potential complexity of the food web in which it is embedded, the dynamics of A. varians appears to be driven predominantly by a single factor, i.e. interactions with natural enemies.


Synthesis of new Mannich bases of arylpyridazinones as analgesic and anti-inflammatory agents.
A series of 2-[[4-(substituted-phenyl/ benzyl)-1-piperazinyllmethyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone derivatives was prepared and examined for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and 1H-NMR spectra and elementary analysis. Among the compounds prepared, 2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone IVe was found to be a most promising analgesic and anti-inflammatory agent. Compound IVe showed more potent analgesic activity than acetylsalicyclic acid in the phenylbenzoquinone-induced writhing test. Also IVe showed anti-inflammatory activity comparable to that of the standard compound indometacin against the carrageenan-induced paw edema. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed a gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. On the basis of the available data, the structure-activity relationship of the series of 2-[[4-(substituted-phenyl/benzyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H) pyridazinones is also discussed.


The meaning of menorrhagia: an investigation into the association between the complaint of menorrhagia and depression.
Although it is generally assumed that the complaint of menorrhagia indicates gynaecological pathology, there is evidence to suggest that it can also be a manifestation of psychological disturbance. In order to investigate this hypothesis 50 women with this complaint were assessed by means of a semi-structured interview, General Health Questionnaire (GHQ) and Eysenck Personality Questionnaire (EPQ), and blood investigations (haemoglobin and serum iron). The main finding was that 31/50 women had positive GHQ screening (GHQ+) and features consistent with mild to moderate depression. The tendency for the GHQ+ women to have evidence of less severe menstrual bleeding and greater psychological vulnerability is consistent with the original hypothesis and implies that further research in this area is warranted.


Adriamycin downregulates the expression of KLF4 in cardiomyocytes in vitro and contributes to impaired cardiac energy metabolism in Adriamycin-induced cardiomyopathy.
Adriamycin is a well-known anthracycline chemotherapeutic agent widely used in treating a variety of malignancies. However, Adriamycin's clinical use is limited due to its adverse side-effects, most importantly cardiomyopathy. Adriamycin-induced cardiotoxicity reportedly includes mitochondrial dysfunction. We hypothesize that modulation of KLF4, a key regulator of cardiac mitochondrial homeostasis might play a role in the development of Adriamycin-induced cardiomyopathy. Therefore, in the current work, we evaluated the interaction of Adriamycin with KLF4 and its subsequent downstream targets. Molecular docking revealed that Adriamycin interacts strongly with KLF4 at residues Thr 448, Arg 452, Ser 444 falls within C2H2 motif which is the active site. Quantitative real-time PCR also revealed that KLF4 is downregulated by Adriamycin in cardiomyocytes in vitro. The expression of KLF4 is downregulated in a dose-dependent manner, with a 0.12 ± 0.09-fold (p ≤ 0.05, n = 3) downregulation at a low dosage and 0.21 ± 0.02-fold (p ≤ 0.05, n = 3) downregulation at high dosage. Deficiency of KLF4 leads to an impairment of PPARγ that consequently supresses the proteins/enzymes involved in the fatty acid metabolism. Adriamycin-mediated suppression of KLF4 also affected the expression of PPARα in vitro. PPARα dysfunction is likely to cause defects in β-oxidation which ultimately results in impaired ATP synthesis. Cardiac cells are thus forced to switch over the substrate from free fatty acid to glucose. Moreover, Adriamycin elevates the expression of PPARβ due to downregulation of KLF4 leads to increased myocardial glucose utilization. Thus, a change in substrate preference affects the flexibility of metabolic network culminating in diminished energy production and other regulatory activities, altogether contributing to the development of cardiomyopathy. Thus, we conclude that the effect of Adriamycin on KLF4 disrupts mitochondrial homeostasis and lipid/glucose homeostasis resulting in a reduction of ATP synthesis which ultimately results in dilated cardiomyopathy.


Molecular cloning and characterization of an endo-1,3-beta-D-glucanase from the mollusk Spisula sachalinensis.
cDNA encoding the endo-1,3-beta-d-glucanase from Spisula sachalinensis (LIV) was amplified by PCR using oligonucleotides deduced from the N-terminal end peptide sequence. Predicted enzyme structure consists of 444 amino acids with a signal sequence. The mature enzyme has 316 amino acids and its deduced amino acid sequence coincides completely with the N-terminal end (38 amino acids) of the beta-1,3-glucanase (LIV) isolated from the mollusk. The enzyme sequence from Val 121 to Met 441 reveals closest homology with Pacifastacus leniusculus lipopolysaccharide- and beta-1,3-glucan-binding protein and with coelomic cytolytic factors from Lumbricus terrestris. The mollusk glucanase also shows 36% identity and 56% similarity with beta-1,3-glucanase of the sea urchin Strongylocentrotus purpuratus. It is generally considered that invertebrate glucanase-like proteins containing the bacterial glucanase motif have evolved from an ancient beta-1,3-glucanase gene, but most of them lost their glucanase activity in the course of evolution and retained only the glucan-binding activity. A more detailed evaluation of the protein folding elicited very interesting relationships between the active site of LIV and other enzymes, which hydrolyze native glucans.


Microvascular disturbances and edema formation after repetitive ischemia of gerbil brain.
Three transient episodes of 5 min ischemia spaced at 1-h intervals were produced in Mongolian gerbils by bilateral carotid artery occlusion with an implanted vascular occlusion device. The interval of 1 h was chosen to allow for the development of post-ischemic hypoperfusion between the ischemic episodes. Three minutes and 1 h after each ischemic episode, and 6 and 24 h after the third occlusion, Evan's blue (EB) was injected intravenously to trace circulating blood, and the number of perfused capillaries was determined in various brain regions by fluorescence microscopy. Brain edema was evaluated by measuring specific gravity in tissue samples taken from adjacent areas. Repetitive ischemia caused progressively increasing brain edema and a progressive reduction of the number of perfused capillaries. Immediately after each ischemic episode, transient recruitment of capillaries occurred, thus excluding no-reflow as a main pathogenetic factor of microcirculatory disturbances. The pattern of microcirculation 6 and 24 h after the last occlusion revealed a redistribution of circulating blood, characterized by a reduction in the number of EB-filled capillaries associated with a noticeable dilatation of the larger vascular channels. Our studies suggest a close interrelationship between post-ischemic microcirculatory hypoperfusion and the development of brain edema, the degree and extent of which progresses with the repetition of ischemic episodes when they are carried out during the periods of hypoperfusion.


A comparative study on schizophrenia diagnosed by ICD-9 and DSM-III: course, family history and stability of diagnosis.
Data from the Taipei Center of the International Pilot Study of Schizophrenia were reanalyzed using the ICD-9 and DSM-III diagnoses at 7-year follow-up. Patients diagnosed as schizophrenic according to DSM-III were shown to be a more homogeneous group in terms of their clinical manifestations, social functions and family psychiatric history than those defined as schizophrenic by ICD-9. The discordant cases of ICD-9 schizophrenia and DSM-III affective disorders were found to be different from the concordant schizophrenic group, but similar to the concordant group of affective disorders diagnosed by ICD-9 and DSM-III. Thirty-five per cent of mood-incongruent psychotic major depressive disorders defined by DSM-III at initial evaluation were diagnosed as schizophrenia at 7-year follow-up.


Enhancing radium solubilization in soils by citrate, EDTA, and EDDS chelating amendments.
The effect of three chelating agents (citrate, EDTA, and EDDS) on the solubilization of radium from a granitic soil was studied systematically, considering different soil pH values, chelating agent concentrations, and leaching times. For all the chelating agents tested, the amount of radium leached proved to be strongly dependent on the pH of the substrate: only for acidic conditions did the amount of radium released increase significantly relative to the controls. Under the best conditions, the radium released from the amended soil was greater by factors of 20 in the case of citrate, 18 for EDTA, and 14 for EDDS. The greatest improvement in the release of radium was obtained for the citrate amendment at the highest concentration tested (50 mmol kg(-1)). A slightly lower amount of radium was leached with EDTA at 5 mmol kg(-1) soil, but the solubilization over time was very different from that observed with citrate or EDDS. With EDTA, a maximum in radium leaching was reached on the first day after amendment, while with citrate, the maximum was attained on the fourth day. With EDDS, radium leaching increased slightly but steadily with time (until the sixth day), but the net effect for the period tested was the lowest of the three reagents.


Hearing Preservation Outcomes With Standard Length Electrodes in Adult Cochlear Implantation and the Uptake of Electroacoustic Stimulation.
Cochlear implantation with preservation of residual low-frequency hearing enables patients to utilize acoustic and electrical stimulation. It is widely accepted that preservation of residual low-frequency hearing is beneficial in both background noise and for music appreciation. The extent to which patients may benefit is not fully understood, but the importance of these concepts is reflected in electrode design developments and also refinement of surgical technique. Greater understanding is needed around factors that may affect hearing preservation. This study reports experience in adults using standard length cochlear implant arrays. The study reviews hearing preservation outcomes using the HEARRING GROUP method for factors such as gender, electrode type, insertion depth, laterality, preoperative hearing level, and time between surgery and audiogram. Furthermore, the study reviews rates of electroacoustic stimulation use in those with postoperative functional residual low-frequency hearing. Retrospective case series. preoperative ≤ 85 dB HL at 250 Hz and aged ≥ 18 years. The hearing preservation percentages were calculated using the HEARRING group formula S=[1 - ((PTApost - PTApre)/(PTAmax - PTApre))*100]%. Preservation of > 75% was considered complete, 25 to 75% partial, and 1 to 25% minimal. Standardized operative technique with facial recess approach, posterior tympanotomy, and minimally traumatic round window insertion was performed for each implant. Fifty-three implantations in 52 patients met the inclusion criteria. The mean age at implantation was 55.5 years. The average time since the last audiogram was 10 months. The mean average total pre and postoperative pure-tone averages were 92.4 dB, 99.2 dB, respectively, using minimum reporting standards for adult cochlear Implant (CI). Thirty percent demonstrated complete hearing preservation, 35.8% partial hearing preservation, and 20.8% minimal hearing preservation. Overall, mean hearing preservation was 52.9%. Sex, age at implantation, insertion depth, lateral versus perimodiolar electrode, and preoperative hearing level did not statistically significantly affect rates of hearing preservation in our study. There was a statistically significant deterioration in hearing preservation outcomes difference at 3 months compared with 12 months postoperatively. Only two patients within our study out of 17 with functional postoperative hearing went on to use electroacoustic stimulation. Hearing preservation varies between patients and postoperative outcomes are difficult to predict. This study adds to existing literature in terms of likelihood of hearing preservation following cochlear implantation. In turn, this improves our ability to counsel patients as to the chances of preserving residual low-frequency hearing postoperatively and their ability to use electroacoustic stimulation.


Cimetidine enhances cisplatin toxicity in mice.
The combination of the histamine H2 antagonist cimetidine (CMT) and the anticancer agent cisplatin (CDDP) was studied in normal and tumorbearing mice. CMT doses of 100 mg/kg produced no alteration in the survival of DBA/2J mice bearing P388 leukemia treated with CDDP doses of 3 mg/kg or 6 mg/kg. In these groups, the median survival was 13 days and 16 days, respectively, compared to 10 days in untreated controls. However, when adult CD-1 mice were given higher but nonlethal CDDP doses of 10, 15, or 18 mg/kg, the addition of CMT significantly increased CDDP lethality (P less than 0.05 by Wilcoxon analysis). For the 3 groups, CMT-enhanced lethality occurred in 10% of mice given 10 mg/kg CDDP, 80% of mice given 15 mg/kg, and 100% of mice given 18 mg/kg CDDP. Thus, CMT can acutely alter CDDP toxicity without affecting antitumor efficacy in mice.


Developmental capacity is unevenly distributed among single blastomeres of 2-cell and 4-cell stage mouse embryos.
During preimplantation development, mammalian embryo cells (blastomeres) cleave, gradually losing their potencies and differentiating into three primary cell lineages: epiblast (EPI), trophectoderm (TE), and primitive endoderm (PE). The exact moment at which cells begin to vary in their potency for multilineage differentiation still remains unknown. We sought to answer the question of whether single cells isolated from 2- and 4-cell embryos differ in their ability to generate the progenitors and cells of blastocyst lineages. We revealed that twins were often able to develop into blastocysts containing inner cell masses (ICMs) with PE and EPI cells. Despite their capacity to create a blastocyst, the twins differed in their ability to produce EPI, PE, and TE cell lineages. In contrast, quadruplets rarely formed normal blastocysts, but instead developed into blastocysts with ICMs composed of only one cell lineage or completely devoid of an ICM altogether. We also showed that quadruplets have unequal capacities to differentiate into TE, PE, and EPI lineages. These findings could explain the difficulty of creating monozygotic twins and quadruplets from 2- and 4-cell stage mouse embryos.


Disseminated Ureaplasma polyarthritis in a renal transplant recipient.
The risk of infection following kidney transplant increases substantially in the setting of hypogammaglobulinemia and T-cell-depleting therapy. Ureaplasma has been described to cause invasive disease in immunocompromised hosts with humoral immunodeficiency. We describe a kidney transplant recipient with history of antineutrophil cytoplasmic autoantibody (ANCA) vasculitis remotely treated with rituximab who developed Ureaplasma polyarthritis following transplant. The purpose of this report is to highlight the unique risks that kidney transplant patients face particularly if hypogammaglobulinemic. Patient is a 16-year-old female with history of granulomatosis with polyangiitis (GPA) treated with maintenance dose of rituximab 13 months prior to transplant. Patient underwent deceased donor kidney transplant with thymoglobulin induction. IgG was 332 mg/dL and CD20 was zero at the time of transplant. One month posttransplant, the patient developed polyarticular arthritis without fever, pyuria, or evidence of GPA reactivation. MRI had diffuse tenosynovitis, myositis, fasciitis, cellulitis, and effusions of three involved joints. Bacterial, fungal, and AFB cultures remained negative, but 16 s ribosomal PCR testing from joint aspirates detected Ureaplasma parvum. The patient was treated with levofloxacin for 12 weeks with the resolution of symptoms. Ureaplasma infection is an under-recognized pathogen in kidney transplant patients. A high index of clinical suspicion should be employed to identify Ureaplasma infection, especially in those with secondary hypogammaglobulinemia, as this is often missed due to its lack of growth on standard media and the need for molecular testing. In patients with prior B-cell depletion, routine monitoring for B-cell recovery to identify risk factors for opportunistic infections is indicated.


SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1.
Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.


Growth factor production by polytetrafluoroethylene vascular grafts.
In earlier studies, we have shown that porous (60 micron internodal distance) PTFE grafts develop a complete endothelial layer 2 weeks after being implanted in baboons. Subsequently, the intima of the graft thickens on account of SMC proliferation only where an overlying endothelial layer is present. SMCs in normal endothelialized artery proximal and distal to the graft show no detectable proliferation. The purpose of this study was to investigate the possibility that growth factors released from the graft endothelium or SMCs regulate SMC proliferation. PTFE grafts (4 mm I.D., 60 micron internodal distance) were placed in the aortoiliac circulation of baboons and removed at 2 weeks. The grafts were perfused ex vivo with tissue culture medium (Ham's F12 + 25 mmol/L HEPES and 2% calf plasma-derived serum) at 2.5 ml/hr for 5 hours. Perfused native carotid, aorta, and femoral arteries served as controls. After this period of perfusion, graft and arterial endothelium was intact as shown by scanning electron microscopy. The mitogenic activity (thymidine incorporation) of the perfusates was measured in an assay with quiescent 3T3 cells and baboon aortic SMCs and corrected for the surface area of the perfused vessels. These studies demonstrated markedly increased mitogenic activity in the perfusates of grafts compared with perfusates of native vessels. These results provide support for the hypothesis that the vascular wall cells in healing grafts can produce factors that regulate smooth muscle cell growth.


Relationship between estradiol and progesterone concentrations and cognitive performance in normally cycling female cynomolgus monkeys.
Preclinical research has demonstrated that cognitive function may be influenced by estradiol (E2) and progesterone (P4) concentrations, although few cognition studies involve normally cycling females. The present study examined cognitive performance in normally cycling female cynomolgus macaques (n = 14), a species with similarities to humans in brain organization and a nearly identical menstrual cycle to women. Initial assessments compared cognitive measures to circulating concentrations of E2 and P4 (n = 12). Once a relationship was characterized between hormones and cognitive performance, the menstrual cycle was divided into four distinct phases: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL), verified by the onset of menses and serum concentrations of E2 and P4. Concentrations of E2 were highest during the LF phase and P4 concentrations peaked during the EL phase. All monkeys were trained on two cognitive tasks: reversal learning, involving simple discrimination (SD) and reversal (SDR), which measured associative learning and behavioral flexibility, respectively (n = 3-4 per phase) and a delayed match-to-sample (DMS) task which assessed working memory (n = 11). P4 concentrations were positively correlated with number of trials and errors during acquisition of SD performance, but not during acquisition of the SDR task or maintenance of the reversal-learning task. Across the menstrual cycle, significantly fewer errors were made in the SDR task during the LF phase, when E2 concentrations were high and P4 concentrations low. Working memory, assessed with the DMS task, was not consistently altered based on previously characterized menstrual cycle phases. These findings demonstrate a relationship between P4, E2 and cognitive performance in normally cycling cynomolgus monkeys that is task dependent. Knowledge of these interactions may lead to a better understanding of sex-specific cognitive performance.


Production of penitrem A by Penicillium crustosum isolated from foodstuffs.
Sixty one isolates of Penicillium crustosum originating from various foodstuffs were screened for penitrem A production by thin-layer chromatography. The highest producers of penitrem A (4 isolates) were grown in various liquid media. Skimmed milk (2%)/potato extract (2%)/sucrose (2%) (SPS) medium supported the highest toxin production and P. crustosum Sp 1552 was selected as the best producer of penitrem A. Optimal conditions for the production of penitrem A were to grow the isolate Sp 1552 (stationary) in 100 ml of SPS medium (with 4% sucrose) in 500-ml flasks for 3 weeks at 25 degrees C with initial pH 5.7. The isolation and purification of penitrem A is described. Approximately 246 mg of pure penitrem A was obtained from 200 flasks each containing 100 ml of SPS medium.


Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization.
In response to many apoptotic stimuli, oligomerization of Bax is essential for mitochondrial outer membrane permeabilization and the ensuing release of cytochrome c. These events are accompanied by mitochondrial fission that appears to require Drp1, a large GTPase of the dynamin superfamily. Loss of Drp1 leads to decreased cytochrome c release by a mechanism that is poorly understood. Here we show that Drp1 stimulates tBid-induced Bax oligomerization and cytochrome c release by promoting tethering and hemifusion of membranes in vitro. This function of Drp1 is independent of its GTPase activity and relies on arginine 247 and the presence of cardiolipin in membranes. In cells, overexpression of Drp1 R247A/E delays Bax oligomerization and cell death. Our findings uncover a function of Drp1 and provide insight into the mechanism of Bax oligomerization.


Modeling tumor cell adaptations to hypoxia in multicellular tumor spheroids.
Under hypoxic conditions, tumor cells undergo a series of adaptations that promote evolution of a more aggressive tumor phenotype including the activation of DNA damage repair proteins, altered metabolism, and decreased proliferation. Together these changes mitigate the negative impact of oxygen deprivation and allow preservation of genomic integrity and proliferative capacity, thus contributing to tumor growth and metastasis. As a result the presence of a hypoxic microenvironment is considered a negative clinical feature of many solid tumors. Hypoxic niches in tumors also represent a therapeutically privileged environment in which chemo- and radiation therapy is less effective. Although the negative impact of tumor hypoxia has been well established, the precise effect of oxygen deprivation on tumor cell behavior, and the molecular signals that allow a tumor cell to survive in vivo are poorly understood. Multicellular tumor spheroids (MCTS) have been used as an in vitro model for the avascular tumor niche, capable of more accurately recreating tumor genomic profiles and predicting therapeutic response. However, relatively few studies have used MCTS to study the molecular mechanisms driving tumor cell adaptations within the hypoxic tumor environment. Here we will review what is known about cell proliferation, DNA damage repair, and metabolic pathways as modeled in MCTS in comparison to observations made in solid tumors. A more precise definition of the cell populations present within 3D tumor models in vitro could better inform our understanding of the heterogeneity within tumors as well as provide a more representative platform for the testing of therapeutic strategies.


Gene polymorphism and protein of human pro- and anti-inflammatory cytokines in Chinese healthy subjects and chronic periodontitis patients.
Periodontal disease is thought to arise from the interaction of various factors, including the susceptibility of the host, the presence of pathogenic organisms, and the absence of beneficial species. The genetic factors may play a significant role in the risk of periodontal diseases. Cytokines initiate, mediate and control immune and inflammatory responses. The aim of this study is to compare genotypes and soluble protein of pro and anti-inflammatory cytokines (IL-1α, IL-1β, IL-6, IFN-γ, IL-10, TNF-α and IL-4) in subjects with or free of chronic periodontitis. A total of 1,290 Chinese subjects were recruited to this clinical trial: 850 periodontally healthy controls and 440 periodontal patients. All subjects were free of systemic diseases. Oral examinations were performed, and the following parameters were recorded for each subject: supragingival/subgingival calculus, gingival recession, bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), gingival recession and tooth mobility. The peripheral blood samples were collected for genetic and enzyme linked immunosorbent assay (ELISA) analysis. Restriction enzymes were used for digestion of amplified fragments of IL-1α, IL-1β, IL-6, IFN-γ, IL-10, TNF-α and IL-4. The protein expressions of patient and control samples for IL-1α, IL-1β, IL-6, TNF-α, IFN-γ, IL-10, and IL-4 measured by ELISA confirmed a statistically significant difference (p < 0.001). The digestion of fragments of various genes showed that the pro-inflammatory cytokines IL-1α and TNF-α, and the anti-inflammatory cytokines IL-4 and IL-10 demonstrated a correlation with chronic inflammation in patients (X2: p < 0.001). The remaining genes investigated in patients and healthy subjects (IL-1β, IL-6, IFN-γ and IL-10) did not show any significant difference. The cytokine gene polymorphisms may be used as a marker for periodontitis susceptibility, clinical behaviour and severity. This detection offers early diagnosis and induction of prophylaxis to other family members against disease progression.


Optic disk edema with cotton-wool spots.
A 43-year-old man with high blood pressure developed visual loss in his left eye. He was found to have bilateral disk edema with cotton wool spots present in the temporal arcades and peripapillary hemorrhages. The presence of the cotton wool spots in the arcades is highly suggestive of hypertension as the etiology of the disk edema. The pathophysiology of cotton wool spots (inner retinal ischemic spots) due to focal ischemia from occlusion of terminal retinal arterioles is discussed.


Mass spectrometric assignment of Leu/Ile in neuropeptides from single neurohemal organ preparations of insects.
Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF-TOF) tandem mass spectrometry has been applied for the first time on an insect/arthropod target, focusing on PVK/CAP2b neuropeptides in the housefly Musca domestica and flesh fly Neobellieria bullata. The peptidomic analysis of single neurohemal organ preparations allows the unambiguous assignment of internal Leu/Ile positions not distinguishable by previous mass spectrometric techniques. The confirmation of side-chain fragments which allows assignment of Leu/Ile even from samples as small as neurohemal organs will greatly accelerate the identification of novel neuropeptides that are implicated in the regulation of critical physiological processes in insects. The unnatural Ile analog is 4.5 times more active than the native Leu sequence in a housefly Malpighian tubule fluid secretion assay, which reinforces the caveat that potency values in a biological assay cannot be relied upon to predict the native sequence.


Evidence for the effectiveness of botulinum toxin for writer's cramp.
We performed a comprehensive literature search of clinical studies published between 1989 and 2007 concerning the use of botulinum neurotoxin (BoNT) in the treatment of writer's cramp (WC). Publications were categorized as Classes I-IV using the scale developed by the Therapeutics and Technology Assessment (TTA) subcommittee of the American Academy of Neurology. Our search resulted in 17 clinical publications discussing the treatment of WC with BoNT. The literature search results were: one publication being Class I, two being Class II, 11 being Class III, and three being Class IV.


Comparison of the C-MAC D-blade video laryngoscope and the McCoy laryngoscope for double-lumen endotracheal tube intubation: A prospective randomized controlled study.
Inserting a double-lumen endotracheal tube (DLT) poses more challenge than inserting a single-lumen tube. The C-MAC D-blade videolaryngoscope is a useful alternative to the direct laryngoscope. However, no study has compared its performance with that of the McCoy laryngoscope, which has a hyperangulated blade tip similar to that of the C-MAC D-blade. We aimed to compare the performance of the C-MAC D-blade videolaryngoscope with that of the McCoy laryngoscope in DLT intubation. In this prospective randomized controlled study, 90 patients requiring DLT intubation were randomly allocated to either the C-MAC D-blade videolaryngoscope group (group C, n = 47) or McCoy laryngoscope group (group M, n = 43). During intubation, the percentage of glottic opening, modified Cormack-Lehane grade, time taken for intubation, malposition of the bronchial lumen, and hemodynamic parameters were recorded. After intubation, we assessed the intubation difficulty scale score and, a postoperative sore throat in the recovery room. The time taken for intubation was 35.85 ± 10.77 seconds and 33.18 ± 11.97 seconds in groups C and M, respectively (P = .269). The modified Cormack-Lehane grade was significantly lower in group C than in group M (P = .000). Percentage of glottic opening was significantly higher in group C (79.36 ± 13.42%) than in group M (53.49 ± 29.83%) (P = .000). The intubation difficulty scale score was significantly lower in group C than in group M (P = .030). There were no significant differences between the 2 groups in terms of malposition status, hemodynamic parameters, or visual analog scale score for a postoperative sore throat. Although the time taken for intubation was comparable between the 2 intubation devices, the C-MAC D-blade videolaryngoscope facilitated glottis visualization and reduced the intubation difficulty scale better than the McCoy laryngoscope in patients undergoing DLT intubation.


Distinct Brain-Oscillatory Neuroanatomical Architecture of Perception-Action Integration in Adolescents With Tourette Syndrome.
Gilles de la Tourette Syndrome (GTS) is a neurodevelopmental disorder with a peak of symptom severity around late childhood and early adolescence. Previous findings in adult GTS suggest that changes in perception-action integration, as conceptualized in the theory of event coding framework, are central for the understanding of GTS. However, the neural mechanisms underlying these processes in adolescence are elusive. A total of 59 children/adolescents aged 9 to 18 years (n = 32 with GTS, n = 27 typically developing youths) were examined using a perception-action integration task (event file task) derived from the theory of event coding. Event-related electroencephalogram recordings (theta and beta band activity) were analyzed using electroencephalogram-beamforming methods. Behavioral data showed robust event file binding effects in both groups without group differences. Neurophysiological data showed that theta and beta band activity were involved in event file integration in both groups. However, the functional neuroanatomical organization was markedly different for theta band activity between the groups. The typically developing group mainly relied on superior frontal regions, whereas the GTS group engaged parietal and inferior frontal regions. A more consistent functional neuroanatomical activation pattern was observed for the beta band, engaging inferior parietal and temporal regions in both groups. Perception-action integration processes lag behind in persisting GTS but not in the GTS population as a whole, underscoring differences in developmental trajectories and the importance of longitudinal investigations for the understanding of GTS. The findings corroborate known differences in the functional/structural brain organization in GTS and suggest an important role of theta band activity in these patients.


Identifying current uses of return to work screening tests and their effectiveness of reducing the risk of reinjury in athletic occupations - A systematic review.
To identify the current return-to-work (RTW) screening tests conducted for athletic occupations following injury and their effectiveness of reducing reinjury risk. A search was made of multiple databases (BioMed Central, CINAHL through ebscohost, EMBASE, Google Scholar, PUBMED, Scopus, SPORTDiscus and Web of Science) from their inception to March 2022, using relevant terms to identify articles meeting predefined inclusion/exclusion criteria. The search, data extraction, risk of bias, and evaluation of the certainty of the findings were completed independently by two authors. To understand the effectiveness of screening tests and their impact in reducing in reinjury rates, results were split into the following three time points: "Short-term" (≤1 year), "Medium-term" (≥2 years) and "Long-term" (≥3 years). Five studies (n = 507) met the inclusion criteria. There was a very low level of certainty for the effectiveness of screening tools reducing reinjury risk at short-term, medium-term and long-term follow ups. Only one study recorded a large effect in the reducing reinjury risk. The results demonstrated very low level of certainty for the effectiveness of screening tests reducing the risk of reinjury. A gap in our understanding currently exists for the effectiveness of RTW screening tests in tactical athletic occupations following injury and further research investigating is required.


Evaluation of Pain Assessment and Management in Critically Ill Intubated Patients in a Referral University Hospital in Iran.
This study aims to evaluate current pain assessment and management in critically ill patients and to describe (1) pain management episode, according to the behavioral pain scale (BPS), and (2) the effectiveness of analgesics, according to the recommendation of guidelines. In this cross-sectional study, a sample of 60 intubated critically ill patients was selected from the intensive care units (ICUs). A researcher evaluated the patient' pain severity using the BPS tool in patients receiving analgesics according to nurses' note. At each time of analgesic administration, the BPS score was recorded, and this process was repeated 72 h later. The appropriateness of pharmacological interventions was assessed according to the American College of Critical Care Medicine guideline. The most prescribed analgesic was morphine sulfate (48.3%) followed by fentanyl (23.3%). 55% of analgesics on day 1 and 25% on day 3 were prescribed appropriately according to the guideline recommendation and BPS score. Morphine was the most effective drug (17 patients out of 29). Even though a BPS score was <5, 26 patients received analgesics. Quality of pain assessment and management in our setting is inappropriate and inadequate, which leads to over- or under-use of analgesics. The lack of an established pain protocol may contribute to this situation.


Reductions in regional cerebral blood flow associated with chronic consumption of alcohol.
Neurotoxic effects of habitual alcohol consumption were investigated by correlating the subjects' estimates of abstinence or frequency and amount of alcohol consumed with measurements of gray matter blood flow utilizing the 133Xe inhalation method. Two hundred and twenty-two subjects were studied, including 136 healthy subjects, 82 subjects with well-established risk factors for stroke (hypertension, hyperlipidemia, heart disease, and diabetes mellitus), and four subjects with chronic alcoholic dementia of the Wernicke-Korsakoff type. Subjects were classified according to average quantitative amounts of alcohol consumed per day, week, or month for the past five years. Comparisons of mean values for hemispheric gray matter blood flow indicated significant inverse relationships with the average amounts of alcohol consumed. This linear relationship occurred regardless of whether or not other risk factors were present and indicated that alcohol itself was a risk factor reducing gray matter blood flow and had additive effects of reducing cerebral blood flow further when combined with other risk factors. Patients who had chronic Wernicke-Korsakoff syndrome had the most severely reduced blood flow levels, as might be predicted from extrapolation of the regression line comparing cerebral blood flow values with the degree of chronic alcohol consumption.


Recognition and Management of Urologic Injuries With Laparoscopic Hysterectomy.
Injuries to the urinary tract during laparoscopic hysterectomy are quite rare, but are among the most serious injuries that occur during gynecologic surgery. Injury rates among subtypes of laparoscopic hysterectomy have been found to be similar. The most effective way to avoid urinary tract injury is knowledge of urinary tract anatomy and careful and thoughtful dissection.


Anion transport across the erythrocyte membrane, in situ proteolysis of band 3 protein, and cross-linking of proteolytic fragments by 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonate.
Extracellular chymotrypsin cleaves the 95 000 dalton protein that migrates in band 3 of SDS-polyacrylamide gel electropherograms of the erythrocyte membrane into fragments of 60 000 and 35 000 daltons, but not further. Minor components of band 3 that remain at the original 95 000 dalton location may be eluted from the membrane by 0.1 N NaOH, indicating that, in contrast to the major component and the chymotryptic fragments, they are not integral membrane constituents. Incubation at neutral pH of chymotrypsinized erythrocytes with the bifunctional anion transport inhibitor 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonic acid results in covalent binding of that inhibitor primarily to the 60 000 dalton fragment and some cross-linking of the 60 000 dalton fragment with the 35 000 dalton fragment. Increasing the pH to 9.5 leads to a cross-linking of virtually all of the pairs of chymotryptic fragments and thus to a reconstitution of band 3 with its typical diffuse appearance in the 95 000 dalton region of the SDS-polyacrylamide gels. This indicates that (1) each integral 95 000 dalton protein molecule is capable of binding at least one 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonic acid molecule; (2) the 35 000 dalton fragment, though it is only weakly stained with Coomassie blue, is present in an amount that is equimolar with that of the 60 000 dalton fragment. Since the number of 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonic acid binding sites on the protein in band 3/cell is known to be close to the number of band 3 molecules/cell, it is suggested that the cross-linking takes place at a region of the band 3 molecule that is involved in the control of anion transport, Like chymotrypsin, papain digests the band 3 protein from the outer membrane surface. Unlike chymotrypsin, however, papain digestion results in an inhibition of anion exchange. Papain produces a major fragment of 60 000 daltons that differs from the major chymotryptic fragment by at most six amino acid residues. The only detectable difference between the noninhibitory action of chymotrypsin and the inhibitory action of papain on the band 3 protein is that papain is capable of partially digesting the 35000 dalton fragment. No reconstitution of band 3 by cross-linking of the fragments with 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonic acid can be achieved. Since the 35 000 dalton fragment reacts with one of the two reactive groups of 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonic acid and is also susceptible to digestion by the inhibitory papain, we suggest that a portion of this peptide participates, together with a portion of the 60 000 dalton fragment, in the control anion transport.


Perspective of biopharmaceutics knowledge and practice of pharmacy personnel toward the effect of medication route and medical procedure on nullifying fasting.
In Ramadan, most of the dosing schedules for the patients are changed, and to ensure patient compliance to medications and to healthy life among patients, appropriate guidelines and educations are needed. This can be achieved by pharmacy personnel in all clinical settings who are recognized as biopharmaceutical experts and integral educators of medications. This study aimed to identify the perspective knowledge of pharmacy personnel about effect of medication route and medical procedure on nullifying fasting in Ramadan and to determine the predictors of this knowledge. A cross-sectional study was conducted in Jordan during March-April 2022. An internet-based self-administrated questionnaire on knowledge, and views was distributed using social media groups to the pharmacy personnel among different geographical areas in Jordan. A descriptive and univariate analysis were performed. Binary logistic regression was conducted to determine the predictors of knowledge including all variables with p < 0.20 on univariate analysis. A total of 1003 responses to the study questionnaire were collected and included in the analysis. The most common source that pharmacy personnel used to get information on medication intake and medical procedures during fasting in Ramadan was Fatwa (57.8%) followed by Islamic materials "books and brochures" (47.1%). The majority of respondents were knowledgeable about the effect of administration route of medication and medical procedures on nullifying fasting in Ramadan (greater than70%). The univariate analysis showed that more than half of respondents (56.1%) were considered knowledgeable, and the binary logistic regression analysis identified that both professional degree type and confidence of respondents to modify the patient's medication schedule as predictors for knowledge (OR = 1.791, 95% CI = 1.035-3.098, p = 0.037), (OR = 1.375, 95% CI = 1.04-1.817, p = 0.025), respectively. Most of pharmacy personnel in Jordan are knowledgeable in biopharmaceutics principles and practice toward effect of medication route and medical procedure on nullifying fasting, and the identified predictors for this knowledge, can provide an opportunity to improve safe and effective use of medications and medical procedures during the holy month of Ramadan.


Applications and challenges of thermoplasmonics.
Over the past two decades, there has been a growing interest in the use of plasmonic nanoparticles as sources of heat remotely controlled by light, giving rise to the field of thermoplasmonics. The ability to release heat on the nanoscale has already impacted a broad range of research activities, from biomedicine to imaging and catalysis. Thermoplasmonics is now entering an important phase: some applications have engaged in an industrial stage, while others, originally full of promise, experience some difficulty in reaching their potential. Meanwhile, innovative fundamental areas of research are being developed. In this Review, we scrutinize the current research landscape in thermoplasmonics, with a specific focus on its applications and main challenges in many different fields of science, including nanomedicine, cell biology, photothermal and hot-electron chemistry, solar light harvesting, soft matter and nanofluidics.


Children's injuries in a Scottish district general hospital.
Injury is a common cause of emergency department (ED) attendance but there are few data published on the spectrum of paediatric injury in a typical district general hospital (DGH). This study aimed to provide a complete picture of injury presentations to such a centre. Prospective questionnaire study of consecutive paediatric attendances at a DGH ED in Scotland (annual attendance 53,500 patients) due to injury or poisoning. Paediatric in this context was defined as less than 14 years on the day of presentation. Admission rates were identified from the hospital information system and information on deaths was sought from the local Procurator Fiscal (the Scottish equivalent of the Coroner). One thousand three hundred and seventy-eight questionnaires were completed from a potential 10,697 eligible patients. Safety devices (helmets, belts, etc.) were in use in only 99 cases. Cycle helmets were used in 26% of cycle incidents and seat belts were used in 71% of car incidents. Cycling and pedestrian incidents were more common during the summer months and outside school hours. Adult supervision was present in 49% of incidents. Seventy-three percent of incidents at school were unsupervised. There were 5.6 admissions to hospital per day in the 0-13 years age group for all causes, with little seasonal variation in admission rates. There were three deaths during the year, two from SIDS and one due to choking, all in infants. Trauma is a common cause of ED attendance in children. Preventative measures are still underutilised and could make a significant impact on the incidence of children's injuries and possibly ED attendances. Cycle helmets could play a major role in injury prevention in school age children in this area.


ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro.
Asbestos is a known carcinogen and co-carcinogen. It is a persisting risk in our daily life due to its use in building material as asbestos-cement powder. The present study done on V79-cells (Chinese hamster lung cells) demonstrates the cytotoxic and genotoxic potential of asbestos-cement powder (ACP) in comparison with chrysotile asbestos. A co-exposure of chrysotile and ACP was tested using the cell viability test and the micronucleus assay. The kinetochore analysis had been used to analyse the pathway causing such genotoxic effects. Thiobarbituric acid-reactive substances were determined as evidence for the production of reactive oxygen species. Both, asbestos cement as well as chrysotile formed micronuclei and induced loss of cell viability in a concentration- and time-dependent way. Results of TBARS analysis and iron chelator experiments showed induction of free radicals in ACP- and chrysotile exposed cultures. CaSO4 appeared to be a negligible entity in enhancing the toxic potential of ACP. The co-exposure of both, ACP and chrysotile, showed an additive effect in enhancing the toxicity. The overall study suggests that asbestos-cement is cytotoxic as well as genotoxic in vitro. In comparison to chrysotile the magnitude of the toxicity was less, but co-exposure increased the toxicity of both.


Self-Worth Beliefs Predict Willingness to Engage in Psychotherapy for Fatigue in Inflammatory Bowel Disease.
Fatigue in inflammatory bowel disease (IBD) is poorly controlled, with few existing interventions. Psychotherapy interventions for IBD fatigue show promise; however, due to mixed findings in efficacy and attrition, current interventions need improvement. Some research shows beliefs about psychotherapy and stigma toward psychotherapy may impact engagement in psychotherapy interventions. This study aimed to examine the effects of IBD activity, fatigue, mental health status, previous experience with psychotherapy, and stigma toward psychotherapy on willingness to use psychotherapy as a fatigue intervention. An online cross-sectional survey was conducted, and linear regression models were used to examine willingness to engage in psychotherapy for fatigue. Overall, 834 participants completed the survey. Regression analysis examining demographics, mental health status, IBD activity, fatigue, pain, antidepressant use, psychotherapy experience, and self-worth intervention efficacy belief significantly explained 25% of variance in willingness to use psychotherapy for fatigue. Significant factors included antidepressant use (b = .21, p < .01), pain (b = - .05, p < .001), and self-worth intervention belief (b = - .27, p < .001), which uniquely explained 18% of variance in the outcome. Willingness to engage in psychotherapy for fatigue in IBD appears to be driven by expectations related to specific self-worth beliefs, rather than stigma, IBD activity, or any prior experience with psychotherapy. Clinicians should directly address these expectations with their patients.


Vectors of disease at the northern distribution limit of the genus Dermacentor in Eurasia: D. reticulatus and D. silvarum.
The two ixodid tick species Dermacentor reticulatus (Fabricius) and Dermacentor silvarum Olenev occur at the northern distribution limit of the genus Dermacentor in Eurasia, within the belt of [Formula: see text] latitude. Whilst the distribution area of D. reticulatus extends from the Atlantic coast of Portugal to Western Siberia, that of D. silvarum extends from Western Siberia to the Pacific coast. In Western Siberia, the distribution areas of the two Dermacentor species overlap. Although the two tick species are important vectors of disease, detailed information concerning the entire distribution area, climate adaptation, and proven vector competence is still missing. A dataset was compiled, resulting in 2188 georeferenced D. reticulatus and 522 D. silvarum locations. Up-to-date maps depicting the geographical distribution and climate adaptation of the two Dermacentor species are presented. To investigate the climate adaptation of the two tick species, the georeferenced locations were superimposed on a high-resolution map of the Köppen-Geiger climate classification. The frequency distribution of D. reticulatus under different climates shows two major peaks related to the following climates: warm temperate with precipitation all year round (57%) and boreal with precipitation all year round (40%). The frequency distribution of D. silvarum shows also two major peaks related to boreal climates with precipitation all year round (30%) and boreal winter dry climates (60%). Dermacentor silvarum seems to be rather flexible concerning summer temperatures, which can range from cool to hot. In climates with cool summers D. reticulatus does not occur, it prefers warm and to a lesser extent hot summers. Lists are given in this paper for cases of proven vector competence for various agents of both Dermacentor species. For the first time, the entire distribution areas of D. reticulatus and D. silvarum were mapped using georeferenced data. Their climate adaptations were quantified by Köppen profiles.


Clustered and non-clustered GABAA receptors in cultured hippocampal neurons.
In cultured hippocampal neurons, gamma2 subunit-containing GABA(A) Rs form large postsynaptic clusters at GABAergic synapses and small clusters outside GABAergic synapses. We now show that a pool of non-clustered gamma2 subunit-containing GABA(A) Rs are also present at the cell surface. We also demonstrate that myc- or EGFP-tagged gamma2, alpha2, beta3 or alpha1 subunits expressed in these neurons assemble with endogenous subunits, forming GABA(A) Rs that target large postsynaptic clusters, small clusters outside GABAergic synapses or a pool of non-clustered surface GABA(A) Rs. In contrast, myc- or EGFP-tagged delta subunits only form non-clustered GABA(A) Rs, which can be induced to form clusters by antibody capping. A myc-tagged chimeric gamma2 subunit possessing the large intracellular loop (IL) of the delta-subunit IL (myc gamma2S/delta-IL) assembled into GABA(A) Rs, but it did not form clusters, therefore behaving like the delta subunit. Thus, the large intracellular loops of gamma2 and delta play an important role in determining the synaptic clustering/non-clustering capacity of the GABA(A) Rs.


Cerebral massive hemorrhage in congophilic angiopathy and its medicolegal significance.
The principles of a special type of senile cerebromeningeal angiopathy, these days usually named "congophilic angiopathy", are demonstrated on the basis of eight cases, complicated by spontaneous massive intracranial hemorrhages in seven and late traumatic hemorrhage in one of them. The occurrence of massive hemorrhages associated with congophilic angiopathy has until now only rarely been reported. The medicolegal significance of this vascular disease is emphasized by the eighth, traumatic, case, which became forensically relevant; the late massive hemorrhage had to be regarded as significantly favoured by amyloid angionecrosis, which is the main feature of congophilic angiopathy.


Toughening of POSS-MPS composites with low dielectric constant prepared with structure controllable micro/mesoporous nanoparticles.
In this work, we developed a modified calcination and extraction method to obtain controllable micro/mesoporous nanoparticle samples POSS-MPS, which were synthesized through glycidyl polyhedral oligomeric silsesquioxane (G-POSS) grafting with aminopropyl-functionalized mesoporous silica (AP-MPS). The POSS-MPS was introduced into the cyanate ester (CE) matrix to optimize the dielectric properties and enhance the toughness of the POSS-MPS/CE nanocomposite. The structure of the hybrid was characterized by FTIR and SEM. The dispersion properties, mechanical properties, dielectric properties and thermal performance were also studied. The results showed that both the C-POSS-MPS and E-POSS-MPS uniformly distribute in the CE matrix with the content of 0.5-4 wt%. The impact strength increased 52% and 60% separately with 2 wt% C-POSS-MPS and E-POSS-MPS addition respectively. The introduction of E-POSS-MPS particles can significantly decrease the dielectric loss value of the POSS-MPS/CE composites to 0.00498, which is of potential in wave transparent composites and structures.


[Deep Vein Thrombosis in Intensive Care Patients with COVID-19 Infection - Impact of a Standardised Therapeutic Regimen].
It has been reported that the risk of deep vein thrombosis is greater in patients with COVID-19 infection. We have now investigated whether a standardised therapy can reduce the risk of DVT. After establishing standard therapy with anticoagulation, steroids and convalescent plasma, we screened 20 patients with COVID-19 pneumonia for DVT by ultrasound examination. The comparison group contained 20 COVID patients with inconsistent therapy, who were examined for the presence of thrombosis during the first wave. In the current patient population with standard therapy, we could not detect any thrombosis, and in the prior patients group only 25% of patients developed DVT. Pulmonary embolism was found in one patient in the first cohort and two in the second. The risk of DVT could be reduced through anticoagulation, and administration of steroids and convalescent plasma. The specific significance of the individual components has not yet been clarified. Since bleeding is a rarely observed in SARS-CoV-2 infections, a generous indication for anticoagulation seems to be justified.


Healthcare professionals' views of palliative care for American war veterans with non-malignant respiratory disease living in a rural area: a qualitative study.
Chronic lung diseases, such as COPD, are a growing health concern within the veteran population. Palliative care programs have mainly focused on the needs of people with malignant disease in the past, however the majority of those worldwide needing palliative care have a non-malignant diagnosis. Additionally, palliative care provision can often be fragmented and varied dependent upon a patient's geographical location. This study aimed to explore palliative care provision for veterans with non-malignant respiratory disease, and their family carers, living in a rural area of America. Qualitative study involving a convenience sample of 16 healthcare professionals from a large veteran hospital in Boise, Idaho. Data collection consisted of 5 focus groups which were transcribed verbatim and analysed using thematic analysis. Healthcare professionals perceived that a lack of education regarding disease progression enhanced feelings of anxiety amongst veterans with NMRD, and their family carers. Additionally, the uncertain disease trajectory impeded referral to palliative and hospice services due to healthcare professionals own ambiguity regarding the veteran's prognosis. A particular barrier also related to this particular patient population, was a perceived lack of ability to afford relevant services and a lack of local palliative service provision. Healthcare professionals expressed that a compounding factor to palliative care uptake was the perceptions held by the veteran population. Healthcare professionals expressed that alongside aligning palliative care with dying, veterans also viewed accepting palliative care as 'surrendering' to their disease. Findings indicated that telemedicine may be a beneficial platform to which palliative care can be provided to veterans with NMRD, and their family carers, in rural areas using a digital platform. Non-malignant respiratory disease is a life limiting condition commonly experienced within the veteran population. A new model of palliative care utilising a dynamic digital platform for this particular veteran population may provide an optimal way of providing efficient holistic care to areas with limited palliative services.


Knowledge of cervical cancer risk factors among Palestinian women: a national cross-sectional study.
High awareness of cervical cancer (CC) risk factors is important to decrease the morbidity and mortality associated with CC. This study aimed to assess the knowledge level of Palestinian women about CC risk factors and to determine the factors associated with good knowledge. This was a national cross-sectional study. Adult women from hospitals, primary healthcare centers, and public spaces of 11 governorates in Palestine were recruited using a stratified convenience sampling. A translated-into-Arabic version of the validated CC awareness measure (CeCAM) was used to assess the knowledge about the 11 CC risk factors. For each correctly identified risk factor, the participant was given one point. The total score was calculated and was categorized into three categories: poor knowledge (0-3), fair knowledge (4-7), and good knowledge (8-11). A total of 7223 participants completed the Arabic CeCAM (response rate = 89.3%) and 7058 questionnaires were included in the final analysis: 2655 from the Gaza Strip and 4403 from the West Bank and Jerusalem. Participants recruited from the Gaza Strip were younger, getting lower monthly incomes, and with less chronic diseases than participants recruited from the West Bank and Jerusalem. The most frequently identified risk factor was 'having a weakened immune system' (n = 5458, 77.3%) followed by 'infection with a sexually transmitted infection' (n = 5388, 76.3%). The least identified risk factor was 'having many children' (n = 1597, 22.6%). Only 1670 women (23.7%) had good knowledge of CC risk factors. Women living in the Gaza Strip were more likely than women living in the West Bank and Jerusalem to have good knowledge (25.2% vs 22.7%). Completing a secondary or diploma degree, being employed, and having a monthly income of ≥ 1450 NIS (around $450) were all associated with lower likelihood of having good knowledge of CC risk factors. Conversely, knowing someone with cancer was associated with higher likelihood of having good knowledge. The overall awareness of CC risk factors was low. There is a substantial need to establish educational programs to promote Palestinian women's awareness of CC.


Premorbid self-disorders and lifetime diagnosis in the schizophrenia spectrum: a prospective high-risk study.
The notion of a disordered self as a core disturbance of schizophrenia was proposed in many foundational texts. Recent studies, spurred by the development of the Examination of Anomalous Self-Experience (EASE), seem to indicate that self-disorders are a specific manifestation of schizophrenia vulnerability. Follow-up studies of help-seeking, prodromal and first-admission patients have demonstrated the utility of self-disorders for predicting later schizophrenia-spectrum disturbance. We wished to extend these findings by gauging the predictive value of self-disorders in a premorbid, non-clinical population at high risk for schizophrenia. Children from the Copenhagen High-Risk Project with high-genetic risk for schizophrenia (N = 212) were assessed premorbidly (average age = 15), and diagnostically re-evaluated after 10 and 25 years. Since the EASE was not available at the time of premorbid assessment, we hypothesized that a proxy scale drawn from the Minnesota Multiphasic Personality Inventory (MMPI) could distinguish those who later developed a schizophrenia-spectrum disorder (N = 68) from those who remained healthy (N = 64). The Self-Disorder Scale comprised 32 items whose content suggested an aspect of self-disorder as measured by the EASE. Premorbid Self-Disorder Scale scores significantly predicted lifetime schizophrenia-spectrum diagnosis in the high-risk cohort. Although there was considerable item overlap between the new scale and an existing MMPI scale (psychoticism), the overlap did not account for the Self-Disorder Scale's predictive efficacy. The results support the notion of self-disorders as a core vulnerability feature in schizophrenia, detectable premorbidly in those developing later schizophrenia-spectrum disorders.


Evaluation of vascular calcinosis risk factors in patients on chronic hemodialysis: lack of influence of calcium carbonate.
Linear calcifications of the abdominal aorta and of the iliac and femoral arteries were measured yearly for 3 years on X rays of 24 patients on chronic hemodialysis taking variable amounts of calcium carbonate and Al(OH)3 but no pharmacological doses of vitamin D or 1 alpha-hydroxylated vitamin D derivatives. The speed of their extension appeared exponential and covariant with the male sex, age only for men and, independently of these two factors, with diastolic blood pressure and blood triglycerides. Plasma concentrations of calcium, phosphate and glucose were covariant with the extension of calcinosis only at a borderline level. The doses of calcium carbonate and the levels of plasma alkaline phosphatase were not at all covariant. (1) The effect of high doses of calcium carbonate is possibly harmful only when supraphysiological levels of plasma calcium are induced, whereas plasma phosphate is not adequately decreased. The doses of calcium carbonate per se have no deleterious effect (2). Since alkaline phosphatase is not covariant with the extension of calcinosis, the degree of hyperparathyroidism per se does not seem to play a causative role in vascular calcinosis (3). The main risk factors of vascular calcinosis are: age, the male sex, diastolic blood pressure and blood triglycerides.


The effect of nature-based music intervention on adaptation and anxiety levels in patients with COVID-19 placed in the prone position: A randomized controlled trial.
To examine the effect of listening to nature-based music on anxiety, physiological parameters, and adjustment to the prone position in conscious and hypoxemic COVID-19 patients. A single-blinded randomized control trial design. The study was conducted in the intensive care unit of a state hospital in Turkey. Sixty-four patients were randomized into an intervention group and a control group. A nature-based music intervention was applied in addition to routine care to the intervention group in the prone position, while the control group received routine care in the same position. The study outcomes included state-trait anxiety, physiological parameters, and prone time within 24 h. Measurements were performed in the supine position (Time: T0), in the 30th minute in the prone position (T1), and in the 30th minute of the supine position given following the prone position (T2). Data analysis included independent samples t-test in independent groups and repeated measures ANOVA in dependent groups. State anxiety fell statistically significantly in the intervention group compared to that of the control group (39.1 ± 6.6 vs. 43.4 ± 7.9, p = 0.025). At T2, the heart rate of the intervention group did not increase, but it increased significantly in the control group compared to T0 and T1 values (87.8 ± 9.8 vs. 91.1 ± 10.8; p = 0.000). The oxygen saturation of the intervention group increased significantly compared to that of the control group (94.5 ± 2.3 vs. 93.4 ± 1.9, p = 0.035). The prone position time of the intervention group was significantly greater than that of the control group (11.5 ± 1.5 vs. 10.8 ± 1.1, p = 0.04). It was found that nature-based music intervention applied to conscious and hypoxemic COVID-19 patients in the prone position improved anxiety and oxygen saturation and increased the prone position time. Listening to nature-based music in prone position may reduce anxiety in conscious patients with hypoxemic respiratory failure, it may increase adjustment to the prone position, and it may improve oxygenation and heart rate.


A possible relationship between cord blood transferrin and birth length in infants.
Cord blood levels of transferrin (Tf) and insulin-like growth factor I (IGF-1) were measured in 33 normal and 12 preterm infants. Tf was measured by the single radial immunodiffusion technique, while IGF-1 was measured by specific RIA. Tf levels in normal term infants (195 +/- 27 mg/dl) were significantly below normal adult levels (261 +/- 12 mg/dl). Tf levels in preterm infants (159 +/- 30 mg/dl) were lower than those in normal term infants. Tf levels showed a positive correlation with birth length, weight, gestational age and albumin levels in all infants. There was no correlation between Tf and IGF-1 levels in term and preterm infants.


Legal criteria for involuntary mental health admission: clinician performance in recording grounds for decision.
Mental health laws set criteria that limit the use of involuntary admission to specific circumstances, and clinicians are expected to justify the lawfulness of such detention by referral to these criteria. The South Australian Mental Health Act 1993 required grounds to be documented on the detention form, specifically with respect to the presence of a mental illness, risk to self or others, and a need for immediate treatment. This investigation sought to determine whether the grounds provided for detention met legislative requirements. 2491 consecutive forms authorising the initial detention of involuntary patients in South Australia between July 2008 and June 2009 were rated to determine whether criteria stipulated by legislation were addressed. Only 985 forms (40%) addressed all the legal requirements for detention. 1471 forms (59%) did not comment on a requirement for immediate treatment, 540 (22%) did not state the presence of mental illness, and 359 (14%) did not discuss risk to self or others. Given the particularly poor performance of clinicians in addressing the need for immediate treatment, the data was reanalysed with respect to the presence of mental illness and risk only; 1697 forms (68%) addressed both these criteria. This low compliance rate with legal requirements is concerning. It may reflect clinical decision making, the attention given to the form by the physician filling it, or a combination of both. Stating the grounds for involuntary admission should provide protection for the rights of patients, and the requirement to do so reflects the gravity that the loss of liberty entails for the patient. Our findings are relevant to jurisdictions that are currently reviewing mental health legislation and the need to document the grounds for involuntary treatment, including South Australia.


Treatment of type 2 diabetes mellitus in a primary care setting in Taiwan: comparison with secondary/tertiary care.
This study investigated the status of diabetes control and management in patients treated in a primary healthcare setting and compared the results with data previously obtained for secondary/tertiary care patients in Taiwan. This study was conducted at 51 primary healthcare stations randomly selected island-wide in Taiwan in 2001. A total of 1302 type 2 diabetes patients who had been followed-up for more than 1 year were included. Blood was collected for centralized HbA1c assay. The remaining data and information were collected by review of medical records and patient interview. Compared with the results of a previous study on patients treated in a secondary/tertiary care setting, a significantly smaller percentage of primary care patients were receiving insulin therapy. Primary care patients also had a shorter duration of diabetes, a higher HbA1c level, better blood pressure control and a lower prevalence of complications. The proportion of patients achieving optimal control of glycemia and blood pressure was low. Patients aged < 65 years had a significantly shorter duration of diabetes, poorer diabetes control and better blood pressure control than elderly patients aged > or = 65 years. Primary care patients aged > or = 65 years had a significantly higher frequency of stroke than those aged < 65 years. The elderly group of secondary/tertiary care patients had a significantly higher frequency of coronary heart disease and stroke. Duration of diabetes and hypertension were the leading risk factors for complications in diabetes patients treated in both primary and secondary/tertiary care settings. Diabetes control was poorer in primary care than in secondary/tertiary care patients, but control of blood pressure was better in primary care patients. The shorter duration of diabetes and better control of blood pressure in primary care patients and in patients aged < 65 years compared with their elderly counterparts might be related to a lower prevalence of complications.


Frequency-specific alterations of the frontal-cerebellar circuit in first-episode, drug-naive somatization disorder.
With the development of imaging techniques, evidence of abnormal neural activity has been implicated in patients with somatization disorder (SD). It remains unclear whether abnormal spontaneous neural activities are related to specific frequency bands. In this study, resting-state functional magnetic resonance imaging (fMRI) using the frequency-specific amplitude of low frequency fluctuation (ALFF) approach was applied to investigate changes in spontaneous neural activity in different frequency bands in patients with SD. Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education-matched healthy controls (HCs) underwent resting-state fMRI. The ALFF method with the classical low-frequency (0.01 - 0.08 Hz), slow-5 (0.01 - 0.027 Hz) and slow-4 (0.027 - 0.08 Hz) bands was employed to analyze the data. With the classical low-frequency and slow-5 bands, patients with SD showed significantly increased ALFF in the left orbitofrontal cortex (OFC) and reduced ALFF in the right cerebellum compared with HCs. With the slow-4 band, patients with SD exhibited significantly reduced ALFF in the right cerebellum compared with HCs. However, no significant correlation was observed between the ALFF value in the left OFC or right cerebellum and clinical/cognitive variables. Our findings indicate that there are abnormal regional activities of the left OFC and right cerebellum in first-episode, treatment-naive patients with SD, suggesting that these alterations occur early in the course of the disease and are independent of medication status. Our study provides novel evidence that different regional activities of the frontal-cerebellar circuit may be involved in the pathophysiology of SD.


Assessment of myocardial function of the systemic right ventricle in patients with D-transposition of the great arteries after atrial switch operation by tissue Doppler echocardiography.
The long-term follow-up of patients with D-transposition of the great arteries after atrial switch operation shows specific problems such as tricuspid valve insufficiency, rhythm disturbances and failure of the morphologic right ventricle in systemic position. Assessment of the myocardial contractility of the subaortic right ventricle by conventional echocardiography is limited. The usage of tissue Doppler echocardiography with strain combined with strain rate imaging provides a new approach for quantitative analysis of longitudinal myocardial function. The aim of this study was to assess patterns of wall motion and regional contractile function of the systemic right ventricle in patients after atrial switch operation for D-transposition of the great arteries and to compare them to those of normal subjects. Twenty-four patients with Dtransposition of the great arteries after atrial switch operation with a mean age of 21.3 (range, 13 to 31) years and a postoperative period of 16.9 years were examined and compared to 22 control individuals with a mean age of 21.5 (range, 3 to 43) years. Tissue Doppler studies were obtained from apical 4- chamber view to determine regional systolic (Syst(T)) and diastolic (E(T), A(T)) velocities as well as E(T)/A(T) ratio at the basal free wall. The presystolic isovolumic contraction peak was assessed and the ratio of the presystolic peak velocity to the isovolumic acceleration time as the IVA index was calculated. Strain and peak systolic and diastolic strain rates were assessed on basal, middle and apical segments of the right ventricular free wall. Data obtained from the morphologic right systemic ventricle in patients were compared to those derived from the left and the right ventricle in controls. The right ventricular free wall systolic velocities were significantly reduced in patients compared to velocities obtained from the normal right and left ventricle. On the other hand, the IVA index was only reduced in patients compared to the IVA index in the normal subpulmonary right ventricle. Compared to data obtained from the normal systemic left ventricle, the IVA index in patients was not significantly different. In contrast, strain and strain rate parameters in all analyzed segments mostly showed a highly significant reduction compared to normal right and left ventricular data. Tissue Doppler echocardiography is a promising tool for the evaluation of regional myocardial contractile function of the morphologic right systemic ventricle in patients following atrial switch operation for D-transposition of the great arteries. Presystolic, systolic and diastolic regional ventricular function was reduced in the systemic right ventricle. However, further comparative studies using other quantitative parameters of global and regional myocardial function derived from cardiac catheterization or MRI should be performed in order to evaluate the reliability of tissue Doppler echocardiography for the assessment of global right ventricular function in these patients.


Interaction of Silver Nanoparticles with Triosephosphate Isomerase from Human and Malarial Parasite (Plasmodium falciparum): A Comparative Study.
Recombinant triosephosphate isomerase from Plasmodium falciparum (PfTIM) and humans (hTIM) were expressed, purified and characterised. High specific activity (1207 U x mg(-1)) with a fold purification of -1.8 and a yield of 48% were obtained for hTIM after gel filtration while, in contrast PfTIM afforded a specific activity of 1387 U x mg(-1) with a fold purification of -6.8 and a yield of 57% after gel filtration and prior to dialysis. PfTIM had an optimal pH and temperature, K(m) and V(max) of 5.25, 25 degrees C, 12.8 mM and 1.13 μmol x mL(-1) min(-1) respectively while for hTIM the pH and temperature optima, K(m) and V(max) were 6.75, 30 degrees C; 8.2 mM and 1.35 μmol x ml(-1) min(-1). Polyvinylpyrrolidone stabilised silver nanoparticles (60 nM; 2-6 nm diameter) selectively inhibited PfTIM with a 7-fold decrease in enzyme catalytic efficiency (K(cat)/K(m)) over hTIM. Respective K(i) values were 283 nM [hTIM] and 85.7 nM [PfTIM]. Key structural differences between the two enzyme variants, especially with Cys13 at the dimer interface of PfTIM, were significant enough to suggest unique characteristics allowing for selective targeting of PfTIM by AgNPs.


Cardiovascular responses to dynamic and static effort soon after myocardial infarction. Application to occupational work assessment.
Static and dynamic work involving the arms and the legs was performed by 40 men seven weeks after myocardial infarction. Leg ergometry produced a significantly higher peak work load, systolic blood pressure (BPs), heart rate (HR), and HR X BPs X 10(-2) product (DP) than did arm ergometry: 842 +/- 178 vs 546 +/- 135 kg-m/min, 176 +/- 24 vs 154 +/- 19 mm Hg and 256 +/- 54 vs 219 +/- 48 (SD). Peak heart rates were 145 and 142. Endpoints were primarily muscular and generalized fatigue and dyspnea. Ischemic abnormalities and ventricular ectopy were more frequent with leg ergometry. Sustained forearm lifting elicited higher HR, PBs and DP responses than sustained handgrip contraction: 95 +/- 16 vs 91 +/- 16 beats/min, 162 +/- 18 vs 152 +/- 17 mm Hg and 154 +/- 33 vs 139 +/- 33 (SD). Ischemic ST segment depression and significant ventricuar arrhythmias were infrequent with static effort. Dynamic leg testing is superior to dynamic or static arm testing in assessing the capacity of patients to perform physical work tasks after myocardial infarction.


Integrated algorithm combining plasma biomarkers and cognitive assessments accurately predicts brain β-amyloid pathology.
Accurate prediction of cerebral amyloidosis with easily available indicators is urgently needed for diagnosis and treatment of Alzheimer's disease (AD). We examined plasma Aβ42, Aβ40, T-tau, P-tau181, and NfL, with APOE genotypes, cognitive test scores and key demographics in a large Chinese cohort (N = 609, aged 40 to 84 years) covering full AD spectrum. Data-driven integrated computational models were developed to predict brain β-amyloid (Aβ) pathology. Our computational models accurately predict brain Aβ positivity (area under the ROC curves (AUC) = 0.94). The results are validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Particularly, the models have the highest prediction power (AUC = 0.97) in mild cognitive impairment (MCI) participants. Three levels of models are designed with different accuracies and complexities. The model which only consists of plasma biomarkers can predict Aβ positivity in amnestic MCI (aMCI) patients with AUC = 0.89. Generally the models perform better in participants without comorbidities or family histories. The innovative integrated models provide opportunity to assess Aβ pathology in a non-invasive and cost-effective way, which might facilitate AD-drug development, early screening, clinical diagnosis and prognosis evaluation.


A randomized, prospective, double-blind trial comparing 3% chloroprocaine followed by 0.5% bupivacaine to 2% lidocaine followed by 0.5% bupivacaine for interscalene brachial plexus block.
The combination of 2-chloroprocaine and bupivacaine (C/B) for regional anesthesia has been described, but its use was largely abandoned due to equivocal results in efficacy. In this prospective, double-blind, randomized study, we compared the onset of an interscalene block using C/B versus a combination of lidocaine and bupivacaine (L/B). Thirty patients scheduled for shoulder arthroscopy under interscalene block were divided into two groups of 15 each. One group (C/B) received 3% 2-chloroprocaine combined with bicarbonate and epinephrine, immediately followed by 0.5% bupivacaine and epinephrine, whereas the other group (L/B) received 2% lidocaine instead of 3% 2-chloroprocaine. Motor and sensory block were assessed every 15 s. The primary end-point was the time of onset to complete motor block. Time-to-event (survival) statistical analysis tests were applied. One L/B patient had a failed block, and was excluded. The median time to motor block for C/B and L/B was 90 (15-575) and 180 (15-3720) s, respectively (P = 0.0325), and to sensory block for C/B and L/B was 90 (30-600) and 210 (30-3900) s, respectively (P = 0.0185). Survival analysis showed that in 5 min, 13 of 15 patients from the C/B group but only 7 of 14 from the L/B group had a successful motor block. In 10 min, 15 of 15 patients from the C/B group but only 10 of 14 from the L/B group had a successful motor block. It took as long as 60 min to assess block success/failure for blocks in the L/B group. This study demonstrates that a successful block was more rapid using C/B than L/B for interscalene blocks.


Activated Carbons From Winemaking Biowastes for Electrochemical Double-Layer Capacitors.
Revalorizing organic biowaste is critical to achieve a full circular economy, where waste is transformed into resources. One of the main strategies is to produce activated carbons and use them as functional materials for electrochemical energy storage. In this study, winemaking wastes, bagasse (BAG), and cluster stalks (CS) were recovered and used in the preparation of activated carbons by a hydrothermal process. Then, they were chemically activated using KOH and investigated for electrochemical capacitor applications. The activation treatment resulted in microporous structures, characterized by a type I isotherm for low partial pressures (P/P 0), and a type IV for higher pressures, as observed by Brunauer-Emmett-Teller surface analysis, with specific surfaces of 1,861 and 2,662 m2·g-1 for BAG and CS, respectively. These microporous structures were also investigated by means of scanning electron microscopy, revealing a high porous degree. Micro-Raman spectroscopy and X-ray photoelectron spectroscopy measurements displayed bands associated to disorder of the structure of the carbonaceous material. The electrochemical performance of the resulting materials was investigated for electrochemical energy storage applications, as supercapacitor electrode, in 1 M KOH aqueous electrolyte. These biowaste-derived materials displayed electrochemical double-layer capacitance, with 129 F·g-1 at 10 A·g-1 in the 0.1 to -1.0 V vs. saturated calomel electrode. For that reason, they are pin-pointed as potential negative electrodes for electrochemical double-layer supercapacitors and hybrid or asymmetric supercapacitors.


Comparative epidemiology of three tropical whitefly-transmitted geminiviruses.
Spatial and temporal patterns of spread of African cassava mosaic, okra leaf curl and tobacco leaf curl viruses in West Africa, East Africa and India share some general characteristics. By comparing the results and running new analyses on available data, it is shown that the epidemiology of these viruses is controlled by the same key variables. For instance, spatial spread is characterised by strong border effects due to accumulation of whitefly vectors (Bemisia tabaci) on the wind-exposed field borders under the influence of the prevailing wind. This results in pronounced environmental gradients of disease. Temporal patterns of virus spread are driven by the sinusoidal fluctuation of temperature over the year which correspond with changes of whitefly populations.


A hybrid model for automatic identification of risk factors for heart disease.
Coronary artery disease (CAD) is the leading cause of death in both the UK and worldwide. The detection of related risk factors and tracking their progress over time is of great importance for early prevention and treatment of CAD. This paper describes an information extraction system that was developed to automatically identify risk factors for heart disease in medical records while the authors participated in the 2014 i2b2/UTHealth NLP Challenge. Our approaches rely on several nature language processing (NLP) techniques such as machine learning, rule-based methods, and dictionary-based keyword spotting to cope with complicated clinical contexts inherent in a wide variety of risk factors. Our system achieved encouraging performance on the challenge test data with an overall micro-averaged F-measure of 0.915, which was competitive to the best system (F-measure of 0.927) of this challenge task.


Evaluation Framework for Telemedicine Using the Logical Framework Approach and a Fishbone Diagram.
Technological advances using telemedicine and telehealth are growing in healthcare fields, but the evaluation framework for them is inconsistent and limited. This paper suggests a comprehensive evaluation framework for telemedicine system implementation and will support related stakeholders' decision-making by promoting general understanding, and resolving arguments and controversies. This study focused on developing a comprehensive evaluation framework by summarizing themes across the range of evaluation techniques and organized foundational evaluation frameworks generally applicable through studies and cases of diverse telemedicine. Evaluation factors related to aspects of information technology; the evaluation of satisfaction of service providers and consumers, cost, quality, and information security are organized using the fishbone diagram. It was not easy to develop a monitoring and evaluation framework for telemedicine since evaluation frameworks for telemedicine are very complex with many potential inputs, activities, outputs, outcomes, and stakeholders. A conceptual framework was developed that incorporates the key dimensions that need to be considered in the evaluation of telehealth implementation for a formal structured approach to the evaluation of a service. The suggested framework consists of six major dimensions and the subsequent branches for each dimension. To implement telemedicine and telehealth services, stakeholders should make decisions based on sufficient evidence in quality and safety measured by the comprehensive evaluation framework. Further work would be valuable in applying more comprehensive evaluations to verify and improve the comprehensive framework across a variety of contexts with more factors and participant group dimensions.