Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals.
The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.


Interactions between drebrin and Ras regulate dendritic spine plasticity.
Dendritic spines are major sites of morphological plasticity in the CNS, but the molecular mechanisms that regulate their dynamics remain poorly understood. Here we show that the association of drebrin with actin filaments plays a major role in regulating dendritic spine stability and plasticity. Overexpressing drebrin or the internal actin-binding site of drebrin in rat hippocampal neurons destabilized mature dendritic spines so that they lost synaptic contacts and came to resemble immature dendritic filopodia. Drebrin-induced spine destabilization was dependent on Ras activation: expression of constitutively active Ras destabilized spine morphology whereas drebrin-induced spine destabilization was rescued by co-expressing dominant negative Ras. Conversely, RNAi-mediated drebrin knockdown prevented Ras-induced destabilization and promoted spine maturation in developing neurons. Together these data demonstrate a novel mechanism in which the balance between stability and plasticity in dendritic spines depends on binding of drebrin to actin filaments in a manner that is regulated by Ras.


Quantitative proton MRS of cerebral metabolites in laminin alpha2 chain deficiency.
Congenital muscular dystrophy (CMD) due to merosin (laminin alpha2 chain) deficiency is an autosomal recessively inherited disorder characterized by severe muscular weakness and hypotonia from birth on. Brain involvement is the rule and characterized by variable T2 hyperintensities of white matter which appears swollen on cranial MRI. The pathophysiology of these white matter changes is not clear. In five patients with laminin alpha2 deficient CMD we performed short-echo time localized proton MRS with determination of absolute metabolite concentrations in grey and white matter. In affected white matter, a consistent pattern of metabolites was detected comprising reduced concentrations of N-acetylaspartate and N-acetylaspartylglutamate, creatine, and phosphocreatine, and to a milder degree of choline-containing compounds. In contrast, concentrations of myo-inositol were in the normal range. Spectra of cortical and subcortical grey matter were normal. The observed metabolite profile is consistent with white matter edema, that is reduced cellular density, and relative astrocytosis. This interpretation is in line with the hypothesis that laminin alpha2 deficiency results in leakage of fluids across the blood-brain barrier and a histopathological report of astrocytic proliferation in CMD.


Radiation dose reduction without compromise of image quality in cardiac angiography and intervention with the use of a flat panel detector without an antiscatter grid.
To test the hypothesis that replacing the antiscatter grid with an air gap will reduce patient radiation exposure without significant compromise of image quality. 457 patients having either uncomplicated diagnostic studies or a single vessel angioplasty (percutaneous transluminal coronary angioplasty (PTCA)) on a flat plate system (GE Innova) were studied. For two months their total dose-area product score was recorded on standard gridded images and then for two months on images made with the grid out, with an air gap used to reduce scatter. Detector magnification was reduced one step when an air gap was used to achieve the same final image size. A sample set of studies was reviewed blind by five observers, who scored sharpness and contrast on a non-linear scale. The average dose-area product was significantly reduced, both in the diagnostic group (n = 276), from a mean (SD) of 26.2 (14.7) Gy.cm2 with the grid in to 16.1 (12) Gy.cm2 with the grid out (p = 0.01), and in the PTCA group (n = 181), from 48.2 (36.2) to 37 (27.5) (p = 0.01). The mean image quality scores of the gridless cohort were not significantly different from those of the gridded cohort. With the use of a flat plate detector, air gap gridless angiography reduces the radiation dose to the patient and, in consequence, to the operator without significantly affecting image quality. It is proposed that gridless imaging should be the default technique for adults and children and in most installations.


Ventriculoperitoneal shunt infection with non-typhoidal Salmonella species in an infant.
Shunt infections are common in pediatric neurosurgery. We present a case of a 3-month-old male with a history of a ventriculoperitoneal shunt for posthemorrhagic hydrocephalus after premature birth who presented to the emergency department with irritability and decreased oral intake. His presentation was concerning for shunt infection and evaluation for this was undertaken. He was found to have a shunt infection due to non-Salmonellatyphi species, a rare cause of meningitis in children in the United States and rarer cause of shunt infection. With effective treatment for this organism, the patient did well and was discharged home in good condition.


Pd(II)-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation.
A palladium-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation is described. This protocol provides efficient access to a range of ortho-acyl phenylacetamides, which can be easily converted to 3-isochromanone derivatives.


A Q-band low noise GaAs pHEMT MMIC power amplifier for pulse electron spin resonance spectrometer.
We present the design and development of a single stage pulse power amplifier working in the frequency range 32-38 GHz based on a monolithic microwave integrated circuit (MMIC). We have designed the MMIC power amplifier by using the commercially available packaged GaAs pseudomorphic high electron mobility transistor. The circuit fabrication and assembly process includes the elaboration of the matching networks for the MMIC power amplifier and their assembling as well as the topology outline and fabrication of the printed circuit board of the waveguide-microstrip line transitions. At room ambient temperature, the measured peak output power from the prototype amplifier is 35.5 dBm for 16.6 dBm input driving power, corresponding to 19 dB gain. The measured rise/fall time of the output microwave signal modulated by a high-speed PIN diode was obtained as 5-6 ns at 20-250 ns pulse width with 100 kHz pulse repetition rate frequency.


Association Of Abo And Rh Blood Group Types To Hepatitis B, Hepatitis C, Hiv And Syphilis Infection, A Five Year' Experience In Healthy Blood Donors In A Tertiary Care Hospital.
Aim of the study: The aim of the study was to find out the frequency of Hepatitis B Hepatitis C, Syphilis, HIV and malaria in apparently healthy blood donors and to find out any association between ABO and Rh blood groups. It was a descriptive study carried out at Rehman Medical Institute laboratory. All blood donors who volunteered for blood donation from Jan 2008 to Dec 2014 were reviewed for blood groups and screening tests. Those who were eligible were then screened for Hepatitis B, Hepatitis C, HIV, syphilis and malaria on Architect 8200i through chemiluminescent immunoassay whereas malaria was screened by a thin film. Blood group was determined by both forward and reverse grouping. Statistical analysis was carried out using SPSS software and expressed as frequencies. A total of 41033 apparently healthy donors were included in the study. All of them were voluntary donors. Their age ranged from 18-70 years with a mean age of 38±10.5years. Out of these 41033, 40245 (98.3%) were males and 788 (1.9%) were females. The most frequent blood group was B positive followed by O positive. Out of 41033 donors 961 (2.30%) had Hepatitis B, 566 (1.30%) had Hepatitis C, 363 (0.90%) had syphilis, 311 (0.76%) had malaria and 30 (0.07%) had HIV. There is a significant association between A blood group and HIV and hepatitis B. Donors with blood group O had no significant association with any blood transmitted infection. Blood group O may have some influence in protecting against blood transmitted infection. People having Blood group A are more prone to get Hepatitis B and HIV.


Exchange interactions and theoretical analysis of (31)P NMR spectra in VO(HPO(4)).0.5H(2)O.
Based on combined DFT/broken symmetry approach, a theoretical analysis of the exchange interactions in the VO(HPO(4)).0.5H(2)O solid is performed. Depending on the crystallographic structures reported in the literature, two very different spin models are formulated. In addition, a complete fit of the temperature-dependent (31)P NMR chemical shift is performed to determine exchange and hyperfine constants. The magnetic models used in the fit are those obtained by our theoretical calculations. The comparison between the calculated and fitted exchange constants confirms the adequacy of an isolated dimer model and rules out the alternating antiferromagnetic chain model for VO(HPO(4)).0.5H(2)O.


Ultrasound elastography in the head and neck. Part II. Accuracy for malignancy.
Ultrasound elastography (USE) describes a variety of ultrasound-based imaging techniques that measure tissue stiffness properties, and is currently under intense investigation for tissue characterization in several anatomic sites. This article summarizes the evidence regarding the accuracy of USE for malignancy in the head and neck. Currently, most published data pertains to small pilot studies with varied methodologies. Encouragingly, most studies have documented promising results for USE in terms of high accuracy for malignancy in thyroid nodules and cervical lymph nodes, which have surpassed conventional sonographic criteria. However, a minority of studies have documented opposite findings. USE seems to be suboptimal for salivary malignancies, and some evidence suggests that USE does not provide useful diagnostic information compared with conventional ultrasonography for miscellaneous neck masses. Further larger studies are required to validate these findings although, in view of the predominance of highly optimistic results for thyroid nodules and cervical lymph nodes, USE may become a useful ancillary technique in the routine diagnostic work-up of lesions in these tissues in the near future.


Attention avoidance of the threat conditioned stimulus during extinction increases physiological arousal generalisation and retention.
Exposure therapy is a key component of efficacious treatment for anxiety. Biases in the allocation of attention towards versus away from threat assessed prior to exposure-based treatments such as cognitive-behavioural therapy differentially predict treatment outcomes. However, it is unclear whether monitoring versus avoiding threat stimuli influences learning during exposure. Extinction paradigms are the experimental analogue of exposure therapy. Therefore, manipulating attention towards versus away from threat during extinction trials may shed light on the role of attention during exposure therapy. This study utilised a Pavlovian fear conditioning and extinction paradigm to examine whether directing attention towards versus away from the threat conditioned stimulus (CS+) related to differences in extinction, as indexed by skin conductance responses (SCR), CS evaluations and subjective measures of anxiety. Following a fear conditioning phase in which a dog image (CS+) was paired with an aversive tone unconditioned stimulus (US) and another dog image (CS-) was presented alone, 57 participants were randomly assigned to one of three conditions during extinction in which both CSs were presented alone: monitor the CS+ (N = 19), avoid the CS+ and attend to another stimulus (N = 18), no attention manipulation control (N = 20). Eye movements were monitored for visual adherence to assigned location using horizontal electro-oculogram. In the context of the acquisition of differential conditioning and visual adherence during extinction, both active groups exhibited larger SCRs to the CS + relative to the CS- during the first extinction block compared to the control group, and the avoid group exhibited significantly larger SCRs on CS+ and CS- trials throughout the extinction phase compared to the other groups. The avoid group also exhibited less decline in SCRs to the CS+ during the extinction retest phase relative to the control group. No significant group differences were observed in between-phase CS evaluations and subjective anxiety ratings. Avoidance of threat conditioned stimuli may impair extinction learning and increase physiological arousal generalisation to safe stimuli.


Dynamic heterogeneity and non-Gaussian statistics for ganglioside GM1s and acetylcholine receptors on live cell membrane.
We have carried out a comparative study of the lateral motion of ganglioside GM1, which is a glycosphingolipid residing on the outer leaflet of the plasma membrane, and acetylcholine receptor (AChR), which is a well-characterized ion channel. Both the lipid molecules and the transmembrane proteins reside on the plasma membranes of live Xenopus muscle cells. From a thorough analysis of a large volume of individual molecular trajectories obtained from more than 300 live cells over a wide range of sampling rates and long durations, we find that the GM1s and AChRs share the same dynamic heterogeneity and non-Gaussian statistics. Our measurements with the ATP-depleted cells reveal that the diffusion dynamics of the GM1s and AChRs is uniformly affected by the intracellular ATP level of the living muscle cells, further demonstrating that membrane diffusion is strongly coupled to the dynamics of the underlying cortical actin network, as predicted by the dynamic picket-fence model.


Two regimes in conductivity and the Hall coefficient of underdoped cuprates in strong magnetic fields.
We address recent experiments shedding light on the energy spectrum of under and optimally doped cuprates at temperatures above the superconducting transition. Angle resolved photoemission reveals coherent excitation only near nodal points on parts of the 'bare' Fermi surface known as the Fermi arcs. The question debated in the literature is whether the small normal pocket, seen via quantum oscillations, exists at higher temperatures or forms below a charge order transition in strong magnetic fields. Assuming the former case as a possibility, expressions are derived for the resistivity and the Hall coefficient (in weak and strong magnetic fields) with both types of carriers participating in the transport. There are two regimes. At higher temperatures (at a fixed field) electrons are dragged by the Fermi arcs' holes. The pocket being small, its contribution to conductivity and the Hall coefficient is negligible. At lower temperatures electrons decouple from holes behaving as a Fermi gas in the magnetic field. As the mobility of holes on the arcs decreases in strong fields with a decrease of temperature, below a crossover point the pocket electrons prevail, changing the sign of the Hall coefficient in the low temperature limit. Such behavior finds its confirmation in recent high-field experiments.


[A Study on the establishment of immune thrombocytopenia model induced by anti-platelet GPⅠbα antibodies].
Objective: To establish primary immune thrombocytopenia (ITP) animal model induced by anti-platelet membrane glycoprotein GPⅠbα antibodies AN51 and R300. Methods: Twenty guinea pigs (6-8 week) were divided into 4 groups. Five guinea pigs in each group were intravenously injected with different doses of AN51 (0.05, 0.1, 0.2 μg/g) and 0.2 μg/g IgG as control. The whole blood was collected from inner angular venous plexus. Platelets number was determined by an automated cell counter and Swiss-Jim method. Then, the similar protocol was used to establish ITP nude mice model by intraperitoneal injection of different concentrations of anti-platelet GPⅠbα antibody R300, respectively. Results: ①Five minutes after intravenous injection of AN51 at 0.05, 0.1 and 0.2 μg/g, the platelet counts of guinea pigs reduced about 0-5%, 50%-60% and 70%-80% compared to the control group, respectively. The difference was statistically significant (P<0.01) . ②Six hours after intraperitoneal injection of R300 at 0.05, 0.1, 0.2 μg/g, the platelet counts of nude mice decreased about 20%-30%, 60%-70% and 80%-90% compared to the control group, respectively. The difference was statistically significant (P<0.01) . The nude mice, injected 0.2 μg/g R300 once a day for 2 weeks, showed typical ITP clinical manifestations including large number of petechiaes or ecchymoses on limbs, head and abdomen. Conclusion: AN51 at 0.2 μg/g and R300 at 0.2 μg/g could establish stable ITP model in guinea pigs and nude mice respectively.


Comparison of abdominal muscle activity and peak expiratory flow between forced vital capacity and fast expiration exercise.
[Purpose] The purpose of this investigation was to compare the activities of the abdominal muscles and peak expiratory flow between forced vital capacity and fast expiration exercise. [Subjects and Methods] Fifteen healthy male participated in this study. Peak expiratory flow and electromyographic activities of the rectus abdominis, external oblique, and internal oblique/transversus abdominis muscles were measured during forced vital capacity and fast expiration exercise and then peak amplitude and its appearance time were obtained. [Results] Peak expiratory flow values were significantly higher during fast expiration exercise than during forced vital capacity. The internal oblique/transversus abdominis muscles showed significantly higher peak amplitude during fast expiration exercise than during forced vital capacity. However, there were no significant differences between forced vital capacity and fast expiration exercise in the rectus abdominis and external oblique muscles. There was no difference in the appearance time of the peak amplitude between forced vital capacity and fast expiration exercise in any muscle. [Conclusion] Fast expiration exercise might be beneficial for increasing expiratory speed and neuromuscular activation of the internal oblique/transversus abdominis muscles compared to forced vital capacity. These findings could be considered when recommending a variation of expiratory muscle strength training as part of pulmonary rehabilitation programs.


Emergency department patient 'dumping': an analysis of interhospital transfers to the Regional Medical Center at Memphis, Tennessee.
To study the extent and nature of transfers of emergency department (ED) patients because of inability to pay, we audited all telephone requests and actual patient transfers from private hospital EDs and their affiliated free-standing emergency centers to the ED of the Regional Medical Center at Memphis (the Med), a publicly subsidized hospital, between June 1 and August 31, 1986. Transfers to the Med's "special care" centers were assumed to represent tertiary care referrals and were excluded. During the 92-day study interval, ED physicians at the Med handled 190 telephone requests for transfer. Requesting physicians explicitly identified "no money" or "no insurance" as the primary reason for transfer in 89 per cent of 164 cases in which these data were recorded. Thirty-seven per cent of requests were refused; half were too unstable or required an intensive care unit (ICU) bed when none were available. One hundred forty-six transfers (55 per cent) arrived without prior telephone authorization, most by private automobile. Almost all transferred patients (91 per cent) were sent for primarily economic reasons. One out of four was found to be unstable on arrival by explicit clinical criteria. Eighty-two patients transferred for economic reasons (34 per cent) required emergency hospitalization and accounted for 564 bed days during a period of extreme inpatient crowding. Three patients died prior to discharge. Two had been transferred for primarily economic reasons.


Sex differences in lipolysis-regulating mechanisms in overweight subjects: effect of exercise intensity.
To explore sex differences in the regulation of lipolysis during exercise, the lipid-mobilizing mechanisms in the subcutaneous adipose tissue (SCAT) of overweight men and women were studied using microdialysis. Subjects matched for age, BMI, and physical fitness performed two 30-minute exercise bouts in a randomized fashion: the first test at 30% and 50% of their individual maximal oxygen uptake (Vo(2max)) and the second test at 30% and 70% of their Vo(2max). In both groups, an exercise-dependent increment in extracellular glycerol concentration (EGC) was observed. Whatever the intensity, phentolamine [alpha-adrenergic receptor (AR) antagonist] added to a dialysis probe potentiated exercise-induced lipolysis only in men. In a probe containing phentolamine plus propranolol (beta-AR antagonist), no changes in EGC occurred when compared with the control probe when exercise was performed at 30% and 50% Vo(2max). A significant reduction of EGC (when compared with the control probe) was observed in women at 70% Vo(2max). At each exercise power, the plasma non-esterified fatty acid and glycerol concentrations were higher in women. Exercise-induced increase in plasma catecholamine levels was lower in women compared with men. Plasma insulin decreased and atrial natriuretic peptide increased similarly in both groups. Overweight women mobilize more lipids (assessed by glycerol) than men during exercise. alpha(2)-Anti-lipolytic effect was functional in SCAT of men only. The major finding is that during low-to-moderate exercise periods (30% and 50% Vo(2max)), lipid mobilization in SCAT relies less on catecholamine-dependent stimulation of beta-ARs than on an increase in plasma atrial natriuretic peptide concentrations and the decrease in plasma insulin.


Colloidal bismuth subcitrate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease.
Colloidal bismuth subcitrate (CBS) possesses at least equal efficacy with histamine H2-receptor antagonist drugs in the treatment of peptic ulcer disease. However, CBS has the advantage of slower ulcer relapse rates than those seen after initial healing with the H2-antagonists. It has been postulated that this effect may be partly due to the antibacterial properties of CBS against Campylobacter pylori, a bacterium found in the gastric mucosa and gastric metaplasia within the duodenum of most patients with peptic ulcer and closely associated with gastritis. However, the role of C. pylori in the aetiology of peptic disease is far from clear. The mechanism by which CBS heals ulcers has not been fully elucidated, but several actions may be involved. CBS and mucus form a glycoprotein-bismuth complex in vitro. This provides a diffusion barrier to HCl and may, therefore, provide a protective coating in the ulcer crater which allows healing of the lesion to occur. Prostaglandin E2 production is also stimulated by CBS with subsequent secretion of alkali into the mucus layer. In addition, CBS has a direct inhibitory effect on C. pylori. Administration of CBS results in low levels of bismuth absorption. Most of the ingested bismuth is excreted as bismuth sulphide, causing blackening of the faeces, and the small amount absorbed is excreted in the urine. Bismuth intoxication (encephalopathy) has been reported with prolonged administration of bismuth salts, and there has been 1 report of similar intoxication in a patient receiving unusually high doses of CBS for a prolonged period. However, no such intoxication has been reported with CBS used at its recommended dosage in the acute treatment of peptic ulcer disease, and no other serious adverse effects have been associated with CBS. Tissue accumulation during prolonged therapy seems likely, and the safety of CBS during long term maintenance therapy has not been established. The lack of effect on gastric acid secretion is seen as an added advantage for CBS, since prolonged drug-induced hypochlorhydria has been postulated to have potentially detrimental effects. Thus, while the role of C. pylori in peptic ulceration requires further clarification, CBS would appear to have an important place in the treatment of peptic ulcer disease with the advantage of relatively slow relapse rates after initial healing and treatment discontinuation.


Passive transepithelial cationic fluxes across the frog skin under short-circuit conditions.
The short-circuit current (Isc) across the frog skin in the steady state reflects the active Na+ transport. Inhibition of the Na+-K+ pump by ouabain causes slow decay of Isc. It has been suggested that this slow ouabain effect on Isc could be due to the asymmetric ionic permeations of frog skin. That is, Na+ flux at the apical membrane and K+ flux at the basolateral membrane transiently generate the transepithelial cationic fluxes and are measured as the Isc even under the condition of active Na+ transport arrest. However, this hypothesis on the transient Isc has not been studied experimentally. In the present study, transient inward and outward Isc were observed alternately even after pump arrest by changing the ionic compositions of the bathing solutions in a Ussing's chamber. The time constant of Isc decay was 20-30 min. The Isc responses were quicker and stronger on the isolated epithelia than on the whole skin. Both Isc responses were blocked by amiloride, a Na+ channel blocker. Measurements of the ionic composition of isolated epithelia under experimental conditions indicate that the passive Na+ flux across the apical membrane and the passive K+ flux across the basolateral membrane cause both transient inward and outward Isc under the ouabain-treated condition of frog skin.


Applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections: a systematic review of preclinical in vivo evidence.
Chagas disease and sleeping sickness are neglected tropical diseases closely related to poverty, for which the development of plant-derived treatments has not been a promising prospect. Thus, we systematicaly review the preclinical in vivo evidence on the applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections. Characteristics such as disease models, treatments, toxicological safety and methodological bias were analysed. We recovered 66 full text articles from 16 countries investigating 91 plant species. The disease models and treatments were highly variable. Most studies used native (n = 36, 54·54%) or exotic (n = 30, 45·46%) plants with ethnodirected indication (n = 45, 68·18%) for trypanosomiasis treatment. Complete phytochemical screening and toxicity assays were reported in only 15 (22·73%) and 32 (48·49%) studies, respectively. The currently available preclinical evidence is at high risk of bias. The absence of or incomplete characterization of animal models, treatment protocols, and phytochemical/toxicity analyses impaired the internal validity of the individual studies. Contradictory results of a same plant species compromise the external validity of the evidence, making it difficult determine the effectiveness, safety and biotechnological potential of plant-derived products in the development of new anti-infective agents to treat T. cruzi and T. brucei infections.


Interatomic scattering in energy dependent photoelectron spectra of Ar clusters.
Soft X-ray photoelectron spectra of Ar 2p levels of atomic argon and argon clusters are recorded over an extended range of photon energies. The Ar 2p intensity ratios between atomic argon and clusters' surface and bulk components reveal oscillations similar to photoelectron extended X-ray absorption fine structure signal (PEXAFS). We demonstrate here that this technique allows us to analyze separately the PEXAFS signals from surface and bulk sites of free-standing, neutral clusters, revealing a bond contraction at the surface.


Nurses' experiences of caring for people with COVID-19 in Hong Kong: a qualitative enquiry.
Nurses are the largest group of healthcare workers on the front line of efforts to control the COVID-19 pandemic. An understanding of their nursing experiences, the challenges they encountered and the strategies they used to address them may inform efforts to better prepare and support nurses and public health measures when facing a resurgence of COVID-19 or new pandemics. This study aimed to explore the experiences of nurses caring for people with suspected or diagnosed COVID-19 in Hong Kong. A qualitative study was conducted using individual, semistructured interviews. All interviews were audio-recorded and transcribed verbatim for thematic analysis. Participants were recruited from acute hospitals and a public health department in Hong Kong from June 2020 to August 2020. A purposive sample of registered nurses (N=39) caring for people with COVID-19 in Hong Kong were recruited. Two-thirds of the nurses had a master's degree and over a third had 6-10 years of nursing experience. Around 40% of the nurses cared for people with COVID-19 in isolation wards and a quarter performed COVID-19-related work for 31-40 hours/week. Most (90%) had training in COVID-19 and three-quarters had experience of working in infection control teams. Six key themes emerged: confronting resource shortages; changes in usual nursing responsibilities and care modes; maintaining physical and mental health; need for effective and timely responses from relevant local authorities; role of the community in public health protection and management; and advanced pandemic preparedness. Our study found that nurses possessed resilience, self-care and adaptability when confronting resource shortages, changing nursing protocols, and physical and mental health threats during the COVID-19 pandemic. However, coordinated support from the clinical environment, local authorities and community, and advanced preparedness would likely improve nursing responses to future pandemics.


Phosphorylation of the human interleukin-2 receptor and a synthetic peptide identical to its C-terminal, cytoplasmic domain.
The recombinant human interleukin-2 (IL-2) receptor was expressed in mouse mammary epithelial cells following the transfection of these cells with an expression vector containing the human IL-2 receptor cDNA. The recombinant IL-2 receptor in these cells was rapidly phosphorylated in response to phorbol myristate acetate (PMA), but its phosphorylation could not be detected in the absence of PMA or upon addition of human IL-2. The C-terminal, cytoplasmic peptide domain of the IL-2 receptor, Gln-Arg-Arg-Gln-Arg-Lys-Ser-Arg-Arg-Thr-Ile, was synthesized and used as a substrate for protein kinase C. The Km for phosphorylation of the peptide by protein kinase C was 23 microM. The stoichiometry of phosphorylation was 1 mol of phosphate/mol of peptide and serine was the predominant amino acid phosphorylated. Because this peptide was a good substrate for protein kinase C in vitro, it was possible that the same serine (serine 247) was also phosphorylated in the receptor in the cell. The IL-2 receptor gene in the expression vector was therefore altered by site-directed mutagenesis to code for an IL-2 receptor containing an alanine in the place of serine 247. The IL-2 receptor expressed by these cells was not phosphorylated in the presence of PMA. These data suggest that protein kinase C, in response to PMA, phosphorylates the C-terminal serine residue (serine 247) in the human IL-2 receptor.


Effect of cold air cooling on the incidence of postinflammatory hyperpigmentation after Q-switched Nd:YAG laser treatment of acquired bilateral nevus of Ota like macules.
To investigate the effect of cold air cooling on the incidence of postinflammatory hyperpigmentation (PIH) after laser treatment in Asian patients. Randomized, controlled, split-face study. Skin laser center of a university hospital. Twenty-three Thai women with acquired bilateral nevus of Ota-like macules. Patients were treated using a 1064-nm Q-switched Nd:YAG laser at an average fluence of 7.0 J/cm(2) using a 3-mm spot size. The same laser fluence was used on both sides of the face in individual patients. One randomly selected face side of each patient was cooled using a cold air cooling device during and 30 seconds before and after laser irradiation, and the other side was irradiated without cooling. Occurrence of PIH was objectively evaluated by measuring the melanin index using a spectrometer, and it was subjectively assessed by 2 nontreating physicians before treatment and once weekly for 4 weeks. Of the 21 patients who completed the study, 13 (62%) and 5 (24%) developed PIH on the cooled and uncooled sides, respectively. One patient (5%) had PIH on both the cooled and uncooled sides, and 2 (10%) did not experience PIH. The cooled sides were significantly more likely to become hyperpigmented after laser irradiation than the uncooled sides (relative risk, 2.6; 95% confidence interval, 1.13-6.00; P = .03). The clinical evaluation corresponded to the spectrometer reading. Epidermal cooling with cold air is associated with an increased risk of PIH after Q-switched Nd:YAG laser treatment. clinicaltrials.gov Identifier: NCT00287001.


Older Adults Engaging in Online Dating: What Gerontological Nurses Should Know.
Many older adults maintain interest in intimate partner relationships and actively seek dates. Online dating websites are gaining popularity as being a convenient way to link with potential dates, particularly for women and individuals who live in independent dwellings or rural areas. Several online dating websites market exclusively to individuals 50 and older. Although connecting with others via the Internet can decrease social isolation, there are potential risks involved in online dating. Health care providers do not always assess dating and sexual health in the older adult population. Nurses are in a position to assess the dating relationships of older patients and can ask targeted questions to determine if patients are in a potentially risky relationship. A non-judgmental attitude and compassionate approach is essential. Knowledge of safe practices, alerting red flags, and available resources are essential tools for gerontological nurses to possess.


Structural, vibrational and electronic properties of α'-Ga2S3 under compression.
We report a joint experimental and theoretical study of the low-pressure phase of α'-Ga2S3 under compression. Theoretical ab initio calculations have been compared to X-ray diffraction and Raman scattering measurements under high pressure carried out up to 17.5 and 16.1 GPa, respectively. In addition, we report Raman scattering measurements of α'-Ga2S3 at high temperature that have allowed us to study its anharmonic properties. To understand better the compression of this compound, we have evaluated the topological properties of the electron density, the electron localization function, and the electronic properties as a function of pressure. As a result, we shed light on the role of the Ga-S bonds, the van der Waals interactions inside the channels of the crystalline structure, and the single and double lone electron pairs of the sulphur atoms in the anisotropic compression of α'-Ga2S3. We found that the structural channels are responsible for the anisotropic properties of α'-Ga2S3 and the A'(6) phonon, known as the breathing mode and associated with these channels, exhibits the highest anharmonic behaviour. Finally, we report calculations of the electronic band structure of α'-Ga2S3 at different pressures and find a nonlinear pressure behaviour of the direct band gap and a pressure-induced direct-to-indirect band gap crossover that is similar to the behaviour previously reported in other ordered-vacancy compounds, including β-Ga2Se3. The importance of the single and, more specially, the double lone electron pairs of sulphur in the pressure dependence of the topmost valence band of α'-Ga2S3 is stressed.


Rhenium-germanium triple bonds: syntheses and reactions of the germylidyne complexes mer-[X2(PMe3)3Re≡Ge-R] (X=Cl, I, H; R=m-terphenyl).
A general approach to the first compounds that contain rhenium-germanium triple and double bonds is reported. Heating [ReCl(PMe3)5] (1) with the arylgermanium(II) chloride GeCl(C6H3-2,6-Trip2) (2; Trip=2,4,6-triisopropylphenyl) results in the germylidyne complex mer-[Cl2 (PMe3)3Re≡Ge-C6H3-2,6-Trip2] (4) upon PMe3 elimination. An equilibrium that is dependent on the PMe3 concentration exists between complexes 1 and 4. Removal of the volatile PMe3 shifts the equilibrium towards complex 4, whereas treatment of 4 with an excess of PMe3 gives a 1:1 mixture of 1 and the PMe3 adduct of 2, GeCl(C6H3-2,6-Trip2)(PMe3) (2-PMe3). Adduct 2-PMe3 can be selectively obtained by addition of PMe3 to chlorogermylidene 2. The NMR spectroscopic data for 2-PMe3 indicate an equilibrium between 2-PMe3 and its dissociation products, 2 and PMe3 , which is shifted far towards the adduct site at ambient temperature. NMR spectroscopic monitoring of the reaction of complex 1 with 2 and the reaction of complex 4 with PMe3 revealed the formation of two key intermediates, which were identified to be the chlorogermylidene complexes cis/trans-[Cl(PMe3)4 Re=Ge(Cl)C6H3-2,6-Trip2] (cis/trans-3) by using NMR spectroscopy. Labile chlorogermylidene complexes cis/trans-3 can be also generated from trans-[Cl(PMe3)4 Re≡Ge-C6H3-2,6-Trip2]BPh4 (9) and (nBu4N)Cl at low temperature, and decompose at ambient temperature to give a mixture of complexes 1 and 4. Complex 4 reacts with LiI to give the diiodido derivative mer-[I2(PMe3)3Re≡Ge-C6H3-2,6-Trip2] (5), which undergoes a metathetical iodide/hydride exchange with Na(BEt3H) to give the dihydrido germylidyne complex mer-[H2(PMe3)3Re≡Ge-C6H3-2,6-Trip2] (6). Carbonylation of 4 induces a chloride migration from rhenium to the germanium atom to afford the chlorogermylidene complex mer-[Cl(CO)(PMe3)3Re=Ge(Cl)C6H3-2,6-Trip2] (7). Similarly, MeNC converts complex 4 into the methylisocyanide analogue mer-[Cl(MeNC)(PMe3)3Re=Ge(Cl)C6H3-2,6-Trip2] (8). Chloride abstraction from 4 by NaBPh4 in the presence of PMe3 gives the cationic germylidyne complex trans-[Cl(PMe3)4 Re≡Ge-C6H3-2,6-Trip2]BPh4 (9). Heating complex 4 with cis-[Mo(PMe3)4(N2)2] induces a germylidyne ligand transfer from rhenium to molybdenum to afford the germylidyne complex trans-[Cl(PMe3)4Mo≡Ge-C6H3-2,6-Trip2] (10). All new compounds were fully characterized and their molecular structures studied by X-ray crystallography, which led to the first experimentally determined Re-Ge triple- and double-bond lengths.


Microarray expression profiles of long non-coding RNAs in germinal center-like diffuse large B-cell lymphoma.
Long non-coding RNAs (lncRNAs) are continuously transcribed and are involved in various cellular activities. However, their contributions to the occurrence and development of germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL) remain largely unknown. We applied microarray technology to profile the expression of lncRNAs in two different GCB-DLBCL cell lines (OCI-ly1 and OCI-ly19) and normal B lymphocytes. We demonstrated that 21,539 lncRNAs were expressed in all of the samples analyzed. This included 1,648 lncRNAs that showed a ≥2-fold upregulation and 2,671 lncRNAs that displayed a ≥2-fold downregulation in tumor cell lines (P<0.05). The expression levels of 8 lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatic analyses (Gene Ontology, pathway and network analysis) were performed to predict how the differentially expressed lncRNAs may function in GCB-DLBCL. Results from the pathway analysis suggested that totals of 64 and 62 biological pathways corresponded to upregulated and downregulated transcripts, respectively (P<0.05). Additionally, we constructed a lncRNA‑mRNA network for the purpose of identifying specific coding genes which were co-expressed with 5 selected lncRNAs. Conclusively, our results may contribute to a better understanding of GCB-DLBCL pathogenesis.


Comparison of the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler on exhaled inflammatory markers in childhood asthma.
Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma. To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC). In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period. Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment. The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.


Description of a new weakfish, Cynoscion nortoni, from Ecuador with a note on the distribution of Umbrina bussingi (Perciformes: Sciaenidae).
A new sciaenid was found at a fish market on the Ecuadorian coast. Cynoscion nortoni, described from 11 specimens, is characterised by a relatively large eye, a long head and pectoral fin, a high dorsal fin-ray count and a dark, steel grey colour on its dorsum. The specimens were captured over the continental shelf with a long line at depths between 100 and 200 meters. Another deep water species, Umbrina bussingi, is recorded for the first time from southern Colombia.


Successful combination therapy with vancomycin and arbekacin against infective endocarditis caused by MRSA.
Infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) is a serious disease and sometimes leads to poor prognosis. We should have several therapeutic options. Arbekacin is one of the aminoglycoside antibiotics, which is more active against MRSA and less nephrotoxic than gentamicin. Here we presented a successfully treated case of severe MRSA endocarditis without any adverse effect by monitoring therapeutic level of vancomycin and arbekacin.


Recent advances in diagnosis and treatment of colorectal T1 carcinoma.
Colorectal T1 tumors (submucosally invasive carcinoma) have special characteristics in terms of pathology, diagnosis, and treatment. The clinicopathologic features of T1 tumors are reviewed. Incidence of T1 tumors was approximately 10 percent, and the percentage of node metastasis was 10 to 11 percent, whereas hepatic metastasis was <1 percent. Macroscopically they were divided into three types: polypoid, ulcerating, and flat. The ulcerating type was divided into two subgroups: polypoid growth and nonpolypoid growth based on the histologic appearance of resected specimens. The tools for detecting T1 tumors were fecal occult blood test and colonoscopy, and magnifying colonoscopy and chromography facilitate more precise diagnosis. Ultrasonography also was useful for the correct diagnosis of the depth of cancer invasion. Most polypoid and some flat T1 tumors were safely treated by polypectomy or endoscopic mucosal resection alone; however, when resected specimens contained risk factors for metastasis, such as deep invasion (sm2, sm3) and vessel invasion, additional surgery was necessary for cure. For rectal T1 tumors, the most appropriate procedure should be carefully selected from several therapeutic options to preserve anal function. The management of colorectal T1 tumors should be determined according to the types of macroscopic appearances. The risk of node metastasis could be predicted based on risk factors that were characterized by the level of cancer invasion and the presence or absence of vessel invasion. Minimally invasive treatment should be chosen for colorectal T1 tumors.


Optimization of pressurized liquid extraction using a multivariate chemometric approach for the determination of anticancer drugs in sludge by ultra high performance liquid chromatography-tandem mass spectrometry.
The present paper describes an analytical method for the determination of 2 widely administered anticancer drugs, ifosfamide and cyclophosphamide, contained in sewage sludge. The method relies on the extraction from the solid matrix by pressurized liquid extraction, sample purification by solid-phase extraction and analysis by ultra high performance liquid chromatography coupled with tandem mass spectrometry. The different parameters affecting the extraction efficiency were optimized using an experimental design. Solvent nature was the most decisive factor for the extraction but interactions between some parameters also appeared very influent. The method was applied to seven different types of sludge for validation. The performances of the analytical method displayed high variability between sludges with limits of detection spanning more than one order of magnitude and confirming the relevance of multi-sample validation. Matrix effect has been determined as the most limiting analytical step for quantification with different extent depending on analyte and sludge nature. For each analyte, the use of deuterated standard spiked at the very beginning ensured the complete compensation of losses regardless of the sample nature. The suitability of the method between freshly spiked and aged samples has also been verified. The optimized method was applied to different sludge samples to determine the environmental levels of anticancer drugs. The compounds were detected in some samples reaching 42.5μg/kgDM in ifosfamide for the most contaminated sample.


Short-term residential psychotherapy: psychotherapy in a nutshell.
Psychotherapy in a psychotherapeutic community often is characterized by absence of time limits and by long duration. In this article an account is given of the adaptions that are necessary when short-term treatment is carried out in such a residential setting. Implications for focus, therapy program, and treatment style are presented.


Postpsychotic depression and negative symptoms: an investigation of syndromal overlap.
The authors studied 46 patients with the operationally defined syndrome of postpsychotic depression following episodes of schizophrenia or schizoaffective disorder. Half of these patients were also found to satisfy criteria for negative symptoms. The patients with negative symptoms were rated as more severely ill on global measures, but there was only limited evidence that they were more depressed. Nevertheless, in a randomized double-blind trial of imipramine versus placebo as an adjunct to the fluphenazine decanoate and benztropine regimens of the patients with negative symptoms, the patients who received imipramine seemed to show more improvement.


Time Utilization Among Immunization Clinics Using an Electronic Immunization Registry (Part 2): Time and Motion Study of Modified User Workflows.
Digital health interventions have the potential to improve the provision of health care services through digitized data collection and management. Low- and middle-income countries are beginning to introduce electronic immunization registries (EIRs) into their routine immunization services to better capture and store childhood vaccination information. Especially in Africa, where 25% of children remain unimmunized or underimmunized, technologies that can help identify children due for a vaccination are particularly important for improving vaccination coverage. However, an improved understanding of the effectiveness of these systems is needed to develop and deploy sustainable EIRs in low- and middle-income countries. We conducted an interventional pretest-posttest design study that sought to improve time efficiency through workflow modifications in Kenyan immunization clinics. Our aim was to describe how activity times differed after introducing workflow modifications that could potentially reduce the time needed to perform routine data entry activities. Our intent was to demonstrate changes in efficiency when moving from the existing dual-data entry workflow to a future paperless workflow by health facility size and experience length of health care workers (HCWs). We tested how 3 workflow modifications would affect time utilization among HCWs using the EIR at the point of care compared with baseline immunization clinic workflows. Our outcome of interest was the time taken to complete individual activities and a patient's total time in the clinic where we compared the time spent during the baseline workflow with that during the modified workflow. We used a standardized tool to observe and document the immunization clinic workflow. To estimate differences in time utilization, we used bivariate analyses and fit multivariate linear mixed-effects models. Our study found that for HCWs using an EIR, the introduction of modified workflows decreased the amount of time needed to provide services to children seen in the immunization clinic. With a baseline mean time of 10 minutes spent per child, this decreased by about 3 minutes when the preparation modification was introduced and almost 5 minutes for the paperless and combined modifications. Results pertaining to the EIR's performance and ability to connect to the internet were particularly insightful about potential causes of delays. We were able to conduct a concise clinical simulation exercise by introducing modified workflows and estimating their impact on time utilization in immunization clinics using an EIR. We found that the paperless workflow provided the largest time savings when delivering services, although this was threatened by poor EIR performance and internet connectivity. This study demonstrated that not only should digital health interventions be built and adapted for particular use cases but existing user workflows also need to adapt to new technology.


X-ray Spectroscopy of a Rare-Earth Molecular System Measured at the Single Atom Limit at Room Temperature.
We investigate the limit of X-ray detection at room temperature on rare-earth molecular films using lanthanum and a pyridine-based dicarboxamide organic linker as a model system. Synchrotron X-ray scanning tunneling microscopy is used to probe the molecules with different coverages on a HOPG substrate. X-ray-induced photocurrent intensities are measured as a function of molecular coverage on the sample, allowing a correlation of the amount of La ions with the photocurrent signal strength. X-ray absorption spectroscopy shows cogent M4,5 absorption edges of the lanthanum ion originated by the transitions from the 3d3/2 and 3d5/2 to 4f orbitals. X-ray absorption spectra measured in the tunneling regime further reveal an X-ray excited tunneling current produced at the M4,5 absorption edge of the La ion down to the ultimate atomic limit at room temperature.


In vitro susceptibility of Blastocystis hominis isolated from patients with irritable bowel syndrome.
This study aims to determine the growth pattern and in vitro susceptibility of clinical isolates of Blastocystis hominis to different concentrations of metronidazole, furazolidone and ciprofloxacin. Stool specimens from 25 consecutive patients with irritable bowel syndrome presenting to the gastroenterology department of Aga Khan University Hospital between January and May 2003 are examined by microscopy and cultured for B. hominis. Drug susceptibility assays are performed for metronidazole, furazolidone, and ciprofloxacin using final concentrations of 0.01 mg/mL and 0.1 mg/mL. The effect of the drugs is assessed after B. hominis culture for 48 h. With furazolidone and metronidazole, 68% (17/25) and 60% (15/25) of B. hominis isolates, respectively, failed to grow at drug concentrations of both 0.01 mg/mL and 0.1 mg/mL. However, ciprofloxacin failed to suppress growth completely at both concentrations. B. hominis resistance to furazolidone, metronidazole and ciprofloxacin at 0.01 mg/mL was 32% (8/25), 40% (10/25) and 100% (25/25), respectively. B. hominis isolates varied in their degree of susceptibility to the three drugs studied, being greater with furazolidone than with metronidazole, and complete resistance with ciprofloxacin.


A study of the bio-accessibility of welding fumes.
The respiratory bio-accessibility of a substance is the fraction that is soluble in the respiratory environment and is available for absorption. In the case of respiratory exposure the amount of absorbed substance plays a main role in the biological effects. Extensive bio-accessibility studies have always been an essential requirement for a better understanding of the biological effects of different workplace aerosols, such as welding fumes. Fumes generated using three different welding techniques, manual metal arc (MMA) welding, metal inert gas (MIG) welding, and tungsten inert gas (TIG) welding were investigated in the present study. Each technique was used for stainless steel welding. Welding fumes were collected on PVC membrane filters in batches of 114 using a multiport air sampler. Three different fluids were applied for the solubility study: deionised water and two kinds of lung fluid simulants: lung epithelial lining fluid simulant (Gamble's solution) and artificial lung lining fluid simulant (Hatch's solution). In order to obtain sufficient data to study the tendencies in solubility change with time, seven different leaching periods were used (0.5, 1, 2, 4, 8, 16, 24 h), each of them with three replicates. The effect of dissolution temperature was also studied. The total amounts of selected metals in the three different welding fumes were determined after microwave-assisted digestion with the mixture of aqua regia and hydrofluoric acid. The most obvious observation yielded by the results is that the solubility of individual metals varies greatly depending on the welding technique, the composition of the leaching fluid and leaching time. This study shows that the most reasonable choice as a media for the bio-assessment of solubility might be Hatch's solution by a dissolution time of 24 h.


Comparison of Physician-Documented Versus Patient-Reported Collection of Comorbidities Among Patients With Prostate Cancer Upon First Visit to the Urology Clinic.
To determine whether patient-reported collection of comorbidities online is sufficiently accurate to warrant use as part of a physician-reviewed, baseline medical history. Comorbidities were collected for a sample of 213 new prostate cancer visits to our urology clinic through an online survey (called Baseline Medical History) before the clinical encounter. The frequency distributions of comorbidities as reported by patients before physician review were compared with those documented by physicians for a sample of 298 consecutive patients presenting to the same urology clinic before the survey went live. The overall frequency distribution of comorbidities and life expectancy estimates were similar between the two groups. A few comorbidity categories were reported with higher frequency in the patient-reported group compared with the physician-documented group, including neurologic comorbidities (7.5% v 1.7%; difference 6%; 95% CI, 2.0% to 10%; P = .001) and back pain (24% v 13%; difference 12%; 95% CI, 4.8% to 19%; P = .001). A similar trend was seen for vascular conditions, although the difference did not meet conventional levels of statistical significance. Genitourinary comorbidities, including problems with urination and erectile dysfunction, were better captured by the physician-reported group compared with the patient-reported group (68% v 53%; difference 15%; 95% CI, 7% to 24%; P = .001), as were other musculoskeletal comorbidities (8.7% v 1.9%; difference 7%; 95% CI, 3.2% to 11%; P = .001). Patients completing a medical history, at their own pace and in the comfort of their own home, provide relatively accurate and complete information, even before physician review. Patient reporting of comorbidities thus seems to be a reliable starting point for the documentation of the medical history in the clinic.


Tug of war between Acinetobacter baumannii and host immune responses.
Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen with growing clinical significance. Acinetobacter baumannii has an exceptional ability to rapidly develop drug resistance and to adhere to abiotic surfaces, including medical equipment, significantly promoting bacterial spread and also limiting our ability to control A. baumannii infections. Consequently, A. baumannii is frequently responsible for ventilator-associated pneumonia in clinical settings. In order to develop an effective treatment strategy, understanding host-pathogen interactions during A. baumannii infection is crucial. Various A. baumannii virulence factors have been identified as targets of host innate pattern-recognition receptors, which leads to activation of downstream inflammasomes to develop inflammatory responses, and the recruitment of innate immune effectors against A. baumannii infection. To counteract host immune attack, A. baumannii regulates its expression of different virulence factors. This review summarizes the significance of mechanisms of host-bacteria interaction, as well as different bacteria and host defense mechanisms during A. baumannii infection.


[Construction and expression of regulatable recombinant adenovirus vector for mouse PLP-Ig chimeric protein].
To construct a regulatable recombinant adenovirus vector expressing mouse proteolipid protein (PLP)-Ig. Total RNA was extracted from WT-1 hybridoma cells to clone Ig heavy chain Fc fragment gene. PCR was carried out to link PLP(139-151) gene and signal peptide with Fc fragment gene. pTRE-shuttle vector was used to ligate PLP-Ig gene and the backbone of the replication-incompetent adenoviral vector. After confirming the desired recombinant adenovirus by PCR and restriction endonuclease digestion analysis, it was packaged and propagated in HEK 293 cells. Tetracycline was used to regulate the expression of PLP-Ig, and Western blot was used to detect the gene expression. The expression of PLP-Ig was confirmed by Western blot and its expression could be regulated by tetracycline. The regulatable recombinant adenovirus vector for mouse PLP-Ig was constructed and expressed successfully, which lays the foundation for further study on gene therapy of EAE and induction of immune tolerance.


Effective anti-leishmanial activity of minimalist squaramide-based compounds.
In order to evaluate the in vitro leishmanicidal activity of N,N'-Squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against Leishmania infantum, Leishmania braziliensis and Leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. Infectivity and cytotoxicity tests were performed on J774.2 macrophage cells using meglumine antimoniate (Glucantime) as the reference drug. Changes in metabolite excretion by 1H-NMR and the ultrastructural alterations occurring in the parasites treated using transmission electron microscopy (TEM), was analyzed. Compounds 1, 7, 11, 14 and 17 were the more active and less toxic. Infection rates showed that the order of effectiveness was 17 > 11 > 14 > 7 for both L. infantum and L. braziliensis and in the same way, the compound 1 for L. donovani. All these compounds have altered the typical structure of the promastigotes, glycosomes and mitochondria. These severe modifications by the compounds are the ultimate reasons for the alterations observed in the excretion products. The Squaramide 17 (3-(butylamino)-4-((3-(dimetilamino)propyl)(methyl)amino)cyclobut-3-en-1,2-dione) was clearly the most efficient of all compounds. The data appear to confirm that the severe modifications generated in organelles such as glycosomes or mitochondria by the compounds are the ultimate reasons for the alterations observed in the excretion products of all species. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-leishmanial agent.


Controlling surface roughness in vapor-deposited poly(amic acid) films by solvent-vapor exposure.
A series of vapor-deposited poly(amic acid) (PAA) films were exposed to dimethyl sulfoxide (DMSO) vapors to investigate sorption kinetics and surface smoothing phenomena. Gravimetric sorption and secondary-ion mass spectrometry (SIMS) results are both consistent with frontal (case II) diffusion. These experiments suggest that the solvent front is defined by a sharp interface that delineates the swollen material from the unswollen material. Solvent-vapor smoothing was studied by first depositing PAA onto rough aluminum surfaces, and then, during solvent-vapor exposure, the surface topology was continuously monitored using a light interference microscope. The resulting time-dependent power spectra indicate that high-frequency defects smooth faster than low-frequency defects. This frequency dependence was further investigated by depositing PAA onto a series of sinusoidal surfaces and exposing them to solvent vapor inside a flow channel. The sinusoidal amplitudes decay exponentially with time, with decay constants that are proportional to the surface frequency. To explain the physics of surface smoothing, a two-parameter model is presented and agrees qualitatively with experimental data.


Why are we afraid to love?
The crisis of the couple in today's society, increases the number of singles and causes difficulty in creating stable and lasting relationships over time. The last two censuses of the Italian population show an increase in the number of singles, especially among the young generation. From this figure we have tried to understand the causes of this phenomenon both from the point of view of sociology and psychology. The sociologist Baumann considers the crisis of the couple and the increase in singles as a result of the crisis of modern society. The author says that we live in a fluid world where everything changes quickly and there is nothing stable and this also affects the couple. From a psychological point of view, reference has been made to all that psychoanalytic writers from Freud, have said about the crisis of the couple. It is clear that some subjects have difficulty maintaining stable and long-lasting relationships because they are suffering from philophobia (fear of love). We have tried to understand what the causes of different types of philophobia for both men and women are. It was found that the origins are created in the early childhood relationships with their parents. It 'was found that people who have had problems in their childhood relationships with their parents, because of their lack of love, tend to reproduce in adulthood the same dysfunctional relational model, learned in childhood.


Methylnaltrexone antagonizes opioid-mediated enhancement of HIV infection of human blood mononuclear phagocytes.
Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. We and others have recently demonstrated that opioid enhances HIV infection of human macrophages through modulation of beta-chemokines and the CCR5 receptor and that this effect is reversed by naltrexone, a tertiary opioid antagonist. Tertiary opioid antagonists cannot be used in opioid-dependent patients because they precipitate withdrawal or reversal of analgesia. We determined whether the quaternary opioid antagonist methylnaltrexone (MNTX), now in phase III clinical trials for opioid-induced constipation, reverses the opioid-mediated enhancement of HIV infection of macrophages at clinically relevant doses. MNTX completely abrogated morphine-induced HIV Bal strain infection of macrophages. MNTX also inhibited the R5 strain (ADA) envelope-pseudotyped HIV replication induced by morphine. Furthermore, MNTX abolished morphine-mediated up-regulation of CCR5 receptor expression. The ability of MNTX to block opioid-induced CCR5 expression and HIV replication at clinically relevant doses may have additional benefit for opioid abusers with HIV infection, or patients with AIDS pain receiving opioids.


Accelerating progress towards universal health coverage in Asia and Pacific: improving the future for women and children.
Universal health coverage generates significant health and economic benefits and enables governments to reduce inequity. Where universal health coverage has been implemented well, it can contribute to nation-building. This analysis reviews evidence from Asia and Pacific drawing out determinants of successful systems and barriers to progress with a focus on women and children. Access to healthcare is important for women and children and contributes to early childhood development. Universal health coverage is a political process from the start, and public financing is critical and directly related to more equitable health systems. Closing primary healthcare gaps should be the foundation of universal health coverage reforms. Recommendations for policy for national governments to improve universal health coverage are identified, including countries spending < 3% of gross domestic product in public expenditure on health committing to increasing funding by at least 0.3%/year to reach a minimum expenditure threshold of 3%.


In situ probing behaviors of single LiNiO2 nanoparticles by merging CAFM and AM-FM techniques.
Probing single active nanoparticles of Li-ion battery electrodes is challenging but important to reveal their behaviors including morphology, mechanical properties and electrochemical reactions with an electrolyte. In this work, we in situ investigated voltage-induced behaviors of single LiNiO2 nanoparticles by merging conductive atomic force microscopy (CAFM) and amplitude modulation-frequency modulation (AM-FM) techniques. The former was used to apply a voltage between a selected single nanoparticle and a substrate through its tip, while the latter was done for imaging. Evolution in the morphology and stiffness of the nanoparticles induced by different voltages under air and dried argon atmospheres was tracked, respectively. The evolution mechanisms related to electrochemical reactions were discussed in detail. These results suggest that the merged techniques would provide an indirect and effective approach to study the behaviors and electrochemical reactions of electrode materials on the nanometer scale and even single nanoparticles.


Uterine flushing proteome of the tammar wallaby after reactivation from diapause.
The marsupial tammar wallaby has the longest period of embryonic diapause of any mammal, up to 11 months, during which there is no cell division or blastocyst growth. Since the blastocyst in diapause is surrounded by acellular coats, the signals that maintain or terminate diapause involve factors that reside in uterine secretions. The nature of such factors remains to be resolved. In this study, uterine flushings (UFs) were used to assess changes in uterine secretions of tammars using liquid chromatography-mass spectrometry (LC-MS/MS) during diapause (day 0 and 3) and reactivation days (d) 4, 5, 6, 8, 9, 11 and 24 after removal of pouch young (RPY), which initiates embryonic development. This study supports earlier suggestions that the presence of specific factors stimulate reactivation, early embryonic growth and cell proliferation. A mitogen, hepatoma-derived growth factor and soluble epidermal growth factor receptors were observed from d3 until at least d11 RPY when these secreted proteins constituted 21% of the UF proteome. Binding of these factors to specific cellular receptors or growth factors may directly stimulate DNA synthesis and division in endometrial gland cells. Proteins involved in the p53/CDKN1A (p21) cell cycle inhibition pathway were also observed in the diapause samples. Progesterone and most of the oestrogen-regulated proteins were present in the UF after d3, which is concomitant with the start of blastocyst mitoses at d4. We propose that once the p21 inhibition of the cell cycle is lost, growth factors including HDGF and EGFR are responsible for reactivation of the diapausing blastocyst via the uterine secretions.


Safety of perioperative cerebral oxygen saturation during debranching in patients with incomplete circle of Willis.
The consequences of common carotid artery (CCA) cross-clamping during debranching before thoracic endovascular aortic repair are unclear. We examined the safety of a simple CCA cross-clamping procedure under regional cerebral oxygen saturation monitoring (rSO2) in patients with a complete or incomplete circle of Willis (CoW) anatomy. Twenty-eight patients with thoracic aneurysm underwent elective debranching thoracic endovascular aortic repair with bilateral frontal rSO2 monitoring at our institution between January 2012 and October 2015. Before CCA cross-clamping, we maintained a systemic mean arterial pressure of >100 mm Hg with a vasopressor. We recorded the bilateral frontal rSO2 before, during and after CCA cross-clamping. The CoW was incomplete in 11 (39.3%) patients. Of these, 6 patients had a complication of ischaemic potential. The left frontal rSO2 was <50% in 3 patients but did not fall below 40%. Compared with baseline values (mean ± SD 64.6 ± 6.9%), the left frontal rSO2 showed no significant change perioperatively in those with a complete CoW on the left CCA cross-clamping (during: 61.0 ± 7.9%, P = 0.17; after: 65.1 ± 5.9%, P = 0.09). In patients with an incomplete CoW with ischaemic potential, the left frontal rSO2 did not change significantly after cross-clamping (baseline: 59.8 ± 3.2%, during: 55.5 ± 5.0%; P = 0.10) but increased significantly on declamping (62.8 ± 4.5%, P = 0.023). The extent of the changes in the mean left frontal rSO2 on clamping and declamping decreased and increased by 7.3% and 11.7%, respectively, in patients with an incomplete CoW, when compared with 5.3% and 5.8% in those with a complete CoW (P = 0.65 and 0.31, respectively). No perioperative cerebrovascular events were observed. Simple CCA cross-clamping during debranching was safe when arterial pressure was supported and rSO2 was monitored, even with an incomplete CoW and ischaemic potential.


The small intestine: prospects for therapeutic approaches in secretory diarrhoeal diseases.
In many diarrhoeal diseases the intestinal mucosa is stimulated to secrete salt and water. This occurs in diarrhoea as a result of several bacterial toxins, is associated with inflammation and release of inflammatory mediators, and, in many instances, occurs when a neural element is evident. An understanding of the basic underlying mechanisms of secretion could lead to improvements in therapy. Development of vaccines against cholera is showing promise, and a knowledge of the complex field of inflammatory mediators, many of which provoke secretion, provides a foundation for development of more specific and selective anti-inflammatory agents. A detailed understanding of the complicated intracellular second-messenger systems, which are switched on by externally perceived signals, and of the ion transport responses, which are responsible for secretion, may lead to the development of specific anti-diarrhoeal drugs. Meanwhile, the message that oral rehydration therapy for severe diarrhoea, including cholera, is successful, should continue to be widely promulgated and taken up.


Sphingomonas spermidinifaciens sp. nov., a novel bacterium containing spermidine as the major polyamine, isolated from an abandoned lead-zinc mine and emended descriptions of the genus Sphingomonas and the species Sphingomonas yantingensis and Sphingomonas japonica.
A yellow-pigmented bacterial strain, designated 9NM-10T, was isolated from an abandoned lead-zinc mine in Meizhou, Guangdong Province, China. Cells were strictly aerobic, Gram-stain-negative and motile with a polar monotrichous flagellum. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain 9NM-10T belongs to the genus Sphingomonas and was most closely related to Sphingomonas yantingensis JCM 19201T and Sphingomonas japonica JCM 15438T. DNA-DNA relatedness values between strain 9NM-10T and these two type strains were 43.6±1.3 and 35.4±0.9 %, respectively. It contained Q-10 as the predominant respiratory quinone and the major cellular fatty acids were C18 : 1ω7c, C16 : 0, C17 : 1ω6c and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The genomic DNA G+C content of strain 9NM-10T was 68.7±0.2 mol%. The polar lipids were sphingoglycolipid, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, diphosphatidylglycerol, an unidentified phospholipid and three unidentified lipids. Strain 9NM-10T contained spermidine as the major polyamine. On the basis of phenotypic, phylogenetic and chemotaxonomic analyses, strain 9NM-10T is considered to represent a novel species of the genus Sphingomonas, for which the name Sphingomonas spermidinifaciens sp. nov. is proposed. The type strain is 9NM-10T (=GDMCC 1.657T=DSM 27571T). Descriptions of the genus of Sphingomonas and the species Sphingomonas yantingensis and Sphingomonas japonica were also emended in this study.


The impact of chronic diseases on psychological distress among the older adults: the mediating and moderating role of activities of daily living and perceived social support.
Previous literature has shown that chronic diseases and psychological distress are correlated. However, the mediating and moderating mechanisms underlying this relationship have not been sufficiently studied. The purpose of this study was to explore the role played by activities of daily living (ADL) and perceived social support. Face-to-face questionnaire-based surveys were conducted with 3250 valid participants (age ≥60 years). Participants were assessed using the Barthel Index, Perceived Social Support Scale, and Depression Anxiety Stress Scale-21. 1) Chronic diseases had a significant direct effect on psychological distress in older adults; 2) the relationship between chronic diseases and psychological distress was partially mediated by ADL; and 3) the impact of chronic diseases on psychological distress was significantly moderated by perceived social support. More importantly, perceived social support was a protective factor that could effectively alleviate the adverse effects of chronic diseases on psychological distress. The results add to the existing literature by uncovering the underlying mechanisms between chronic diseases and mental health. These findings have implications for early intervention and prevention of mental health problems in older adults.


[Use of transesophageal atrial stimulation in the treatment of atrial flutter. Clinical experience].
Transesophageal atrial pacing with relatively low current output and wide pulse duration has been recently reported. With this method supraventricular tachycardias can be successfully induced and terminated. In this study 23 episodes of spontaneous common atrial flutter (21 patients) were treated by rapid transesophageal atrial pacing (output of 16 Volts and pulse duration of 10 msec). Sinus rhythm resumption was obtained in 18 episodes (78.2%), directly after interruption of stimulation in 7 and following brief periods of atrial fibrillation in 11. All patients tolerated the procedure well with moderate discomfort; no complications were observed. Esophageal pacing offers a useful, rapid, minimally invasive, well tolerated method of terminating atrial flutter in the clinical practice.


α-Cyperone (CYP) down-regulates NF-κB and MAPKs signaling, attenuating inflammation and extracellular matrix degradation in chondrocytes, to ameliorate osteoarthritis in mice.
Inflammation and extracellular matrix (ECM) degradation have been implicated in the pathological process of osteoarthritis (OA). α-Cyperone is the main active component of the traditional Chinese medicine Cyperus rotundus L. In this study, we found that α-Cyperone abolished the IL-1β-induced production of inflammatory cytokines in isolated rat chondrocytes, such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), in a dose-dependent manner (0.75, 1.5 or 3 μM). Also, the results showed that α-Cyperone downregulated the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5), and upregulated the expression of type-2 collagen. Mechanistically, molecular docking tests revealed that α-Cyperone stably and effectively binds to p65, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). α-Cyperone inhibited NF-κB activation by blocking its nuclear transfer, and decreasing the phosphorylation of mitogen-activated protein kinase (MAPKs). In addition, in vivo studies based on a mouse model of arthritis showed that α-Cyperone prevented the development of osteoarthritis. Therefore, α-Cyperone may be a potential anti-OA drug.


Study of population dynamic for a recombinant bacterium during continuous cultures: application of data filtering and smoothing.
A numerical method to process experimental data concerning plasmid stability of a recombinant bacteria during continuous cultures with nonselective media is proposed here. This method differs from previous ones in that it uses the derivatve form of the state equation of the Imanaka-Aiba model for recombinant cultures. The methodology proposed here allows one to estimate values for the two model parameters without forcing them to be constant. Until now, this could not be done using classical analytical techniques because these parameters have been considered invariable because of the integration used in the evaluation of the model. These parameters are (1) the difference in the specific growth rates between plasmid-carrying cells and plasmid-free cells (deltamu), and (2) the probability of plasmid loss by plasmid-containing cells (rho(r) mu(+)). The derivative technique used here is completed by mathematical treatments involving data filtering and smoothing. The values of the two parameters are in agreement with those already published. The current technique does not impose preconditions and permit us to further study related phenomena.


Design and Development of a Model to Study the Effect of Supplemental Oxygen on the Cystic Fibrosis Airway Microbiome.
Airway microbial communities are thought to play an important role in the progression of cystic fibrosis (CF) and other chronic pulmonary diseases. Microbes have traditionally been classified based on their ability to use or tolerate oxygen. Supplemental oxygen is a common medical therapy administered to people with cystic fibrosis (pwCF); however, existing studies on oxygen and the airway microbiome have focused on how hypoxia (low oxygen) rather than hyperoxia (high oxygen) affects the predominantly aerobic and facultative anaerobic lung microbial communities. To address this critical knowledge gap, this protocol was developed using an artificial sputum medium that mimics the composition of sputum from pwCF. The use of filter sterilization, which yields a transparent medium, allows optical methods to follow the growth of single-celled microbes in suspension cultures. To create hyperoxic conditions, this model system takes advantage of established anaerobic culturing techniques to study hyperoxic conditions; instead of removing oxygen, oxygen is added to cultures by daily sparging of serum bottles with a mixture of compressed oxygen and air. Sputum from 50 pwCF underwent daily sparging for a 72-h period to verify the ability of this model to maintain differential oxygen conditions. Shotgun metagenomic sequencing was performed on cultured and uncultured sputum samples from 11 pwCF to verify the ability of this medium to support the growth of commensal and pathogenic microbes commonly found in cystic fibrosis sputum. Growth curves were obtained from 112 isolates obtained from pwCF to verify the ability of this artificial sputum medium to support the growth of common cystic fibrosis pathogens. We find that this model can culture a wide variety of pathogens and commensals in CF sputum, recovers a community highly similar to uncultured sputum under normoxic conditions, and creates different culture phenotypes under varying oxygen conditions. This new approach might lead to a better understanding of unanticipated effects induced by the use of oxygen in pwCF on airway microbial communities and common respiratory pathogens.


Change in gait after high tibial osteotomy: A systematic review and meta-analysis.
We conducted a meta-analysis to analyze how high tibial osteotomy (HTO) changes gait and focused on the following questions: (1) How does HTO change basic gait variables? (2) How does HTO change the gait variables in the knee joint? Twelve articles were included in the final analysis. A total of 383 knees was evaluated. There were 237 open wedge (OW) and 143 closed wedge (CW) HTOs. There were 4 level II studies and 8 level III studies. All studies included gait analysis and compared pre- and postoperative values. One study compared CWHTO and unicompartmental knee arthroplasty (UKA), and another study compared CWHTO and OWHTO. Five studies compared gait variables with those of healthy controls. One study compared operated limb gait variables with those in the non-operated limb. Gait speed, stride length, knee adduction moment, and lateral thrust were major variables assessed in 2 or more studies. Walking speed increased and stride length was increased or similar after HTO compared to the preoperative value in basic gait variables. Knee adduction moment and lateral thrust were decreased after HTO compared to the preoperative knee joint gait variables. Change in co-contraction of the medial side muscle after surgery differed depending on the degree of frontal plane alignment. The relationship between change in knee adduction moment and change in mechanical axis angle was controversial. Based on our systematic review and meta-analysis, walking speed and stride length increased after HTO. Knee adduction moment and lateral thrust decreased after HTO compared to the preoperative values of gait variables in the knee joint.


Understanding the pro- and anti-inflammatory properties of IL-27.
The recent identification of IL-27 (IL-27p28/EBV-induced gene 3) and IL-27R (WSX-1/gp130) has provided new insights for the biology of IL-6/IL-12 family cytokines. Initial studies indicated that IL-27 can directly regulate T cell functions and suggested an important role for it in promoting Th1 type responses. However, subsequent studies have revealed that IL-27R signaling influences a variety of immune cell types and can inhibit either Th1 or Th2 type responses. Though elucidation of the Jak/STAT signaling pathways activated by IL-27R ligation has unveiled some of the molecular mechanisms used by IL-27 to promote inflammation, little is known about the anti-inflammatory activities of this cytokine. Thus, the aim of this review is to discuss the pleotropic nature of the IL-27/IL-27R interaction and attempt to reconcile the pro- and anti-inflammatory properties of this immunomodulator.


The speed of response to synthesized voice messages.
The experiment evaluates the effectiveness of synthesized cockpit voice warning messages using measures of reaction time (RT). Research has shown that voice messages are comparable to audio warnings and that synthesized voice messages are easily recognizable at low signal to noise ratios. This study evaluates synthesized voice messages are easily recognizable at low signal to noise ratios. This study evaluates synthesized voice messages by observing their performance in combination with auditory and visual indicators. Four different warning arrangements were used of which three had a Votrax voice component. The four warning systems represented future possible warning combinations for transport aircraft. Subjects had to deal with simulated emergencies whilst performing a psychomotor tracking task and monitoring ATC messages. Thirty commercial pilots took part in the study. Overall the four warning systems were equally effective in terms of RT. However, voice messages had significantly slower RTs than audio warnings. Voice messages and illuminated legends caused significantly less disruption of ATC monitoring than audio warnings. Pilots also consistently cross-checked voice and audio inputs with visual indicators. It is suggested that the proliferation of cockpit voice inputs should be avoided until human factor evaluations of simpler but equally effective warning systems have been completed.


Effect of epidermal growth factor (EGF) on steroid and cyclic nucleotide secretion, proliferation and ERK-related MAP-kinase in cultured rabbit granulosa cells.
The aim of our in vitro experiments was to study the effects of EGF on rabbit ovarian cells, as well as the possible mechanisms of these effects. The influence of EGF on steroidogenesis, proliferation, cyclic nucleotides and MAP-kinase in rabbit granulosa cells were studied. Results of RIA showed, that EGF stimulated the release of progesterone (1-100 ng/ml), cAMP (at 100 ng/ml), cGMP (1-100 ng/ml). EGF effect on estradiol output was biphasic: at dose 1 ng/ml it inhibited, whilst at 100 ng/ml it strongly increased estradiol secretion. Immunocytochemical study demonstrated an EGF-induced (10 ng/ml) increase in the proportion of cells revealing proliferating cell nuclear antigen (41% vs 24.7% in control, p < 0.01). EGF (10 ng/ml) increased the proportion of cells with immunoreactivity to ERK-1 (more than two-fold) and ERK-3 (three-fold) members of the MAP-kinase family. Moreover, EGF induced the translocation of ERK-1 to the nucleus, whilst preferentially cytoplasmic localization of ERK-3 was not changed after EGF addition. This can indicate regulation of ERK-1 and -3 by EGF, as well as differential patterns of ERK-1 and ERK-3 expression in response to EGF in cultured granulosa cells. - These results indicate that EGF can be a stimulator of proliferation, steroidogenesis and cyclic nucleotide release by rabbit granulosa cells. Stimulation of cAMP and cGMP release, and activation of ERK-related MAP kinase in granulosa cells after EGF addition indicates the involvement of these intracellular messengers in mediating the EGF action on the ovary.


Isolation and characterization of an amphipathic antigen from Corynebacterium diphtheriae.
Amphipathic antigen was isolated from Corynebacterium diphtheriae Park-Williams number 8 cells by extraction with 47.5% phenol, nuclease treatment and gel filtration on Sepharose 6B. The chemical composition of the amphipathic antigen was hexose (73.8%), pentose (4.6%), fatty acids (9.8%) and glycerol (4.5%). The amphipathic antigen contained arabinose and mannose as sugars at a molar ratio of 1:6 and the major fatty acids were palmitic (C16:0) acid and palmitoleic (C16:1) acid (64.2% and 26.2%, respectively). The amphipathic antigen sensitized sheep erythrocytes and had definite immunobiological activities: viz mitogenic activity on murine splenocytes, stimulatory activity on guinea pig peritoneal macrophages and human complement activation. Deacylation of the amphipathic antigen with alkali treatment lost the sheep erythrocyte-sensitizing ability and some immunobiological activities. The isolated amphipathic antigen described is not a lipoteichoic acid and is different from the teichoic acid of C. diphtheriae.


The IgG-specific endoglycosidase EndoS inhibits both cellular and complement-mediated autoimmune hemolysis.
EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human immunoglobulin G and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody-mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti-human-RBC antibodies (anti-RBC) mediated destruction of RBC, ie, phagocytosis, complement activation, and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pretreatment of anti-D with EndoS before sensitization of RBCs and abrogated by direct addition of EndoS to blood containing sensitized RBCs. The toxic effects of monocytes stimulated with anti-D-sensitized RBCs, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBCs and complement-mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBCs was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC immunoglobulin G2a monoclonal autoantibody and complement activation and erythrophagocytosis by Kupffer cells in the liver were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody-mediated destruction of RBCs.


Foraging activity rhythms of Dinoponera quadriceps (Hymenoptera: Formicidae) in its natural environment.
This study characterizes the foraging activity of the queenless ant Dinoponera quadriceps (Kempf) (Hymenoptera: Formicidae) in its natural environment by testing the hypotheses that foraging activity presents both daily and seasonal rhythmic variations, and that these rhythms are related to environmental variables. Four colonies of D. quadriceps were observed in an area of secondary Atlantic forest in northeastern Brazil. Data collection was performed over 72 h every three months during an annual cycle. Both daily and seasonal foraging activity rhythms of D. quadriceps colonies were related to environmental factors, but colony differences also explained part of foraging variations. Foraging activity of D. quadriceps colonies was predominantly diurnal independently of season. In the early dry season, the colonies had two activity peaks, one in the morning and another in the afternoon, with a decrease in foraging at midday; however, during the rest of the year, foraging activity was distributed more evenly throughout the daylight hours. The daily rhythm of foraging activity was likely determined by an endogenous circadian rhythm year-round, but in the dry season, temperature and relative humidity also influenced daily foraging activity, with a negative effect of temperature and a positive effect of relative humidity. On a seasonal scale, foraging activity peaked in the early dry season and suddenly declined at the end of this season, increasing again at the late rainy season. The seasonal rhythm of foraging was negatively related to relative humidity and positively related to prey availability.


An imbalance in cluster sizes does not lead to notable loss of power in cross-sectional, stepped-wedge cluster randomised trials with a continuous outcome.
The current methodology for sample size calculations for stepped-wedge cluster randomised trials (SW-CRTs) is based on the assumption of equal cluster sizes. However, as is often the case in cluster randomised trials (CRTs), the clusters in SW-CRTs are likely to vary in size, which in other designs of CRT leads to a reduction in power. The effect of an imbalance in cluster size on the power of SW-CRTs has not previously been reported, nor what an appropriate adjustment to the sample size calculation should be to allow for any imbalance. We aimed to assess the impact of an imbalance in cluster size on the power of a cross-sectional SW-CRT and recommend a method for calculating the sample size of a SW-CRT when there is an imbalance in cluster size. The effect of varying degrees of imbalance in cluster size on the power of SW-CRTs was investigated using simulations. The sample size was calculated using both the standard method and two proposed adjusted design effects (DEs), based on those suggested for CRTs with unequal cluster sizes. The data were analysed using generalised estimating equations with an exchangeable correlation matrix and robust standard errors. An imbalance in cluster size was not found to have a notable effect on the power of SW-CRTs. The two proposed adjusted DEs resulted in trials that were generally considerably over-powered. We recommend that the standard method of sample size calculation for SW-CRTs be used, provided that the assumptions of the method hold. However, it would be beneficial to investigate, through simulation, what effect the maximum likely amount of inequality in cluster sizes would be on the power of the trial and whether any inflation of the sample size would be required.


Negligible immunogenicity of induced pluripotent stem cells derived from human skin fibroblasts.
Human induced pluripotent stem cells (hiPSCs) have potential applications in cell replacement therapy and regenerative medicine. However, limited information is available regarding the immunologic features of iPSCs. In this study, expression of MHC and T cell co-stimulatory molecules in hiPSCs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral blood mononuclear cells were examined. We found that no-integrate hiPSCs had no MHC-II and T cell co-stimulatory molecules expressions but had moderate level of MHC-I and HLA-G expressions. In contrast to human skin fibroblasts (HSFs) which significantly induced allogeneic T cell activation and proliferation, hiPSCs failed to induce allogeneic CD45+ lymphocyte and CD8+ T cell activation and proliferation but could induce a low level of allogeneic CD4+ T cell proliferation. Unlike HSFs which induced allogeneic lymphocytes to produce high levels of IFN-γ, TNF-α and IL-17, hiPSCs only induced allogeneic lymphocytes to produce IL-2 and IL-10, and promote IL-10-secreting regulatory T cell (Treg) generation. Our study suggests that the integration-free hiPSCs had low or negligible immunogenicity, which may result from their induction of IL-10-secreting Treg.


Personality Traits and Fatigue in Multiple Sclerosis: A Narrative Review.
(1) Background: Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease. Fatigue is a prevalent and debilitating symptom that significantly impacts the quality of life of these patients. A relationship between personality traits and fatigue in MS has been hypothesized but not clearly defined. (2) Methods: A literature search was carried out from databases up to April 2023 for studies correlating personality traits and fatigue in patients suffering from MS. (3) Results: A total of ten articles was included; most of the studies depict a neuroticism-fatigue correlation; however, they were not consistent in terms of the fatigue, personality, and covariate assessments. (4) Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the link between personality traits and fatigue in MS. Several models of personality and different fatigue assessments have been found. Despite this, a common pathway shows that the neuroticism trait or similar personality patterns has a role in fatigue diagnosis. This may be a useful target to improve the quality of life and enhance the modification of the disease treatment results. Further homogeneous and longitudinal studies are needed.