The Concept of the Arch Window in the Spiral Switch of the Great Arteries.
When the arterial switch operation includes the Lecompte maneuver, the arterial trunks are reconnected in parallel, rather than the spiral fashion observed in the normal heart. Thus, although the ventriculo-arterial connections are hemodynamically corrected, the anatomic arrangement cannot be considered normal. We hypothesized that, if feasible, it would be advantageous to restore a spiral configuration for the arterial trunks. In 58 patients, we reconstructed the arterial trunks such that, postoperatively, the pulmonary channel spirals round the aorta, passing to either the right or the left, and branches posteriorly. We compared the outcomes with those in 95 patients undergoing a standard non-spiraling operation over the same period. Average follow-up was 8.2 ± 4.5 years. The estimated 10-year survival was similar in the cohorts, at 94.7 % for those with spiraling trunks, as compared to 90.4 % for those with parallel outflow tracts. Reoperation-free survival at 10 years was not significantly different (87.6 vs. 90.5 %). Supravalvar pulmonary stenosis, aortic neo-coarctation, or left bronchial stenosis, however, was encountered in one-eighth of those undergoing a standard operation. None of these complications occurred in those patients who, postoperatively, had spiraling outflow tracts (P = 0.002). Reconstruction of spiraling trunks after the arterial switch has, thus far, avoided the complications of supravalvar pulmonary stenosis, neo-aortic kinking, or bronchial stenosis. The spiraling arrangement prevents compression of the pulmonary vessels and bronchial tree by the aorta, since it provides a wide window in the new aortic arch.


Very rapid assay of gamma-aminobutyric acid in mouse brain regions within 3 minutes by high-performance liquid chromatography with electrochemical detection.
For assay of gamma-aminobutyric acid (GABA) in brain tissue, a very rapid and simple chromatographic procedure using high-performance liquid chromatography (HPLC) with electrochemical detection (ECD) in combination with precolumn o-phthalaldehyde (OPA) derivatization is described. Perchloric acid extracts of the tissue were mixed with OPA/beta-mercaptoethanol solution and the mixture was injected onto the HPLC system. The present method permits GABA assay within less than 3 min in one chromatographic run. Up to 100 samples a working day can be analyzed in the present method. The present method has been applied to the measurement of GABA levels in discrete brain regions of mice treated with aminooxyacetic acid and isoniazid.


[FOLFOX].
In metastatic colorectal cancer, a combination of Leucovorin (LV) and fluorouraci (l FU) with oxaliplatin (FOLFOX) is a standard first-line regimen. The two limiting toxicities of FOLFOX are neutropenia and the specific reversible sensory neuropathy of oxaliplatin. The cumulative neurotoxicity often requires therapy to be stopped. Immediate hypersensitive reactions (anaphylaxis) have been noted as often as to 0.6 percent. We should pay sufficient attention to side effects of FOLFOX.


The differential diagnosis of malignant melanoma of the iris. A clinical study of 200 patients.
The records of 200 consecutive patients referred to the Ocular Oncology Service of Wills Eye Hospital because of an iris lesion suspected of being an iris melanoma were reviewed. On clinical evaluation, 24% of the lesions met the criteria for the diagnosis of iris melanoma and 76% were diagnosed as simulating lesions (pseudomelanomas). The most common pseudomelanomas included primary iris cyst (38%), iris nevus (31%), essential iris atrophy (5.7%), iris foreign body (4.5%), peripheral anterior synechia (2.5%), and iris metastasis (2.5%). Less frequently encountered pseudomelanomas included aphakic iris cysts, leiomyoma, melanocytoma, reactive lymphoid hyperplasia, adenoma of iris pigment epithelium, iridoschisis, and other miscellaneous entities. The clinical features that are helpful in differentiating the more common iris pseudomelanomas from true melanomas are discussed. Correct clinical identification of these simulating lesions may prevent unnecessary surgery or other treatment.


Quantum computational advantage with a programmable photonic processor.
A quantum computer attains computational advantage when outperforming the best classical computers running the best-known algorithms on well-defined tasks. No photonic machine offering programmability over all its quantum gates has demonstrated quantum computational advantage: previous machines1,2 were largely restricted to static gate sequences. Earlier photonic demonstrations were also vulnerable to spoofing3, in which classical heuristics produce samples, without direct simulation, lying closer to the ideal distribution than do samples from the quantum hardware. Here we report quantum computational advantage using Borealis, a photonic processor offering dynamic programmability on all gates implemented. We carry out Gaussian boson sampling4 (GBS) on 216 squeezed modes entangled with three-dimensional connectivity5, using a time-multiplexed and photon-number-resolving architecture. On average, it would take more than 9,000 years for the best available algorithms and supercomputers to produce, using exact methods, a single sample from the programmed distribution, whereas Borealis requires only 36 μs. This runtime advantage is over 50 million times as extreme as that reported from earlier photonic machines. Ours constitutes a very large GBS experiment, registering events with up to 219 photons and a mean photon number of 125. This work is a critical milestone on the path to a practical quantum computer, validating key technological features of photonics as a platform for this goal.


Serine hydroxymethylase. Specificity of bond cleaveage to form quinonoid intermediates and rate of holoenzyme formation.
L-Serine transhydroxymethylase (5,10-methylenetetrahydrofolate:glycine hydroxymethyltransferase, EC 18.104.22.168) a pyridoxal phosphate-dependent enzyme, has been obtained as a homogeneous preparation with a specific activity of 6.7 mumol benzaldehyde per minute at 30 degrees C at pH 7.5 in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes) buffer, with DL-threo-beta-phenylserine as a substrate. This enzyme has been used to study the specificity of bond cleavage in forming quinonoid intermediates from DL and non-asymmetric amino acids. The ability of the generated quinonoids to react with formaldehyde and acetaldehyde has also been studied and evidence obtained for formation of the corresponding beta-hydroxymethyl and beta-hydroxyethyl amino acid derivaties. Apotranshydroxymethylase has been prepared and the rate of holoenzyme formation was found to be 0.52 min-1 by measuring Schiff base formation at 425 nm and 0.66 min-1 as determined from restoration of enzymic activity. A requirement for the presence of mercaptoethanol for complete reactivation was also established by these studies.


More extensive structural damage in temporal lobe epilepsy with hippocampal sclerosis type 1.
To explore clinical and structural differences between mesial temporal lobe epilepsy (mTLE) patients with different hippocampal sclerosis (HS) subtypes. High-resolution T1-weighted MRI and diffusion tensor imaging data were obtained in 41 refractory mTLE patients and 52 age- and sex-matched healthy controls. Postoperative histopathological examination confirmed HS type 1 in 30 patients and HS type 2 in eleven patients. Clinical features, postoperative seizure outcomes, hippocampal subfields volumes, fractional anisotropy (FA) values of white matter regions and graph theory parameters were explored and compared between the HS type 1 and HS type 2 groups. No significant differences in clinical features and postsurgical seizure outcomes were found between the HS type 1 and type 2 groups. However, the HS type 1 group showed extra atrophy in ipsilateral parasubiculum than healthy controls and more severe atrophy in contralateral hippocampal fissure than the HS type 2 group. More extensive FA decrease were also observed in the HS type 1 group, involving ipsilateral optic radiation, superior fronto-occipital fasciculus, contralateral uncinate fasciculus, tapetum, bilateral hippocampal cingulum, corona radiata, etc. Furthermore, in spite of similar impairments in characteristic path length, global efficiency and local efficiency in two HS groups, the HS type 1 group showed additional decrease of clustering coefficient than healthy controls. HS type 1 and 2 groups had similar clinical characteristics and postoperative seizure outcomes. More widespread neuronal cell loss in the HS type 1 group contributed to more extensive structural damage and connectivity abnormality. These results shed new light on the imaging correlates of different HS pathology.


[Intracoronary radiation therapy in controlled and open clinical trials with afterloading systems and "hot" balloon catheters. Analysis of 6,692 patients].
The prevention and treatment of a restenosis, which occurs in ca. 30% of the cases following balloon dilatation of coronary stenoses, using intravascular radiation relies on the inhibition of proliferation that is inherent in every radiation therapy. The analysis is based on 6,692 patients assigned to either a control group (1,717 patients) or to radiation therapy (4,975 patients) in 41 studies. A total of 14 placebo-controlled, randomized and 27 open trials have been completed: 22 regarding in-stent restenosis, ten regarding de-novo stenosis (or restenosis without a stent) as strict inclusion criteria, and nine with all types of stenoses. For in-stent restenoses, vessel size as defined for inclusion was between 2.0 mm and 5.5 mm, stenosis length between 10 mm and 80 mm. In all trials with in-stent restenosis, the primary endpoints were reached; the restenosis rate in the longest coronary segment analyzed was between 45% and 100% in the control groups and between 7.7% and 53.5% in the brachytherapy groups. The respective values for the TVR were between 24.1% and 80% in the control groups and between 2.0% and 41.7% in the brachytherapy groups. In the control groups, MACE was between 25.9% and 80%; it was between 2.0% and 41.7% in the brachytherapy groups. Attaining results for de-novo stenoses was problematic due to "geographic miss" apparently playing a larger role in these cases; but when taking this into consideration, good results were also attained. The known limitations due to late stent thromboses (4-15% in older trials) were to the most part eliminated by administration of clopidogrel for 1 year and the limitations due to the "edge effect" by the application of longer radiation sources. With antiproliferative coated stents as treatment for de-novo stenoses, we can count on intracoronary brachytherapy losing significance in this area. But for in-stent restenoses, intracoronary brachytherapy is the only evidence-based interventional form of therapy.


[Detection of tartrate-resistant isoenzyme 5 of acid phosphatase in the white blood cells by disc electrophoresis in a case of hairy cell leukemia].
In a case of hairy cell leukemia the evidence of tartrate-resistant isoenzyme 5 of phosphatase (TRISP 5) developed to findings important for the diagnosis. The evidence was achieved by means of disc electrophoresis by separating the cell lysate of white blood cells. The percentage of TRISP 5 in the total activity of acid phosphatase in leukocytes amounted to 17.6%. In cytochemical respect the evidence of TRISP 5 proved to be negative. The classification of these findings and their differential-diagnostic significance are discussed.


Prognostic factors for time to treatment failure and time to 12 months of remission for patients with focal epilepsy: post-hoc, subgroup analyses of data from the SANAD trial.
Epilepsy is a heterogeneous disorder, with outcomes ranging from immediate remission after taking a first antiepileptic drug to frequent unremitting seizures with multiple treatment failures. Few prognostic models enable prediction of outcome; we therefore aimed to use data from the SANAD study to predict outcome overall and for patients receiving specific treatments. The SANAD study was a randomised controlled trial in which standard antiepileptic drugs were compared with new treatments. Arm A included patients for whom carbamazepine was considered the first-line treatment, most of whom were newly diagnosed with focal epilepsy. Patients were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Outcomes were time to treatment failure overall, because of inadequate seizure control, and because of adverse events, and time to 12 months of remission from seizures. In this post-hoc study we used regression multivariable modelling to investigate how clinical factors affect the probability of treatment failure and the probability of achieving 12 months of remission. For time to treatment failure, we identified several significant risk factors: sex (male vs female, hazard ratio [HR] 0·86, 95% CI 0·75-0·99), treatment history (taking non-SANAD antiepileptic drugs [other than those listed above] vs treatment naive, 1·27, 1·05-1·53), age (eg, older than 71 years vs 10 years or younger, 0·68, 0·51-0·91), total number of seizures (eg, four to 11 seizures vs two or fewer, 1·08, 1·05-1·11), electroencephalogram results (epileptiform abnormality vs normal, 1·26, 1·07-1·50), seizure type (eg, secondary generalised vs simple or complex partial only, 0·78, 0·66-0·91), site of onset (not localised vs temporal lobe, 1·25, 1·06-1·47), and treatment (lamotrigine vs carbamazepine, 0·76, 0·61-0·95). Significant factors for time to 12 months of remission were sex (male vs female, 1·19, 1·05-1·35), treatment history (taking a non-SANAD antiepileptic drug vs treatment naive, 0·64, 0·52-0·78), age (eg, older than 71 years vs 10 years or younger, 1·60, 1·26-2·03), time from first seizure (60-239 months vs ≥2 months, 1·14, 1·01-1·29; >240 months vs ≤2 months, 1·39, 1·04-1·86), neurological insult (present vs absent, 0·75, 0·61-0·93), total number of seizures before randomisation (eg, four to 11 vs two or fewer, 0·87, 0·85-0·90), and treatment (gabapentin vs carbamazepine, 0·71, 0·59-0·86; topiramate vs carbamazepine, 0·81, 0·68-0·98). We present a thorough investigation of prognostic factors from a large randomised controlled trial in patients starting antiepileptic monotherapy. If validated, our models could aid in individual patient risk stratification and the design and analysis of epilepsy trials. National Institute for Health Research (UK).


Design and experiment of array Rayleigh wave-EMAT for plane stress measurement.
The Rayleigh wave excited by the electromagnetic acoustic transducer (EMAT) is an effective selection for surface plane stress measurement. However, the propagation velocity of Rayleigh wave on the metal surface is easily affected by the original rolling process. Besides, the direction of the plane stress state is usually unknown, which means that the propagation velocity cannot be expressed linearly by the stress. As a result, the traditional measurement model of one transmitter and one receiver can only realize the decouple of plane stress components by rotating method, which not only brings position error but also low measurement efficiency. Therefore, this paper focuses on a novel Rayleigh wave-EMAT for plane stress ultrasonic measurement. Firstly, the Rayleigh wave measurement model is established based on the acoustoelastic equation and displacement expression. Furthermore, an array Rayleigh wave-EMATintegrating three transmitters and three receivers is designed. Finally, the typical plane stress state of 5052 aluminum alloy plate after friction stir welding (FSW) is measured. The experimental results show good agreement compared with the hole-drilling method, which verifies the effectiveness of proposed method and designed EMAT.


An examination of the vibration transmissibility of the hand-arm system in three orthogonal directions.
The objective of this study is to enhance the understanding of the vibration transmission in the hand-arm system in three orthogonal directions (X, Y, and Z). For the first time, the transmitted vibrations distributed on the entire hand-arm system exposed in the three orthogonal directions via a 3-D vibration test system were measured using a 3-D laser vibrometer. Seven adult male subjects participated in the experiment. This study confirms that the vibration transmissibility generally decreased with the increase in distance from the hand and it varied with the vibration direction. Specifically, to the upper arm and shoulder, only moderate vibration transmission was measured in the test frequency range (16 to 500 Hz), and virtually no transmission was measured in the frequency range higher than 50 Hz. The resonance vibration on the forearm was primarily in the range of 16-30 Hz with the peak amplitude of approximately 1.5 times of the input vibration amplitude. The major resonance on the dorsal surfaces of the hand and wrist occurred at around 30-40 Hz and, in the Y direction, with peak amplitude of more than 2.5 times of the input amplitude. At higher than 50 Hz, vibration transmission was effectively limited to the hand and fingers. A major finger resonance was observed at around 100 Hz in the X and Y directions and around 200 Hz in the Z direction. In the fingers, the resonance magnitude in the Z direction was generally the lowest, and the resonance magnitude in the Y direction was generally the highest with the resonance amplitude of 3 times the input vibration, which was similar to the transmissibility at the wrist and hand dorsum. The implications of the results are discussed. Prolonged, intensive exposure to hand-transmitted vibration could result in hand-arm vibration syndrome. While the syndrome's precise mechanisms remain unclear, the characterization of the vibration transmissibility of the system in the three orthogonal dimensions performed in this study can help understand the syndrome and help develop improved frequency weightings for assessing the risk of the exposure for developing various components of the syndrome.


Identification of lactate, threonine and alanine in rat thymus and tumorigenic lymphoid cells using 1H 2-D COSY NMR spectroscopy.
One- and two-dimensional 1H NMR spectra were obtained for normal murine thymus and malignant lymphoma tissue, as well as for the supernatant fractions from high speed centrifugal separations. Crosspeaks in the two-dimensional spectra resembled those reported by others for adenocarcinoma and leukemic lymphoblast cells, assigned tentatively to the carbohydrate fucose. However, for the present systems, spectral analysis and the spectral response to addition of known compounds led to assignment of the crosspeaks as follows: 1.33-4.12 ppm, lactate anion; 1.33-4.26 ppm, threonine; 1.48-3.78 ppm, alanine. Differences between the NMR data for the normal and malignant specimens were only in the relative intensities of the peaks. No peaks characteristic of fucose were found in spectra of cytosol, tissue or membrane lipids. Thus, the NMR data for malignant lymphoma cells are significantly different from those for adenocarcinoma and leukemic lymphoblasts. The NMR characteristics of different types of cancer cell must be individually determined.


Duration of hepatitis B antibody response in children immunised with hepatitis B and compulsory vaccines.
Twenty four subjects were simultaneously administered DT toxoids, OPV and HBV vaccines at the age of 3, 4-5 and 11 months and then followed up for 2 and 4 years in order to evaluate the duration of the immune response and the need and the timing of HBV revaccination. A fall in anti-HBs titre below 10 mIU/ml was observed at the follow up in 4/24 (16.7%) of the subjects. In other 5 children (20.8%) anti-HBs titre was found to be just above 10 mIU/ml. This would suggest that a revaccination is indicated and it could be performed at the age of 5-6 years when children enter school. This schedule is simple, effective and money saving since it reduces the cost/benefit ratio and the number of visits for immunisations, and it is expected to improve the compliance for the vaccination.


The violence triad and common single precipitants to psychiatric patient assaults on staff: 16-year analysis of the Assaulted Staff Action Program.
Psychiatric patient assaults are a serious community health hazard. Risk management strategies to identify common single precipitants have had limited value and this limitation has resulted in the emergence of multiple determinant studies. This 16-year retrospective study of assault precipitants in one, public sector mental health-care system assessed single common, immediate precipitants; the multiple clinical precipitants of history of violence, personal victimization, and substance use disorder (the violence triad); and both combined. Denial of services, acute psychoses, and excess sensory stimulation were the most common single precipitants. The multicomponent violence triad yielded greater association with subsequent assault than single precipitants. The combination of the violence triad and single precipitants did not yield statistically significant greater associations. Discussion of the clinical risk management implication, and methodological issues are presented.


Extra-hepatic cancer represses hepatic drug metabolism via interleukin (IL)-6 signalling.
In many cancer patients, the malignancy causes reduced hepatic drug clearance leading to potentially serious complications from the use of anticancer drugs. The mechanisms underlying this phenomenon are poorly understood. We aimed to identify tumor-associated inflammatory pathways that alter drug response and enhance chemotherapy-associated toxicity. We studied inflammatory pathways involved in extra-hepatic tumor mediated repression of CYP3A, a major hepatic drug metabolizing cytochrome P450 subfamily, using a murine Engelbreth-Holm-Swarm sarcoma model. Studies in IL-6 knockout mice determined the source of elevated IL-6 in tumor-bearing animals and monoclonal antibodies against IL-6 were used to intervene in this inflammatory pathway. Our studies confirm elevated plasma IL-6 levels and reveal activation of Jak/Stat and Mapk signalling pathways and acute phase proteins in livers of tumor-bearing mice. Circulating IL-6 was predominantly produced by the tumor xenograft, rather than being host derived. Anti IL-6 antibody intervention partially reversed tumor-mediated inflammation and Cyp3a gene repression. IL-6 is an important player in cancer-related repression of CYP3A-mediated drug metabolism and activation of the acute phase response. Targeting IL-6 in cancer patients may prove an effective approach to alleviating cancer-related phenomena, such as adverse drug-related outcomes commonly associated with cancer chemotherapy.


Impaired regulation of natural killer cells in immunoglobulin synthesis by peripheral blood mononuclear cells from patients with ulcerative colitis.
Immunoglobulin (Ig) synthesis, natural killer (NK) cell activity, and lymphokine production by peripheral blood mononuclear cells (PBMC) were studied in 34 patients with ulcerative colitis (UC). Levels of Ig produced by PBMC were significantly higher in patients with active UC as compared to controls. However, there were no significant differences in Ig-synthesis between patients with inactive UC and controls. NK cell activity was significantly decreased in patients with active UC as compared to controls, and a significant negative correlation was observed between the level of IgA and NK cell activity in patients with UC. Reconstitution experiments demonstrated that CD56+ cells from controls suppressed the levels of IgA, when added to the culture containing a constant number of B cells and CD4+ cells. In contrast, CD56+ cells from patients with active UC completely lacked the capacity to suppress IgA production. In addition, the activities of interleukin-2 and interferon-gamma were significantly decreased in patients with active UC. The present study suggests that immunoregulatory abnormality of NK cells exists in patients with UC and impaired NK cell activity may be related to increased Ig-synthesis observed in these patients.


Structure of rDNA in the mosquito Anopheles gambiae and rDNA sequence variation within and between species of the A. gambiae complex.
The structure of the rDNA repeating unit of Anopheles gambiae (Diptera: Culicidae) was determined by restriction endonuclease mapping and hybridization analyses on four independent clones obtained from a genomic library of a colony (G3) from the Gambia (West Africa). rDNA gene coding sequences are conserved, but much intragenomic and intraspecific (geographic) variation occurs in the intergenic spacer. Hybridization of subclones from spacer and coding sequences to genomic DNA that was isolated from single mosquitoes from laboratory colonies of four other A. gambiae complex species reveals conservation of coding sequences but concerted evolution in the intergenic spacers.


Lipid composition and lidocaine effect on immediate and delayed injection pain following propofol administration.
Propofol has been used for the induction and maintenance of anesthesia. However, patients experience vascular pain during its injection. The objective of this study was to compare the effect of the lipid type used in propofol preparations and that of lidocaine on the immediate and delayed vascular pain induced by propofol administration. In this double-blinded clinical study, 150 patients at American Society of Anesthesiologists level I-II were randomly divided into three equally sized groups. A propofol with medium and long-chain triglycerides (propofol-MCT/LCT) was administered to the first group. The second group received propofol containing propofol-LCT, and the third group received propofol-LCT and pretreatment lidocaine 20 mg. The incidence and the intensity of immediate (during injection) and delayed injection pain (after 20 s) were evaluated on a verbal analog scale (1-10) until patients' unconsciousness. Sample size was calculated with SigmaPlot version 12.5 software. Data were analyzed with Statistical Package for the Social Sciences (SPSS) version 16, one-way analysis of variance, and post-hoc Tukey. P < 0.05 was considered statistically significant. The demographic parameters of the three groups were similar. The lidocaine group experienced the least immediate vascular pain. The intensity of pain was highest in the propofol-LCT group (P = 0.04). Additionally, the intensity of delayed pain was lowest in the propofol-MCT/LCT group (P = 0.01). The incidence of pain associated with the propofol administration was 26.5, 44, and 18%, respectively, in propofol-MCT/LCT, propofol-LCT, and lidocaine and propofol-LCT groups. The results indicate an effect of the lipid type on delayed pain reduction, especially propofol-MCT/LCT. On the other hand, the lidocaine decreases immediate propofol-LCT vascular pain.


Measuring empathic behaviour among undergraduate dietetics students.
Empathic behaviour has a direct link to the positive clinical outcomes. Health professionals, which include dietitians, are increasingly expected to demonstrate the impact of their care on patient outcomes. To date, there is limited research exploring the empathic behaviour of dietetics students. This cross-sectional study evaluated the psychometric properties of Jefferson Scale of Empathy-Healthcare Provider Student (JSE-HPS) and empathic behaviour of dietetics students. Undergraduate dietetics students from one private and two public universities in Malaysia participated (n = 455). Item and scale psychometric properties were examined using principal component analysis and differences in mean empathy scores for students were assessed across years of study and types of universities. A 3-factor solution emerged in the results, accounting for 26.76%, 10.75% and 6.3% of the variance. The JSE-HPS demonstrated good internal consistency (α = 0.83). Despite students enroled at public universities scoring higher mean empathy scores than students enroled at the private university, the difference was not significant. The only significant difference was between the empathy level of first and third year students (p = 0.033). As empathy underpins patient-centred management in the nutrition care process, it should be well integrated into curriculum delivery so that appropriate levels of empathy can be developed to prepare work-ready healthcare professionals.


Metacognition, cognition and social anxiety: A test of temporal and reciprocal relationships.
Cognitive models of social anxiety give prominence to dysfunctional schemas about the social self as the key underlying factors in maladaptive self-processing strategies and social anxiety symptoms. In contrast, the metacognitive model argues that beliefs about cognition represent a central belief domain underlying psychopathology and cognitive schemas as products of a thinking style regulated by metacognition. The present study therefore evaluated the temporal and reciprocal relations between metacognitive beliefs, social self-beliefs, and social anxiety symptoms to shed light on possible causal relationships among them. Eight hundred and sixty-eight individuals gathered at convenience participated in a four-wave online survey with each measurement wave 6 weeks apart. Using autoregressive cross-lagged panel models, we found significant temporal and reciprocal relations between metacognition, social self-beliefs (schemas), and social anxiety. Whilst social self-beliefs prospectively predicted social anxiety this relationship was reciprocal. Metacognitive beliefs prospectively predicted both social interaction anxiety and social self-beliefs, but this was not reciprocal. The results are consistent with metacognitive beliefs causing social anxiety and social self-beliefs and imply that negative social self-beliefs might be a product of metacognition. The clinical implications are that metacognitive beliefs should be the central target in treatments of social anxiety.


A few ethical criteria for evaluating the risks for "marginal" living kidney donors.
The transplant of so-called "marginal" organs carries an added risk not only for the recipient but also for the living donor. To assess the acceptability of these risks from an ethical viewpoint, the relevant scientific data and institutional documents should be consulted. The ethical evaluation is approached from three aspects: general policies to promote organ donation, the reference guidelines, and the altruistic and philanthropic motivations of the living donor.


Interleukin 10 deficiency exacerbates halothane induced liver injury by increasing interleukin 8 expression and neutrophil infiltration.
The prediction and prevention of drug-induced liver injury (DILI) have been hindered by limited knowledge of the underlying mechanisms, in part the result of a lack of animal models. Using a newly established DILI model induced by halothane, we found increased liver damage susceptibility in interleukin 10 (IL-10) knockout (KO) mice. Extensive neutrophil infiltration and chemoattractant factor interleukin 8 (IL-8) expression in IL-10 KO mice were observed after halothane administration. The elevation of IL-8 expression was NF-kappaB- and P38 MAPK-dependent. In addition, increased signal transducer and activator of transcription factors (STAT) 1 and STAT3 were observed in halothane treated IL-10 KO mice. Exogenous IL-10 treatment protected susceptible mice from halothane induced liver injury (HILI). In conclusion, IL-10 deficiency increases susceptibility to HILI and increased IL-8 expression as well as neutrophil infiltration may be responsible for this phenomenon.


One year intensive PM2.5 bound polycyclic aromatic hydrocarbons monitoring in the area of Tuscany, Italy. Concentrations, source understanding and implications.
Polycyclic aromatic hydrocarbons (PAHs) associated to PM(2.5) particles were monitored at three sites in the region of Tuscany, Italy, during the period March 2009-March 2010. PAH concentrations ranged between 0.92 ng m(-3) and 13 ng m(-3). The spatial and seasonal differences observed at the three sites are discussed and attributed to specific PAH sources. Benzo[a]Pyrene average annual values were below the EU limit value of 1.0 ng m(-3). The results of this study suggest that emissions from commuting and work related traffic play an important role for the city of Florence, whereas for the city of Livorno, the harbor activities seem to impact the PAH burden substantially, as well. The PAH cancer risk (expressed as the "BaPE index") has shown a 6-fold decline compared to early 1990's concentrations and 2- to 3-fold decline compared to the late 1990's.


The coexistence of three species of daphnia in the Klostersee : I. Field studies on the dynamics of reproduction.
1. In the Klostersee in southern Bavaria three species of Daphnia have coexisted for at least several decades: Daphnia hyalina (H), D. galeata (G) and D. cucullata (C). These three species differ in size and compete for food. 2. All three species show marked seasonal fluctuation of abundance, with H and G dominating during spring and late autumn and C dominating during summer. The fluctuations of H and G are stronger correlated than H and C or G and C. 3. The three species are vertically segregated. C preferes the upper strata, H the lower and G the intermediate. This behaviour favours the smaller species C. On the average (from early spring to late autumn), C develops 1.2 times faster than G and 1.5 times faster than H. 4. H and G show higher clutch sizes than C throughout the year. This advantage however is compensated by the higher speed of development of C during thermally stratified seasons. 5. The egg ratio is influenced by both the age structure of the populations and the cluth size of the gravid females. 6. The clutch size depends mainly on the size of the females. The reaction of clutch size to environmental factors follows with a time lag of approximately D (duration of embryonic development). C and G depend more on meteorological influences than H. which is probably related to the vertical distribution. 7. The importance of the differential vertical distribution and the reaction to environmental stress as well as the impact on the size-efficiency hypothesis are discussed.


Imaging of eyelid lymphatic drainage.
Traditional descriptions of lymphatic drainage show eyelids emptying into the submandibular or preauricular basin. However recent studies based on in vivo lymphatic imaging show a possible predilection for the preauricular basin. We describe lymphoscintigraphy and report findings in patients with eyelid malignancies undergoing sentinel lymph node biopsy (SLNB). Retrospective chart review of 15 consecutive patients at a single institution with eyelid carcinoma undergoing SLNB. The primary outcome measure was primary facial lymphatic drainage site from the eyelid as determined by lymphoscintigraphy. The preauricular basin was the site of focal radioactive uptake in all 15 patients. The location of the primary tumor was as follows: medial upper eyelid (1), medial canthus (3), medial lower eyelid (3), lateral upper eyelid (3), and lateral lower eyelid (5). The types of tumor were: invasive squamous cell carcinoma (7), malignant melanoma (3), and sebaceous cell carcinoma (2), Merkel cell carcinoma (2), and conjunctival spindle cell carcinoma (1). Lymphoscintigraphy is increasingly used in the context of SLNB for periocular malignancy. The recent literature suggests that the preauricular lymph node basin may be the primary site of eyelid lymphatic drainage and this is corroborated by our series. Further data will elucidate the biology of eyelid lymphatic channels in humans but the preauricular basin may be the prime lymphatic metastastic site in eyelid malignancies.


Deciphering the underlying mechanisms of the oxidative perturbations and impaired meat quality in Wooden breast myopathy by label-free quantitative MS-based proteomics.
The study aimed to investigate biochemical mechanisms occurred in Wooden breast (WB) chicken meat, with attention to the impact on meat quality. Commercial chicken breasts were classified as Normal (N, n = 12), WB-M (moderate degree; focal hardness on cranial region, n = 12) and WB-S (severe degree; extreme and diffused hardness over the entire surface, n = 12). Samples were analyzed for physico-chemical properties, oxidative damage to lipids and proteins, and discriminating sarcoplasmic proteins by using a Q-Exactive mass spectrometer. WB meat presented impaired composition and functionality and higher levels of lipid and protein oxidation markers than N meat. The proteomic profile of WB-S presents a dynamic regulation of the relevant proteins involved in redox homeostasis, carbohydrate, protein and lipid metabolisms. Proteomics results demonstrate that the physiological and metabolic processes of muscles affected by WB myopathy are involved in combating the inflammatory process and in repairing the damaged tissue by oxidative stress.


Optimism and survival: health behaviors as a mediator-a ten-year follow-up study of Chinese elderly people.
Optimism-the generalized expectation that good things will happen-is a promising health asset. Mounting evidence indicates that there are specific associations between optimism and survival rates. However, for public health purposes, it is critical to consider whether the relationship between optimism and survival holds for older adults as a whole and to explore the role of health behaviors as potential mediators. Prospective data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Optimism was measured in 2008, and survival was measured by survival time of the interviewees during the whole observation period from 2008 to 2018. Cox proportional hazard models were employed to evaluate the association between optimism and survival among the elderly. The mediating effect analysis method was used to explore the potential mediating role of health behaviors on the association between optimism and survival. Compared to less optimistic older adults, optimistic individuals were associated with lower odds of mortality (HR = 0.94, 95% CI = 0.89 - 0.99). Health behaviors are key elements that play a positive role in survival (HR = 0.95, 95% CI = 0.94 - 0.96). Health behaviors played an intermediary role in the relationship between optimism and mortality, and the mediating effect was -0.005. Optimism and health behaviors were broadly and robustly associated with a lower risk of mortality. Health behaviors mediate the relationship between optimism and mortality. Appropriate intervention should be carried out on optimism and health behaviors among elderly people to improve the likelihood of health in aging.


Determinants of infant carrying behavior in rural Papua New Guinea.
The determinants of variability in infant carrying within and across societies is an understudied area within parental investment research. Carrying has positive and negative consequences as it may protect the infant from predators and pathogens but is energetically costly for caregivers. Moreover, carrying may delay independent locomotor development and exposure to antigens necessary for immunological competence. The purpose of this study is to compare infants' ages and developmental milestone attainment as predictors of carrying behavior and to identify other determinants of carrying behavior among traditional forager-horticulturalists in Papua New Guinea. We analyze quantitative data collected among 107 infant-caregiver dyads during 354 hours of focal follows on infant carrying. Random effects logistic regression was used to model carrying behavior in these dyads. Infants' chronological age and milestone achievement are equally reliable predictors of abatement of carrying and increased time on the ground. Further, the presence or absence of the mother and the location of the infant-caregiver pair are significantly associated with carrying behavior. Indices of mother's and infants' condition such as anthropometric measures were not predictive of carrying behaviors. Mothers vary the amount of carrying based on assessment of infant and local environmental conditions. Age and milestone attainment are equally predictive of time on the ground and therefore increased exposure to antigens, pathogens and other dangers. High levels of infant carrying function as offspring protection by increasing exposure to ground level pathogens gradually, thus allowing for the naïve immune system to develop immunocompetence incrementally.


Internet Public Opinion Diffusion Mechanism in Public Health Emergencies: Based on Entropy Flow Analysis and Dissipative Structure Determination.
As an empirical case, this study selected the illegal production process incidents of rabies and DPT (Diphtheria, Pertussis, Tetanus) vaccines by Changchun Longevity Biotechnology Co., Ltd., which occurred in July 2018. Based on the four factors involved in the spread of public opinion, the public health emergency, netizen, network media, and government, Brusselator model, and entropy method were applied to calculate the positive and negative entropy-to verify whether the Internet public opinion system is a dissipative structure. This study verified four evolution mechanisms in Internet public opinion diffusion, among which the trigger point of entropy-control occurred in the germination mechanism, the entropy-controlled disposal point occurred in the outbreak and fluctuating mechanism, and then became latency in the elimination mechanism. It provides a theoretical reference for the government to judge the stage of such diffusion and improve the governance ability of the opinion mentioned above.


Seasonal distributions and other risk factors for Giardia duodenalis and Cryptosporidium spp. infections in dogs and cats in Chiang Mai, Thailand.
The objectives of this study were to explore risk factors associated with Giardia and Cryptosporidium infections in dogs and cats in Chiang Mai, Thailand, to describe the seasonal distributions of Giardia and Cryptosporidium prevalence, and to determine the potential for zoonotic transmission through genetic characterization of isolates. Fecal samples from 301 dogs and 66 cats were collected between August 2009 and February 2010. The presence of Giardia cysts and Cryptosporidium oocysts was determined using zinc sulfate centrifugal flotation and immunofluorescent assay (IFA). Genotype/species were determined by DNA sequence analyses of PCR products from Giardia glutamate dehydrogenase (gdh), beta-giardin (bg), and triosephosphateisomerase (tpi) and Cryptosporidium heat shock protein 70KDa (hsp70) and small subunit-rRNA (SSU-rRNA) genes. Information related to specific risk factors was collected from owners of each animal using a questionnaire. The risk factor data were analyzed for associations with Giardia and Cryptosporidium infections using logistic regression. The overall estimated prevalence of Giardia and Cryptosporidium in dogs was 25.2% and 7.6%, respectively and in cats, 27.3% and 12.1%, respectively. The estimated prevalence of Giardia infection in dogs in the rainy season (31.7%) was significantly higher than in the drier, winter season (17.2%) (p < 0.01). The estimated prevalence of Cryptosporidium infection in dogs and of Giardia and Cryptosporidium infections in cats was not associated with season (p > 0.05). Multivariable analysis indicated that Giardia cysts were more likely to be detected in fecal samples of dogs that resided in high-density environments, drank untreated water, were shedding Cryptosporidium oocysts, were having acute diarrhea or a history of chronic diarrhea, and were collected in the rainy season. All 19 Giardia PCR positive samples typed as G. duodenalis canine adapted genotypes (assemblages C or D). In cats, of six Giardia PCR positive samples, five typed as dog assemblages and one typed as assemblage AI. Of ten dogs with Cryptosporidium PCR positive samples, eight typed as C. canis, one as C. parvum (a zoonotic species) and one had both C. canis and C. parvum. Of three Cryptosporidium PCR positive samples in cats, one typed as C. felis and two typed as C. parvum. The presence of zoonotic G. duodenalis assemblage AI in a cat, and C. parvum in feces of dogs and cats suggests a potential role for a reservoir for zoonotic transmission. Whether or not these presences were from exposure to other animal or human hosts or environment are needed to be confirmed.


Intra-articular ganglion cysts of the cruciate ligaments.
Intra-articular ganglion cysts of the cruciate ligaments are associated with non-specific clinical signs and symptoms. Familiarity with the MR appearances in particular is important to make an accurate diagnosis, exclude associated abnormalities, and avoid misdiagnosis.


Molecular Diagnosis of Urinary Tract Infections by Semi-Quantitative Detection of Uropathogens in a Routine Clinical Hospital Setting.
The objective of our study was the development of a semi-quantitative real-time PCR to detect uropathogens. Two multiplex PCR reactions were designed to detect Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Enterococcus faecalis, and Pseudomonas aeruginosa. 16S based PCR was performed in parallel to detect Gram-positive and Gram-negative bacteria. Firstly to identify non-targeted agents of infection in the same urine specimen, and secondly to quantify background flora. The method was evaluated in comparison with standard bacterial culture, and a commercial PCR kit for detection of uropathogens. Analysis with a known panel of 116 clinical isolates yielded a PCR specificity of 100%. Analysis of urine specimens from 211 patients revealed a high correlation of PCR Cq values with both culture positivity and quantity. Concordance between PCR and culture was 98% when both methods yielded results. PCR was found to be more sensitive than culture. With a cut-off Cq value of 33, the negative predictive value of PCR was 94%. The 16S PCR confirmed most results. One specimen was positive by 16S PCR suggesting another cause of infection not detected by the specific PCR assays. We conclude that it is feasible to detect and identify uropathogens by multiplex real-time PCR assay.


Internet use predicts Chinese character spelling performance of junior high school students: multiple mediating roles of pinyin input proficiency and net-speak experience.
To examine the complex relationship between Internet use experience and character spelling performance among Chinese junior high school students, the study explored the multiple mediating roles of Pinyin input proficiency and net-speak experience. A total of 447 Chinese junior high school students aged 12-15 years old completed the Internet Use Experience and Pinyin Input Proficiency Assessment, the Net-speak Experience Questionnaire and the Chinese Spelling Test. The results showed that: (1) All investigated variables were significantly correlated with each other, but there was no direct relationship between Internet use and Chinese spelling performance. (2) Pinyin input proficiency and net-speak experience play a chain mediating role in the relationship between Internet use and Chinese character spelling performance. Teens' Internet use experience indirectly and positively predicted Chinese character spelling performance through the mediation of Pinyin input method use and net-speak experience. The implication of this study is that Chinese children should be guided to engage in Internet activities that require Pinyin typing and use net-speak creatively in order to promote the traditional Chinese character spelling skills when instructing teenagers to engage in Internet activities.


Retraction Note: Bone mesenchymal stem cell-derivedexosomal microRNA-29b-3p preventshypoxic-ischemic injury in rat brain byactivating the PTEN-mediated Aktsignaling pathway.
An amendment to this paper has been published and can be accessed via the original article.


[Detection and long-term treatment of ventricular extrasystole in patients with ischemic heart disease].
One-hour monitoring and bicycle ergometric testing revealed frequent (more than 10 per hour) and complicated ventricular extrasystoles in 105 patients. They were distributed between the treatment and control groups. Long-term treatment with beta-blocking agents reduced the frequency of sudden death and repeated myocardial infarction in the treated group as compared to the controls.


Backbone and side chain 1H, 15N and 13C chemical shift assignments of the molten globule state of L94G mutant of horse cytochrome-c.
Proteins fold via a number of intermediates that help them to attain their unique native 3D structure. These intermediates can be trapped under extreme conditions of pH, temperature and chemical denaturants. Similar states can also be achieved by other processes like chemical modification, site directed mutagenesis (or point mutation) and cleavage of covalent bonds of natural proteins under physiological conditions usually taken as dilute buffer (near neutral pH) and 25 °C. Structural characterization of molten globules is hampered due to (i) their transient nature, (ii) very low population at equilibrium, and (iii) prone to aggregation at high concentration. Furthermore, the dynamic nature of these folding intermediates makes them unsuitable for X-ray diffraction. Hence, understanding their structures at the atomic level is often a challenge. However, characterization of these intermediates at the atomic level is possible by NMR, which could possibly unravel new details of the protein folding process. We have previously shown that the L94G mutant of horse cytochrome-c displays characteristics of the molten globule (MG) state at pH 6.0 and 25 °C. As a first step towards characterizing this MG state at the atomic level by NMR, we report its complete backbone, side chain and heme chemical shift assignments.


From retinal circuitry to eye diseases--in memory of Henk Spekreijse.
This article summarizes our recent works on stratum-by-stratum structure-function rules for synaptic contacts between retinal bipolar cells and third-order retinal neurons in the inner plexiform layer. These rules were derived from large-scale voltage clamp recordings of various types of bipolar cells in the tiger salamander retina, and they appear applicable to bipolar cells in the mouse and other mammalian species. This review also gives a brief account of how we used pathway-specific knockout mouse models to dissect rod and cone signaling channels in the mammalian retina. Furthermore, studies on cellular and genetic mechanisms underlying several neurodegenerative retinal disorders are described.


The contribution of foot problems to mobility impairment and falls in community-dwelling older people.
To investigate the relationship between foot problems, balance, and functional ability in community-dwelling older people and to determine whether older people with a history of multiple falls exhibit greater foot impairment than those who have not fallen or who have fallen once only. A cross-sectional, retrospective study. Falls and Balance Laboratory, Royal North Shore Hospital, Sydney, Australia. One hundred thirty-five community-dwelling men and women age 75 to 93 (mean age +/- standard deviation, 79.8 +/- 4.1). Foot problem score; postural sway; coordinated stability; stair ascent and descent; an alternate stepping test; timed 6-meter walk; and tests of vision, sensation, strength, and reaction time. Eighty-seven percent of the sample had at least one foot problem. Women had a significantly higher foot problem score than did men. The foot problem score was significantly associated with performance on the coordinated stability test, stair ascent and descent, alternate stepping test, and timed 6-meter walk. Multiple regression analyses revealed that the foot problem score was a significant independent predictor of performance in the coordinated stability test, stair ascent and descent, and the alternate stepping test. Subjects with a history of multiple falls had a significantly higher foot problem score than did those who had not fallen or who had fallen once only, but the prevalence of individual foot conditions or the presence of foot pain did not differ between these groups. Foot problems are common in older people and are associated with impaired balance and performance in functional tests. Furthermore, older people with a history of multiple falls have greater foot impairment than non- or once-only fallers. These findings provide further evidence that foot problems are a falls risk factor and suggest that the cumulative effect of multiple foot problems is more important in increasing falls risk than the presence or absence of individual foot conditions.


The role of protease in immunoregulation.
Whilst immunodepression is widely recognized in patients subject to trauma or chronic disease, the mechanism of this process is poorly understood. We found that most of the lymphocyte suppressive activity of plasma from severely ill patients was attributable to the protein alpha 2-macroglobulin (alpha 2 M) and low molecular weight peptide (less than 10000). The only major variation in alpha 2 M concentration was found in patients subject to trauma, when it was depressed at times of high plasma suppressive activity. In order to explain qualitative immunosuppressive differences in alpha 2 M we studied its functional role as the main route for binding and degrading proteolytic enzyme (protease). In normal plasma minor degrees of protease complex formation to alpha 2 M caused greatly increased suppressive activity due principally to alpha 2 M and the abnormal appearance of low molecular weight peptide (less than 10000). Study of protease inhibitor function in patients suffering from acute or chronic illness suggested that in these patients their plasma becomes immunosuppressive due to inadequate handling of protease, resulting in alpha 2 M-protease complexes or inhibitory peptides persisting in the circulation. Opportunities for background immunoregulation by altering protease metabolism are considered.


An improved procedure for the preparation of rat uterine cell suspensions.
In the present paper we report on an improved procedure for the preparation of free uterine cells which avoids the use of trypsin and employs very low concentration of collagenase. The cells released mechanically from the digested tissue are constantly removed from the enzyme containing medium, thus minimizing exposure to collagenase. 60%-70% of the cells which make up the intact uterus are obtained as free cells and 95% of these cells are viable for at least 15 hours at 37 degrees. Metabolic integrity was assessed by measuring the cell's ability to oxidize glucose and synthesize proteins over extended periods of time. The membrane leucine carrier protein and the membrane Na+/K+ ATPase were found to be fully functional. Electron microscopic analysis of the cells confirmed their structural integrity. Data are presented illustrating that with this system the estrogen binding protein is stable at physiological temperatures. The cells contain approximately 30,000 specific estrogen binding sites, with an apparent KA of 5--6 x 10(9) M-1. At 37 degrees 80% of the hormone receptor complexes were in the nuclear fraction, 20% in the cytoplasm. The similarity of the estrogen receptor binding parameters with those measured in the intact tissue after in vivo hormone adminsistration, together with the cells' structural and metabolic integrity make this procedure for the preparation of uterine cell suspensions in high yields particularly suitable for studies in which minimal cell injury is an essential prerequisite.


Toxicity assessment of Erythrophleum ivorense and Parquetina nigrescens.
Erythrophleum ivorense and Parquetina nigrescens are found growing in tropical regions and they are used in African traditional medicine to treat various ailments including wounds, boils and anaemic conditions. Some species of plant in the Erythrophleum genus are also known to be poisonous and toxic to several livestock. However, there is no information on the toxicity of E. ivorense and P. nigrescens. This study is to determine the cytotoxicity and subchronic toxicity properties of methanol leaf extract (EIML) and methanol stem barks extract (EIMB) of E. ivorense and methanol leaf and aerial part extract of P. nigrescens (PNML). Concentrations from 0.1 to 100 μg/mL of the extracts were used to determine the influence of the extracts on the release of lactate dehydrogenase (LDH) from HaCaT keratinocytes. The EIML and EIMB extracts showed increase in LDH released from HaCaT keratinocytes at 0.1-10 μg/mL and 1-100 μg/mL for the PNML extracts (p > 0.05). Wistar rats were orally administered with 100, 300 and 1000 mg/kg body weight of the extracts (EIML, EIMB and PNML, respectively) for 35 days. Tissues from the kidney and liver of the rats treated with lower doses (100-300 mg/kg body weight) of EIML extract showed highly vascularized kidneys with numerous glomerular tufts, healthy hepatocytes and sinusoids in liver. However, there were persistent renal tissue inflammation and glomerular degeneration in kidney, and increased inflammatory infiltrates with few vacuolations and scarrings in liver in rats treated with higher extract dose of 1000 mg/kg body weight of rat. The rats treated with EIMB extract showed persistent renal and hepatocyte inflammations with glomerular and hepatocyte necrosis at all administered doses (100, 300 and 1000 mg/kg body weight) which are indications of renal and hepatic toxicities. Though rats administered with 100 and 300 mg/kg of PNML extract showed renal haemorrhage and inflammation and hepatic inflammation, the rats administered with 1000 mg/kg body weight showed restoring glomerular tufts and improved vasculature and liver with reduced inflammatory infiltrates with healthy hepatocytes. Phytochemical screening of EIML, EIMB and PNML extracts revealed the presence of alkaloids, tannins, flavonoids, sterols, cardiac glycosides and terpenoids.


Estrogen Receptor and Immune Checkpoint Inhibitors: New Partners in Lung Cancer?
The influence of sex on immunotherapy response in patients with non-small cell lung cancer (NSCLC) had been studied with no clear conclusions. An article in this issue reports that a key determinant of response is not sex but the existence of a 17β-estradiol/ERα/PDL1 signaling loop in NSCLC. This intriguing result opens new therapeutic options. See related article by Anobile et al., p. 3958.


Multicomponent PFAS sorption and desorption in common commercial adsorbents: Kinetics, isotherm, adsorbent dose, pH, and index ion and ionic strength effects.
The adsorption and desorption of 9 PFAS, including 3 perfluoroalkyl sulphonic and 6 perfluoroalkyl carboxylic acids, in artificial groundwater was investigated using 3 commercial adsorbents that comprised a powdered activated carbon (PAC), a surface-modified organoclay (NMC+n), and a carbonaceous organic amendment (ROAC). Sorption kinetics and isotherms of PFAS, as well as the effects of adsorbent dose, pH, index ion and ionic strength on PFAS adsorption and desorption were investigated. Sorption of multicomponent PFAS in the adsorbents was rapid, especially for NMC+n and ROAC, regardless of PFAS chain length. The sorption and (and especially) desorption of PFAS in the adsorbents was impacted by the pH, index ion, and ionic strength of simulated groundwater, especially for the short chain PFAS, with only minimal impacts on NMC+n and PAC compared to ROAC. Although the potential mineral and charged constituents of the adsorbents contributed to the adsorption of short chain PFAS through electrostatic interactions, these interactions were susceptible to variable groundwater chemistry. Hydrophobic interactions also played a major role in facilitating and increasing PFAS sorption, especially in adsorbents with aliphatic functional groups. The desorption of PFAS from the adsorbents was below 8 % when the aqueous phase was deionised water, with no measurable desorption for NMC+n. In contrast, the desorption of short chain PFAS in simulated groundwater increased substantially (30-100 %) in the adsorbents, especially in ROAC and NMC+n, but more so with ROAC. In general, the three adsorbents exhibited strong stability for the long chain PFAS, especially the perfluoroalkyl sulphonic acids, with minimal to no sorption reversibility under different pH and ionic composition of simulated groundwater. This study highlights the importance of understanding not only the sorption of PFAS in groundwater using adsorbents, but also the desorption of PFAS, which may be useful for decision making during the ex-situ and in-situ treatment of PFAS-contaminated groundwater.


Passive sodium fluxes across toad bladder in the presence of simultaneous transepithellal gradients of concentration and potential.
Bidirectional sodium fluxes were measured across toad bladder sacs after eliminating active transport with ouabain. Transepithelial potential was clamped to 100 mV or the Nernst potential, psieq, at varying sodium concentrations, Cm, in the mucosal medium. Serosal sodium concentration, Cs, was held constant. Equations were derived for permeability, partial ionic conductance, and unidirectional fluxes as functions of Cm and Cs, based in part on the assumption that the ratio, Q, of bulk sodium permeability to tracer sodium permeability is a constant, independent of concentration and potential. The results conformed closely to these equations.


A treatment prediction strategy for overactive bladder using a machine learning algorithm that utilized data from the FAITH study.
To use machine learning algorithms to develop a model to accurately predict treatment responses to mirabegron or antimuscarinic agents in patients with overactive bladder (OAB), using real-world data from the FAITH registry (NCT03572231). The FAITH registry data included patients who had been diagnosed with OAB symptoms for at least 3 months and were due to initiate monotherapy with mirabegron or any antimuscarinic. For the development of the machine learning model, data from patients were included if they had completed the 183-day study period, had data for all timepoints and had completed the overactive bladder symptom scores (OABSS) at baseline and end of study. The primary outcome of the study was a composite outcome combining efficacy, persistence, and safety outcomes. Treatment was deemed "more effective" if the composite outcome criteria for "successful," "no treatment change," and "safe" were met, otherwise treatment was deemed "less effective." To explore the composite algorithm, a total of 14 clinical risk factors were included in the initial data set and a 10-fold cross-validation procedure was performed. A range of machine learning models were evaluated to determine the most effective algorithm. In total, data from 396 patients were included (266 [67.2%] treated with mirabegron and 130 [32.8%] treated with an antimuscarinic). Of these, 138 (34.8%) were in the "more effective" group and 258 (65.2%) were in the "less effective" group. The groups were comparable in terms of their characteristic distributions across patient age, sex, body mass index, and Charlson Comorbidity Index. Of the six models initially selected and tested, the decision tree (C5.0) model was chosen for further optimization, and the receiver operating characteristic of the final optimized model had an area under the curve result of 0.70 (95% confidence interval: 0.54-0.85) when 15 was used for the min n parameter. This study successfully created a simple, rapid, and easy-to-use interface that could be further refined to produce a valuable educational or clinical decision-making aid.


The presence of Plasmodium malariae and Plasmodium knowlesi in near malaria elimination setting in western Indonesia.
Indonesia is progressing towards malaria elimination. To achieve this goal, intervention measures must be addressed to cover all Plasmodium species. Comprehensive control measures and surveillance programmes must be intensified. This study aims to determine the prevalence of microscopic and submicroscopic malaria in Langkat district, North Sumatera Province, Indonesia. A cross-sectional survey was conducted in six villages in Langkat district, North Sumatera Province in June 2019. Data were recorded using a standardized questionnaire. Finger pricked blood samples were obtained for malaria examination using rapid diagnostic test, thick and thin blood smears, and polymerase chain reaction. A total of 342 individuals were included in the study. Of them, one (0.3%) had a microscopic Plasmodium malariae infection, no positive RDT examination, and three (0.9%) were positive for P. malariae (n = 1) and Plasmodium knowlesi (n = 2). The distribution of bed net ownership was owned by 40% of the study participants. The participants had a house within a radius of 100-500 m from the forest (86.3%) and had the housing material of cement floor (56.1%), a tin roof (82.2%), wooden wall (35.7%), bamboo wall (28.1%), and brick wall (21.6%). Malaria incidence has substantially decreased in Langkat, North Sumatera, Indonesia. However, submicroscopic infection remains in the population and may contribute to further transmission. Surveillance should include the detection of microscopic undetected parasites, to enable the achievement of malaria elimination.


High left ventricular outflow tract gradient: Aortic stenosis, obstructive hypertrophic cardiomyopathy or both?
The authors report the case of a patient diagnosed with both hypertrophic cardiomyopathy and aortic stenosis. Due to clinical deterioration, additional investigation was performed, and a high left ventricular outflow tract gradient was identified. Correct identification of the condition causing the symptoms was challenging, and involved several imaging techniques, the contribution of transesophageal echocardiography being crucial. The final diagnosis of severe aortic stenosis led to successful valve replacement surgery. The presence of these two conditions in the same patient has been documented, although it is uncommon. This association poses particular diagnostic and therapeutic challenges, which are discussed in this paper.


Significance of lung shrinkage on CXR as a prognostic factor in patients with idiopathic pulmonary fibrosis.
The aim of this study was to determine whether the presence of lung shrinkage on CXR can predict diminished survival in patients with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). In a hospital-based cohort study 68 subjects diagnosed with IPF/UIP by surgical lung biopsy or at autopsy were observed for a mean of 7.6 years. The radiographic scores from Cherniack's method, pulmonary function tests, arterial blood gas, and haematological data were obtained at initial presentation. Longitudinal radiographic changes over a mean interval of 2.7 years were measured. Survival analysis was performed using Kaplan-Meier and Cox's proportional hazards regression analysis. At some point during the observation period 36 (53%) of 68 patients did not exhibit lung shrinkage and 32 (47%) of 68 patients showed lung shrinkage. Patients with lung shrinkage were more likely to have a diminished survival than those with lung preservation; median survival was 4.4 vs 7.8 years, respectively. Lung shrinkage during the observation period (hazard ratio, 3.89; 95% CI = 1.68-9.01; P= 0.001) was associated with lower rates of survival. In patients with IPF/UIP, lung shrinkage on CXR during the observation period was a poor prognostic factor.


The effect of interdialytic interval on protein metabolism: evidence suggesting dialysis-induced catabolism.
While examining protein metabolism in hemodialysis patients, we noted that lengthening the interdialytic intervals from two to three days reduced the dialysate nitrogen waste excretion (D-N2; mg/min) and lowered the patient's protein catabolic rate (PCR; g/kg/d). D-N2 was measured in the spent dialysate and PCR derived from urea kinetics while patients maintained a constant dietary intake. In the basal state (B), D-N2 decreased from 5.43 to 4.32 mg/min when the interdialytic interval was increased from two to three days (P less than 0.001). Similarly, PCR was reduced from 0.96 to 0.82 g/kg/d when the interdialytic period was extended. The same phenomenon was observed when subjects were taking either thyroid hormone (T3) or ipodate (lp) to increase or decrease body metabolism. In the T3 period, D-N2 was 6.12 and 5.06 mg/min and PCR was 1.08 and 0.92 g/kg/d, respectively, when the interdialytic intervals were two and three days (P less than 0.001). During the lp period, N-D2 was 4.78 and 4.03 mg/min and PCR was 0.88 and 0.76 g/kg/d, respectively, for the two- and three-day intervals (P less than 0.05). These data are consistent with dialysis-related protein catabolism. It appears that the longer interdialytic interval allowed the body to shift to a more anabolic state.


The Cochrane Library: more systematic reviews on nutrition needed.
The knowledge and relevance of nutrition as well as the demand for well-funded advices increase. The Cochrane Collaboration plays a leading role within the evidence-based medicine and practice. We advocate therefore more specialized nutritional interest within the Cochrane Collaboration. In case 'Nutrition' needs more attention within the Cochrane Library, one of the first priorities is deciding about whether to include non-randomized studies into the Specialized Register and generating lists of journals to handsearch for such a Specialized Register. Preparatory to these activities an inventory of Nutritional content within the Cochrane Library is needed. We estimate that reviews directly related to nutrition and those of borderline interest to nutrition represent less than 4% of all published reviews in The Cochrane Library.


Do any kinds of perceived stressors lead to hypertension? A longitudinal cohort study.
Stress has been suggested as a contributing factor in the etiology and progression of hypertension in prior investigations. For a more comprehensive understanding of this concept, in this study, we aim to evaluate different domains of perceived stress and their possible contribution to the development of hypertension (HTN). This is a secondary analysis of the Isfahan Cohort Study (ICS). We used data from 2007 and 2013. The 12-item General Health Questionnaire (GHQ-12) and Stressful Life Events Questionnaire (SLEQ) were used to evaluate psychological distress and perceived stress in subjects, and a generalized linear mixed model (GLMM) was used to assess their association with HTN. Psychological distress had a significant positive relation with HTN that remained after full adjustment for other covariates. Individuals with high stress levels were 38% more likely to develop HTN (OR 1.38, 95% CI 1.18, 1.59). After full adjustment, total perceived stress was significantly associated with a 15% increase in HTN development (OR 1.15, 95% CI 1.01-1.29). Domains of perceived stress that were significantly associated with HTN independent of sociodemographic and lifestyle covariates were job conflict, job security, personal conflict, sexual life and daily life in both genders and financial problems in males (P < 0.01). The findings from this study underline the importance of identifying the effect of different sources of perceived stress to organize community-based strategies for the management of hypertension and help health professionals prioritize and efficiently allocate their resources for interventions.


Regulation of nuclear PKA revealed by spatiotemporal manipulation of cyclic AMP.
Understanding how specific cyclic AMP (cAMP) signals are organized and relayed to their effectors in different compartments of the cell to achieve functional specificity requires molecular tools that allow precise manipulation of cAMP in these compartments. Here we characterize a new method using bicarbonate-activatable and genetically targetable soluble adenylyl cyclase to control the location, kinetics and magnitude of the cAMP signal. Using this live-cell cAMP manipulation in conjunction with fluorescence imaging and mechanistic modeling, we uncovered the activation of a resident pool of protein kinase A (PKA) holoenzyme in the nuclei of HEK-293 cells, modifying the existing dogma of cAMP-PKA signaling in the nucleus. Furthermore, we show that phosphodiesterases and A-kinase anchoring proteins (AKAPs) are critical in shaping nuclear PKA responses. Collectively, our data suggest a new model in which AKAP-localized phosphodiesterases tune an activation threshold for nuclear PKA holoenzyme, thereby converting spatially distinct second messenger signals to temporally controlled nuclear kinase activity.


Prediction accuracy of Dolphin software for soft-tissue profile in Class I patients undergoing fixed orthodontic treatment.
Simulation and prediction can facilitate the decision between an extraction versus nonextraction treatment plan. This study aimed to assess the accuracy of Dolphin Imaging software in predicting profile changes in class I borderline cases. In this retrospective study, class I borderline patients (i.e., both extraction and nonextraction treatment plans were possible for them) aged 15-35 years were enrolled. All of the cephalometric analyses were done by Dolphin Imaging software, version 11.8 Premium. The initial cephalograms were superimposed on initial photographs. The final values for the 7 angular and linear landmarks of the upper and lower incisors were extracted from post-treatment cephalograms and inserted in the "Goals" tab of the Dolphin Imaging software. Post-treatment images of patients were simulated. Final post-treatment photographs were superimposed on the simulated pictures. The differences between the real and simulated pictures were calculated in relation to the reference lines. The P value was set at 0.05. A total of 70 patients (36 with tooth extraction, and 34 without tooth extraction) were included. In the extraction group, the horizontal position of both lips was predicted to be significantly more protruded than it actually was, whereas in the nonextraction group, the only difference between the simulated and actual results was that the vertical position of the lower lip, which was simulated as being more inferior than it actually was. Despite the statistically significant differences between the real and simulated pictures, the differences were small and clinically insignificant. Prediction via Dolphin Imaging software can be an appropriate guide in extraction-nonextraction borderline cases.


Assessment of tumour invasion into the mandible: the value of different imaging techniques.
In oral carcinomas close to the mandible, tumour invasion of the mandible is important in selecting segmental or marginal resection. Imaging may play a role in assessing tumour invasion. This study compares the accuracy of panoramic X-ray, CT and MR imaging in assessing invasion of the mandible in 29 patients. At histopathology, 6 patients had mandible erosion, 12 had invasion and 11 had an intact mandible. Magnetic resonance imaging had the highest sensitivity (94%), but a low specificity (73%), with 3 of 11 intact mandibles interpreted as positive. Furthermore, MR often overestimated the extent of tumour invasion. On the other hand, CT and panoramic X-ray had a lower sensitivity (64 and 63%, respectively) and a higher specificity (89 and 90%, respectively). Computed tomography (using 5-mm sections) and panoramic X-ray had a similar accuracy, and negative findings do not exclude invasion. Magnetic resonance imaging was the most sensitive technique but had more false positives and frequently overestimated the extent of tumour invasion. Because none of the radiological techniques are accurate enough, clinical examination seems at present to remain the most important modality in deciding between segmental and marginal resection. Tumour invasion at CT or panoramic X-ray is a strong argument for a segmental resection.


Changes in physical activity after abdominal sacrocolpopexy for advanced pelvic organ prolapse.
The objective of the study was to describe changes in physical activity 1 year after sacrocolpopexy for pelvic organ prolapse. This was a prospective cohort of 301 randomized trial participants. Compared with baseline, 1 year after surgery, 36% increased, 18% decreased, and 47% did not change preoperative exercise intensity level. In contrast, women were more likely to reduce (24%) than increase (11%) the frequency of major effort activities, like heavy lifting. Of 99 women who reported preoperatively that prolapse interfered substantially with doing exercise or recreation, house/yard work, or work outside the home, 83 (84%) reported no substantial interference 1 year later. After surgery, women reporting substantial interference from prolapse or treatment had similar rates of interval treatment for stress incontinence or prolapse as women not reporting substantial interference. After sacrocolpopexy, one third of women increased exercise intensity, few increased major effort activities, and most reported that prolapse no longer interfered with activities.


Modulation of functional activities of the neurotoxin from black widow spider venom.
We have studied the action of an alpha-latrotoxin (alpha-LTX) complex of two polypeptides (LTX 130 kDa and low molecular weight protein (LMWP) 8 kDa) and the action of a venom fraction containing LTX with excess LMWP on calcium influx into synaptosomes and PC12 cells as well as on [14C]GABA release from synaptosomes. Both preparations considerably activate calcium influx and stimulate [14C]GABA release from synaptosomes. Preincubation of both preparations with antibodies against a 14 amino acid residue C-terminal peptide of LMWP differentially modulates these effects. Antibodies inhibit induced calcium influx and enhance induced GABA release.


Prevalence of mesiobuccal-2 canals in maxillary first and second molars among the Bruneian population-CBCT analysis.
Identification of the second mesiobuccal canal (MB-2) in maxillary molars is considered an endodontic concern of many practitioners due to its complex morphology. The use of Cone-beam Computed Tomography (CBCT) is a necessity for easier location of this elusive canal during endodontic treatment. To study the prevalence of the MB-2 canal in the maxillary first and second molars amongst the Bruneian population. A retrospective study involving a review of scans taken from a CBCT scanner (J Morita; Veraviewepocs 3D R100 Panoramic/Cephalometric) over a 5-year period, from May 2016 to May 2021 was carried out. A total of 342 maxillary molars were evaluated independently by two observers. Any contradicting outcomes were discussed by both observers until a consensus was reached. In addition, the correlation of MB-2 canals with gender and age were calculated using the chi-squared test. The prevalence of MB-2 canal in the maxillary first and second molars are 51.3% and 29.8% respectively. Both males and females have a similar prevalence of MB-2 canals in the maxillary first and second molars. The incidence of MB-2 canals in both maxillary first and second molars significantly decreases with increasing age. No significant correlation between the prevalence of MB-2 canals with different gender groups in the population. It is crucial for clinicians to identify the presence of MB-2 canals when performing endodontic treatment of the maxillary first and second molars. Varying prevalence has been reported for different populations. Recognising this wide-ranging prevalence amongst different populations will allow for greater predictability in ensuring endodontic treatment success.


[The impact of mental disorders on health care utilization and illness behaviour in the elderly].
The differential impact of mental disorders on health care utilization and illness behaviour in old age should be studied. In a representative population sample of men and women aged 50 years and older (n = 1.185) mental disorders (depression, somatisation and panic syndrome), health care utilization and illness behaviour were assessed by means of self rating instruments. About 10 % of the study sample fulfil the criteria of at least one mental disorder. Older people with mental disorders showed a significantly increased health care utilization compared to people without mental disorders. They especially visit general practitioners but did not show an extended number of psychiatrists' or psychotherapists' visits. Mental disorders are associated with divergent illness behaviour. Regression analysis revealed that somatic complaints and depression were independent predictors of illness behaviour and health care utilization. General practitioners get a central function in the health care system for older people with mental disorders. More attention should be paid to the detection of mental disorders in older people and the special requirements of this subgroup of patients.


Interrelationships among measures of somatic, skeletal, dental, and sexual maturity.
The interrelationships among five measures of physiologic maturity for 50 French-Canadian girls are evaluated--menarche, peak height velocity (PHV), 75% skeletal maturity, appearance of the ulnar sesamoid, and 90% dental development. The mean ages of occurrence of the events differed significantly (P less than 0.01). Menarche and 90% dental maturity showed the least variability. Ages of PHV, menarche, and 75% skeletal maturity were significantly correlated (P less than 0.05). Age of menarche was most closely associated with PHV. The appearance of the ulnar sesamoid was highly correlated with 75% skeletal maturity; both were equally related to the ages of PHV and menarche. The age at which French-Canadian girls attain 90% of their dental development showed no significant relationships with the other maturity indicators. The results imply that the mechanisms controlling dental development are independent of somatic and/or sexual maturity.


Hormonal Contraceptive Use and Risk of Depression Among Young Women With Attention-Deficit/Hyperactivity Disorder.
Women with attention-deficit/hyperactivity disorder (ADHD) have an increased risk of becoming teenage mothers. Adverse effects of hormonal contraception (HC), including depression, may affect adherence to user-dependent contraception and increase the risk for unplanned pregnancies and teenage births in women with ADHD. The current study analyzed whether girls and young women with ADHD are at increased risk for depression during HC use compared with women without ADHD. A linkage of Swedish national registers covering 29,767 girls and young women with ADHD aged 15 to 24 years and 763,146 without ADHD provided measures of ADHD and depression diagnoses (International Classification of Diseases [ICD] code) and prescription of stimulant medication, HC, and antidepressant medication (Anatomical Therapeutic Chemical [ATC] code). Cox regression models applying an interaction term (ADHD diagnosis × HC use) evaluated the excess risk of HC-induced depression in women with ADHD. Women with ADHD had a 3-fold higher risk of developing depression, irrespective of HC use (adjusted hazard ratio [aHR] = 3.69, 95% CI = 3.60-3.78). Oral combined HC users with ADHD had a 5 times higher risk of depression compared with women without ADHD who were not using oral combined HC (aHR = 5.19, 95% CI = 4.94-5.47), and a 6 times higher risk in comparison with women without ADHD who were on oral combined HC (aHR = 6.10 (95% CI = 5.79-6.43). The corresponding risk of depression in women with ADHD who used a progestogen-only pill (aHR = 5.00, 95% CI = 4.56-5.49). The risk of developing depression when using non-oral HC was similarly moderately increased in both groups. Girls and young women with ADHD have an increased risk of developing depression when using oral HC compared with their unaffected peers. Information on risks with HCs as well as potential benefits with long-acting reversible contraceptives needs to be an integrated part of the shared decision making and contraception counseling for young women with ADHD.


The self-association of ATP: thermodynamics and geometry.
The concentration and temperature dependence of the self-association of ademosin-5'-triphosphate (ATP) in aqueous solution was studied by means of ultraviolet absorption spectroscopy and circular dichroism (CD). Of several possible models, a model was indefinite linear self-association, in which each step has the same equilibrium constant, describes the data best. The two different methods lead within experimental error to the same thermodynamic parameters. At pH 8.7, IN 1 M Tris and 0.5 M 7gCl-2, we find deltaH-0 equals -5.1 kcal/mole and deltaS-0 equals -13.0 e.u. These values do not differ much from those found for the self-association of uncharged bases and nucleosides in aqueous solution. The CD spectrum that results from the self-association is conservative and quite similar in shape to that observed for some stacked dinucleotides: it is interpreted as a first approximation within the framework of the exciton model.


Interaction of charged amphiphilic drugs with phosphatidylcholine vesicles studied by NMR.
Small unilamellar vesicles from egg phosphatidylcholine in NaCl solutions were exposed to some amphiphilic pharmaca. The aromatic drugs (chlorpromazine, dibucaine, tetracaine, imipramine and propranolol) were in their cationic form of the amines. By 1H- (100 and 400 MHz) and 31P- (40.5 and 161.7 MHz) NMR the membrane signals were observed. In particular, the N-methyl choline proton signals were followed upon drug addition. The intrinsic chemical shift difference (0.02 ppm) between the inner (upfield) and outer choline signals was influenced by the drug concentration. Packing properties of the lipid head groups and ring current shift probably contributed. At very high drug concentration, the vesicles are destroyed. A transformation into a micellar state with a high sample viscosity took place in a narrow concentration range of drug. The anion effects of Cl- were studied from the 35Cl-NMR linewidth at 9.8 and 39.1 MHz. A continuous increase in the signal linewidth followed upon drug addition to the vesicles. Only chlorpromazine produced a broadening in the absence of vesicles (NaCl blank). The linewidth reflected a critical micelle concentration of this drug around 7 mM in 0.1 M NaCl. The 35Cl-NMR experiments demonstrated the existence of an anionic counterion effect. This phenomenon should be accounted for when quantitatively analysing drug-membrane interactions in electrostatic terms.


mTOR in squamous cell carcinoma of the oesophagus: a potential target for molecular therapy?
The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been shown to significantly improve survival. An in vitro study has revealed that mTOR is activated in oesophageal squamous cell carcinoma (OSCC) cell lines and that mTOR expression is inhibited by rapamycin. The objectives of this histological study were to determine the proportion of OSCC tissues with activated mTOR (p-mTOR) expression, thereby assessing the percentage of patients with OSCC that would possibly benefit from neoadjuvant rapamycin therapy, and to identify the clinicopathological features of these potentially rapamycin-sensitive tumours. The expression of p-mTOR (Ser2448) was immunohistochemically assessed in a validated tissue microarray comprising triplicate tissue biopsy cores of 108 formalin-fixed, paraffin-embedded OSCCs. Staining results were correlated with clinicopathological data. Normal oesophageal epithelium was negative for p-mTOR. Activated mTOR expression was located in the cytoplasm of oesophageal tumour cells. 26 (25%) of 105 assessable OSCCs showed tumour cells with positive staining for activated mTOR. Activated mTOR expression was associated with a lesser degree of differentiation only (p = 0.024). No correlation was detected between p-mTOR and the proliferation marker Ki-67. Activated mTOR can be detected in one-quarter of OSCCs. Since this subset of patients may potentially benefit from mTOR inhibiting therapy, a phase II clinical trial of neoadjuvant mTOR-inhibiting therapy in patients with OSCC may be considered.


Changes in cyclic AMP binding and protein kinase activities during growth and differentiation of Blastocladiella emersonii.
Multiple protein kinases in the water mould Blastocladiella emersonii are described. A cyclic AMP-independent protein kinase which prefentially phosphorylates casein remains unchanged during vegetative growth of the cells and in the two phases of differentiation: germination and sporulation. In contrast, cyclic AMP-dependent protein kinase activity and cyclic AMP binding components are induced during the sporulation.


[Ductal carcinoma in situ of the breast (DCIS) under 40: a specific management?].
Ductal carcinoma in situ of the breast (DCIS) is rare in younger women, accounting for about 4% of all cases of DCIS in France, and tends to be diagnosed by clinical findings or casually, after plastic surgery. After breast conserving treatment, young age ( less than 40) is a predictive factor of relapses in patients with DCIS. Age may serve as one more parameter that should be considered in the complex decision-making process necessary to create a treatment plan for a woman with DCIS. Breast conservative treatment (BCT) could be used if: margins are free and more than 10 mm; if DCIS size is less than 11 mm and DCIS is free of necrosis and comedocarcinoma. Mastectomy ought to be proposed in case of: multifocal DCIS, or DCIS size more than 30 mm; invaded margins after re-excision; radiotherapy contraindicated; small breasts and patient choice. Immediate breast reconstruction should be proposed for patients with all the poor predictive factors. In other cases, treatment procedure will be explained to the patient and the treatment will be chosen by the patient in consultation with the medical team (radiologist, surgeon, pathologist and oncologist). Radiotherapy with boost or hormonotherapy with tamoxifen should not be used routinely but may be proposed individually.


Obstructive sleep apnea in children.
Despite increasing recognition of childhood obstructive sleep apnea syndrome (OSAS) as a significant public health problem, treatment of the condition remains inconsistent. Some children are screened using polysomnography and treated only when objective respiratory disturbances are identified. Many others receive adenotonsillectomy based only on signs and symptoms of upper airway obstruction without ever having a formal sleep study. Outcome-based data regarding the effectiveness of adenotonsillectomy, continuous positive airway pressure, and other treatments for childhood OSAS remain extremely limited. In this article, the major therapeutic options for treatment of childhood OSAS are reviewed. Adenotonsillectomy remains the most frequently used treatment for uncomplicated OSAS in children, but residual airway obstruction persists in a notable minority of patients. Nasal continuous positive airway pressure is used for children who are not good surgical candidates or who have failed previous surgical treatment, but is sometimes not tolerated by young children or their parents. Various alternative treatments are used on an individualized basis for children who cannot use the two first-line therapies for sleep apnea.


Stress, and coping strategy of university students during COVID-19 in Korea: The mediating role of ego-resiliency.
We aimed to identify the level of stress, ego-resiliency (ER), and coping strategies of university students during the onset of coronavirus disease 2019 (COVID-19) and examine the mediating role of ER in the relationship between stress and coping strategies (e.g., problem-solving, social support seeking, and avoidance). We analyzed responses from 160 university students and found that problem-solving was the most common coping strategy (26.02 ± 4.65), followed by social support-seeking (25.08 ± 5.23), and avoidance (19.21 ± 3.78). ER was negatively associated with stress and showed a mediating effect on the relationship between stress and social support, and stress and problem-solving coping strategies. These findings indicate that ER helps decrease stress caused by the pandemic among university students and should be considered a significant factor for developing adaptive stress coping strategies.


The cytotoxic effects of indoleamine 2, 3-dioxygenase inhibitors on triple negative breast cancer cells upon tumor necrosis factor α stimulation.
Overexpressed indoleamine 2,3-dioxygenase (IDO) has been observed in many types of cancer and plays an essential role in the tumor microenvironment through immune cells function. In our study, the therapeutic potentials of two different IDO inhibitors (Epacadostat [EPA] and 1-methyl-L-tryptophan [L-1MT]) in triple-negative breast cancer (TNBC) cells were assessed with and without tumor necrosis factor-α (TNF-α) stimulation. The anticancer activity of EPA and L-1MT alone and in combination with TNF-α was analyzed by WST-1, annexin V, cell cycle analysis, and acridine orange/ethidium bromide staining. In addition, the relationship between IDO1 and programmed death-ligand 1 (PD-L1) expressions in TNBC cells upon treatment with IDO inhibitors was evaluated by reverse transcription-polymerase chain reaction analysis. SPSS 22.0 was conducted for statistical analysis. The one-way analysis of variance with Tukey's multiple comparison test was performed for multiple groups. Independent (unpaired) t -test was used for the comparison of two groups. EPA and L-1MT alone significantly suppressed the TNBC cell viability through the induction of apoptotic cell death and G0/G1 arrest (P < 0.05). TNF-α alone induced the overexpression of IDO1 and PD-L1 in TNBC cells compared with MCF-10A control cells. However, IDO inhibitors significantly inhibited overexpressed IDO1 mRNA levels. Furthermore, EPA alone and co-treated with TNF-α suppressed the mRNA level of PD-L1 in TNBC cells. Therefore, TNF-α stimulation enhanced the therapeutic effects of IDO inhibitors on TNBC. Our findings showed that the efficacy of IDO inhibitors was mediated by pro-inflammatory cytokine. However, different molecular signaling pathways are associated with pro-inflammatory cytokines production, and the expression of IDO1 and PD-L1 calls for further investigations.


Identifying and Treating Ocular Manifestations in Psoriasis.
Psoriasis is a chronic immune-mediated inflammatory skin condition that commonly presents with red, thickened, and scaling plaques. Given the prominent cutaneous manifestations of psoriasis, more subtle ophthalmic findings of the disease may initially go undetected, with the potential for significant ocular morbidity. Associated ocular disease can involve nearly any structure of the eye, with the eyelids most commonly being affected, resulting in relatively common signs and symptoms of ocular surface discomfort. The presence of intraocular inflammation (i.e., uveitis) or retinal involvement carry a heightened risk of vision loss, and are often more difficult to diagnose outside of the ophthalmology clinic. Early detection and treatment of ocular disease can limit morbidity and are critical to the management of these patients, which requires coordination of care between dermatologists and ophthalmologists. The objective of this article was to review the most common ocular conditions that affect psoriatic patients, when to consider referral to an ophthalmologist, and to summarize the adverse ocular effects of current psoriasis treatments.


Life-threatening biopsy of an iliopsoas pseudotumour in a patient with haemophilia: a case report.
Iliopsoas pseudotumour is a serious complication of haemophilia. We present the case of a 20-year-old male patient with a six-month history of left leg weakness, limitation of movement and wasting of the muscles. Clinically he was diagnosed as having a psoas muscle rhabdomyosarcoma. During a computed tomography (CT) scan-guided Tru-cut biopsy he developed a serious and life-threatening bleeding from a retroperitoneal muscular haematoma. The patient underwent laparotomy prior to his final diagnosis of an Iliopsoas pseudotumour, which is a serious, as well as rare, complication of haemophilia.


Divergent reactivities in fluoronation of allylic alcohols: synthesis of Z-fluoroalkenes via carbon-carbon bond cleavage.
An unconventional cleavage of an unstrained carbon-carbon bond in allylic alcohols can be induced by the use of N-fluorobenzenesulfonimide (NFSI) under catalyst-free conditions. By using this simple procedure, a wide range of functionalized Z-fluoroalkenes can be accessed in high yield and selectivity from cyclic and acyclic allylic alcohols.


A pre-existing coordinated inflammatory microenvironment is associated with complete response of vulvar high-grade squamous intraepithelial lesions to different forms of immunotherapy.
Immunotherapy of vulvar high-grade squamous intraepithelial lesion (vHSIL) is investigated as an alternative for surgery, because of high comorbidity and risk of recurrence. Limited evidence exists on the role and composition of the immune microenvironment in current immunotherapeutic approaches for vHSIL. The vHSIL of 29 patients biopsied before treatment with imiquimod were analyzed by two multiplex seven-color immunofluorescence panels to investigate the pre-existing T-cell and myeloid cell composition in relation to treatment response. The samples were scanned with the Vectra multispectral imaging system. Cells were automatically phenotyped and counted with inForm advanced image analysis software. Cell counts and composition were compared to that of vHSIL patients before therapeutic vaccination (n = 29) and to healthy vulva (n = 27). Our data show that the immune microenvironment of complete responders (CR) to imiquimod resembled the coordinated infiltration with type 1 CD4+ and CD8+ T cells and CD14+ inflammatory myeloid cells also found in healthy vulva. However, more CD8+ T cells and FoxP3+ regulatory T cells were present in CR. The lesions of partial responders (PR) lacked such a coordinated response and displayed an impaired influx of CD14+ inflammatory myeloid cells. Importantly, complete responses after imiquimod or therapeutic vaccination showed the same dependency on a pre-existing coordinated type 1 T-cell and CD14+ myeloid cell infiltration. In conclusion, a good clinical outcome after two different forms of immunotherapy for vHSIL is associated with the presence of a primary inflammatory process resulting in the coordinated influx of several types of immune cells which is then amplified.