The surgical management of fungal pulmonary infections in children with acute myelogenous leukemia.
Infections are the primary cause of complications and death in patients with acute myelogenous leukemia. Current aggressive treatment protocols have improved patient survival but produce extended periods of profound neutropenia during which the patients are particularly susceptible to opportunistic infections. Candida and Aspergillus species are the most common of the fungi causing invasive infections in these patients. In a group of 77 previously untreated children with acute myelogenous leukemia begun on treatment from March 1976 to June 1984, four patients developed localized fungal infections of the lung. These initially appeared as pulmonary infiltrates on chest roentgenograms during periods of severe neutropenia (three during remission induction and one after intensive consolidation therapy). Endobronchial cultures failed to identify the infectious organism in all cases. Computerized axial tomography best defined the cavitary nature of the lesions in 2 patients. All four patients underwent surgical resection, both to establish a diagnosis (three patients) and as part of therapy. There was no operative morbidity. The organisms involved were Aspergillus (2), Torulopsis (1), and Penicillium (1). Three patients were cured of their fungal infections. The fourth patient failed to enter remission and died of a cerebral fungal abscess that developed shortly after thoracotomy. We report these cases to encourage early surgical intervention in leukemics with a localized pulmonary process consistent with a fungal infection. Resection of the primary focus obviates the risk of life threatening pulmonary hemorrhage or dissemination of the fungus and allows for early reinstitution of chemotherapy which is vital to these patients' survival.


Once-daily high-dose pindolol for SSRI-refractory depression.
Selective serotonin reuptake inhibitor (SSRI) augmentation with the 5-HT1A antagonist pindolol has met with mixed results. Recent studies using positron emission tomography (PET) suggest that pindolol doses used in these studies were too low to effect 5-HT1A autoreceptor blockade. To test the hypothesis that a single higher dose of pindolol would effectively augment antidepressant responses in SSRI-refractory patients, nine subjects with major depression unresponsive to paroxetine 40 mg/day given for 2 months or more were randomized to AM pindolol 7.5 mg (n=4) or placebo (n=5). Subjects were administered the Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), the Bech-Rafaelsen Melancholia Scale, and the Zung Depression Inventory at baseline and weeks 1, 2, 3, and 4. Subjects receiving pindolol exhibited significant improvements in all ratings beginning at week 2 which continued through week 4. Aside from transient dizziness and a five-point decrease in systolic/diastolic blood pressure associated with pindolol, no adverse effects were reported. Although results must be verified in a larger sample, these findings support previous studies indicating that pindolol can accelerate antidepressant responses during SSRI therapy. In addition, results reported here suggest that a single high dose of pindolol (7.5 mg) is a more effective augmentation strategy in SSRI-refractory patients compared with the same total dose given at 2.5 mg tid.


Experimental evaluation of the effect of positioning and operating parameters on the performance of a surface-piercing propeller.
Today, surface-piercing propellers have been recognized as a suitable choice for higher speeds. Yet, the development of design algorithms for such has been challenged by insufficient knowledge about the parameters affecting their performance. For this reason, developing experimental data and studying the influence of various parameters on their performance is crucial. Aiming to develop experimental knowledge of these propellers, this study investigates the impact of position parameters and Froude Number on model test results of a custom-designed propeller. Moreover, ventilation wake development at different Froude numbers was studied. The experimental results pointed to the favorable impact of increased immersion ratio on propeller's thrust, a positive impact of increasing the inclination angle by 6° on higher thrust and efficiency in the advance direction, and a slight increase of thrust with higher yaw angles up to 10°. The propeller's lateral forces were also extracted in different positions and operational conditions to identify the propeller's behavior and design the required shaft and supports. Finally, regression equations for projecting hydrodynamic coefficients used at the design phase were compared and verified by the experimental results. The results pointed to the insufficient precision of this model for estimating the hydrodynamic coefficients affecting the propeller.


Rational Design of Nile Red Analogs for Sensing in Membranes.
Development of next-generation fluorescent probes is a key element in the quest for a greater understanding of complex biological environments (e.g., membranes) by bioimaging. Such fluorescence-based techniques rely on specialized small molecules that possess excellent fluorescent properties but also do not perturb the native biological environment in which they reside. Herein we present a theoretical/computational strategy for the design of novel optical probes for sensing in membranes based on the parent chromophore Nile Red. Using a combination of time-dependent density functional theory (TD-DFT) and molecular dynamics (MD), we have studied the optical properties and accommodation in a model membrane of Nile Red and eight analogs. Special attention has been given to the design of probes with improved solvatochromism and two-photon absorption (2PA) without altering the membrane properties. Of the eight studied analogs, two probes were found to possess attractive probe features and are hence suggested to be taken forward to chemical synthesis and experimental exploration.


Effects of magnesium citrate and clidinium bromide on the excretion of activated charcoal in normal subjects.
The efficacy of cathartics in shortening the gastrointestinal transit time of activate charcoal (AC) in the presence of drugs that alter gastrointestinal motility has not been determined. We evaluated the effects of magnesium citrate (MC) on the excretion of activated charcoal in healthy volunteers alone and with concurrent administration of the anticholinergic drug clidinium bromide. Forty subjects were randomized to clidinium bromide 5 mg or placebo capsule (PC), followed by activated charcoal 15 g and magnesium citrate or a placebo liquid (PL). The onset and duration of excretion of activated charcoal were noted. Mean onset times for activated charcoal were: group I (CB, MC) 4.5 +/- 2.1 h; group II (CB, PL) 17.0 +/- 10.0 h; group III (PC, MC) 6.3 +/- 5.8 h; and group IV (PC, PL) 20.6 +/- 8.4 h. The onset of excretion of activated charcoal was statistically different in both magnesium citrate groups as compared with the placebo liquid groups. The duration of activated charcoal in the stool was similar among the groups. The addition of clidinium bromide did not appear to affect gastrointestinal transit time. These results support previous studies of the effects of cathartics on the excretion of activated charcoal, and suggest that cathartic efficacy is not inhibited by anticholinergic drugs when used in therapeutic doses.


Lupus anticoagulant acquired hypoprothrombinemia syndrome in childhood: two distinct patterns and review of the literature.
Lupus anticoagulant associated with acquired prothrombin deficiency also known as 'lupus anticoagulant hypoprothrombinemia syndrome' (LAHS) is an entity that is well described in adults and is usually associated with autoimmune conditions (LAHS-AI). However, in children, LAHS has unique features that are distinct from the adult type. We report two paediatric cases of LAHS, describe their distinct patterns and review the paediatric literature on LAHS. Case studies on two patients with LAHS were reviewed, details on their presentation, work up and management were extracted. A Medline search was conducted on LAHS in children between 1960 and 2014; Articles in languages other than English were excluded. The case studies highlight the differences in the two patterns of childhood LAHS. Additionally the review of the literature reveals that there are 15 case reports and 5 case series that report 25 children with LAHS-AI, 9 case reports and 6 case series report 26 children of LAHS associated with viral infections (LAHS-VI). At presentation, all patients with LAHS-AI had positive laboratory tests for autoimmune diseases, most commonly for systemic lupus erythematosus while these tests were negative in LAHS-VI. All patients with LAHS-AI had a protracted course and needed prolonged treatment with immune-suppressive therapy while patients with LAHS-VI resolved spontaneously or needed short-term immune-modulating therapy. In childhood, two distinct patterns of LAHS are observed, either associated with infection or autoimmune disease. Initial diagnostic investigations are critical to differentiating these two patterns as the prognosis and outcome for each is distinct.


Bone marrow aspiration in dogs and cats.
This column describes how to obtain a bone marrow sample by way of aspiration from the iliac crest and proximal humerus of the dog and cat for the assessment and diagnosis of bone marrow disease.


Evolutionary relationships within the Phytophthora cactorum species complex in Europe.
The Phytophthora cactorum species complex in Europe is composed of P. cactorum, Phytophthora hedraiandra, and a hybrid species Phytophthora × serendipita. Evolutionary analyses using the amplified fragment length polymorphism (AFLP) method were carried out on 133 isolates from 19 countries. The AFLP data were complemented by sequence analysis of three genes (ITS region of ribosomal RNA gene, phenolic acid decarboxylase - Pheca I, and Cytochrome oxidase - Cox I), morphometric analysis and cardinal temperature data. The high proportion of clonal genotypes, low gene flow among groups, which was defined by the structure analysis, and low Nei's gene diversity confirms the homothallic life cycle of the groups. On the other hand, the ITS, Cox I and Pheca I sequence data support occasional hybridization between species. The structure K = 5 grouping revealed two groups of hybrid origin (C2 and F). While the C2 group resembles P. × serendipita, the F group includes Finnish isolates characterized by high oogonial abortion rates and slow growth. The morphological characters routinely used in identification of Phytophthora species are not useful for delimitation of species from the P. cactorum complex. Therefore, we discuss the status of P. hedraiandra as a separate species. The epitypification of P. cactorum is proposed.


Multi-Domain Negative Capacitance Effects in Metal-Ferroelectric-Insulator-Semiconductor/Metal Stacks: A Phase-field Simulation Based Study.
We analyze the ferroelectric domain-wall induced negative capacitance (NC) effect in Metal-FE-Insulator-Metal (MFIM) and Metal-FE-Insulator-Semiconductor (MFIS) stacks through phase-field simulations by self-consistently solving time-dependent Ginzburg Landau equation, Poisson's equation and semiconductor charge equations. Considering Hf0.5Zr0.5O2 as the ferroelectric material, we study 180° ferroelectric domain formation in MFIM and MFIS stacks and their polarization switching characteristics. Our analysis signifies that the applied voltage-induced polarization switching via soft domain-wall displacement exhibits non-hysteretic characteristics. In addition, the change in domain-wall energy, due to domain-wall displacement, exhibits a long-range interaction and thus, leads to a non-homogeneous effective local negative permittivity in the ferroelectric. Such effects yield an average negative effective permittivity that further provides an enhanced charge response in the MFIM stack, compared to Metal-Insulator-Metal. Furthermore, we show that the domain-wall induced negative effective permittivity is not an intrinsic property of the ferroelectric material and therefore, is dependent on its thickness, the gradient energy coefficient and the in-plane permittivity of the underlying insulator. Similar to the MFIM stack, MFIS stack also exhibits an enhanced charge/capacitance response compared to Metal-Oxide-Semiconductor (MOS) capacitor. Simultaneously, the multi-domain state of the ferroelectric induces non-homogeneous potential in the underlying insulator and semiconductor layer. At low applied voltages, such non-homogeneity leads to the co-existence of electrons and holes in an undoped semiconductor. In addition, we show that with the ferroelectric layer being in the 180° multi-domain state, the minimum potential at the ferroelectric-dielectric interface and hence, the minimum surface potential in the semiconductor, does not exceed the applied voltage (in-spite of the local differential amplification and charge enhancement).


4-(2,3-Di-chloro-phen-yl)piperazin-1-ium picrate.
The title compound, C6H2N3O7 -·C10H13Cl2N2 +, crystallizes with one 1-(2,3-di-chloro-phen-yl)piperazine (DP) cation and one picrate (PA) anion in the asymmetric unit. In the crystal structure, the DP cation and PA anion are inter-connected via several N-H⋯O and C-H⋯O hydrogen bonds. The DP cation and PA anion are further connected through C-Cl⋯π [3.8201 (4), 3.7785 (4) Å] and N-O⋯π [3.7814 (4) Å] inter-actions. The DP cations are further inter-connected via a weak inter-molecular Cl⋯Cl [3.2613 (4) Å] halogen-halogen inter-action. The combination of these supra-molecular inter-actions leads to a herringbone like supra-molecular architecture.


Prevalence and factors associated with surgery anxiety in hospitalized patients: a point-prevalence study.
Preoperative anxiety is a challenging problem in the preoperative care of patients. Identifying risk factors helps nurses provide psychological support during the pre-operative visit so that stress can be reduced. This study aimed to determine the prevalence of surgical anxiety and related factors in hospitalized surgical patients. This research was designed as a point-prevalence study. The study was completed with 223 patients hospitalized in the surgical clinics of a tertiary hospital in Turkey. Surgical anxiety questionnaire (SAQ) and State-trait anxiety inventory (STAI) were used for the assessment of anxiety. Preoperative anxiety prevalence was 69.5% according to the SAQ and 49.3% according to STAI. Women, participants with no primary school education, those who were unemployed and had low income, those with no previous surgery, those living in fear of surgery, the participants who underwent major surgery and general anesthesia, and those who did not have knowledge about the surgical procedure and anesthesia had higher anxiety according to the two scales. A highly significant and positive correlation was found between total STAI and total SAQ. The importance of surgical anxiety for the health system, which affects two out of every three hospitalized patients, should not be underestimated. Therefore, national and global plans should be made to prevent and manage surgical anxiety.


A clinical decision rule for triage of children under 5 years of age with hydrocarbon (kerosene) aspiration in developing countries.
Unintended hydrocarbon ingestion is a common reason for pediatric hospitalization in the developing world. To derive a clinical decision rule, to identify patients likely to require a higher level facility (resource-requiring cases), that can be used at primary health care facilities with limited diagnostic and therapeutic resources. A prospective study of children 2 to 59 months old presenting to a poison treatment facility within 2 hours of oral hydrocarbon exposure. History and objective signs were recorded at admission and at 6, 12, 24 and, if present, 48 hours. Inclusion in the resource-requiring outcome group required: oxygen saturation <94%; any CNS depression; any treatment with (salbutamol); any care in the ICU; or death. 256 met the inclusion criteria and completed the study. Of these, 170 had a course requiring resources unavailable at most primary health care facilities, and 86 did not. The presence of wheezing, any alteration in consciousness (lethargy or any restlessness), or a rapid respiratory rate for age (RR >or= 50/min if age < 12 mo, >or= 40/min if age >or= 12 mo) at presentation identified 167 of 170 of these patients (sensitivity 0.98). Thirty-six of 86 patients classified as non-resource requiring were correctly identified (specificity 0.42). No combination of clinical symptoms provided better discrimination while preserving sensitivity. This study suggests a triage decision rule based on the presence of wheezing, altered consciousness, or a rapid respiratory rate within 2 hours of hydrocarbon exposure. Such a rule requires validation in other settings.


CO2 laser application to the mineralized dental tissues--the possibility of iatrogenic sequelae.
From the many types of laser that are available commercially, the CO2 laser is presently thought to have the greatest potential for use in dentistry. An outline of the generation of emitted radiation from such a laser is given together with a review of work previously carried out and reported in the literature regarding application to the teeth. The main points of interest are the effects of radiation on the enamel and dentine, but concern is felt towards the possible iatrogenic damage of thermal origin that may occur within the pulp following irradiation of the dental tissues.


The estimation of quinidine in human plasma by ion pair extraction and high-performance liquid chromatography.
A rapid, sensitive, accurate method for determination of quinidine in plasma has been developed using ion-pair extraction and high-performance liquid chromatography. The method, which is capable of distinguishing between quinidine and dihydroquinidine, involves acidification of plasma with perchloric acid, extraction with methyl isobutyl ketone and chromatography of the carbonate-washed extract on a silica gel column with a mobile phase of methylene chloride-hexane-methanol--perchloric acid (60:35:5.5:0.1) followed by fluorometric detection. The procedure is sensitive to below 50 ng/ml (coefficient of variation 6.6%) and compares favourably with a standard spectrofluorometric method when tested with plasma from volunteer subjects.


Between-sessions test-retest reliability of prefrontal cortical activity during usual walking in patients with Parkinson's Disease: A fNIRS study.
Examining between-sessions test-retest reliability of functional near-infrared spectroscopy (fNIRS) data is crucial to better interpret rehabilitation-related changes in the hemodynamic response. This study investigated test-retest reliability of prefrontal activity during usual walking in 14 patients with Parkinson's Disease with a fixed retest intervals of five weeks. Fourteen patients performed usual walking in two sessions (T0 and T1). Relative changes in cortical activity (oxy and deoxyhemoglobin: ∆HbO2 and ∆HbR, respectively) in the dorsolateral prefrontal cortex (DLPFC) using fNIRS system and gait performance were measured. Test-retest reliability of mean ∆HbO2 for the total DLPFC and for each hemisphere were measured using paired t-test, intraclass correlation coefficient (ICC), and Bland-Altman plots with 95% agreement. Pearson correlations between cortical activity and gait performance were also performed. Moderate reliability was found for ∆HbO2 in the total DLPFC (mean difference of ∆HbO2 between T1 and T0 = -0.005 µmol, p = 0.93; ICC average = 0.72). However, test-retest reliability of ∆HbO2 was poorer when considering each hemisphere. Findings suggest that fNIRS may be used as a reliable tool for rehabilitation studies in patients with PD. Test-retest reliability of fNIRS data between 2 sessions during walking tasks should be interpreted respectively of gait performance.


Anterior and pan-endophthalmitis caused by Candida albicans and Aspergillus fumigatus: report of two cases.
We report two posttraumatic fungal endophthalmitis cases with anterior and entire segment involvement caused, respectively, by Candida albicans and Aspergillus fumigatus. The anterior endophthalmitis induced by C. albicans presented multifocal lesions with hyphael structures in anterior chamber, but without involvement of posterior vitreous. The pan-endophthalmitis caused by A. fumigatus displayed significant hypopyon and vitritis. Treatment strategies are anterior chamber cleaning for anterior endophthalmitis and vitrectomy for pan-endophthalmitis, excepting systemic and topical antifungal drug applications including intravitreal injection for both types of endophthalmitis. There is a much better outcome in the case with anterior segment involvement than that with entire segment involvement. This case report provides evidence that the different types of posttraumatic fungal endophthalmitis related to different fungal infections indeed existed and should be managed with different strategies.


Direct cost and predictive factors for treatment in patients with ocular hypertension or early, moderate and advanced primary open-angle glaucoma: the CoGIS study in Germany.
The main objectives of this analysis were to assess the treatment costs and to identify major cost drivers and factors predicting direct costs in German patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG). This non-interventional cross-sectional study was conducted in two university hospitals and 13 ophthalmology practices in Germany regions (Bavaria, Rhineland-Palatinate, North Rhine-Westphalia, Hamburg and Mecklenburg-Western Pomerania) between May 2009 and January 2010 to assess resource utilisation in patients with OHT (ICD-10: 40.0) or POAG (ICD-10: 40.1) at early, moderate or advanced stages, according to the European Glaucoma Society classification Guidelines. Treatment patterns and direct costs were evaluated retrospectively for 5 years. Resource utilisation data (medication, hospitalisation, outpatient surgery, visits to ophthalmologists) were abstracted from the charts, and unit costs were applied to estimate direct costs per year (in Euros, 2009), calculated from the perspective of the statutory health insurance in Germany (Gesetzliche Krankenversicherung). Factors predicting costs were assessed in multivariate regression analysis. One hundred and fifty-four patients (17.5% OHT, 27.9% early, 22.7% moderate, and 31.8% advanced POAG), on average 67 years old (SD 11) were included in the study. Average total annual direct costs per patient for OHT were <euro>226 (SD 117), for early POAG <euro>423 (SD 647), moderate <euro>493 (SD 385) and advanced POAG <euro>809 (SD 877). Glaucoma-related medications and hospitalisation represented the two major components of direct costs, increasing with the progression of glaucoma. In addition to treatment switches (p = 0.0001), factors predictive of an increase in total direct costs included the number of hospital interventions (p < 0.0001), disease-state changes since the start of treatment (p = 0.05), and current disease state (p = 0.05). Direct costs of treatment are higher in glaucoma compared to OHT and further increase in more severe glaucoma states. Additional treatment changes are major contributing factors to the increased treatment costs of glaucoma. If intraocular pressure can be controlled over the long term, progression to moderate and advanced states avoided, and patients remain on initial treatments, treatment costs could decline due to reduced and less expensive healthcare resource utilisation.


Newer components of enteral formulas.
The past decade has seen a paradigm shift in the goals of nutritional care from basic delivery of macronutrient calories to the provision of specific nutrients, which, in addition to supporting growth, have health and disease modulating effects. The appreciation of the central role of nutrition in heath and disease may lead to increased use of a new array of diets that are more specific for underlying health and disease pathophysiologic processes. An improved understanding of disease-specific pathophysiology, and limited but promising data from ongoing clinical trials, are fueling this positive change. Therefore, a greater understanding of rationale for the newer products may lead to improved nutritional and clinical care during health and disease.


Complete 1H and 13C NMR assignments of clerodane diterpenoids of Salvia splendens.
Unambiguous and complete assignments of 1H and 13C NMR chemical shifts for five clerodane diterpenes, four of them isolated from Salvia splendens (salviarin, splendidin and splenolides A and B) and one obtained by acetylation of splenolide A, are presented. The assignments are based on 2D shift-correlated [1H,1H-COSY, 1H,13C-gHSQC-1J(C,H) and 1H,13C-gHMBC-nJ(C,H) (n=2 and 3)] and nuclear Overhauser effect (NOE) experiments. The conformation of the rings of these compounds is supported by the 3J(H,H) values and NOE results.


Modeling and evaluation of urban pollution events of atmospheric heavy metals from a large Cu-smelter.
Metal smelting and processing are highly polluting activities that have a strong influence on the levels of heavy metals in air, soil, and crops. We employ an atmospheric transport and dispersion model to predict the pollution levels originated from the second largest Cu-smelter in Europe. The model predicts that the concentrations of copper (Cu), zinc (Zn), and arsenic (As) in an urban area close to the Cu-smelter can reach 170, 70, and 30 ng m−3, respectively. The model captures all the observed urban pollution events, but the magnitude of the elemental concentrations is predicted to be lower than that of the observed values; ~300, ~500, and ~100 ng m−3 for Cu, Zn, and As, respectively. The comparison between model and observations showed an average correlation coefficient of 0.62 ± 0.13. The simulation shows that the transport of heavy metals reaches a peak in the afternoon over the urban area. The under-prediction in the peak is explained by the simulated stronger winds compared with monitoring data. The stronger simulated winds enhance the transport and dispersion of heavy metals to the regional area, diminishing the impact of pollution events in the urban area. This model, driven by high resolution meteorology (2 km in horizontal), predicts the hourly-interval evolutions of atmospheric heavy metal pollutions in the close by urban area of industrial hotspot.


Medication errors--an enduring problem for children and elderly patients.
To analyze the types and reasons of medication errors, committed by health care professionals, which led to toxicological consultations at the Czech Toxicological Information Centre (TIC). Inquiries arising from medication errors for 2000-2010 were extracted and evaluated from the database of the TIC, recording the consultations of poisonings due to drugs, household products, plants, and mushrooms. From a total of 44,344 calls concerning pharmaceuticals, 215 (0.5%) were denoted by the caller as medication errors; 130 involved children (90 below 5 years of age) and 85 involved adults (30-60 years of age). The most common errors were: improper dosage (60.9%), wrong medication (19.3%), or erroneous route of administration (12.9%). The most frequent medication errors appeared using drugs affecting the nervous system (psycholeptics and antiepileptics), antibiotics, and drugs affecting the respiratory system. Nurses administering the drugs were responsible for 43.0%, physicians prescribing the drugs for 36.8%, and pharmacists dispensing the drugs for 20.2% of the errors. Of 25 patients with severe drug intoxications, 60.0% were children under 5 years of age treated with pharmaceuticals affecting the CNS, and 28.0% patients over 60 years of age with chronic application of theophylline, digoxin, or lithium. The trend in medication errors has remained relatively stable over the past 11 years. The analysis of medication errors shows two high-risk categories: children of less than 5 years of age, in whom the dose was not correctly adjusted, and elderly people with chronic medication and insufficient control of their medication level. Therefore, the measures for risk reduction should focus primarily on them.


Resting energy metabolism and sweet taste preference during the menstrual cycle in healthy women.
Differences in blood concentration of sex hormones in the follicular (FP) and luteal (LP) phases may influence energy metabolism in women. We compared fasting energy metabolism and sweet taste preference on a representative day of the FP and LP in twenty healthy women (25·3 (sd 5·1) years, BMI: 22·2 (sd 2·2) kg/m2) with regular self-reported menses and without the use of hormonal contraceptives. From the self-reported duration of the three prior menstrual cycles, the predicted FP and LP visits were scheduled for days 5-12 and 20-25 after menses, respectively. The order of the FP and LP visits was randomly assigned. On each visit, RMR and RQ by indirect calorimetry, sweet taste preference by the Monell two-series forced-choice tracking procedure, serum fibroblast growth factor 21 by a commercial ELISA (FGF21, a liver-derived protein with action in energy balance, fuel oxidation and sugar preference) and dietary food intake by a 24-h dietary recall were determined. Serum progesterone and oestradiol concentrations displayed the expected differences between phases. RMR was lower in the FP v. LP (5042 (sd 460) v. 5197 (sd 490) kJ/d, respectively; P = 0·04; Cohen effect size, d rm = 0·33), while RQ showed borderline significant higher values (0·84 (sd 0·05) v. 0·81 (sd 0·05), respectively; P = 0·07; d rm = 0·62). Also, in the FP v. LP, sweet taste preference was lower (12 (sd 8) v. 16 (sd 9) %; P = 0·04; d rm = 0·47) concomitant with higher serum FGF21 concentration (294 (sd 164) v. 197 (sd 104) pg/ml; P < 0·01; d rm = 0·66). The menstrual cycle is associated with changes in energy expenditure, sweet taste preference and oxidative fuel partitioning.


Bilateral Silicone Granulomas Mimicking Breast Cancer Recurrence on 18F-FDG PET/CT.
We report the case of a 45-year-old woman with a history of right breast reconstruction with silicone implant for breast cancer. An 18F-FDG PET/CT performed several years later revealed the presence of 18F-FDG-avid nodules at the periphery of the silicone implant, in the right internal mammary chain, and in the contralateral breast. Needle core biopsies were positive for bilateral silicone granulomas, without any sign of malignancy. This case displays intense 18F-FDG uptake in silicone granulomas affecting the contralateral breast after implant reconstruction.


Analysis of volatile compounds emitted from fresh Syringa oblata flowers in different florescence by headspace solid-phase microextraction-gas chromatography-mass spectrometry.
In this study, a simple and solvent-free method was developed for determination of the volatile compounds from fresh flowers of Syringa oblata using headspace solid-phase microextraction and gas chromatography-mass spectrometry. The SPME parameters were studied, the optimum conditions of a 65mum polydimethylsiloxan/divinylbenezene (PDMS/DVB), extraction temperature of 25 degrees C and extraction time of 30 min were obtained and applied to extraction of the volatile compounds emitted from fresh flowers of S. oblata. The volatile compounds released from fresh flowers of S. oblata were separated and identified by GC-MS. Lilac aldehyde A, lilac aldehyde B, lilac aldehyde C, lilac aldehyde D, lilac alcohol A, lilac alcohol B, lilac alcohol C, lilac alcohol D, alpha-pinene, sabinene, beta-pinene, myrcene, d-limonene, eucalyptol, cis-ocimene, benzaldehyde, terpinolene, linalool, benzene acetaldehyde, alpha-terpineol, p-methoxyanisole, p-anisaldehyde, (Z,E)-alpha-farnesene and (E,E)-alpha-farnesene were the most abundant volatiles released from fresh flowers of S. oblata var. alba. The relative contents of main volatile fragrance were found to be different in emissions from two varieties of S. oblata flowers (white or purple in color). The four isomers of lilac alcohol and four isomer lilac aldehyde were the characteristic components of the scent of fresh flowers of S. oblata. The main volatile fragrance from fresh flowers of S. oblata var. alba in different florescence ((A) flower buds; (B) at the early stage of flower blooming; (C) during the flower blooming; (D) at the end of flower blooming; (E) senescence) were studied in this paper. The results demonstrated that headspace SPME-GC-MS is a simple, rapid and solvent-free method suitable for analysis of volatile compounds emitted from fresh flowers of S. oblata in different florescence.


Thyroliberin blocks the potassium A-current in neurons in the respiratory center of adult rats in vitro.
Thyroliberin is a neuropeptide with marked respiratory activity. The neuronal mechanisms underlying this activity were addressed in experiments on transverse slices of brainstem from adult rats in conditions of membrane potential clamping to study effect effects of thyroliberin (10 nM) on the potassium A-current in neurons of two areas of the respiratory center--the ventrolateral areas of the solitary tract nucleus and the pre-Betzinger complex. The A-current, seen in all study neurons in the respiratory center, was partially and reversibly blocked by thyroliberin. A significant reduction in the amplitude of the current was accompanied by an increase in the inactivation constant. The effect of thyroliberin on the amplitude of the A-current was analogous to that of 5 mM 4-aminopyridine. These results show that the stimulatory effects of thyroliberin at the level of respiratory center neurons is at least partly explained by its ability to block the potassium A-current.


Turner's syndrome: a qualitative and quantitative analysis of EEG background activity.
A qualitative and quantitative analysis was performed on the EEG background activity in 62 Danish girls and women with Turner's syndrome (30 with karyotype 45,X and 32 with other karyotypes) whose ages ranged from 6 to 47 years (87% were aged 15 years or more) and age-matched controls. The pooled data and a case-control study showed characteristic features in Turner subjects, including: (1) more rapid frequency, larger amplitude and lower amount of alpha waves, (2) higher amount of theta waves, (3) larger amplitude and higher amount of delta waves and (4) larger amplitude and higher amount of beta waves than in controls. These findings in Turner subjects were more pronounced in the left hemisphere, and more typical, except for the amplitude in alpha waves, in Turner subjects with 45,X than in those with other karyotypes. The effects of advancing age on the EEG background activity observed in controls--including more rapid frequency, decreased amplitude and amount of alpha waves, increased amount of theta and delta waves, and increased amount of beta waves, particularly after 35 years of age--were found in some Turner subjects. Hemispheric differences with higher activity (i.e. more rapid frequency, larger amplitude and higher amount of alpha waves, particularly at Fp1 and F3, and, inversely, lower amount of theta or delta waves) at P3, T3, T5 and O2 than at the opposite side were found in many Turner subjects. However, these findings were not specific for Turner subjects, since the same hemispheric differences were also observed much more markedly in controls. These topographic distributions with hemispheric differences did not provide evidence for hypofunction in the temporo-parieto-occipital tertiary area of the right hemisphere in Turner subjects, though this had been expected on the basis of neuropsychological examinations. Our findings, including transiently appearing brain hypofunction at the parietal, temporal and occipital areas, most often in the right hemisphere, indicate a relationship between the chromosomal constitution 45,X and EEG background activity. They suggest the presence of functional brain disturbance in the thalamus and in the ascending reticular activating system, which tends to disturb the thalamo-cortical circuit. Further studies, including topographic and sequential power spectrum analysis of EEG background activity, 24-h continuous EEG recording, blood flow studies (positron computerized tomography) and neuropathological examination, may be needed.


Detection of ethylene receptor protein Cm-ERS1 during fruit development in melon (Cucumis melo L.).
Antibodies against melon ethylene receptor, Cm- ERS1 was prepared. Cm-ERS1 protein formed a disulphide-linked homodimer and it was present in microsomal membranes but not in soluble fractions. Cm-ERS1 protein was present at high levels in melon fruit during early developmental stages. This transition pattern was also observed in another melon cultivar.


Valvular heart disease and pregnancy: part II: prosthetic valves.
A large number of prosthetic heart valves (PHV) are being implanted in patients with both congenital and acquired valvular disease. Many of the recipients of such valves are women of childbearing age who desire to have children. The main issues involved with pregnancy in a patient with PHV include the selection of PHV in women during their childbearing age, risks to both the mother and the fetus associated with pregnancy and the management of the patients with PHV during gestation.


Transcriptomic analysis suggested the involvement of impaired lipid droplet biogenesis in graphene oxide-induced cytotoxicity in human umbilical vein endothelial cells.
Previous studies revealed that direct contact with graphene oxide (GO) induced cytotoxic effects, but the importance of involvement of metabolic pathways, in particular lipid metabolism pathways, might be overlooked. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to GO with large size (denoted as GO-L) or small size (denoted as GO-S), and transcriptomics were used to understand the mechanisms of cytotoxicity of GO at systemic levels. It was shown that GO-L more significantly induced cytotoxicity compared with GO-S. Transcriptomic analysis revealed that compared with GO-S, GO-L had larger impact on gene ontology terms related with mitochondrial function as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related with cell death and growth. But GO-S showed greater influence on KEGG pathways related with lipid metabolism. Both types of GO showed minimal impact on oxidative stress but increased de novo lipogenesis protein fatty acid synthase (FASN). However, only GO-S significantly promoted acyl-CoA synthetase 3 (ACSL3), a key enzyme responsible for esterification of free fatty acids and lipid droplet biogenesis. Not surprisingly, GO-L but not GO-S impaired lipid droplet biogenesis, and increasing lipid levels by oleic acid or α-linolenic acid reduced the cytotoxicity of GO-L to HUVECs. Combined, the results from this study suggested that impaired lipid droplet biogenesis was involved in GO-induced cytotoxicity in HUVECs, and inducing lipid droplet biogenesis could prevent the cytotoxicity of GO.


The dairy sector in the Azores Islands: possibilities and main constraints towards increased added value.
The Azores archipelago is the most suitable region for dairy production in Portugal, representing 30% of the overall Portuguese dairy production. It has a production system characterized by an average milk yield of 6216 kg/cow/year, and the predominance of pasture-based feeding and cows that have longer productive lives and lower incidence of metabolic/production diseases, such as acidosis or mastitis. The biggest problem with the Azores Islands dairy sector is the cost of transport, as the main markets are located in continental Portugal, over 1500 km away, and local dairy products have to compete with dairy products produced in mainland Portugal and in the rest of the European Union. Herein, the evolution of the dairy sector in the Azores Islands from 2007 to 2017 is presented. A SWOT (Strength, Weakness, Opportunity, and Threat) analysis was performed to find potential solutions to increase the value of the Azorean dairy sector. The most relevant solution considered was the valorization of the dairy production through three major aspects: higher milk quality, namely, better organoleptic properties; lower carbon footprint (not considering transport costs); and higher levels of animal welfare. Three examples are shown of such valorization: protected denomination of origin (PDO) cheeses, the "happy cows" program, and the production of an organic milk, from the Terceira Island. Some of these programs are relatively recent, so, it will be interesting to see how their sales and acceptance by consumers evolve, particularly under the current economic framework.


Artificial womb technology, pregnancy, and EU employment rights.
This article considers challenges for the European Union (EU) maternity and pregnancy rights framework when faced with advances in reproductive technology. Specifically, we consider how the introduction of the 'artificial womb' technology, an alternative to bodily gestation, would impact the availability of rights that exist under the maternity and discrimination framework. Employment rights in the EU context have already been confronted by the challenges of advancements in reproduction. We use the case law on in vitro fertilization (IVF) and surrogacy as a baseline for unpacking the challenges that 'artificial wombs' will bring. This analysis of the legal framework on maternity rights and sex discrimination will highlight potential avenues for integrating this technology and ensuring the continuation of rights for those opting for it. We advocate against the stratification of maternity and pregnancy rights based on the reproductive and gestational choices made by the pregnant person.


[Fenton syndrome].
Scaphocapitate, or Fenton syndrome, is a rare injury. This article presents three new cases that were treated by open reduction and internal fixation with miniscrews, obtaining good results at 16 months follow-up.


Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis.
The optimal therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is undefined. We studied patients with SR aGVHD, comparing extracorporeal photopheresis (ECP; n = 57) and anticytokine therapy (n = 41). In multivariate analyses, ECP, adjusted for steroid dose (odds ratio, 3.42; P = .007), and grade >II aGVHD (odds ratio, 68; P < .001) were independent predictors of response. ECP therapy, adjusted for conditioning regimen intensity and steroid dose, was associated with superior survival (hazard ratio [HR], 4.6; P = .016) in patients with SR grade II aGVHD. Grade >II aGVHD at onset of salvage therapy (HR, 9.4; P < .001) and lack of response to therapy (HR, 3.09; P = .011) were associated with inferior survival. These findings require validation in a prospective randomized study.


Sodium nitroprusside alleviates nanoplastics-induced developmental toxicity by suppressing apoptosis, ferroptosis and inflammation.
The health damage caused by nanoplastics (NPs) pollution has become one of the global scientific problems to be solved urgently. However, the toxicological mechanism of NPs is complex, and the research progress of anti-toxicity is limited. Thus, it has potential application value to explore or develop drugs that can effectively alleviate or remove NPs with biological toxicity. In this research, 8 μM sodium nitroprusside (SNP) solution was used to treat zebrafish larvae with 20 mg/L NPs for up to 12 days, and the results showed that SNP treatments were effective in alleviating NPs-caused developmental toxicity in zebrafish larvae. Further examination of its signaling pathway revealed that NPs-induced oxidative stress was mitigated by activating the NO-sGC-cGMP signaling pathway and reduced most of the reactive oxygen species (ROS). Subsequently, we detected the key substances and the key enzymes involved in apoptosis and ferroptosis, and found that oxidative stress-induced mitochondria-dependent apoptosis and lipid peroxidation-caused ferroptosis were alleviated. Finally, observed the accumulation of NPs and ROS in the liver of zebrafish larvae, which is the target organ of immunotoxicity, and we found that SNP could alleviate NPs-caused inflammation by analyzing the fluorescence intensity of neutrophils and macrophages in transgenic zebrafish and detecting the expression of key immune genes. In conclusion, this research has shown for the first time that SNP treatment can significantly inhibit NPs-induced developmental toxicity, resulting from oxidative stress-induced apoptosis, ferroptosis and inflammation in zebrafish larvae.


Work-family and family-work conflict: does intrinsic-extrinsic satisfaction mediate the prediction of general job satisfaction?
The objective of this study is to analyze the mediating role of intrinsic and extrinsic job satisfaction in the relationship between the 2 dimensions of work-family conflict-family interfering with work (FIW) and work interfering with family (WIF)-and general job satisfaction. Step-by-step hierarchical regression analyses were carried out on a sample of 151 men and women from a Spanish public organization. The results confirmed the mediating role of intrinsic job satisfaction in the case of FIW. This highlights the importance of taking into account the level of satisfaction with the intrinsic facets of one's job as a measure for understanding why FIW has a negative impact on general job satisfaction.


Successful use of extra-corporeal membrane oxygenation in a patient with streptococcal sepsis: a case report and review of literature.
A young patient with streptococcal sepsis due to the phlegmon of his left thigh was admitted to the general intensive care unit. He developed a multi-organ failure and septic cardiomyopathy with subsequent cardiogenic shock. This resulted in hemodynamic instability unresponsive to conservative medical treatment. We report a successful application of veno-arterial extra-corporeal membrane oxygenation, which was used to overcome the period of critically low cardiac output caused by severe septic myocardial dysfunction.


Atrial Fibrillation in Kidney Failure: Challenges in Risk Assessment and Anticoagulation Management.
Management of atrial fibrillation (AF) is a clinical conundrum in people with kidney failure. Stroke risk is disproportionately high, but clinicians have a limited armamentarium to improve outcomes in this population in whom there is a concurrently high bleeding risk. Direct oral anticoagulants may have a superior benefit-risk profile compared with vitamin K antagonists in people on hemodialysis. Although research has predominantly focused on identifying a safe and effective oral anticoagulation option to reduce stroke risk in people with kidney failure (and predominantly those on hemodialysis), it remains uncertain how clinicians discriminate between people who would derive net clinical benefit as opposed to net harm. The recommended CHA2DS2-VASc score cutoffs provide poor discriminatory value, and there is an urgent need to identify robust markers of thromboembolic risk in kidney failure. There is increasing data to challenge the prior dogma of risk equivalence across AF type, and the American Heart Association highlights moving beyond AF as a binary entity to consider the prognostic significance of AF burden. Implantable cardiac monitor studies reveal high rates and varied burden of subclinical and paroxysmal AF in people on hemodialysis. The association between AF burden and the proarrhythmic environment of hemodialysis with cyclical volume loading, offloading, and electrolyte changes is not well studied. We review the significance of AF burden as a contributor to thromboembolic risk, its potential as the missing link in risk assessment, and updated evidence for anticoagulation in people with kidney failure.


Online 'chats': fostering communitas and psychosocial support for people working across arts and play for health and wellbeing.
Loss of work, furlough, and increased social isolation were prevalent for many working in the broad context of cultural and community engagement for health and wellbeing. This study set out to explore if and how regular online group interactions may foster social cohesion and provide support for these individuals during the critical time of the COVID-19 global pandemic. It was conducted in the context of the 'social cohesion chat' series led by a network called the Arts Play Health Community which was initiated in response to the pandemic as a way to bring those working in or connected to arts, play and health together during times of social isolation. Two qualitative focus groups with creative, participatory components were conducted with artists, researchers, evaluators, and arts/play managers (n = 11), and then analyzed using thematic analysis. Researcher ethnographic reflections and fieldnotes were also collected and analyzed. The authors engaged in reflexive online discussions to integrate and synthesize findings across different data. Four themes were constructed through the analysis procedure: (1) 'Building an online community as processes of communitas', spotlighting the importance of the non-hierarchical structure of the 'chats' particularly in relation to there being 'no end goal' to the online dialogues; (2) 'Individual and shared emotional experiences' that underpinned feelings of connection to others and the online space; (3) 'Psychosocial benefits' such as improving confidence and providing an opportunity to 'have a voice' in the community; and (4) 'The importance of facilitation', highlighting the opportunities the chats provided for participants to feel validated and valued as an active member of the community. The article concludes that constructing an inclusive and welcoming online community, where active participation is at the heart of regular social interactions can provide support for those working across arts and play for health and wellbeing. This was particularly important during the societal turbulence of the COVID-19 pandemic. It further concludes by noting the unique structure of these online dialogues as not being connected to institutions, with this playing a key role in allowing those in the community to 'be themselves' within it.


Regulation of nucleotide and pentose synthesis in resting and stimulated 3T6 fibroblasts.
A two-step procedure has been used to follow the activation of one metabolic system involved in the return of cells to a proliferative state after resting in a Go state as a result of serum limitation. One feature of the resting state is a limited capacity to synthesize nucleotides. The limitation apparently is in the rate of synthesis of 5-phosphoribosylpyrophosphate from glucose and indirectly in the capacity of the resting cells to turn over the triphosphopyridine nucleotide pair, NADPH:NADP+. A reaction utilizing NADPH is apparently greatly diminished in resting cells and is substantially increased by only brief contact of cells with the hormonal elements in dialyzed calf serum. Insulin together with platelet-derived growth factor can substitute for calf serum. Aside from stimulating the turnover of the pyridine nucleotide coenzyme pair, serum also stimulates the utilization and reformation of ATP, principally from AMP. Among the NADPH-linked reactions that have been examined for their physiological significance in the initiation of growth stimulation are two steps in the conversion of glutamate to proline in the cytoplasm. Pyrroline 5-carboxylate, an intermediate in this metabolic pathway, has been shown to stimulate PRPP synthesis when added to cultures of resting 3T6 cells. Proline, the product of the reduction of this 5-membered heterocycle is also a stimulant of PRPP synthesis. In addition, dehydroascorbic acid is a potent stimulant of PRPP synthesis. As a working hypothesis, we are exploring the role of a series of reactions that form a pyrroline 5-carboxylate/proline cycle operating between the cytoplasm and mitochondria. The net result is the oxidation of NADPH by molecular oxygen to yield NADP+ and water. The NADP+ is then used in the hexose monophosphate pathway for the conversion of glucose to PRPP. We wish to determine whether dehydroascorbate is operating in this cycle as an oxidant of proline in the mitochondria or whether it participates in some other reaction in the cell that redistributes the ratio of NADPH to NADP.


Probit analysis of the atrioventricular (AV) junctional tissues of the ferret heart.
Probit frequency analysis, a graphic method for determining whether a population is normally distributed, skewed, or multinodal, was used to determine whether P cells are present in different regions of the AV junction in the ferret heart. This analysis indicated that at least 95% of the cells of the transitional zone, superficial AV node, deep AV node, and distal AV bundle of the ferret heart are morphologically homogeneous. In the proximal AV bundle a large cell population is found in addition to the AV bundle cells. The probit analysis was also used to characterize the shape of the cells of each region of the AV junction further. AV nodal cells are not as elongated as the atrial muscle cells and AV bundle cells. These nodal cells also do not branch as extensively as the AV bundle cells.


Decreased Reoperations and Improved Outcomes With Reverse Total Shoulder Arthroplasty in Comparison to Hemiarthroplasty for Geriatric Proximal Humerus Fractures: A Systematic Review and Meta-Analysis.
We sought to compare range of motion, clinical outcome scores, and complications after reverse total shoulder arthroplasty (RSA) and hemiarthroplasty (HA) in geriatric patients with acute proximal humerus fractures. We searched MEDLINE (1946-2017), EMBASE (1947-2017), the Cochrane Central Register of Controlled Trials (1898-2017) and ClinicalTrials.gov in October 2017. No limits were used in the database search. We also manually reviewed reference lists of included studies. We did not restrict studies based on language. We included all randomized controlled trials and cohort studies in which the study population had a mean age of 65 years or older, received RSA or HA to treat an acute proximal humerus fracture, and had a minimum follow-up of 6 months. Two independent reviewers used a standardized data collection form to extract relevant information from included studies. Discrepancies were resolved by a consensus or a third party if consensus could not be reached. Study authors were contacted for missing or incomplete data. Using a random effects model, we calculated mean differences (MD) and standardized mean differences (SMD) for continuous outcomes; we calculated relative risk for dichotomous outcomes. Fifteen studies were included in the meta-analysis, including 421 patients treated with RSA and 492 treated with HA for a total of 913 patients. Compared with HA, the RSA group had significantly improved pain scores (SMD = 0.74, P < 0.001), outcome scores (SMD = 0.63, P < 0.001), and forward flexion (MD = 24.3 degrees, P < 0.001). Compared with RSA, the HA group had a significantly increased risk of reoperation (relative risk = 2.8, P = 0.02). There were no differences between the groups with regard to external rotation (P = 0.31) or deep infection (P = 0.90). Aggregating available research suggests that RSA results in improved range of motion, clinical outcome scores, and rates of all-cause reoperation with no difference in infection rates. Using RSA for the treatment of acute proximal humerus fractures in the elderly population may result in improved short- and medium-term outcomes compared with HA. Future work should evaluate long-term outcomes to see if the benefits of RSA persist. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Entanglements in Health and Well-being: Working with Model Organisms in Biomedicine and Bioscience.
Drawing on collaborative ethnographic fieldwork, this article explores how human health becomes entangled with that of model organisms in day-to-day biomedical science. Social science scholarship on modeling has explored either how specific models impact and shape our knowledge of human disease or how animal technicians and scientists affect laboratory animals. This article extends this relational approach by asking how embodied and institutional care practices for model organisms affect the health and well-being of animal technicians and scientists. We focus on two interspecies bodily experiences: pathogenic exchange and stress. We then explore enrichment as a strategy for producing health and well-being across species. We suggest that relations of care form a crucial part of biomedical knowledge production. Not only does care figure in the shaping of model organisms; care for technicians and scientists also plays a role in bioscientific knowledge production. We conclude by proposing an interspecies approach to occupational health.


Investigation of the validity of modeling the Achilles tendon as having a single insertion site.
To assess the propriety of modeling the Achilles tendon insertion on the calcaneus as a single point when musculoskeletal models are used to predict subtalar joint moment arms. The sensitivity of model-predicted subtalar joint moment arms to insertion site position was investigated and measurements of Achilles tendon function were made in cadaver specimens. The insertion site of the Achilles tendon is typically modeled as having a single-point insertion. A more sophisticated representation may be required, however, when subtalar joint function is considered. Achilles tendon moment arms about the subtalar joint axis were assessed using a computer model in which a single-point insertion was systematically displaced. The effective insertion site was located at three positions in three cadaver specimens using a six-degree-of-freedom load cell. Model-predicted moment arms of the Achilles tendon about the subtalar joint axis were substantially affected by medial-lateral displacement of the insertion site. The medial-lateral location of the effective insertion site varied linearly with subtalar joint angle in cadaver specimens, shifting medially when the foot was everted and laterally when the foot was inverted. More sophisticated representations of the Achilles tendon are needed when the subtalar joint is of interest. A single-segment tendon with an insertion that is fixed throughout subtalar joint motion may not permit accurate predictions of moment arms about the subtalar joint. Accurate prediction of the large moments produced by the triceps surae when simulating movement or investigating the effects of orthopaedic surgeries requires a realistic representation of the Achilles tendon insertion.


Synthesis of (E)-1,2-divinyl-1,2-diethynylethene (DVDEE) via the palladium-catalyzed reaction of conjugated diynes. A new building block for molecular scaffolding.
Conjugated diynes undergo dimerization in the presence of acetic acid and catalytic amounts of Pd(PPh3)4. The unprecedented reaction gives a novel chromophore containing the (E)-1,2-divinyl-1.2-diethynylethene (DVDEE) module, which is a potentially viable building block for acetylenic scaffolding.


[Disseminated tuberculosis with severe multi- organ failure in a patient with AIDS].
Tuberculosis is the most common infectious complication in HIV infected patients. The incidence of tuberculosis and the proportion of disseminated disease increase with more severe immuno-suppression. Septic shock and multiple organ failure are uncommon but are of markedly bad prognostic significance. A forty-four year old HIV seropositive man was admitted to the intensive care unit (ICU) with acute respiratory distress. The patient had been febrile for the previous two weeks. His thoracic radiograph showed a discrete interstitial infiltrate and at bronchoscopy small whitish granulations were observed in the main bronchi. All bacteriological investigations remained negative at the time of ICU admission. The patient died sixteen hours later due to multiple organ failure. Mycobacteria were identified after patient's death on the smear from BAL, from blood cultures, and in a postmortem liver biopsy. Septic shock is an infrequent complication of disseminated tuberculosis. Mortality is very high. Treatment should be started early in cases with a high diagnostic suspicion.


A novel carbon-nitrogen coupled metabolic pathway promotes the recyclability of nitrogen in composting habitats.
This study revealed a novel carbon-nitrogen coupled metabolic pathway. Results showed that the addition of inorganic carbon sources slowed down the decomposition of urea and conserved more nutrients in composting. Metagenomic analysis showed that the main bacteria involved in this new pathway were Actinobacteria, Proteobacteria and Firmicutes. During the late composting period, the dominant genus Microbacteium involved in denitrification accounted for 22.18% in control (CP) and only 0.12% in treatment group (T). Moreover, ureC, rocF, argF, argI, argG were key genes involved in urea cycle. The abundance of functional gene ureC and denitrification genes decreased in thermophilic and cooling phases, respectively. The genes hao, nosZ, ureA and nifH were more closely associated with Chloroflexi_bacterium and Bacillus_paralichenformis. In conclusion, composting habitats with additional inorganic carbon sources could not only weaken denitrification but also allow more nitrogen to be conserved through slow-release urea to improve resource utilization and decrease the environmental risk.


The frequency-domain infrared spectrum of ammonia encodes changes in molecular dynamics caused by a DC electric field.
Ammonia is special. It is nonplanar, yet in v = 1 of the umbrella mode (ν2) its inversion motion is faster than J = 0↔1 rotation. Does the simplicity of the Chemist's concept of an electric dipole moment survive the competition between rotation, inversion, and a strong external electric field? NH3 is a favorite pedagogical example of tunneling in a symmetric double-minimum potential. Tunneling is a dynamical concept, yet the quantitative characteristics of tunneling are expressed in a static, eigenstate-resolved spectrum. The inverting-umbrella tunneling motion in ammonia is both large amplitude and profoundly affected by an external electric field. We report how a uniquely strong (up to 108 V/m) direct current (DC) electric field causes a richly detailed sequence of reversible changes in the frequency-domain infrared spectrum (the v = 0→1 transition in the ν2 umbrella mode) of ammonia, freely rotating in a 10 K Ar matrix. Although the spectrum is static, encoded in it is the complete inter- and intramolecular picture of tunneling dynamics.


Machine learning vs. conventional statistical models for predicting heart failure readmission and mortality.
This study aimed to review the performance of machine learning (ML) methods compared with conventional statistical models (CSMs) for predicting readmission and mortality in patients with heart failure (HF) and to present an approach to formally evaluate the quality of studies using ML algorithms for prediction modelling. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search using MEDLINE, EPUB, Cochrane CENTRAL, EMBASE, INSPEC, ACM Library, and Web of Science. Eligible studies included primary research articles published between January 2000 and July 2020 comparing ML and CSMs in mortality and readmission prognosis of initially hospitalized HF patients. Data were extracted and analysed by two independent reviewers. A modified CHARMS checklist was developed in consultation with ML and biostatistics experts for quality assessment and was utilized to evaluate studies for risk of bias. Of 4322 articles identified and screened by two independent reviewers, 172 were deemed eligible for a full-text review. The final set comprised 20 articles and 686 842 patients. ML methods included random forests (n = 11), decision trees (n = 5), regression trees (n = 3), support vector machines (n = 9), neural networks (n = 12), and Bayesian techniques (n = 3). CSMs included logistic regression (n = 16), Cox regression (n = 3), or Poisson regression (n = 3). In 15 studies, readmission was examined at multiple time points ranging from 30 to 180 day readmission, with the majority of studies (n = 12) presenting prediction models for 30 day readmission outcomes. Of a total of 21 time-point comparisons, ML-derived c-indices were higher than CSM-derived c-indices in 16 of the 21 comparisons. In seven studies, mortality was examined at 9 time points ranging from in-hospital mortality to 1 year survival; of these nine, seven reported higher c-indices using ML. Two of these seven studies reported survival analyses utilizing random survival forests in their ML prediction models. Both reported higher c-indices when using ML compared with CSMs. A limitation of studies using ML techniques was that the majority were not externally validated, and calibration was rarely assessed. In the only study that was externally validated in a separate dataset, ML was superior to CSMs (c-indices 0.913 vs. 0.835). ML algorithms had better discrimination than CSMs in most studies aiming to predict risk of readmission and mortality in HF patients. Based on our review, there is a need for external validation of ML-based studies of prediction modelling. We suggest that ML-based studies should also be evaluated using clinical quality standards for prognosis research. Registration: PROSPERO CRD42020134867.


The multilevel effects of occupational stressors on soldiers' well-being, organizational attachment, and readiness.
The U.S. Army typifies the stressful nature of many contemporary work settings, as soldiers face a climate of increasing work demands coupled with declining resources. The authors used social identity theory to propose hypotheses regarding contextual and cross-level effects of shared stressors on individual outcomes critical to the functioning of military units (well-being, attachment, readiness). Although the authors found weak support for direct effects of shared stressors on individual outcomes, they found several compelling moderating effects for shared stressors on person-level stressor-outcome relationships. For most effects, shared stressors intensified the effects of person-level stressors on morale, commitment, and depression. However, some shared stressors exerted counterintuitive effects on stressor-outcome relationships. Implications for research and military personnel management are discussed.


[Study of the sonographic functions in targeted high-intensity focused ultrasound using nanoscale bubbles].
To improve the detection sensitivity of coagulative necrosis caused by high intensity focused ultrasound (HIFU) exposure. Sixty rabbits bearing VX2 breast neoplasms at the second bilateral breast were divided randomly into 3 groups (n=20) for targeted HIFU exposure at 90, 120, or 150 W for 3 s. With the right breast neoplasms as the control, the left ones were irradiated following nanoscale bubble injection. The ultrasonograms generated before and immediately after the exposure were analyzed for changes in the gray scale values and for computation of the related functions in the target area. The accuracy and sensitivity of gray evaluation and analysis of the related functions were compared in the detection of coagulative necrosis. Analysis of the related functions of the 120 samples showed an significantly higher accuracy (83.3%) than gray scale-based evaluation (68.3%) in detecting the coagulative necrosis (P<0.05). Under the same irradiation conditions, the mean values of the related function was significantly lower in microbubble group than in the control group (P<0.05). Analysis of the related functions of the ultrasonographic data can be used to evaluate the coagulative necrosis in the target exposure area following HIFU with a greater sensitivity and accuracy than gray-scale evaluation.


The clinical significance of soluble PD-1 and PD-L1 in lung cancer.
Soluble PD-1 and PD-L1 are detected in the serum and plasma of lung cancer patients. The significance of these soluble proteins as prognostic or predictive markers in lung cancer is uncertain. The testing methods used to detect soluble PD1/PD-L1 are variable with no agreement on a common definition of a positive test. The advantages of validating soluble PD1/PD-L1 relevance in lung cancer include easiness of obtaining blood samples for testing, serial measurements to assess response to treatments such as immunotherapy, and potentially early identification of cancer relapse in cases treated with curative intent. In this review, we present the available data published on soluble PD1 and PD-L1 in lung cancer.


Evolution of urban black and odorous water: The characteristics of microbial community and driving-factors.
Urban black blooms that are primarily caused by organic carbon are deleterious environmental problems. However, detailed studies on the microbial characteristics that form urban black blooms are lacking. In this study, we observed the composition, diversity, and function of bacterial community in the overlying water and sediments during the occurrence and remediation of urban black blooms using high-throughput 16S rRNA gene amplicon sequencing analysis. First, we found that pivotal consortia in the overlying water increased significantly during the formation of black blooms, including the genera Acidovorax, Brevundimonas, Pusillimonas, and Burkholderiales involved in the degradation of refractory organics, as well as the genera Desulfovibrio, Dechloromonas, and Rhizobium related to the production of black and odorous substances. An RDA analysis revealed that chemical oxygen demand, dissolved oxygen, and oxidation reduction potential were related to the changes in microbial community composition. Furthermore, aeration was found to accelerate the removal of ammonia nitrogen and enhance the function of microbial community by stimulating the growth of order Planktomycetes during the remediation of black blooms, but aeration substantially damaged the microbial diversity and richness. Therefore, the health of the aquatic ecosystem should be comprehensively considered when aeration is applied to restore polluted waterbodies. Notably, we observed a large number of pathogenic bacteria in urban black blooms, which emphasizes the importance of treating domestic sewage so that it is harmless. Together, these findings provide new insights and a basis to prevent and manage urban black blooms.


Pan-cancer transcriptomic data of ABI1 transcript variants and molecular constitutive elements identifies novel cancer metastatic and prognostic biomarkers.
Abelson interactor 1 (ABI1) is associated with the metastasis and prognosis of many malignancies. The association between ABI1 transcript spliced variants, their molecular constitutive exons and exon-exon junctions (EEJs) in 14 cancer types and clinical outcomes remains unsolved. To identify novel cancer metastatic and prognostic biomarkers from ABI1 total mRNA, TSVs, and molecular constitutive elements. Using data from TCGA and TSVdb database, the standard median of ABI1 total mRNA, TSV, exon, and EEJ expression was used as a cut-off value. Kaplan-Meier analysis, Chi-squared test (X2) and Kendall's tau statistic were used to identify novel metastatic and prognostic biomarkers, and Cox regression analysis was performed to screen and identify independent prognostic factors. A total of 35 ABI1-related factors were found to be closely related to the prognosis of eight candidate cancer types. A total of 14 ABI1 TSVs and molecular constitutive elements were identified as novel metastatic and prognostic biomarkers in four cancer types. A total of 13 ABI1 molecular constitutive elements were identified as independent prognostic biomarkers in six cancer types. In this study, we identified 14 ABI1-related novel metastatic and prognostic markers and 21 independent prognostic factors in total 8 candidate cancer types.


Insights into the minimization of excess sludge production in micro-aerobic reactors coupled with a membrane bioreactor: Characteristics of extracellular polymeric substances.
The production of excess sludge by the activated sludge system of wastewater treatment plants is a problem. In this study, the EPS characteristics on production and degradation were investigated in the real-scale food processing wastewater treatment system (i.e., a micro-aerobic reactor coupled with a membrane bioreactor (MAR-MBR)) with a treatment capacity of 150 t d-1, which could cater for the low production of excess sludge (i.e., 9 t·a-1; 76% moisture content). The total organic carbon concentrations in the different EPS fractions were in the following order: soluble EPS (S-EPS) < loosely bound EPS (LB-EPS) < tightly bound EPS (TB-EPS). Although the components (e.g., protein and humic acid-like substances) of each EPS fraction changed significantly throughout the MAR-MBR process owing to the low production of excess sludge, the degrees of change in S-EPS, LB-EPS, and TB-EPS were significantly different from the corresponding change in their relative molecular weights. Furthermore, the microbial community composition was beneficial for the release and degradation of EPS, and the regulation of gene functions via the MAR-MBR enhanced this process.


Vesicle-associated microRNAs are released from blood cells on incubation of blood samples.
MicroRNAs (miRNAs) circulating extracellularly in the blood are currently intensively studied as novel disease markers. However, the preanalytical factors influencing the levels of the extracellular miRNAs are still incompletely explored. In particular, it is unknown, whether the incubation of blood samples as occurring in clinical routine can lead to a release of miRNAs from blood cells and thus alter the extracellular miRNA levels before the preparation of serum or plasma from the blood cells. Using a set of marker miRNAs and quantitative RT-PCR, we found that the levels of extracellular miRNA-1, miRNA-16, and miRNA-21 were increased in EDTA and serum collection tubes incubated for 1-3 hours at room temperature and declined thereafter; the levels of the liver-specific miRNA-122 declined monophasically. These events occurred in the absence of significant hemolysis. When the blood was supplemented with Ribonuclease A inhibitor, the levels of miRNA-1, miRNA-16, and miRNA-21 increased substantially during the initial 3 hours of incubation and those of miRNA-122 remained unchanged, indicating that the release of blood cell-derived miRNAs occurred during the initial 3 hours of incubation of the blood tubes, but not at later time points. Separation of 5-hour preincubated blood into vesicle and nonvesicle fractions revealed a selective increase in the portion of vesicle-associated miRNAs. Together, these data indicate that the release of vesicle-associated miRNAs from blood cells can occur in blood samples within the time elapsing in normal clinical practice until their processing without significant hemolysis. This becomes particularly visible on the inhibition of miRNA degradation by Ribonuclease A inhibitor.


Left ventricular fibrosis in atrial fibrillation.
Excessive atrial fibrosis is involved in the pathogenesis of atrial fibrillation (AF), but little is known of left ventricular (LV) fibrotic status in patients with AF. In the present study, we investigated the presence of abnormal LV fibrosis in AF, its effect on cardiac function, a possible association with arterial stiffness (i.e., systemic cardiovascular fibrosis), and the parameters of endothelial activation, dysfunction, and damage. We also studied whether LV fibrosis could be linked to the future risk of AF onset. In a cross-sectional study, the severity of LV fibrosis was assessed by echocardiographic acoustic densitometry in patients with permanent AF (n = 49), patients with paroxysmal AF (n = 44), AF-free "disease controls" (n = 42) and "healthy controls" (n = 48). Arterial stiffness (pulse wave velocity), plasma markers of endothelial activation (E-selectin), endothelial damage/dysfunction (von Willebrand factors), and microvascular endothelial function (laser Doppler flowmetry) were quantified. In a longitudinal study, 93 patients with pacemakers (22 with AF) were followed up for ≥1 year to assess the predictive value of LV fibrosis for the development of new-onset AF. More severe LV fibrosis was present in both paroxysmal and permanent AF than in the AF-free controls (p <0.001), with more LV fibrosis in permanent than in paroxysmal AF (p = 0.002). The severity of LV fibrosis in AF wais independently associated with diastolic dysfunction (p = 0.03), but not with LV contractility, arterial stiffness, or endothelial damage/dysfunction. In conclusion, LV fibrosis might contribute to LV diastolic dysfunction and the high prevalence of heart failure with preserved ejection fraction in subjects with AF.


Evaluation of Qualidem: a dementia-specific quality of life instrument for persons with dementia in residential settings; scalability and reliability of subscales in four Dutch field surveys.
To evaluate the scalability and reliability of Qualidem, a quality of life observation instrument rated by professional caregivers of persons with mild to very severe dementia living in residential settings. Data from four field surveys in the Netherlands were used. The instrument consists of nine subscales for mild to severe dementia; of which six can be applied in very severe dementia. The Mokken scaling model was used to compute scalability and reliability coefficients for each subscale and dementia group. Seven hundred fifty nine persons with mild to severe dementia and 214 persons with very severe dementia residing in 36 nursing homes and 4 homes for the elderly were included. In general, the subscales for the mild to severely demented group were scalable and (moderate) sufficiently reliable; the results confirmed the results of previous research to develop Qualidem. For the very severe demented group, four out of six subscales were scalable (Care relationship, H = 0.56; Positive affect, H = 0.55; Restless tense behavior, H = 0.42; and Social isolation, H = 0.34); they were also sufficiently reliable to measure quality of life (0.57 ≤ ρ ≤ 0.82). From the other two measured subscales, Social relations was considered not scalable (H = 0.26) and Negative affect was scalable (H = 0.36), but insufficiently reliable (ρ = 0.40). Qualidem is an easy to administer and overall moderately sufficient reliable rating scale that provides a quality of life profile of persons with mild to even very severe dementia living in residential settings.


Characterising sedimentation velocity of primary waste water solids and effluents.
Sedimentation in waste water is a heavily studied topic, but mainly focused on hindered and compression settling in secondary sludge, a largely monodispersed solids, where bulk sedimentation velocity is effectively described by functions such as double Vesilind (Takacs). However, many waste water solids, including primary sludge and anaerobic digester effluent are polydispersed, for which application of velocity functions is not well understood. These systems are also subject to large concentration gradients, and poor availability of settling velocity functions has limited design and computational fluid dynamic (CFD) analysis of these units. In this work, we assess the use of various sedimentation functions in single and multi-dimensional domains, comparing model results against multiple batch settling tests at a range of high and low concentrations. Both solids concentration and sludge bed height (interface) over time are measured and compared. The method incorporates uncertainty analysis using Monte Carlo regression, DIRECT (dividing rectangles), and Newton optimisation. It was identified that a double Vesilind (Takacs) model was most effective in the dilute regime (<1%v/v), but could not effectively fit high solids concentrations (>1%v/v) without a substantial (50%) decrease in effective maximum sedimentation velocity (V0). Other parameters (Rh, Rp) did not change. A power law velocity model (Diehl) was significantly less predictive at low concentrations, and not significantly better at higher concentrations. The optimised model (with reduction in V0) was tested vs a standard (optimised) double Vesilind velocity model in a simple primary sedimentation unit, and resulted in deviation from -12% to +18% in solids capture prediction from underload to overload (washout) conditions, indicating that the effect is important in CFD based analysis of these systems.


Clinicopathologic characteristics of FBXW7-mutated colorectal adenocarcinoma and association with aberrant beta-catenin localization.
Oncogenic mutations in the adenomatous polyposis coli (APC)/Wnt signaling pathway are well documented. The FBXW7 gene (F-box and WD repeat domain-containing 7) encodes a member of the ubiquitin-proteasome complex that is more recently described to antagonize the oncogenic Wnt pathway by promoting the degradation of β-catenin encoded by the CTNNB1 gene. The pathologic significance of FBXW7 mutation in colorectal carcinoma (CRC) remains under-reported. In this study, we report the clinicopathologic and β-catenin immunohistochemical features of a single-institution cohort (83 cases) of FBXW7-mutated CRC compared with CTNNB1-mutated CRC. FBXW7-mutated CRC was more common in older patients (p = 0.031) and in the left/distal colon (p = 0.022). Immunohistochemical analysis revealed that aberrant nuclear/cytoplasmic β-catenin localization was identified in a significantly high proportion of FBXW7-mutated CRCs. When compared with CTNNB1-mutated CRC, FBXW7-mutated CRC showed a significantly higher proportion of microsatellite instability-stable tumors with intact expression of DNA mismatch repair proteins and had significantly more frequent co-occurrence of missense TP53 and KRAS mutations. The most frequently mutated FBXW7 residues/hotspots were located within the WD repeat domains (aa 378-659), which were also associated with aberrant nuclear/cytoplasmic localization of β-catenin protein. Our results indicate the unique pathologic characteristics of FBXW7-mutated CRC with frequent co-occurrence of missense mutant TP53 and KRAS. The mutated FBXW7 residues/hotspots and its association with aberrant nuclear/cytoplasmic β-catenin localization further support the oncogenic role of FBXW7 in colon carcinogenesis.


Social Media Interventions for Patients and Public: Opportunities and Challenges for the Urology Community.
Interactive interventions represent a new application of social media in urology that involves multidirectional communication within a group. Such interventions have the potential to influence health behaviours in patients and the public and result in a significant impact on urological diseases.


In vitro and in vivo metabolism of VP 16-213 in the rat.
A high-performance liquid chromatographic procedure utilizing u.v. and radioactivity detection was employed to examine the metabolism of the epipodophyllotoxin derivative VP 16-213 by the rat in vivo and in liver extracts and subcellular fractions. VP 16-213 has been shown to be metabolized extensively by rat liver homogenates and rat liver microsomes, with the formation of one major metabolite. The metabolite formed in vitro was the only metabolite present in plasma samples of rats treated with i.p. injections of VP 16-213. Based on its chromatographic and solubility characteristics, the metabolite is probably a cis- or trans-hydroxy acid derivative. The liver is involved in the metabolism of VP 16-213, and the localization of the enzyme(s) responsible for the formation of the major metabolite is in the microsomal fraction.


Minimally invasive plate osteosynthesis via posterior approach for type B and C fractures of distal humeral shaft: surgical tactics and a clinical series.
The optimal technique and implant for fixation of multifragmentary fractures of the distal humeral shaft remain inconclusive. We describe the use of minimally invasive plate osteosynthesis (MIPO) via posterior approach and extra-articular distal humerus locking compression plate (LCP-EADH) fixation for 18 such fractures. All fractures were united with a mean union time of 17.6 weeks (range 12-20). Transient radial nerve palsy was demonstrated in 2 patients. Six patients had 5° varus angulation and 1 had 5° valgus angulation. Triceps power was Grade 5 in all patients. The mean arc of elbow motion was 127.5 degrees (range 115-140). Six patients had an excellent MEP score and 12 had a good MEP score. As the results, posterior MIPO and LCP-EADH fixation could be an alternative for multifragmentary fractures of the distal humeral shaft, particularly for fractures with a very short distal fragment.


Hormone replacement therapy and the breast.
Increasing numbers of women are using hormone replacement therapy (HRT) in their 50s and 60s. Oestrogen alone or oestrogen and progestogen combined given in this age group increase breast density and this has the effect of reducing both the sensitivity and specificity of breast screening in HRT users. HRT significantly increases the risk of developing breast cancer with combinations of oestrogen and progestogens increasing the risk to a greater degree than oestrogen alone. The longer HRT is used the greater the risk with 5 years use being associated with risks of 1.05-1.16 for oestrogen alone and 1.24-1.45 for oestrogen and progestogen combined. No consistent effect of HRT on breast cancer mortality has been demonstrated. Two studies have reported that more than 5 years HRT use is associated with an increased risk of death from breast cancer. A variety of non-oestrogenic agents are available to control menopausal symptoms and these may be of particular value in breast cancer survivors. HRT has been used in breast cancer survivors and although published data are reassuring, none have included sufficient patient numbers to detect small effects of HRT on breast cancer outcome. Prospective randomised trials are underway but are unlikely to include sufficient numbers to exclude a small adverse influence of HRT on breast cancer mortality. Tibolone, a gonadomemetic agent which has been used to control menopausal symptoms, appears to have less direct effects on the breast and is being evaluated as an alternative to oestrogen in breast cancer survivors who develop significant menopausal symptoms resistant to non-hormonal therapies. There is clear evidence that HRT causes breast cancer and the challenge for the physician is to control the menopausal symptoms using HRT or alternatives while at the same time limiting the risks associated with this treatment.


Study of the in vivo antiviral activity against TMV treated with novel 1-(t-butyl)-5-amino-4-pyrazole derivatives containing a 1,3,4-oxadiazole sulfide moiety.
A series of new 1-tert-butyl-5-amino-4-pyrazole bioxadiazole sulfide derivatives containing a 1,3,4-oxadiazole moiety were designed and synthesized. The bioactivity results showed that some title compounds exhibited excellent protective activity against TMV and certain insecticidal activity. Among the tested compounds, the EC50 values of 5d, 5j, 5k and 5l were 165.8, 163.2, 159.7 and 193.1 mg/L, respectively, which are better than the EC50 value of ningnanmycin (271.3 mg/L). The chlorophyll contents and the defense enzyme activities of the tobacco leaves after treatment with 5j were significantly increased, which indicated that this series of title compounds may induce the systemic acquired resistance of host to defend against diseases. Further in vivo protective activity research on 5j using TMV with a GFP gene tag found that it can effectively inhibit the spread of TMV in inoculated tobacco. A morphological study with TEM revealed that title compound 5h can cause a distinct break of the rod-shaped TMV. Moreover, the insecticidal activity revealed that the fatality rates of 5a, 5b and 5m against aphidoidea were 85%, 83% and 87%, respectively, which indicated that the title compounds can effectively block the common carrier of plant viruses, thereby effectively reducing the TMV infection risk of tobacco. This series of synergistic effects provide key information for the research and development of antiviral agents.


Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreatic β-cells.
Islet fibrosis, pancreatic β-cell dysfunction, and β-cell apoptosis are features of pancreatic diabetes and type 2 diabetes; however, the underlying mechanisms remain largely unknown. We hypothesized that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, might affect the phenotype of pancreatic β-cells. α-Smooth muscle actin (a marker of activated PSC)-positive cells were found within and around the fibrotic islets. Indirect co-culture with PSCs reduced insulin expression and induced apoptosis in RIN-5F pancreatic β-cells. Induction of β-cell apoptosis was associated with activation of the caspase pathway and mitochondrial depolarization. Diphenylene iodonium, an inhibitor of PSC activation, inhibited islet fibrosis and protected islets in vivo. Our findings suggest a novel mechanism linking PSCs, islet fibrosis, and diabetes mellitus.


Intravitreal injections as a leading cause of acute postoperative endophthalmitis-a regional survey in England.
To evaluate the characteristics, treatment patterns and outcomes of acute postoperative endophthalmitis. Patients presenting with acute postoperative endophthalmitis between January 2017 to December 2019 were identified from hospital records in this multicentre retrospective cohort study. Clinical records were reviewed for visual acuity (VA) at various timepoints, cause of endophthalmitis, microbiological results, treatments and complications. Forty-six eyes of 46 patients were included. Intravitreal injections were the leading cause of acute postoperative endophthalmitis (n = 29; 63%), followed by cataract surgery (n = 8; 17%), vitreoretinal surgery (n = 7; 15%), and secondary intraocular lens insertion (n = 2, 4%). The absolute risk of endophthalmitis was 0.024% (1:4132) for intravitreal injections, 0.016% (1:6096) for cataract surgery, and 0.072% (1:1385) for vitreoretinal surgery. The majority of patients (n = 38; 83%) had better VA at 6 months compared to presentation, although fewer (n = 13; 28%) maintained similar or better VA compared to before the precipitating surgery. Twenty-four cases yielded positive culture results, of which staphylococcus epidermidis was the most commonly isolated organism. Microbiological yield was not associated with better final visual outcomes. Patients who underwent therapeutic vitrectomy (n = 15; 33%) had poorer VA at presentation, but subsequently achieved visual outcomes comparable to those who received medical treatment alone. There was no difference in time to presentation, visual outcome and retinal detachment rates among the different causative procedures. Intravitreal injections were the most common cause of endophthalmitis in our region, primarily because of their higher frequency compared to other intraocular procedures. In this cohort, the primary procedure had no effect on presentation, management or visual outcomes.


Insecure and Unresolved/Disorganized Attachment in Patients With Psychogenic Nonepileptic Seizures.
Psychogenic nonepileptic seizures (PNES) are still poorly understood and difficult to treat. Attachment theory could add new aspects to the understanding of the multifactorial genesis and maintenance of PNES and the therapeutic needs of this patient group. The aim of the present study is to systematically assess attachment in adult patients with PNES with a focus on the role of unresolved/disorganized attachment. A cross-sectional design was chosen to compare patients with confirmed PNES (n = 44) and healthy controls (n = 44) matched for gender, age, and education. Attachment was assessed using the Adult Attachment Projective Picture System. Psychometric questionnaires included the Childhood Trauma Questionnaire; Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) axis II disorders, Patient Questionnaire; the Somatoform Dissociation Questionnaire; and the Patient Health Questionnaire. We found significantly less secure (P = 0.006) and more unresolved/disorganized (P = 0.041) attachment classifications in the PNES group. Among patients with PNES, 7% were classified secure and 43% were classified unresolved/disorganized. Patients with an unresolved attachment representation were significantly more likely to be screened positive for personality pathology in the Structured Clinical Interview for DSM-IV axis II disorders, Patient Questionnaire (P = 0.03) and to report more emotional abuse in the Childhood Trauma Questionnaire (P = 0.007) than patients with other attachment classifications. Our findings suggest that unresolved/disorganized attachment might be the predominant attachment style in patients with PNES and might be associated with more severe personality pathology. This could be of therapeutic relevance. The present study is the first to assess adult attachment in patients with PNES using a semi-structured interview in comparison to matched healthy controls.


Use of a multivariate approach to assess the incidence of Alicyclobacillus spp. in concentrate fruit juices marketed in Argentina: results of a 14-year survey.
The purpose of this study was to determine the incidence of Alicyclobacillus spp. in fruit/vegetable juices (concentrated pulps and clarified and non-clarified juices) marketed in Argentina between 1996 and 2009. The presence of Alicyclobacillus was determined in a total of 8556 samples of fruit and vegetable juices (apple, pear, grape, peach, blend of juices, tangerine, pineapple, orange, mango, plum, guava, apricot, lemon, banana, kiwi, carrot, strawberry, grapefruit, and beetroot) collected in seven Argentinean provinces. Multiple factor analysis (MFA) was carried out on a data matrix that contained the percentage of positive samples, type of juice, raw material and production year. Except for kiwi and orange, Alicyclobacillus was found in juices from all the evaluated raw materials. The highest percentage of positive samples was found for beetroot, strawberry, banana, peach, mango, carrot and plum juices. The percentage of positive samples for these juices ranged from 100% to 24%. Furthermore, the application of multivariate techniques provided an insight on the relationship between the incidence of Alicyclobacillus and production variables. This approach enabled the identification of the most relevant variables that increased the percentage of positive samples among the juices, which could help in developing strategies to avoid the incidence of this bacterium. By means of hierarchical cluster analysis seven groups (clusters) of juices which showed different percentages of positive samples for Alicyclobacillus spp. were identified. This analysis showed that pineapple, peach, strawberry, mango and beetroot juices had higher rates of positivity for Alicyclobacillus than the rest of the evaluated juices. MFA analysis also showed that some clear relationships could be highlighted between the percentage of samples positive for Alicyclobacillus and five types of fruit juices (strawberry, beetroot, grapefruit, pineapple and mango). It was observed that a large proportion of juices produced in 2000, 2005 and 2008 were located in clusters with higher incidence of Alicyclobacillus spp., whereas a larger proportion of clarified concentrate juice and concentrate pulp samples showed higher probability of incidence of Alicyclobacillus in these products. Data presented in this study brings a contribution to the ecology of Alicyclobacillus in fruit/vegetable juices marketed in Argentina. This information would be useful to enhance the microbiological stability of fruit juices regarding the presence of Alicyclobacillus spp.


A remote-controlled generation of gold@polydopamine (core@shell) nanoparticles via physical-chemical stimuli of polydopamine/gold composites.
We present the synthesis of polydopamine particle-gold composites (PdopP-Au) and unique release of Au@Pdop core@shell nanoparticles (NPs) from the PdopP-Au upon external stimuli. The PdopP-Au was prepared by controlled synthesis of AuNPs on the Pdop particles. Upon near infrared (NIR) irradiation or NaBH4 treatment on the PdopP-Au, the synthesized AuNPs within the PdopPs could be burst-released as a form of Au@Pdop NPs. The PdopP-Au composite showed outstanding photothermal conversion ability under NIR irradiation due to the ultrahigh loading of the AuNPs within the PdopPs, leading to a remote-controlled explosion of the PdopP-Au and rapid formation of numerous Au@Pdop NPs. The release of the Au@Pdop NPs could be instantly stopped or re-started by off or reboot of NIR, respectively. The structure of the released Au@Pdop NPs is suitable for a catalyst or adsorbent, thus we demonstrated that the PdopP-Au composite exhibited excellent and sustained performances for environmental remediation due to its capability of the continuous production of fresh catalysts or adsorbents during the reuse.


Steroid receptors and proliferative activity in non-neoplastic and neoplastic endometria.
In the glands of cyclic endometria, proliferative activity (PA), as revealed by expression of the Ki-67 antigen, is highest in the proliferative phase (P) and early secretory phase (S1). The PA decreases in the middle secretory phase (S2). In the stroma the PA is low during the whole cycle. In P and S1, the oestrogen receptor (ER) and the progesterone receptor (PR) are strongly expressed in glands and stroma. The number of positive cells and the staining intensity decreases in S2, particularly in the glands. In atrophic endometria, fibro-glandular polyps and in endometria with arrested secretion the PA is low in both glands and stroma. ER and PR can be detected in glands and stroma. The PA in atypical hyperplasias is only slightly higher than in cyclic endometria and endometria with simple hyperplasia. The ER and PR levels are comparable to those in proliferative endometria. The PA of endometrial adenocarcinomas is positively and the ER and PR negatively correlated with the degree of de-differentiation. No ER-negative carcinoma displays the PR. Immunohistologically, non-neoplastic receptor positive tissue can be seen in many ER- and PR-negative carcinomas. These structures may falsify the biochemical receptor analysis.