Stroke mimics under the drip-and-ship paradigm.
Recent reports suggested better outcomes associated with the drip-and-ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We hypothesized that a higher rate of stroke mimics (SM) among AIS treated in nonspecialized stroke centers that are transferred to comprehensive centers is responsible for such outcomes. Consecutive patients treated with thrombolysis according to the admission criteria were reviewed in a single comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012). Information on the basic demographic, hospital complications, psychiatric diagnoses, and discharge disposition was collected. We identified those patients who were treated at a facility and then transferred to the tertiary center (ie, drip-and-ship paradigm). In addition to comparative and adjusted analysis to identify predictors for SM, a stratified analysis by the drip-and-ship status was performed. One hundred twenty patients were treated with thrombolysis for AIS included in this analysis; 20 (16.7%) were discharged with the final diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger (55.6 ± 15.0 versus 69.4 ± 14.9, P = .0003) and more likely to harbor psychiatric diagnoses (45% versus 9%; P ≤ .0001). Eighteen of 20 SM patients (90%) had the drip-and-ship treatment paradigm compared with 65% of those with AIS (P = .02). None of the SM had hemorrhagic complications, and all were discharged to home. Predictors of SM on adjusted analysis included the drip-and-ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83 drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37 patients (5.4%) presented directly to the hub hospital (P = .02). The drip-and-ship paradigm and any psychiatric history predict the diagnosis of SM. None of the SM had thrombolysis-related complications, and all were discharged to home. These findings may explain the superior outcomes associated with the drip-and-ship paradigm in the treatment for AIS.


The chick embryo appears as a natural model for research in beta-amyloid precursor protein processing.
This study reveals that the chick embryo has active the machinery for the production and degradation of the amyloid beta peptide characteristic of Alzheimer's disease. We cloned the principal beta-amyloid precursor protein isoforms in the chick embryo and observed that they are highly homologous to the human sequences and identical at the C-terminal sequence, including the amyloid beta domain. Mammals such as rat or mouse, more commonly used as animal models of human diseases, have a distinct amyloid beta sequence. The distribution of beta-amyloid precursor protein isoforms in the chick embryo revealed that, as in humans, their expression is ubiquitous and the prototype beta-amyloid precursor protein-695 predominated in the nervous system. We also found that the chick embryo expresses the genes for the main proteolytic proteases implicated in the production of amyloid beta, including BACE-1, BACE-2, presenilin-1, presenilin-2 and nicastrin, as well as the amyloid beta-degrading enzyme neprilysin, or ADAM-17, a protease implicated in the non-amyloidogenic processing of beta-amyloid precursor protein. We have also found that between amyloid beta40 and amyloid beta42, this latter seems to be the major amyloid beta peptide produced during chick embryogenesis. The chick embryo appears as a suitable natural model to study cell biology and developmental function of beta-amyloid precursor protein and a potential assay system for drugs that regulate beta-amyloid precursor protein processing.


Structural disconnection-based prediction of poststroke depression.
Poststroke depression (PSD) is a common complication of stroke. Brain network disruptions caused by stroke are potential biological determinants of PSD but their conclusive roles are unavailable. Our study aimed to identify the strategic structural disconnection (SDC) pattern for PSD at three months poststroke and assess the predictive value of SDC information. Our prospective cohort of 697 first-ever acute ischemic stroke patients were recruited from three hospitals in central China. Sociodemographic, clinical, psychological and neuroimaging data were collected at baseline and depression status was assessed at three months poststroke. Voxel-based disconnection-symptom mapping found that SDCs involving bilateral temporal white matter and posterior corpus callosum, as well as white matter next to bilateral prefrontal cortex and posterior parietal cortex, were associated with PSD. This PSD-specific SDC pattern was used to derive SDC scores for all participants. SDC score was an independent predictor of PSD after adjusting for all imaging and clinical-sociodemographic-psychological covariates (odds ratio, 1.25; 95% confidence interval, 1.07, 1.48; P = 0.006). Split-half replication showed the stability and generalizability of above results. When added to the clinical-sociodemographic-psychological prediction model, SDC score significantly improved the model performance and ranked the highest in terms of predictor importance. In conclusion, a strategic SDC pattern involving multiple lobes bilaterally is identified for PSD at 3 months poststroke. The SDC score is an independent predictor of PSD and may improve the predictive performance of the clinical-sociodemographic-psychological prediction model, providing new evidence for the brain-behavior mechanism and biopsychosocial theory of PSD.


Heterogeneous oxygen extraction in the visual cortex during activation in mild hypoxic hypoxia revealed by quantitative functional magnetic resonance imaging.
Functional magnetic resonance imaging (fMRI) techniques were used to study haemodynamic and metabolic responses in human visual cortex during varying arterial blood oxygen saturation levels (Y(sat), determined by pulse-oximeter) and stimulation with contrast-reversing checkerboards. The visual-evoked potential amplitude remained constant at lowered Y(sat) of 0.82+/-0.03. Similarly, fMRI cerebral blood flow (CBF) responses were unchanged during reduced Y(sat). In contrast, visual cortex volume displaying blood oxygen level-dependent (BOLD) fMRI response decreased as a function of Y(sat), but the BOLD signal change of 3.6%+/-1.4% was constant. Oxygen extraction ratio (OER) during visual activation showed values of 0.26+/-0.03 for normal Y(sat). At lowered Y(sat), two OER patterns were observed. Firstly, a reduced OER of 0.14+/-0.03 in the visual cortex structures showing BOLD in hypoxia was observed. Secondly, signs of much higher OER in other parts of visual cortex were obtained. T2*-weighted magnetic resonance imaging revealed signal increases by 0.8%+/-0.4% with visual activation during lowered Y(sat) in the visual cortex structures, which showed BOLD of 3.6% in magnitude under normoxia. Because the CBF response in the visual cortex was quantitatively similar during stimulation in normoxia and hypoxia, attenuated T2*-weighted signal increase in parts of visual cortex indicated high OER during visual activation in hypoxia, which was close to that encountered in the resting brain. These spatially localised regions of tissue oxygen extraction and metabolism argue for dissociation between CBF and BOLD fMRI signals in mild hypoxia. The findings point to heterogeneity with regard to oxygen requirement and its coupling to the haemodynamic response in the brain.


Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn's Disease Might Be Associated With Increased Rates of Stoma Construction.
Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn's disease (CD) with radiologically guided percutaneous drainage (PD) was debated. This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors.


Evaluation of the effectiveness of platelet crossmatching by the solid-phase red cell adherence assay in adult patients of a tertiary care hospital in Thailand: A retrospective study.
Platelet transfusion refractoriness is well aware to be associated with poor clinical outcomes. Patients with the alloantibody causing refractoriness required cross-matched compatible products to improve the platelet number. This study aims to evaluate the effectiveness and availability of platelet crossmatching provided by the solid-phase red cell adherence (SPRCA) technique in the context of a tertiary university hospital. A retrospective chart review was performed of the records of 214 patients with platelet refractoriness in Siriraj Hospital, a tertiary university hospital in Thailand, between January 1, 2017, and December 31, 2020. The SPRCA technique successfully provided cross-matched compatible platelets to 114 patients (69.7%). Platelet crossmatching significantly improved the platelet counts, as shown by the increased 1- and 24-h corrected-count increments (p< 0.0001). No acute transfusion reactions were observed in these patients. Of the 114 patients who received cross-matched platelets, 82 patients (71.9%) survived at 30-day posttransfusion; whereas, 16 patients (14.0%) died within 7-day posttransfusion. The SPRCA method can provide a high availability rate of cross-matched platelets, which is effective at stopping and preventing clinical bleeding conditions. This method is appropriate to apply for platelet crossmatching in the context of a hospital blood bank.


Effect of sorbin on electrolyte transport in rat and human intestine.
Stimulating water absorption in the colon represents an important target to reduce stool output in secretory diarrhea. Recently, a 153-amino-acid peptide was isolated from porcine upper small intestine and purified, taking into account the increase of water absorption in guinea pig gallbladder. Accordingly, this peptide was named sorbin. The aim of the present study was to determine if the COOH-terminal heptapeptide of sorbin (C7-sorbin) participates in the regulation of electrolyte transport in the colon. Different regions (from duodenum to colon) of stripped intestinal mucosa from rats or humans were mounted in Ussing chambers to measure the changes in short-circuit current (DeltaIsc) and net 22Na and 36Cl fluxes (JNanet and JClnet) after serosal exposure of 10(-7) to 10(-3) M C7-sorbin. In fasted rat intestine, C7-sorbin (10(-4) M) induced an immediate reduction in Isc in the distal ileum and proximal and distal colon but not in the duodenum and jejunum. In the colon, Isc reduction and JNanet and JClnet stimulation were dose dependent (EC50 = 2 x 10(-5) M). At 10(-3) M, maximal effect was observed (DeltaIsc = -1.14 +/- 0.05, DeltaJNanet = +4.97 +/- 1.38, and DeltaJClnet = +9.25 +/- 1.44 microeq. h-1. cm-2). C7-sorbin (10(-3) M) inhibited the increase in Isc induced by a series of 10 secretory agents such as secretin, vasoactive intestinal peptide, PGE2, and serotonin. In HT-29-Cl19A cells, C7-sorbin induced an increase in Isc, with a maximal effect at 10(-3) M (DeltaIsc = 0.29 +/- 0.10 microeq. h-1. cm-2). In human intestine, a dose-dependent decrease in Isc was observed in right and sigmoid colons in basal and stimulated conditions (EC50 congruent with 10(-5) M; at 10(-4) M, DeltaIsc = -2.66 +/- 0.17 microeq. h-1. cm-2) but not in the jejunum. The results indicate that C7-sorbin stimulated NaCl neutral absorption and inhibited electrogenic Cl- in rat and human intestinal epithelia. In addition, the antisecretory effect was essentially observed in the distal part of both rat and human intestine and the magnitude of the proabsorptive effect was directly related to the magnitude of the previously induced secretion.


Cancer/testis antigens, gametogenesis and cancer.
Cancer/testis (CT) antigens, of which more than 40 have now been identified, are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumour types, including melanoma, and carcinomas of the bladder, lung and liver. These immunogenic proteins are being vigorously pursued as targets for therapeutic cancer vaccines. CT antigens are also being evaluated for their role in oncogenesis--recapitulation of portions of the germline gene-expression programme might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, hypomethylation and metastatic capacity.


Inhibition of nonlysosomal calcium-dependent proteolysis by glycine during anoxic injury of rat hepatocytes.
The mechanism by which glycine protects against hepatocyte death during anoxia remains unclear. Nonlysosomal proteolysis, including calpain proteolysis, has been implicated as a mechanism of lethal cell injury. However, the effect of glycine on nonlysosomal proteolysis is unknown. The aim of this study was to ascertain if glycine cytoprotection is associated with inhibition of nonlysosomal proteolysis. Rat hepatocyte suspensions were rendered anoxic using an anaerobic chamber. Cell viability was measured by propidium iodide fluorometry. Nonlysosomal protease activity was quantitated by the release of trichloroacetic acid-soluble free amines or tyrosine. Calpain protease activity was measured using a fluorogenic substrate. Glycine and alanine (but not valine) markedly improved cell viability during anoxia in a concentration-dependent manner. During anoxia, the majority of nonlysosomal proteolysis (60%) was dependent on extracellular Ca2+. Glycine only inhibited that portion of nonlysosomal proteolysis that was dependent on extracellular Ca2+. Amino acids inhibited the anoxia-stimulated increase in calpain protease activity with the same specificity and concentration-dependence observed for cytoprotection. Glycine was more potent in directly inhibiting purified m-calpain as compared with mu-calpain protease activity. Glycine may exert its cytoprotective activity during lethal anoxic hepatocyte injury, in part by inhibiting Ca(2+)-dependent degradative, nonlysosomal proteases, including calpains.


Strategies for optimizing recovery of the biogas process following ammonia inhibition.
Strategies for recovery of ammonia-inhibited thermophilic biogas process, were evaluated in batch and lab-scale reactors. Active methane producing biomass (digested cattle manure) was inhibited with NH4Cl and subsequently, 3-5 days later, diluted with 50% of water, or with 50% digested manure, or with 50% fresh manure or kept undiluted. Dilution with fresh cattle manure resulted in the highest methane production rate during the recovery period while dilution with digested cattle manure gave a more balanced recovery according to the fluctuations in volatile fatty acids. Furthermore, the process recovery of a 7600m3 biogas plant suffering from ammonia inhibition was observed. The ammonia concentration was only gradually lowered via the daily feeding with cattle manure, as is the normal procedure at Danish full-scale biogas plants. Recovery took 31 days with a 40% methane loss and illustrates the need for development of efficient process recovery strategies.


[Detection of a soluble serum antigen by a new monoclonal antibody ED8 in patients with breast cancer].
A murine hybridoma, secreting monoclonal antibody ED8, was generated by immunization with the breast cancer cell line H466B. ED8 reacts with a 300 kDa antigen present on H466B cell surface. The antigen can be detected in serum from breast cancer patients, using ELISA and immunoblotting.


Mycoses of the Sudan.
Mycoses in the Sudan are still significant and, as well as mycetoma, there are a number of fungal diseases: paranasal aspergillus granuloma, which came into eminence in 1966; actinomycosis; subcutaneous phycomycosis; systemic phycomycosis; post-operative opportunistic infection of the eye with Trichosporon cutaneum and rhinosporidiosis. Mycetoma and paranasal aspergillus granuloma are discussed in detail.


Production of 'kedondong' (Spondias cytherea Sonnerat) powder as affected by different drying methods.
'Kedondong' fruit is regarded as an exotic fruit that is gaining popularity due to its deliciousness and pleasant flavour. However, this fruit has a short shelf life, leading to problems with postharvest loss. In order to prevent losses, the fruit could be produced as a value-added product. In this study, the 'kedondong' fruit was preserved by drying into powder using different drying methods. The kedondong powder was dried using five methods: convection oven drying, vacuum drying, spray drying, drum drying and freeze drying. The physical properties, flowability and DPPH radical scavenging ability of dried kedondong powder were examined. Spray-dried powder provided the significantly (p ≤ 0.05) highest process yield, which was 54.93%. All the powder produced had a low moisture content (3.03 to 5.66%) and water activity (0.19–0.37). Visually, whitish and fine powders were observed on spray-dried and freeze-dried samples, while convection oven-dried and vacuum-dried powder appeared yellowish and coarse. The pH of the reconstituted powders varied from 2.71 to 2.83, where drum-dried powder was the most acidic. Spray-dried powder showed the highest wettability and shortest dissolution time, which was 172.65 s and 10.55 s, respectively. With the exception of drum-dried powder, all the dried powders were classified as non-caking powders. The bulk and tapped density of the powders ranged from 0.32 to 0.70 g/mL and 0.38 to 0.86 g/mL, respectively. Vacuum-dried powder had very good flowability, convection oven-dried and drum-dried powder had good flowability, while spray-dried and drum-dried powder had fair flowability. Antioxidant assay showed that freeze-dried powder exhibited the highest free radical scavenging activity (IC50 = 701.29 μg/mL). This study indicates that spray-dried kedondong powder has great potential in the food industry due to its high process yield and better powder quality. Meanwhile, freeze drying best preserved the antioxidant properties of the powder, which could potentially be used as a functional ingredient as a result. This study is important for the fruit processing industry as it offers an alternative for the farmer to produce kedondong fruit powder because the fruit has a short shelf life. Converting the fruit into powder can diversify the resulting produce into different applications, such as fruit juice, beverages, jam and other food products.


Identification and Characterization of a New Regulator, TagR, for Environmental Stress Resistance Based on the DNA Methylome of Streptomyces roseosporus.
DNA methylation is a defense that microorganisms use against extreme environmental stress, and improving resistance against environmental stress is essential for industrial actinomycetes. However, research on strain optimization utilizing DNA methylation for breakthroughs is rare. Based on DNA methylome analysis and KEGG pathway assignment in Streptomyces roseosporus, we discovered an environmental stress resistance regulator, TagR. A series of in vivo and in vitro experiments identified TagR as a negative regulator, and it is the first reported regulator of the wall teichoic acid (WTA) ABC transport system. Further study showed that TagR had a positive self-regulatory loop and m4C methylation in the promoter improved its expression. The ΔtagR mutant exhibited better hyperosmotic resistance and higher decanoic acid tolerance than the wild type, which led to a 100% increase in the yield of daptomycin. Moreover, enhancing the expression of the WTA transporter resulted in better osmotic stress resistance in Streptomyces lividans TK24, indicating the potential for wide application of the TagR-WTA transporter regulatory pathway. This research confirmed the feasibility and effectiveness of mining regulators of environmental stress resistance based on the DNA methylome, characterized the mechanism of TagR, and improved the resistance and daptomycin yield of strains. Furthermore, this research provides a new perspective on the optimization of industrial actinomycetes. IMPORTANCE This study established a novel strategy for screening regulators of environmental stress resistance based on the DNA methylome and discovered a new regulator, TagR. The TagR-WTA transporter regulatory pathway improved the resistance and antibiotic yield of strains and has the potential for wide application. Our research provides a new perspective on the optimization and reconstruction of industrial actinomycetes.


An all-silk-derived bilayer hydrogel for osteochondral tissue engineering.
Osteochondral repair remains a challenge in clinical practice nowadays despite extensive advances in tissue engineering. The insufficient recruitment of endogenous cells in the early stage and incomplete cell differentiation in the later stage constitute the major difficulty of osteochondral repair. Here, a novel all-silk-derived multifunctional biomaterial platform for osteochondral engineering is reported. The bilayer methacrylated silk fibroin (SilMA) hydrogel was fabricated through stratified photocuring as the basic provisional matrix for tissue regeneration. Platelet-rich plasma (PRP) incorporation promoted the migration and pre-differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the early stage of implantation. The long-term regulation of BMSCs chondrogenesis and osteogenesis was realized by the stratified anchoring of the silk fibroin (SF) microspheres respectively loaded with Kartogenin (KGN) and berberine (BBR) in the hydrogel. The composite hydrogels were further demonstrated to promote BMSCs chondrogenic and osteogenic differentiation under an inflammatory microenvironment and to achieve satisfying cartilage and subchondral bone regeneration with great biocompatibility after 8 weeks of implantation. Since all the components used are readily available and biocompatible and can be efficiently integrated via a simple process, this composite hydrogel scaffold has tremendous potential for clinical use in osteochondral regeneration.


Long term determinants of functional decline of mobility: an 11-year follow-up of 5464 adults of late middle aged and elderly.
This confirmatory study aims at investigating the long term determinants of mobility limitation among late middle aged and elderly in a physically less active population. Five thousand four hundred and sixty-four participants aged 50-97 in 1996 enrolled the Taiwan Longitudinal Study on Aging (TLSA) for four waves of interview during 11 years. Social and health-related determinants were collected in each interview. Mobility limitation was enquired level of difficulty in eight movement tasks, including lifting 11kg weight, squatting, running 20-30m, standing for 15min, walking 200-300m, climbing up two to three floors, raising arms up and grasping with fingers. According to the mixed models with repeated measurements, more frequent gardening and longer time for each exercise predicted subsequent better mobility function in Taiwanese elderly while controlling demographics and current comorbidities. The protective effect of gardening was robust in all models. Frequent alcohol consumption was harmful to future mobility function, but less as harmful when participants aged. Besides, the depression-related somatic complaints were predictive to future mobility limitation among those without limitation at baseline. It shall be worthy to explore the dosage as well as the mechanism of these protective factors, especially the most significant but the least explored factor, gardening. Additionally, efforts should be made to understand the relationship between depression-related somatic complaints and mobility decline and so as the relevant interventions.


[Burnout syndrome in health professionals at a university hospital in Spain].
To evaluate the risk of Burnout in the health professionals of the Huesca University Hospital, 50 years after its inauguration, to investigate the variables related to the work motivation of the hospital health personnel and to assess the predisposing and protective factors of the risk of Burnout. An observational, analytical, prospective and unicentric study was conducted from September 2017 to April 2019, evaluating all the health professionals who worked at the Hospital San Jorge de Huesca (n=209). The mean age was 42.86 years. 72.2% were women. 12.4% had moderate risk of burnout. There was 12.4% of high emotional exhaustion, 36.8% of high depersonalization and 44.5% of low personal accomplishment. Burnout was statistically significant associated with the professional category (P=.010), work experience (P=.026), hours of work per week (P=.036), choice of the same profession (P=.001) and recommendation to the offspring (P<.001). One tenth of the sample had a moderate risk of burnout. Almost half of the health workers confirmed a high degree of satisfaction with the work environment and the majority expressed an adequate use of well-being strategies and a high degree of autonomy, recognition and satisfaction at work.


Blading of Conformal Electron-Transport Layers in p-i-n Perovskite Solar Cells.
Perovskite solar cells (PSCs) are promising to reduce the cost of photovoltaic system due to their low-cost raw materials and high-throughput solution process; however, fabrication of all the active layers in perovskite modules using a scalable solution process has not yet been demonstrated. Herein, the fabrication of highly efficient PSCs and modules in ambient conditions is reported, with all layers bladed except the metal electrode, by blading a 36 ± 9 nm-thick electron-transport layer (ETL) on perovskite films with a roughness of ≈80 nm. A combination of additives in phenyl-C61 -butyric acid methyl ester (PCBM) allows the PCBM to conformally cover the perovskites and still have a good electrical conductivity. Amine-functionalized molecules are added to enhance both the dispersity of PCBM and the affinity to perovskites. A PCBM dopant of 4-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-N,N-dimethylbenzenamine (N-DMBI) recovers the conductivity loss induced by the small amine molecules. PSCs (0.08 cm2 ) fabricated by the all-blading process reache an average efficiency of 22.4 ± 0.5% and a champion efficiency of 23.1% for perovskites with a bandgap of 1.51 eV, with much better stability compared to evaporated ETL PSCs. The all-bladed minimodule (25.03 cm2 ) shows an aperture efficiency of ≈19.3%, showing the good uniformity of the bladed ETLs.


Iron-regulated assembly of the cytosolic iron-sulfur cluster biogenesis machinery.
The cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway delivers Fe-S clusters to nuclear and cytosolic Fe-S proteins involved in essential cellular functions. Although the delivery process is regulated by the availability of iron and oxygen, it remains unclear how CIA components orchestrate the cluster transfer under varying cellular environments. Here, we utilized a targeted proteomics assay for monitoring CIA factors and substrates to characterize the CIA machinery. We find that nucleotide-binding protein 1 (NUBP1/NBP35), cytosolic iron-sulfur assembly component 3 (CIAO3/NARFL), and CIA substrates associate with nucleotide-binding protein 2 (NUBP2/CFD1), a component of the CIA scaffold complex. NUBP2 also weakly associates with the CIA targeting complex (MMS19, CIAO1, and CIAO2B) indicating the possible existence of a higher order complex. Interactions between CIAO3 and the CIA scaffold complex are strengthened upon iron supplementation or low oxygen tension, while iron chelation and reactive oxygen species weaken CIAO3 interactions with CIA components. We further demonstrate that CIAO3 mutants defective in Fe-S cluster binding fail to integrate into the higher order complexes. However, these mutants exhibit stronger associations with CIA substrates under conditions in which the association with the CIA targeting complex is reduced suggesting that CIAO3 and CIA substrates may associate in complexes independently of the CIA targeting complex. Together, our data suggest that CIA components potentially form a metabolon whose assembly is regulated by environmental cues and requires Fe-S cluster incorporation in CIAO3. These findings provide additional evidence that the CIA pathway adapts to changes in cellular environment through complex reorganization.


Calcium, phosphorus, and bone metabolism in the fetus and newborn.
The placenta actively transports minerals whereas the intestines and kidneys may be nonessential for fetal mineral homeostasis. Mineral concentrations are higher in fetal blood than in adults in order for the developing skeleton to accrete adequate mineral content. Fetal bone development and serum mineral regulation are dependent upon parathyroid hormone (PTH) and PTH-related protein (PTHrP), but not calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, a switch from fetal to neonatal regulatory mechanisms is triggered by loss of the placental calcium infusion, onset of a breathing, and a postnatal fall in serum calcium and rise in phosphorus. This is followed by an increase in PTH, then a rise in calcitriol, and developmental changes in kidneys and intestines. Serum calcium increases and phosphorus declines over days. The intestines become the main source of mineral, while kidneys reabsorb mineral, and bone turnover contributes additional mineral to the circulation.


A longitudinal study of parents' expectations about infants' emerging behaviors and their safety strategies to moderate injury risk.
Unintentional injuries are the leading cause of preventable deaths for children under 19 years of age. Infancy has been identified as a high-risk stage for injury. Throughout infancy, infants acquire increasing motor competencies but have limited capabilities to appraise danger. This longitudinal multi-method study examined parents' expectations about their infant's emerging behaviors and their in-home safety practices when their infants were at two stages of motor development: pre-mobile (i.e. sitting independently) and mobile (i.e. walking independently). At each motor development stage, parents completed an interview and rating scales to report on their infants' current and anticipated (3 months later) behavioral competencies, as well as their own safety practices and anticipated changes in these. Findings revealed that parents engaged in poorer supervision (reduced proximity, decreased attention) when infants were mobile than pre-mobile, while at the same time doing less to constrain their infants' movements around the room when mobile than pre-mobile. At both stages of motor development, parents reported expecting increased unpredictability in how their infants would behave in the upcoming months, due primarily to motor development (pre-mobile infants) or cognitive curiosity (mobile infants). In response, they planned to change their safety practices by decreasing supervision and increasing teaching about safety, despite the young ages of the children. Implications for injury risk to infants and prevention initiatives focusing on parents are discussed.


Particle dispersion for further Cryptosporidium and Giardia detection by flow cytometry.
The aim of this study was to overcome the analytical problems encountered during the detection of protozoans by flow cytometry resulting from particle compaction. Malvern Mastersizer (Malvern Instruments, Malvern, UK) was used to characterize the particle distribution of four different water samples and/or particle concentrates incubated with (i) low ionic strength solution or sequestring agent, (ii) anionic or non-ionic surfactants (iii) industry detergent formulations and (iv) physical treatment. The recovery of oocysts and cysts in seeded and treated particle concentrates was estimated by cytometry and microscopy. The decrease in ionic strength of the aqueous solution was most efficient in particle dispersion for different types of water. Moreover, samples treated with deionized water or tetrasodium pyrophosphate showed the highest recovery with more than 80% of the oocysts and cysts recovered. Chemical treatments that act by altering the ionic strength of the medium are the most efficient for all water types tested here but the overall detergency performance cannot be predicted for all water types. Flow cytometric detection has been replaced largely by immunomagnetic separation but the data recorded still have relevance in this technique as well as in molecular techniques requiring DNA or RNA extraction.


The PCB pollution of Lake Iseo (N. Italy) and the role of biomagnification in the pelagic food web.
Several models of varying complexity have been used to predict pollutant concentrations in the higher levels of the food web from those in lower levels, but the role of the biomagnification process in aquatic food chains is still controversial. We used the fugacity-based approach to verify the transfer of PCBs through the pelagic food chain of Lake Iseo (N. Italy), sampling several zebra mussel specimens and some fish belonging of different trophic levels. The zebra mussel seems to be a suitable starting species for modelling the bioaccumulation process through the trophic web, not only because its physiological characteristics and population size do not change much with time (as do algae and zooplankton) but also because it takes up toxicants exclusively from the water, as shown by the application of two predictive trophic models commonly used. The data provided by one of those models were in good agreement with our experimental data on fish in Lake Iseo, that show a not negligible uptake from food for the top predator species (pike and perch) with an increase of about three times in comparison with the PCB levels measured in the zebra mussel specimens.


Antibodies against a retinal guanine nucleotide-binding protein cross-react with a single plasma membrane protein in non-retinal tissues.
Antisera (AS/1-AS/6) to purified bovine retinal transducin, a guanine nucleotide-binding protein, were produced in 6 rabbits. Immunoblots showed that the antisera varied in their reactivity with the subunits of transducin; AS/1 reacted strongly with all 3 subunits, while the others reacted with only the beta and/or gamma subunits. Only AS/1 specifically immunoprecipitated the alpha subunit radiolabeled with non-covalently bound guanine nucleotides. Immunostaining of plasma membrane proteins from non-retinal tissues with AS-1 revealed a single protein (approx. 35 kDa), most likely representing the beta subunit of the guanine nucleotide-binding proteins (Gs and Gi) associated with adenylate cyclase. Cerebral cortex showed the highest content of this protein. Antisera against transducin provide a highly specific and sensitive probe for quantitation of the beta subunit of Gs and Gi.


Postactivation potentiation can counteract declines in force and power that occur after stretching.
Stretching can decrease a muscle's maximal force, whereas short but intense muscle contractions can increase it. We hypothesized that when combined, postactivation potentiation induced by reactive jumps would counteract stretch-induced decrements in drop jump (DJ) performance. Moreover, we measured changes in muscle twitch forces and ankle joint stiffness (KAnkle ) to examine underlying mechanisms. Twenty subjects completed three DJs and 10 electrically evoked muscle twitches of the triceps surae subsequent to four different conditioning activities and control. The conditioning activities were 10 hops, 20s of static stretching of the triceps surae muscle, 20s of stretching followed by 10 hops, and vice versa. After 10 hops, twitch peak torque (TPT) was 20% and jump height 5% higher compared with control with no differences in KAnkle . After stretching, TPT and jump height were both 9% and KAnkle 6% lower. When hops and stretching were combined as conditioning activities, jump height was not different compared with control but significantly higher (11% and 8%) compared with stretching. TPTs were 16% higher compared with control when the hops were performed after stretching and 9% higher compared with the reverse order. KAnkle was significantly lower when stretching was performed after the hops (6%) compared with control, but no significant difference was observed when hops were performed after stretching. These results demonstrate that conditioning hops can counteract stretch-related declines in DJ performance. Furthermore, the differences in TPTs and KAnkle between combined conditioning protocols indicate that the order of conditioning tasks might play an important role at the muscle-tendon level.


Microsurgery for macrodefects: microvascular free-tissue transfer for massive defects of the head and neck.
Despite defect location and the fear of creating complex massive defects, coverage of large areas of soft tissue loss, with or without exposed calvaria, dura, and brain, can be reconstructed reliably with microvascular free tissue transfer. This technique permits separation of the oronasopharynyx from the intracranial contents, coverage of dural grafts, restoration of composite tissue loss, and achievement of superior aesthetic results in a single stage. When choosing vascular anastomotic sites, free-flap transfer permits a greater latitude in flap orientation, tailoring, and inset than is possible when using fixed pedicled rotation flaps. When confronted with a deeply invasive or gigantic malignancy, a multidisciplinary team approach is optimal. The risk associated with sophisticated ablative and reconstructive operative procedures is justified when dealing with potentially curable lesions. The success of these extensive procedures is related not only to the functional result and the aesthetic appearance, but most importantly to the resultant quality of life they allow.


Impact of collection conditions on the metabolite content of human urine samples as analyzed by liquid chromatography coupled to mass spectrometry and nuclear magnetic resonance spectroscopy.
There is a lack of comprehensive studies documenting the impact of sample collection conditions on metabolic composition of human urine. To address this issue, two experiments were performed at a 3-month interval, in which midstream urine samples from healthy individuals were collected, pooled, divided into several aliquots and kept under specific conditions (room temperature, 4 °C, with or without preservative) up to 72 h before storage at -80 °C. Samples were analyzed by high-performance liquid chromatography coupled to high-resolution mass spectrometry and bacterial contamination was monitored by turbidimetry. Multivariate analyses showed that urinary metabolic fingerprints were affected by the presence of preservatives and also by storage at room temperature from 24 to 72 h, whereas no change was observed for urine samples stored at 4 °C over a 72-h period. Investigations were then focused on 280 metabolites previously identified in urine: 19 of them were impacted by the kind of sample collection protocol in both experiments, including 12 metabolites affected by bacterial contamination and 7 exhibiting poor chemical stability. Finally, our results emphasize that the use of preservative prevents bacterial overgrowth, but does not avoid metabolite instability in solution, whereas storage at 4 °C inhibits bacterial overgrowth at least over a 72-h period and slows the chemical degradation process. Consequently, and for further LC/MS analyses, human urine samples should be kept at 4 °C if their collection is performed over 24 h.


Extremely large chromosomal deletions are intimately involved in genetic instability and genomic rearrangements in Streptomyces glaucescens.
Genetic instability in Streptomyces glaucescens characteristically involves the occurrence of gross genomic rearrangements including high-level sequence amplification and extensive deletion. We investigated the relationship of the unstable melC and strS loci and a 100 kb region of the chromosome which frequently gives rise to intense heterogeneous DNA amplification. Standard chromosome walking using a cosmid bank in conjunction with a "reverse-blot" procedure enabled us to construct a contiguous genomic BamHI map of the unstable region exceeding 900 kb. The unstable genes and the amplifiable region (AUD locus) are physically linked within a 600 kb segment of the chromosome. The previously characterized deletions which affect these loci are merely components of much larger deletions ranging from 270 to over 800 kb which are polar in nature, effecting the sequential loss of the strS and melC loci. The more extensive deletions terminate either adjacent to, or in the vicinity of DNA reiterations at the AUD locus. Additionally, a deletion junction fragment and the corresponding deletion ends were cloned and analysed at the sequence level.


Anti-angiogenic activity of a homoisoflavanone from Cremastra appendiculata.
A homoisoflavanone, 5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one ( 1), was isolated from the bulb of Cremastra appendiculata (D. Don) Makino (Orchidaceae) as a potent inhibitor of angiogenesis. It inhibited basic fibroblast growth factor (bFGF)-induced in vitro angiogenesis and in vivo angiogenesis of the chorioallantoic membrane (CAM) of chick embryo without showing any toxicity.


The first documented case of true botulinum toxin granuloma.
We report a unique case of foreign-body granuloma following botulinum neurotoxin type A (BoNTA) injection. A 44-year-old woman was injected with BoNTA by a dermatologist. Within 2 months of treatment, palpable nodules developed on injection site and biopsy revealed foreign-body granuloma.


Bioremediation of petroleum hydrocarbons from crude oil-contaminated soil with the earthworm: Hyperiodrilus africanus.
A study on the bioremediation potentials of the earthworm Hyperiodrilus africanus (Beddard) in soil contaminated with crude oil was investigated. Dried and sieved soils were contaminated with 5 ml each of crude oil with replicates and inoculated with earthworms and monitored daily for 12 weeks. Physicochemical parameters such as pH, total organic carbon, sulfate, nitrate, phosphate, sodium, potassium, calcium and magnesium were determined using standard procedures. Total petroleum hydrocarbon (TPH) was determined using atomic absorption spectrophotometer (AAS), while BTEX constituents and earthworms tissues were analyzed using Gas Chromatography with Flame Ionization Detector (GC-FID). The results showed that the earthworm significantly enhanced the physicochemical parameters of the contaminated soil resulting in a decrease of the total organic carbon (56.64 %), sulfate (57.66 %), nitrate (57.69 %), phosphate (57.73 %), sodium (57.69 %), potassium (57.68 %), calcium (57.69 %) and magnesium (57.68 %) except pH (3.90 %) that slightly increased. There was a significant decrease in the TPH (84.99 %), benzene (91.65 %), toluene (100.00 %), ethylbenzene (100.00 %) and xylene (100.00 %). Analyses of the tissues of the earthworm at the end of the experiment showed that the earthworms bioaccumulated/biodegraded 57.35/27.64 % TPH, 38.91/52.73 % benzene, 27.76/72.24 % toluene, 42.16/57.85 % ethylbenzene and 09.62/90.38 % xylene. The results showed that the earthworms H. africanus could be used to bioremediate moderately polluted soil with crude oil contamination in the Niger Delta region of Nigeria.


Comparison of proton density fat fraction, simultaneous R2*, and apparent diffusion coefficient for assessment of focal vertebral bone marrow lesions.
To investigate the diagnostic performance of proton density fat fraction (PDFF) and simultaneous R2* for focal vertebral bone marrow lesion (VBML) assessment, compared with the apparent diffusion coefficient (ADC). One hundred and ninety-two spinal magnetic resonance imaging (MRI) examinations performed in 126 patients with focal VBMLs from March 2016 to November 2018 were reviewed retrospectively. The lesions were divided into metastases and benign VBMLs. The protocol consisted of routine morphological MRI sequences, followed by complex-based chemical shift imaging (CSE)-MRI and diffusion-weighted (DW)-MRI with a 1.5 T system. PDFF, R2*, and the ADC values were compared using the Mann-Whitney U-test. Receiver operating characteristic curve analysis was carried out to assess the diagnostic performance for differentiating metastases from focal benign VBMLs. PDFF, R2*, and mean ADC values in metastases were significantly lower than those in benign VBMLs (p<0.05). The PDFF (area under the curve [AUC]= 0.968; 95% confidence interval [CI]=0.932-0.988) showed a significantly larger AUC compared with R2* (AUC=0.670; 95% CI=0.599-0.736) and ADC (AUC=0.801; 95% CI=0.738-0.855). The optimal cut-off value of the PDFF for predicting metastases was 9%; this threshold corresponded to a sensitivity of 96.67%, specificity of 90.28%, and accuracy of 94.27%. PDFF is significantly more accurate than ADC and R2* for differentiating focal benign VMBLs from metastases.


Calcemic and phosphaturic response to parathyroid hormone in normal and chronically uremic dogs.
It is well established that the calcemic response to parathyroid hormone (PTH) is blunted in chronic uremia and is corrected partially by 1,25(OH)2D treatment. Recent evidence suggests that PTH(1-34) and not PTH(1-84) may be the actual calcemic fragment. Equivalent doses of both peptides were infused into five normal dogs (GFR = 51 ml/min) and eight dogs with a remnant kidney and chronic renal insufficiency (GFR = 15 ml/min). Both the calcemic and phosphaturic responses were studied. Remnant dogs had a blunted calcemic response to bPTH(1-84). The increase in fractional phosphate excretion was similar. In contrast, the calcemic response to bPTH(1-34) was equivalent in remnant and normal dogs. Treatment of uremic dogs with 400 ng 1,25(OH)2D daily for 3 days restored the effect of bPTH(1-84) on serum calcium and increased the control value for tubular phosphate reabsorption from 28 +/- 3 micrograms/ml GFR to 37 +/- 4 micrograms/ml GFR (P less than 0.01). These results suggest that there is an impaired conversion of PTH(1-84) to PTH(1-34) in chronic renal insufficiency and that 1,25 (OH)2D may be involved in metabolism of PTH(1-84). In addition, the effect of PTH on fractional phosphate excretion is not magnified in nonparathyroidectomized uremic dogs.


Antibody dependent cell-mediated cytotoxicity to herpes simplex virus in man: the influence of drugs on polymorphonuclear leucocyte and mononuclear effector cells.
We have shown that the function of the effector cells in antibody mediated cell dependent cytotoxicity (ADCC) can be reduced by the use of a number of drugs and prostaglandins. Both polymorphonuclear leucocyte and mononuclear effector cells were studied. Aminophylline and isoproterenol markedly reduced this activity. All the prostaglandins tested--PGA1, A2, E1 and E2 had a similar but more profound effect. At a dose of 100 mg/ml hydrocortisone had relatively little influence and neither ASA nor indomethacin had any effect on the effector cells tested. It is suggested that the effect of PGE1 in stimulating a recrudescent herpes simplex infection may be by reducing the efficacy of ADCC in host defence.


Multimodality management and outcomes of brain arterio-venous malformations (AVMs) in children: personal experience and review of the literature, with specific emphasis on age at first AVM bleed.
The purpose of this paper is to study the presentation and analyse the results of multimodality treatment of brain arterio-venous malformations (AVMs) in children at our centre and review age at first AVM rupture in the literature. Of 52 patients aged <18 years, 47 with brain AVMs (27 males and 20 females) aged 4-17 years (mean 12.2) were retrospectively reviewed. PubMed search revealed five additional studies including 267 patients where the prevalence of age-related AVMs rupture was analysed. In our study, 37 patients had bled, 9 were symptomatic without haemorrhage and 1 was incidental. Spetzler-Martin score distribution was 5 cases grade I, 18 grade II, 21 grade III and 3 grade IV. Appropriate imaging was performed, either CT/MRI angiogram only (in emergency cases) or catheter angiogram, prior to definitive treatment. There were 40 supratentorial and 7 infratentorial AVMs. Twenty-nine patients had microsurgery alone and 9 patients were treated by radiosurgery only. Three patients were embolised, all followed by radiosurgery, with one requiring surgery too, while 4 patients had combined surgery and radiosurgery. One patient is awaiting radiosurgery while another was not treated. Good outcomes, classified as modified Rankin score (mRS) 0-2 improved significantly after intervention to 89.4% from 38.3% pre-treatment (p value <0.0001). Angiography confirmed 96.6% obliteration after first planned operation. Repeat cerebral angiogram around age 18 was negative in all previously cured patients. Reviewing the literature, 82.0% (95% CI = [77-87]; N = 267) of children diagnosed with brain AVMs (mean age 11.4 ± 0.4) presented with a bleed in the last 22 years. Males significantly outnumbered females (136 vs 84) (p < 0.001). Ninety-five patients underwent surgical intervention alone when compared to other treatment modalities (p < 0.001). Microsurgical excision of surgically accessible intracranial AVMs remains the primary treatment option with very good outcomes. A significant number of patients' AVMs ruptured around puberty; therefore, understanding the pathophysiology of AVM instability at this age may aid future therapy.


Mineral density of the os calcis in primary osteoarthritis of the hip and geriatric femoral neck fractures.
The calcaneal bone mineral density (BMD) was measured in 22 female patients operated on for femoral neck fractures on average 4.7 years ago, and 35 patients who had undergone total hip replacement for primary osteoarthritis on average 3.7 years ago, to test the hypothesis of an inverse relationship between bone density and osteoarthritis. After adjustment for the linear correlation between age and BMD, there was no significant difference between the groups with regard to BMD of the os calcis.


Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues.
L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.


Epidermal growth factor does not cross the blood-brain barrier.
To measure the passage of epidermal growth factor (EGF) through the blood-brain barrier (BBB) 125I-labeled EGF was injected intravenously into adult rats. The distribution of 125I-EGF in the blood and cerebrospinal fluid (CSF) was determined over a time period of several hours. Between 2 to 6 h a stable distribution of intact 125I-EGF in CSF was measured to be approximately 1/500 of the blood-borne EGF, an equilibrium value below those obtained by other investigators for BBB-impermeable compounds, such as inulin and bovine serum albumin. Our data indicate that 125I-EGF, although clearly detectable in the CSF, does not cross the BBB at a higher rate or in higher quantities than would be expected from its molecular size.


Facile fabrication of water-dispersible nanocomposites based on hexa-peri-hexabenzocoronene and Fe3O4 for dual mode imaging (fluorescent/MR) and drug delivery.
The facile fabrication of multifunctional nanocomposites (Fe3O4/HBC@F127) consisting of superparamagnetic Fe3O4 nanoparticles and fluorescent organic hexa-peri-hexabenzocoronene (HBC) molecules incorporated in block copolymer diacylphospholipid-polyethyleneglycol F127 have been demonstrated for dual mode imaging (fluorescent/MR) and drug delivery. The obtained nanocomposites were water-dispersible, stable and biocompatible, as confirmed by dynamic light scattering (DLS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Relativity measurements showed a T 2 relaxivity (r 2) of 214.61 mM-1 s-1, which may be used as T 2-weighted MR imaging agents. In vitro imaging studies indicated that the nanocomposites had good MR and fluorescence imaging effects with low cytotoxicity. Besides, the developed nanocomposites could also be applied as drug delivery vehicles. Doxorubicin (DOX) loaded Fe3O4/HBC@F127 nanocomposites significantly inhibited the growth of human hepatoma cells (HepG2). These findings suggested that the facile synthesized multifunctional nanocomposites may be used as a platform for dual mode imaging (both MR and fluorescence) and drug delivery.


Leukocyte migration inhibitory factor: a serine esterase released by stimulated human lymphocytes. Kinetic analysis and inhibition by cyclic GMP.
Lymphocytes, stimulated with concanavalin A, release small amounts of non-immunoglobulin, highly reactive proteins called lymphokines. One of these, a serine esterase, termed leukocyte migration inhibitory factor according to its function in vitro, is found in supernatants of stimulated human lymphocytes at concentrations less than 1 ng/ml. The esterase was purified in good yield and its esterolytic activity was measured by a sensitive radioenzymic assay. The kinetics of the esterolytic activity were studied and the effect of various nucleotides examined. Competitive inhibition of esterolysis was seen with cyclic GMP at concentrations down to 10(-7) M, and with 2',3'-cyclic CMP at a concentration of 10(-3) M. A role of this esterase, not only as a mediator acting upon polymorphonuclear leukocytes, but also as an intracellular regulator of lymphocyte activation, is discussed.


Impaired in vivo feto-placental development is associated with neonatal neurobehavioral outcomes.
Fetal growth restriction (FGR) is a risk factor for neurodevelopmental problems, yet remains poorly understood. We sought to examine the relationship between intrauterine development and neonatal neurobehavior in pregnancies diagnosed with antenatal FGR. We recruited women with singleton pregnancies diagnosed with FGR and measured placental and fetal brain volumes using MRI. NICU Network Neurobehavioral Scale (NNNS) assessments were performed at term equivalent age. Associations between intrauterine volumes and neurobehavioral outcomes were assessed using generalized estimating equation models. We enrolled 44 women diagnosed with FGR who underwent fetal MRI and 28 infants underwent NNNS assessments. Placental volumes were associated with increased self-regulation and decreased excitability; total brain, brainstem, cortical and subcortical gray matter (SCGM) volumes were positively associated with higher self-regulation; SCGM also was positively associated with higher quality of movement; increasing cerebellar volumes were positively associated with attention, decreased lethargy, non-optimal reflexes and need for special handling; brainstem volumes also were associated with decreased lethargy and non-optimal reflexes; cerebral and cortical white matter volumes were positively associated with hypotonicity. Disrupted intrauterine growth in pregnancies complicated by antenatally diagnosed FGR is associated with altered neonatal neurobehavior. Further work to determine long-term neurodevelopmental impacts is warranted. Fetal growth restriction is a risk factor for adverse neurodevelopment, but remains difficult to accurately identify. Intrauterine brain volumes are associated with infant neurobehavior. The antenatal diagnosis of fetal growth restriction is a risk factor for abnormal infant neurobehavior.


Effects of Mind-Body Interventions Involving Meditative Movements on Quality of Life, Depressive Symptoms, Fear of Falling and Sleep Quality in Older Adults: A Systematic Review with Meta-Analysis.
Background: The aim of the present systematic meta-analytical review was to quantify the effects of different mind-body interventions (MBI) involving meditative movements on relevant psychological health outcomes (i.e., quality of life (QoL), depressive symptoms, fear of falling (FoF) and sleep quality) in older adults without mental disorders. Methods: A structured literature search was conducted in five databases (Ovid, PsycINFO, PubMed, SPORTDiscus, Web of Science). Inclusion criteria were: (i) the study was a (cluster) randomized controlled trial, (ii) the subjects were aged ≥59 years without mental illnesses, (iii) an intervention arm performing MBI compared to a non-exercise control group (e.g., wait-list or usual care), (iv) psychological health outcomes related to QoL, depressive symptoms, FoF or sleep quality were assessed and (v) a PEDro score of ≥5. The interventions of the included studies were sub-grouped into Tai Chi/Qigong (TCQ) and Yoga/Pilates (YP). Statistical analyses were conducted using a random-effects inverse-variance model. Results: Thirty-seven randomized controlled trials (RCTs) (comprising 3224 participants) were included. Small to moderate-but-significant overall effect sizes favoring experimental groups (Hedges' g: 0.25 to 0.71) compared to non-exercise control groups were observed in all outcomes (all p values ≤ 0.007), apart from one subdomain of quality of life (i.e., social functioning, p = 0.15). Interestingly, a significant larger effect on QoL and depressive symptoms with increasing training frequency was found for TCQ (p = 0.03; p = 0.004). Conclusions: MBI involving meditative movements may serve as a promising opportunity to improve psychological health domains such as QoL, depressive symptoms, FoF and sleep quality in older adults. Hence, these forms of exercise may represent potential preventive measures regarding the increase of late-life mental disorders, which need to be further confirmed by future research.


Creatine kinase concentration on the second post-match day is not associated with risk of subsequent muscle injury in professional football players: a four-season cohort study.
The objective of this study was to examine the relationship between creatine kinase (CK) concentration following official matches and the risk of subsequent muscle injury in professional male football (soccer) players. Blood samples were collected on the second post-match day for CK analysis over four consecutive seasons in a professional football club. Players were then followed for five days to observe any occurrence of indirect muscle injury (structural or functional in nature). Players exposed to at least 45 minutes in two consecutive matches within seven days were considered valid cases for analysis. Eighty players participated in the study, generating 1,656 cases eligible for analysis, of which 229 resulted in muscle injuries. The hamstrings were the most frequently injured muscle group (54%), followed by the adductor (21%), triceps surae (19%), quadriceps (5%), and psoas (1%). While CK concentration was higher in muscle injury cases [783 ± 507 U/L (95%CI, 717 to 849; min-max, 105-2,800)] compared with uninjured cases [688 ± 446 U/L (95%CI, 665 to 711; min-max, 100-2,950)], it was not an accurate predictor of subsequent muscle injury risk in professional football players (sensitivity = 56%; specificity = 55%; odds ratio = 1.00; area under curve = 0.557). CK concentration on the second post-match day cannot be used to effectively screen subsequent muscle injury risk in professional male football players.


[Hydroxy 9-methyl 2-ellipticinium acetate (NSC 264-137). Toxicologic study and therapeutic effect in 100 cancers (author's transl)].
A new derivative of ellipticine, hydroxy-9-methyl-2-ellipticinium acetate, was found to be a useful anti-tumor drug in advanced cancers which could not be treated any longer successfully by any other procedure. In our series of 100 patients, the best results were obtained with bone metastases from breast carcinomas and with anaplastic thyroid carcinomas. Most patients usually received a weekly perfusion of 80 mg/m2. The main characteristic of this drug is its lack of hematologic, and hepatic toxicity. No renal trouble was observed during the first year, but 2 deaths from renal insufficiency occured during the 18th and 15th month of treatment. The most frequent side effect consists of digestive troubles (nausea, vomiting) which rarely compelled to stop the treatment (4 times in 100 patients).


Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum combination chemotherapy in metastatic testis cancer--a 1-year program.
Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum were given in 31 men with stage III or bulky stage II malignant germ cell tumors of the testis and no previous chemotherapy, 25 of whom were evaluable. This regimen was given for 1 year and began with 3 successive inductions at 3 to 4-week intervals: 600 mg./m.2 intravenous cyclophosphamide, 4 mg./m.2 intravenous vinblastine, 30 mg. intravenous bleomycin and 1 mg./m.2 intravenous actinomycin D on day 1, followed by continuous 24-hour infusion of 20 mg./m.2 bleomycin per day on days 1 to 3 and 120 mg./m.2 intravenous cis-platinum with mannitol-enhanced diuresis on day 4. Any residual disease was resected 1 month after the third induction. If the resected specimen contained malignant tissue an additional 2 inductions (total 5) were given before brief maintenance with 6 mg./m.2 intravenous vinblastine and 1 mg./m.2 intravenous actinomycin D every 3 weeks for the remainder of 1 year. Complete remission occurred in 23 of 25 evaluable patients (92 per cent) and 20 (80 per cent) remain free of disease with a median followup of more than 27 months. Patients with minimal metastatic deposits and those without teratoma in the testis tumor had high complete remission rates with chemotherapy alone. Patients with advanced disease and with teratoma in the primary tumor benefited more frequently from the combined approach. Myelosuppression was the major potentially serious toxic effect. Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum were superior to prior vinblastine, actinomycin D and bleomycin programs because higher complete remission rates were achieved with shorter duration of treatment and lesser disability.


Current practice of genomic profiling of patients with advanced solid tumours in Italy: the Italian Register of Actionable Mutations (RATIONAL) study.
The Italian Register of Actionable Mutations (RATIONAL) is a multicentric, observational study collecting next-generation sequencing (NGS)-based tumour profiling data of patients with advanced solid tumours. The study enrols patients who had available an NGS-based tumour profiling (Pathway-A) or undergo comprehensive genomic profiling (CGP) with FoundationOne CDx assays within the trial (Pathway-B). The primary endpoint was the rate of actionable mutations identified. Sequencing data were available for 738 patients in Pathway-A (218) and -B (520). In Pathway-A, 154/218 (70.6%) tests were performed using NGS panels ≤52 genes, and genomic alterations (GAs) were found in 164/218 (75.2%) patients. In Pathway-B, CGP revealed GAs in 512/520 (98.5%) patients. Levels I/II/III actionable GAs according to the European Society of Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) were identified in 254/554 (45.8%) patients with non-small-cell lung cancer, cholangiocarcinoma, colorectal, gastric, pancreatic and breast cancer. The rate of patients with level I GAs was similar in Pathways A and B (69 versus 102). CGP in Pathway-B revealed a higher number of patients with level II/III GAs (99 versus 20) and potentially germline pathogenic/likely pathogenic variants (58 versus 15) as compared with standard testing in Pathway-A. In patients with cancer of unknown primary, CGP detected OncoKB levels 3B/4 GAs in 31/58 (53.4%) cases. Overall, 67/573 (11.7%) of patients received targeted therapy based on genomic testing. The Italian Register of Actionable Mutations represents the first overview of genomic profiling in Italian current clinical practice and highlights the utility of CGP for identifying therapeutic targets in selected cancer patients.


[Study of long-term effects of zeolites on the body of laboratory animals].
The aim of present study was an investigations of embryotoxic, teratogenic and gonadotoxic effects of zeolites of Pashensky and Chongurinsky (chongurin) deposits. Zeolites are suggested as feed additives in stock-breeding animal and poultry-keeping. In long-term experiments it was shown that zeolites included in animal diet as much as 5% of diet mass had no unfavourable effect on animals. Negative effect on growth and development of generation, hematologic parameters of blood and activity of some enzymes were also not observed.


Donepezil use in children and adolescents with tics and attention-deficit/hyperactivity disorder: an 18-week, single-center, dose-escalating, prospective, open-label study.
Striatal cholinergic dysfunction may be important in tics and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to determine the safety profile of donepezil and whether it improves chronic tics in young patients with comorbid ADHD. This 18-week (14 weeks of open treatment followed by a 4-week washout period), single-center, dose-escalating, prospective, open-label trial was conducted in patients aged 7 to 17 years with tics, including chronic motor or vocal tics and Tourette's syndrome, and ADHD. Patients were treated with once-daily oral donepezil doses of 2.5 mg for 2 weeks, 5 mg for the next 6 weeks, and 10 mg for the last 6 weeks, followed by a 4-week washout period. Patients were evaluated using the Children's Global Assessment Scale; the Yale Global Tic Severity Scale (YGTSS); the Revised Conners' Parent Rating Scale; the Symbol and Digit Wisconsin Card Sorting Test; the Stroop black/white, color, and interference tests; the Rey Complex Figure Test; and the Children's Yale-Brown Obsessive Compulsive Scale at 4 visits: baseline, week 8 (5-mg dose), week 14 (10-mg dose), and week 18 (washout). Seventeen males and 3 females (mean [SD] age, 11.3 [1.9] years [range, 8-14 years]; tic duration, 5.3 [1.9] years; ADHD duration, 6.5 [1.7] years) were included in this study. Tics were significantly reduced at the 10-mg (week-14) donepezil visit compared with the baseline and washout visits based on the total mean (SD) tic score of the YGTSS (18.6 [9.3] vs 12.2 [11.0]; P = 0.006). Fifty percent of patients withdrew and 65% experienced adverse events. These preliminary results suggest that donepezil significantly reduced tics in these children and adolescents with comorbid ADHD who completed the study. No significant improvement in the symptoms of comorbid ADHD was found with the use of donepezil 10 mg. Donepezil 5 and 10 mg were not well tolerated in these children and adolescents.


Cemento-ossifying fibroma of the mandible.
Cemento-ossifying fibroma is a rare benign tumor most often discovered incidentally. A 72-year-old patient was referred for a subclinical lesion of the mandible. The orthopantomogram showed a well-circumscribed radiolucent osteolytic image, 1 cm in diameter, on the mandibular angle. On CT, the single lesion had a tissue aspect with a peripheral halo without enhancement after contrast injection. A cortical lacuna on the lingual side was noted. Surgical enucleation of the lesion was performed. The pathological examination confirmed the ossifying fibroma. Slow and progressive, cemento-ossifying fibroma is a rare benign tumor that reaches the maxilla and more frequently the mandible. The ossifying and cementifying fibromas are differentiated by their clinical, radiological, and histological findings. The authors discuss the pathogenesis and radiological signs guiding the choice of diagnostic and therapeutic methods. The treatment is surgical with an enucleation or wider resection with bone reconstruction for large fibromas.


Prognostic value of high-sensitivity C-reactive protein in a population of post-acute coronary syndrome patients receiving optimal medical treatment.
High-sensitivity C-reactive protein (hsCRP) has been reported to have a prognostic value immediately after acute coronary syndrome (ACS) and to be associated with the onset of cardiovascular (CV) events in patients with stable and unstable angina pectoris. To evaluate whether or not hsCRP levels can be used to predict future CV events in a prospective study of post-ACS patients receiving an optimized medical treatment (OMT) secondary-prevention regimen. OMT along with therapeutic and dietary education programmes were started during the acute phase, then monitored and adjusted as needed at 3 months post ACS. hsCRP was measured at 3 months after the ACS, and a global evaluation of atherosclerosis burden and risk factors were also evaluated at this time point. The study population was divided into tertiles based on their hsCRP value and followed for CV events. A total of 1202 consecutive patients with hsCRP <15 mg/l were included in the study, 795 of which were followed for an average of 22 months. LDL-cholesterol, HbA(1c), waist circumference, systolic blood pressure, metabolic syndrome, tobacco consumption, and atherosclerosis burden were higher in patients in the second and third tertile of hsCRP (p < 0.001) than those in the first tertile, at 3 months. hsCRP level was not found to be associated with recurrence of total CV events (HR 1.29, CI 0.83-2.00) in univariate analysis. We further examined the effect of adding hsCRP levels to the Framingham risk evaluation score, and found no significant improvement the C-statistics of the Framingham risk evaluation score. hsCRP is associated with CV risk factors, but is not an independent predictor of future events in post-ACS patients receiving an OMT secondary-prevention regimen.


Frontal tDCS reduces alcohol relapse rates by increasing connections from left dorsolateral prefrontal cortex to addiction networks.
Brain-based interventions are needed to address persistent relapse in alcohol use disorder (AUD). Neuroimaging evidence suggests higher frontal connectivity as well as higher within-network connectivity of theoretically defined addiction networks are associated with reduced relapse rates and extended abstinence during follow-up periods. /Hypothesis: A longitudinal randomized double-blind sham-controlled clinical trial investigated whether a non-invasive neuromodulation intervention delivered during early abstinence can (i) modulate connectivity of addiction networks supporting abstinence and (ii) improve relapse rates. Active transcranial direct current stimulation (tDCS) will (i) increase connectivity of addiction networks known to support abstinence and (ii) reduce relapse rates. Short-term abstinent AUD participants (n = 60) were assigned to 5 days of either active tDCS or sham during cognitive training. Causal discovery analysis (CDA) examined the directional influence from left dorsolateral prefrontal cortex (LDLPFC, stimulation site) to addiction networks that support abstinence. Active tDCS had an effect on the average strength of CDA-determined connectivity from LDLPFC to the incentive salience and negative emotionality addiction networks - increasing in the active tDCS group only. Active tDCS had an effect on relapse rates following the intervention, with lower probability of relapse in the active tDCS vs. sham. Active tDCS showed an unexpected sex-dependent effect on relapse rates. Our results suggest that LDLPFC stimulation delivered during early abstinence has an effect on addiction networks supporting abstinence and on relapse rates. The unexpected sex-dependent neuromodulation effects need to be further examined in larger clinical trials.


Spectral CT reconstruction via Spectral-Image Tensor and Bidirectional Image-gradient minimization.
It is challenging to obtain good image quality in spectral computed tomography (CT) as the photon-number for the photon-counting detectors is limited for each narrow energy bin. This results in a lower signal to noise ratio (SNR) for the projections. To handle this issue, we first formulate the weight bidirectional image gradient with L0-norm constraint of spectral CT image. Then, as a new regularizer, bidirectional image gradient with L0-norm constraint is introduced into the tensor decomposition model, generating the Spectral-Image Tensor and Bidirectional Image-gradient Minimization (SITBIM) algorithm. Finally, the split-Bregman method is employed to optimize the proposed SITBIM mathematical model. The experiments on the numerical mouse phantom and real mouse experiments are designed to validate and evaluate the SITBIM method. The results demonstrate that the SITBIM can outperform other state-of-the-art methods (including TVM, TV + LR, SSCMF and NLCTF). INDEX TERMS: -spectral CT, image reconstruction, tensor decomposition, unidirectional image gradient, image similarity.


Ameliorative Effects of Prolotherapy on Histomorphology of Tibial Articular Cartilage of Chemically Induced Osteoarthritic Knee Joint in a Rat Model.
To determine the ameliorative effects of prolotherapy on monosodium iodoacetate (MIA) induced and histomorphological changes in the articular cartilage of tibial condyles at rat knee joint. An experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College Rawalpindi, NUMS, Rawalpindi, from August to November 2021. Thirty adult male Sprague Dawley rats were divided into three groups, each having 10 rats. Group A was control. Group B was injected with single dose of 1mg MIA intraarticularly in the right knee to induce osteoarthritic changes. Group C was injected with single dose of 1mg MIA intraarticularly, in right knee was followed by 0.1ml Prolotherapy (3ml of 25% dextrose, 2ml of 2% xylocaine, 1ml of injection neurobion, and 1ml of injection methecobal) as intra articular injection at week 2, 6 and 10 in right knee. Rats were sacrificed after one month of the last dose of Prolotherapy. Articular cartilage was collected for gross and histological examination and compared among the groups. Articular cartilage belonging to control group A was normal. While group B showed statistically significant deterioration in gross appearance (p = 0.001**), reduction in number of chondrocytes (p = 0.005*) and thickness of articular cartilage (p = 0.001**) in comparison to group A. In group C due to prolotherapy statistically significant improvement in gross appearance (p = 0.034*), increase in number of chondrocytes (p = 0.003*), and thickness of articular cartilage (p = 0.001**) was observed as compared to group B. Prolotherapy significantly ameliorates histomorphology of tibial articular cartilage against MIA induced osteoarthritic changes in rat knee joint. Articular cartilage, Knee joint, Monosodium iodoacetate, Osteoarthritis, Prolotherapy.


Imaging of aortico-left ventricular tunnel by three-dimensional echocardiography.
Aortico-left ventricular tunnel (ALVT) is a rare congenital heart disease presenting as congestive heart failure in the neonatal or early infantile period due to severe aortic regurgitation (AR). We presented a 1-month-old boy with ALVT, originally diagnosed by two-dimensional echocardiography; however, the detailed anatomical features were not ascertained. Real-time three-dimensional echocardiography (RT3DE) could provide clear images of the three-dimensional structures of ALVT, just the same as those of surgical findings. ALVT originated from the left coronary cusp and ran an oblique path to the subvalvular orifice, having a narrow segment in the middle. RT3DE is a clinically useful diagnostic tool to clarify the detailed anatomy of ALVT.


Response of Bemisia tabaci Genn. (Hemiptera: Aleyrodidae) biotype B to genotypes of pepper Capsicum annuum (Solanales: Solanaceae).
Bemisia tabaci Genn. biotype B is a widely distributed plant pest that represents one of the major constraints for horticultural crop production. The purpose of the present work was to evaluate the oviposition preference, survivorship, and development of B. tabaci biotype B on semi-cultivated genotypes of Capsicum annuum from southeast Mexico. In free-choice experiments to evaluate the oviposition preference, lower number of eggs laid by B. tabaci biotype B was observed in the genotypes Maax and Xcat´ik relative to that in the commercial genotype Parado. Egg hatchability was significantly lower in Pico Paloma, Bolita, Blanco, Chawa, Payaso, and Xcat´ik than in the rest of the genotypes, including the commercial genotype Jalapeño. Likewise, survivorship of nymphs was significantly lower in Pico Paloma, Bolita, and Blanco than in the remaining genotypes. Nymph developmental time and the period of development from egg to adult were the shortest in Amaxito. Therefore, sources of resistance to B. tabaci biotype B by antibiosis (accumulation of plant defense compounds) might be found in the semi-cultivated genotypes Pico Paloma, Bolita, and Blanco.


The stress of coming out.
To conclude, (1) although homosexuality has been recognized for hundreds of years, we still do not understand it completely. (2) This paper places emphasis on the process of individuation and gender-identity that takes place very early in childhood as the cause of homosexuality. (3) If the process is not completed properly, the individual's gender-identity will deviate from that of the vast majority of people. Homosexuality is, therefore, considered by me as a deviation from, rather than a variation of, human sexuality. (4) The degree of neurosis or psychosis associated with homosexuality or heterosexuality is not causal in nature, although the two are intimately intertwined. (5) The stress of coming out varies a great deal in intensity and depends on the degree of integration of the individual and the support given to him by his friends, associates, and family. (6) Although the last decade has brought about a greater acceptance of homosexuality than ever before, sufficient prejudice, ignorance, and fear remain to keep many homosexuals "in the closet." (7) Even today the disclosure of one's homosexuality threatens the individual with the loss of so many important aspects of his life, such as his job, his friends, and even his family, that there is little wonder that coming out of the closet poses such problems for so many homosexuals.


Regulation of axon number in primate optic nerve by prenatal binocular competition.
We report here that in mature rhesus monkeys in which one eye was removed during the first half of gestation, the optic nerve of the remaining eye is larger and contains significantly more retinal axons than in age-matched control animals. Such supernumerary fibres in monocularly enucleated monkeys probably result from an arrest in the normal process of elimination of excess embryonic optic axons. Although the function of retained supernumerary optic axons is unknown, this finding demonstrates that (1) competition between the two eyes for synaptic territory occurs prenatally, before visual experience and (2) an early lesion in one brain area can adjust or enhance the size and perhaps the performance of other synaptically related structures.


Current practice of preoperative fasting: a nationwide survey in Japanese anesthesia-teaching hospitals.
We conducted a nationwide survey to investigate the current practice of the preoperative fasting period in Japanese anesthesia-teaching hospitals. Acceptance of the clinical practice guideline published by the American Society of Anesthesiologists (ASA) was also surveyed. A written type of questionnaire was mailed to 795 teaching hospitals. The response rate of the questionnaires was 57%. Most (>90%) of the respondents had been applying a longer fasting period than the ASA-recommended minimum period specifically in adults; the median duration of fasting was 12-13 h for solids and 6-9 h for liquids. Children or infants were allowed a more liberalized fasting period, frequently being permitted an oral intake of clear fluids up to 3 h before anesthesia. The incidence of pulmonary aspiration was 1/12,500 general anesthesia cases, and application of the ASA guideline appeared not to affect the incidence. Japanese anesthesiologists were still reluctant to depart from their traditional long fasting periods, as most of them could find little benefit in reducing the fasting periods. The long preoperative fasting period is still common practice in Japanese anesthesia-teaching hospitals. A national guideline for a preoperative fasting policy is worth exploring to change the current practice.


Technical and Clinical Outcomes Following Colonic Stenting: A Seven-Year Analysis of 268 Procedures.
To assess the factors contributing to the technical and clinical success of colorectal stenting for large bowel obstruction. 268 cases of colonic stenting for large bowel obstruction were performed in 249 patients of mean age of 72 years (28-98) between 2006 and 2013. The majority of strictures were due to malignant disease, 244/268 (91 %). Diverticular strictures accounted for 24/268 (9 %). Overall technical success rate was 81 % (217/268), with a clinical success rate of 65 % (174/268). Duration of symptoms ranged from 0 to 180 days (mean 8 days). Technical success rate was seen to decrease with increasing symptom duration. For symptom duration of less than 1 week, technical success was 85.4 % (181/212) versus 69.6 % (39/56) for those with symptoms of greater than a week (p < 0.05). Clinical success rates fell from 71.3 % (107/150) to 59.3 % (70/118) (p < 0.05) when attempting to stent lesions of greater than 5 cm. There was also a significant reduction in clinical success when stenting lesions on a bend rather than a straight segment of colon 75.7 % (109/144) versus 59.7 % (74/124) (p < 0.05). A total of 20 (7.46 %) perforations were identified during the study. Stent migration occurred in 6.6 % of cases. In-stent stenosis occurred in 3.3 %. The overall 30-day all cause mortality rate was 9 %. Lesion size, location and duration of obstructive symptoms are statistically significant determinants of patient outcome. These factors could be used to advise patient selection for colonic stenting or direct progression to surgical intervention.


Influences of Wastewater Treatment on the Occurrence of Parabens, p-Hydroxybenzoic Acid and Their Chlorinated and Hydroxylated Transformation Products in the Brazos River (Texas, USA).
Parabens are ubiquitous, being found in surface waters around the world. Although little is known about the release of paraben transformation products and fate of transformation products in surface water. This study evaluates both parabens and paraben transformation products in the Brazos River upstream and downstream of a wastewater facility located in Waco, Texas. Concentrations of thirteen compounds were reported in this study, five parent parabens and eight paraben disinfection by-products. Analyte concentrations were spatially evaluated to determine if release of wastewater effluent affects their concentrations in the river. Two Brazos River tributaries were also sampled to determine if they released parabens and related compounds to the Brazos. Sampling occurred weekly for one year with at least 40 samples collected at each site. Analyses were completed for both yearly and seasonal data. Sites downstream of wastewater treatment outfalls had lower concentrations of methyl paraben during the yearly analysis and across multiple seasons in the seasonal analysis with average yearly annual methyl paraben concentrations decreasing from 0.83 ng/L at site 3 to 0.09 ng/L at site 4. Para-hydroxybenzoic acid was the compound present in greatest concentration at most sites across most seasons, with the highest average annual concentration of 10.30 ng/L at site 2. Spatial changes in para-hydroxybenzoic acid varied by season, with seasonal trends only identifiable after normalization by flow. Dichlorinated paraben concentrations increased in the river at sites downstream of wastewater treatment with a yearly average dichlorinated methyl paraben concentration of 0.490 ng/L at site 3 to 1.53 at site 4, just downstream of the major wastewater treatment plant. Concentration increases indicate that wastewater effluent contains sufficiently high dichlorinated paraben concentrations to effect concentrations downstream of effluent discharges. Dichlorinated species also persisted in the environment, with no significant decreases at sites further downstream during any season with an annual average dichlorinated methyl paraben concentration of 1.23 ng/L at site 6. Methyl paraben concentrations decreased at the site furthest downstream to a concentration of 0.081 ng/L, while dichlorinated methyl paraben concentrations remained stable with a concentration of 1.10 ng/L at the site furthest downstream. Due to the dichlorinated species being released in higher concentrations in effluent than parents and being more resistant to degradation, the dichlorinated parabens are more likely to be environmentally relevant than are parent parabens.


Morphology and ultrastructure of the infrabuccal pocket and its lining epithelium in workers of Ectomomyrmex javanus (Hymenoptera: Formicidae).
This paper describes the morphology and ultrastructure of the infrabuccal pocket in workers of the carnivorous ant Ectomomyrmex javanus, using SEM and TEM. The infrabuccal pocket is a flexible bag with a diameter of 330 ± 30 μm. In its anterior part, the pocket wall reaches a thickness of 24.45 ± 3.45 μm, which is thicker than the wall lining the rest of the infrabuccal pocket, where it measures 6.87 ± 1.12 μm. The epidermal cells of the wall form a thickened epithelium with a thickness of 10.18 ± 2.50 μm. There are different kinds of hairs inside the pocket, that help in filtering solid pellets. Literature data on the infrabuccal pocket are limited and the function of the thicker epithelium is not yet known. It may provide mechanical strength as the pocket undergoes daily size changes because of the filling up and spitting out of pellets.


T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis.
Proteoglycan (PG) aggrecan, a major macromolecular component of cartilage, is highly immunogenic; it induces arthritis in genetically susceptible BALB/c mice. The present study maps the T-cell epitope repertoire of cartilage PG by identifying a total of 27 distinct T-cell epitopes. An epitope hierarchy, accounting for the different effector functions of PG-specific T cells, and determinant spreading, has been found. T-cell responses to four epitopes were associated with arthritis induction. Some of the T-cell epitopes were full T-cell activators, whereas a number of subdominant and cryptic epitopes proved to be partial activators in vitro, inducing either cytokine secretion or T-cell proliferation, but not both. A few T-cell epitopes of the core protein of cartilage PG were clearly recognized by T cells in PG-immunized arthritic animals, but the corresponding peptides did not induce T-cell responses when injected into naive BALB/c mice; thus these T-cell epitopes were designated as "conditionally immunogenic."


Influence of dexmedetomidine and lidocaine on perioperative opioid consumption in laparoscopic intestine resection: a randomized controlled clinical trial.
The consumption of opioid analgesics could be reduced by the use of analgesics with different mechanisms of action. We investigated whether additional treatment with dexmedetomidine or lidocaine could reduce opioid consumption. We randomized 59 study participants into three groups and examined: (i) fentanyl consumption, (ii) consumption of piritramide, and (iii) cognitive function and neuropathic pain. The control group received continuous propofol infusion and fentanyl boluses. Continuous intravenous infusion of dexmedetomidine (0.5 µg/kg/h) was administered to the dexmedetomidine group and lidocaine (1.5 mg/kg/h) was administered to the lidocaine group. No reduction in fentanyl consumption was observed among the groups. However, we noted a significantly lower consumption of piritramide on the first and second postoperative day in the lidocaine group. Total consumption of piritramide was significantly lower in the lidocaine group compared with the control group. Lidocaine and dexmedetomidine reduced intraoperative propofol consumption, while lidocaine reduced postoperative piritramide consumption. Clinical trial registration: NCT02616523.


Assessment of quality of life and chronic pain in dogs.
Assessment of chronic pain and quality of life (QOL) are integral to clinical veterinary research and practice, and recent years have seen an increase in the published tools available for the assessment of both. However, the relationship between chronic pain and QOL in veterinary patients has received insufficient attention. This narrative review for the first time explores similarities, differences and interactions between chronic pain and quality of life and identifies common challenges to their assessment in dogs. In the opinion of these authors, assessments of both chronic pain and quality of life should be pro-active, global, regular, applied to answer specific questions for researchers and decision makers, and transparent about what has, and has not, been assessed. Collaboration in this field between animal welfare scientists, veterinary researchers and clinicians appears rare, and should be prioritised.


Mercapto thiadiazole-based sensor with colorimetric specific selectivity for AcO- in aqueous solution.
A novel acetate selective anion sensor 3 based on azophenol and mercapto thiadiazole had been designed and synthesized. Sensor 3 behaves a single selectivity and sensitivity in the recognition for AcO(-) anion over other anions such as F(-), Cl(-), Br(-), I(-), H(2)PO(4)(-), HSO(4)(-) and ClO(4)(-) by naked-eyes and UV-vis spectra changes in aqueous solution (H(2)O/DMSO, 5:5, v/v). The color of the solution containing sensor 3 had an obvious change from colorless to orange only after the addition of AcO(-) in aqueous solution while other anions did not cause obvious color change. (1)H NMR titration results revealed that the binding process includes two steps: (i) hydrogen bonding interactions (for small quantities of acetate) and (ii) proton transfer between the sensor 3 and the coordinated anion (for high quantities of acetate). The association constant K(a) was 7.35×10(3) M(-1). The detection limitation of AcO(-) with the sensor 3 was 1.0×10(-6) mol L(-1).


Point mutations causing the McLeod phenotype.
The McLeod phenotype is defined by absence of Kx, weakening of Kell system antigens, and acanthocytosis. Individuals with the McLeod phenotype usually develop late-onset neuromuscular abnormalities. Gene deletions, insertions, and point mutations that affect RNA splicing or that lead to premature stop codons have been reported to cause the McLeod phenotype. The McLeod phenotype may also be caused by mutations at a different splice site and by a novel mutation encoding an amino acid substitution that prevents transport to the cell surface. The coding and flanking intron regions of XK from four male, unrelated individuals with the McLeod phenotype and non-chronic granulomatous disease were sequenced and compared with the wild type sequence. Genomic DNA was amplified by PCR, and the products were sequenced. In one case, the mutant cDNA was expressed in a heterologous cell, and cell surface expression was determined. Three individuals with the McLeod phenotype had mutations that disrupted conserved GT sequences present at RNA splice sites. Two of them had G>C mutations at the 5' splice site of intron 1, and one had a G>A mutation at the 5' splice site of intron 2. One person with the McLeod phenotype had a 746C>G mutation in exon 3 encoding an R222G substitution. In a transfected cell, the expressed protein from the latter mutant did not travel to the cell surface. The McLeod phenotype may be caused by several different mutations.


Overall clinical and economic impact of non-alcoholic fatty liver disease.
to establish the clinical and economic consequences (resource utilization and healthcare costs) of non-alcoholic fatty liver in the setting of the usual clinical practice in Spain. an observational, retrospective study was performed based on a review of the medical records of adult patients ≥ 18 years of age who sought medical care from 2017 to 2018. Patients were categorized into two groups according to fibrosis stage (estimation method: FIB-4): a) F0-F2; and b) F3-F4 (advanced fibrosis). Follow-up lasted one year. Primary endpoints included comorbidity, concomitant medication, resource utilization and costs. Results were analyzed using a multivariate approach with p < 0.05. a total of 8,151 patients were recruited with a mean age of 61.1 years and 51.5 % were male. By group: a) mild fibrosis n = 7,127, 87.4 %; and b) advanced fibrosis n = 1,024, 12.6 % (6.8 % with liver cirrhosis). The most common comorbidities included 63 % dyslipidemia, 52 % obesity, 52 % hypertension and 35 % diabetes. The average number of drugs used was 2.1 per patient. Patients with advanced fibrosis (F3-F4) had a higher average number of concomitant medications (2.5 vs 2.1; p < 0.001) and a higher AST/ALT ratio (1.1 vs 0.8; p < 0.001). The average cost (patient-year) for subjects with advanced fibrosis, corrected for covariates, was higher (€1,812 vs €1,128, p < 0.001). Age, morbidity, concomitant medication, fibrosis stage and total costs were higher in patients with diabetes. patients with advanced fibrosis were associated with more comorbidity and concomitant medications, which resulted in higher healthcare costs for the National Health System.


How can we explain the frontal presentation of insular lobe epilepsy? The impact of non-linear analysis of insular seizures.
For a decade it has been known that the insular lobe epilepsy can mimic frontal lobe epilepsy. We aimed to clarify the pattern of functional coupling occurring during the frontal presentation. We analyzed five insular lobe epilepsy patients. Frontal semiology was predominant for three of them, whereas insular semiology was predominant for the two others. We applied the non-linear regression analysis to stereoelectroencephalography-recorded seizures. A directed functional coupling index was calculated during clonic discharge periods that were accompanied either with frontal or insular semiology. We found significant functional coupling between the insula and mesial frontal/cingulate regions, with the former being a leader region for seizures propagation. Extra-insular regions showed significantly less or even no coupling with the mesial hemispheric regions. The three patients with frontal semiology showed strong couplings with the mesial frontal as well as cingulate regions, including the medial orbitofrontal cortex, pre-SMA/SMA, and the anterior to posterior cingulate. The two patients with the insular semiology only showed couplings between the insula and cingulate regions. The frontal semiology was expressed by strong functional couplings between the insula and mesial frontal regions. The insular origin of seizure should be considered in cryptogenic mesial frontal epilepsies.