Effect of stimulant medication on loss of control eating in youth with attention deficit/hyperactivity disorder: a prospective, observational case series study protocol.
Loss of control eating (LOC-E) in youth predicts the later development of full-syndrome binge-eating disorder (BED), and therefore, could be a relevant target for prevention treatments. To develop these treatments, it is important to understand the underlying disease processes and mechanisms. Based on the putative role of neurocognitive impairments in the pathogenesis of LOC-E, treatments that modulate these neurocognitive factors warrant further exploration. For instance, stimulants are an effective treatment for impulsivity in youth with attention deficit/hyperactivity disorder (ADHD) and have been shown to improve symptoms of BED in adults. Notably, stimulants have not been examined as a treatment for LOC-E in youth. To explore this gap, we aim to measure change in LOC-E episodes and secondary outcomes in youth with comorbid ADHD and LOC-E who are being started on stimulants. We will collect prospective observational data on forty 8-to-13-year-old youth diagnosed with comorbid ADHD and LOC-E who are initiating a stimulant for ADHD. Prior to stimulant initiation, participants will complete baseline measures including LOC-E episode frequency in the last 3 months (primary outcome), and secondary outcomes including disordered eating cognitions, emotions and behaviors, ADHD symptom severity, parental LOC-E, impulsivity and reward sensitivity, and anxiety/mood severity. Outcome measurements will be gathered again at 3-months after initiating the stimulant. Within-patient standardized effect sizes with 95% confidence intervals will be calculated from baseline to 3-month follow-up for all outcomes. Many individuals with LOC-E or binge eating do not fully remit over the course of psychotherapy. Whereas psychotherapy may address psychological and sociocultural domains associated with LOC-E, some individuals with neurocognitive impairments (e.g., ADHD) and neurobiological deficits (e.g., low intrasynaptic dopamine or norepinephrine) may benefit from adjunctive treatment that targets those factors. This will be the first study to provide pilot data for future studies that could examine both the effect of stimulants on LOC-E in youth and underlying mechanisms. Trial registration number: NCT05592119.


Feasibility of coronary angiography and percutaneous coronary intervention after transcatheter aortic valve replacement using a Medtronic™ self-expandable bioprosthetic valve.
With aging, the progression of atherosclerosis in the coronary arteries is expected. The Medtronic™ self-expandable aortic bioprosthetic valve is deployed in the supra-annular position, and it has been challenging to selectively engage coronary arteries post-transcatheter aortic valve replacement (TAVR) even though there are diamond-shaped spaces in the mesh frame within the valve. Given the scarcity of data, we analyzed angiographic and clinical data from all patients requiring coronary angiography (CA) or intervention post-TAVR. From January 2012 to December 2016, 403 patients were treated for severe aortic stenosis with TAVR at our center using the Medtronic™ self-expandable valve. This study included patients who underwent CA with or without percutaneous coronary intervention (PCI) after TAVR. Twenty-eight patients underwent 43 CAs after TAVR at our institution. Eleven patients (39%) were women. More than 90% of the procedures were performed for acute coronary syndrome. Thirty-six cases were performed using the transfemoral approach (83%). Forty-two of 43 (97%) left coronary arteries were selectively engaged, and 29 of 32 (90%) right coronary arteries were selectively engaged. We were able to engage 11 saphenous vein grafts and two left internal mammary artery grafts selectively (100%). The mean fluoroscopy time for diagnostic CA was 11.5 min, and for PCI, instantaneous wave-free ratio, or intravascular ultrasound (IVUS) interrogation, it was 19 minutes. The mean amount of contrast used for diagnostic CA was 102 cc per case, and for PCI, iFR, or IVUS, it was 146 cc per case. No periprocedural complication was noted. CA with or without PCI after TAVR is feasible with supra-annular self-expandable valves. With the proper technique in experienced hands, it can be conducted safely.


The extremely narrow-caliber esophagus is a treatment-resistant subphenotype of eosinophilic esophagitis.
Some patients with eosinophilic esophagitis (EoE) have an extremely narrow esophagus, but the characteristics of this group have not been extensively described. We aimed to characterize the narrow-caliber phenotype of EoE, determine associated risk factors, and identify differences in treatment response in this subgroup of patients. This retrospective cohort study from 2001 to 2014 included subjects with a new diagnosis of EoE per consensus guidelines. Demographic, endoscopic, histologic, and treatment response data were extracted from medical records. An extremely narrow-caliber esophagus was defined when a neonatal endoscope was required to traverse the esophagus due to the inability to pass an adult endoscope. Patients with and without an extremely narrow-caliber esophagus were compared. Multivariable logistical regression was performed to assess treatment outcomes. Of 513 patients with EoE, 46 (9%) had an extremely narrow-caliber esophagus. These patients were older (33 vs 22 years; P < .01), had longer symptom duration (11 vs 3 years; P < .01), more dysphagia (98% vs 66%; P < .01), and food impactions (53% vs 31%; P < .01). Dilation was more common with extreme narrowing (69% vs 17%; P < .01). Patients with a narrow-caliber esophagus were more refractory to steroid treatment, with lower symptom (56% vs 85%), endoscopic (52% vs 76%), and histologic (33% vs 63%) responses (P < .01 for all), and these differences persisted after multivariate analysis. The extremely narrow-caliber esophagus is a more treatment-resistant subphenotype of EoE and is characterized by longer symptom duration and the need for multiple dilations. Recognition of an extremely narrow-caliber esophagus at diagnosis of EoE can provide important prognostic information.


Melatonin suppresses Akt/mTOR/S6K activity, induces cell apoptosis, and synergistically inhibits cell growth with sunitinib in renal carcinoma cells via reversing Warburg effect.
Metabolic alteration drives renal cell carcinoma (RCC) development, while the impact of melatonin (MLT), a neurohormone secreted during darkness, on RCC cell growth and underlying mechanisms remains unclear. We detected concentration of metabolites through metabolomic analyses using UPLC-MS/MS, and the oxygen consumption rate was determined using the Seahorse Extracellular Flux analyzer. We observed that MLT effectively inhibited RCC cell growth both in vitro and in vivo. Additionally, MLT increased ROS levels, suppressed antioxidant enzyme activity, and induced apoptosis. Furthermore, MLT treatment upregulated key TCA cycle metabolites while reducing aerobic glycolysis products, leading to higher oxygen consumption rate, ATP production, and membrane potential. Moreover, MLT treatment suppressed phosphorylation of Akt, mTOR, and p70 S6 Kinase as well as the expression of HIF-1α/VEGFA in RCC cells; these effects were reversed by NAC (ROS inhibitors). Conversely, MLT synergistically inhibited cell growth with sunitinib and counteracted the Warburg effect induced by sunitinib in RCC cells. In conclusion, our results indicate that MLT treatment reverses the Warburg effect and promotes intracellular ROS production, which leads to the suppression of Akt/mTOR/S6K signaling pathway, induction of cell apoptosis, and synergistically inhibition of cell growth with sunitinib in RCC cells. Overall, this study provides new insights into the mechanisms underlying anti-tumor effect of MLT in RCC cells, and suggests that MLT might be a promising therapeutic for RCC.


Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of cancer pain: a retrospective analysis of 51 cases.
A retrospective analysis of 51 patients with cancer pain treated with a continuous i.t. morphine infusion through a tunnelled percutaneous catheter was undertaken. Because of insufficient pain relief with morphine only, 17 of these patients received a morphine/bupivacaine mixture. Pain relief subsequently improved significantly in 10 patients and a moderate improvement was present in 4 patients. An additional analgesic effect of bupivacaine was not shown in 3 patients with clinical signs of severe mental depression. Bupivacaine-induced side effects were absent below a daily dosage of 30 mg by continuous infusion. In all patients a gradual dose increment was observed. No serious complications, neurologic sequelae or meningitis occurred. It is concluded that long-term i.t. infusion of morphine through a tunnelled catheter can provide adequate pain relief in cancer patients with an acceptable risk-benefit ratio. The effects of long-term intrathecal co-administration of local anesthetics, especially bupivacaine, await further prospective evaluation.


Can low level exposure to ochratoxin-A cause parkinsonism?
Mycotoxins are fungal metabolites with pharmacological activities that have been utilized in the production of antibiotics, growth promoters, and other classes of drugs. Some mycotoxins have been developed as biological and chemical warfare agents. Bombs and ballistic missiles loaded with aflatoxin were stockpiled and may have been deployed by Iraq during the first Gulf War. In light of the excess incidence of amyotrophic lateral sclerosis (ALS) in veterans from Operation Desert Storm, the potential for delayed neurotoxic effects of low doses of mycotoxins should not be overlooked. Ochratoxin-A (OTA) is a common mycotoxin with complex mechanisms of action, similar to that of the aflatoxins. Acute administration of OTA at non-lethal doses (10% of the LD(50)) have been shown to increase oxidative DNA damage in brain up to 72 h, with peak effects noted at 24 h in midbrain (MB), caudate/putamen (CP) and hippocampus (HP). Levels of dopamine (DA) and its metabolites in the striatum (e.g., CP) were shown to be decreased in a dose-dependent manner. The present study focused on the effects of chronic low dose OTA exposure on regional brain oxidative stress and striatal DA metabolism. Continuous administration of low doses of OTA with implanted subcutaneous Alzet minipumps caused a small but significant decrease in striatal DA levels and an upregulation of anti-oxidative systems and DNA repair. It is possible that low dose exposure to OTA will result in an earlier onset of parkinsonism when normal age-dependent decline in striatal DA levels are superimposed on the mycotoxin-induced lesion.


Hyphomonas pacifica sp. nov., isolated from deep sea of the Pacific Ocean.
Three Gram-negative, aerobic, non-spore-forming, oval- to pear-shaped bacterial strains (T16B2(T), T24B3, and C76AD) were isolated from petroleum-degrading microbial communities through an enrichment of sediments and seawater samples from the Pacific Ocean. Phylogenetic analysis showed strains T16B2(T), T24B3, and C76AD to form a robust clade together with Hyphomonas atlanticus 22II1-22F38(T) and Hyphomonas beringensis 25B14_1(T) (16S rRNA identity ≥99.6 %). Genomic average nucleotide identity and DNA-DNA hybridization estimate values between strain T16B2(T) and nine type strains of the genus Hyphomonas are in the range of 82.9-88.2 and 18.3-33.6 %, respectively. The major cellular fatty acids in strains T16B2(T), T24B3, and C76AD are C16:0, C17:0, C18:1 ω7c-methyl, and summed feature 8 (C18:1 ω6c/ω7c). The DNA G+C content of strain T16B2(T) is 58.5 %. The predominant respiratory quinone of strain T16B2(T) is Q-11. Polar lipids comprise three unidentified glycolipids, one unidentified phospholipid, and two polar lipids. Combined phenotypic and genotypic data show strains T16B2(T), T24B3, and C76AD to represent a novel species of the genus Hyphomonas, for which the name Hyphomonas pacifica sp. nov. is proposed, with type strain T16B2(T) (=LMG 27911(T) = MCCC 1A04387(T)).


Bilateral motor coordination during upper limb symmetric pushing movements at two levels of force resistance in healthy and post-stroke individuals.
Impairments of the upper limb (UL) are common after a stroke and may affect bilateral coordination. A better understanding of UL bilateral coordination is required for designing innovative rehabilitation strategies. To assess bilateral coordination after stroke using time-distance, velocity and force parameters during an UL bilateral task performed by simultaneously pushing handles on a bilateral exerciser at two levels of force. Two groups were included to assess bilateral coordination on a newly designed bimanual exerciser- One group of individuals at least 3 months post-stroke (n = 19) with moderate impairment and one group of healthy individuals (n = 20). Participants performed linear movements by pushing simultaneously with both hands on instrumented handles. The task consisted of two one-minute trials performed in sitting at two levels of participants' maximum force (MF): 30% and 15%, with visual feedback. Time-distance parameters, spatial, velocity and force profiles were compared between groups, between levels of resistance and the first part (0-50%) and entire duration of the pushing cycles (0-100%). The mean pushing time was longer at 30% MF compared to 15% MF in the stroke group. Spatial profiles, represented by hand positions on the rail, revealed that the paretic hand lagged slightly behind throughout the cycle. For velocity, both groups displayed good coordination. It was less coupled at 30% than 15% MF and a trend was observed toward more lag occurrence in the stroke group. Except for lower forces on the paretic side in the stroke group, the shape of the force profiles was similar between groups, sides and levels of resistance. For all parameters, the coordination was good up to 75% of the pushing cycle and decreased toward the end of the cycle. Individuals after stroke presented with overall spatial and temporal coupling of the UL during bilateral pushing movements. The relay of information at different levels of the nervous system might explain the coordinated pushing movements and might be interesting for training UL coordination.


Peripheral cone contrast sensitivity in glaucoma.
Colour vision tests for detection of glaucomatous damage frequently suffer from two problems: most tests are confined to foveal vision, whereas defects tend to appear first extrafoveally; and the modulation directions in colour space are not optimal. This paper deals with peripheral testing à la Yu, Falcao-Reis, Spileers and Arden [(1991) Investigative Ophthalmology and Visual Science, 32, 2779-2789], and investigates whether there are modulation directions that show preferential sensitivity reduction in glaucoma. In 14 eyes with early glaucoma, 17 risk eyes and 10 normals, 12 deg peripheral colour contrast thresholds were determined for L, M, S, L-M and L+M test directions. Threshold elevations were correlated in all test directions, with S modulation yielding the largest elevations.


[Principles in prevention, early detection, treatment and after care of endometrial cancer].
The paper is the summary of a workshop and contains guidelines for prophylaxis, early detection, treatment and follow-up of endometrial cancer recommended by the Central Institute of Cancer Research as well as the Medical Associations of the German Democratic Republic.


Bis[tetrakis(triphenylphosphine-kappaP)silver(I)] di-mutrifluoroacetato-kappa4O:O'-bis[bis(trifluoroacetato-kappaO)stannate(IV)].
The crystal structure of the title compound, [Ag(C18H15P)4]2[Sn2(CH3)4(CF3CO2)6], consists of discrete tetrahedral cations and trans-C2SnO4 octahedral dianions [C-Sn-C = 154.6 (2) degrees ]. The dianion lies about a center of inversion and the two Sn atoms are linked unevenly by the carboxylate unit [Sn-O = 2.291 (3) A and Sn <-- O = 2.818 (3) A].


Intravenous antidepressants: a review.
Antidepressant medications have an onset of action of several weeks and have moderate efficacy. Their mode of administration is oral (p.o.). Some clinicians wondered whether intravenous (i.v.) administration would speed onset of action and increase efficacy. In this article we review controlled studies on i.v. administration of antidepressants. These include clomipramine, citalopram, and other antidepressants. Overall these studies do not support increased efficacy of i.v. over p.o.administration but there are suggestions of a faster onset of action. In one study i.v. citalopram showed superior response rates over p.o. citalopram (79% vs. 63%) in severely depressed patients at 8 weeks.


Two-way avoidance and acute shock stress induced alterations of regional noradrenergic, dopaminergic and serotonergic activity in Roman high- and low-avoidance rats.
Various brain regions of male RHA/Verh and RLA/Verh rats were dissected out and deep-frozen immediately after 30 min in a shuttle box involving a) no shock (control), b) 40 inescapable shocks or c) 40 avoidable shocks. The RHA/Verh rats used in the "c" category exhibited about 80-85% learned avoidance. 5-HT, 5-HIAA, NA, MHPG-SO4, DA, DOPAC and HVA levels were subsequently measured in selected regions. NA levels were considerably reduced in the hypothalamus and pons/medulla of both selected lines of rats after acute shock stress, supporting the results of numerous studies which have indicated that NA turnover is nonspecifically increased by all types of stress, at least in those regions. An increase in cortical MHPG-SO4 and a reduction in hypothalamic 5-HT seen after avoidance learning also occurred after shock stress in RHA/Verh rats. Whereas RLA/Verh rats showed an increased metabolism of 5-HT in the hypothalamus and pons/medulla after shock stress, RHA/Verh rats showed the opposite response in the hypothalamus after the same treatment. A reduction in 5-HT metabolism was also evident in RHA/Verh rats, after avoidance learning, in the cortex, hippocampus and hypothalamus. These results indicated, pending further studies regarding, for example, possible genetic differences in tryptophan uptake and utilization, that 5-HT probably plays at least a modulatory role in the reaction to stress, and in avoidance behavior. That role may be either active or passive, depending upon the emotional status of the subjects. In regard to the DA responses measured in striatum and hypothalamus of the two rat lines, some divergent inter-treatment tendencies, as well as some similarities, were seen in DA metabolism in both regions, but almost none of the differences were significant.


The chemokine CXCL12 and regulation of HSC and B lymphocyte development in the bone marrow niche.
Chemokines are a family of small structurally related molecules that were recognized originally for their ability to regulate cell trafficking in inflammation. We have found that a chemokine, CXC chemokine ligand 12/stromal cell-derived factor/pre-B-cell growth stimulating factor (CXCL12/ SDF-1/PBSF) and its physiologic receptor CXCR4 are essential for hematopoiesis including B lymphocyte development and colonization of bone marrow by hematopoietic cells including hematopoietic stem cells (HSCs) during ontogeny as well as cardiovascular formation. Recently, we have shown that a small population of reticular stromal cells, which has high levels of CXCL 12 expression, termed CXCL 2-abundant reticular (CAR) cells have several long processes and are scattered throughout adult bone marrow. In addition, most of the earliest B cell precursors, pre-pro-B cells and end-stage B cells, plasma cells, which require CXCL12, as well as primitive hematopoietic progenitors were attached to the CAR cells. These results suggest that the CAR cells function as cellular niches for B-cell development and that CXCL12 plays a role in maintaining the blood cells in the niches. It has been hypothesized that osteoprogenitors reside in the stromal tissues of bone marrow and play an important role in hematopoiesis. The nature and functions of CAR cells are important issues for the future.


Outcomes of Restrictive and Hypertrophic Cardiomyopathies After LVAD: An INTERMACS Analysis.
Patients with restrictive (RCM) and hypertrophic (HCM) cardiomyopathies are felt to be a difficult population to treat with left ventricular assist device (LVAD) therapy. Scarce data exist on outcomes of continuous-flow (CF) LVAD support in these challenging patient cohorts. The Interagency Registry for Mechanically Assisted Circulatory Support Registry was queried for all patients with RCM (n = 94) and HCM (n = 104) who underwent CF LVAD implantation between March 2008 and March 2014. Survival, adverse event rates, baseline demographics, echocardiography parameters, and competing outcomes were compared with patients with dilated cardiomyopathy (DCM) (n = 8749). Left ventricular size was smaller and baseline EF was higher in RCM and HCM compared with DCM patients. Nonetheless, these parameters were not completely normal in the RCM and HCM groups, suggesting that most of these patients exhibited features of a DCM and represented a mixed phenotype. In these specific patient populations, survival up to 4 years was not different among the 3 groups (log rank 0.25) and competing outcomes at 1 year were similar. In the subgroup of patients with very small ventricles (ie, < 5.0 cm), survival was far inferior. Finally, overall rates of right ventricular assist device requirement, hemolysis, pump dysfunction, and cardiac arrhythmias were similar among the 3 groups. Relatively few patients with HCM and RCM undergo CF LVAD implantation, and most that do display some features of a DCM. Overall survival and adverse event profiles of these patients were similar to traditional DCM patients; however, in those with very small ventricles, survival was inferior.


Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results From a Randomized, Double-Blind, Placebo-Controlled, Phase III Study.
Treating upper facial lines (UFL)-a combination of glabellar frown lines (GFL), horizontal forehead lines (HFL), and lateral periorbital lines (LPL)-is a common aesthetic practice. To provide the first placebo-controlled evidence of the efficacy and safety of incobotulinumtoxinA for UFL. Healthy subjects (≥18 years) with moderate-to-severe GFL, HFL, and LPL on the Merz Aesthetics Scales (MAS) at maximum contraction were randomized to incobotulinumtoxinA or placebo. For incobotulinumtoxinA, 54 to 64 U were administered (GFL, 20 U; HFL, 10-20 U; LPL, 24 U). Investigator-assessed MAS scores were evaluated for each area at maximum contraction on Day 30, both separately (responder = score of "none" [0] or "mild" [1]) and combined (UFL; sum score ≤3). Adverse events were recorded until 120 ± 7 days after treatment. Overall, 156 subjects were treated (incobotulinumtoxinA: 105; placebo: 51). On Day 30 at maximum contraction, a significant (p ≤ .0001) effect of incobotulinumtoxinA versus placebo for GFL (84.5% vs 0.0%, respectively), HFL (70.9% vs 2.1%), LPL (64.1% vs 2.1%), and UFL combination (55.3% vs 0.0%) was demonstrated for investigator-assessed "none" or "mild" scores. Two cases of mild eyelid ptosis occurred with incobotulinumtoxinA. IncobotulinumtoxinA demonstrated significant efficacy in treating GFL, HFL, and LPL separately and combined, as well as a good safety profile.


Is it important to decipher the heterogeneity of "normal karyotype AML"?
Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease.


Phosphorylation of three proteins in the signaling pathway of bacterial chemotaxis.
Six cytoplasmic che gene products are required for signal transduction in bacterial chemotaxis, but the nature of their biochemical interactions is not known. We show that in vitro the CheA protein becomes autophosphorylated in the presence of ATP. In addition, the phosphate group on CheA can be rapidly transferred to CheB, a protein involved in adaptation to stimuli, or to CheY, a protein involved in the excitation response. The phosphorylation of CheB and CheY is transient; they readily dephosphorylate. We have also found that CheZ, a protein that appears to antagonize CheY function in vivo, accelerates the hydrolysis of the phosphate on CheY. These results suggest that signal transduction in bacterial chemotaxis may involve the flow of phosphate through a cascade of phosphorylated protein intermediates.


Modified nonlinear complex diffusion filter (MNCDF).
Speckle noise removal is the most important step in the processing of echocardiographic images. A speckle-free image produces useful information to diagnose heart-related diseases. Images which contain low noise and sharp edges are more easily analyzed by the clinicians. This noise removal stage is also a preprocessing stage in segmentation techniques. A new formulation has been proposed for a well-known nonlinear complex diffusion filter (NCDF). Its diffusion coefficient and the time step size are modified to give fast processing and better results. An investigation has been performed among nine patients suffering from mitral regurgitation. Images have been taken with 2D echo in apical and parasternal views. The peak signal-to-noise ratio (PSNR), universal quality index (Qi), mean absolute error (MAE), mean square error (MSE), and root mean square error (RMSE) have been calculated, and the results show that the proposed method is much better than the previous filters for echocardiographic images. The proposed method, modified nonlinear complex diffusion filter (MNCDF), smooths the homogeneous area and enhances the fine details.


Effects of amputation and Corynebacterium parvum on tumour metastases in mice.
The effects of operation (lower-limb amputation) on the growth of the Lewis lung tumour and its metastases were studied. The role of C. parvum in counteracting these effects was investigated. Anaesthesia alone or with amputation did not affect primary tumour growth. C. parvum depressed this growth. Anaesthesia did not affect the number of pulmonary metastases, but amputation caused a significant increase. C. parvum inhibited metastases and completely counteracted the effects of operation on them. Large doses of cortisone acetate significantly increased metastases but small doses had no effect. Experiments with adrenalectomized mice suggested the effects of operation were due to non-specific stress.


Pediatric Oral Diseases.
General dentists usually serve as first-line providers for pediatric patients and the gateway to their oral health. Even though general dentists are trained to be able to treat children, dental education instruction can vary greatly. These differences heavily influence the individual practitioner's knowledge base and comfort level in providing care to this vulnerable population. It is important for general dentists to be able to identify the presence of pediatric oral lesions. This article provides an overview of common pediatric oral lesions that general dentists may encounter in everyday practice.


Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): dose-dependent expulsion of adult worms.
The survival of Heligmosomoides polygyrus was monitored during primary infections in female C57Bl10, NIH and BALB/c mice at low and high intensities of infection. Survivorship curves were fitted for each data set and analysed. C57Bl10 mice, given either low or high intensities of infection, harboured parasites for 28-37 weeks, heavier infections surviving marginally but significantly longer. Essentially the survivorship curves of H. polygyrus in C57Bl10 mice could be accounted for by senility, the increased probability of worms with a longer life-span occurring at high infection intensities and, possibly, by a contribution from host-protective immune mechanisms in the terminal stages of infection. The pattern of survivorship was different in NIH and BALB/c mice. NIH mice showed weak but significant density-dependent suppression of parasite loss and infections in this strain did not exceed 27.5 weeks in duration. Primary infections in BALB/c mice were briefer still and showed marked dependence on parasite density. Thus low-level infections lasted 10-15 weeks whereas heavier infections survived for 21-34 weeks. The data suggested that both strains developed host-protective responses to adult H. polygyrus and that parasite survival was curtailed earlier than would be expected if senility alone was involved. The hybrid strains (C57Bl10 x NIH)F1 and (B10G x NIH)F1 both expelled H. polygyrus in a dose-dependent manner, worm loss commencing within 10 weeks of infection. In some experiments worm loss was clearly evident by weeks 4 and 6. These hybrid strains showed gene complementation in that adult worms were cleared considerably earlier than in parental strains.


Microdetermination of proteoglycans and glycosaminoglycans in the presence of guanidine hydrochloride.
This report describes a microprocedure that may be used for direct measurement of proteoglycans and glycosaminoglycans, after chromatographic elution with chaotropic reagents. The assay is based on the ability of the sulfated glycosaminoglycans to bind to the cationic dye, dimethylmethylene blue, in solution. Inclusion of guanidinium chloride (0.24 M) in the assay resulted in a stable dye-proteoglycan interaction, but eliminated the interference of other anionic macromolecules such as DNA. The assay is rapid, sensitive, and reproducible and therefore useful for processing several samples. Finally, the procedure can be used for quantitative determination of several types of proteoglycans and glycosaminoglycans.


Vibrio cholerae-loaded poly(DL lactide co-glycolide) microparticles.
Vibrio cholerae (VC)-loaded microparticles were prepared using poly(DL lactide-co-glycolide) with a water-in-oil-in-water emulsion/solvent extraction technique. Particle characteristics including size distribution, VC-loading efficiencies, and in-vitro release pattern were investigated. The dispersed phase was PLG dissolved in dichloromethane, and the continuous phase was water containing PVP as a stabilizer with varied sodium chloride concentrations. VC was successfully entrapped in the microparticles with trapping efficiencies up to 97.8%, a loading level of 55.4 g/mg, and particle size of 3.8 microm. Using 10% w/v PVP with 5% w/v NaCl in the continuous phase resulted in a higher loading level (55.4 +/- 6.9 g/mg), loading efficiency (97.8%), core region content (25.7 +/- 1.9 g/mg) and lower surface content (6.2 +/- 0.9 g/mg) than without NaCl (loading content: 40.7 +/- 5.1 g/mg; loading efficiency 52.1%; core region content: 8.3 +/- 0.5 g/mg; surface content: 19.5 +/- 1.1 g/mg). A linear release profile from VC-loaded microparticles was found. A preliminary animal oral administration study indicated that the VC-loaded microparticles, as an oral delivery system, have shown effective immunogencity in rats for 2 months. The VC incorporation and physicochemical characterization data obtained in this study may be relevant in optimising the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.


Arrhythmia and exercise intolerance in Fontan patients: current status and future burden.
Long-term survival after the Fontan procedure shows excellent results but is associated with a persistent risk of arrhythmias and exercise intolerance. We aimed to analyze the current burden of clinically relevant arrhythmia and severe exercise intolerance in Danish Fontan patients and furthermore, to estimate the future burden from analysis of mortality and the current burden related to age. All Danish citizens with Fontan completion from 1981 to 2009 were identified (n=235). Surviving patients performed exercise test, Holter monitoring, echocardiography, pulmonary function test, and blood sampling and medical history was retrieved from medical records. Twenty-six (11%) patients died or had heart transplantation (HTx) after a mean (± SD) post-Fontan follow-up of 8.3 ± 5.7 years. Excluding perioperative deaths (n=8), a linear probability of HTx-free survival was observed and estimated to 99.1% per year. Prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age and was found in 32% and 85% of patients ≥ 20 years, respectively. Thus, from survival data and logistic regression models the future prevalence of patients, clinically relevant arrhythmia and severe exercise intolerance were estimated, revealing a considerable augmentation. Furthermore, resting and maximum cardiac index, resting stroke volume index and pulmonary diffusing capacity decreased significantly with age while diastolic and systolic ventricular function was unchanged. The prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age in Danish Fontan patients. The future Fontan burden was estimated showing an increase in the prevalence of older patients, clinically relevant arrhythmia, and severe exercise intolerance.


HIV-1 propagation is highly dependent on basal levels of the restriction factor BST2.
BST2 is an interferon-inducible antiviral host protein antagonized by HIV-1 Vpu that entraps nascent HIV-1 virions on the cell surface. Unexpectedly, we find that HIV-1 lacking Nef can revert to full replication competence simply by losing the ability to antagonize BST2. Using gene editing together with cell sorting, we demonstrate that even the propagation of wild-type HIV-1 is strikingly dependent on BST2, including in primary human cells. HIV-1 propagation in BST2−/− populations can be fully rescued by exogenous BST2 irrespective of its capacity to signal and even by an artificial BST2-like protein that shares its virion entrapment activity but lacks sequence homology. Counterintuitively, our results reveal that HIV-1 propagation is critically dependent on basal levels of virion tethering by a key component of innate antiviral immunity.


Association of food allergy and atopic dermatitis exacerbations.
Atopic dermatitis (AD) and food allergy frequently coexist in children. To examine the association between food allergy and AD. Between 2001 and 2011, children referred to our tertiary care center underwent double-blind, placebo-controlled food challenges (DBPCFCs) for one or more suspected food allergies as part of regular care. Immediate reactions were observed and recorded by allergy nursing staff, whereas late reactions were ascertained by semistructured telephone interview 48 hours after challenge. To test to which degree specific IgE results were predictive in the outcome of DBPCFCs in children with and without (previous and current) AD, logistic regression analysis was performed. A total of 1186 DBPCFCs were studied. Sensitization to foods occurred significantly more often in children with previous AD. The association between specific IgE results and the outcome of DBPCFCs was significant for children with and without (previous and current) AD but stronger for children without current AD. The positivity rate of DBPCFCs in children with mild, moderate, and severe AD was 53.3%, 51.7%, and 100%, respectively. Children with AD and a history of worsening AD as their only symptom reacted as often to placebo as to challenge food. Children with current AD are more frequently asymptomatically sensitized to the foods in question than those without AD. In addition, children suspected of food allergy should be considered for testing, regardless of the severity of their AD. Our results suggest that children with exacerbation of AD in the absence of other allergic symptoms are unlikely to be food allergic.


Neurocognitive Effects of Sleep Disruption in Children and Adolescents.
A main childhood task is learning. In this task, the role of sleep is increasingly demonstrated. Although most literature examining this role focuses on preadolescence and middle adolescence, some studies apply napping designs in preschoolers. Studies overall conclude that without proper sleep a child's cognitive abilities suffer, but questions on how and to what extent linger. Observational studies show the hazards of potential confounders such as an individual's resilience to poor sleep as well as developmental risk factors (eg, disorders, stressors). A better understanding of cognitive sleep neuroscience may have a big impact on pediatric sleep research and clinical applications.


Enantioselective effects of paclobutrazol and its enantiomers on glycolipid metabolism in zebrafish (Danio rerio).
Paclobutrazol is a plant growth inhibitor widely used in agricultural production. However, toxicology studies of paclobutrazol enantiomers towards aquatic organisms are limited. Herein, effects of paclobutrazol and its two enantiomers (2R, 3R; 2S, 3S) on glycolipid metabolism of zebrafish have been systemically explored at the concentration of 10 mg/L through biochemical analyses, LC-MS/MS, molecular dynamics simulation, and gene expression. In all treatments, the contents of glucose, citric acid and lactate significantly were increased while the glycogen and pyruvate contents were decreased, in which (2R, 3R)-paclobutrazol exhibited a greater effect than the (2S, 3S)-enantiomer (P < 0.05). Then, activities of hexokinase and lactate dehydrogenase in (2R, 3R)-paclobutrazol treatment were 0.74- and 1.18-fold higher than (2S, 3S)-enantiomer treatment, respectively (P < 0.001), and the results of molecular dynamics simulation revealed that the binding free energy of hexokinase 1 to (2R, 3R)-paclobutrazol was higher than that to the antipode. Moreover, lipids including triglycerides, total cholesterol, fatty acids, bile acids and glycerophospholipids in zebrafish were strikingly affected after paclobutrazol exposure. The (2R, 3R)-paclobutrazol-treated group showed the most obvious changes, indicating that it possessed much stronger disruption ability on the lipid metabolism of zebrafish. Furthermore, qRT-PCR analysis results revealed that (2R, 3R)-enantiomer significantly impacted expressions of glycolipid metabolism-related genes (hk1, g6pc, pck1, pk, aco, cebpa, cyp51, fasn and ppara) in zebrafish than (2S, 3S)-enantiomer (P < 0.05). Briefly, this study provides new evidences for the toxicity of paclobutrazol to aquatic organisms and the potential risk to human health at the chiral level.


Infectivity of cryopreserved Babesia bovis, Babesia bigemina and Anaplasma centrale for cattle after thawing, dilution and incubation at 30 degrees C.
Blood containing either Babesia bovis, Babesia bigemina or Anaplasma centrale was mixed with an equal volume of 3 M glycerol in phosphate-buffered saline with or without glucose and then stored in liquid nitrogen for 2-30 days. After being thawed, the parasitized blood was subjected to various procedures, including dilution up to 1000-fold followed by incubation at 30 or 4 degrees C for 8 h, before infectivity of the parasites was tested in a total of 70 cattle. The results showed that the blood cryopreserved with glycerol remained highly infective after thawing, despite dilution and incubation for 8 h at 30 degrees C. The results have practical application in the use of frozen, live vaccines against bovine babesiosis and anaplasmosis.


Comparison of Clinical Outcomes Following One versus Two Stage Hybrid Repair of Thoraco-Abdominal Aortic Aneurysms: A Comprehensive Meta-Analysis.
For thoraco-abdominal aortic aneurysms (TAAA), it is unclear whether it is better to perform hybrid repair in one (single) or two stages (staged). This study aimed to compare the clinical outcomes of single vs. staged hybrid repair of TAAA. The Medline, Embase, and Cochrane Databases (1 January 1994 to 11 May 2020) were searched for studies on hybrid repair of TAAA. Cohort studies and case series reporting outcomes of single and staged hybrid repair of TAAA were eligible for inclusion. The Newcastle-Ottawa scale and an 18 item tool were used to assess the risk of bias. The primary outcome was 30 day mortality, and the secondary outcomes included post-operative complications, overall survival, and other mid term events. A random effects model was used to calculate pooled estimates. A total of 37 studies was included in the meta-analysis. The quality assessment of the included studies suggested low or moderate risk of bias. The pooled estimates for aneurysm rupture and death during stage interval were 2% (95% CI 0%-4%, I2 = 0%) and 4% (95% CI 2%-7%, I2 = 0%), respectively. Single repair was associated with a significantly higher 30 day risk of death when compared with patients who completed staged procedures successfully (OR 2.64, 95% CI 1.36-5.12, I2 = 0%). Staged repair also had lower incidence of major adverse cardiac events (MACE) (single: 10%, 95% CI 5%-16%; staged: 2%, 95% CI 0%-5%) and intestinal complications (single: 15%, 95% CI 8%-25%; staged: 3%, 95% CI 1%-6%). For mid term outcomes, single and staged repair had comparable 12 month overall survival, aneurysm related mortality, rate of re-intervention, and graft patency. Two stage hybrid repair may represent a better choice for patients with controlled risk of aneurysm rupture, because it can provide lower 30 day mortality risks, MACE, and intestinal complications, as well as comparable mid term outcomes. Randomised controlled trials are needed to ascertain the effect of repair staging in patients for elective TAAA.


Effects of fishing on parasitism in a sparid fish: contrasts between two areas of the Western Mediterranean.
This study addressed the impacts of fishing on the rates of parasitism using the sparid Boops boops as a model fish species. Using a large suite of parasite species in B. boops, with different life histories, transmission pathways and host specificity, we compared parasite diversity, prevalence, abundance and community structure at two Mediterranean localities in the Balearic Sea, Santa Pola Bay and the Gulf of Oran, that are characterised by a contrasting pattern of fishing of B. boops. A total of 360 fish were examined comprising nine distinct samples collected during the warm and the cold weather months. A total of 29 parasite species were identified, with eight species in common for the two localities. Parasite component communities at Santa Pola Bay were more species rich and abundant than those at the Gulf of Oran and exhibited a different community structure. Of the eight common taxa used in the quantitative comparisons, five exhibited significant difference for prevalence between the two localities, four having substantially higher prevalence at Santa Pola and only one being more prevalent at the Gulf of Oran. Two specialist trematodes and the sparid generalist monogenean exhibited consistently higher prevalence and abundance at Santa Pola Bay than at the Gulf of Oran; the two specialists were also identified as key species for assigning individual fish to their locality of origin. The consistent differences in the richness, abundance and structure of parasite communities in B. boops from Santa Pola Bay and the Gulf of Oran may reflect the contrasting patterns of exploitation of the populations of this fish host at the two localities.


The mechanism of electron transfer in laccase-catalysed reactions.
1. The reaction of the electron acceptors in Rhus vernicifera laccase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 18.104.22.168) have been studied with stopped-flow and rapid-freeze EPR techniques. The studies have been directed mainly towards elucidation of the role of the type 2Cu2+ as a possible pH-sensitve regulator of electron transfer. 2. Anaerobic reduction experiments with Rhus laccase indicate that the type 1 and 2 sites contribute one electron each to the reduction of the two-electron-accepting type 3 site. There is also evidence that the reduction of the type 1 Cu2+ triggers the reduction of the type 2 Cu2+. 3. Only at pH values at which the reduction of the two-electron acceptor is limited by a slow intramolecular reaction can an OH- be displaced from the type 2 Cu2+ by the inhibitor F-. 4. A model describing the role of the electron-accepting sites in catalysis is formulated.


Studies on the use of NE-4C embryonic neuroectodermal stem cells for targeting brain tumour.
Neural stem cells were suggested to migrate to and invade intracranial gliomas. In the presented studies, interactions of NE-4C embryonic neural stem cells were investigated with C6 and Gl261, LL and U87, glioblastoma cells or with primary astrocytes. Glioma-derived humoral factors did not influence the proliferation of stem cells. NE-4C-derived humoral factors did not alter the proliferation of Gl261 and U87 cells, but increased the mitotic activity of C6 cells and that of astrocytes. In chimera-aggregates, all types of glioma cells co-aggregated with astrocytes, but most of them segregated from stem cells. Complete intercalation of stem and tumour cells was detected only in chimera-aggregates of Gl261 glioma and NE-4C cells. If mixed suspensions of NE-4C and Gl261 cells were injected into the brain, stem cells survived and grew inside the tumour mass. NE-4C stem cells, however, did not migrate towards the tumour, if implanted near to Gl261 tumours established in the adult mouse forebrain. The observations indicate that not all types of stem cells could be used for targeting all sorts of brain tumours.


Meniscal Load and Load Distribution in the Canine Stifle after Modified Tibial Tuberosity Advancement with 9 mm and 12 mm Cranialization of the Tibial Tuberosity in Different Standing Angles.
The aim of this study was to investigate the kinetic and kinematic changes in the stifle after a modified tibial tuberosity advancement (TTA) with 9 and 12 mm cranialization of the tibial tuberosity in different standing angles. Biomechanical ex vivo study using seven unpaired canine cadaver hindlimbs. Sham TTA surgery was performed. Motion sensors were fixed to the tibia and the femur for kinematic data acquisition. Pressure mapping sensors were placed between femur and both menisci. Thirty percent body weight was applied to the limbs with the stifle in 135 or 145 degrees of extension. Each knee was tested in 135 degrees with intact cranial cruciate ligament (CCL) and deficient CCL with 12 mm cranialization of the tibial tuberosity in 135 and 145 degrees of extension. The last two tests were repeated with 9 mm. Transection of the CCL altered kinematics and kinetics. Tibial tuberosity advancement with 12 mm cranialization sufficiently restored stifle kinematics in 135 and 145 degrees but 9 mm TTA failed to do so in 135 degrees. The same effects were seen for internal rotation of the tibia. After TTA, a significant reduction in the force acting on both menisci was detected. Tibial tuberosity advancement could restore stifle kinematics and meniscal kinetics after transection of the CCL ex vivo in the present study. Tibial tuberosity advancement reduced the contact force ratio on both menisci significantly. No changes of peak pressure and peak pressure location occurred following TTA under any of the tested experimental settings. Increased stifle extension (145 degrees) might lead to more stability, contradictory to biomechanical theory.


Constitutively active Src facilitates NGF-induced phosphorylation of TrkA and causes enhancement of the MAPK signaling in SK-N-MC cells.
Here we investigated a biological association of constitutively active Src with TrkA in SK-N-MC human neuroblastoma cells. Activation of TrkA and extracellular signal-regulated kinase (ERK) by nerve growth factor (NGF) was inhibited by pretreatment with PP2, an inhibitor of Src family kinases. Moreover, NGF-induced phosphorylation of TrkA and ERK was also attenuated by the transfection with a dominant-negative src construct. On the other hand, the transfection with a constitutively active src construct enhanced these phosphorylations. In addition, we showed that active Src phosphorylates TrkA directly in vitro, and that Src associates with TrkA through Grb2 after NGF stimulation. These results suggest that constitutively active Src that associates with TrkA through Grb2 after NGF stimulation participates in TrkA phosphorylation and in turn enhances the mitogen-activated protein kinase signaling in SK-N-MC cells.


The Second Edition of Motivations Associated with Food Choices and Eating Practices.
Eating patterns are linked with both environmental and behavioural factors [...].


Controls upon biomass losses and char production from prescribed burning on UK moorland.
Prescribed burning is a common management technique used across many areas of the UK uplands. However, there are few data sets that assess the loss of biomass during burning and even fewer data on the effect of burning on above-ground carbon stocks and production of char. During fire the production of char occurs which represents a transfer of carbon from the short term bio-atmospheric cycle to the longer term geological cycle. However, biomass is consumed leading to the reduction in litter formation which is the principal mechanism for peat formation. This study aims to solve the problem of whether loss of biomass during a fire is ever outweighed by the production of refractory forms of carbon during the fire. This study combines both a laboratory study of char production with an assessment of biomass loss from a series of field burns from moorland in the Peak District, UK. The laboratory results show that there are significant effects due to ambient temperature but the most important control on dry mass loss is the maximum burn temperature. Burn temperature was also found to be linearly related to the production of char in the burn products. Optimisation of dry mass loss, char production and carbon content shows that the production of char from certain fires could store more carbon in the ecosystem than if there had been no fire. Field results show that approximately 75% of the biomass and carbon were lost through combustion, a figure comparable to other studies of prescribed fire in other settings. Char-C production was approximately 2.6% of the carbon consumed during the fire. This study has shown that there are conditions (fast burns at high temperatures) under which prescribed fire may increase C sequestration through char production and that these conditions are within existing management options available to practitioners.


Biofilm formation by Pseudomonas aeruginosa in solid murine tumors - a novel model system.
The ability of opportunistic bacterial pathogens to grow in biofilms is decisive in the pathogenesis of chronic infectious diseases. Growth within biofilms does not only protect the bacteria against the host immune system but also from the killing by antimicrobial agents. Here, we introduce a mouse model in which intravenously administered planktonic Pseudomonas aeruginosa bacteria are enriched in transplantable subcutaneous mouse tumors. Electron microscopy images provide evidence that such bacteria reside in the tumor tissue within biofilm structures. Immunohistology furthermore demonstrated that infection of the tumor tissue elicits a host response characterized by strong neutrophilic influx. Interestingly, the biofilm defective PA14 pqsA transposon mutant formed less biofilm in vivo and was more susceptible to clearance by intravenous ciprofloxacin treatment as compared to the wild-type control. In conclusion, we have established an experimentally tractable model that may serve to identify novel bacterial and host factors important for in vivo biofilm formation and to re-evaluate bactericidal and anti-biofilm effects of currently used and novel antibacterial compounds.


The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD.
Posttraumatic Stress Disorder (PTSD) is commonly treated with exposure-based cognitive therapies that are based on the principles of fear acquisition and extinction learning. Elevations in one of the major endocannabinoids (anandamide) either via inhibition of the primary degrading enzyme (fatty acid amide hydrolase; FAAH) or via a genetic variation in the FAAH gene (C385A; rs324420) has resulted in accelerated extinction learning and enhanced extinction recall among healthy adults. These results suggest that targeting FAAH may be a promising therapeutic approach for PTSD. However, these effects have not yet been comprehensively examined in a PTSD population. The current study examined whether genetic variation in the FAAH gene (CC [n = 49] vs AA/AC [n = 36] allele carriers) influences physiological (skin conductance), cognitive (threat expectancy), and neural (network and voxel-wise activation) indices of fear acquisition and extinction learning among a sample of adult women with PTSD (N = 85). The physiological, cognitive, and neural signatures of fear acquisition and extinction learning varied as a function of whether or not individuals possess the FAAH C385A polymorphism. For instance, we report divergent responding between CC and AA/AC allele carriers to CS + vs CS- in limbic and striatum networks and overall greater activation throughout the task among AA/AC allele carriers in several regions [e.g., inferior frontal, middle frontal, parietal] that are highly consistent with a frontoparietal network involved in higher-order executive functions. These results suggest that genetic variation within the FAAH gene influences physiological, cognitive, and neural signatures of fear learning in women with PTSD. In order to advance our understanding of the efficacy of FAAH inhibition as a treatment for PTSD, future clinical trials in this area should assess genetic variation in the FAAH gene in order to fully depict and differentiate the acute effects of a drug manipulation (FAAH inhibition) from more chronic (genetic) influences on fear extinction processes.


Toward a SERS Diagnostic Tool for Discrimination between Cancerous and Normal Bladder Tissues via Analysis of the Extracellular Fluid.
Vibrational spectroscopy provides the possibility for sensitive and precise detection of chemical changes in biomolecules due to development of cancers. In this work, label-free near-infrared surface enhanced Raman spectroscopy (SERS) was applied for the differentiation between cancerous and normal human bladder tissues via analysis of the extracellular fluid of the tissue. Specific cancer-related SERS marker bands were identified by using a 1064 nm excitation wavelength. The prominent spectral marker band was found to be located near 1052 cm-1 and was assigned to the C-C, C-O, and C-N stretching vibrations of lactic acid and/or cysteine molecules. The correct identification of 80% of samples is achieved with even limited data set and could be further improved. The further development of such a detection method could be implemented in clinical practice for the aid of surgeons in determining of boundaries of malignant tumors during the surgery.


Further studies of a staggered hybrid zone in Mus musculus domesticus (the house mouse).
In the extreme north-east of Scotland (near the village of John o'Groats) there is a small karyotypic race of house mouse (2n = 32), characterized by four metacentric chromosomes 4.10, 9.12, 6.13 and 11.14. We present new data on the hybrid zone between this form and the standard race (2n = 40) and show an association between race and habitat. In a transect south of John o'Groats we demonstrate that the clines for arm combinations 4.10 and 9.12 are staggered relative to the clines for 6.13 and 11.14, confirming previous data collected along an east-west transect (Searle, 1991). There are populations within the John o'Groats-standard hybrid zone dominated by individuals with 36 chromosomes (homozygous for 4.10 and 9.12), which may represent a novel karyotypic form that has arisen within the zone. Alternatively the type with 36 chromosomes may have been the progenitor of the John o'Groats race. Additional cytogenetic interest is provided by the occurrence of a homogeneous staining region on one or both copies of chromosome 1 in some mice from the zone.


HLA-DP diversity is associated with improved response to SARS-Cov-2 vaccine in hematopoietic stem cell transplant recipients.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients show lower humoral vaccine responsiveness than immunocompetent individuals. HLA diversity, measured by the HLA evolutionary divergence (HED) metrics, reflects the diversity of the antigenic repertoire presented to T cells, and has been shown to predict response to cancer immunotherapy. We retrospectively investigated the association of HED with humoral response to SARS-CoV-2 vaccine in allo-HSCT recipients. HED was calculated as pairwise genetic distance between alleles at HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci in recipients and their donors. Low anti-spike IgG levels (<30 BAU/mL) were associated with short time from allo-SCT and low donor DPB1-HED, mostly related to donor DPB1 homozygosity. The diversity of donor HLA-DP molecules, assessed by heterozygosity or sequence divergence, may thus impact the efficacy of donor-derived CD4 T cells to sustain vaccine-mediated antibody response in allo-HSCT recipients.


Placental Impact of Dietary Supplements: More Than Micronutrients.
Maternal nutrition is a key modifier of fetal growth and development. However, many maternal diets in the United States do not meet nutritional recommendations. Dietary supplementation is therefore necessary to meet nutritional goals. The effects of many supplements on placental development and function are poorly understood. In this review, we address the therapeutic potential of maternal dietary supplementation on placental development and function in both healthy and complicated pregnancies. This is a narrative review of original research articles published between February 1970 and July 2020 on dietary supplements consumed during pregnancy and placental outcomes (including nutrient uptake, metabolism and delivery, as well as growth and efficiency). Impacts of placental changes on fetal outcomes were also reviewed. Both human and animal studies were included. We found evidence of a potential therapeutic benefit of several supplements on maternal and fetal outcomes via their placental impacts. Our review supports a role for probiotics as a placental therapeutic, with effects that include improved inflammation and lipid metabolism, which may prevent preterm birth and poor placental efficiency. Supplementation with omega-3 fatty acids (as found in fish oil) during pregnancy tempers the negative effects of maternal obesity but may have little placental impact in healthy lean women. The beneficial effects of choline supplementation on maternal health and fetal growth are largely attributable to its placental impacts. l-arginine supplementation has a potent provascularization effect on the placenta, which may underlie its fetal growth-promoting properties. The placenta is exquisitely sensitive to dietary supplements. Pregnant women should consult their health care practitioner before continuing or initiating use of a dietary supplement. Because little is known about impacts of many supplements on placental and long-term offspring health, more research is required before robust clinical recommendations can be made.


Fungal Keratitis Secondary to Trametes betulina: A Case Report and Review of Literature.
We report the first case of human infection and keratitis secondary to Trametes betulina, a rare filamentous fungus. Clinical examination including external and slit-lamp examination and corneal scrapings with microbiologic evaluation were performed on a patient with chronic allergic conjunctivitis, entropion and a long-standing corneal ulcer resistant to treatment. The culture from the corneal scraping revealed a basidiomycetous fungus which was submitted for identification. DNA extraction with sequencing and analysis of the ITS and D1/D2 regions were performed on the isolate and demonstrated 100% similarity to Lenzites betulina/Trametes betulina. Susceptibility testing demonstrated potent in vitro activity of voriconazole (MIC < 0.03 μg/ml). The patient was treated with voriconazole, and the corneal ulcer and infiltrate resolved. The infection resulted in corneal thinning and a dense central corneal scar. Penetrating keratoplasty was performed 5 months after diagnosis and treatment and revealed stromal scarring without fungal elements. This is the first reported case of keratitis caused by Trametes betulina. This organism should be considered in the differential diagnosis for rare filamentous fungal keratitis and its treatment with voriconazole also noted.


Clinical features of Behçet's disease in patients in the Sultanate of Oman; the significance of antiphospholipid antibodies?
The prevalence of symptoms in 34 Omani patients with Behcet's disease (BD) was: recurrent oral ulceration 100%, arthritis/arthralgia and genital ulceration 74% each, folliculitis 64%, neurological lesions 62%, retinal vasculitis 30%, iritis and hypopyon 26%, gastrointestinal lesions 12%, venous thrombosis and cardiovascular lesions 9% each, and pleuropulmonary lesions and epididymitis 6% each. Antiphospholipid (APL) antibodies (both anticardiolipin [ACAs] and anti-beta2 glycoprotein I [abeta2GPIs]) were present in 11/34 (32%) of the BD patients and in 54/73 (74%) of Omani patients with systemic lupus erythematosus (SLE) (chi2 = 21.2, P<0.001). In patients possessing APL antibodies, there was no significant difference in mean antibody levels between BD and SLE patients. IgM isotype antibodies, in the absence of IgG, were more prevalent in BD (5/11) than in SLE (10/54) patients (chi2 =3.8, P = 0.05). The frequency of organ involvement was similar in patients with and without APL antibodies (chi2 = 1.226, P > 0.05). This study fails to demonstrate a pathognomonic role for APL antibodies in BD.


Abnormal mammography and sonography associated with foreign-body giant-cell reaction after stereotactic vacuum-assisted breast biopsy with carbon marking.
Carbon marking of the biopsy site and needle track following stereotactic breast biopsy in nonpalpable mammography-detected lesions provides for safe and accurate localization for subsequent surgical excision. No significant complications of carbon marking have been reported to date. To report follow-up imaging findings and histological changes (foreign-body giant-cell reaction) attributable to the use of carbon marking after vacuum breast biopsies. This was a retrospective study of 130 patients in a mammographic screening program with nonpalpable suspicious breast lesions that were referred for stereotactic directional vacuum-assisted breast biopsy with carbon marking. Histological diagnosis was benign in all cases, but 1-year follow-up mammograms demonstrated suspect findings in four of them. For all four patients, the results of the initial stereotactic vacuum-assisted biopsy were benign, but mammographic follow-up and ultrasound findings revealed suspicious changes that, in all cases, were histologically shown to be foreign-body giant-cell reactions attributable to the use of carbon. In four of 130 lesions (3%) that were carbon marked following stereotactic vacuum-assisted breast biopsy, and in which surgical excision was not required, the mammographic and ultrasound follow-up appearance of the breast simulated malignancy. The abnormality was attributable to the use of carbon, which represents a potential source of misdiagnosis.


[Breast cancer radiation therapy: Current questions in 2023].
Radiation therapy is a corner stone of breast cancer treatment as it has been shown postoperatively that it improves local control and overall survival. In recent years, multidisciplinary therapeutic strategies have evolved considerably for early-stage breast cancer, both surgically and in terms of systemic treatments or radiation therapy. Each of these developments affects other treatment components and open up new questions allowing even more personalized treatments. Essentially normofractionated a few years ago, breast radiation therapy is today very largely moderately or even ultra hypofractionated. De-escalation of the surgery of the axilla has changed the indications for lymph node radiation therapy keeping similar efficacy with reduced toxicity. Indications for radiation therapy after neoadjuvant chemotherapy remain based on pre-chemotherapy staging pending the results of ongoing randomized studies. The addition of a boost to the tumor bed significantly reduces the risk of local recurrence, but the magnitude of this benefit decreases with increasing age. The main risk factors for local recurrence are young age, the associated extended ductal in situ component, hormone receptor negative and high-grade status. The results of the simultaneous integrated boost (SIB) seem similar with normo- or moderately hypofractionated radiation therapy regimen.


Factors influencing disaster nursing core competencies of emergency nurses.
Emergency nurses are expected to provide required nursing services by using their professional expertise to reduce the risk posed by disasters. Thus, emergency nurses' disaster nursing core competencies are essential for coping with disasters. The purpose of the study reported here was to identify factors influencing the disaster nursing core competencies of emergency nurses. A survey was conducted among 231 emergency nurses working in 12 hospitals in South Korea. Data were collected on disaster-related experience, attitude, knowledge, and disaster nursing core competencies by means of a questionnaire. In multiple regression analysis, disaster-related experience exerted the strongest influence on disaster nursing core competencies, followed by disaster-related knowledge. The explanatory power of these factors was 25.6%, which was statistically significant (F=12.189, p<0.001). These findings indicate that the disaster nursing core competencies of emergency nurses could be improved through education and training programs that enhance their disaster preparedness. The nursing profession needs to participate actively in the development of disaster nursing education and training programs.


Aeromonas hydrophila upper extremity infection.
A severe soft tissue infection of the upper extremity caused by Aeromonas hydrophila followed a water skiing injury in which a tow rope caused degloving of a portion of the skin and severe contusion to underlying muscle. Infection was established within 36 hours of the injury, accompanied by fever, leukocytosis, and a foul odor. Rapid clinical improvement occurred following radical debridement of all nonviable tissue and antibiotic therapy. In cases involving water contamination, Aeromonas hydrophila infection should be suspected with the onset of a rapidly developing infection with a febrile response. Rapid surgical intervention and treatment with an aminoglycoside or a third-generation cephalosporin antibiotic is the treatment of choice.


Effect of anti-oxidants and adsorbents on tissue browning associated metabolism in Cocculus pendulus callus cultures.
Explants and callus of C. pendulus produced intense brown substances in the medium which caused necrosis. Various anti-oxidants (ascorbic acid, cysteine and dithiothreitol) and adsorbents (activated charcoal and polyvinyl pyrrolidone) were used in different concentrations to prevent browning of the tissues. These in MS medium affected differently the growth, colour and texture of the tissues. It was concluded that both peroxidase and phenolase were involved in the browning. Increased peroxidase activity and decreased phenolase activity were probably due to more peroxidative oxidation of phenols and unavailability of substrate for phenolase activity. This resulted in faster growth of tissues, which further reduced the phenolase activity.


Treatment of acute abscesses by incision, curettage and primary suture without antibiotics: a controlled clinical trial.
One hundred and thirty-seven consecutive acute superficial abscesses were randomly allocated to incision, curettage and primary suture without parenteral antibiotics (64 cases) or to conventional treatment with incision, drainage and dressings (73 cases). Wound healing was faster; 7.0 days: 25.1 days (P less than 0.01, Wilcoxon's rank sum test), the number of hospital visits was smaller; 3.8 visits: 11.1 visits (P less than 0.01) and the time off work was shorter; 4.0 days: 14.1 days (P less than 0.01) in the group treated by primary closure compared with those managed conventionally. In this study no complications attributable to the withholding of antibiotics occurred. Incision and primary closure of abscesses is safe and more economic than conventional drainage. Routine antibiotic cover is not necessary.


Estradiol--induced redistribution of glial fibrillary acidic protein immunoreactivity in the rat brain.
The immunohistochemical distribution of the glial fibrillary acidic protein (GFAP), a marker of glial filaments, was studied on coronal sections of the globus pallidus, the area CA4 of the hippocampus and the arcuate nucleus of the hypothalamus, 3 estrogen-sensitive areas of the rat brain. The number and the surface density of the GFAP-immunoreactive cells were evaluated in 6 adult ovariectomized rats injected with a single dose (20 mg/kg) of estradiol valerate (OVX + E2 rats) and in 6 ovariectomized littermates injected with vehicle (OVX rats). Two days after the injection, a similar distribution of the GFAP was observed in the arcuate nucleus of OVX + E2 rats when compared to OVX rats, whereas a significantly (P less than 0.001) increased surface density of GFAP immunoreactive material was observed in the globus pallidus and hippocampus of estradiol-treated rats. Since the number of GFAP-positive cells was unchanged by the estradiol injection, the enhanced surface density of GFAP immunoreactive material in the hippocampus and globus pallidus suggest a possible influence of estradiol on GFAP-immunoreactive glial processes.


PIASy-mediated repression of the androgen receptor is independent of sumoylation.
PIASy, a member of the protein inhibitor of activated STAT (PIAS) family, represses the transcriptional activity of the androgen receptor (AR). In this report, we investigate the mechanism of PIASy-mediated repression of AR. We show that AR binds to the RING-finger like domain of PIASy. PIASy contains two transcriptional repression domains, RD1 and RD2. RD1, but not RD2, is required for PIASy-mediated repression of AR. We show that the RD1 domain binds HDAC1 and HDAC2 and that HDAC activity is required for PIASy-mediated AR repression. PIAS proteins possess small ubiquitin-related modifier (SUMO) E3 ligase activity. Conjugation of SUMO-1 to AR has been implicated in the regulation of AR activity. We examine if the SUMO ligase activity of PIASy is required for PIASy to repress AR. We show that a mutant PIASy, defective in promoting sumoylation, retains the ability to repress AR transcription. In addition, mutation of all the known sumoylation acceptor sites of AR does not affect the transrepression activity of PIASy on AR. Our results suggest that PIASy may repress AR by recruiting histone deacetylases, independent of its SUMO ligase activity.


Short-Term Patient Outcomes Using the Interlaminar Endoscopic Surgical System Ilessys® Delta System versus Bilateral Laminotomy: A Single-Center Study of 80 Patients with Degenerative Lumbar Spinal Stenosis.
BACKGROUND This study from a single center aimed to compare short-term patient outcomes from the Interlaminar Endoscopic Surgical System iLESSYS® Delta system vs bilateral laminotomy in 80 patients with degenerative lumbar spinal stenosis (DLSS). MATERIAL AND METHODS We selected 80 patients with DLSS for the study. Of these, 40 were treated with the iLESSYS® Delta system and 40 were treated with bilateral laminotomy. We followed these patients for 1 year. We recorded and compared data on incision length, operation time and intraoperative blood loss, hospitalization time, postoperative complications, the visual analog scale (VAS), and Oswestry Disability Index (ODI) before, 1 week, 3 months, 6 months, and 12 months after surgery, and the Modified Macnab evaluation criteria. RESULTS The incision length, intraoperative blood loss, and hospitalization time were significantly better in group A than in group B (P<0.05); however, the operation time in group B was shorter than that in group A, and the differences were statistically significant (P<0.05). The VAS and ODI in both groups improved significantly after surgery compared with before the operation. The VAS and ODI in group A patients after surgery were lower than those in group B, and only at 1 week after surgery,(P<0.05). The excellent rate of modified MacNab criteria was not statistically significant between groups A and B (P>0.05). CONCLUSIONS Use of the Interlaminar Endoscopic Surgical System iLESSYS® Delta system can effectively manage DLSS and speed patient recovery.


Mechanisms and product toxicity of activated carbon/peracetic acid for degradation of sulfamethoxazole: implications for groundwater remediation.
Carbon-based materials activated peracetic acid (PAA) to repair groundwater is an environmentally friendly and low-cost technology to overcome secondary pollution problems. In this study, thermally modified activated carbon (AC600) was applied to activate PAA to degrade sulfamethoxazole (SMX). And the effect of groundwater pH, chloride ion (Cl-), bicarbonate (HCO3-), sulfate ion (SO42-), and natural organic matter (NOM) on SMX removal by AC600/PAA process was studied in detail. PAA could be effectively activated by AC600. Increasing AC600 dose (10-100mg/L) or PAA dosages (0.065-0.39 mM) generally enhanced the SMX removal, the excellent performance in SMX removal was achieved at 50 mg/L AC600 and 0.26 mM PAA. The removal of SMX was well-described by second-order kinetic, with the rate constant (kobs) of 10.79 M-1s-1, both much greater than the removal constants of PAA alone (0.034 M-1s-1) and AC600 alone (1.774 M-1s-1). R-O·(CH3C(O)OO·, CH3C(O)O·) and electron-transfer process were proved to be responsible for the removal of SMX while HO· and 1O2 made little to no contribution to the novel PAA/AC600 system, which differs from typical advanced oxidation processes. The SMX can be removed effectively over a wide pH range (3-9), exhibiting a remarkable pH-tolerant performance. Sulfate ion (SO42-), dissolved oxygen (DO), NOM displayed negligible influence on the SMX removal. Bicarbonate (HCO3-) exerted an inhibitory effect on SMX abatement, while chloride ion (Cl-) promoted the removal of SMX. This showed excellent anti-interference capacity and satisfactory decontamination performance under actual groundwater conditions. Furthermore, the degradation pathways of SMX were proposed, there was no obvious difference in the acute toxicity of the mixed products during the degradation process. It will facilitate further research of metal-free catalyst/PAA system as a new strategy for groundwater in-situ remediation technology.


Sacral nerve stimulation in the treatment of severe faecal incontinence: long-term clinical, manometric and quality of life results.
Faecal incontinence (FI) is a complex and multifactorial health problem. Treatment has to be individualised, analysing the aetiology and gravity in every case. Sacral nerve stimulation (SNS) has been shown to effectively improve treatment of FI. Fifty patients with severe FI treated with SNS between March 2002 and December 2010 were analysed. Preoperative assessment included physical examination, anorectal manometry and anal endosonography. Anal continence was evaluated using the Wexner continence grading system. Quality of life was evaluated using the Fecal Incontinence Quality of life Scale (FIQLS). Follow-up appointments were scheduled at 1, 6 and 12 months and annually thereafter. Wexner score, FIQLS and the ability to defer defecation were assessed at each visit. Fifty patients underwent a permanent implant. The overall mean follow-up period was 55.52 ± 31.84 months. After 6 months, SNS significantly improved FI and positively impacted quality of life, as evidence by significant improvements in all 4 scales of the FIQLS. Anorectal manometry showed a trend towards an increase in maximum resting pressure and maximum pressure. After the first assessment at 6 months, Wexner score and FIQLS remained stable. Ability to defer defecation was also maintained. During follow-up, 3 patients (6 %) experienced implant site pain and episodes of extremity pain and paresthesias that were refractory to medical management and required device explantation. The implant site infection rate was 2 %. Analysis of our long-term results confirms the safety and effectiveness of SNS in the management of patients with FI.


Attachment in adolescents with attention deficit hyperactivity disorder and oppositional defiant disorder.
To assess attachment styles among adolescents (13-16 years) with ADHD or ADHD and oppositional defiant disorders (ODD). The Parents and Peers Attachment (IPPA) and the Parent Bonding Questionnaire (PBI) were used in three groups of teenagers raised in biological families: (1) ADHD/ODD group (n = 40), (2) ADHD group (n = 40) and (3) K (control) group of teenagers (n = 40) who have not benefited from psychological or psychiatric care in the past or at present. Parental attachment styles in the area of "Trust", "Communication" and "Alienation" (IPPA), and "Care" and "Control" (PBI) in the ADHD/ODD group differ significantly compared to the control group. Teens from the ADHD/ODD group report to have experienced significantly less "Trust" and "Communication" (IPPA), and "Care" (PBI) in relationships with parents and more "Alienation" (IPPA) and "Control" (PBI) than adolescents in the ADHD group. Attachment patterns with peers in both clinical and control groups differ significantly. The ADHD/ODD group is dominated by the anxious-avoidant style of attachment to the mother and father, in the ADHD group, a secure style in relation to the mother and anxious-avoidant in relation to the father. In relations with peers in the ADHD/ODD group and the ADHD group, the anxious-avoidant style dominates. The attachment style is significantly different in adolescents diagnosed with ADHD and ODD than in adolescents with only ADHD. In the ADHD/ODD group and the ADHD group, unlike in the group of adolescents without a psychiatric diagnosis, insecure attachment styles for parents and peers dominate (mainly anxious-avoidant style).


Aesthetic aspects of nasal reconstruction.
Reconstructive nasal surgery aims not just to rebuild a nose or part of a nose, but to blend and tailor the new and old tissues in such a way as to create a nearly ideal shape that is likely to be an improvement on the original. The challenge of the reconstruction is enhanced by the complexity of the defect. Differences in color, texture, and thickness between the nasal remnants and the sources of skin available for the reconstruction impose aesthetic limits that are often difficult to overcome.


Adaptation and validation of the Distress Scale for Mexican patients with type 2 diabetes and hypertension: a cross-sectional survey.
The aim of this study was to adapt and validate the Distress Scale for Mexican patients with type 2 diabetes and hypertension (DSDH17M). Two family medicine clinics affiliated with the Mexican Institute of Social Security. 722 patients with type 2 diabetes and/or hypertension (235 patients with diabetes, 233 patients with hypertension and 254 patients with both diseases). A cross-sectional survey. The validation procedures included: (1) content validity using a group of experts, (2) construct validity from exploratory factor analysis, (3) internal consistency using Cronbach's α, (4) convergent validity between DSDH17M and anxiety and depression using the Spearman correlation coefficient, (5) discriminative validity through the Wilcoxon rank-sum test and (6) test-retest reliability using intraclass correlation coefficient. The DSDH17M has 17 items and three factors explaining 67% of the total variance. Cronbach α ranged from 0.83 to 0.91 among factors. The first factor of 'Regime-related Distress and Emotional Burden' moderately correlated with anxiety and depression scores. Discriminative validity revealed that patients with obesity, those with stressful events and those who did not adhere to pharmacological treatment had significantly higher distress scores in all DSDH17M domains. Test-retest intraclass correlation coefficient for DSDH17M ranged from 0.92 to 0.97 among factors. DSDH17M is a valid and reliable tool to identify distress of patients with type 2 diabetes and hypertension.


[Primary care in Sweden].
Sweden was one of the first European Union countries that saw the opportunity in the free movement of professionals. First offers for jobs were managed in 2000. Since then, a large number of professionals have taken the opportunity of a decent job and have moved from Spain to Sweden. The Swedish health care model belongs to the group of national health systems. The right to health care is linked to legal citizenship. Health is financed through regional taxes, but there is a compulsory co-payment regardless of the financial situation of the patient. The provision of health care is decentralised at a regional level, and there is a mixture of private and public medical centres. Primary care is similar to that in Spain. Health professionals work as a team with a division of tasks. Like in Spain, waiting lists and coordination between primary and specialised care are a great problem. Patients may register with any public or private primary care centre and hospital provider within their region. Access to diagnostic tests and specialists are restricted to those selected by specialists. Doctors are salaried and their job and salary depend on their experience, professional abilities and regional needs. Medicine is curative. General practitioners are the gateway to the system, but they do not act as gatekeeper. Hospitals offer a number of training post, and the access is through an interview. Continuing medical education is encouraged and financed by the health centre in order to increase its revenues.


Knowing your bariatric practice: what's your insurance fee? What's your leverage?
Healthcare today is a complex environment, and many states, regions and hospitals have been having problems in being solvent. Insurance co-payments have decreased, and the contract made with the physician depends on market leverage. We address contract problems in bariatric surgery and discuss how to try to divide bariatric surgery from general surgery practice, to get better insurance reimbursement. Creating leverage is also important: 1) how to attract new patients, and 2) how to add additional procedures, when necessary, to the initial bariatric surgery scheduled. Leverage can also be created by offering additional services, such as access to a dietician and exercise programs. By offering a variety of services, this will enhance not only the quality of care provided, but also the number of patients who will take advantage of your services, including bariatric surgery.


The nucleotide exchange factor Cdc24p may be regulated by auto-inhibition.
Site-specific activation of the Rho-type GTPase Cdc42p by its guanine-nucleotide exchange factor (GEF) Cdc24p is critical for the establishment of cell polarity. Here we show that binding of Cdc24p to the small GTPase Rsr1p/Bud1p is required for its recruitment to the incipient bud site. Rsr1p/Bud1p binds to the CH-domain of Cdc24p, which is essential for its function in vivo. We have identified a cdc24-mutant allele, which is specifically defective for bud-site selection. Our results suggest that Cdc24p is auto-inhibited by an intramolecular interaction with its carboxy-terminal PB1-domain. Rsr1p/Bud1p appears to activate the GEF activity of Cdc24p in vivo, possibly by triggering a conformational change that dissociates the PB1-domain from its intramolecular binding site. Genetic experiments suggest that Bem1p functions as a positive regulator of Cdc24p by binding to the PB1-domain of Cdc24p, thereby preventing its re-binding to the intramolecular inhibitory site. Taken together, our results support a two-step molecular mechanism for the site-specific activation of Cdc24p, which involves Rsr1p/Bud1p and the adaptor protein Bem1p.


Difference of depression between widowed and non-widowed older people in China: A network analysis approach.
In this study, the difference of depression network structures between the widowed and non-widowed older people and the associations of family capital, neighborhood cohesion, and neighborhood built environment with depressive symptoms were explored by using network analysis. This study fitted network models to two subsamples extracted from a nationally representative and cross-sectional data from China Family Panel Studies (CFPS). Depressive symptom levels and the effect of the three possible influencing factors related on depression were compared. The network structures of depression across the widowed and the non-widowed older people were different to some extent but significantly associated with one another. Neighborhood cohesion were significantly related to severe depressive symptoms in both subsamples. Neighborhood built environment mattered for the non-widowed older people, but not for their counterparts. Family capital also functioned in a different way for the two subsamples. Investigation was carried out using cross-sectional data, and changes in contents could alter the network structure. In addition, grief-related variables were not included. New studies replicating the current findings with a wider range of contents, multiple time points and a larger sample are warranted. This study added evidence to a growing body of literature on depressive symptom patterns for the widowed older people and their counterparts. Tailored service and treatment could be developed for the widowed and non-widowed older people based on their features of depression. The contextual factors including family, neighborhood, and physical environment could be taken into account when considering their association with depressive symptoms.


Electroacupuncture alters pain-related behaviors and expression of spinal prostaglandin E2 in a rat model of neuropathic pain.
To investigate the role of spinal prostaglandin E2 (PGE2) in electroacupuncture (EA) analgesia and assess the theoretical basis for selection of acupoints in the treatment of neuropathic pain. A rat model of neuropathic pain was established. Rats were randomly divided into normal, model, sham, EA 1, EA 2, and EA 3 groups. In EA 1 group, the rats were needled at bilateral L5 Jiaji (EX-B2), Dachangshu (BL 25), Weizhong (BL 40) and Kunlun (BL 60). In EA 2 group, the rats were needled at bilateral Weizhong (BL 40) and Kunlun (BL 60). In EA 3 group, the rats were needled at bilateral L5 Jiaji (EX-B2) and Dachangshu (BL 25). EA stimulation was administered once daily over 7 days. Motor function and thermal withdrawal latencies were evaluated at 1 day preoperatively and at 3, 5, and 7 days postoperatively. After 7 days of intervention, enzyme-linked immunosorbnent assay (ELISA) was used to quantify the expression of the spinal PGE2. Rats in the model group exhibited evident hyperalgesia in responses to thermal withdrawal latencies compared with those in the control group (P < 0.01), and EA reversed thermal withdrawal latencies (P < 0.01). The expression level of the spinal PGE2 was significantly higher in the model group than that in the control group and was reversed by EA (P < 0.01; P < 0.05). The effect of EA on neuropathic pain might alleviate the hyperalgesia state by an inhibition of local prostaglandin E2 secretion.


Albumin synthesis in surgical patients.
Albumin plasma concentrations are being used as indicators of nutritional status and hepatic function based on the assumption that plasma levels reflect the rate of albumin synthesis. However, it has been shown that albumin levels are not reliable markers of albumin synthesis under a variety of clinical conditions including inflammation, malnutrition, diabetes mellitus, liver disease, and surgical tissue trauma. To date, only a few studies have measured albumin synthesis in surgical and critically ill patients. This review summarizes the findings from these studies, which used different tracer methodology in various surgical or critically ill patient populations. The results indicate that the fractional synthesis rate of albumin appears to decrease during surgery, followed by an increase during the postoperative phase. In the early postoperative phase, albumin fractional synthesis rate can be stimulated by perioperative nutrition, if enough amino acids are being provided and if nutrition is being initiated before the operation. The physiologic meaning of albumin synthesis after surgery, however, still needs to be further clarified.


Biome-scale temperature sensitivity of ecosystem respiration revealed by atmospheric CO2 observations.
The temperature sensitivity of ecosystem respiration regulates how the terrestrial carbon sink responds to a warming climate but has been difficult to constrain observationally beyond the plot scale. Here we use observations of atmospheric CO2 concentrations from a network of towers together with carbon flux estimates from state-of-the-art terrestrial biosphere models to characterize the temperature sensitivity of ecosystem respiration, as represented by the Arrhenius activation energy, over various North American biomes. We infer activation energies of 0.43 eV for North America and 0.38 eV to 0.53 eV for major biomes therein, which are substantially below those reported for plot-scale studies (approximately 0.65 eV). This discrepancy suggests that sparse plot-scale observations do not capture the spatial-scale dependence and biome specificity of the temperature sensitivity. We further show that adjusting the apparent temperature sensitivity in model estimates markedly improves their ability to represent observed atmospheric CO2 variability. This study provides observationally constrained estimates of the temperature sensitivity of ecosystem respiration directly at the biome scale and reveals that temperature sensitivities at this scale are lower than those based on earlier plot-scale studies. These findings call for additional work to assess the resilience of large-scale carbon sinks to warming.


Formation of 8-nitroguanosine in cellular RNA as a biomarker of exposure to reactive nitrogen species.
Reactive nitrogen species, such as peroxynitrite, nitrogen oxides and nitryl chloride, have been implicated as a cause of diverse pathophysiological conditions, including inflammation, neurodegenerative and cardiovascular diseases and cancer. We previously reported that 8-nitroguanine is formed by reactions of guanine or calf-thymus DNA with peroxynitrite in vitro. In the present study, we have studied the formation of 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine in reactions of calf-liver RNA with various reactive nitrogen species. 8-Nitroguanosine in RNA was found to be much more stable than 8-nitro-2' -deoxyguanosine in DNA, which rapidly depurinates to release 8-nitroguanine. Both 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine were formed in calf-liver RNA following exposure to various reactive nitrogen species, such as synthetic peroxynitrite. They were also formed in RNA by reactive species formed from nitric oxide and superoxide anion generated concomitantly from 3-morpholino-sydnonimine (SIN-1) and those formed with myeloperoxidase or horseradish peroxidase in the presence of nitrite and hydrogen peroxide. 8-Nitroguanosine was detected by HPLC with an electrochemical detector in enzymatic hydrolyzates of RNA isolated from human lung carcinoma cells incubated with synthetic peroxynitrite. Our results indicate that 8-nitroguanosine in cellular RNA could be measured as a marker of damage caused by endogenous reactive nitrogen species in tissues and cells.


Surgical treatment for Graves' disease: a long term follow-up of 325 patients.
Postoperative thyroid status was classified into 6 categories on the basis of serum free thyroxine index (FTI), serum triiodothyronine (T-3) and serum TSH concentration. Review of 325 patients who underwent thyroidectomy for Graves' disease more than 4 years previously showed that 25 patients (7.7 per cent) had recurrent hyperthyroidism. Six patients (1.8 per cent) were classified as equivocal hyperthyroid since either FTI or T-3 was above the normal range. Two hundred and twenty-two patients (68.3 per cent) were unequivocally euthyroid and 33 patients (10.3 per cent) were euthyroid with elevated TSH levels. Twenty patients (6.2 per cent) were equivocal hypothyroid since either their FTI or T-3 values were below the normal range and TSH were increased. Hypothyroidism was present in 19 patients (5.8 per cent), of whom 11 had no clinical manifestation of thyroid dysfunction. The incidence of hypothyroidism did not correlate with the intervals between operation and review. The second review, performed in 189 patients 18 months after the first, showed that there was a change in thyroid functional status in 46 patients, of whom 32 had an increased level of function, including one hypothyroid and 7 equivocal hypothyroid patients who became euthyroid spontaneously. Thus postoperative hypothyroidism in some patients can recover without medication. Also thyroid function in some postoperative patients is not maintained at a fixed level but may fluctuate.


[Clinical study on acupuncture, moxibustion, acupuncture plus moxibustion at Weiwanxiashu (EX-B3) for treatment of diabetes].
To compare clinical therapeutic effects of acupuncture, moxibustion, acupuncture plus moxibustion at Weiwanxiashu (EX-B 3) on diabetes. Seventy-nine cases of type 2 diabetes were randomly divided into 3 groups: acupuncture group (A), moxibustion group (B) and acupuncture plus moxibustion group (C) and Weiwanxiashu (EX-B 3) was selected in the 3 groups. The main clinical symptoms, fasting blood glucose, 24 hurinal glucose, glycosylated hemoglobin, and blood lipids were investigated and compared before and after treatment. After treatment, the clinical symptoms significantly improved; fasting blood glucose, 24 h-urinal glucose, glycosylated hemoglobin, and cholesterol, triglyceride, low density lipoprotein all decreased in varying degrees, and the high density lipoprotein increased (P < 0.05) in all of the 3 groups, with the effects being the best in the acupuncture plus moxibustion group. Acupuncture, moxibustion, or acupuncture plus moxibustion at Weiwanxiashu (EX-B 3) is an effective therapy for diabetes, and the acupuncture plus moxibustion has a better result.


Epidemiology and outcomes of surgical site infections among pediatric liver transplant recipients.
Surgical site infections (SSI) are a significant cause of morbidity in liver transplant recipients, and the current data in the pediatric population are limited. The goal of this study was to identify the incidence, classification, risk factors, and outcomes of SSIs among children undergoing liver transplantation (LT). A single-center, retrospective descriptive analysis was performed of patients age ≤18 years undergoing LT between September 2007 and April 2017. SSI identified within the first 30 days were analyzed. Primary endpoints included incidence, classification, risk factors, and outcomes associated with SSIs. We included 86 patients, eight patients (9.3%) developed SSIs. Among segmental grafts (SG) recipients, 7/61 (11.4%) developed SSI. Among whole grafts recipients, 1/25 (4%) developed SSI. SSIs were associated with the presence of biliary complications (35% vs. 3%, p < .01; odds ratios 24, 95% CI: 3.41-487.37, p<.01). There were no differences in long term graft or patient survival associated with SSI. Patients who developed SSI were more likely to undergo reoperation (50% vs. 16.7%, p = .045) and had an increased total number of hospital days in the first 60 days post-transplant (30.5 vs. 12.5 days, p = .001). SSIs after pediatric LT was less frequent than what has been previously reported in literature. SSIs were associated with the presence of biliary complications without an increase in mortality. SG had an increased rate of biliary complications without an association to SSIs but, considering its positive impact on organ shortage barriers, should not be a deterrent to the utilization of SGs.