Effects of reading media on reading comprehension in health professional education: a systematic review protocol.
To evaluate the effect of digital-based reading versus paper-based reading on reading comprehension among students, trainees, and residents participating in health professional education. Several reviews have examined the effects of reading media on reading comprehension; however, none have considered health professional education specifically. The growing use of electronic media in health professional education, as well as recent data on the consequences of digital-based reading on learning, justify the necessity to review the current literature to provide research and educational recommendations. Studies conducted with health professions students, trainees, and residents individually receiving educational material written in their first language in a paper-based or a digital-based format will be considered. Studies conducted among participants with cognitive impairment or reading difficulties will be excluded. Observational, experimental and quasi-experimental studies that assess reading comprehension measured by previously validated or researcher-generated tests will be considered. Relevant studies will be sought from CINAHL, Embase, ERIC, Google Scholar, MEDLINE, PsycINFO, and Web of Science (SCI and SSCI), without date or language restrictions. Two independent reviewers will perform title and abstract screening, full-text review, critical appraisal, and data extraction. Disagreements will be resolved through discussion or with a third independent reviewer. Synthesis will occur at four levels (i.e., study, participant, intervention, and outcome levels) in a table format. Data will be synthesized descriptively and with meta-analyses if appropriate. PROSPERO CRD42020154519.


Estimating Heritability from Twin Studies.
This chapter describes how the heritability of a trait can be estimated using data collected from pairs of twins. The principles of the classical twin design are described, followed by the assumptions, and some possible extensions of the design. In the second part of this chapter, two example scripts are presented and the basic steps for estimating heritability using the statistical program OpenMx are explained. OpenMx and the scripts used for this chapter can be downloaded so that readers can adapt and use the scripts for their own purposes.


Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature.
Leber congenital amaurosis (LCA) is a severe retinal dystrophy, typically manifesting in the first year of life. Mutations in more than 18 genes have been reported to date. In recent studies, biallelic mutations in NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 have been found to cause LCA. To broaden the knowledge regarding the phenotype of NMNAT1-associated LCA. Clinical ophthalmologic examinations were performed in two sisters with LCA. Whole exome sequencing was performed in one of the affected girls, with subsequent segregation analysis in the affected sister and unaffected parents. The literature was reviewed for reports of NMNAT1-associated LCA. Exome sequencing revealed the known NMNAT1 mutation c.25G>A (p.Val9Met) in a homozygous state. Segregation analysis showed the same homozygous mutation in the affected younger sister. Both parents were found to be heterozygous carriers of the mutation. The two girls both presented with severe visual impairment, nystagmus, central atrophy of the pigment epithelium, and pigment clumping in the periphery before the age of 6 months. Retinal vessels were attenuated. Both children were hyperopic. In the older sister, differential diagnosis included an inflammatory origin, but electrophysiology in her as well as her sister confirmed a diagnosis of LCA. Pallor of the optic nerve head was not present at birth but developed progressively. We confirmed a diagnosis of NMNAT1-associated LCA in two siblings through identification of the mutation (c.25G>A [p. Val9Met]) in a homozygous state. In infants with non-detectable electroretinogram (ERG), along with severe congenital visual dysfunction or blindness and central pigment epithelium atrophy with pigment clumping resembling scarring due to chorioretinitis, LCA due to NMNAT1 mutations should be considered.


Post-transcriptional regulation of IGF1R by key microRNAs in long-lived mutant mice.
Long-lived mutant mice, both Ames dwarf and growth hormone receptor gene-disrupted or knockout strains, exhibit heightened cognitive robustness and altered IGF1 signaling in the brain. Here, we report, in both these long-lived mice, that three up-regulated lead microRNAs, miR-470, miR-669b, and miR-681, are involved in posttranscriptional regulation of genes pertinent to growth hormone/IGF1 signaling. All three are most prominently localized in the hippocampus and correspond to reduced expression of key IGF1 signaling genes: IGF1, IGF1R, and PI3 kinase. The decline in these genes' expression translates into decreased phosphorylation of downstream molecules AKT and FoxO3a. Cultures transfected with either miR-470, miR-669b, or miR-681 show repressed endogenous expression of all three genes of the IGF1 signaling axis, most significantly IGF1R, while other similarly up-regulated microRNAs, including let-7g and miR-509, do not induce the same levels of repression. Transduction study in IGF1-responsive cell cultures shows significantly reduced IGF1R expression, and AKT to some extent, most notably by miR-681. This is accompanied by decreased levels of downstream phosphorylated forms of AKT and FoxO3a upon IGF1 stimulation. Suppression of IGF1R by the three microRNAs is further validated by IGF1R 3'UTR reporter assays. Taken together, our results suggest that miR-470, miR-669b, and miR-681 are all functionally able to suppress IGF1R and AKT, two upstream genes controlling FoxO3a phosphorylation status. Their up-regulation in growth hormone signaling-deficient mutant mouse brain suggests reduced IGF1 signaling at the posttranscriptional level, for numerous gains of neuronal function in these long-lived mice.


Selective inhibitory actions of sodium-p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenyl propyl] phenyl phosphonate (N-0161) and indomethacin on the biosynthesis of prostaglandins and thromboxanes from arachidonic acid.
1 Sodium p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenyl propyl]phenyl phosphonate (N-0164) selectively inhibited the formation of thromboxane-A(2) from prostaglandin endoperoxides by human platelet microsomes in a dose-dependent manner (IC(50) 2.2 x 10(-5) M or 11.6 mug/ml).2 N-0164 was approximately 15 to 20 times as potent as indomethacin as an inhibitor of thromboxane-A(2) formation. In contrast, indomethacin was 20 times as potent as N-0164 as an inhibitor of prostaglandin endoperoxide formation from arachidonic acid (IC(50) 2.6 x 10(-5) M or 9.4 mug/ml).3 Spiral strips of dog coronary arteries relaxed in the presence of prostaglandin endoperoxides and were contracted by prostaglandin E(2) and thromboxane-A(2) and were therefore used to distinguish between prostaglandins and their intermediate precursors, the endoperoxides.4 Neither indomethacin nor N-0164 (both 50 mug/ml) significantly inhibited the formation of prostaglandin-like activity from the endoperoxides following incubation with indomethacin-pretreated rabbit kidney medulla microsomes.5 It is not known whether this action of N-0164 is related to its ability to antagonize certain actions of prostaglandins (and related compounds) or whether N-0164 can penetrate the cell membrane to inhibit thromboxane formation in the intact cell.6 Selective inhibition of thromboxane formation by drugs such as N-0164 may be useful both clinically and as a pharmacological tool to elucidate the patho-physiological roles of the thromboxanes.


Potent analogues of etiprednol dicloacetate, a second generation of soft corticosteroids.
Loteprednol etabonate (LE) is the first, highly successful soft corticosteroid (SC) designed using the 'inactive metabolite' approach, starting with ∆1 -cortienic acid (d-CA). The next generation of SCs based on d-CA was etiprednol dicloacetate (ED). The 17α-dichloroacetyl function serves both as a unique pharmacophore and as the source of the molecule's softness. Highly potent SCs were designed based on a combination of ED and LE, introducing 6, 9 and 16 substituents in the molecule. The new 6α, 9α, 16α and β 17α-dichloroacetyl 17β-esters were synthesized from the correspondingly substituted ∆1 -cortienic acids. The anti-inflammatory activity was assessed using LPS-induced TNF α-release under various conditions to determine intrinsic activity vs. systemic biological stability. In vivo anti-inflammatory activity was studied in the widely used ovalbumin-sensitized and ovalbumin-challenged Brown Norway rat model. The 6α or 9α-fluoro substitution produced highly potent corticosteroids, but the 17α-dichloroacetyl substituent provided 'softness' in all cases. Local application of these steroids will significantly reduce systemic activity, due to the facile hydrolytic deactivation of these molecules. A 17α-dichloroacetyl derivative of fluticasone (FLU) is highly potent but much safer than the currently used propionate or furoate ester.


Vandetanib in patients with inoperable hepatocellular carcinoma: a phase II, randomized, double-blind, placebo-controlled study.
Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC. Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups. Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies.


High-strength, ultra-thin and fiber-reinforced pHEMA artificial skin.
Membranes of pHEMA-based composites were manufactured by adding various kinds of weaved and knitted fabrics and fibers into a deionized water solution of HEMA monomer, EGDMA cross-linker and BIE initiator, and followed by polymerization under ultraviolet radiation. By varying the amount of initial water addition (IWA), the dimensional change of pHEMA matrix from the newly fabricated state to the eventually swollen state could be adjusted to reduce the swellability mismatch with the fabrics and the possibility of the swollen membranes becoming folded and curled was avoided. Mechanical properties of the fiber-reinforced pHEMA composites, including yielding strength, maximum strength, Young's modulus and elongation at break, are improved evidently depending on the mechanical characteristics of additives applied. The involvement of fabrics and fibers in the soft pHEMA matrix also provides an alternative of making the ultra-thin membranes to overcome the problem of easily being torn during handling. In addition, some of these membranes also exhibit an improvement in water transmission rate.


The Need to Standardize the Reanalysis of Genomic Sequencing Results: Findings from Interviews with Underserved Families in Genomic Research.
The reanalysis of genomic sequencing results has the potential to provide results that are of considerable medical and personal importance to recipients. Employing interviews with forty-seven predominantly medically underserved families and ethnographic observations we argue that there is pressing need to standardize the approach taken to reanalysis. Our findings highlight that study participants were unclear as to the likelihood of reanalysis happening, the process of initiating reanalysis, and whether they would receive revised results. Their reflections mirror the lack a specific focus upon reanalysis within consent and results sessions as observed in clinical settings. Mechanisms need to be put into place that standardize the approach to reanalysis in research and in clinical contexts. This would enable clinicians and genetic counsellors to communicate clearly with research participants with respect to potential for reanalysis of results and the process of reanalysis. We argue that that the role of reanalysis is too important to be referred to in an ad-hoc manner. Furthermore, the ad-hoc nature of the current process may increase health inequities given the likelihood that only those families who have the means to press for reanalysis are likely to receive it.


The design, synthesis, and structure-activity relationships of a series of macrocyclic MMP inhibitors.
A series of succinate-derived hydroxamic acids incorporating a macrocyclic ring were designed, synthesized, and evaluated as inhibitors of matrix metalloproteinases. The inhibitors were designed based on the published X-ray crystal structure of batimastat (1) complexed with human neutrophil collagenase (MMP-8). The synthesized compounds were shown to inhibit selected MMPs in vitro with low nanomolar potency.


Cosmetic and shoulder functional outcomes in posterolateral minithoracotomy atrial septal defect closure: A retrospective study.
Transcatheter device closure has become the first treatment option for atrial septal defects (ASD). Surgical ASD closure, although still implemented, is cosmetically inferior to transcatheter closure. This study aimed to evaluate the feasibility as well as short- and long-term clinical outcomes of the right posterolateral minithoracotomy approach for surgical ASD closure. In total, 102 consecutive patients underwent posterolateral minithoracotomy for ASD between January 2014 and December 2021 at our center. Early surgical outcomes, cosmetic findings, and skin perception were evaluated over 1 year of postoperative follow-up using a self-satisfaction survey (1: very good, 2: good, 3: normal, 4: not good, 5: bad), Cavendish score, and shoulder joint function (angles of flexion, extension, and abduction). No patient required conversion to median sternotomy. Only one patient required reoperation due to bleeding. Postoperative echocardiography revealed no residual shunt at discharge in all patients. The mean follow-up period was 3.7 years (range: 0.3-7.1 years), during which the questionnaire was answered by 69 of 98 patients who were evaluated after more than 1 year. The mean self-satisfaction survey scores for cosmetic findings and skin perception were 1.3 ± 0.6 and 1.2 ± 0.5, respectively. The Cavendish score was under Grade 1 in all patients. Shoulder flexion and abduction were normal at 180° in all patients, except one, while extension was normal at 50° in all patients, except three. Our procedure achieved not only good early surgical outcomes but also excellent long-term cosmetic and shoulder function results.


Hereditary motor and sensory neuropathy type I: clinical and neurographical features of the 17p duplication subtype.
Forty-four affected individuals, aged 8-68 years (mean 34 years), from six families with hereditary motor and sensory neuropathy type I (HMSN I, Charcot-Marie-Tooth disease type 1) were investigated to determine the clinical and electroneurographical characteristics of the HMSN I subtype that is defined by the presence of a DNA duplication on chromosome 17p. Motor nerve conduction velocity (MNCV) and, to a lesser extent, compound muscle action potential amplitude, were inversely related to clinical severity. Neither clinical severity nor MNCV were significantly related to age. These results suggest that the primary pathological process is not, or only slightly active after childhood.


Prevalence and risk factors of burden among caregivers of older emergency department patients.
The number of older individuals that live independently at home is rising. These older individuals often rely on caregivers who have a similar age and health status. Therefore, caregivers may experience a high burden. We determined the prevalence and associating factors of burden among caregivers of older patients in the emergency department (ED). A cross-sectional study of primary caregivers of patients aged ≥ 70 years visiting the ED of a Dutch teaching hospital was performed. Structured interviews were conducted with patients and their caregivers. Caregiver burden was measured using the caregiver strain index (CSI). Additionally, data from questionnaires and medical records were extracted to determine potential associating factors. Univariate and multivariate regression analyses were conducted to identify independent determinants for burden. Seventy-eight caregivers (39%) experienced a high burden. Multivariate analysis showed a significant association between high caregiver burden and patients with cognitive impairment or dependency for instrumental activities of daily living (IADL) and more self-reported hours of care per day. Almost 40% of older patients in the ED have a caregiver who experiences a high burden. Formal assessment in the ED may help provide adequate care to the patients and their caregivers.


Considerations on the role of chemotherapy and modern radiotherapy in the treatment of childhood low grade glioma.
The treatment of childhood low grade glioma (LGG), if not amenable to complete resection, quite often is a relevant clinical challenge. LGG in many instances are indeed slow growing tumors, which, if not controlled, can cause severe morbidity and ultimately jeopardize life. Most of the time children bearing an unresectable LGG can be considered affected by a chronic disease, deserving protracted cures. The treatment philosophy, which has dictated the treatment of malignant cancers, has also inspired the therapeutic concepts for managing childhood LGG. However, it is getting more and more evident that different strategies are needed for them. LGG represent a highly heterogeneous group of neoplasm and comprehensive treatment concepts rarely meet the individual patient's needs. After more than 20 years of clinical research it can be stated with confidence that for unresectable, progressive LGG, chemotherapy (CT) represents an effective treatment modality. It delays tumor growth and postpones the use of radiotherapy (RT), thus sparing the deleterious effects of irradiation on a developing brain. However, CT rarely cures LGG and definitively obviates the need of RT or aggressive surgery. Furthermore, little is known on the actual impact of CT on patients' overall health status. Recent progresses in RT delivering techniques, which allow reducing the safety margins, are tempering the concerns related to the use of this treatment modality in children. This manuscript reviews and expands these data, trying to combine them in a coherent picture that it is hoped can help in directing future research in this field.


Angiogenesis with pericyte abnormalities in a transgenic model of prostate carcinoma.
Previous studies of the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model vasculature suggest that, as tumors develop, vessels invade the glandular epithelium. However, changes in the vasculature are difficult to study in conventional thin tissue sections. The authors used a new approach to characterize morphologic and architectural changes of blood vessels and pericytes during tumor development in TRAMP mice. Eighty-micron cryostat sections of normal prostate and three histopathologic stages of TRAMP tumor sections, classified by epithelial cell E-cadherin immunoreactivity, were immunostained with vascular endothelial cell and pericyte receptor antibodies and evaluated by confocal microscopy. In the normal mouse prostate, capillaries were most abundant in the fibromuscular tunica between the epithelium and smooth muscle of the ductules. In the prostatic intraepithelial neoplasia (PIN) stage, vessels accompanied epithelial cell protrusions into the ductule lumen but remained in the connective tissue at the basal side of the epithelium. Well differentiated tissues had extensive angiogenesis with five times the normal mean vascularity outside ductules. Vessels were of variable diameter, were associated with an increased number of pericytes, and some had endothelial sprouts. Angiogenic blood vessels from poorly differentiated adenocarcinomas were tortuous, variable in caliber, and lacked the normal hierarchy. Pericytes on these vessels had an abnormal phenotype manifested by alpha-smooth muscle actin expression and loose association with endothelial cells. Angiogenesis and loss of vascular hierarchy were also found in human prostate carcinoma. Vascular abnormalities, which begin at the PIN stage and intensify in well differentiated and poorly differentiated tumors, may be useful readouts for early detection and treatment assessment in prostate carcinoma.


Trabecular Architecture and Mechanical Heterogeneity Effects on Vertebral Body Strength.
We aimed to synthesize the recent work on the intra-vertebral heterogeneity in density, trabecular architecture and mechanical properties, its implications for fracture risk, its association with degeneration of the intervertebral discs, and its implications for implant design. As compared to the peripheral regions of the centrum, the central region of the vertebral body exhibits lower density and more sparse microstructure. As compared to the anterior region, the posterior region shows higher density. These variations are more pronounced in vertebrae from older persons and in those adjacent to degenerated discs. Mixed results have been reported in regard to variation along the superior-inferior axis and to relationships between the heterogeneity in density and vertebral strength and fracture risk. These discrepancies highlight that, first, despite the large amount of study of the intra-vertebral heterogeneity in microstructure, direct study of that in mechanical properties has lagged, and second, more measurements of vertebral loading are needed to understand how the heterogeneity affects distributions of stress and strain in the vertebra. These future areas of study are relevant not only to the question of spine fractures but also to the design and selection of implants for spine fusion and disc replacement. The intra-vertebral heterogeneity in microstructure and mechanical properties may be a product of mechanical adaptation as well as a key determinant of the ability of the vertebral body to withstand a given type of loading.


[Ocular side effects of modern oncological therapy : Immunological checkpoint and MEK/BRAF signal transduction inhibitors].
In recent years, checkpoint inhibitors have revolutionized the treatment of previously untreatable malignant tumors, significantly improving the life expectancy as well as quality of life in many cases. Checkpoint inhibitors comprise a group of drugs with different mechanisms of action. These include immunological checkpoint inhibitors (iCPI) and intracellular signal transduction inhibitors; however, both substance classes can cause inflammatory or toxic ocular side effects. The frequency of intraocular inflammation (uveitis) is reported to be ca. 1-2%, toxic side effects were observed in up to more than 50% of the patients treated with signal transduction inhibitors. In the following article the main mechanisms of these forms of treatment are characterized. Furthermore, this article presents the currently most frequently used therapeutic agents and their typical ophthalmological side effects to increase awareness and to draw attention to these still rare but increasingly more frequent findings.


Brain damage in former association football players. An evaluation by cerebral computed tomography.
Thirty-three former football players from the National Football Team of Norway were examined by cerebral computer tomography (CT). The CT studies, evaluated for brain atrophy, visually and by linear measurements compared two different normal materials. One third of the players were found to have central cerebral atrophy. It is concluded that the atrophy probably was caused by repeated small head injuries during the football play, mainly in connection with heading the ball.


Immunofractionation of high density lipoprotein subclasses 2 and 3. Similarities and differences of fractions isolated from male and female populations.
High density lipoprotein (HDL) subclasses 2 and 3 isolated from male and female populations were further subfractionated by immunoaffinity techniques. Each subclass gave rise to 2 fractions: one contained apolipoprotein (apo) A-I but no apo A-II (LpAI); the other contained apo A-I and apo A-II (LpAI,AII). The bulk fraction (HDL-3(LpAI,AII)) comprised over 70% of total HDL and was present in similar concentrations in both populations. There were, however, significant male-female differences in plasma levels of the minor HDL-3 fraction i.e. HDL-3(LpAI). Females had significantly higher plasma concentrations of both fractions within HDL-2. These fractions also exhibited strong, positive correlations with total HDL cholesterol concentrations, both in males as well as females. It suggests that metabolic activities giving rise to both HDL-2(LpAI) and HDL-2(LpAI,AII) determine plasma HDL cholesterol concentrations. Several similarities were noted between the male and female populations. Triglyceridaemia was negatively correlated with HDL-2 derived fractions and positively correlated with the bulk fraction HDL-3(LpAI,AII). Compositional data showed that the fraction (LpAI) had a lower esterified cholesterol to total cholesterol ratio than the fraction (LpAI,AII), the differences being more apparent at the HDL-3 level. Additionally, analysis of the surface components of HDL-3 fractions suggested that (LpAI,AII) had a greater potential than (LpAI) for absorbing lipoprotein surface material. Finally, the relative concentrations of the individual components of fractions within the same population and defined by the same apolipoprotein criterion showed highly significantly, positive correlations. Such correlations were not apparent for apolipoprotein dissimilar fractions. These observations could reflect a metabolic link between apolipoprotein similar fractions.


Evaluation of the pH-dependent, stationary-phase acid tolerance in Listeria monocytogenes and Salmonella Typhimurium DT104 induced by culturing in media with 1% glucose: a comparative study with Escherichia coli O157:H7.
To comparatively evaluate the adaptive stationary-phase acid tolerance response (ATR) in food-borne pathogens induced by culturing in glucose-containing media, as affected by strain variability and antibiotic resistance, growth temperature, challenge pH and type of acidulant. Antibiotic resistant or sensitive strains of Listeria monocytogenes, Salmonella including S. Typhimurium DT104, and Escherichia coli O157:H7 were cultured (30 degrees C for 24 h; 10 degrees C for up to 14 days) in trypticase soya broth with yeast extract (TSBYE) with 1% or without glucose to induce or prevent acid adaptation, respectively. Cultures were subsequently exposed to pH 3.5 or 3.7 with lactic or acetic acid at 25 degrees C for 120 min. Acid-adapted cultures were more acid tolerant than nonadapted cultures, particularly those of L. monocytogenes and Salmonella. No consistent, positive or negative, influence of antibiotic resistance on the pH-inducible ATR or acid resistance (AR) was observed. Compared with 30 degrees C cultures, growth and acid adaptation of L. monocytogenes and S. Typhimurium DT104 at 10 degrees C markedly reduced their ATR and AR in stationary phase. E. coli O157:H7 had the greatest AR, relying less on acid adaptation. A 0.2 unit difference in challenge pH (3.5-3.7) caused great variations in survival of acid-adapted and nonadapted cells. Culturing L. monocytogenes and Salmonella to stationary phase in media with 1% glucose induces a pH-dependent ATR and enhances their survival to organic acids; thus, this method is suitable for producing acid-adapted cultures for use in food challenge studies. Bacterial pathogens may become acid-adapted in foods containing glucose or other fermentable carbohydrates. Low storage temperatures may substantially decrease the stationary-phase ATR of L. monocytogenes and S. Typhimurium DT104, but their effect on ATR of E. coli O157:H7 appears to be far less dramatic.


Serosal involvement in adult-onset Still's disease: A multicentre and retrospective study.
This study evaluated the characteristics of serosal involvement in adult-onset Still's disease (AOSD). Patients meeting the Yamaguchi classification criteria were classified into AOSD with and without serosal involvement according to their manifestations and sonography/radiography. Clinical data was retrospectively reviewed from 102 patients with AOSD in two centres. Forty-two patients (41.2%) had serosal involvement. The frequencies of pulmonary infiltrate and impaired liver function were significantly higher in patients with serosal involvement (p = .002 and p = .007, respectively), who also had a higher modified systemic score (p = .009). In addition, the percentages of CD3+ T cells (p < .001) and, especially, the CD8+ T cells (p = .004) were significantly increased in the peripheral blood of AOSD patients with serosal involvement. Notably, patients with serosal involvement were more likely to develop macrophage activation syndrome (p = .047) and a chronic pattern (p = .016) during the follow-up. Patients with serosal involvement demonstrated the more severe disease activity and different immune phenotypes; these patients were more likely to develop macrophage activation syndrome, and they may require more aggressive treatment at an early time to control their systemic inflammation.


A modified goldfrank sniffing bar improves accuracy in identifying simulated toxins in a case-based teaching model.
To determine if olfactory analysis of toxin proxies aid in the identification of poisons when compared to case histories alone. A convenience sample of 42 emergency medicine residents participated in a prospective single-blind observational study using a sniffing bar designed with the technique described by Goldfrank et.al. Each subject received 12 written cases describing a patient with a chemical exposure. Ten chemicals with odors corresponding to a specific case history and 2 chemical case controls with no odor comprised the sniffing bar. Each subject was asked to identify the toxin first by reading the case history alone, then again after smelling the corresponding odor. All subjects were asked to record their level of confidence for each case before and after the addition of the sniffing bar using a 5-point Likert scale. Percentages correct before and after the sniffing bar intervention were calculated and two-tailed p-values and 95% confidence intervals were measured. Continuous comparative variables such as the means of the Likert scale confidence measurements were analyzed with the two-tailed t-test. Median percentage of toxins correctly identified was 64.3% (range 9.5-97.6) when based on case description alone and 86.9% (range 9.5-95.2) with addition of the sniffing bar. The percentage of initially incorrect identification reversed after additional data provided by the sniffing bar was 11.5% (range 0-14). Of the 10 actual toxins, correct identification of 6 achieved statistical significance after introduction of the sniffing bar (p=0.0017; 95% CI 4.6-11.4). There was no association between level of training and improved accuracy with use of the sniffing bar, and overall confidence did not improve significantly after addition of the sniffing bar. Diagnostic accuracy of poisons in case-based scenarios is improved with the use of a sniffing bar. The sniffing bar is a useful adjunct to a traditional case-based emergency medicine toxicology teaching curriculum.


Dissociation of endogenous cellular ceramide from NF-kappa B activation.
The participation of cell ceramide in tumor necrosis factor (TNF)-alpha-stimulated NF-kappa B activation in Jurkat T cells and HL-60 cells was studied. TNF-alpha readily stimulated NF-kappa B activity in both cell lines as assayed by electrophoretic mobility shift assay and the use of a human immunodeficiency virus-chloramphenicol acetyltransferase reporter construct. However, TNF-alpha stimulation did not increase cell ceramide levels in either cell line. The exogenous addition of a short chain ceramide, N-acetylsphingosine, to Jurkat cells had no effect on NF-kappa B activity. When Jurkat T cells were exposed to the glucosylceramide synthase inhibitor, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, endogenous ceramide levels increased 4-fold. The increase in ceramide, however, did not result in NF-kappa B activation nor did it potentiate TNF-alpha or phorbol ester-stimulated activity. We conclude that TNF-alpha-induced NF-kappa B activation occurs in Jurkat and HL-60 cell lines that do not demonstrate an increase in TNF-alpha-induced ceramide. Increasing ceramide levels by the addition of short chain ceramides or the use of a glucosylceramide synthase inhibitor can be dissociated from activation of NF-kappa B by TNF-alpha.


Postoperative Outcomes in Cold Dissection Versus Bipolar Electrocautery Tonsillectomy: A Randomized Double-Blind Controlled Study.
Tonsillectomy is one of the oldest and most common procedures worldwide. This surgery is performed by different methods include cold dissection technique (CDT) and bipolar electrocautery technique (BET). Assessment and comparison of postoperative outcomes in cold dissection and bipolar electrocautery is the aim of present study. This randomized controlled clinical trial study was conducted as double-blind on 534 patients. The enrolled patients underwent tonsillectomy in Vali-e-Asr Hospital of Birjand city from Oct. 2013-Oct. 2015. Al patients systematically allocated into two groups treated with cold dissection or bipolar electrocautery methods. Intensity of throat pain scores, Otalgia, analgesic consumption, resume normal diet, body temperature and also wound healing on 10th day after operation were measured and compared between the two groups. The gathered data were analyzed by SPSS software (Ver-22) and using necessary tests. The differences between studied groups less than 0.5 (p < 0.05) considered significant statically. 51.7 and 50.6% in the CDT and the BET groups were male respectively. In comparison between the groups the mean of pain scores 4 and 24 h after operation in the BET group were higher significantly (p < 0.001). Otalgia only 4 h after surgery was higher significantly in the BET group (p = 0.008). All the other studied parameters were significantly more desirable in the CDT group (p < 0.001). According to the findings of present study it seems that the CDT is safer and more favorable than the BET in tonsillectomy.


The neuropeptide head activator stimulates amylase release from rat pancreas in vitro.
The neuropeptide head activator previously located in neural cells of the freshwater hydra was found to stimulate release of amylase from rat pancreatic lobules in vitro. It is unknown whether this effect may have physiological implications.


Intravenous midazolam suppression of pentylenetetrazol-induced epileptogenic activity in a porcine model.
Generalized tonic-clonic seizures are a neurologic emergency. Duration of ictal activity has been associated with neurologic sequelae. The purpose of this study was to determine if midazolam, a short-acting benzodiazepine, could effectively ablate ictal activity in an animal model without significant cardiorespiratory compromise. Ten domestic swine (10 to 20 kg) were ventilated and hemodynamically monitored. Bifrontal craniotomies were performed and electrocortical activity was recorded throughout the experiment. Pentylenetetrazol (100 mg/kg) was administered iv to induce seizures. Midazolam (0.1 mg/kg) was administered iv and serum levels were drawn at 1, 2, 5, 10, 15, and 20 min after administration. There was no significant difference between the baseline and postmidazolam vital signs. Seizure activity was seen periodically as generalized spikes, as well as individual spikes for 29 +/- 5 sec after midazolam administration. A period of attenuation of 24 +/- 7 sec was seen before returning to baseline electrocortical activity. Our study demonstrates that midazolam effectively ablated induced ictal activity without significant cardiorespiratory depression and with similar EEG effect as other benzodiazepines.


Pharmacokinetics of fluoride in man after single and multiple oral doses.
The doses of fluoride (F) recommended in the literature for caries prevention and for the treatment of osteoporosis vary. This partly reflects inadequate knowledge of F pharmacokinetics. In the present study various single and multiple oral doses of F were given to eight volunteers, who had a strictly controlled F intake in the diet. The resulting plasma and parotid saliva concentrations as well as urinary output of F were measured. The plasma data fitted a two-compartment open model with a beta-slope half-life ranging between 2 and 9 h. Plasma clearance was 0.15+/-0.02 (SD) liter/kg/h. Data from the highest dose (10 mg) were fitted to both two- and three-compartment models, and there was no significant difference between them. Multiple doses of F 3.0 Or 4.5 mg yielded steady state concentrations ranging from 54 to 145 ng/ml. About 50 per cent of the given dose was recovered in the urine, which is indicative of considerable accumulation in the body. The saliva F/plasma F concentration ratio was 0.64 with a coefficient of variation of 5%.


Prehospital peripheral intravenous vascular access success rates in children.
Achieving successful peripheral intravenous (PIV) vascular access in children can be difficult. In the prehospital setting, opportunities are rare. Obtaining access becomes vital in emergent and life-threating conditions, such as seizures, hypoglycemia, and cardiac arrest. This study examines prehospital pediatric PIV attempts, success rates, and the impact of patient age. This was a retrospective chart review of patients aged 18 years or younger receiving prehospital PIV attempts from January 1, 2003, through May 31, 2011. Included cases were identified by querying electronic patient care reports for PIV attempts within the specified age range. The documentation of PIV attempts and successes was reported by emergency medical service providers. This study was approved by an institutional review board. Throughout the 101-month study period, there were 261,008 ambulance responses. PIV attempts were made in 4188 patients aged 18 years or younger. PIV placement was successful in 3699 patients (88.3%) and failed in 489 (11.7%). Age was significantly associated with success. Each 1-year increase in age was associated with an 11% increase in odds of PIV success (odds ratio, 1.11; 95% CI, 1.09-1.12; p < 0.001). Success was lowest in patients younger than 2 years old, with an overall success rate of 64.1% (141/220). Accounting for multiple attempts, success was achieved in 53.0% of attempts (141/266). Prehospital PIV attempts are uncommon (2% of emergent responses). Success rates are significantly associated with patient age in the pediatric population and lowest in those aged 2 years or less. Consideration of alternative forms of vascular access in this population may be beneficial.


No Association Between Interleukin 6 and Inducible Nitric Oxide Synthase Polymorphisms and Dengue Infection: A Case-Control Study.
Dengue is a life-threatening disease. The factors that lead to severe cases are not completely understood. The host immune system is involved in the response to infections and plays an important role in dengue infection. IL-6 and iNOS are components of the immune system and genetic polymorphisms in these genes may be involved in dengue virus infection. The study aimed to investigate the association of genetic polymorphisms in the IL6 and iNOS genes and dengue. We performed a case-control study using 60 dengue-infected individuals and 119 healthy controls. Polymorphisms in the IL6 (T15A) and iNOS (-1173CT) genes were amplified by Real-Time PCR. Statistical analyses were performed using BioEstat 5.0. We identified that the frequency of T/A genotype of IL6 was higher in dengue fever patients and C/T genotype of iNOS was higher in dengue hemorrhagic fever patients, however, no association was found between these polymorphisms and dengue. Polymorphisms in iNOS and IL6 were not associated with dengue infection.


Ion Complexation Explains Orders of Magnitude Changes in the Equilibrium Constant of Biochemical Reactions in Buffers Crowded by Nonionic Compounds.
The equilibrium constant (K) of biochemical complex formation in aqueous buffers with high concentration (>20 wt %) of nonionic compounds can vary by orders of magnitude in comparison with the K in a pure buffer. The precise molecular mechanisms of these profound changes are not known. Herein, we show up to a 1000-fold decrease of the K value of DNA hybridization (at nM concentration) in standard molecular crowder systems such as PEG, dextrans, Ficoll, and glycerol. The effect responsible for the decrease of K is the complexation of positively charged ions from a buffer by nonionic polymers/small molecules. We determined the average equilibrium constant for the complexation of ions per monomer (∼0.49 M-1). We retrieve K's original value for a pure buffer if we properly increase the ionic strength of the buffer crowded by the polymers, compensating for the loss of complexed ions.


Advantages and safety of local treatment with MMC/Beriplast P for cancer tumors.
To target the treatment of small points of cancer, Beriplast P, already used clinically as a physiological tissue adherent drug carrier, was mixed with the anticancer drug, mitomycin C (MMC). In this in vitro study, MMC did not release quickly from the clot of MMC/Beriplast P. The antitumor effect of this mixture was examined for its effect on cancer growth. In one series of experiments, tumor tissues were inoculated with MMC/100 microliters Beriplast P and in another series, MMC/100 microliters Beriplast P was injected into tumors at a weight of 300 mg. In the first series of experiments, tumor tissue treated with 0.3 mg MMC/100 microliters Beriplast P was replaced with plasma cells and lymphocytes, and no viable cancer cells could be found. In the second series, MMC/100 microliters Beriplast P delayed tumor growth, and the survival of Balb/c mice injected with 0.08 mg MMC/100 microliters Beriplast P was significantly longer than that of mice injected with 0.08 mg MMC/100 microliters saline solution (P = 0.026). In addition, the abdominal aorta, vena cava, and intestine around the area of treatment with 1.6 mg MMC/100 microliters Beriplast P were not damaged. These results indicate that the mixture of Beriplast P and MMC is more effective than MMC solution alone in the local treatment of residual cancer.


Inhibition of CXorf56 promotes PARP inhibitor-induced cytotoxicity in triple-negative breast cancer.
Poly(ADP-ribose) polymerase inhibitors (PARPis) induce DNA lesions that preferentially kill homologous recombination (HR)-deficient breast cancers induced by BRCA mutations, which exhibit a low incidence in breast cancer, thereby limiting the benefits of PARPis. Additionally, breast cancer cells, particularly triple-negative breast cancer (TNBC) cells, exhibit HR and PARPi resistance. Therefore, targets must be identified for inducing HR deficiency and sensitizing cancer cells to PARPis. Here, we reveal that CXorf56 protein increased HR repair in TNBC cells by interacting with the Ku70 DNA-binding domain, reducing Ku70 recruitment and promoting RPA32, BRCA2, and RAD51 recruitment to sites of DNA damage. Knockdown of CXorf56 protein suppressed HR in TNBC cells, specifically during the S and G2 phases, and increased cell sensitivity to olaparib in vitro and in vivo. Clinically, CXorf56 protein was upregulated in TNBC tissues and associated with aggressive clinicopathological characteristics and poor survival. All these findings indicate that treatment designed to inhibit CXorf56 protein in TNBC combined with PARPis may overcome drug resistance and expand the application of PARPis to patients with non-BRCA mutantion.


Dream anxiety attacks (nightmares).
Nightmares--disturbances of dreaming sleep experienced at some point in time by most patients--are often seen in adults as a consequence of physical or emotional trauma. The presence of nightmares on a chronic basis in adult life may reflect specific personality characteristics and may define a population at risk for other psychiatric disturbances. Treatment, if indicated, may include psychotherapy and pharmacotherapy, with the regimen determined by the patient's specific history and symptoms.


Arthroscopic knee chondroplasty using a bipolar radiofrequency-based device compared to mechanical shaver: results of a prospective, randomized, controlled study.
Both mechanical shavers and radiofrequency-based devices are used to treat symptomatic partial thickness chondral lesions. Controversy exists as to which mode of treatment provides better outcomes. The purpose of this study was to compare clinical results after bipolar radiofrequency-based chondroplasty (RFC) to mechanical shaver debridement (MSD). Patients (n = 60) included in the study presented with knee pain associated with a medial meniscus tear and idiopathic ICRS grade III defect of the medial femoral condyle. Patients who had osteoarthritis, grade II or higher cartilage defects of the tibial joint surface, the lateral compartment, or the femoro-patellar joint, or had previously undergone surgery on the affected knee were excluded. Patients underwent partial meniscectomy; during the procedure, they were randomly assigned to receive bipolar RFC (Paragon, ArthroCare Corporation, Austin, TX) or MSD (Full radius resector LR 4.85 x 12.5 cm), Arthrex, Naples, FL). Postoperatively, the same physiotherapist provided instructions for a daily 2-h home training program consisting of isometric, isotonic, and leg lifting exercises; patients were provided the option of using crutches. Clinical outcomes were assessed using the Tegner score, visual analogue scale (VAS) score, and Knee and Osteoarthritis Outcome Score (KOOS) assessment, which consists of five principal domains including pain, symptoms, function in daily living (ADL), and knee related quality of life (QOL), where a score of 0 indicates extreme symptoms and 100 represents no symptoms. Age and time from injury onset did not differ significantly between the RFC and MSD groups (43 +/- 10 vs. 44 +/- 9 years, P = 0.732; 8 +/- 3 vs. 7 +/- 4 months, P = 0.279). No complications or adverse events were observed. Preoperatively, mean (+/-SD) scores for all KOOS principal domains were <20 and did not differ significantly (P > 0.05) between treatment groups. Postoperatively, the RFC patients returned to activity significantly earlier than MSD patients (17 +/- 7 vs. 22 +/- 6 days, P = 0.002). VAS pain scores at 6 h, 24 h, 6 weeks, and 1 year were significantly (P < 0.001) lower for the RFC group than for the MSD group (4 +/- 2, 2 +/- 0.5, 2 +/- 1, 2 +/- 1 vs. 8 +/- 1, 4 +/- 1, 4 +/- 1, 3 +/- 1, respectively). At 1 year, RFC patients had significantly better Tegner score (4.1 +/- 0.8 vs. 2.8 +/- 0.6, P < 0.001) and KOOS domain scores for pain, symptoms, ADL, QOL, respectively (81.1 +/- 8, vs. 59.4 +/- 12.8; 80.7 +/- 7.5 vs. 59.6 +/- 7.5; 81.5 +/- 6.5 vs. 60.1 +/- 6.9; 80 +/- 10 vs. 61.3 +/- 12.5; P < 0.001) than MSD patients. Significantly fewer RFC patients (2% vs 23%, p = 0.026) reported using NSAIDS for knee pain at 1 year. Patients undergoing radiofrequency-based chondroplasty for ICRS grade III medial femoral condyle chondral lesions in conjunction with partial meniscectomy had significantly better clinical outcomes through 1 year than patients with similar pathology receiving chondral debridement using the mechanical shaver.


Nerve ultrasound findings differentiate Charcot-Marie-Tooth disease (CMT) 1A from other demyelinating CMTs.
Ulnar/median motor nerve conduction velocity (MNCV) is ≤38 m/s in demyelinating Charcot-Marie-Tooth disease (CMT). Previous nerve high resolution ultrasound (HRUS) studies explored demyelinating CMT assuming it as a homogeneous genetic/pathological entity or focused on CMT1A. To explore the spectrum of nerve HRUS findings in demyelinating CMTs, we recruited patients with CMT1A (N = 44), CMT1B (N = 9), CMTX (N = 8) and CMT4C (N = 4). They underwent nerve conduction study (NCS) and HRUS of the median, ulnar, peroneal nerve, and the brachial plexus. Median, ulnar and peroneal MNCV significantly differed across CMT subtypes. Cross sectional area (CSA) was markedly and diffusely enlarged at all sites, except entrapment ones, in CMT1A, while it was slightly enlarged or within normal range in the other CMTs. No significant right-to-left difference was found. Age had limited effect on CSA. CSAs of some CMT1A patients largely overlapped with those of other demyelinating CMTs. A combination of three median CSA measures could separate CMT1A from other demyelinating CMTs. Nerve HRUS findings are heterogeneous in demyelinating CMTs. Nerve HRUS may separate CMT1A from other demyelinating CMTs. The large demyelinating CMTs HRUS spectrum may be related to its pathophysiological variability.


Assaying peptide translocation by the peptide transporter TAP.
MHC class I molecules display peptides at the cell surface that are mostly derived from cytosolic or nuclear proteins. Since peptide loading of MHC class I molecules occurs in the ER lumen, cytosolic peptides have to pass the ER membrane. The peptide transporter TAP translocates peptides over this ER membrane which is critical for successful MHC class I antigen presentation. How peptide translocation by TAP can be assayed and inhibitors of chemical or viral origin can be identified, will be described here.


Self-assembly of palladium nanoparticles on functional TiO2 nanotubes for a nonenzymatic glucose sensor.
Polydiallyldimethylammonium chloride, PDDA, was used as a stabilizer and linker for functionalized TiO2 nanotubes (TiO2 NTs). Self-assembled process with palladium nanoparticles (NPs) was successfully synthesized and used for the oxidation of glucose on glassy carbon electrodes. Based on the voltammetric and amperometric results, Pd NPs efficiently catalyzed the oxidation of glucose at -0.05 V in the presence of 0.1 M NaCl and showed excellent resistance toward interference poisoning from such interfering species as ascorbic acid, uric acid and urea. To further increase sensitivity, the Pd NPs-PDDA-TiO2 NTs/GCE was electrochemically treated with H2SO4 and NaOH, the glucose oxidation current was magnified 2.5 times than that before pretreatments due to greatly enhancing the electron transport property of the sensor based on the increased defect sites and surface oxide species. In view of the physiological level of glucose, the wide linear concentration range of glucose (4×10(-7)-8×10(-4)M) with a detection limit of 8×10(-8)M (S/N=3) was obviously good enough for clinical application.


Stereochemistry and mechanism of the GDP-mannose dehydratase reaction.
The reaction catalyzed by bacterial GDP-mannose dehydratase (E.C. 188.8.131.52), the conversion of GDP-D-mannose to GDP-4-keto-6-deoxymannose (GDP-6-deoxy-D-lyxo-hexos-4-ulose), was studied with (6R)- and (6S)-GDP-D-[4-2H1,6-3H]mannose. Conversion of these stereospecifically labeled substrates in the presence of excess unlabeled GDP-mannose into the 4-keto-6-deoxy derivatives followed by Kuhn-Roth oxidation gave acetic acid samples which were subjected to configurational analysis of the isotopically chiral methyl group. The observed F values of 64 for the material from the (6S) substrate and 31 for that from the (6R) isomer, corresponding to 48% e.e. R and 66% e.e. S configuration, respectively, of the methyl group indicate that (a) the oxidoreductase reaction involves transfer of H-4 to C-6, (b) the transfer is predominantly intramolecular, and (c) the transfer is stereospecific, H-4 replacing the C-6 hydroxyl group with inversion of configuration. A mechanism for the reaction is proposed on the basis of these results.


Vasopressin and thirst in patients with posterior pituitary ectopia and hypopituitarism.
Partial diabetes insipidus has been documented in patients with congenital hypopituitarism and posterior pituitary ectopia, some cases being clinically silent except for enuresis. The objective of our study was to evaluate vasopressin (AVP) secretion and thirst appreciation in hypopituitary patients with posterior pituitary ectopia. Twelve males and three females, aged between 13 and 38 years (median 19 years). Eleven had multiple pituitary deficiencies, adequately replaced at the time of the study, and four were only growth hormone deficient. None of the patients suffered from polyuria, polydipsia or nocturnal enuresis. We tested the patients with a 5% NaCl infusion. Five patients with abnormal vasopressin production were also tested with nitroprusside, which affects baroceptor vasopressin secretion. We found that only two out of 12 patients had normal AVP secretion. Thirst assessment showed severe hypodipsia in one patient, hyperdipsia in three out of 15 and more subtle abnormalities in two out of 15 patients. Concordance was found between osmotically and baroceptor-stimulated vasopressin. Patients with posterior pituitary ectopia showed a high prevalence of subclinical subnormal vasopressin response to the osmolar stimulus and moreover an impairment of thirst appreciation. Our data on nonosmotically stimulated AVP release suggest the existence of a damage in the hypothalamic vasopressin secreting centres.


The chest X-ray in antiglomerular basement membrane antibody disease (Goodpasture's syndrome).
The chest radiographs of 25 patients with proven antiglomerular basement membrane antibody disease (Goodpasture's syndrome) were analysed. All except two of the patients had pulmonary haemorrhage at some stage of their disease. Altogether there were 39 episodes of pulmonary haemorrhage, 25 being relapses. During seven episodes the chest radiograph was normal. Relapses of pulmonary haemorrhage never occurred in isolation but were usually associated with infection (not necessarily a chest infection) or occasionally fluid overload. Conversely fluid overload or infection were always associated with pulmonary haemorrhage provided there were high or rising titres of circulating antibodies at the time. Therefore in a patient with antiglomerular basement membrane antibody disease, the presence of shadowing in the lung fields on the chest radiograph almost invariably means the patient has pulmonary haemorrhage whether or not pulmonary oedema or a chest infection are present. Limitation of shadowing by a fissure, loss of major portions of the diaphragmatic or cardiac silhouette, involvement of the lung apex or costophrenic angles suggest an underlying chest infection. Septal lines suggest fluid overload. Pleural effusions are seen with chest infections and fluid overload. The carbon monoxide uptake (KCO) was invariably high in the presence of pulmonary haemorrhage even if the chest radiograph was normal. A combined use of KCO and chest radiographs is the best method of monitoring lung disease in these patients.


Lack of peptidoglycan in the cell walls of Methanosarcina barkeri.
Neither muramic acid and glucosamine nor D-glutamic acid or other amino acids typical of peptidoglycan were found in cell walls of two strains of Methanosarcina barkeri. The main components are galactosamine, neutral sugars and uronic acids. Therefore, the structural component of the cell wall most likely consists of an acid heteropolysaccharide, resembling that of Halococcus morrhuae. It is, however, not sulfated.


Shoot and inflorescence branching.
A major aspect of postembryonic plant development is the formation of secondary axes of growth: vegetative branches, inflorescence branches, or flowers. The first step in side-shoot development is the establishment of lateral meristems in the axils of leaves. GRAS-, MYB-, and bHLH-type transcription factors act as key regulators of early steps in this process. The REVOLUTA subfamily of HD-ZIP transcription factors controls the organization of lateral meristems. Whereas the development of lateral meristems into lateral buds is only poorly understood, recent studies have provided new insights into the regulation of lateral bud outgrowth. The MORE AXILLARY GROWTH (MAX) genes of Arabidopsis and the RAMOSUS (RMS) genes of pea are involved in the production, perception, and transduction of a signal that inhibits lateral bud outgrowth. Synthesis of this not-yet-identified hormone is positively regulated by the main shoot tip through auxin signalling.


OSA patients not treated with PAP - Evolution over 5 years according to the Baveno classification and cardiovascular outcomes.
The evolution of patients with obstructive sleep apnea (OSA) non-eligible for PAP-therapy at diagnosis is unknown. Currently, the severity of OSA is based on the apnea-hypopnea index (AHI), but its prognostic relevance has raised concerns. The Baveno classification may allow a better stratification of severity and therapeutic guidance in OSA. Patients with AHI≥5/h in 2015, classified into Baveno groups A and B and non-eligible for PAP therapy at diagnosis and over 5 years, were analyzed. Patients were reclassified into Baveno groups (A-D) and changes in groups over 5 years were explored. Patients in Baveno groups C and D, who developed major cardiovascular comorbidities (CVC) or end-organ damage (EOD group), were compared with patients in Baveno groups A and B (non-EOD group). To identify predictors of the development of major CVC or EOD, a logistic regression analysis was performed. There were 76 patients, 58% male, mean age 51.9 ± 10.1 years, mean body mass index (BMI) of 30.3 ± 5.0 kg/m2 and median AHI of 8.9 (5.9-12.0) events/h. At diagnosis, 46% and 54% of patients were classified into Baveno group A and group B, respectively. In total, 21% of patients developed major CVC or EOD (Baveno group C or D); higher age (p = 0.011) and BMI (p = 0.004) and a higher percentage of central apneas (p = 0.012) at diagnosis significantly predicted it, while sex, sleepiness, insomnia, AHI, ODI and T90 were not. A significant percentage of patients non-eligible for PAP-therapy at diagnosis of OSA developed CVC or EOD; higher age and BMI and a higher percentage of central apneas were significant predictors.


Relationship between response of gamma-glutamyltransferase to alcohol consumption and levels of fasting plasma glucose.
To examine whether the response of fasting plasma glucose (FPG) to alcohol consumption differs among individuals, a cross-sectional study was conducted in 6100 men with a body-mass index below 24 who did not take medication for diabetes. Information regarding current medication and lifestyle habits was obtained by a self-reported questionnaire. The subjects were divided into four groups according to their level of alcohol consumption: non-drinkers, light drinkers (1-188ml/week), intermediate drinkers (189-377ml/week), and heavy drinkers (>or=378ml/week). The frequency of subjects with an FPG of 110mg/dl or more rose significantly as alcohol consumption increased, from 6.7% in non-drinkers to 10.1% in intermediate drinkers and 12.1% in heavy drinkers. In contrast, when only the subjects with a gamma-glutamyltransferase level of less than 40IU/L were analyzed, no difference was observed in the frequency of subjects with an FPG level of 110mg/dl or more among the four groups. Multiple logistic regression analysis also revealed similar results. The findings suggested individual variability in the response of FPG to drinking. Appropriate levels of drinking could be different among individuals.


Synthesis of a non-nucleoside reverse transcriptase inhibitor in the alkenyldiarylmethane (ADAM) series with optimized potency and therapeutic index.
A novel alkenyldiarylmethane (ADAM) analog has been synthesized with enhanced potency as an anti-HIV agent. The new compound (ADAM II) inhibits the cytopathic effect of HIV-1RF in CEM-SS cells with an EC50 of 13 nM, while it shows cytotoxicity with a CC50 of 31.6 microM, providing a therapeutic index of 2430. ADAM II is a non-nucleoside reverse transcriptase inhibitor, displaying an IC50 of 0.3 microM with poly(rC) oligo(dG) as the template/primer.


Adhesion obstruction following Nissen fundoplication in children.
The incidence of postoperative adhesion intestinal obstruction among 156 children who had undergone Nissen fundoplication for intractable gastro-oesophageal reflux was determined. There were 18 episodes of obstruction in 16 patients (10.3 per cent). The mean interval between fundoplication and adhesion obstruction was 10 months (range 10 days-4 years). Additional procedures performed at the original laparotomy substantially increased the risk of developing obstruction. Relaparotomy for adhesion obstruction was required by 21 per cent of patients who had a Ladd's procedure and 12 per cent who had appendicectomy. Presenting symptoms were not typical of intestinal obstruction because many of these children were unable to vomit. Only three did vomit but all had radiological appearance suggestive of small bowel obstruction. There were two deaths directly related to adhesion obstruction.


Adherence, internalization, and persistence of Helicobacter pylori in hepatocytes.
Although Helicobacter pylori have been identified in the liver, the role of Helicobacter sp. in human liver diseases remains unclear. This study explored whether H. pylori were internalized and could persist in hepatocytes. The majority of an inoculum of H. pylori (1 x 10(7) colony forming units) adhered to hepatocytes. Using the gentamicin invasion assay we found that approximately 2% were internalized and persisted following passage for more than 2 months. Electron microscopy confirmed the presence of intracellular Helicobacter. The number of adherent or internalized H. pylori was significantly greater with hepatocytes than with gastric epithelial cells (P < 0.05) and was also dependent on cag pathogenicity island (PAI), VacA, OipA, or BabA status. Transmission electron microscopy was used to confirm adherence and invasion of H. pylori into hepatocytes. Internalization of H. pylori was inhibited by antibodies to beta1-integrin receptors, genistein, and cytochalasin D (P < 0.05) consistent with beta1-integrin acting as a surface receptor with additional requirements for tyrosine kinase phosphorylation and actin polymerization. In summary, H. pylori both adhered to and invaded into hepatocytes in vitro, depending on the virulent factors, and persisted within hepatocytes during subcultures. beta1-integrin is likely a receptor involved in internalization of H. pylori into hepatocytes.


Rat C3 conversion by rat anti-2,4,dinitrophenyl (DNP) hapten IgA immune precipitates.
Monomeric (m-) and polymeric (p-) anti-DNP monoclonal (MC) rat IgA antibodies (Ab) were tested for precipitation with DNP-bovine serum albumin (DNP-BSA) and C3 conversion in rat serum, with rat MC anti-DNP IgG2b used as reference. At equivalence, p-IgA rapidly precipitated DNP-BSA, with little antigen (Ag) left in the supernatant. In contrast, m-IgA at five-fold higher concentration precipitated Ag very slowly, with less than 50% of Ag precipitated at equivalence. The Ag/Ab weight ratio at equivalence was 0.13 for both m- and p-IgA, but the molar ratio was 0.3 for m-IgA and close to 1.0 for p-IgA, suggesting a higher avidity of p-IgA. Rat C3 conversion by rat IgA immune precipitates (IP) was about 20% with m-IgA and 40% with p-IgA. EGTA did not significantly affect these figures. Therefore, rat MC IgA IP activated the rat alternative C pathway. Neither rat nor mouse IgA anti-DNP IP activated C3 in normal human serum.


Novel predictors of soil genesis following natural weathering processes of bauxite residues.
Bauxite residue often has chemical and physical limitations to support plant growth, and improving its matrix properties is crucial to support sustainable vegetation in the long term. Spontaneous vegetation colonization on deposits in Central China, over a period of 20 years, has revealed that natural weathering processes may convert bauxite residue to a soil-like medium. Residue samples from different stacking ages were collected to determine the effect of natural processes on matrix properties over time. It was demonstrated that natural processes decreased pH (10.98 to 9.45), electrical conductivity (EC) (3.73 to 0.36 mS/cm), and exchangeable sodium percentage (ESP) (72.51 to 28.99 %), while increasing bulk density (1.91 to 1.39 g/cm(3)), improving the mean weight diameter (MWD) of water-stable aggregates (0.24 to 0.52 mm), and the proportion of >0.25-mm water-stable aggregates (19.91 to 50.73 %). The accumulation of organic carbon and the reduction of ESP and exchangeable Na had positive effects on soil aggregate formation, while exchangeable Ca and Mg were significantly beneficial to aggregation of water-stable aggregates. Climate, stacking time, and biological factors appear to improve the structure of bauxite residue. Our findings demonstrate soil genesis occurring following natural weathering processes of bauxite residues over time.


Transient Ischemic Attack (TIA) Incidence with Geographic Information Systems (GIS) Mapping for Stroke Prevention Interventions.
GIS mapping as a public health tool has been increasingly applied to chronic disease control. While evaluating TIA incidence from an existing regional stroke registry in Ludhiana city, India, we aim to apply the innovative concept of regional TIA GIS mapping for planning targeted stroke prevention interventions. TIA patient data was obtained from hospitals, scan centers and general practitioners from March 2010 to March 2013 using WHO-Stroke STEPS based surveillance as part of establishing a population-based stroke registry in Ludhiana city. From this registry, patients with TIA (diagnosed by MRI image-based stroke rule-out, or clinically) were chosen and data analyzed. A total of 138 TIA patients were included in the final analysis. The annual TIA incidence rate for Ludhiana city was 7.13/100,000 (95% confidence interval: 5.52 to 8.74) for 2012-2013. Mean age was 58.5 ± 13.9 years (range: 22-88 years) and 87 (63%) were men. Majority of the TIA cases had anterior circulation TIAs. Hypertension (87.4%) was the most common risk factor. Using Geographic Information System (GIS) mapping, high TIA incidence was seen in central, western, and southern parts and clustering of TIA cumulative incidence was seen in the central part of Ludhiana city. Incidence rate of TIA was lower than that expected from a low- and middle-income country (LMIC). TIA GIS mapping, looking at regional localization, can be a novel option for developing targeted, cost-effective stroke prevention programs.


Effect of aqueous extract from root and leaf of Sphenocentrum jollyanum pierre on wounds of diabetic rats: Influence on wound tissue cytokines, vascular endothelial growth factor and microbes.
Sphenocentrum jollyanum is a flowering plant of the Menispermaceae family with bright yellow roots and wedged-shaped leaves. The plant is reputed to possess exceptional wound healing properties and used in folkloric medicine to dress chronic wounds. Wound repair in a hyperglycemic state is known to be impaired and delayed making treatment a difficult challenge. This study sought how the aqueous extracts of root and leaf of Sphenocentrum jollyanum facilitated wound healing by modulating pro-inflammatory cytokines, vascular endothelial growth factor and microbial colonization on excision wound created in diabetic rats. Diabetes (blood glucose >250 mg/dl) was induced by feeding normal rats with high fat diet for 14 days after which intraperitoneal injection of low dose streptozotocin (35 mg/kg b.w.) was administered. Wounds were subsequently created and treatments administered afterwards for 14 days. Administration of Sphenocentrum jollyanum root and leaf extracts both orally and topically (100 and 200 mg/kg b.w) significantly (p < 0.05) reduced secretion of pro-inflammatory cytokines (TNF-α, IL-6), number of microbial colonies (CFU/ml × 102), activity of myeloperoxidase and significantly increased growth factor secretion on wounds of the diabetic rats. Histological evaluations of wound tissues of treated diabetic rats revealed matured tissue granulation, presence of new blood vessels, collagen and fibroblast with fewer inflammatory cells. The use of Sphenocentrum jollyanum effectively enhanced wound healing which may be related to constituents identified by GC-MS analysis and can thus, be suggested as a therapeutic agent for diabetic wound management.


Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update.
Clinical data show that a 1% increase in serum concentrations of high-density lipoprotein cholesterol (HDL-C) can decrease cardiovascular risk by 2% to 3%. Therefore, mechanisms affecting the level and functionality of high-density lipoprotein (HDL) and its constituents are being investigated as targets for the rational development of drugs to prevent or treat cardiovascular disease. High-density lipoprotein-related research may also increase our understanding of the link between atherosclerosis and metabolic disorders. This report and update of the HDL Working Group discusses HDL metabolism and reverse cholesterol transport, impaired HDL as a marker and a cause of proatherogenic states, and experimental and current approaches to HDL-related therapy.


Vape shop identification, density and place characteristics in six metropolitan areas across the US.
Vaping is increasingly prevalent and controversial. Vape shops and convenience stores are common but distinct sources of vaping products, and where they locate may reflect likely target markets. This study examined the density and neighborhood demographics of vape shops and convenience stores in six metropolitan statistical areas (MSAs): Atlanta, Boston, Minneapolis, Oklahoma City, San Diego, Seattle. We identified 459 vape shops using Yelp and Google application programming interfaces and 10,777 convenience stores using ReferenceUSA and Dun & Bradstreet. Retailers were geocoded to census tracts (n = 4,442), and logistic regressions were conducted using as predictors percent non-White, percent youth (5-17 years or 5-20 years), and median household income from the American Community Survey, 2013-2017. Per 10,000 young adults, vape shop density ranged from 0.6 (Boston, San Diego) to 1.7 (Oklahoma City), and convenience store density ranged from 12.6 (San Diego) to 26.3 (Oklahoma City). Logistic regressions indicated that vape shops more likely resided in tracts with lower percentages of youth in Boston, but higher percentages of youth in Atlanta, as well as with lower incomes in Boston and Seattle. Convenience stores more likely resided in tracts with lower percentages of non-Whites in Atlanta and Boston; lower incomes in Atlanta, Boston, San Diego, and Seattle; and higher percentages of youth in Atlanta, Boston, and Minneapolis. These common retail sources of vaping products differentially locate in relation to neighborhood sociodemographics across MSAs. Findings suggest that, in some MSAs, vape shops and convenience stores may target youth and lower income populations.


A complex array of sequences enhances ribosomal transcription in Xenopus laevis.
The ribosomal DNA spacer in Xenopus laevis was shown in previous studies to be involved in regulating the expression of the ribosomal genes. Here transcription enhancement by this spacer has been studied in some detail, to fully identify the sequences involved and to determine their relative importance in this phenomenon. It is shown that the 60/81 base-pair (bp) repeats, which were reported to be enhancer elements, act as part of a mode of enhancement whose effect is amplified by the spacer promoters or Bam islands. The "Bam super repeat", a combination of spacer promoter and 60/81 bp elements, is the major enhancer unit. Within a Bam super repeat, a near linear correlation between the number of 60/81 bp elements and enhancer activity is observed. Thus, there is no significant co-operativity in the binding of transcription factors to an array of these elements. Multiple Bam super repeats do not act additively and may actually interfere with each others action. Surprisingly this effect is observed both in the presence and absence of active spacer promoters. Sequences between the 3' end of the 28 S coding region and the first spacer promoter may also be involved in enhancement but only in a very minor fashion. In confirmation of recent studies, the presence of the unique ribosomal termination sequence, 213 bp upstream from the pre-rRNA initiation site, is essential for efficient promotion, as deletion of this sequence virtually abolishes pre-rRNA- transcription. These data are discussed in terms of the possible mechanisms of transcription enhancement.


Evidence-based imaging guidelines and Medicare payment policy.
This study examines the relationship between evidence-based appropriateness criteria for neurologic imaging procedures and Medicare payment determinations. The primary research question is whether Medicare is more likely to pay for imaging procedures as the level of appropriateness increases. The American College of Radiology Appropriateness Criteria (ACRAC) for neurological imaging, ICD-9-CM codes, CPT codes, and payment determinations by the Medicare Part B carrier for Florida and Connecticut. Cross-sectional study of appropriateness criteria and Medicare Part B payment policy for neurological imaging. In addition to descriptive and bivariate statistics, multivariate logistic regression on payment determination (yes or no) was performed. The American College of Radiology Appropriateness Criteria (ACRAC) documents specific to neurological imaging, ICD-9-CM codes, and CPT codes were used to create 2,510 medical condition/imaging procedure combinations, with associated appropriateness scores (coded as low/middle/high). As the level of appropriateness increased, more medical condition/imaging procedure combinations were payable (low = 61 percent, middle = 70 percent, and high = 74 percent). Logistic regression indicated that the odds of a medical condition/imaging procedure combination with a middle level of appropriateness being payable was 48 percent higher than for an otherwise similar combination with a low appropriateness score (95 percent CI on odds ratio=1.19-1.84). The odds ratio for being payable between high and low levels of appropriateness was 2.25 (95 percent CI: 1.66-3.04). Medicare could improve its payment determinations by taking advantage of existing clinical guidelines, appropriateness criteria, and other authoritative resources for evidence-based practice. Such an approach would give providers a financial incentive that is aligned with best-practice medicine. In particular, Medicare should review and update its payment policies to reflect current information on the appropriateness of alternative imaging procedures for the same medical condition.


Single Atom Nucleation of Cobalt over Graphene Oxide: Theory and Experimental Study.
Nucleation and growth mechanism of Co electrodeposition over graphene oxide (GO) was studied using cyclic voltammetry (CV) and chronoamperometry techniques. The studies were performed over an aqueous electrolyte containing 10 mM CoSO4·7H2O maintained at an initial pH of 2.5. CV studies established that the deposition mechanism was diffusion-controlled and irreversible. Chronoamperometry studies revealed the presence of three concurrent processes: an initial adsorption current, which indicated adatom layer formation, 3D nucleation and growth of Co islands over GO, and hydrogen evolution over the deposited Co nanoclusters. It was observed that the nucleation rate increased with increasing the overpotential (η) for deposition (from 2.71 × 104 cm-2 s-1 at η = 0.35 V to 3.62 × 106 cm-2 s-1 at η = 0.90 V). Application of the classical theory of nucleation over the chronoamperometry results suggested that the free energy of formation of the critical nucleus was lower than room temperature thermal energy. This indicated that the nucleation and growth process was not activation-controlled but rather a kinetically controlled process. Application of Milchev's atomistic theory revealed that every single atom of Co deposited over the GO sheet was a supercritical nucleus that could grow into a cluster irreversibly.


The relationship of availability of alcoholic beverages to per capita consumption and alcoholism rates.
A study of the relationship between availability of beverage alcohol and per capita consumption and alcoholism rates in the U.S.A. indicates that income and urbanism are more closely related to consumption and alcoholism rates than is availability.


Production of Staphylococcus membranes and their enzymatic and protein characteristics.
Three methods of decomposition of Staphylococcus aureus 209-P cells were compared for the production of membranes-ultrasound, a press, and enzymatic lysis. All the tested methods permitted the isolation of enzymatically active membranes, differing somewhat in protein composition.


Effect of probenecid on the formation and elimination of acyl glucuronides: studies with zomepirac.
When 100 mg oral zomepirac was taken with 500 mg b.i.d. oral probenecid by six healthy subjects, the disposition of zomepirac was markedly altered. Probenecid decreased total plasma clearance of zomepirac by 64%, which resulted in an increase in bioavailability from 0.55 without probenecid to 0.84 when given concurrently. The apparent metabolic clearance of zomepirac to form zomepirac acyl glucuronide was reduced 71% and zomepirac renal clearance, a minor elimination route, was reduced by 79%. When assayed by a method that prevents degradation of the labile acyl glucuronide, zomepirac glucuronide concentrations in plasma were comparable to those of zomepirac. Probenecid decreased the renal clearance of zomepirac glucuronide by 72%, which, together with the increased zomepirac levels, resulted in a 2.8-fold increase in the AUC of the conjugate. Urinary excretion of zomepirac glucuronide was reduced from 72% to 58% of the dose, but the excretion of free zomepirac was unchanged at 5% of the dose. The ratio of the total clearance/bioavailability of zomepirac in control subjects was 682 +/- 246 ml/min, which is double the value reported in previous studies of zomepirac disposition. We believe that this difference is due to degradation of the unstable zomepirac acyl glucuronide in the previous analytic methodologies used. Qualitatively, the effects of probenecid on zomepirac disposition are similar to those previously reported for other drugs of this class that are metabolized to acyl glucuronides. However, zomepirac appears unusual in that significant levels of its acyl glucuronide metabolite are found in vivo.


[Expression of HOXA10 gene in human endometrium and its relationship with unexplained infertility].
To study the expression of HOXA10 gene in the endometrium of normal fertile women and patients with unexplained infertility during different phases of menstrual cycle. Endometrium samples were obtained by curettage in 52 normal fertile women and 38 patients with unexplained infertility during different phases of menstrual cycle, HOXA10 mRNA expression were detected by in situ hybridization and reverse polymerase chain reaction (RT-PCR). (1) HOXA10 mRNA were detected in the glandular and stromal cells of endometrium of fertile women during the menstrual cycle. By in situ hybridization (positive unite, PU), HOXA10 mRNA levels were significantly higher in the mid-secretory phase [glandular cells (G) 5.69 +/- 0.57, stromal cells (S) 7.48 +/- 0.67] and late-secretory phase(G 5.99 +/- 0.40, S 7.98 +/- 1.08) than those in late proliferative phase (G 3.35 +/- 0.20, S 3.20 +/- 0.37) and early secretory phase (G 3.07 +/- 0.26, S 3.18 +/- 0.27)(P < 0.01). HOXA10 mRNA levels of endometrial stromal cells of mid and late secretory were higher than those of glandular cells (P < 0.01). By RT-PCR, HOXA10 mRNA levels were significantly higher in the mid secretory phase (57.0 +/- 3.4)% and late secretory phase (56.2 +/- 2.9)% than those in early proliferative phase (31.8 +/- 2.6)%, late proliferative phase (32.2 +/- 2.3)% and early secretory phase (32.5 +/- 1.6)% (P < 0.01). (2) Patients with unexplained infertility did not have an increase of endometrial HOXA10 mRNA level in mid and late secretory phase, as compared with the controls (P < 0.01). (1) High expression of HOXA10 gene during mid and late secretory phase indicated that HOXA10 gene may involve in implantation. (2) Aberrant HOXA10 expression of patients with unexplained infertility suggests that altered development of endometrium at the molecular level may contribute to the aetiology of infertility. (3) HOXA10 gene may play a role in decidua lization of endometrium during early pregnancy.


Regression of glomerular injury by losartan in experimental diabetic nephropathy.
Many features of chronic kidney disease may be reversed, but it is unclear whether advanced lesions, such as adhesions of sclerotic glomerular tufts to Bowman's capsule (synechiae), can resolve during treatment. We previously showed, using a renal ablation model, that the renoprotective effect of the AT-1 receptor blocker, losartan, is dose-dependent. Here we determined if moderate and advanced glomerular lesions, associated with streptozotocin-induced diabetes, regress with conventional or high-dose losartan treatment. Using daily insulin injection for 10 months, we maintained diabetic adult male Munich-Wistar rats in a state of moderate hyperglycemia. Following this period, some rats continued to receive insulin with or without conventional or high-dose losartan for an additional 2 months. Diabetic rats pretreated with insulin for 10 months and age-matched non-diabetic rats served as controls. Mesangial expansion was found in the control diabetic rats and was exacerbated in those rats maintained on only insulin for an additional 2 months. Conventional and high-dose losartan treatments reduced this mesangial expansion and the severity of synechiae lesions below that found prior to treatment; however, the frequency of the latter was unchanged. There was no dose-response effect of losartan. Our results show that regression of mesangial expansion and contraction of sclerotic lesions is feasible in the treatment of diabetes, but complete resolution of advanced glomerulosclerosis may be hard to achieve.


Stable and luminescent halide perovskite fabricated in water.
Lead bromide perovskite nanoparticles are fabricated in the water, which has been recognized previously as a severe source of damage to halide perovskite materials and devices. The perovskite nanoparticles exhibit a high photoluminescence quantum yield and excellent material stability.


The Use of Release-Active Antibody-Based Preparations for Vertigo Prevention in Adults.
The effectiveness of antibody-based release-active preparations Impaza (antibodies to eNOS), Tenoten (antibodies to brain-specific protein S-100), Dietressa (antibodies to type 1 cannabinoid receptor), Brizantin (combined preparation, antibodies to brain-specific protein S-100 and type 1 cannabinoid receptor), and Divaza (combined preparation, antibodies to brain-specific protein S-100 and eNOS) in the prevention of vertigo was studied on the model of intermittent accumulation of Coriolis accelerations (ICCA). Modification of activity of vestibular receptors and signal systems by release-active preparations contributed to an increase in ICCA tolerance time. Combined preparation Impaza possessed the most significant antinaupathic properties. Brizantin was less potent in this respect.


Treatment of congenital clubfoot using Ponseti method.
To quantitatively and qualitatively analyze the results from treatment of congenital clubfoot with a mean follow-up of 4.6 years. 26 patients who underwent treatment by means of the Ponseti method were analyzed (total of 39 feet). The mean age at the start of the treatment was 5.65 months. The mean length of the follow-up subsequent to tenotomy of the Achilles tendon was 4.6 years. Patients with secondary clubfoot were excluded. Epidemiological data, radiographic measurements on the Kite angle and data from a satisfaction questionnaire and the Laaveg questionnaire were analyzed. Among the 26 patients treated, one presented recurrence of the deformity and had to return to the beginning of the treatment. The mean score from the questionnaire and physical examination was 89.76 points, and this result was considered good. 99% of the patients responded that their feet never hurt or hurt only upon great activity; 88% said that their feet did not limit their activities; and 96% said that they were very satisfied or satisfied with the results from the treatment. The mean Kite angle in anteroposterior view was 28.14° and it was 26.11° in lateral view. Treatment for idiopathic congenital clubfoot by means of the Ponseti method brings better results together with less soft-tissue injury, thus confirming the effectiveness and good reproducibility of this method.


Children's Early Spontaneous Comparisons Predict Later Analogical Reasoning Skills: An Investigation of Parental Influence.
Laboratory studies have demonstrated beneficial effects of making comparisons on children's analogical reasoning skills. We extend this finding to an observational dataset comprising 42 children. The prevalence of specific comparisons, which identify a feature of similarity or difference, in children's spontaneous speech from 14-58 months is associated with higher scores in tests of verbal and non-verbal analogy in 6th grade. We test two pre-registered hypotheses about how parents influence children's production of specific comparisons: 1) via modelling, where parents produce specific comparisons during the sessions prior to child onset of this behaviour; 2) via responsiveness, where parents respond to their children's earliest specific comparisons in variably engaged ways. We do not find that parent modelling or responsiveness predicts children's production of specific comparisons. However, one of our pre-registered control analyses suggests that parents' global comparisons-comparisons that do not identify a specific feature of similarity or difference-may bootstrap children's later production of specific comparisons, controlling for parent IQ. We present exploratory analyses following up on this finding and suggest avenues for future confirmatory research. The results illuminate a potential route by which parents' behaviour may influence children's early spontaneous comparisons and potentially their later analogical reasoning skills.


Intracanalicular dexamethasone insert for post-corneal crosslinking inflammation and pain: the LINK study.
To compare the efficacy of an intracanalicular dexamethasone insert with tapered topical steroid over 28 days after corneal cross-linking (CXL). Single private practice, outpatient setting. Prospective observational randomized study. This prospective randomized study investigated the efficacy of a dexamethasone intracanalicular insert on post-CXL pain and inflammation in progressive keratoconus patients. 20 patients (40 eyes) were enrolled; half were randomized to the dexamethasone intracanalicular insert group; half were prescribed a 28-day topical tapering steroid regimen. All patients were evaluated for pain scores, rate of re-epithelialization, ease of the post-CXL regimen, and need for rescue pain medication after standard bilateral epithelium-off CXL on postoperative day (POD) 1, POD3, and POD4 to 7, as well as postoperative week (POW) 1, POW2, POW3, and POW4. 20 patients (40 eyes) underwent standard-of-care epithelium-off bilateral CXL for progressive keratoconus. 10 patients were randomized to receive prednisolone eyedrops on a tapering schedule after CXL; 10 patients received dexamethasone intracanalicular inserts at the time of CXL. Regardless of the postoperative steroid regimen, there was no significant difference in the rate of re-epithelialization or use of rescue pain medication between groups. There was a nominal, however, statistical difference in pain scores between groups, favoring prednisolone eyedrops. Both groups stated no difficulty in following postoperative regimens. There were no adverse events noted in relation to treatment or the CXL procedure. Using a dexamethasone insert to alleviate pain and inflammation can be considered as a safe and efficacious part of a post-CXL regimen.


Control of center of mass motion during walking correlates with gait and balance in people with incomplete spinal cord injury.
There is evidence that ambulatory people with incomplete spinal cord injury (iSCI) have an impaired ability to control lateral motion of their whole-body center of mass (COM) during walking. This impairment is believed to contribute to functional deficits in gait and balance, however that relationship is unclear. Thus, this cross-sectional study examines the relationship between the ability to control lateral COM motion during walking and functional measures of gait and balance in people with iSCI. We assessed the ability to control lateral COM motion during walking and conducted clinical gait and balance outcome measures on 20 ambulatory adults with chronic iSCI (C1-T10 injury, American Spinal Injury Association Impairment Scale C or D). To assess their ability to control lateral COM motion, participants performed three treadmill walking trials. During each trial, real-time lateral COM position and a target lane were projected on the treadmill. Participants were instructed to keep their lateral COM position within the lane. If successful, an automated control algorithm progressively reduced the lane width, making the task more challenging. If unsuccessful, the lane width increased. The adaptive lane width was designed to challenge each participant's maximum capacity to control lateral COM motion during walking. To quantify control of lateral COM motion, we calculated lateral COM excursion during each gait cycle and then identified the minimum lateral COM excursion occurring during five consecutive gait cycles. Our clinical outcome measures were Berg Balance Scale (BBS), Timed Up and Go test (TUG), 10-Meter Walk Test (10MWT) and Functional Gait Assessment (FGA). We used a Spearman correlation analysis (ρ) to examine the relationship between minimum lateral COM excursion and clinical measures. Minimum lateral COM excursion had significant moderate correlations with BBS (ρ = -0.54, p = 0.014), TUG (ρ = 0.59, p = 0.007), FGA (ρ = -0.59, p = 0.007), 10MWT-preferred (ρ = -0.59, p = 0.006) and 10MWT-fast (ρ = -0.68, p = 0.001). Control of lateral COM motion during walking is associated with a wide range of clinical gait and balance measures in people with iSCI. This finding suggests the ability to control lateral COM motion during walking could be a contributing factor to gait and balance in people with iSCI.


The epileptic encephalopathies.
The term epileptic encephalopathy refers to the condition where epileptic activity, clinical or subclinical, is thought to be responsible for any disturbance of cognition, behavior, or motor control. Although currently described as a concept that may occur in any of the epilepsies, children with the severe early onset epilepsies are thought to be more at risk than others. These epilepsies have been termed the "epileptic encephalopathies." The degree to which epileptic activity is responsible for neurodevelopmental compromise may be variable in each individual case, and the degree to which this may be reversible unclear. Data from the laboratory and the clinic may provide greater insight into the degree to which epileptic activity may contribute in individual syndromes, although much is yet to be learnt. The aim in epilepsy management remains one of seizure control; in some specific circumstances this may include subclinical epileptic activity. However, avoidance of treatment that may lead to deterioration of seizure control may be equally important.


Evaluation of congenital extracranial masses by waterpath sonography.
Congenital scalp masses pose a diagnostic and management challenge. In the past the relationship of the lesion to the skull and intracranial contents have been assessed by skull x-rays and computed cranial tomography. Waterpath sonography is a non-invasive technique that utilizes no ionizing radiation for evaluating and monitoring congenital scalp masses. In two illustrative cases this method of imaging assisted in assessing the size, contents, and relationship of the congenital scalp masses to the intracranial contents. It enabled the surgeon to anticipate the avascular cystic nature of the congenital scalp masses, the intact underlying calvarium, and non-violation of the CSF pathways prior to surgery. The technique was also useful for monitoring progress after surgery.


AKT/mTOR Signal Cascade and Expression of PD-1, PD-L1, and PD-L2 in Gastric Cancer.
The peculiarities of gastric cancer development associated with the expression levels of components of the AKT/mTOR signaling cascade and PD, PD-L1, PD-L2 have not yet been identified. We revealed the fundamental changes in the expression AKT/mTOR and PD receptors and their ligands associated with dissemination of gastric cancer. An increase in the mRNA level of all components of this cascade was demonstrated. The expression of mTOR and AKT decreased against the background of enhanced expression of PTEN phosphatase. The increase in the expression of PD-1 receptors and PD-L1 and PD-L2 ligands was most pronounced in patients with distant metastases.


Visual number sense for real-world scenes shared by deep neural networks and humans.
Recently, visual number sense has been identified from deep neural networks (DNNs). However, whether DNNs have the same capacity for real-world scenes, rather than the simple geometric figures that are often tested, is unclear. In this study, we explore the number perception of scenes using AlexNet and find that numerosity can be represented by the pattern of group activation of the category layer units. The global activation of these units increases with the number of objects in the scene, and the variations in their activation decrease accordingly. By decoding the numerosity from this pattern, we reveal that the embedding coefficient of a scene determines the likelihood of potential objects to contribute to numerical perception. This was demonstrated by the more optimized performance for pictures with relatively high embedding coefficients in both DNNs and humans. This study for the first time shows that a distinct feature in visual environments, revealed by DNNs, can modulate human perception, supported by a group-coding mechanism.


Parallel Accelerator and Molecular Mass Spectrometry Measurement of Carbon-14-Labeled Analytes.
Parallel accelerator and molecular mass spectrometry (PAMMS) is a powerful analytical technique capable of simultaneous quantitation of carbon-14 tracer and structural characterization of 14C-labeled biomolecules. Here we describe the use of PAMMS for the analysis of biological molecules separated by high-performance liquid chromatography. This protocol is intended to serve as a guide for researchers who need to perform PAMMS experiments using instrumentation available at resource centers such as the National User Resource for Biological Accelerator Mass Spectrometry at Lawrence Livermore National Laboratory.


Veni, vidi, vici: in vivo molecular imaging of immune response.
"I came, I saw, I conquered," Julius Caesar proclaimed, highlighting the importance of direct visualization as a winning strategy. Continuing the "From the Field" series (see Editorial [2007] 26, 131), Gross et al. summarize how modern molecular imaging techniques can successfully dissect the complexities of immune response in vivo.


Modified Maxillary-Swing Approach for Resection of Primary Malignancies in the Pterygopalatine Fossa.
En bloc resection of malignancies in the pterygopalatine fossa (PPF) poses critical challenges. Using the modified maxillary-swing (MMS) approach, we achieved monobloc removal of primary malignancies in this region. This study provides a detailed account of the surgical techniques and indications used. We enrolled seven patients with primary malignancies in the PPF during a period from January 2012 to January 2019 in this retrospective study. After malignancies were confirmed by biopsy as well as evaluation with computed tomography (CT) and magnetic resonance imaging (MRI) scans, all of the patients underwent MMS surgery under general anesthesia to extirpate these tumors. We performed regular postoperative follow-up using CT and MRI scans. En bloc resection was successfully performed in all cases. We observed negative margins in six cases and positive margins in one patient with adenoid cystic carcinoma, who received postoperative radiotherapy. The most common complication was facial numbness. During the follow-up period (range, 6-69 months), one patient suffered from recurrence, while the others did not. The advantages of the MMS include a wide surgical field, full exposure, and easy manipulation. We expect this approach to become an alternative to the monobloc resection of malignancies in the PPF that involve the infratemporal fossa, maxillary sinus, nasal cavity, orbit, or oral cavity.