Clustering DNA sequences by feature vectors.
We represent all DNA sequences as points in twelve-dimensional space in such a way that homologous DNA sequences are clustered together, from which a new genomic space is created for global DNA sequences comparison of millions of genes simultaneously. More specifically, basing on the contents of four nucleotides, their distances from the origin and their distribution along the sequences, a twelve-dimensional vector is given to any DNA sequence. The applicability of this analysis on global comparison of gene structures was tested on myoglobin, beta-globin, histone-4, lysozyme, and rhodopsin families. Members from each family exhibit smaller vector distances relative to the distances of members from different families. The vector distance also distinguishes random sequences generated based on same bases composition. Sequence comparisons showed consistency with the BLAST method. Once the new gene is discovered, we can compute the location of this new gene in our genomic space. It is natural to predict that the properties of this new gene are similar to the properties of known genes that are locating near by. Biologists can do various experiments to test these properties.


The effects of light on foliar chemistry, growth and susceptibility of seedlings of a canopy tree to an attine ant.
Seedlings of Inga oerstediana Benth. (Mimosaceae) growing in three different light environments (the understory, tree-fall gaps and full sun) were tested for differences in chemistry (nutrients and tannins), wound-induced increases in tannins, growth, and susceptibility to leaf-cutter ants, Atta cephalotes (L.) (Formicidae: Attini). I hypothesized that seedlings of I. oerstediana would contain higher concentrations of tannins when growing in high light conditions and, therefore, would be less susceptible to leaf-cutter ants.Foliar concentrations of condensed tannins were much higher in plants growing in full sun compared to those growing in the understory. The concentrations of condensed tannins did not increase following damage. Despite higher concentrations of condensed tannins in sun foliage, leaf-cutter ants found these leaves more acceptable. The preference for sun leaves was consistent with higher concentrations of foliar nutrients. I suggest that the magnitude of the increase in condensed tannins was not great enough to override the benefits of increased concentrations of foliar nutrients. Finally, based on these results and those of others, I suggest that foraging by leaf-cutter ants may be an important factor determining patterns of succession in early successional habitats.


Momentary and wide aortic regurgitation as an indicator of aortic dissection.
A 55-year-old female with a history of hypertension was admitted for dyspnea, epigastralgia and nausea. A chest X-ray showed pulmonary congestion. Transthoracic echocardiography (TTE) revealed severe left ventricular dysfunction with akinesis of the infero-posterior wall and Doppler color-flow mode showed mild aortic regurgitation (AR). Noninvasive positive pressure ventilation, intravenous heparin and diuretics were administered. Follow-up TTE revealed a dissection flap as well as momentary and wide AR only during isovolumetric relaxation. Contrast-enhanced computed tomography of the chest revealed Stanford type A aortic dissection. A momentary and wide AR in echocardiograms might serve as an important and useful indicator of aortic dissection in patients with acute myocardial infarction and congestive heart failure.


Specific patterns of coherence and phase lag index in particular regions as biomarkers of cognitive impairment in Parkinson's disease.
Cognitive impairment is a persistent and increasingly reported symptom of patients with Parkinson's disease (PD), significantly affecting daily functioning quality. This study aims to evaluate the functional connectivity of the brain network in patients with Parkinson's disease with various severities of cognitive decline using quantitative electroencephalography (EEG) analysis. Based on the EEG recorded in the resting state, the coherence and phase lag index were calculated to evaluate functional connectivity in 108 patients with Parkinson's disease divided into three groups according to their cognitive condition: dementia due to PD (PD-D), PD and mild cognitive impairment (PD-MCI) and cognitively normal patients (PD-CogN). It was found that there were significantly different coherence values in the PD-D group compared to PD-CogN in different frequency bands. In most cases, there was a decrease in coherence in PD-D compared to PD-CogN. The most specific changes were revealed in the theta frequency band in the temporal right-frontal left and temporal right-frontal right regions. In the alpha frequency band, the most significant decreases were shown in the occipital right-frontal left and occipital left-frontal right areas. There were also statistically significant differences in phase lag index between many areas, especially in the theta frequency range. These findings indicate that the functional connectivity patterns of coherence and phase lag index - found in a particular frequency band and region - could become a reliable biomarker for identifying cognitive impairment and differentiating its severity in PD patients.


Impact of obesity on surgical and oncologic outcomes in patients with endometrial cancer treated with a robotic approach.
The surgical treatment of endometrial cancer (EC) can be more complicated in obese patients. Robotic surgery could simplify the surgical approach in these patients. The aim of our study was to compare the outcomes of robotic surgery in obese (body mass index ≥30 kg/m2 ) and nonobese patients. We performed a retrospective study on patients with EC benefitting from a robotic approach in our institution. The primary outcome was the 5-year overall survival (OS). We also assessed the 5-year recurrence-free survival (RFS), type of surgery, laparotomy conversion rate, adjuvant treatment and postoperative morbidity. We analyzed 175 consecutive patients with EC who underwent robotic surgery, 42 patients with obesity and 133 patients without. The median follow-up length was 37 months [1-120]. The OS rate was 97% in the whole population and the RFS was 74%. Obesity did not impact prognosis. Laparotomy conversion rate was low in both groups (5% in patients with obesity vs 3%, P = 0.619). There were no significant differences in terms of postoperative complications (5 vs 9%, P = 0.738). There were significantly less pelvic lymphadenectomies in patients with obesity (5 vs 12%, P = 0.005). In the subgroup of patients with high-risk EC, rate of lymphadenectomy and of adjuvant treatments did not differ between patients with or without obesity. Obese patients with EC can be safely treated with a robotic approach, with a low complication rate and similar oncological outcomes compared to nonobese patients.


Individual differences in schedule-induced polydipsia and the role of gabaergic and dopaminergic systems.
The research of individual differences has opened new possibilities for better exploring the neurobiological basis of vulnerability to psychopathological disorders. We extended this approach by using schedule-induced polydipsia (SIP). Outbred male Wistar rats were characterized as either high (HD) or low (LD) drinker according to their behavior in SIP. Subsequently, their performance in the elevated plus maze (EPM) was studied for possible differences in anxiety-like behaviors. Finally, the effects of pentylenetetrazol (PTZ), diazepam, d-amphetamine, and cocaine on individual differences in SIP were investigated. HD rats acquired SIP faster and reached higher asymptotic levels than LD. Nose pokes, however, were greater in LD. In the EPM, there were no differences between HD and LD animals. Gabaergic drug effects on SIP did not differ between HD and LD rats. Compared to saline, PTZ reduced and diazepam increased water SIP drinking. On the other hand, amphetamine dose-dependently reduced SIP in HD, whereas the highest dose was required to reduce SIP in LD. HD rats also showed reductions in SIP drinking after cocaine administration. However, the effects of these drugs on nose pokes did not differ between HD and LD. These data provide novel evidence that individual differences in SIP are not predictive of behavioral reactivity in animal models of anxiety and suggest an important role for the dopaminergic system in such individual differences. These findings point to SIP as a useful animal model for investigating the neurobiological basis of vulnerability to several psychopathologies in which the dopaminergic system is involved.


Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus.
Repeated administration of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) to rodents causes long-lasting deficits in cognition and memory, and has effects on behaviors that have been suggested to be models of the cognitive impairment associated with schizophrenia (CIAS). Despite this being a widely studied animal model, little is known about the long lasting changes in synapses and circuits that underlie the altered behaviors. Here we examined synaptic transmission ex-vivo in the hippocampus of mice after a subchronic PCP (scPCP) administration regime. We found that after at least one week of drug free washout period when mice have impaired cognitive function, the threshold for long-term potentiation (LTP) of CA1 excitatory synapses was elevated. This elevated LTP threshold was directly related to increased inhibitory input to CA1 pyramidal cells through increased activity of GABAergic neurons. These results suggest repeated PCP administration causes a long-lasting metaplastic change in the inhibitory circuits in the hippocampus that results in impaired LTP, and could contribute to the deficits in hippocampal-dependent memory in PCP-treated mice. Changes in GABA signaling have been described in patients with schizophrenia, therefore our results support using scPCP as a model of CIAS. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.


Highly efficient coherent conformal projection system based on adaptive fiber optics collimator array.
Coherent beam combination (CBC) of fiber laser array, which is a promising approach to overcome the power scaling limitations of the single fiber laser and to achieve high-brightness laser with good beam quality, can be employed in coherent conformal projection system (CCPS) for beam projection and free space laser communication system with enormous potential. To date, all the demonstrated CBC system through several kilometers atmospheric turbulence have employed collimated beams, which significantly decrease the final CBC effect because of the inefficient wavefront overlap. On the other hand, focused CCPS has lots of advantages over collimated projection system since the wave front of the projected beam is closer to that of a convergent spherical wave. In this paper, we design and manufacture focused CCPS based on an adaptive fiber optics collimator array for the first time, which is achieved by introducing controllable spherical aberration through the adaptive fiber optics collimator. A CBC system is setup to evaluate and validate its performance. Results show that compared with the collimated CCPS, the energy portion of the central lobe could be increased by a factor of 44%, which agrees well with the theoretical analysis.


[Lithogenicity and bile acid pattern in choleretic administration (3-n-butoxy-1-phenoxy-propanol: febuprol) in patients with functional right upper quadrant pain].
10 patients with right upper quadrant pain were treated with a choleretic agent (Febuprol; 3 X 200 mg t. i. d.) and placebo in a cross-over double dummy technique for 16 weeks. Lithogenic index, bile acid profile and serum lipids were determined every 4 weeks. During Febuprol application the clinical symptoms were relieved (0.87 +/- 1.3 vs. 1.39 +/- 0.21 (placebo); p less than 0.05, semiquantitative score). Biliary lithogenicity (1.45 +/- 0.6 vs. 1.09 +/- 0.12; n. s.), bile acid profile and serum lipids showed no statistically significant change, although serum cholesterol levels seemed to fall during Febuprol application.


Convergence to stationary distributions in two-species stochastic competition models.
Two sets of sufficient conditions are given for convergence to stationary distributions, for some general models of two species competing in a randomly varying environment. The models are nonlinear stochastic difference equations which define Markov chains. One set of sufficient conditions involves strong continuity and phi-irreducibility of the transition probability for the chain. The second set has a much weaker irreducibility condition, but is only applicable to monotonic models. The results are applied to a stochastic two-species Ricker model, and to Chesson's "lottery model with vacant space", to illustrate how the assumptions can be checked in specific models.


17Beta-estradiol prevents retinal ganglion cell loss induced by acute rise of intraocular pressure in rat.
Glaucoma, is a progressive optic neuropathy often associated with increased intraocular pressure (IOP) and characterized by progressive death of retinal ganglion cells (RGCs). High acute rise of IOP is a model for retinal ischemia and may represent a model of acute angle closure glaucoma. Here we have used this experimental model in combination with a neurochemical and neuropathological approach to gain more insight in the neuroprotective profile of 17beta-estradiol (E2), a steroid hormone, which has been shown to increase the viability, survival, and differentiation of primary neuronal cultures from different brain areas including amygdala, hypothalamus, and neocortex. Our data demonstrate that systemic administration of E2 significantly reduces RGC loss induced by high IOP in rat. In addition, pretreatment with E2, 30 min before ischemia, minimizes the elevation of glutamate observed during the reperfusion period. These effects seem to be in part mediated by the activation of the estrogen receptor, since a pretreatment with ICI 182-780, a specific estrogen receptor antagonist, partially counteracts the neuroprotection afforded by the estrogen.


Fluctuation in grip and pinch strength among normal subjects.
Grip and pinch strength testing are commonly used to evaluate hand strength for disability ratings and to assess responses to various forms of therapy. This study determined the variations in grip and pinch strength in normal individuals. Ninety-five healthy subjects--61 women and 34 men--were examined prospectively by use of a Jamar dynamometer and a Preston pinch gauge. Grip and pinch were measured in the morning and afternoon twice a week for 3 weeks, giving a total of 12 testing periods. Mean grip strength fluctuated between 5.1 and 8.4 kg, or between 19.2% and 23.7%. Mean lateral pinch strength fluctuated between 2.6 and 3.8 pounds, or between 13.8% and 17.6%. There were no differences between the morning and afternoon values. Grip and pinch strength fluctuate over time. Repeat testing is necessary to accurately assess hand strength. Grip and pinch strength do not vary from morning to afternoon.


How normal is variable, or how variable is normal?
Variability is an important property of the central nervous system, and it shows characteristic changes during infancy and childhood. The large amount of variations in the performance of sensomotor functions in infancy is called indiscriminate or primary variability. During toddling age the child develops the capacity to select adaptive variations, and then automatize them: secondary or adaptive variability. The latter is required for the development of motor skills during later preschool age and school age. The question 'How normal is variable or how variable is normal is a wrong question, as any form of variability must be interpreted according to its extent, type and age adequacy.


Cytotoxic cardenolides and antibacterial terpenoids from Crossopetalum gaumeri.
From the methanol extract of the roots of (Crossopetalum gaumeri, four new highly cytotoxic cardenolides, securigenin-3beta-O-beta-6-deoxyguloside (2), 19-hydroxy-sarmentogenin-3beta-O-beta-6-deoxyguloside (4), sarmentogenin-3beta-O-[alpha-allosyl-(1-->4)-beta-6-deoxy alloside] (5), and securigenin-3beta-O-[alpha-allosyl-(1-->4)-beta-6-deoxyal loside] (6) were isolated. The dichloromethane extract afforded the new diterpene 3,15-dihydroxy-18-norabieta-3,8,11,13-tetraene (7) as well as the new triterpene 2,3,7-trihydroxy-6-oxo-1,3,5(10),7-tetraene-24-nor-friedelane-29-o ic acid methylester (11). The new terpenoids lack cytotoxicity and the antibacterial activity is moderate to low.


Effects of nonpeptide vasopressin V2 antagonist tolvaptan in rats with heart failure.
Similar to other neurohormones that are activated in chronic heart failure (CHF), circulating arginine vasopressin (AVP) is elevated in patients with CHF. The precise role of AVP in the pathophysiology of cardiovascular disease is controversial. AVP is a peptide hormone that contributes to water retention and vasoconstriction in CHF through effects on V(2) and V(1a) receptors, respectively. In the present study, the effect of V(2) receptor (V(2)R) blockade using tolvaptan was assessed in a rat model of myosin-induced experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan (3 or 10mg/(kg day)) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Chronic V(2)R blockade increased urine volume and urinary AVP excretion and decreased urine osmolality but had no natriuretic effect, and as a result caused increases in plasma osmolality and sodium. High doses of tolvaptan markedly elevated electrolyte-free water clearance. V(2)R blockade did not activate the renin-angiotensin system, not influence cardiac remodeling, cardiac function, or survival. The upregulation of aquaporin 2 protein in the kidney of CHF rats was inhibited by the administration of V(2)R antagonist. These results suggest that in a rat model of CHF, AVP plays a major role in water retention through the renal V(2)R.


Latency compensation analysis of the auditory brain-stem evoked response.
Latency compensation analysis (LCA) was applied to single trial samples of the auditory brain-stem evoked response (ABR, IV-V complex). By this means it was possible to characterize properties of temporal variability in the ABR, including certain cases of temporal outliners. A lagged cross-correlogram analysis provided information for each trial that included the largest r2 and associated lead/lag value. The distribution of lag values (based on all trials) was statistically different when ABRs were evoked by stimuli differing by 5 dB. Recomputing the ABR by eliminating temporal outliers, and by adjusting for temporal variability, showed a range of individual patterns of increased amplitude. However, a comparison of Down syndrome (DS) and non-retarded individuals showed a significantly greater amplitude increase in the DS group after LCA. This suggests that certain forms of mental retardation may be characterized by reduced stability in a neural system that is thought to depend upon 'synaptically secure' neurons.


Macrophages are metabolically heterogeneous within the tumor microenvironment.
Macrophages are often prominently present in the tumor microenvironment, where distinct macrophage populations can differentially affect tumor progression. Although metabolism influences macrophage function, studies on the metabolic characteristics of ex vivo tumor-associated macrophage (TAM) subsets are rather limited. Using transcriptomic and metabolic analyses, we now reveal that pro-inflammatory major histocompatibility complex (MHC)-IIhi TAMs display a hampered tricarboxylic acid (TCA) cycle, while reparative MHC-IIlo TAMs show higher oxidative and glycolytic metabolism. Although both TAM subsets rapidly exchange lactate in high-lactate conditions, only MHC-IIlo TAMs use lactate as an additional carbon source. Accordingly, lactate supports the oxidative metabolism in MHC-IIlo TAMs, while it decreases the metabolic activity of MHC-IIhi TAMs. Lactate subtly affects the transcriptome of MHC-IIlo TAMs, increases L-arginine metabolism, and enhances the T cell suppressive capacity of these TAMs. Overall, our data uncover the metabolic intricacies of distinct TAM subsets and identify lactate as a carbon source and metabolic and functional regulator of TAMs.


Coexistence of malakoplakia and multifocal diffuse large B cell lymphoma of colorectum.
We report a case of concurrent multifocal diffuse large B cell lymphoma and malakoplakia of colorectum in a 36-year-old man presenting with recurrent bloody diarrhoea. Malakoplakia has been described in association with a variety of malignant and nonmalignant conditions. To the best of our knowledge, this is the third report of coexistence or association of malignant non-Hodgkin lymphoma and malakoplakia in the literature, and the first report ever in the colorectum.


DNA-directed capture of primary cells from a complex mixture and controlled orthogonal release monitored by SPR imaging.
Many biological samples are composed of several cell types. Qualitative and quantitative analysis of these complex mixtures is of major interest for both diagnostic and biomedical applications. Because large amounts of biological material are often challenging to collect, tremendous efforts have been made for a decade to design miniaturized platforms-such as lab-on-a-chip or microarrays-to run sensitive and reliable analysis from tiny quantities of starting material. Although barely explored so far, the release of resolved cellular samples constitutes an exciting strategy for further cell analysis. Herein, we propose a DNA-based biochip suitable for cell-type analysis in a label-free manner. The DNA-array is firstly converted into antibody-array using antibody-DNA conjugates. These protein-DNA hybrid molecules are chemically synthesized by covalent coupling of short oligonucleotides to antibodies directed against cell-type specific markers. We show not only specific capture of primary spleen cells on protein-DNA microarray spots but also their fast and specific orthogonal release according to the antibody-DNA combinations by incorporating restriction sites in DNA. Both molecular and cellular interactions occurring on the biochip are monitored by surface plasmon resonance (SPR) imaging. This optical technique turns out to be a powerful way to monitor, in real-time, biological interactions occurring on the microarrayed features.


Infectious genomic RNA of Rhopalosiphum padi virus transcribed in vitro from a full-length cDNA clone.
Availability of a cloned genome from which infectious RNA can be transcribed is essential for investigating RNA virus molecular mechanisms. To date, no such clones have been reported for the Dicistroviridae, an emerging family of invertebrate viruses. Previously we demonstrated baculovirus-driven expression of a cloned Rhopalosiphum padi virus (RhPV; Dicistroviridae) genome that was infectious to aphids, and we identified a cell line (GWSS-Z10) from the glassy-winged sharpshooter, that supports RhPV replication. Here we report that RNA transcribed from a full-length cDNA clone is infectious. Transfection of GWSS-Z10 cells with the RhPV transcript resulted in cytopathic effects, ultrastructural changes, and accumulation of progeny virions, consistent with virus infection. Virions from transcript-infected cells were infectious in aphids. This infectious transcript of a cloned RhPV genome provides a valuable tool, and a more tractable system without interference from baculovirus infection, for investigating replication and pathogenesis of dicistroviruses.


Framework and Strategies to Eliminate Disparities in Colorectal Cancer Screening Outcomes.
Preventable differences in colorectal cancer (CRC) mortality across racial/ethnic, economic, geographic, and other groups can be eliminated by assuring equitable access and quality across the care continuum, but few interventions have been demonstrated to do so. Multicomponent strategies designed with a health equity framework may be effective. A health equity framework takes into account social determinants of health, multilevel influences (policy, community, delivery, and individual levels), screening processes, and community engagement. Effective strategies for increasing screening uptake include patient navigation and other interventions for structural barriers, reminders and clinical decision support, and data to continuously track metrics and guide targets for improvement. Community resource gaps should be addressed to assure high-quality services irrespective of racial/ethnic and socioeconomic status. One model combinespopulation-based proactive outreach screening with screening delivery at in-person or virtual points of contact, as well as community engagement. Patient- and provider-based behavioral interventions may be considered for increasing screening demand and delivery. Providing a choice of screening tests is recommended for CRC screening, and access to colonoscopy is required for completion of the CRC screening process.


Impacts of viability and purification on the specific gravity of Cryptosporidium oocysts.
The specific gravity of unpurified and purified Cryptosporidium oocysts was measured using an isopycnic gradient centrifugation technique. Specific gravity varied depending on the viability of the oocysts, as defined by permeabilty to 4',6-diamidino-2-phenylindole (DAPI) and propidium iodide (PI), the presence or absence of internal structures, and whether or not oocysts were purified. The modal range of densities for a population of 1.4-week-old unpurified oocysts, was 1070-1073 kg/m3. This range was higher than that determined for 14-week-old purified oocysts, 1067-1070 kg/m3. Eleven- and 12-week-old unpurified populations exhibited a bimodal distribution of densities, with densities most frequently in the 1005-1041 and in the 1077-1108 kg/m3 range. In these populations, a high percentage of the oocysts having densities greater than 1077 kg/m3 were viable, while oocysts in the 1005-1024 kg/m3 range were predominately nonintact, and oocysts in the 1024-1041 kg/m3 range were intact, but permeable to DAPI and PI (nonviable). This work demonstrates the importance of controlling factors that may impact the viability of oocysts when conducting studies that examine the transport of these microorganisms in the environment and through water treatment processes.


Effect of amiodarone therapy on mortality in patients with left ventricular dysfunction and asymptomatic complex ventricular arrhythmias: Argentine Pilot Study of Sudden Death and Amiodarone (EPAMSA).
The efficiency of prophylactic antiarrhythmic treatment with amiodarone in reducing 1-year mortality in patients with reduced left ventricular ejection fraction ( < 35%) and asymptomatic ventricular arrhythmias (Lown classes 2 and 4) was investigated in a prospective, multicenter, randomized, controlled study. Among 127 patients who entered the study, 61 were assigned to no antiarrhythmic therapy (control group [CG] and 66 to amiodarone treatment (amiodarone group [AG]). Amiodarone was administered at a dosage of 800 mg/day for 2 weeks followed by 400 mg/day thereafter. A 12-month follow-up was completed for 106 patients (57 in the AG and 49 in the CG). Amiodarone reduced the overall mortality rate, which was 10.5% in the AG versus 28.6% in the CG (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.10 to 0.84; log-rank test 0.02) and sudden death rate, which was 7.0% in the AG versus 20.4% in the CG (OR 0.29; 95% CI 0.08 to 1.00; log-rank test 0.04). Side effects were rare, and in only three patients did amiodarone treatment have to be discontinued.


Mass screening for urinary tract cancer with urine cytology.
A rapid and simple cytologic screening technique for fresh urine specimens stained with toluidine blue is described. As to the validity and description of cell structure, the accuracy of urine cytology with this procedure is very similar to that of the Papanicolaou technique. Utilizing this technique, a hospital population was screened for urinary tract cancer from specimens sent for routine urinalysis. In this study of 16,062 fresh urine sediments selected at random from nonurologic patients, a total of three cases of histologically proven bladder cancer were detected, corresponding to a rate of one bladder cancer in 5,000 individuals. The results emphasize the usefulness of this simple screening technique in combination with clinical urinalysis and cytology for early detection of urinary tract malignancy.


Parent Perceptions of Pediatric Primary Care Providers' Mental Health-Related Communication and Practices.
The pediatric primary care office is an ideal setting to address children's socioemotional-behavioral health. However, research is limited regarding parents' experiences and satisfaction in sharing mental-health concerns about their children during well-child visits. One thousand seven hundred sixty-three parents and caregivers with children aged 3-17 years completed an online survey that addressed mental-health-related communication. Findings supported the key role that primary care providers play in communicating about mental-health issues; 75% of parents who had such a concern about their child raised it during the visit, although the majority desired more time devoted to discussing mental health. Parents' comfort discussing mental-health concerns was inversely related to providers' dismissing those concerns. Despite satisfaction with how providers addressed mental-health issues, results suggested that nonjudgmental, knowledgeable staff and discussion of child and parent strengths could facilitate both parental comfort and communication between parents and pediatricians.


Auxological data in patients clinically suspected of Sotos syndrome with NSD1 gene alterations.
Nuclear receptor-binding SET domain-containing protein 1 (NSD1) gene mutations and deletions (NSD1+/-) are the major cause of Sotos syndrome. The aim was to investigate which auxology parameters relate to NSD1+/- in patients clinically suspected of Sotos syndrome. In 32 patients clinically suspected of Sotos syndrome, we compared auxology parameters between NSD1+/- patients and patients without NSD1 gene alterations (NSD1+/+). The statistical performance of these parameters to predict NSD1+/- was assessed. Arm span-for-height standard deviation score (SDS) and hand length SDS were significantly higher in NSD1+/- patients. Arm span for height and hand length are discriminating parameters between NSD1+/- and NSD1+/+.


Design and analysis of a wireless power transfer system for capsule robot using an optimised planar square spiral transmitting coil pair.
The wireless power transfer system (WPTS) is a promising way to continuously provide efficient and stable power for gastrointestinal capsule robots with active movement ability. The proposed WPTS using an optimised planar square spiral transmitting coil pair with space-saving structure can flexibly adjust the distance between the coils according to the patient's condition, and thus has better applicability. To improve power transfer efficiency and uniformity of the generated magnetic field, design parameters are discussed and optimised based on the analytical calculation and simulation analysis. The power demand can be guaranteed with spacing distance of 350-500 mm and the peak received power of 1124 mW with a remarkable transfer efficiency of 7.8% can be obtained when the spacing reaches the minimum. The human electromagnetic exposure safety in different situations is also discussed and verified. The WPTS can provide power for capsule robots safely and efficiently.


Anatomic basis of a dorso-commissural flap from the 2nd, 3rd and 4th intermetacarpal spaces.
This study relates to an island skin-flap constructed on the dorsal aspect of the hand, between the heads of the 2nd, 3rd, 4th and 5th metacarpals. The vascular pedicle consists of the subcutaneous fatty tissue of the dorsal aspect of the proximal phalanx. This fatty tissue is richly vascularized by the dorsal branches of the proper palmar digital artery and by the periarticular circle of the proximal interphalangeal joint. The point of rotation of the flap is situated at the level of the proximal interphalangeal joint. The length of the pedicle allows the skin flap to cover losses of substance of the dorsal aspect of the middle and distal phalanges. Its chief advantage is that it does not sacrifice the proper palmar digital artery.


Modulation effect of Smilax glabra flavonoids on ryanodine receptor mediated intracellular Ca2+ release in cardiomyoblast cells.
Smilax glabra rhizome, a plant material from Liliaceae family, is a widely used traditional Chinese medicine for anti-cardiac hypertrophy treatment. We have previously found that Smilax glabra flavonoids (SGF) exerted such anti-cardiac hypertrophy activity. However, the mechanism of this activity of SGF has not been clarified yet. This study was aimed to investigate the inhibitory role of SGF on intracellular Ca(2+) release in rat cardiomyoblast cells (H9C2). Intracellular Ca(2+) release was determined by Ca(2+) indicator fluorescence (fluo 4-AM) in H9C2 cell line. SGF at concentrations of 0.25, 0.5, 1.0mg/ml significantly inhibited the phenylephrine or angiotensin II induced intracellular Ca(2+) release in a dose-dependent manner. Furthermore, SGF could also inhibit ryanodine receptor (RyR) agonist caffeine induced Ca(2+) release and phenylephrine (PE)-induced Ca(2+) release under the condition in which inositol trisphosphate (IP3) receptors were blocked with 2-Aminoethoxydiphenyl borate (2-APB). Nevertheless, SGF had no impact on PE-induced Ca(2+) release under the condition in which RyRs were blocked with tetracaine. Our results suggest that the protective effects of SGF are mediated via targeting inhibition of RyR mediated intracellular Ca(2+) release.


Comparative evaluation of Polymerase Chain Reaction-Restriction Enzyme Analysis (PRA) and sequencing of heat shock protein 65 (hsp65) gene for identification of aquatic mycobacteria.
Traditional identification of mycobacteria based on cultural and biochemical tests can take several weeks and may fail to provide a precise identification. Polymerase Chain Reaction-Restriction Enzyme Analysis (PRA) of the gene encoding heat shock protein 65 kDa (hsp65) gene has been proposed as a rapid and inexpensive alternative approach. Despite being widely used for differentiation of mammalian mycobacteria, this method has only been applied in the identification of a small number of aquatic mycobacteria. The present study aimed to evaluate the potential use of PRA of hsp65 for the identification of aquatic mycobacteria compared with sequence analysis. Seventy one mycobacterial isolates including, 10 type/reference strains and the remainder field isolates, were subjected to PRA of a 441 bp fragment of this gene. For 68 representative isolates, sequence analysis was performed. All rapidly and slowly growing mycobacteria had best matches with 99.3% to 100% similarity with their corresponding species in the databanks. PRA proved to be a simple and rapid method for identifying aquatic mycobacteria. However, the incidence of similar or identical restriction patterns for some species of mycobacteria, and in particular, identification of new species of mycobacteria is a major problem using such a method. In contrast, the nucleic acid sequencing of the hsp65 gene yielded unambiguous results.


Is beta-thalassemia trait a protective factor against ischemic cerebrovascular accidents?
In this research, we sought to determine the association between beta-thalassemia trait and ischemic cerebrovascular accident (CVA). In acase-control study, 148 patients with thromboembolic cerebrovascular events were evaluated for the presence of hypertension, diabetes mellitus, hyperlipidemia, and beta-thalassemia trait. A total of 156 age- and sex-matched patients with no cardiac or cerebrovascular diseases, serving as the control group, were also investigated for the above-mentioned risk factors. We found that 6.1% of patients with ischemic CVA and 12.2% of the control group had beta-thalassemia trait (P = .066). In male patients, the negative association between ischemic CVA and presence of beta-thalassemia trait was significant (P = .008). In patients, the prevalence of hypertension was also significantly different between those with and without beta-thalassemia trait (P = .01); those with beta-thalassemia trait had a lower mean blood pressure than those without the trait. beta-Thalassemia trait may have a protective effect against ischemic CVA that might be caused by the lower arterial blood pressure observed in those with this trait.


Audit of surgeon billing in workers compensation-insured elective spinal surgery in New South Wales, Australia from 2010 to 2018.
Medical billing practices have received increasing scrutiny in Australia and worldwide. In 2015, the Australian Government initiated a comprehensive review of the Medicare Benefits Schedule (MBS), including spinal surgery. This study provides a snapshot of five spinal surgeon billing patterns and associated costs in the workers compensation system in New South Wales prior to these changes. This retrospective cohort study used workers compensation billing data from the State Insurance Regulatory Authority to capture elective spinal surgeries in New South Wales from 2010 to 2018. The main outcome measures were: proportion of items billed within recommended limits (up to 150% of the listed Australian Medical Association (AMA) fee); surgical billing patterns including repeat billing of items during a single episode of surgery; use of paediatric or scoliosis items; use of surgical items from outside the spinal surgery schedule; co-billing of items not permitted as per the AMA Fees List item descriptions and associated costs. There were 12 622 spinal surgeries in 9520 patients. While only 2.2% of items were billed above the recommended limits, 38% of surgeries included at least one of the five billing patterns. The average cost increase was AU$4700 per surgery, 47% greater than surgeries which did not include the specified billing patterns, for a total additional cost of AU$22.9 M over the 9-year study period. Five spinal surgery billing patterns accounted for an additional AU$22.9 million in direct surgical costs from 2010 to 2018.


The role of microbial metabolites in diabetic kidney disease.
Growing evidence suggests a complex bidirectional interaction between gut microbes, gut-derived microbial metabolites, and diabetic kidney disease (DKD), known as the "gut-kidney axis" theory. The present study aimed to characterize the role of microbial metabolites in DKD. Six-week-old db/db and littermate db/m mice were raised to 20 weeks old. The serum, urine, feces, liver, perinephric fat, and kidney were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomic analyses. The db/db mice showed obvious pathological changes and worse renal functions than db/m mice. Indoleacetaldehyde (IAld) and 5-hydroxy-l-tryptophan (5-HTP) in kidney samples, and serotonin (5-HT) in fecal samples were increased in the db/db group. Phosphatidylcholine (PC), phosphatidate (PA), and 1-acylglycerophosphocholine (lysoPC) were decreased in liver and serum samples of the db/db group, while PC and lysoPC were decreased in kidney and perinephric fat samples. Suggested metabolomic homeostasis was disrupted in DKD mice, especially glycerophospholipid and tryptophan metabolism, which are closely related to the gut microbiome. Our findings reveal the perturbation of gut microbial metabolism in db/db mice with DKD, which may be useful for building a bridge between the gut microbiota and the progression of DKD and provide a theoretical basis for the intestinal treatment of DKD.


Evaluating the Dietary Intake of Children With Esophageal Atresia: A Prospective, Controlled, Observational Study.
Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.


Representation of sound source direction in the superior colliculus of the guinea pig in a virtual auditory environment.
The deep layers of the superior colliculus (SC) receive visual, auditory, and somatosensory input. A major function of the SC is the control of orientation movements of the eye, head, and pinna. While a topographical map for sound source direction remains elusive in primary auditory structures of mammals, such a map for azimuthal sound source directions has been reported in the deep layers of the SC. Moreover, a gradient of elevation tuning has been also seen in the SC of ferrets and cats. Here we demonstrate that a virtual auditory environment can be used to reveal azimuthal and elevational topography for auditory spatial receptive fields in neurons in the SC of guinea pigs. Individual, head-related transfer functions (HRTF) were measured in ten guinea pigs for 122 directions in the upper hemispheric field and convolved with white noise. Many neurons (39%) in the deep layers showed robust responses to these virtual sounds, and the majority of these neurons had small spatial receptive fields that were restricted to the contralateral hemifield. Best directions varied from 0 degree to 135 degree azimuth along the contralateral side and from --10 degree to 60 degree elevation. Like previous studies using free-field stimulation, a gradient of best azimuth direction was found along the rostral-caudal axis, with rear directions represented caudally and front directions rostrally. The topographical organization for best elevations had not been studied previously in the guinea pig. We found that it roughly followed the mediolateral axis, with preference for high elevations represented medially and low elevations laterally. A similar organization using free-field stimulation has been reported in the ferret.


A Unifying Model of Orientation Crowding in Peripheral Vision.
Peripheral vision is fundamentally limited not by the visibility of features, but by the spacing between them [1]. When too close together, visual features can become "crowded" and perceptually indistinguishable. Crowding interferes with basic tasks such as letter and face identification and thus informs our understanding of object recognition breakdown in peripheral vision [2]. Multiple proposals have attempted to explain crowding [3], and each is supported by compelling psychophysical and neuroimaging data [4-6] that are incompatible with competing proposals. In general, perceptual failures have variously been attributed to the averaging of nearby visual signals [7-10], confusion between target and distractor elements [11, 12], and a limited resolution of visual spatial attention [13]. Here we introduce a psychophysical paradigm that allows systematic study of crowded perception within the orientation domain, and we present a unifying computational model of crowding phenomena that reconciles conflicting explanations. Our results show that our single measure produces a variety of perceptual errors that are reported across the crowding literature. Critically, a simple model of the responses of populations of orientation-selective visual neurons accurately predicts all perceptual errors. We thus provide a unifying mechanistic explanation for orientation crowding in peripheral vision. Our simple model accounts for several perceptual phenomena produced by crowding of orientation and raises the possibility that multiple classes of object recognition failures in peripheral vision can be accounted for by a single mechanism.


Oral vaccine that breaks the transmission cycle of the Lyme disease spirochete can be delivered via bait.
Borrelia burgdorferi causes Lyme disease, a potentially debilitating human disease for which no vaccine is currently available. We developed an oral bait delivery system for an anti-B. burgdorferi vaccine based in OspA. Mice were immunized orally via gavage and bait feeding. Challenge was performed via Ixodes scapularis field nymphs carrying multiple B. burgdorferi strains. Vaccination protected 89% of the mice and the systemic immune response was skewed toward IgG2a/2b production. Moreover, this oral vaccine reduced the pathogen in the tick vector by eight-fold. We conclude that this oral vaccine induces a protective systemic immune response against a variety of infectious B. burgdorferi strains found in nature and therefore it can eliminate this zoonotic pathogen from its major host reservoirs. Because we observed elimination of the spirochete from the tick vector, a broad delivery of this oral vaccine to wildlife reservoirs is likely to disrupt the transmission cycle of this pathogen.


Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres.
The in vivo efficacy of engineered tissue constructs depends largely on their integration with the host vasculature. Prevascularisation has been noted to facilitate integration of the constructs via anastomosis of preformed microvascular networks. Here we report a technique to fabricate aligned, spatially defined prevascularised tissue constructs with endothelial vessels by assembling individually tailored cell-laden polyelectrolyte hydrogel fibres. Stable, aligned endothelial vessels form in vitro within these constructs in 24 h, and these vessels anastomose with the host circulation in a mouse subcutaneous model. We create vascularised adipose and hepatic tissues by co-patterning the respective cell types with the preformed endothelial vessels. Our study indicates that the formation of aligned endothelial vessels in a hydrogel is an efficient prevascularisation approach in the engineering of tissue constructs.


Assay of Fe(III) Chelate Reductase Activity in Arabidopsis thaliana Root.
A sensitive FerroZine assay is used to measure the membrane-bound ferric-chelate reductase activity in the Arabidopsis thaliana roots. In Arabidopsis, FRO2 (FERRIC CHELATE REDUCTASE 2) encodes the Fe(III) chelate reductase and its expression is induced by iron deficiency. As FRO2 reduces Fe(III) to soluble Fe(II), the resulting Fe(II) forms a purple-colored complex with the dye FerroZine. The concentration of the Fe(II)-FerroZine is directly proportional to the absorbance at 562 nm.


Protamine-agarose non-charged alkyl derivatives of agarose in the purification of rat-liver phosphoprotein phosphatases.
1. Protamine-agarose and hydrophobic interaction chromatography were found to be effective in the purification of phosphoprotein phosphatase(s) (phosphoprotein phosphohydrolase, EC 220.127.116.11) of rat-liver. The phosphoprotein phosphatase of rat-liver cytosol were first resolved into three fractions, termed A, B and C, in order of elution from DEAE-cellulose. Whereas all fractions displayed activity towards [32P]phosphoprotamine, only fractions B and C displayed appreciable activity towards [32P]phosphopyruvate kinase. Since fraction B exhibited the most properties and the highest recovery of enzymatic activity towards [32P]phosphoprotamine and [32P]phosphopyruvate kinase, it was selected for further purification. The method developed involves sequential chromatography of fraction B on Sephadex G-200, protamineagarose, histone-agarose and then again on Sephadex G-200 as a final step. A 400-fold enrichment in the phosphoprotamine phosphatase activity of fraction B was obtained. Purified fraction B also displayed substantial phosphatase activity towards [32P]phosphopyruvate kinase and [32P]phosphohistones. An apparent molecular weight of about 250 000 was estimated for purified fraction B on a calibrated Sephadex G-200 column. The present data indicate that rat-liver cytosol contains multiple forms of phosphoprotein phosphatases and suggest a technique which might be applied for the further purification of at least fraction B. 2. In a separate approach, a combination of pentyl-agarose and protamineagarose chromatography was shown to be a conbenient method for the enrichment (up to 20-fold of phosphoprotein phosphatase activity from crude liver extracts.


Reporting Quality of the Abstracts for Randomized Controlled Trials in Pediatric Dentistry.
The purpose of this study is to systematically appraise the reporting quality of abstracts for randomized controlled trials (RCT) published in pediatric dentistry using Consolidated Standards of Reporting Trials (CONSORT) for abstracts and to analyze the relationship between the characteristics of the RCT to the quality of abstracts. RCTs published in Pediatric Dentistry were retrieved from the PubMed database from 2016 to 2021. The quality of abstracts was appraised using CONSORT for abstracts checklist by two independent reviewers. In descriptive statistics, frequency and percentage analysis were used for categorical variables, whereas mean and standard deviation were used for continuous variables. To find the significant difference between the bivariate samples in independent groups, Mann-Whitney U test was employed. Multivariate analysis was performed using Kruskal-Wallis test and Mann-Whitney U tests. Probability value of p-value less than 0.05 was considered as statistically significant. Two hundred abstracts were included in the study. All the abstracts adequately reported the "objective" item, whereas only 2 and 4% of abstracts adequately addressed "randomization" and "harms" items, respectively. A significant relationship was observed between the continent of first author/corresponding author, number of authors, impact factor, adherence to CONSORT guidelines, word count, focus of study, and a priori protocol registration to the quality of abstracts (p < 0.05). The abstracts of the RCT included in the study did not adequately follow the CONSORT for abstract guidelines. Adherence to the reporting guidelines would improve the overall reporting quality of abstracts of RCT published in Pediatric Dentistry. The overall mean score of the abstracts was 6.80 out of 15 indicating that the abstracts did not adequately follow the CONSORT for abstract reporting guidelines.


To Grow or not to Grow?
The seed to seedling transition in plants is initiated following the termination of seed dormancy. Here, I present a simplified developmental framework describing the events underlying this transition. I discuss putative mechanisms of signal integration and their relation to a global developmental fate switch in seeds within this framework. I delineate the events that occur before and after the flipping of this switch, marking an important distinction between these different developmental states. To end, I propose that the final fate switch resides within the embryo, and is informed by the endosperm in arabidopsis (Arabidopsis thaliana). This framework can serve as a template to focus future research in seed science.


Exotic Mammal Laparoscopy.
Laparoscopy is an evolving field in veterinary medicine, and there is an increased interest in using laparoscopic techniques in nondomestic mammals, including zoo animals, wildlife, and exotic pets. The aim of this article is to summarize the approach to laparoscopic procedures, including instrumentation, patient selection and preparation, and surgical approaches, and to review the current literature on laparoscopy in exotic mammals.


Cathepsin K is a potent disaggregase of α-synuclein fibrils.
The intracellular accumulation of α-synuclein (α-syn) amyloid fibrils is a hallmark of Parkinson's disease. Because lysosomes are responsible for degrading aggregated species, enhancing lysosomal function could alleviate the overburden of α-syn. Previously, we showed that cysteine cathepsins (Cts) is the main class of lysosomal proteases that degrade α-syn, and in particular, CtsL was found to be capable of digesting α-syn fibrils. Here, we report that CtsK is a more potent protease for degrading α-syn amyloids. Using peptide mapping by liquid chromatography with mass spectrometry, critical cleavage sites involved in destabilizing fibril structure are identified. CtsK is only able to devour the internal regions after the removal of both N- and C-termini, indicating their protective role of the amyloid core from proteolytic attack. Our results suggest that if overexpressed in lysosomes, CtsK has the potential to ameliorate α-syn pathology.


Impaired differentiation of fetal hepatocytes in homozygous jumonji mice.
Homozygous jumonji (jmj(-)/jmj(-)) mice were previously shown to exhibit hepatic hypoplasia and defective hematopoiesis in the liver and die at around embryonic day 15.5 (E15.5), suggesting that jmj is essential for liver development. In order to gain insight into the mechanism of liver development, we analyzed the expression and function of jmj in fetal hepatocytes. The number of hepatocytes in jmj(-)/jmj(-) mice was markedly reduced in comparison with control mice and the expression of jmj in hepatocytes increased along with development. As jmj(-)/jmj(-) embryos die by E15.5, we employed an in vitro culture system in which fetal hepatocytes differentiate in response to oncostatin M. The proliferation potential of jmj(-)/jmj(-) hepatocytes was comparable to that of wild type cells in vitro, however maturation of hepatocytes as evidenced by the expression of liver enzymes such as tyrosine amino transferase was severely impaired by the jmj gene inactivation. These results suggested that jmj plays a pivotal role in the development of mid-fetal hepatocytes to the neonatal stage.


Epigenetics of human papillomaviruses.
Human papilllomaviruses (HPVs) are common human pathogens that infect cutaneous or mucosal epithelia in which they cause warts, self-contained benign lesions that commonly regress. The HPV life cycle is intricately tied to the differentiation of the host epithelium it infects. Mucosotropic HPVs are the most common sexually transmitted pathogen known to mankind. A subset of the mucosotropic HPVs, so-called high risk HPVs, is etiologically associated with numerous cancers of the anogenital tract, most notably the cervix, as well as a growing fraction of head and neck cancers. In these cancers, the HPV genome, which normally exists an a double stranded, circular, nuclear plasmid, is commonly found integrated into the host genome and expresses two viral oncogenes, E6 and E7, that are implicated in the development and maintainance of the cancers caused by these high risk HPVs. Numerous studies, primarily on the high risk HPV16, have documented that the methylation status of the viral genome changes not only in the context of the viral life cycle but also in the context of the progressive neoplastic disease that culminates in cancer. In this article, we summarize the knowledge gained from those studies. We also provide the first analysis of available ChIP-seq data on the occupancy of both epigentically modified histones as well as transcription factors on the high risk HPV18 genome in the context of HeLa cells, a cervical cancer-derived cell line that has been the subject of extensive analyses using this technique.


Accumulation and decontamination kinetics of PCBs and PCDD/Fs from grass silage and soil in a transgenerational cow-calf setting.
Polychlorinated biphenyls (PCBs) and dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) are bioaccumulative pollutants that endanger bovine food safety. Bioaccumulation depends, among others, on the physiological dynamics of the cow's reproductive cycle. However, recent studies have focused only on near steady-state situations. Thus, the effects of animal physiology on PCB + PCDD/F transfer from grass silage and soil to cows' blood, adipose tissue, and milk and subsequently to suckling calves during gestation and lactation were investigated. In the exposed group, nine cows ate a grass silage/contaminated soil mixture (6.6 ± 0.8 μg iPCBs and 2.6 ± 0.4 ng dlPCB + PCDD/F TEQ kgDM-1) for 109 days prepartum until 288 days in milk (DIM). Four of these cows underwent decontamination after DIM164, receiving the same clean grass silage as the four control cows during the experiment. Calves were fed the milk of their respective mothers. In the exposed group, transgenerational bioaccumulation occurred until DIM164, with calf blood and adipose tissue PCB + PCDD/F concentrations reaching levels twice as high as those in their respective mothers. Transfer rates from oral intake to milk ranged from 0.1 up to 42%, depending on pollutant congener, dietary treatment, and reproductive parity of the cow. Congener and parity also influenced the decontamination half-lives of milk. In decontaminated calves, declines in adipose tissue PCB + PCDD/F concentrations coincided with increases in body fat mass. Therefore, it is essential to know the physiological characteristics of cattle, exposure dose and duration, and physicochemical compound properties to perform reliable transfer assessments.


Integrin αv in the mechanical response of osteoblast lineage cells.
Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src-JNK-YAP/TAZ pathway in response to mechanical stimulation.


Electrohydraulic lithotripsy combined with laparoscopy and endoscopy for managing difficult biliary stones.
Large or impacted bile duct stones can be difficult to manage with endoscopic and laparoscopic techniques. Electrohydraulic lithotripsy (EHL) seems to be ideally suited for these difficult cases. We report our experience and review the literature. Adjunctive use of EHL was attempted in seven patients with complicated stones. In six, preoperative endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessful. Five were accessed with laparoscopic transcystic technique, one by T-tube tract, and one with open common bile duct (CBD) exploration. EHL was successful in six. The unsuccessful attempt was with a 5-cm CBD stone. No complications of EHL were encountered. In review of the literature, we have found 256 cases of biliary lithiasis successfully treated with EHL without bile duct perforation. Based on our own experience and review of the literature, we conclude that properly used EHL is safe and effective in managing complicated biliary lithiasis.


SENP‑1 enhances hypoxia‑induced proliferation of rat pulmonary artery smooth muscle cells by regulating hypoxia‑inducible factor‑1α.
Hypoxic pulmonary vascular remodeling (HPSR) has an important role in the development of hypoxic pulmonary hypertension. HPSR is predominantly mediated by the proliferation of pulmonary artery smooth muscle cells (PASMCs). Our previous study demonstrated that hypoxia‑inducible factor (HIF)‑1α was able to promote the proliferation of PASMCs. Small ubiquitin‑like modifier (SUMO)ylation is a post‑translational modification that is important in various cellular processes. It has previously been demonstrated that HIF‑1α may be SUMOylated by SUMO. Conversely, SUMO‑specific protease 1 (SENP‑1) was able to increase the stability of HIF‑1α by decreasing SUMOylation of HIF‑1α. In order to investigate whether SUMOylation of HIF‑1α has a role in the proliferation of PASMCs, the present study cultured PASMCs in hypoxic and normoxic chambers in vitro. The proliferation ability of PASMCs was measured using the Cell Counting kit‑8 and 5‑ethynyl‑2'‑deoxyuridine cell proliferation assays. In addition, short hairpin RNA lentiviral particles were used to knockdown the expression of SENP‑1, and the expression levels of HIF‑1α, SENP‑1 and vascular endothelial growth factor (VEGF) were detected at the mRNA and protein levels using semi‑quantitative polymerase chain reaction and western blotting, respectively. The present study demonstrated that SENP‑1 was able to enhance the proliferative ability of PASMCs by initiating deSUMOylation of HIF‑1α and increasing the expression of its downstream responsive gene, VEGF.


Ethoxyquin prevents chemotherapy-induced neurotoxicity via Hsp90 modulation.
Peripheral neurotoxicity is a major dose-limiting side effect of many chemotherapeutic drugs. Currently there are no effective disease-modifying therapies for chemotherapy-induced peripheral neuropathies, but these side effects of chemotherapy are potentially ideal targets for development of neuroprotective therapies, because candidate drugs can be co- or preadministered before the injury to peripheral axons takes place. We used a phenotypic drug screening approach to identify ethoxyquin as a potential neuroprotective drug and carried out additional biochemical experiments to identify its mechanism of action. We validated the screening results with ethoxyquin and its derivatives and showed that they prevented paclitaxel-induced peripheral neuropathy without blocking paclitaxel's ability to kill tumor cells. Furthermore, we demonstrated that ethoxyquin acts by modulating the chaperone activity of heat shock protein 90 (Hsp90) and blocking the binding of 2 of its client proteins, ataxin-2 and Sf3b2. Ethoxyquin-induced reduction in levels of both of these proteins resulted in prevention of axonal degeneration caused by paclitaxel. Ethoxyquin and its novel derivatives as well as other classes of small molecules that act as Hsp90 modulators may offer a new opportunity for development of drugs to prevent chemotherapy-induced axonal degeneration.


In vivo anti-inflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus.
In the present study, liriodendrin isolated by activity-guided fractionation from the ethyl acetate (EtOAc) extracts of the stem bark of Acanthopanax senticosus, was evaluated for anti-inflammatory and antinociceptive activities. Liriodendrin (5, 10 mg/kg/day, p. o.) significantly inhibited the increase of vascular permeability induced by acetic acid in mice and reduced an acute paw edema induced by carrageenan in rats. When the analgesic activity was measured by the acetic acid-induced writhing test and hot plate test, liriodendrin showed a dose-dependent inhibition in animal models. In addition, syringaresinol, the hydrolysate of liriodendrin, more potently inhibited the LPS-induced production of NO, PGE 2 and TNF-alpha production of macrophages than liriodendrin. Consistent with these observations, the expression level of iNOS and COX-2 enzyme was decreased by syringaresinol in a concentration-dependent manner. These results suggest that the anti-inflammatory and antinociceptive effects of liriodendrin after oral administration were attributable to the in vivo transformation to syringaresinol, which may function as the active constituent.


2-(4-Meth-oxy-1H-indol-3-yl)acetonitrile.
In the title compound, C(11)H(10)N(2)O, the cyanide group is twisted away from the indole-ring plane [C(cy)-C(me)-C(ar)-C(ar) = 70.7 (2)°; cy = cyanide, me = methyl-ene, ar = aromatic], whereas the meth-oxy C atom is almost coplanar with the ring system [displacement = 0.014 (5) Å]. In the crystal, N-H⋯N hydrogen bonds link the mol-ecules into C(7) chains propagating in [100].


Comparative clinical assessment of corneal sensation with a new aesthesiometer.
A new version of an aesthesiometer offers particular advantages such as portability without risk of damage to the filament, easy filament replacement, and an expanded stimulus range. We compared the performance of this new instrument to that of the Cochet-Bonnet aesthesiometer in a clinical setting on herpetic patients. Using both instruments, we obtained paired measurements on the normal and diseased corneas from five test loci placed over the corneal surface. Statistical analysis of the normalized data showed that the data obtained by the new instrument were similar to those of the Cochet-Bonnet aesthesiometer.


Immunotoxin therapy.
Immunotoxins are extremely potent agents that recognize specific antigens located on metastatic tumor cells and cause cytotoxicity after cell entry by inhibiting protein synthesis. These agents have considerable in vitro efficacy against numerous metastatic tumor cell lines. In vivo studies have shown complete tumor regression in athymic animals bearing flank tumors or with leptomeningeal neoplasia. Phase I clinical trials have demonstrated therapeutic efficacy in patients with carcinomatous meningitis or with intraparenchymal brain metastases. These agents may be particularly appropriate for patients with widespread intracranial metastatic disease or with radioresistant tumor histology.


Modulation of Asymmetric Division Diversity through Cytokinin and SPEECHLESS Regulatory Interactions in the Arabidopsis Stomatal Lineage.
Coordinated growth of organs requires communication among cells within and between tissues. In plants, leaf growth is largely dictated by the epidermis; here, asymmetric and self-renewing divisions of the stomatal lineage create two essential cell types-pavement cells and guard cells-in proportions reflecting inputs from local, systemic, and environmental cues. The transcription factor SPEECHLESS (SPCH) is the prime regulator of divisions, but whether and how it is influenced by external cues to provide flexible development is enigmatic. Here, we show that the phytohormone cytokinin (CK) can act as an endogenous signal to affect the extent and types of stomatal lineage divisions and forms a regulatory circuit with SPCH. Local domains of low CK signaling are created by SPCH-dependent cell-type-specific activity of two repressive type-A ARABIDOPSIS RESPONSE REGULATORs (ARRs), ARR16 and ARR17, and two secreted peptides, CLE9 and CLE10, which, together with SPCH, can customize epidermal cell-type composition.


Giant aneurysm of the left main coronary artery with fistulous communication to the right atrium.
The giant coronary artery aneurysm combined with coronary artery fistula is extremely uncommon. In our case, there was a giant aneurysm of the left main coronary artery with fistulous communication to the right atrium, combined with moderate aortic valve regurgitation, which was initially found by transthoracic echocardiogram and subsequently confirmed by the 256-slice multidetector computer tomography (MDCT) coronary angiography. After consultation, the patient received surgical treatment, including the closure of the drainage and origin sites of the aneurysm and the aortic valve replacement. The patient recovered uneventfully.


Seroprevalence of bovine immunodeficiency-like virus and bovine leukemia virus in a dairy cattle herd.
To determine the prevalence of single vs. dual infection with bovine immunodeficiency virus (BIV) and bovine leukemia virus (BLV), sera (n = 95) from a dairy cattle herd were analyzed for anti-BIV and anti-BLV antibodies by an enzyme linked immunosorbent assay. Twenty-one percent (20/95) of samples were BIV-seropositive, while 52% (49/95) of the same samples were BLV-seropositive. A significantly greater percentage of BIV-seronegative samples were BLV-seropositive, 57% (43/75), than were BIV-seropositive samples, 30% (6/20). There was no significant correlation between data ranked from least to greatest amount of anti-viral antibody. Five cattle had persistent lymphocytosis (PL); all five were BLV-seropositive and two were BIV-positive. The mean anti-BLV titer was significantly greater in PL cattle, as compared at non-PL cattle, whereas there was no significant difference between the mean anti-BIV titer in PL cattle, as compared with non-PL cattle. These results provide additional information on the seroprevalence of naturally occurring BIV infection, and indicate that BIV can exist independent of other common infectious agents, such as BLV. Further, the results suggest that infection with BIV is not associated with an increased rate of infection with other infectious agents such as BLV.


beta-Hydroxybutyrate dehydrogenase activity in human and kitten odontoclasts and kitten osteoclasts.
beta-Hydroxybutyrate dehydrogenase activity was studied in whole cell preparations of human and kitten odontoclasts and kitten osteoclasts. Strong histochemical reactions occurred within 2--10 min in all three giant cell types. The possible significance of the high levels of beta-hydroxybutyrate dehydrogenase activity in the metabolism of odontoclasts and osteoclasts is discussed.


Bipyridine-mediated fluorescence charge transfer process based on copper ion grafted upconversion nanoparticle platform for ciprofloxacin sensing in aquatic products.
In this work, an ultrasensitive ciprofloxacin (CIP) detection strategy has been established based on copper (Cu2+) ions-induced strong charge transfer in poly acrylic acid (PAA) functionalized upconversion nanoparticles (UCNPs)/2,2-bipyridine (bipy) system. The positively charged Cu2+ ions electrostatically adhere to the surface of the PAA-UCNPs and deactivate the fluorescence via a charge transfer process. The bipy in this hybrid system controls the aggregation by chelating in proximity to the Cu2+ center. Due to the strong affinity between pyridone oxygen and carboxy oxygen, CIP coordinates in high stoichiometry with the bipy-Cu complex as compared to the PAA-UCNPs, causing the trapped fluorescence to be released in an amount equivalent to the target concentration. Under the optimum assay conditions, a good calibration plot (0.05-1000 ng/mL) was acquired with a detection limit of 0.13 ng/mL. The satisfactory recoveries (85.93-96.87%) for real prawn and fish samples were further validated by enzyme-linked immunoassays (P > 0.05).


Isolation of a thioesterase gene from the metagenome of a mountain peak, Apharwat, in the northwestern Himalayas.
The soil metagenome of Apharwat (latitude 34.209° and longitude 74.368°) was explored for the presence of esterase encoding genes using a cultivation-independent approach, metagenomics. Among the various protocols tested, the method developed by Wechter was found to be the best for metagenome isolation from the soil under investigation. The purity of the isolated metagenomic DNA was not suitable for gene cloning. To improve the yield and purity of isolated metagenomic DNA, isothermal amplification of the isolated metagenomic DNA using phi (φ) polymerase in a strand displacement technique was performed. The amplified DNA was comparatively pure and the yield increased 50-fold. A metagenomic library was constructed in Escherichia coli (DH5α) using pUC19 as a vector with an average insert size ranging between 2 and 5 kb. Out of 10,000 clones generated, one clone carrying a ~1,870-bp insert hydrolysed tributyrin, indicating esterase activity. Sequence analysis revealed that the insert harboured three open reading frames (ORFs), of which ORF 3 encoded the esterase. Open reading frame 3 comprises 1,178 bp and encodes a putative 392 amino acid protein whose size correlates with most of the bacterial esterases. The esterase isolated in the present study is suggested to be a 4-methyl-3-oxoadipyl-CoA thioesterase (Accession No. JN717164.1), as it shows 60 % sequence similarity to the thioesterase gene of Pseudomonas reinekei (Accession No. ACZ63623.1) by BLAST, ClustalX and ClustalW analysis.


Hypothalamic-pituitary-adrenocortical axis function in attention-deficit hyperactivity disorder.
The hypothalamic-pituitary-adrenocortical axis plays a critical role in mediating the physiological response to the imposition of stress. There are theoretical reasons to expect reduced basal cortisol secretion and cortisol hyporeactivity in hyperactive/impulsive or combined type attention-deficit hyperactivity disorder (ADHD). Early studies reported profound abnormalities in the diurnal rhythm of cortisol secretion or the cortisol response to stress in children with severe or persistent ADHD. However, subsequent work using larger samples or improved methods has not provided convincing evidence for changes in basal cortisol secretion in non-comorbid forms of ADHD. In contrast, children with ADHD and comorbid oppositional defiant disorder show lower basal cortisol concentrations and a blunted cortisol awakening response. With respect to cortisol reactivity to stress in ADHD, recent evidence has been mixed, with some studies reporting normal cortisol responses and others showing blunted cortisol responses in non-comorbid ADHD. Again, it appears important to consider whether comorbid disorders are present, because children with ADHD and comorbid disruptive behavior disorders exhibit blunted cortisol responses, whereas those with comorbid anxiety disorders show enhanced cortisol responses to stress. Longitudinal studies are required to investigate whether abnormalities in cortisol secretion play a causal role in the etiology of ADHD and related disruptive behavior disorders.


Defining novel parameters for the optimal priming and expansion of minor histocompatibility antigen-specific T cells in culture.
Adoptive transfer of minor histocompatibility antigen (MiHA)-specific T cells is a promising therapy for patients with hematological cancers. However, the efficacy of the transferred cells is hampered by the acquisition of terminal effector differentiation and exhaustion features during expansion in vitro thus preventing their function and persistence in vivo. Yet, the factors that induce T-cell differentiation and functional impairment in culture remain poorly defined and are likely to vary depending on the method used for expansion. Using the clinically relevant HLA-A0201-restricted MiHA HA-1 as well as reagents and procedures that are readily transferable to a clinical environment, we designed a novel culture protocol and defined how exhaustion features appeared in function of time. The optimal time points for the expansion of "fit" MiHA-specific T cells were delineated using phenotypic and functional assessments including KLRG-1 and PD-1 surface markers as well as Ki67 staining and cytokine secretion assays. Following a priming phase, an enrichment step and a rapid expansion stage, our method generates MiHA-specific T-cell lines. Evidence of phenotypic and functional dysfunction appear in function of culture duration, but display different characteristics following the extension of the priming or rapid expansion phases. While repeated antigen exposure during the priming phase induced the decline of the antigen-specific population and the expression of PD-1 and KLRG-1 on antigen-specific CD8+ T cells, the prolongation of an antigen-free expansion phase induced proliferation arrest and the relative loss of antigen-specific cells without impairing polyfunctional cytokine secretion or inducing PD-1 and KLRG-1 expression. A similar pattern was also observed after stimulating a virus-specific memory repertoire, except for the more rapid acquisition of exhaustion features upon repeated antigen exposure. Our results offer novel insights on the impact of culture duration on the acquisition of T-cell exhaustion features. Using a new clinical-compliant protocol, we define critical parameters to monitor in order to optimally differentiate and expand MiHA-specific T cells in culture prior to adoptive transfer.


Selective activation of liver X receptor alpha by 6alpha-hydroxy bile acids and analogs.
We have found that certain natural 6alpha-hydroxylated bile acids are receptor-specific activators of nuclear liver X receptor alpha (LXRalpha) (NR1H3), a nuclear receptor regulating the expression of the cholesterol 7alpha-hydroxylase gene, coding for the rate-limiting enzyme in the major pathway of bile acid synthesis. The LXR homolog, ubiquitous nuclear receptor (UR/LXRbeta) (NR1H2), was also activated by these bile acids, but at higher concentrations than for LXRalpha. Synthetic 6alpha-hydroxylated bile acid analogs were synthesized with LXRalpha-selective agonistic activity, with potential to modulate cholesterol catabolism in hypercholesterolemia.


A comparative assessment of two techniques for investigating initial cardiovascular reflexes under acute orthostatic stress.
The physiological differences between active and passive changes in posture have been previously established. This study determined the extent of the differences in the initial cardiovascular responses to the passive head-up tilt (HUT) and the active squat-stand test (SST). Eleven females and 13 males underwent one +75 degrees HUT and one SST. Beat-to-beat diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were determined non-invasively. Data were recorded 10 s prior to (control) and 30 s after tilt or stand (event). Blood pressure and HR responses were analysed by calculating the deviation from control at 10 s (T10), 20 s (T20) and 30 s (T30) after the onset of each test. The DBP response (reflecting changes in systemic vascular resistance) at T10 was -10 (2) mmHg [mean (SEM)] for the HUT and -25 (2) mmHg for the SST ( P<0.01). DBP returned to control levels by T30 for the HUT, but remained depressed for the SST. MAP responses directly reflected these changes in DBP. HR significantly increased from control values ( P<0.001) for the HUT [+14 (1) bpm] and the SST [+16 (1) bpm], and remained elevated for the entire 30-s period for both tests. This study demonstrates that although the magnitude of the initial blood pressure decrease is greater for the active SST compared with the passive HUT, the reflex compensatory response is no different, making the SST a greater challenge for the cardiovascular reflexes.


Assembly and maintenance of nodes of ranvier rely on distinct sources of proteins and targeting mechanisms.
We have investigated the source(s) and targeting of components to PNS nodes of Ranvier. We show adhesion molecules are freely diffusible within the axon membrane and accumulate at forming nodes from local sources, whereas ion channels and cytoskeletal components are largely immobile and require transport to the node. We further characterize targeting of NF186, an adhesion molecule that pioneers node formation. NF186 redistributes to nascent nodes from a mobile, surface pool. Its initial accumulation and clearance from the internode require extracellular interactions, whereas targeting to mature nodes, i.e., those flanked by paranodal junctions, requires intracellular interactions. After incorporation into the node, NF186 is immobile, stable, and promotes node integrity. Thus, nodes assemble from two sources: adhesion molecules, which initiate assembly, accumulate by diffusion trapping via interactions with Schwann cells, whereas ion channels and cytoskeletal components accumulate via subsequent transport. In mature nodes, components turnover slowly and are replenished via transport.


Prevention, Intervention and Care of Neurodegenerative Diseases.
Chronic neurodegenerative diseases encompass a wide spectrum of disorders and affect millions of people worldwide [...].


Foreign Body in the Hard Palate of Infant.
Foreign bodies adherent to the hard palate often mimic oral lesions. Case report: A 10-month-old female infant presented with the sudden development of a hard palate lesion. With photography and visualization, the "lesion" was a false nail, which belonged to the child's caregiver. Discussion/conclusion: The differential diagnosis of palatal lesions in infants should include foreign bodies, and if identified as such, evaluation under anesthesia may be avoided.


Risks of adverse pregnancy outcome in endometriosis.
Bleeding from endometriotic implants is now an established cause of acute hemoperitoneum in pregnancy. However, the adverse impact of pelvic endometriosis on uterine function before conception may also interfere with subsequent deep placentation, accounting for the increased risk of obstetrical complications, including preterm birth and antepartum hemorrhage.


Prevalence and Associated Factors of Abdominal Pain and Disability at 1-Year Follow-up After an Attack of Acute Pancreatitis.
The aim of the study was to report the prevalence and predictors of abdominal pain and disability 1 year after an acute pancreatitis (AP) attack. Patients were prospectively enrolled between December 2012 and April 2016. Enrolled subjects were contacted at a median of 13 months after enrollment. Multivariable regression models were used to determine factors independently associated with abdominal pain at follow-up. Response rate was 71% (110/155). Of respondents, median age was 51 years, 58% were female, and 14% had severe AP. At follow-up, 24% of patients reported abdominal pain (65% intermittent, 35% constant), 10% used analgesics regularly, and 6% had regular opioids use. Furthermore, 41% of patients experienced pain-related interference with work or daily activities, and 8% developed disability. On regression analysis, idiopathic etiology (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.1-13.6) persistent organ failure (OR, 3.3; 95% CI, 1.1-7.9), and recurrent AP (OR, 2.9; 95% CI, 1.1-10.6) were independently associated with abdominal pain at follow-up. Disability at follow-up was associated with younger age, current smoking, and intensive care unit admission (all P < 0.05). Abdominal pain and disability are potential long-term sequelae of AP. Certain pre-existing factors and pancreatitis features are associated with these outcomes at one-year follow-up of AP.


Development of stable HSPA1A promoter-driven luciferase reporter HepG2 cells for assessing the toxicity of organic pollutants present in air.
HSPA1A (HSP70-1) is a highly inducible heat shock gene up-regulated in response to environmental stresses and pollutants. The aim of our study was to evaluate the sensitivity of the stable metabolically competent HepG2 cells containing a human HSPA1A promoter-driven luciferase reporter (HepG2-luciferase cells) for assessing the toxicity of organic pollutants present in air. The HepG2-luciferase cells were validated by heat shock treatment and testing three organic compounds (pyrene, benzo[a]pyrene, and formaldehyde) that are ubiquitous in the air. The maximal level of HSPA1A (HSP70-1) and relative luciferase activity induced by heat shock were over three and nine times the control level, respectively. Pyrene, benzo[a]pyrene, and formaldehyde all induced significantly elevated levels of relative luciferase activity in a dose-dependent manner. Extractable organic matter (EOM) from urban traffic and coke oven emissions in ambient air were tested on the HepG2-luciferase cells. The traffic EOM induced significant increase in relative luciferase activity at concentrations of picogram per liter. The coke oven EOM produced a strong dose-dependent induction of relative luciferase activity up to six times the control value. Significant increases in relative luciferase activity were observed at concentrations that were as low, or lower than the concentrations that the tested organic pollutants decreased cell viability, and increased malondialdehyde concentration, Olive tail moment, and micronuclei frequency. Therefore, we conclude that the HepG2-luciferase cells are a valuable tool for rapid screening of the overall toxicity of organic pollutants present in air.


Reviewing the current state of virtual reality integration in medical education - a scoping review protocol.
Due to an increasing focus of medical curricula on clinical decision-making skills, new learning tools are constantly developed. Virtual reality (VR) is one of the emerging technologies with the potential to improve health professionals' education. Highly realistic learning experiences with repeatable training scenarios can be created within a protected environment that is independent from real patients' presence. Our project "medical tr.AI.ning" is following this approach aiming to simulate immersive virtual first-person scenarios with intelligent, interactable virtual patients. So far, VR has been mainly used in surgical training, but there is evidence for effectiveness in training different procedural skills, such as cardiopulmonary resuscitation, knowledge acquisition, and improvement of reasoning and creativity, while still being cost-effective. The objective of this scoping review is to explore the usage and identify key areas of VR applications in the field of medical education. Furthermore, the corresponding requirements, evaluation methods and outcomes, advantages, and disadvantages will be covered. This scoping review protocol implements the updated JBI Scoping Review Methodology. In March 2022, a preliminary literature research in PubMed was performed by two independent reviewers to refine search terms and strategy as well as inclusion criteria of the protocol, accounting for actuality and scientific relevance. The final search will be conducted using PubMed, ScienceDirect, Cochrane Library, Web of Science Core Collection, and JBI Evidence Synthesis. Search, study screening, and data extraction will be done in parallel and independently by two reviewers. Discrepancies will be handled by consensus or consulting a third review author. With this scoping review, we anticipate collating the range of application of VR in medical education while using a transparent and reproducible search strategy. This may contribute to the design and development of novel educational VR platforms and their integration into medical curricula while pointing out previous omissions and pitfalls.


Pacific Tracker 2 - expert system (PacTrac2-ES) behavioural assessment and intervention tool for the Pacific Kids DASH for Health (PacDASH) study.
The Pacific Tracker (PacTrac) is a computer program designed to analyse food intakes of individuals from the Pacific Region. PacTrac's original output included servings of daily intake of food groups according to the United States Food Guide Pyramid, nutrient intake recommendations, and a comparison to other national nutrition recommendations. PacTrac was made available for public use through the Hawaii Foods website (hawaiifoods.hawaii.edu). PacTrac2 is an updated and expanded version of PacTrac that uses the United States MyPyramid/MyPlate food groups in household units of daily intake, rather than servings. In addition, the PacTrac2 includes a physical activity analysis tool which quantifies minutes of physical activities and their intensities based on energy estimates from the compendium of physical activity and research on children. An Expert System (ES) - a computerised decision tree to guide behaviour change - was developed using information on self-efficacy and stage of readiness to change, and the fruit and vegetable intake and physical activity information from PacTrac2. The ES produces reports for the child, the parent/guardian, and the child's physician with child-specific strategies, targeted behavioural information, and feedback tailored to the child. PacTrac2-ES was designed for the Pacific Kids DASH for Health (PacDASH) intervention study, conducted in the Kaiser Permanente health care system in Hawaii. The intervention is based on the child's self-efficacy and stage of readiness to change intake of fruits and vegetables and physical activity, with a goal of maintaining body weight to prevent obesity. The intervention is complemented with stage-based mailers addressing the environment for physical activity and fruit and vegetable intake and newsletters that address related behaviours (sedentary activity and a DASH eating approach). This project is the first to expand the PacTrac to contain children's foods and physical activities from the Pacific Region and to use current US MyPyramid/MyPlate food and physical activity analysis and guidance systems, and to develop and implement an Expert System for fruits, vegetables and physical activity of 5-8-year-old children. The PacTrac2-ES was used in the PacDASH study and will be used for other programs to promote healthy eating and physical activity of children in the Pacific Region.


A qualitative study exploring health perceptions and factors influencing participation in health behaviors in colorectal cancer survivors.
The purpose of the study was to explore colorectal cancer survivors' health perceptions following cessation of active treatment for cancer and to explore the factors influencing participation in health-promoting behaviors that may help reduce cardiovascular disease risk. Face-to-face interviews were conducted with participants that had completed active treatment for cancer within the previous 2 years. Participants were colorectal cancer survivors (N = 24, men = 11, women = 13, M age = 69.38 years, SD = 4.19) recruited from a private hospital in Perth, Australia on the basis that they had existing morbidities that put them at increased risk of cardiovascular disease. Interview transcripts were analyzed using thematic analysis. Five main themes emerged: back to normal; the pleasures in life: 'is it worth it?'; beliefs about health behavior; skepticism of eating guidelines; and lack of motivation. The majority of participants felt they were in good health and had made a full recovery. Participants questioned whether it was worth changing their lifestyle given their life stage and referred to the desire to enjoy life. Lay health beliefs, skepticism of eating guidelines, and a lack of motivation were barriers to change. Interventions should target lay beliefs and skepticism in relation to health behaviors in order to reinforce the importance and value of participating in health-related behavior. Findings may inform the development of effective, patient-centered interventions that target lay health beliefs and build motivation for health behavior change. Copyright © 2016 John Wiley & Sons, Ltd.


Midlife diagnosis of Refsum disease in siblings with retinitis pigmentosa -- the footprint is the clue: a case report.
Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations. We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date. It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.


Effect of feeding strategy on a stirred anaerobic sequencing fed-batch reactor containing immobilized biomass.
The present work reports on the influence of feeding strategy on the stability and performance of a stirred anaerobic sequencing fed-batch reactor containing biomass immobilized on polyurethane foam. The reactor treated low-strength wastewater and was operated at 30 degrees C with an agitation rate of 200 rpm. A 180-min cycle was used to treat approximately 0.5 l of synthetic substrate with a chemical oxygen demand concentration of nearly 500 mg/l. The reactor was operated in batch mode with a 3-min feeding step and in constant rate fed-batch mode with feeding steps of 30, 60 and 180 min. During batch operation, the system attained stability and had a removal efficiency of 86% based on non-filtered substrate concentration. However, during fed-batch operation stability and efficiency were impaired and formation of suspended material was identified. Stability was achieved only for the 30-min feeding step. The poor performance and instability observed in the fed-batch experiments were credited to the formation of considerable quantities of extracellular polymers, which impeded contact between substrate and biomass with consequent negative effect on the mass transfer fluxes. The biopolymer formation was very likely a result of the fed-batch operational mode, in which part of the bioparticles were deprived of contact with the liquid medium for a relatively long period of time.


Refugees, water balance, and water stress: Lessons learned from Lebanon.
The Syrian crisis caused a massive influx of displaced people into neighboring countries, with Lebanon hosting the highest per capita number of refugees (3:10). Water remains the most critical natural resource that influences the resilience of host and refugee communities. We provide a new GIS-based updated water balance and water scarcity analysis at the national and the watershed level in Lebanon by comparing current conditions to no-refugee levels. Results show a small (6%) increase in water stress in an average water year at the national level that masks hot spots of water scarcity at the local geography. While domestic water use increased by 20%, we find that refugees' water use is only 10% of agricultural water use in summer. We also show that interventions to rehabilitate the water networks can reduce water stress to better than pre-conflict levels (3% less stress).


Effects of Intermittent Hypoxia on Expression of Glucose Metabolism Genes in MCF7 Breast Cancer Cell Line.
Hypoxic condition induces molecular alterations which affect the survival rate and chemo-resistant phenotype of cancer cells. The aim of this study is to investigate the influence of intermittent hypoxic conditions on the expression of glucose metabolism genes in breast cancer MCF7 cell line. The gene expression was analyzed using a polymerase chain reaction-array method. In addition, the cell resistance, survival and migration rates were examined to assure the hypoxic influence on the cells. 30 hypoxic episodes induced the Warburg effect through significant (p-value < 0.05) upregulation of the expression of PCK2, PHKG1, ALDOC, G6PC, GYS2, ALDOB, HK3, PKLR, PGK2, PDK2, ACO1 and H6PD genes that are involved in glycolysis, were obtained. Furthermore, the expression of the major gluconeogenesis enzyme genes was significantly (ANOVA, p-value < 0.05) downregulated. These molecular alterations were associated with increased MCF7 cell division and migration rate. However, molecular and phenotypic changes induced after 30 episodes were normalized in MCF7 cells exposed to 60 hypoxic episodes. It is concluded, from this study, that 30 intermitted hypoxic episodes increased the survival rate of MCF7 breast cancer cells and induced the Warburg effect through upregulation of the expression of genes involved in the glycolysis pathway. These results may increase our understanding of the molecular alterations of breast cancer cells under hypoxic conditions.


Phytoremediation potential and copper uptake kinetics of Philippine bamboo species in copper contaminated substrate.
The phytoremediation potential of three bamboo species, i.e. Bambusa merilliana, Bambusa blumeana, and Dendrocalamus asper, were evaluated for their total Cu uptake ability in hydroponics. Dendrocalamus asper proved to be the most efficient in terms of Cu phytoremediating potential with a constant positive uptake of 80 μM in a contaminated substrate and a bioconcentration factor of 50.57. Copper accumulation was found to concentrate the most in the roots compared to the amount translocated in the shoots. Analysis of the Cu uptake of D. asper roots at varying concentrations of Cu contamination (40, 80 and 120 μM) allowed for the fitting of the kinetics of Cu uptake and removal with existing kinetic models. The rate of copper removal per mass of plant was the best for the 0th order model in the 80 μM solution with an R2 of 0.954 and rate constant of 3.136 mg-kg-1d-1. The accumulation of Cu within the roots on day 7 (7d) followed the Michaelis-Menten model with an R2 of 0.970. The Michaelis-Menten constant (KM) was 4.87 mg/L and maximum accumulation velocity (Vmax) was 66.26 mg Cu-kg-1-day-1. Results suggest that D. asper is a potential hyperaccumulator plant that can be used in clean-up of domestic and industrial wastes present along river systems in the Philippines.