Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data.
A computer-based pattern recognition (PR) approach has been applied to the interpretation of 1H NMR generated urinalysis data in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous metabolite in urine were regarded as coordinates in multi-dimensional space and analysed using computer pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Initially 17 metabolic dimensions were used which were defined by the scored relative concentrations of a variety of urinary metabolites detected in 1H NMR spectra. By employing the unsupervised learning methods of 2- and 3-dimensional nonlinear mapping (NLM) different types of toxin (hepatotoxins, cortical and papillary nephrotoxins) could be classified according to NMR-detectable biochemical effects in the urine. The robustness of the classification methods, and the influence of the addition of new scored biochemical data reflecting dose response situations, nutritional effects on toxicity, sex differences in biochemical response to toxins and addition of a new toxin class (testicular toxin) to the pattern recognition analysis were also evaluated. We find that the initial training set maps are fundamentally stable to the addition of all data types and that the PR methods correctly 'predicted' the toxicological effects of the test compounds. These results confirm the power and wide applicability of linked PR and 1H NMR urinalysis as an approach to the generation and classification of acute toxicological data.


Noise Exposure Alters Glutamatergic and GABAergic Synaptic Connectivity in the Hippocampus and Its Relevance to Tinnitus.
Accumulating evidence implicates a role for brain structures outside the ascending auditory pathway in tinnitus, the phantom perception of sound. In addition to other factors such as age-dependent hearing loss, high-level sound exposure is a prominent cause of tinnitus. Here, we examined how noise exposure altered the distribution of excitatory and inhibitory synaptic inputs in the guinea pig hippocampus and determined whether these changes were associated with tinnitus. In experiment one, guinea pigs were overexposed to unilateral narrow-band noise (98 dB SPL, 2 h). Two weeks later, the density of excitatory (VGLUT-1/2) and inhibitory (VGAT) synaptic terminals in CA1, CA3, and dentate gyrus hippocampal subregions was assessed by immunohistochemistry. Overall, VGLUT-1 density primarily increased, while VGAT density decreased significantly in many regions. Then, to assess whether the noise-induced alterations were persistent and related to tinnitus, experiment two utilized a noise-exposure paradigm shown to induce tinnitus and assessed tinnitus development which was assessed using gap-prepulse inhibition of the acoustic startle (GPIAS). Twelve weeks after sound overexposure, changes in excitatory synaptic terminal density had largely recovered regardless of tinnitus status, but the recovery of GABAergic terminal density was dramatically different in animals expressing tinnitus relative to animals resistant to tinnitus. In resistant animals, inhibitory synapse density recovered to preexposure levels, but in animals expressing tinnitus, inhibitory synapse density remained chronically diminished. Taken together, our results suggest that noise exposure induces striking changes in the balance of excitatory and inhibitory synaptic inputs throughout the hippocampus and reveal a potential role for rebounding inhibition in the hippocampus as a protective factor leading to tinnitus resilience.


Patients' perceptions of entitlement to time in general practice consultations for depression: qualitative study.
To investigate patients' perceptions of entitlement to time in general practice consultations for depression. Qualitative study based on interviews with patients with mild to moderate depression. Eight general practices in the West Midlands and the regional membership of the Depression Alliance. 32 general practice patients and 30 respondents from the Depression Alliance. An intense sense of time pressure and a self imposed rationing of time in consultations were key concerns among the interviewees. Anxiety about time affected patients' freedom to talk about their problems. Patients took upon themselves part of the responsibility for managing time in the consultation to relieve the burden they perceived their doctors to be working under. Respondents' accounts often showed a mismatch between their own sense of time entitlement and the doctors' capacity to respond flexibly and constructively in offering extended consultation time when this was necessary. Patients valued time to talk and would often have liked more, but they did not necessarily associate length of consultation with quality. The impression doctors gave in handling time in consultations sent strong messages about legitimising the patients' illness and their decision to consult. Patients' self imposed restraint in taking up doctors' time has important consequences for the recognition and treatment of depression. Doctors need to have a greater awareness of patients' anxieties about time and should move to allay such anxieties by pre-emptive reassurance and reinforcing patients' sense of entitlement to time. Far from acting as "consumers," patients voluntarily assume responsibility for conserving scarce resources in a health service that they regard as a collective rather than a personal resource.


Review article: management of hepatic disease following haematopoietic cell transplant.
Hepatic diseases are common complications of haematopoietic cell transplant. The causes are multiple: myeloablative conditioning regimens may cause sinusoidal injury; acute and chronic graft-versus-host disease lead to damaged hepatocytes and small bile ducts; microcrystalline deposits in the gall bladder can cause biliary symptoms; drug-induced liver injury is common; and the liver may be infected by viruses and fungi during the period of severe immune suppression that follows transplant. Pre-transplant evaluation and prevention of liver injury are often more useful than treatment of deeply jaundiced patients in improving transplant outcomes. This review covers pre-transplant evaluation, common hepatobiliary problems in the six months following transplant, and hepatic problems in long-term survivors.


Targeting Hedgehog (Hh) Pathway for the Acute Myeloid Leukemia Treatment.
The Hedgehog (Hh) pathway, containing the Patched (PTCH) and Smoothened (SMO) multitransmembrane proteins, is the main regulator of vertebrate embryonic development. A non-canonical Hh pathway was recently observed in numerous types of solid cancers and hematological malignancies. Although acute myeloid leukemia (AML) is a common and lethal myeloid malignancy, the chemotherapy for AML has not changed in the last three decades. The Hh pathway and other intracellular signaling pathways are important for the tumor cells' cycle or therapeutic resistance of AML cells. In this article, we will review the current trends in Hh pathway inhibitors for treating AML.


The Effects of Nerve and Tendon Gliding Exercises Combined with Low-level Laser or Ultrasound Therapy in Carpal Tunnel Syndrome.
Carpal tunnel syndrome (CTS) is a common medical condition that doctors and physiotherapists come across in clinical practice. There are no explicit recommendations concerning which physical therapy methods should be applied in its treatment; however, there have also been no studies on the effects of combining low-level laser therapy (LLLT) or ultrasound with nerve and tendon gliding exercises. The purpose of this study was to evaluate the therapeutic efficacy of ultrasound and LLLT combined with gliding exercises. A total of seventy patients with mild to moderate CTS, divided into two groups, were included in this study. Group 1 received ultrasound treatment, whereas Group 2 underwent LLLT. The treatment lasted 2 weeks (5 sessions/week). In addition, both groups were treated with nerve and tendon gliding exercises three times daily. The clinical evaluation involved an interview on subjective and objective sensory abnormalities, the intensity of pain, the measurement of grip strength, Phalen's test, Tinel's sign, and the Boston Carpal Tunnel Questionnaire. The assessment was performed before and after the treatment. A decrease in sensory impairments, improvement in visual analog scale, hand grip strength and the Boston Questionnaire results were significant in all patients after therapy. No meaningful differences between groups were noted in any of the examined variables after treatment. No adverse effects were observed. The results of this study may suggest the clinical efficacy of LLLT or ultrasound combined with gliding exercises in patients with mild to moderate CTS.


Influence of thyroxine in vivo on preadipocyte development and insulin-like growth factor-I and IGF binding protein secretion in fetal stromal vascular cell cultures.
Studies were conducted to determine the influence of thyroxine (T4) in vivo on preadipocyte development and insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) secretion in stromal-vascular (S-V) cultures. Fetal pigs were hypophysectomized (hypox) at 70 days of gestation, implanted with T4 pellets, and fetuses from the dam at 75 days of gestation. In a second experiment, hypox and T4 implantation were performed at 75 days and fetal pigs removed at 95 days of gestation. Primary cultures of stromal vascular (S-V) cells derived from fetal adipose tissue were established. Cultures were stained for morphological analysis and conditioned media were collected for IGF-1 determination by radioimmunoassay (RIA) and IGFBP analysis by Western blotting. After only 5 days of T4 treatment, fat cell cluster number and size and lipid deposition in cultures were significantly increased compared to cultures from untreated hypox fetuses. Fetal hypox reduced IGF-I secretion by preadipocytes at both ages and T4 treatment completely normalized IGF-I secretion (p < 0.05). Four IGFBPs (BP-1, BP-2, BP-3 & BP-4) detected in S-V cultures derived from 95-day fetuses were decreased in concentration by hypox by 44 +/- 9.4%, 32 +/- 9.7%, 42 +/- 12% and 53 +/- 6.9%. In cultures derived from T4 treated hypox fetuses, the levels of these four IGFBPs were increased by 187 +/- 25%, 239 +/- 38%, 190 +/- 5% and 347 +/- 43% over control values, respectively. In cultures from 75-day fetuses, only IGFBP-2 (major one) and BP-1 (minor one) were detected and their secretion was also decreased by hypox and elevated by T4 treatment (190 +/- 49.5%, 156 +/- 30%, respectively, of controls). The results provide direct evidence that T4 has a major influence on fetal preadipocyte development. T4 stimulated production of IGF-I and IGFBP in fetal S-V cultures, which in turn, may have mediated the capability of T4 to enhance fetal adipose tissue development.


Structural characterization of the gene for human histidine-rich glycoprotein, reinvestigation of the 5'-terminal region of cDNA and a search for the liver specific promoter in the gene.
Genomic DNA libraries were screened for the human histidine-rich glycoprotein (HRG) gene and a sequence of 15,499 nucleotides was determined. The gene is composed of 7 exons and 6 introns, and all the exon-intron boundaries match the consensus GT/AG sequence for donor and acceptor splice sites. Each of cystatin-like domains I and II of HRG is encoded by three exons, exons I to III and exons IV to VI, respectively, like those of other members of the cystatin superfamily. The entire C-terminal half of the molecule is encoded by the largest exon, VII. The first 103 nucleotides of the cDNA sequence reported for human HRG [Koide, T., Foster, D., Yoshitake, S. , and Davie, E.W. (1986) Biochemistry 25, 2220-2225] could not be found in the determined gene sequence. A homology search of this sequence against a database showed the complete matching to a part of the yeast mitochondrial DNA encoding 21S ribosomal RNA. Rapid amplification of cDNA 5' ends (5'-RACE) analysis revealed that the cDNA has multiple 5'-ends and that a possible starting point is nucleotide 104 of the reported cDNA sequence. These results suggest that the first 103 nucleotides of the cDNA sequence reported for human HRG originated from yeast mitochondrial DNA and were incidentally incorporated into the HRG cDNA in the process of the construction of a cDNA library. Various fragments obtained on restriction endonuclease digestion of the 5'-noncoding region of the HRG gene were ligated to the chloramphenicol acetyltransferase (CAT) gene and then transfected into HepG2 and 293 cells to analyze the promoter activity. The sequence between -262 and -21 from the putative translation initiation site supported the expression of CAT in HepG2 cells but not in 293 cells, suggesting that this segment promotes the liver-specific transcription of the human HRG gene.


The correlation between aerobic fitness and motion sickness susceptibility.
Susceptibility to motion sickness has been linked to aerobic fitness in several studies, however, these studies have not elucidated the underlying physiological mechanism by which increased aerobic fitness is related to a decreased ability to tolerate motion sickness stimuli. This pilot study provides further evidence of a relationship between aerobic fitness and motion sickness susceptibility. It also suggests that aerobic capacity is more specifically linked to signs and symptoms of vasomotor origin including stomach discomfort, nausea and/or vomiting, headache, and diaphoresis. By independently correlating vasomotor susceptibility and neurogenic susceptibility to maximum oxygen uptake, we find that vasomotor symptoms in particular are significantly increased in aerobically fit individuals. Larger studies should be conducted to confirm this relationship.


The funds, friends, and faith of happy people.
New studies are revealing predictors of subjective well-being, often assessed as self-reported happiness and life satisfaction. Worldwide, most people report being at least moderately happy, regardless of age and gender. As part of their scientific pursuit of happiness, researchers have examined possible associations between happiness and (a) economic growth and personal income, (b) close relationships, and (c) religious faith.


Lance-Adams Syndrome in the Pretargeted Temperature Management Era.
Acute posthypoxic myoclonus portends a poor prognosis. Another form of posthypoxic myoclonus, Lance-Adams syndrome, is associated with a better outcome. Differentiating these two entities is important in prognostication and guiding further medical intervention. This can be difficult in the acute setting after hypoxic brain injury but the use of neurophysiologic studies may be helpful. In this article, we present a case of a patient who presented after pulseless electrical activity arrest, underwent targeted temperature management and subsequently developed Lance-Adams syndrome. The neurologic and electroencephalographic findings in Lance-Adams syndrome are discussed with an updated review.


EC-collaborative study on the determination of aflatoxin B1 in animal feeding stuffs.
A collaborative study was conducted to test a method, proposed in the European Community (EC) as a candidate-official method for the determination of aflatoxin B1 in compounded feeding stuffs. The study was undertaken on behalf of the European Commission's Community Bureau of Reference (BCR). It involved 25 laboratories from 11 EC countries. The method, based on chloroform extraction and Sep-Pak Florisil and C18 cartridge clean-up, offered either reverse-phase high performance liquid chromatography (HPLC) with iodine post-column derivatization, or two-dimensional thin-layer chromatography (TLC) as determinative steps. In the study, 22 laboratories applied HPLC, three laboratories applied TLC. The study involved six unknown samples. These consisted of blind duplicate samples of compounded feeding stuff, with target concentrations of aflatoxin B1 at less than 2, 8 and and 14 micrograms/kg. Statistical analysis of the HPLC data was carried out according to ISO 5725. For the less than 2 micrograms/kg sample, all reported aflatoxin concentrations were less than 2 micrograms/kg. At the 8 and 14 micrograms/kg level (pooled), repeatability (r) and reproducibility (R), expressed as ratios, were 1.4 and 1.7 respectively, and within-laboratory and between-laboratory coefficients of variation were 11% and 18% respectively. The study revealed that admittance of daylight in the laboratory caused losses of aflatoxin B1 and must be avoided. New glassware coming into contact with aqueous solutions containing aflatoxin B1 was found to be a potential cause of loss of aflatoxin B1. The method has been recommended to the European Commission to be considered for adoption in EC regulations.


Statistical analysis of X-ray speckle at the NSLS.
A statistical analysis of the static speckle produced by illuminating a disordered aerogel sample by a nominally coherent X-ray beam at wiggler beamline X25 at the National Synchrotron Light Source is reported. The results of the analysis show that the coherence delivered to the X25 hutch is within 35% of what is expected. The rate of coherent photons is approximately two times smaller than expected on the basis of the X25 wiggler source brilliance.


[Adenovirus conjunctivitis diagnosis using RPS Adenodetector].
To evaluate the RPS Adenodetector, a rapid immunochromatographic test, in the diagnosis of patients with clinical overt adenoviral conjunctivitis. Consecutive case series. Patients underwent conjunctiva scraping for RPS Adenodetector test and culture to identify adenovirus. A total of 11 patients were studied, and 10 had unilateral disease. Five (45.5%) had symptoms for 2 days, 5 for three days, and 1 for 7 days. Adenovirus culture was positive in 8 patients (73%) and RPS Adenodetector was positive in 9 (82%) patients. Eight patients had adenovirus identification by both methods. In one patient the RPS Adenodetector was positive in contrast to a negative culture. The two patients revealing negative RPS Adenodetector results also had negative cultures. The sensitivity was 100% and the specificity was 67%. The RPS Adenodetector is a useful tool in the rapid diagnosis of adenovirus conjunctivitis and may contribute to the spread control of this highly contagious disease.


Distribution of hydrolysable tannins in the foliage of Finnish birch species.
On the basis of qualitative and quantitative analysis with liquid chromatography--electrospray ionisation mass spectrometry, the foliage of dwarf birch (Betula nana L.), silver birch (B. pendula Roth) and mountain birch (B. pubescens ssp. czerepanovii (Orlova) Hämet-Ahti) were found, for the first time, to contain the same individual HTs that were described earlier for white birch (B. pubescens Ehrh.). In addition, one previously unidentified ellagitannin was preliminarily identified from the leaves of white and mountain birches, being totally absent from the foliage of the other two species. There were large variations in the contents of HTs between species. Seasonal variation affected significantly the contents of some individual HTs within species, and these changes were mainly in accordance with the biosynthetic pathway of HTs. All species converted galloylglucoses (GGs) into ellagitannins (ETs), dwarf birch being the only one that's efficient ET synthesis resulted in seasonally increased contents of ETs and thereof total HTs as well. The presence of insoluble ETs as well as the absence of insoluble GGs was confirmed in all four birch species for the first time. Furthermore, the amounts of insoluble ETs per one birch leaf were found to accumulate during the growing season. These findings complemented our knowledge of the biosynthetic pathway of birch leaf HTs: from soluble GGs via soluble ETs into insoluble ETs. The possible role of HTs in the herbivore defence of these species is discussed.


Minigene splicing assessment of 20 novel synonymous and intronic glucokinase gene variants identified in patients with maturity-onset diabetes of the young.
The next-generation sequencing (NGS) has become a routine method for diagnostics of inherited disorders. However, assessment of the discovered variants may be challenging, especially when they are not predicted to change the protein sequence. Here we performed a functional analysis of 20 novel or rare intronic and synonymous glucokinase (GCK) gene variants identified by targeted NGS in 1,130 patients with maturity-onset diabetes of the young. Human Splicing Finder, ver 3.1 and a precomputed index of splicing variants (SPIDEX) were used for in silico prediction. In vitro effects of GCK gene variants on splicing were tested using a minigene expression approach. In vitro effect on splicing was shown for 9 of 20 variants, including two synonymous substitutions. In silico and in vitro results matched in about 50% of cases. The results demonstrate that novel or rare apparently benign GCK gene variants should be regarded as potential splicing mutations.


Sharing the British National Health Service around the world: a self-interested perspective.
As the UK reiterates its commitment to protecting and growing its development aid budget amidst an adverse economic environment for the UK and Europe, we discuss the potential to use the country's National Health Service (NHS) model as a vehicle for promoting the country's economic as well as global health diplomacy and development priorities, through a coordinated cross-government plan of action. With the country's Prime Minister serving as a co-chair of the UN post-2015 development agenda panel,a this is a unique opportunity for the UK to put forward its health system architecture as a highly applicable and well-tested model for providing access to efficient and cost-effective care, with minimal financial hardship. Arguably, such a model tailored to the needs of specific countries could consequently lead to commercial opportunities for UK plc. in areas such as consulting, training, education and healthcare products. Finally, this approach would be consistent with the current thinking on the evolving role of UK aid, especially in the case of emerging powers such as India, where the focus has shifted from aid to investment in technical assistance and cooperation as a means of boosting bilateral business and trade.


The effects of intravenous alendronate in Paget's disease of bone.
We studied the effects of intravenous alendronate on disease activity in 36 patients with active Paget's disease of bone. Alendronate was administered to 3 groups of 12 patients at doses of 2.5, 5, and 10 mg intravenously daily for 5 consecutive days. The patients were matched for disease activity. Symptomatic improvement was seen in at least 10 patients in each treatment group. Alendronate induced a dose-dependent suppression of biochemical indices of bone turnover in all patients. A significant reduction in the mean fasting urinary excretion of hydroxyproline occurred within 2 days of starting treatment, reaching a nadir at 2-4 weeks, which was most marked in patients receiving 10 mg of alendronate (p < 0.05). There was a slower fall in serum alkaline phosphatase activity with maximal suppression occurring 3 months after the start of treatment. The degree of suppression was least for those receiving 2.5 mg of alendronate (p < 0.05) but no difference in response was observed for the other dosages. The duration of response was also dose-related. A significant fall in the serum calcium and urinary excretion of calcium occurred from the second day of treatment but returned to pretreatment values by 4 months. A transient fall in the mean lymphocyte count was observed, which was similar for each group. This was associated with a short-lived fever in 3 patients receiving 10 mg, in 4 patients receiving 5 mg, and in 2 patients receiving 2.5 mg.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression and function of endothelins, endothelin receptors, and endothelin converting enzyme in the porcine trachea.
Endothelins (ETs) can modulate the airway smooth muscle tone. Using simultaneous measurements of cytosolic Ca2+ concentration ([Ca2+]i) and tension as well as the reverse transcription polymerase chain reaction (RT-PCR), we examined ET systems in the porcine trachea. In the functional study, the application of ET-1, ET-3 or sarafotoxin S6c (S6c) caused increases in [Ca2+]i and tension, in a concentration-dependent manner. These ET ligands were found to increase the Ca2+ sensitivity of the myofilament of the tracheal smooth muscle cells (SMCs). The contractions induced by ET-1 (10(-7) M), an ET receptor (ET-R) non-selective agonist, were much greater than those induced by S6c, an ET(B)-R selective agonist. BQ-123 (10(-6) M), an ET(A)-R antagonist, inhibited the ET-1 induced contraction. These functional experiments suggested the presence of both functioning ET(A)- and ET(B)-Rs in tracheal SMCs. RT-PCR experiments revealed that the tracheal SMCs expressed both ET(A)-R and ET(B)-R mRNAs, while tracheal epithelial cells (EpCs) predominantly expressed ET(A)-R mRNA. The porcine tracheal SMCs and EpCs also expressed pre-pro ET-1 (ppET-1), ppET-3, and endothelin converting enzyme-1 (ECE-1) mRNAs. These results suggested that ETs induce contraction of porcine tracheal SMCs not only by increasing [Ca2+]i but also increasing the Ca2+ sensitivity of the myofilament and that ETs could potentially be the autocrine and/or paracrine transmitters to regulate the contraction in the porcine airway smooth muscle.


Type II collagen-induced arthritis in mice. II. Passive transfer and suppression by intravenous injection of anti-type II collagen antibody or free native type II collagen.
The passive transfer of high levels of anti-type II collagen antibody from mice with type II collagen-induced arthritis may transfer arthritis to syngeneic recipient animals. However, the transfer of either arthritogenic or sub-arthritogenic doses of polyclonal anti-type II collagen antibody, or non-arthritogenic monoclonal anti-type II collagen antibody may protect mice against the subsequent induction of arthritis by type II collagen. A protective effect was also observed in mice given free native type II collagen intravenously before the administration of collagen in an arthritogenic protocol.


Prophylactic Catheter Ablation for Ventricular Tachycardia: Are We There Yet?
Ventricular tachycardia (VT), often degenerating into ventricular fibrillation, is the leading cause of sudden cardiac death. Catheter ablation of VT is associated with relatively low, long-term success rates, while the optimal timing of ablation in patients with ischaemic and non-ischaemic cardiomyopathy remains unclear. Contemporary practice in most centres is to consider ablation late in the disease process following the failure of anti-arrhythmic medications and/or following recurrent implantable cardioverter-defibrillator shocks. Three major randomised, controlled trials have been published investigating the role of prophylactic catheter ablation for VT. In the present review, we assess the evidence from these and other related trials in VT ablation to understand if there is sufficient evidence to advocate prophylactic catheter ablation in patients with VT.


Inflammatory bowel disease and pregnancy.
The peak age ranges for pregnancy and inflammatory bowel disease (IBD) coincide, and many women develop IBD during their reproductive years. This contribution reviews the major studies on the subject, and is sub-divided into two broad considerations: the effects of the disease on fertility, pregnancy and other factors related to the puerperium, and, conversely, the effects of pregnancy and childbirth on the disease: its natural history and recent surgical treatment options, namely pouch anatomy and function. A systematic review of the literature from 1950 to the present was undertaken using Medline and the keywords inflammatory bowel disease and pregnancy.


The challenge of transplants to an intersubjectively established sense of personal identity.
Face transplants have been performed, in a small number, since 2005. Popular concern over the morality of the face transplant has tended to focus on the role that one's face plays in one's sense of self or one's personal identity. In order to address this concern, the current paper will explore the significance of face transplants in the light of a theory of the self that draws on symbolic interactionism, narrative theory, and accounts of embodiment. The paper will respond to certain presuppositions concerning personal identity made by Huxtable and Woodley. A theory of the self will be articulated that draws on the work of Merleau-Ponty and G. H. Mead, in order to place embodiment and social interaction centrally to an understanding of self-identity. This will allow an account of the nature of the suffering that a face transplant seeks to remedy, and its worth as an operation, and crucially the impact that it may have on the sense of personal identity of the recipient of the transplant. The conclusion will review the treatment in the context of the prejudices that members of contemporary societies may hold against those with disfigurements.


Low Expression of Leucocyte Associated Immunoglobulin Like Receptor-1 (LAIR-1/CD305) in a Cohort of Pediatric Acute Lymphoblastic Leukemia Cases
Background: Immunophenotypic markers can play significant role in prognostic assessment for different cancers and leukocyte-associated Ig-like receptor (LAIR-1) is a recently identified inhibitory immuno-receptor. Methods: We measured LAIR-1 expression in paediatric ALL patients (n-42) and appropriate controls by flow cytometry. Median fluorescence intensities (MFIs) were calculated and correlated with demographic and clinical variables and early treatment outcome parameters. Results: The ALL cohort had an age range of 1 - 11 y and a M:F ratio of 2.5:1. 64% had WBC counts <50 x 109/L and 15 (36%) >50 x 109/L, 52% being standard risk and 48% high risk. There were 6 cases of T-ALL and 36 of B-ALL. AML1-TEL, E2A-PBX, BCR-ABL and MLL-AF4 transcripts were noted in 3, 6, 2 and 1 patient, respectively. Day 8 ABC was <1,000 in 31 and >1,000 in 8 cases, while 30 had low and 7 high MRD (both >0.01) at day 35 of treatment. The median MFI for LAIR-1 expression in control cases was 8.2 (range 7.76-11.69) and in ALL cases 4.02 (range 0.56 to 11.87), with 74% (n-31) of ALL cases showing reduced LAIR-1 expression. However, no significant correlations were found between standard ALL risk factors and LAIR-1 expression. Out of 42 patients, 4 died during induction treatment and one exited therapy, 60% (n-3/5) of these featuring low expression of LAIR-1. Also ALL patients with low LAIR-1 expression had t (12;21), t (1;19) and t (4;11) translocations in 2, 4 and 1 samples, respectively, but none had t (9;22). Of those with high LAIR-1 expression, 2 had t (9;22) (MFIs-14.43 and 11.87). Conclusions: This pilot study of LAIR-1expression in ALL suggests low expression of the inhibitory molecule in leukemic cells. However, the findings need to be confirmed with larger cohort, along with studies focusing on pathophysiological roles in leukemic clone survival and escape from the immune system.


Accuracy and reproducibility of cap thickness in small incision lenticule extraction.
To evaluate the accuracy and reproducibility of cap thickness for small incision lenticule extraction (SMILE) with the VisuMax femtosecond laser (Carl Zeiss Meditec, Inc., Jena, Germany). Artemis very high-frequency digital ultrasound (ArcScan Inc., Morrison, CO) measurements were obtained before and 3 months after SMILE in 70 eyes of 37 patients with intended cap thickness between 80 and 140 μm. True cap thickness at the time of creation was calculated as the addition of the preoperative epithelial thickness and the postoperative stromal component of the flap and mapped for the central 5-mm diameter zone. Cap thickness accuracy was calculated as the difference between the mean and intended cap thickness. Reproducibility was evaluated as the cap thickness standard deviation between eyes. Accuracy and reproducibility of cap thickness were calculated for all eyes and grouped by intended cap thickness. Within-eye variation in cap thickness was calculated as the standard deviation of all data within the central 5-mm diameter zone. Mean cap thickness accuracy was between -2.3 and 6.5 μm and was -0.7 μm centrally (range: -11 to +14 μm), including all eyes. Cap thickness reproducibility was 6 μm or less for the majority of the central 5-mm diameter zone and was 4.4 μm centrally. Cap thickness accuracy and reproducibility were similar for different intended cap thicknesses. Average within-eye variation in cap thickness was 4.3 μm. SMILE cap thickness using the VisuMax femtosecond laser was found to be accurate and reproducible across the central 5-mm diameter zone for intended cap thicknesses over the range of 80 to 140 μm.


Lesions of the triangular fibrocartilage complex: MR findings with a three-dimensional gradient-recalled-echo sequence.
To evaluate the use of a three-dimensional gradient-recalled-echo (GRE) magnetic resonance (MR) imaging sequence in the depiction of lesions of the triangular fibrocartilage (TFC) complex. MR images of the TFC complex were evaluated in 31 patients who underwent wrist arthroscopy less than 6 months after MR imaging. The results were compared with the arthroscopic findings. Eleven of 12 full-thickness TFC tears were depicted, but one partial-thickness tear, one abnormal disk, and one normal disk were overstaged. Lesions in the volar and dorsal radioulnar ligament and lesions of the attachments of the TFC complex to the ulna often were overstaged. Lesions of the ulnolunate and ulnotriquetral ligaments often were understaged. Imaging with the three-dimensional GRE sequence is reliable in the depiction of TFC tears and the exclusion of tears of components of the TFC complex other than those of the ulnolunate and ulnotriquetral ligaments.


Characterization of a new HLA-C allele in a Chinese family by sequence-based typing: HLA-Cw*0348.
The novel human leukocyte antigen (HLA)-Cw*0348 allele was identified by sequence-based typing in a Chinese family. This allele shows that the sequences of exons 1-3 of HLA-Cw*0348 are identical to those of HLA-Cw*030401 except for a nucleotide substitution that changes CCG to CTG at codon 57, resulting in an amino acid change from Pro to Leu in the protein, and this is a unique nucleotide change among the HLA-C alleles, suggesting a point mutation mechanism. The extended haplotype carrying the new allele was deduced from the family group typing and defined as A*110101, B*1301, Cw*0348, DRB1*0405, and DQB1*0402.


Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1α axis inhibition.
Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured in both normoxic and hypoxic conditions. Secondly, based on the concept of a bi-therapy targeting in pHGGs mTORC1 (rapamycin) and HIF-1α (irinotecan), we hypothesized that the balanced expressions between RAS/ERK, PI3K/AKT and HIF-1α/HIF-2α/MYC proteins or genes may provide a modulation of the cell response to this double targeting. Finally, we could evidence three protein, genomic and metabolomic profiles of response to rapamycin combined with irinotecan. The pattern of highly sensitive cells to mTOR/HIF-1α targeting was linked to a MYC/ERK/HIF-1α over-expression and the cell resistance to a major hyper-expression of HIF-2α.


Biofeedback in dialysis.
The traditional control of the dialysis session comes about by means of an open-loop system. At the beginning of the session some parameters are set, such as the kind of dialyzer, the blood flow, the ultrafiltration rate, the dialysate conductivity and the dialysate temperature. Generally speaking, these parameters are not modified unless there occur complications in the patient that call for adjustments to be made. The biofeedback concept, which is synonymous with a closed-loop control of biological variables, presupposes, on the other hand: the continuous measurement of a variable thanks to a specific sensor its evaluation by a sort of expert system--the so-called controller and a series of means--the actuators--that allow the behavior of the variable to be directly or indirectly influenced. In clinical practice, different biofeedback systems are emerging, addressed to the control of blood volume, body temperature, and blood pressure. Each one of these systems has been successfully deployed, especially in the management of "difficult" patients unstable from the hemodynamic point of view. However, the future will be an integrated system that sees a complex adaptive, multi-input, multi-output controller which, with a great simplicity of use and low costs, will allow renal replacement therapy to be increasingly physiological and more efficient.


Atomic resolution duplex structure of the simplified nucleic acid GNA.
Double helix variations of glycol nucleic acids (GNA) are revealed by the atomic resolution crystal structure of a 6mer GNA duplex containing solely Watson-Crick type hydrogen-bonded base pairs.


Measuring the Joint Spectral Mode of Photon Pairs Using Intensity Interferometry.
The ability to manipulate and measure the time-frequency structure of quantum light is useful for information processing and metrology. Measuring this structure is also important when developing quantum light sources with high modal purity that can interfere with other independent sources. Here, we present and experimentally demonstrate a scheme based on intensity interferometry to measure the joint spectral mode of photon pairs produced by spontaneous parametric down-conversion. We observe correlations in the spectral phase of the photons due to chirp in the pump. We show that our scheme can be combined with stimulated emission tomography to quickly measure their mode using bright classical light. Our scheme does not require phase stability, nonlinearities, or spectral shaping and thus is an experimentally simple way of measuring the modal structure of quantum light.


Evaluation of Combinatory Effects of Plasmodium Circumsporozoite Protein and Complement Regulatory Protein Expression of Recombinant Baculovirus Vectors.
Baculovirus vectors (BVs) are safely able to transduce foreign genes and express them in mammalian cells. However, the transduction activity of BVs is strongly reduced by the attack of serum complement, which is one of the major obstacles in the use of BVs for in vivo gene transfer. One strategy to overcome this problem is the display of complement regulatory proteins (CRPs) on BV virions. We previously developed CD46-decay accelerating factor (DAF)-CD59 triple fusion type BV showing potent complement resistance. We also developed BVs expressing Plasmodium circumsporozoite protein (CSP) to enhance transduction efficacy in hepatic cells. In this study, we investigated the combination of CSP and CRPs in a BV system to evaluate transduction efficacy along with complement resistance. To accomplish the combination of CSP and CRPs, we generated insect Sf9 cells stably expressing CRPs, to which CSP type BV was infected. The BVs collected from these infected cells were confirmed to possess both CSP and CRPs in virions. We demonstrated that CSP-CD46-DAF-CD59 type BV, containing both CSP and CD46-DAF-CD59, showed a significant increase in transduction efficacy in human hepatoma HepG2 cells under intact serum exposure compared with control type BV or CSP type BV, retaining both advantages of CSP and CD46-DAF-CD59. Collectively, these results demonstrated that the utilization of stably expressing Sf9 cells to introduce the protein products of interest, e.g., CRPs into BVs, would be useful strategy to generate BVs with novel functions such as resistance against serum complement attack.


Angiotensin II directly stimulates release of atrial natriuretic factor in isolated rabbit hearts.
Previous studies have shown that infusion of angiotensin II (Ang II) increases plasma concentrations of atrial natriuretic factor (ANF) in vivo. This phenomenon has been considered secondary to the effects of Ang II on cardiac and systemic hemodynamics. The present study was designed to assess whether Ang II may exert a direct stimulatory effect on ANF release from the heart independent of changes in hemodynamics. Isolated rabbit hearts were perfused in the Langendorff mode. Heart rate, coronary flow, and atrial and left ventricular (LV) volumes were kept constant. After stabilization, Ang II was infused intracoronary at increasing doses (10(-11) to 10(-8) M) in nine hearts and at a single dose of 10(-10) M in 10 hearts. Each infusion lasted for 5 minutes and was followed by a 10-minute washout period. Four hearts received vehicle alone for 80 minutes. Ang II induced a dose-dependent increase in coronary perfusion pressure and in LV developed pressure. ANF release, measured by radioimmunoassay on the extracts of the cardiac effluent, also increased during Ang II infusion and returned to the basal values during the 10-minute washout period. In the control group, coronary perfusion pressure, LV developed pressure, and LV end-diastolic pressure did not change appreciably over the observation period, whereas ANF release progressively decreased during perfusion. Ang II can directly stimulate cardiac release of ANF in isolated rabbit hearts independently of changes in hemodynamics.


Treatment options in extravasation injury: an experimental study in rats.
Local skin necrosis after extravasation of doxorubicin hydrochloride (Adriamycin), a widely used chemotherapeutic agent, is a common problem in cancer patients. Even though several treatment options have been proposed for extravasation injury, there is still controversy regarding the management of such lesions. The aim of this study was to compare the efficacy of saline infiltration, vitamin C infiltration, suction technique, and early surgical excision as a treatment in a rat extravasation model. The authors planned their study in two stages. In stage 1, the lowest effective dose of doxorubicin at which a homogeneous skin necrosis was formed and the method of administration were investigated. Intradermal and subpannicular injections were made for six rats, using six different concentrations of doxorubicin (0.33, 0.5, 0.66, 1.0, 1.33, and 1.5 mg/ml). In stage 1, the intradermal injection produced homogeneous and uniform tissue necrosis. In stage 2, the efficacy of saline infiltration (group 1), vitamin C infiltration (group 2), suction (group 3), suction and saline washout (group 4), suction and vitamin C washout (group 5), and early surgical excision (group 6) was compared. The treatment options were applied 2 hours after doxorubicin injection. At the end of the seventh day, the presence and size of ulcers at the injection site were calculated. Fourteen days after injection, a histopathologic examination was performed for each treatment and control group. In groups 1 and 3, there was no statistically significant difference in the size of necrosis compared with the control groups. In groups 2, 4, and 5, the size of necrosis was smaller compared with the control groups, and this was statistically significant. Furthermore, in group 4 (suction and saline washout) and group 5 (suction and vitamin C washout), the calculated area of necrosis was smaller compared with other treatment groups, and this was statistically significant. The findings supported the assertion that suction and saline or vitamin C washout reduce necrotic tissue size in extravasation injury.


[Identification of a protective epitope--a fragment of Lassa virus nucleoprotein].
Several peptides from Lassa virus glyco- and nucleoproteins were predicted as probable T-cell epitopes. Their synthesis was performed by solid phase method. The study of possible protective effect in vivo with Lassa-sensitive CBA mice revealed protective epitope within the 277-303 nucleoprotein region. Further studies reduced the protective epitope structure to the 287-300 nucleoprotein fragment.


Differences in sustained alterations in protein expression between livers of mice exposed to high-dose-rate and low-dose-rate radiation.
Molecular mechanisms of radiation dose-rate effects are not well understood. Among many possibilities, long-lasting sustained alterations in protein levels would provide critical information. To evaluate sustained effects after acute and chronic radiation exposure, we analyzed alterations in protein expression in the livers of mice. Acute exposure consisted of a lethal dose of 8 Gy and a sublethal dose of 4 Gy, with analysis conducted 6 days and 3 months after irradiation, respectively. Chronic irradiation consisted of a total dose of 8 Gy delivered over 400 days (20 mGy/day). Analyses following chronic irradiation were done immediately and at 3 months after the end of the exposure. Based on antibody arrays of protein expression following both acute lethal and sublethal dose exposures, common alterations in the expression of two proteins were detected. In the sublethal dose exposure, the expression of additional proteins was altered 3 months after irradiation. Immunohistochemical analysis showed that the increase in one of the two commonly altered proteins, MyD88, was observed around blood vessels in the liver. The alterations in protein expression after chronic radiation exposure were different from those caused by acute radiation exposures. Alterations in the expression of proteins related to inflammation and apoptosis, such as caspase 12, were observed even at 3 months after the end of the chronic radiation exposure. The alterations in protein expression depended on the dose, the dose rate, and the passage of time after irradiation. These changes could be involved in long-term effects of radiation in the liver.


Hemophilus species in the pharynx. Comparison of sampling sites.
In a study of 170 young children, we compared the number and serotype of ampicillin-sensitive and ampicillin-resistant Hemophilus species recovered from throat cultures with those recovered from nasopharyngeal cultures obtained simultaneously. Hemophilus species were recovered from 107 (63%) of the 170 throat cultures and from 79 (46%) of the 170 nasopharyngeal cultures (chi 2 = 12.6). In only five of the pairs of cultures did the nasopharyngeal culture contain Hemophilus species without simultaneous recovery of this organism from the throat culture. Ampicillin-resistant Hemophilus species were recovered from 29 throat swabs and from ten nasopharyngeal swabs.


Automatic set-point titration for monitoring nitrification in SBRs.
Nitrification is usually the bottleneck of biological nitrogen removal processes. In SBRs systems, it is not often enough to monitor dissolved oxygen, pH and ORP to spot problems which may occur in nitrification processes. Therefore, automated supervision systems should be designed to include the possibility of monitoring the activity of nitrifying populations. Though the applicability of set-point titration for monitoring biological processes has been widely demonstrated in the literature, the possibility of an automated procedure is still at its early stage of industrial development. In this work, the use of an at-line automated titrator named TITAAN (TITrimetric Automated ANalyser) is presented. The completely automated sensor enables us to track nitrification rate trend with time in an SBR, detecting the causes leading to slower specific nitrification rates. It was also possible to perform early detection of toxic compounds in the influent by assessing their effect on the nitrifying biomass. Nitrifications rates were determined with average errors+/-10% (on 26 tests), never exceeding 20% as compared with UV-spectrophotometric determinations.


Screw Fixation of Pediatric Tibial Tubercle Fractures.
Tibial tubercle fractures are rare injuries that account for <1% of physeal fractures. These fractures are thought to be increasing in frequency, particularly in young, adolescent males who participate in basketball and other sports with repeated running and jumping. The tibial apophysis becomes mechanically vulnerable as the proximal tibial physis closes from posteromedial to anterolateral, enabling the quadriceps to overpower the chondroepiphysis and avulse the proximal tibial epiphysis from the tibial metaphysis. Position the patient supine with the leg on a bump or bone foam. Perform a longitudinal incision centered over the fracture site (i.e., the tibial tubercle); a medial parapatellar incision may be utilized if an intra-articular component is present. Develop medial and lateral soft-tissue flaps to expose the fracture. Evaluate the soft-tissue stripping and capsule. Debride any hematoma, fracture fragments, and soft tissue from the fracture site with use of irrigation and a curet. Use a towel clip, bone clamp, and/or ballpoint pusher to reduce the fragment. Place 2 to 3 parallel guide pins from anterior to posterior, capturing fracture fragments within the epiphysis and apophysis under fluoroscopic guidance. Carefully place a guidewire in the distal fragment to avoid splitting the fragment, which is often small. An arthrotomy or arthroscopy is utilized to assess intra-articular reduction if necessary. Assess and measure pin lengths and placement with use of fluoroscopy. Place screws sequentially to avoid rotation of the fragment and take care to avoid splitting the fragment when placing distal screws. Repair any patellar, capsular, retinacular, or meniscal damage. A suture anchor may be utilized to repair the patellar tendon if necessary. The skin is closed in a layered fashion. Apply a cylinder cast or hinged knee braced locked in extension. Nonoperative treatment in a long-leg cast in extension may be considered for nondisplaced fractures or fractures that are stably reduced with <2 mm of displacement and acceptable alignment in the cast following reduction. Operative treatment is indicated for fractures with ≥2 mm of displacement, intra-articular extension with an incongruent joint, and for patients who will not tolerate being non-weightbearing in a cast. Closed reduction is generally attempted for fractures without intra-articular extension. If closed reduction is successful, fixation may be performed with Kirschner wires and/or percutaneous screws. Open reduction is often necessary and has been reported to be performed in as many as 98% of surgical cases for tubercle fractures2. This approach allows access to intra-articular displacement and the ability to obtain a stable, anatomic reduction while addressing concomitant soft-tissue injury, if present. The expectation following successful reduction and screw fixation of tibial tubercle fractures is that these young patients will be able to regain their motion and strength, and ultimately return to preinjury activity levels. A consecutive series of 86 patients with surgically treated tibial tubercle fractures found that all patients demonstrated full radiographic healing at the time of the latest follow-up (range, 3 to 34 months), return to full activities between 10 and 42 weeks, return of good to excellent range of motion in 89% of patients, and a 10% to 20% complication rate, including partial physeal arrest, decreased range of motion, quadriceps contracture, and painful implants. Additionally, a systematic review of 23 articles with 336 surgically treated tibial tubercle fractures found 98% of patients return to preinjury activity and knee range of motion with a 28% complication rate (most commonly due to painful implants). Place the fluoroscopic image view across the room from the surgeon for ease of viewing.Use computed tomography or magnetic resonance imaging if the fracture has intra-articular extension.Use 4.5 or 6.5-mm cannulated, partially threaded screws.Carefully monitor for compartment syndrome.Place screws by hand, sequentially.


First principles intensity calculations of the methane rovibrational spectra in the infrared up to 9300 cm(-1).
We report global calculations of rovibrational spectra and dipole transition intensities of methane using our recent ab initio dipole moment and potential surfaces [Nikitin et al., Chem. Phys. Lett., 2011, 501, 179; 2013, 565, 5]. For the full symmetry account, a recently published variational tensor formalism in normal modes [Rey et al., J. Chem. Phys., 2012, 136, 244106] is applied, the convergence of high-J calculations being improved by the use of vibrational eigenfunctions to make a compressed basis set for solving the rovibrational problem. Comparisons of theoretical predictions up to J = 25 for various complex polyads of methane involving strongly coupled vibration-rotation bands support the validity of this new approach. For the first time, positions and line intensities at 80 K and 296 K are shown to be in excellent agreement with raw experimental data, even for high energy ranges. The theoretical predictions also correctly describe the isotopic effects in line positions and intensities due to the CH4 → CD4 substitution which is considered as the test for the method. This work is a first step toward the theoretical interpretation of numerous methane bands which remain still unassigned and detailed line-by-line absorption/emission spectra analyses for atmospheric and planetological applications.


A Simon effect for stimulus-response duration.
A non-spatial variant of the Simon effect for the stimulus-response (S-R) feature of duration is reported. In Experiment 1 subjects were required to press a single response key either briefly or longer in response to the colour of a visual stimulus that varied in its presentation duration. Short keypresses were initiated faster with short than with long stimulus duration whereas the inverse was observed with long keypresses. In Experiment 2 subjects were required to press a left or right key (according to stimulus form) either briefly or longer (according to stimulus colour). The stimuli concurrently varied in their location (left or right) and duration (short or long), which were both task irrelevant. Approximately additive correspondence effects for S-R location and S-R duration were observed. To summarize, the results suggest that the irrelevant stimulus features of location and duration are processed automatically and prime corresponding responses in an independent manner.


pH modulation of large conductance potassium channel from adrenal chromaffin granules.
We report here that large conductance K(+) selective channel in adrenal chromaffin granules is controlled by pH. We measured electrogenic influx of (86)Rb(+) into chromaffin granules prepared from bovine adrenal gland medulla. The (86)Rb(+) influx was inhibited by acidic pH. Purified chromaffin granule membranes were also fused with planar lipid bilayer. A potassium channel with conductance of 432+/-9 pS in symmetric 450 mM KCl was observed after reconstitution into lipid bilayer. The channel activity was unaffected by charybdotoxin, a blocker of the Ca(2+)-activated K(+) channel of large conductance. It was observed that acidification to pH 6.4 cis side of the membrane lowered the channel open probability and single channel conductance. Whereas only weak influence on the single channel current amplitude and open probability were observed upon lowering of the pH at the trans side. We conclude that a pH-sensitive large conductance potassium channel operates in the chromaffin granule membrane.


Carbon dioxide induced soybean protein precipitation: protein fractionation, particle aggregation, and continuous operation.
A novel protein fractionation technique using a volatile electrolyte has been developed. Carbon dioxide was used to isoelectrically precipitate 80% and 95% pure glycinin and beta-conglycinin fractions from soybean isolate. The protein fractions precipitated as primary particles 0.2-0.3 microm in diameter, which under optimum conditions may be recovered as aggregates up to 500 microm in diameter. The dependency of protein fractionation efficiency on aggregate settling rates has been demonstrated. The isoelectric points of the two main soybean fractions, glycinin and beta-conglycinin, were calculated to be pH 5.2 and 4.95, respectively. Solution pH was accurately controlled by pressure in the isoelectric pH range of the different soybean protein fractions, and a pH "overshoot" was eliminated. Volatile electrolyte technology was also applied to a continuous process in order to eliminate the particle recovery concerns associated with batch precipitation and to demonstrate the potential for scale-up. Glycinin was effectively recovered on-line (94% glycinin recovery) with a purity approaching that of the batch process (95%).


Effects of a Saccharomyces cerevisiae fermentation product-supplemented diet on circulating immune cells and oxidative stress markers of dogs.
Feeding Saccharomyces cerevisiae fermentation product (SCFP) has previously altered fecal microbiota, fecal metabolites, and immune function of adult dogs. The objective of this study was to investigate measures of skin and coat health, changes in circulating immune cell numbers and activity, antioxidant status, and oxidative stress marker concentrations of healthy adult dogs fed a SCFP-supplemented extruded diet. Sixteen adult English Pointer dogs (8 M, 8 F; mean age = 6.7 ± 2.1 yr; mean BW = 25.9 ± 4.5 kg) were used in a randomized crossover design study. All dogs were fed a control diet for 4 wk, then randomly assigned to either the control or SCFP-supplemented diet (0.13% of active SCFP) and fed to maintain BW for 10 wk. A 6-wk washout preceded the second 10-wk experimental period with dogs receiving opposite treatments. After baseline/washout and treatment phases, skin and coat were scored, and pre and postprandial blood samples were collected. Transepidermal water loss (TEWL), hydration status, and sebum concentrations were measured (back, inguinal, ear) using external probes. Oxidative stress and immune cell function were measured by ELISA, circulating immune cell percentages were analyzed by flow cytometry, and mRNA expression of oxidative stress genes was analyzed by RT-PCR. Change from baseline data was analyzed using the Mixed Models procedure of SAS 9.4. Sebum concentration changes tended to be higher (P < 0.10; inguinal, ear) in SCFP-fed dogs than in controls. TEWL change was lower (P < 0.05) on the back of controls, but lower (P = 0.054) on the ear of SCFP-fed dogs. Delayed-type hypersensitivity response was affected by diet and time post-inoculation. Other skin and coat measures and scores were not affected by diet. Changes in unstimulated lymphocytes and stimulated IFN-γ secreting T cells were lower (P < 0.05) in SCFP-fed dogs, while changes in stimulated T cells were lower (P < 0.05) in control-fed dogs. Upon stimulation, the percentage of cytotoxic T cells delta trended lower (P < 0.10) in SCFP-fed dogs. Change in serum superoxide dismutase concentrations was higher (P < 0.05) and change in catalase mRNA expression was lower (P < 0.05) in SCFP-fed dogs. All other measurements of immune cell populations, oxidative stress markers, and gene expression were unaffected by treatment. In conclusion, our data suggest that SCFP positively impacts indicators of skin and coat health of dogs, modulates immune responses, and enhances some antioxidant defense markers.


[Transcranial color Doppler ultrasonography: methodology and usefulness for the study of patent foramen ovale in cryptogenic stroke].
Non-invasive Doppler ultrasonographic study of cerebral arteries (transcranial Doppler, TCD) has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays a valid indication for TCD in the outpatient setting is the research of right-to-left shunting, responsible for the so-called "paradoxical embolism", most often due to patency of foramen ovale, which is responsible for the majority of cryptogenic strokes occurring in patients younger than 55 years. TCD also allows to classify the grade of severity of such shunts using the so-called "microembolic signal grading score". Therefore, TCD is an essential cardiological exam for the detection of patent foramen ovale, assuming an important role as a first-level examination to guide the subsequent diagnostic-therapeutic management. In addition, TCD has found many useful applications in neurocritical care practice. It is useful for the identification of intracranial vascular stenosis and for the assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury and brain stem death. It is also used to evaluate cerebral hemodynamic changes after stroke, to investigate cerebral pressure autoregulation, and for the clinical evaluation of cerebral vasomotor reactivity.


Results of Hyaluronic Acid-Based Cell-Free Scaffold Application in Combination With Microfracture for the Treatment of Osteochondral Lesions of the Knee: 2-Year Comparative Study.
To determine the clinical and radiographic efficacy of hyaluronic acid-based cell-free scaffold applied in combination with microfracture versus microfracture alone in patients with focal osteochondral lesion of the knee joint. Clinical data of 43 patients between 24 and 55 years of age were evaluated. Hyaluronic acid-based cell-free scaffold was applied in combination with microfracture for 19 knees (group 1), whereas microfracture alone was the surgical intervention for 24 knees (group 2). All lesions were Outerbridge grade III or IV with a mean size of 3.6 ± 1.3 cm2. The mean follow-up time was 25.7 months. Visual analog scale (VAS), Lysholm knee score, and Tegner activity scale were the instruments used to evaluate the clinical status. Magnetic resonance observation of cartilage repair tissue (MOCART) system was used to analyze the characteristics of repair tissue. Better VAS and Lysholm scores were detected in group 1 at 12 and 24 months (P = .019 and P = .025). According to the Tegner activity scale, group 1 had also better activity level at the end of 24 months after surgery (P = .020). The mean time from surgery to return to nonimpact sports activities was 7.8 months in group 1, whereas it was 9.2 months in group 2 (P = .013). Complete repair with the filling of the defect was achieved in 7 (36.8%) of the knees in group 1, whereas it was 4 (16.6%) of the knees in group 2 according to the MOCART system at 24 months. Single-stage regenerative cartilage surgery using hyaluronic acid-based cell-free scaffold in combination with microfracture for focal osteochondral lesions of the knee revealed promising clinical outcomes at 24 months of follow-up, but the clinical significance of the differences seen is simply not known. Level III, retrospective comparative study.


Family change and support of the elderly in Asia: what do we know?
"After outlining variations in traditional family systems in Asia, this article discusses likely impacts of urbanization, industrialization and migration on family structure and care of the elderly. Evidence about changing family support for the elderly in Asia is then reviewed. The article's main conclusion is that future changes in Asian countries and areas seem likely to erode traditional family-based systems of care for the elderly, even if the overall welfare of the elderly improves because of higher incomes. Problems faced by elderly women are likely to be especially acute and may require special policies to deal with them."


[The effect of plasmapheresis on the function of the calcium-regulating systems in patients with rheumatoid arthritis].
As many as 87 patients with rheumatoid arthritis were examined for changes in the status of the calcium-regulating systems under the influence of therapy. The multimodality treatment of 57 of the patients included discrete plasmapheresis, which allowed the attainment of an earlier and more marked beneficial clinicolaboratory effect. Plasmapheresis contributed to the correction of the status of the calcium-regulating systems: to a decrease of the level of parathyrin, an increase of the concentration of calcitonin, calcidiol, total and ionized calcium.


Insights from selective non-phosphinic inhibitors of MMP-12 tailored to fit with an S1' loop canonical conformation.
After the disappointment of clinical trials with early broad spectrum synthetic inhibitors of matrix metalloproteinases (MMPs), the field is now resurging with a new focus on the development of selective inhibitors that fully discriminate between different members of the MMP family with several therapeutic applications in perspective. Here, we report a novel class of highly selective MMP-12 inhibitors, without a phosphinic zinc-binding group, designed to plunge deeper into the S(1)' cavity of the enzyme. The best inhibitor from this series, identified through a systematic chemical exploration, displays nanomolar potency toward MMP-12 and selectivity factors that range between 2 and 4 orders of magnitude toward a large set of MMPs. Comparison of the high resolution x-ray structures of MMP-12 in free state or bound to this new MMP-12 selective inhibitor reveals that this compound fits deeply within the S(1)' specificity cavity, maximizing surface/volume ratios, without perturbing the S(1)' loop conformation. This is in contrast with highly selective MMP-13 inhibitors that were shown to select a particular S(1)' loop conformation. The search for such compounds that fit precisely to preponderant S(1)' loop conformation of a particular MMP may prove to be an alternative effective strategy for developing selective inhibitors of MMPs.


Renal tubular injury after infrarenal aortic aneurysm repair.
To investigate markers of tubular injury (glutathione-S-transferase [GST] isoforms) as early markers for renal damage in patients undergoing abdominal aortic aneurysm repair. Prospective study. Regional teaching hospital. Eight consecutive patients undergoing elective infrarenal abdominal aortic aneurysm repair. All patients received a standard anesthetic technique including a dopamine infusion (3 microg/kg/min) but without supplemental renoprotective agents. Urine and blood samples were taken at induction, at 1 hour and 3 hours after limb reperfusion, and on days 1 and 2 postoperatively. Urine microalbumin and creatinine concentrations were measured using standard assays, and urine pi-GST and alpha-GST enzyme measurements were performed by a commercial immunoassay (Biotrin, Biotrin International Ltd., Co., Dublin, Ireland). Five patients (63%) showed a postoperative elevation of serum creatinine (median increase from baseline, 35.4%; range, 8.3% to 50.6%) that was associated with significant elevations of urinary microalbumin-to-creatinine, alpha-GST-to-creatinine, and pi-GST-to-creatinine ratios soon after clamp removal. The remaining 3 patients showed no increase in serum creatinine or urine proteins. Peak alpha-GST-to-creatinine levels were different between the 2 groups. The peak levels of GST enzymes were significantly (r(2) > 80%) associated with the percent increase in serum creatinine from baseline. Urinary GST-to-creatinine ratios are a sensitive early biomarker for renal injury after infrarenal abdominal aortic aneurysm repair.


Chimeric Peptide Tat-HA-NR2B9c Improves Regenerative Repair after Transient Global Ischemia.
Transient global ischemia (TGI) is a major public health problem, and it heightens the need of effective treatments. The present study was undertaken to investigate whether recombinant polypeptide Tat-HA-NR2B9c improves spatial learning and memory deficits in rats after TGI. Rats were subjected to 20-min ischemia induced by four-vessel occlusion (4-VO) method and daily injected with Tat-HA-NR2B9c (1.12 mg/kg) for 1 week. Tat-HA-NR2B9c increased CREB activity, upregulated B-cell lymphoma-2 (Bcl-2) expression after treated for 24 h. There was a significant increase in dendrite spine density in hippocampal CA1 region and BrdU-positive cells and BrdU/NeuN-positive cells in the dentate gyrus after Tat-HA-NR2B9c treatment, compared with ischemia group at postischemic day 28. Inhibition of the CREB activation by recombinant lentivirus, LV-CREB133-GFP, abolished the upregulation effects of Tat-HA-NR2B9c on Bcl-2 expression. Moreover, Tat-HA-NR2B9c improved the impaired spatial learning and memory ability in Morris water maze. These results suggest that Tat-HA-NR2B9c substantially ameliorated the TGI-induced loss of dendrite spine in hippocampal CA1, increased neurogenesis in dentate gyrus, and significantly improved cognitive abilities by the CREB pathway in rats after transient global cerebral ischemia. It may be served as a treatment for TGI.


Fruits-Based Critical Nitrogen Dilution Curve for Diagnosing Nitrogen Status in Cotton.
Estimating the precise nutritional status of crop nitrogen (N) after flowering period is not only important to predict deficiency but the excess that could be revised by fertilization in future crops. Critical N dilution curves describing the critical N concentration ([N]c) in plant tissues during crop growth have been used to estimate the N status of whole plants in cotton. Little is known, however, about the critical N dilution curve for specific plant organs such as cotton fruits. The objective of this study was to verify the feasibility of fruits-based critical N dilution curve as a useful diagnostic tool for diagnosing the N status of cotton crops. A 3-year field experiment was conducted with seven N application rates (0-360 kg N ha-1) using the high-yielding cultivars Jimian 228 and Lumian 28, which differ in maturity. The relationship between fruits dry mass (DM) and N concentration ([N]) was analyzed, and a model of [N]c for cotton fruits was constructed and validated. The results showed that fruits [N]c decreased with increasing fruits DM. The critical N dilution curve based on cotton fruits was described by the equation [N]c = 2.49 × DM-0.12 (R 2 = 0.649, P < 0.0001) across cultivar-years. The N nutrition index (NNI) of the fruits (NNIf) with the N dilution curve was significantly related to the NNI of shoot DM, relative yield (RY), and boll density at most sampling dates. For an NNIf of approximately 1, the RY was nearly 95%, while it decreased with a decreasing NNIf below 1. The petiole nitrate-N (NO3-N) concentration was also linearly related to the NNIf, suggesting that the NO3-N concentration in the petiole was a good predictor of the NNIf. Therefore, fruits-based critical N dilution curve and the derived NNIf values will serve as a useful diagnostic tool for diagnosing N status in cotton crops.


Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia.
Tardive dystonia is an iatrogenic complication of dopamine receptor antagonist medication such as first-generation antipsychotics. It occurs in up to 2% of patients and only 10% recover after stopping medication. Deep brain stimulation for primary dystonia has proven to be effective and its application for secondary dystonias is gaining acceptance. We report our experience in treating three ethnic Chinese schizophrenia patients with severe medically refractory tardive dystonia by globus pallidus internus deep brain stimulation. Preoperatively, all required assistance with essential activities of daily living and two were bed-bound. The mean Burke-Fahn-Marsden Dystonia Rating Scale score was 61 (range, 44-80) and mean Global Dystonia Rating Scale score was 47 (range, 40-52). No procedure-related complications were encountered. By 3 months all could return to unassisted living and walk with support with a mean of 77% and 66% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale and Global Dystonia Rating Scale scores, respectively. Quality-of-life assessment performed for two patients using the EuroQol-5 dimensions visual analogue scale showed a mean improvement of 86% at 3 months. On clinical follow-up, the effect was well maintained for a period of 3 to 10 years. Pallidal deep brain stimulation is a safe and highly effective form of symptomatic treatment for patients with medically refractory tardive dystonia.


Data convergence in a brain model.
Assuming the existence of encoding synapses that record presynaptic axonal 'on-off' pattern as the content of memory, the author has presented a brain model. In this brain model, the synapses of a neuron work like a static random access memory (RAM) that may encode 2 the power of 10,000 'on-off' patterns, the cell body like a central processing unit (CPU) that produces a signal of 1 or 0 in response to different presynaptic axonal 'on-off' patterns, and the axon like a data bus to form synapse with another neuron. Accordingly, the brain is analogous with a computer made of serial static RAMs amid 14 billions of parallel processing CPUs. Such a brain model converges data with each tier of computation, because there are always more input presynaptic 'on-off' patterns than output axonal 'on-off' patterns in a cortical area. The more computations of the data from the primary perceptive cortices, the more likely the data involving the synapses of central cortices, and the more abstract the content of the memory--hence, in the retrieval of memory, parts of the 'on-off' patterns of the original stimulus may lead to the converged, abstract memory. This can be the mechanism of pattern recognition in the brain.


[Prognostic outcome of leaking filtering blebs reconstruction with rotational conjunctival flaps].
Late bleb leaks may follow months to years after filtering surgery especially with the use of antimetabolites. Complications related to beb leaks may lead to a decrease in visual acuity through complicated hypotony or ocular infection. Our retrospective study reports the anatomical and functional results of bleb reconstruction involving the resection of the bleb associated with the covering of the trabeculectomy site with a rotational conjunctival flap. and methods: Twelve eyes of eleven patients with filtering bleb leaks occurring 3 months to 5 years after successful trabeculectomy (58.3% with adjunct of antimetabolites) underwent bleb surgical reconstruction between november 1995 and June 1999 and were followed until March 2000. Surgical bleb reconstruction was indicated because of persistent or a recurring bleb leak despite conservative medical treatment and blood bleb injections in seven cases. Complications associated with bleb leaks were chronical hypotony (9 cases), athalamy (1 case), hypotony maculopathy (1 case), and endophtalmitis with athalamy (1 case). Three patients had normal IOP but a bleb leak responsible for epiphora. All eyes were treated surgically through bleb excision and conjunctival closure was performed by rotational conjunctival flap. Mean (+/- SD) preoperative IOP was 5.1+/-3.5mmHg (range: 2 to 14mmHg). Mean (+/- SD) postoperative IOP evaluated before any other operation for uncontrolled IOP was 12.7+/-3.1mmHg (range: 6 to 15mmHg). Mean follow-up was 26.7+/-16.9 months (range: 9 to 64 months). All the complications related to the bleb leak resolved after bleb reconstruction. Surgery definively stopped the leak in 10 cases (83.3%) and allowed IOP control without treatment in 50.0% of the cases. Chronic recurring bleb leaks without hypotony occurred in two eyes and required surgery with conjunctival graft which led to a refractory increase in IOP responsible for loss of vision in one case. Bleb resection associated with the covering of the trabeculectomy site with a rotational conjunctival flap is a safe and effective procedure for the treatment of a late bleb leak and its complications. In most of the cases (83.3%), long-term IOP control can be expected without, medical treatment in 50% of the cases. Patients must be aware of the possibility of a recurring Seidel; however, the incidence of this complication remains low.


Chloroplast DNA inheritance and variation in Leucadendron species (Proteaceae) as revealed by PCR-RFLP.
The inheritance of chloroplast DNA (cpDNA) in Leucadendron species was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A total of 100 progeny from five interspecific crosses involving seven parental species were tested, and all progeny exhibited the cpDNA restriction fragment pattern of the female parent, indicating that cpDNA in Leucadendron is maternally inherited. PCR-RFLP was also employed to study cpDNA variation among 21 Leucadendron species. Parsimony analysis using a heuristic search resulted in a phylogenetic tree that showed limited agreement to the taxonomic classification of Leucadendron species, based on morphological characteristics. The incongruence between cpDNA phylogenetic and taxonomic groupings in Leucadendron may be due to reticulate evolution involving a combination of hybridization and introgression, convergent evolution and/or lineage sorting at the interspecific, intersubsectional and intersectional levels.


Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma.
Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patients with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease.


Impact of cleaning regimens in silver-impregnated and hydrogen peroxide lens cases.
Lens storage case hygiene practices are important for safe contact lens wear. However, the effectiveness of the manufacturer's direction for use and various cleaning regimens in reducing biofilm load is yet to be evaluated and compared. This in vitro study compared the effectiveness of several cleaning methods using silver-impregnated lens case and hydrogen peroxide disinfection systems. Biofilms of Pseudomonas aeruginosa 122 and Staphylococcus aureus ATCC 6538 were grown in silver-impregnated and hydrogen peroxide lens cases. After the establishment of the biofilms, the silver-impregnated case was subjected to one of four cleaning regimens: "manufacturer's directions for use--rinsed and recapped"; "rubbed, rinsed, and recapped"; "rubbed, rinsed, and air dried"; or "rubbed, rinsed, tissue wiped, and air dried." Hydrogen peroxide cases underwent one of two regimens: "manufacturer's directions for use--rinsed with saline and air dried" or "soaked in solution for 6 hrs." The level of residual bacteria was quantified. The efficacy of each cleaning regimen was then compared. Mechanical rubbing and wiping of silver-impregnated cases and soaking hydrogen peroxide cases in hydrogen peroxide were the most effective treatments for reducing biofilms. Once the silver-impregnated cases were rubbed, air drying or recapping the cases did not have any significant effect on the level of the biofilm. The level of initial biofilm formation of silver-impregnated cases was significantly lower than those of polypropylene lens cases (P<0.0001). Rubbing and rinsing with disinfecting solution and wiping with a tissue can be considered to be effective in removing biofilms from silver-impregnated lens cases. Resoaking the basket-type lens case in hydrogen peroxide between use was found to be effective in removing biofilms from these cases.


Transgenic potato expressing Abeta reduce Abeta burden in Alzheimer's disease mouse model.
Beta amyloid (Abeta) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of Abeta is considered a primary therapeutic target. Immunization with Abeta can reduce Abeta burden and pathological features in transgenic AD model mice. Transgenic potato plants were made using genes encoding 5 tandem repeats of Abeta1-42 peptides with an ER retention signal. Amyloid precursor protein transgenic mice (Tg2576) fed with transgenic potato tubers with adjuvant showed a primary immune response and a partial reduction of Abeta burden in the brain. Thus, Abeta tandem repeats can be expressed in transgenic potato plants to form immunologically functional Abeta, and these potatoes has a potential to be used for the prevention and treatment of AD.


Construction of isogenic mutants in Streptococcus gallolyticus based on the development of new mobilizable vectors.
Streptococcus gallolyticus is an emerging cause of infective endocarditis that has been epidemiologically linked to colorectal cancer. S. gallolyticus is poorly transformable using electroporation and no defined mutant has been published yet. Hence, we used mobilization to introduce plasmid DNA from Streptococcus agalactiae into S. gallolyticus using the transfer origin of the conjugative element TnGBS1 (oriTTnGBS1), followed by a classical homologous recombination technique. Two isogenic mutants of S. gallolyticus UCN34, one deleted for the pil1 pilus operon and another for the sortase A gene, were constructed and characterized. This genetic tool should help in unravelling virulence mechanisms of this bacterium.


Psychological Distress and Anxiety Levels Among Health Care Workers at the Height of the COVID-19 Pandemic in the United Arab Emirates.
Objectives: Providing medical care during a global pandemic exposes healthcare workers (HCW) to a high level of risk, causing anxiety and stress. This study aimed to assess the prevalence of anxiety and psychological distress among HCWs during COVID-19. Methods: We invited HCWs from 3 hospitals across the United Arab Emirates (UAE) to participate in an anonymous online survey between April 19-May 3, 2020. The GAD-7 and K10 measures were used to assess anxiety and psychological distress. Logistic regression models assessed associations between knowledge, attitude, worry, and levels of anxiety and psychological distress. Results: A total of 481 HCWs participated in this study. The majority of HCWs were female (73.6%) and aged 25-34 years (52.6%). More than half were nurses (55.7%) and had good knowledge of COVID-19 (86.3%). Over a third (37%) of HCWs reported moderate/severe psychological distress in the K10 measure and moderate/severe anxiety (32.3%) in the GAD-7, with frontline workers significantly reporting higher levels of anxiety (36%). Knowledge of COVID-19 did not predict anxiety and psychological distress, however, HCWs who believed COVID-19 was difficult to treat and those who perceived they were at high risk of infection had worse mental health outcomes. Worry about spreading COVID-19 to family, being isolated, contracting COVID-19 and feeling stigmatized had 1.8- to 2.5-fold increased odds of symptoms of mental health problems. Additionally, HCWs who felt the need for psychological support through their workplace showed increased odds of psychological distress. Conclusion: HCWs in the UAE reported a high prevalence of psychological distress and anxiety while responding to the challenges of COVID-19. The findings from this study emphasize the public, emotional and mental health burden of COVID-19 and highlight the importance for health systems to implement, monitor, and update preventive policies to protect HCWs from contracting the virus while also providing psychological support in the workplace.


[Study on Chinese herb Astragalus membranceus by FTIR fingerprint].
The aim of the study is to find new approach to identifying different growth years and different producing areas of astragalus membranceus simply and rapidly. The FTIR spectrometry, which is accurate, simple and efficient and has high resolution, was used to obtain the sample's FTIR spectrometry. After simple separation and extraction, the drying powder of the sample was detected. In 22 samples, there were 9 common peaks for identifying the authenticity of astragalus membranceus and 5 different peaks. According to the number, shape, and relative intensity of the peak, different growth years and different producing areas of astragalus membranceus can be distinguished. It is convenient and fast to identify different growth years and different producing areas of astragalus membranceus by FTIR fingerprint.


Exome sequencing of 112 trios identifies recessive genetic variants in brain arteriovenous malformations.
Brain arteriovenous malformation (BAVM) is a main cause of cerebral hemorrhage and hemorrhagic stroke in adolescents. Morphologically, a BAVM is an abnormal connection between cerebrovascular arteries and veins. The genetic etiology of BAVMs has not been fully elucidated. In this study, we aim to investigate potential recessive genetic variants in BAVMs by interrogation of rare compound heterozygous variants. We performed whole exome sequencing (WES) on 112 BAVM trios and analyzed the data for rare and deleterious compound heterozygous mutations associated with the disease. We identified 16 genes with compound heterozygous variants that were recurrent in more than one trio. Two genes (LRP2, MUC5B) were recurrently mutated in three trios. LRP2 has been previously associated with BAVM pathogenesis. Fourteen genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2, DNAH14, DNAH5, FCGBP, HERC2, HMCN1, MYH1, NHSL1, PLEC, RP1L1) were recurrently mutated in two trios, and five of these genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2) have been reported to play a role in angiogenesis or vascular diseases. Additionally, abnormal expression of the MYLK protein is related to spinal arteriovenous malformations. Our study indicates that rare recessive compound heterozygous variants may underlie cases of BAVM. These findings improve our understanding of BAVM pathology and indicate genes for functional validation.


Prevention of type 2 diabetes in sub-Saharan Africa, a review.
Type 2 diabetes (T2D) is a significant factor in the overall burden of non-communicable diseases (NCDs) in sub-Saharan Africa (SSA). While many health organizations call for increased attention to this disease, far fewer resources are being allocated to evidence-based prevention programs. The literature demonstrates a lack of reporting on prevention programs, interventions targeted to decrease the development of T2D, and success stories. This review followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases searched were PubMed, Google Scholar, Ovid, Medline, World Health Organization (WHO) Library Information System, and African Journals Online. The following terms were searched individually and in multiple combinations: prevention, intervention, type 2 diabetes, sub-Saharan Africa, education, strategy, strategic plan, risk factors. In total, 253 articles were found and 17 were removed as duplicates. Of these, 78 abstracts were reviewed, with 20 being excluded for not meeting criteria, one was excluded as it was not available in English and one was excluded for lack of availability. After the remaining 56 full-text studies were assessed, seven were included in the review. Throughout the review, the common theme between articles was a lack of resources, lack of prevention strategies, and increasing risk factors. The review highlights the fact that while there are WHO guidelines and packages targeted at primary care level interventions for the prevention and treatment of NCDs, they remain underutilized. Included studies looked at the knowledge level of family members, social marketing and sugar consumption, and primary prevention strategies. There is an overall lack of reporting on interventions targeting the prevention of type 2 diabetes in SSA. Further research is warranted on interventions, prevention strategies, and implementation of the WHO package targeted at NCDs.


Chronic post-operative iris prosthesis endophthalmitis in a patient with traumatic aniridia: a case report.
Post-operative endophthalmitis is a serious complication of intraocular surgery which may present acutely or chronically. Chronic post-operative endophthalmitis is characterized by decreased visual acuity, mild pain, and low-grade uveitis several weeks or months after intraocular surgery which may be responsive to corticosteroids, but recur upon tapering. Low virulence organisms such as Propionibacterium acnes are the most common culprit organisms, and treatment most often consists of both intravitreal antibiotic injections and surgery. Aniridia is a condition defined by total or partial loss of the iris and leads to decreased visual quality marked by glare and photophobia. Treatment of complex or severe cases of traumatic aniridia in which surgical repair is difficult may consist of implantation of iris prostheses, devices designed to reduce symptoms of aniridia. Though chronic, post-operative endophthalmitis has been associated with most intraocular surgeries including intraocular lens implantation after cataract removal, it has never been described in a patient with an iris prosthesis. In this case report, we describe the case of a 49 year old, male construction worker with traumatic aniridia who experienced chronic, recurrent low-grade intraocular inflammation and irritation for months after implantation of the Ophtec 311 prosthetic iris. Symptoms and signs of inflammation improved temporarily with sub-Tenon's capsule triamcinolone injections. Ultimately after more than 2 post-operative years, the iris prosthesis was explanted, and intravitreal cultures showed P. acnes growth after 5 days. Intravitreal antibiotics treated the infection successfully. To our knowledge, this is the first reported case of chronic, post-operative endophthalmitis in a patient with an iris prosthesis. Chronic, post-operative endophthalmitis may be a difficult to identify in the context of traumatic aniridia and iris prosthesis implantation due to other potential etiologies of chronic intraocular inflammation such as implant-induced chafing. Clinicians should suspect chronic, post-operative endophthalmitis in any case of recurrent, low-grade intraocular inflammation.


A paleo-neurologic investigation of the social brain hypothesis in frontotemporal dementia.
The social brain hypothesis posits that a disproportionate encephalization in primates enabled to adapt behavior to a social context. Also, it has been proposed that phylogenetically recent brain areas are disproportionally affected by neurodegeneration. Using structural and functional magnetic resonance imaging, the present study investigates brain-behavior associations and neural integrity of hyperspecialized and domain-general cortical social brain areas in behavioral variant frontotemporal dementia (bvFTD). The results revealed that both structure and function of hyperspecialized social areas in the middle portion of the superior temporal sulcus (STS) are compromised in bvFTD, while no deterioration was observed in domain general social areas in the posterior STS. While the structural findings adhered to an anterior-posterior gradient, the functional group differences only occurred in the hyperspecialized locations. Activity in specialized regions was associated with structural integrity of the amygdala and with social deficits in bvFTD. In conclusion, the results are in line with the paleo-neurology hypothesis positing that neurodegeneration primarily hits cortical areas showing increased specialization, but also with the compatible alternative explanation that anterior STS regions degenerate earlier, based on stronger connections to and trans-neuronal spreading from regions affected early in bvFTD.


The laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion: A protocol for systematic review and meta-analysis.
At present, laser is regarded as an effective treatment for macular edema secondary to branch retinal vein occlusion. With the breakthrough of anti-vascular endothelial growth factor drugs in ophthalmology clinical research, the intravitreal injection of ranibizumab is widely applied, but both methods have their limitations, so some clinical studies have combined and applied them together. However, the clinical results are inconsistent and controversial, and there is no relevant system evaluation for the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion now. Meta analysis is used to analyze and evaluate the effectiveness and safety of the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion. CNKI, VIP, WANFANG, China Biology Medicine disc, Web of Science, PubMed, Embase, Cochrane Library have used random controlled clinical trial of laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion from the establishment of the database to October 2020. Two researchers conducted independent screening, quality assessment and data extraction for the literatures, and used RevMan5.3 to conduct Meta analysis for the included literatures. The research has evaluated the effectiveness and safety of the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion through the aspects of the best corrected visual acuity 6 months after operation, macular center thickness and the incidence of adverse reactions such as elevated intraocular pressure, endophthalmitis, vitreous hemorrhage and cataract. Laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion has good effect, and the research has provided reliable evidence for the use of clinical treatment of the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion.


In-Out Surface Modification of Halloysite Nanotubes (HNTs) for Excellent Cure of Epoxy: Chemistry and Kinetics Modeling.
In-out surface modification of halloysite nanotubes (HNTs) has been successfully performed by taking advantage of 8-hydroxyquinolines in the lumen of HNTs and precisely synthesized aniline oligomers (AO) of different lengths (tri- and pentamer) anchored on the external surface of the HNTs. Several analyses, including FTIR, H-NMR, TGA, UV-visible spectroscopy, and SEM, were used to establish the nature of the HNTs' surface engineering. Nanoparticles were incorporated into epoxy resin at 0.1 wt.% loading for investigation of the contribution of surface chemistry to epoxy cure behavior and kinetics. Nonisothermal differential scanning calorimetry (DSC) data were fed into home-written MATLAB codes, and isoconversional approaches were used to determine the apparent activation energy (Eα) as a function of the extent of cure reaction (α). Compared to pristine HNTs, AO-HNTs facilitated the densification of an epoxy network. Pentamer AO-HNTs with longer arms promoted an Excellent cure; with an Eα value that was 14% lower in the presence of this additive than for neat epoxy, demonstrating an enhanced cross-linking. The model also predicted a triplet of cure (m, n, and ln A) for autocatalytic reaction order, non-catalytic reaction order, and pre-exponential factor, respectively, by the Arrhenius equation. The enhanced autocatalytic reaction in AO-HNTs/epoxy was reflected in a significant rise in the value of m, from 0.11 to 0.28. Kinetic models reliably predict the cure footprint suggested by DSC measurements.


Proteases in Escherichia coli and Staphylococcus aureus confer reduced susceptibility to lactoferricin B.
Lactoferricin B is a cationic antimicrobial peptide derived from the N-terminal part of bovine lactoferrin. The effect of bacterial proteases on the antibacterial activity of lactoferricin B towards Escherichia coli and Staphylococcus aureus was investigated using various protease inhibitors and protease-deficient E. coli mutants. Sodium-EDTA, a metalloprotease inhibitor, was the most efficient inhibitors in both species, but combinations of sodium-EDTA with other types of protease inhibitor gave a synergic effect. The results indicate that several groups of proteases are involved in resistance to lactoferricin B in both E. coli and S. aureus. We also report that genetic inactivation of the heat shock-induced serine protease DegP increased the susceptibility to lactoferricin B in E. coli, suggesting that this protease, at least, is involved in reduced susceptibility to lactoferricin B.