Assessment of publication bias required improvement in oral health systematic reviews.
To examine whether the assessment of publication bias in a broad cross-section of oral health systematic reviews (SRs) is in accordance with established methodology. The electronic databases of 15 dental journals and the Cochrane Database of Systematic Reviews (Oral Health Group) were searched between January 2008 and December 2014 to identify eligible SRs and meta-analyses. The method of publication bias assessment and a range of study characteristics at the SR and the meta-analysis level were recorded. Four hundred fifty-eight systematic reviews were identified. Quantitative synthesis was undertaken in 162. MEDLINE (N = 454, 99%), Cochrane (N = 343, 75%), and EMBASE (N = 283, 62%) were the most frequently searched databases, whereas search for unpublished literature was used in 40% of the reviews. Publication bias was assessed in 46 meta-analyses with only 46% having appropriately used established methodology, such as funnel plots or statistical tests. Of the 38 meta-analyses including at least 10 studies, only 21 (55%) performed the assessment of publication bias. This empirical study highlights the shortcomings related to publication bias assessment in SRs within the field of oral health with publication bias either not assessed or done so inappropriately in more than half of the meta-analyses.


The Impact of Overweight and Obesity on Plantar Pressure in Children and Adolescents: A Systematic Review.
We aimed to synthesise the results of previous studies addressing the impact of overweight and obesity on plantar pressure in children and adolescents. An electronic search of scientific literature was conducted using PubMed, Cochrane and Scopus database, with keywords: "plantar pressure" AND "children" AND "obesity"; "plantar pressure" AND "adolescents" AND "obesity", "plantar pressure" AND "children" AND "overweight", "plantar pressure" AND "adolescents" AND "overweight". Twenty-two articles were included in the review and the following data were recorded: authors, publication year, type of technology (systems, software) for the determination of plantar pressure, study characteristics. Most of the articles used dynamic plantar pressure determination with only four using static plantar pressure measurement. Using ultrasonography with static plantar pressure determination, the correlation between structural and functional changes in the feet of obese children. In overweight and obese children and adolescents, important findings were recorded: higher contact area, increased maximum force beneath the lateral and medial forefoot, increased pressure-time integral beneath the midfoot and 2nd-5th metatarsal regions. Significantly increased foot axis angle and significantly flatter feet were observed in obese subjects in comparison to their normal-weight counterparts. The obese children presented increased midfoot fat pad thickness, with decreased sensitivity of the whole foot and midfoot.


Independent digit contributions to rotational manipulation in a three-digit pouring task requiring dynamic stability.
Many activities of daily living involve multi-digit, voluntary rotational manipulations of grasped objects. Yet, only a few studies have focused on coordination of individual fingertip forces during such tasks. The objective of this study was to investigate individual digit contributions to a three-digit task in which an object was rotationally manipulated against gravity. Center of mass was varied through the use of containers shaped like a water bottle, pint glass, and cocktail glass, from which subjects poured fluid carefully into a nearby receptacle. The center of mass of the grasped object changed continuously as fluid was poured out. Self-selected digit placement and contributions of fingertip forces to rotational manipulation were dependent upon anticipated center of mass location associated with container shape. The thumb resisted the rotation of the top-heavy, cocktail glass container until 79 % of the pouring phase had elapsed, but actively assisted the rotation of the less challenging containers. More directly opposing the thumb, the index finger contributed more to grasp stability. The middle finger contributed more to rotation of the container for pouring. It was found that the thumb, index, and middle fingers acted in unison temporally, but contributed independently to the grip forces and stabilizing moments throughout the dynamic, rotational manipulation task.


Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism.
Binge eating disorder (BED) is the most common eating disorder, yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often comorbid with obesity, a common and highly polygenic trait, and it is underdiagnosed in biobank data sets. To address this limitation, we apply a supervised machine-learning approach (using 822 cases of individuals diagnosed with BED) to estimate the probability of each individual having BED based on electronic medical records from the Million Veteran Program. We perform a genome-wide association study of individuals of African (n = 77,574) and European (n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes and suggest APOE as a risk gene for BED. We identify shared heritability between BED and several neuropsychiatric traits, and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.


Is it time to drop royal patronage of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists?
Historically there is a strong, amiable and mutually respectful relationship between Australian and New Zealand obstetricians and gynaecologists (O&Gs) and the British O&G establishment represented by the Royal College of Obstetricians and Gynaecologists (RCOG). The 'Royal' prefix pays homage to this relationship. With the evolution of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), there have been suggestions that the Royal prefix no longer accurately reflects the raison d'être and aspirations of RANZCOG. This paper will explore the arguments in favour and against dropping the Royal prefix from RANZCOG.


Ductus venosus Doppler velocimetry in normal pregnancies from 11 to 13 + 6 weeks' gestation - a Taiwanese study.
To investigate flow in the ductus venosus at 11-13 + 6 weeks of gestation in women with normal pregnancies in the Taiwanese population. Two hundred and fifty-two normal singleton pregnancies with gestational ages ranging from 11 to 13 + 6 weeks were examined in this study. The pulsatility index for veins (PIV), resistance index (RI), peak velocity during ventricular systole (S-wave), and peak velocity during ventricular diastole (D-wave) were recorded from the ductus venosus. We analyzed 252 participants who all fulfilled the inclusion and exclusion criteria of our study. The mean maternal age was 31 (range 19-45 years), with a corresponding gestational age of 12 + 4 weeks (range 11-13 + 6). No significant change was found in the vascular indices as gestational age increased for the S-wave (S-wave = 1.4214 (GA) + 17.448, r = 0.09, P = 0.154), PIV (PIV = -0.0358 (GA) + 1.4143, r = -0.05, P = 0.378) and RI (RI = -0.035 (GA) + 1.1478, r = -0.064, P = 0.468). In contrast, the D-wave behaved differently from the other variables. There was a significant increase (r = 0.155, P = 0.013) in the D-wave with gestational age (D-wave = 1.4896 (GA) - 7.1547). D-wave velocity in the ductus venosus increased with gestational age. S-wave peak velocity showed an increasing trend and PIV showed a decreasing trend with gestational age, but they did not reach statistical significance.


Vertical distribution of (226)Ra and (210)Po in agricultural soils in Buyuk Menderes Basin, Turkey.
The vertical distribution of (226)Ra and (210)Po was investigated in the cultivated soils of the Buyuk Menderes Basin in Turkey. Five soil cores down to a depth of about 50 cm were taken from each site and divided into strata of 2-3 cm intervals. The samples were analyzed for their (226)Ra and (210)Po activity concentrations using radioanalytical methods. Down-core concentration profiles of (226)Ra and (210)Po in the soil cores from five sites are obtained. The activity concentrations of soil cores range from 80 to 1170 Bq kg(-1) for (226)Ra and from 10 to 870 Bq kg(-1) for (210)Po with the depth. Analysis of the vertical soil profiles indicate that the activity concentrations of (226)Ra and (210)Po for soil strata at all the sites have not extremely changed with depth.


Metastatic Follicular Thyroid Carcinoma of the Mandible: A Case Report at Tertiary Care Rural Centre.
The most common endocrine cancer is thyroid carcinoma, however it seldom spreads to the oral cavity. Follicular thyroid carcinoma is the second most common type of thyroid cancer after papillary thyroid carcinoma. Thyroid carcinoma-related mandibular metastases is not very common, and there aren't many cases reported in the literature. We are describing a case in which the underlying cancer was diagnosed before the metastatic mandibular lesion was found. Total thyroidectomy and excision of the affected structures, with or without adjuvant therapy, appear to be the most effective treatments.


Age differences in learning emerge from an insufficient representation of uncertainty in older adults.
Healthy aging can lead to impairments in learning that affect many laboratory and real-life tasks. These tasks often involve the acquisition of dynamic contingencies, which requires adjusting the rate of learning to environmental statistics. For example, learning rate should increase when expectations are uncertain (uncertainty), outcomes are surprising (surprise) or contingencies are more likely to change (hazard rate). In this study, we combine computational modelling with an age-comparative behavioural study to test whether age-related learning deficits emerge from a failure to optimize learning according to the three factors mentioned above. Our results suggest that learning deficits observed in healthy older adults are driven by a diminished capacity to represent and use uncertainty to guide learning. These findings provide insight into age-related cognitive changes and demonstrate how learning deficits can emerge from a failure to accurately assess how much should be learned.


Overcoming drug resistance to heme-targeted antimalarials by systematic side chain variation of 7-chloro-4-aminoquinolines.
Systematic variation of the branching and basicity of the side chain of chloroquine yielded a series of new 7-chloro-4-aminoquinoline derivatives exhibiting high in vitro activity against four different strains of P. falciparum. Many of the compounds tested showed excellent potency against chloroquine sensitive and resistant strains. In particular 4b, 5a, 5b, 5d, 17a, and 17b were found to be significantly more potent than chloroquine against the resistant strains Dd2 and FCB.


Quantitative Measurement of Ascorbate and Glutathione by Spectrophotometry.
Ascorbate and glutathione are key chemical antioxidants present at relatively high concentrations in plant cells. They are also reducing cofactors for enzymes that process hydrogen peroxide in the ascorbate-glutathione pathway. Due to these two related biochemical functions, the compounds form an interface between reactive oxygen species and sensitive cellular components. Therefore, their status can provide reliable and direct information on cell redox state, signaling, and plant health. While several methods exist for quantification of ascorbate and glutathione, simple enzyme-dependent assays allow them to be measured easily and inexpensively in common extracts. This chapter describes a protocol to measure total contents, as well as the major oxidized and reduced forms, of both compounds in plant tissues.


Using Reaction Time and Equal Latency Contours to Derive Auditory Weighting Functions in Sea Lions and Dolphins.
Subjective loudness measurements are used to create equal-loudness contours and auditory weighting functions for human noise-mitigation criteria; however, comparable direct measurements of subjective loudness with animal subjects are difficult to conduct. In this study, simple reaction time to pure tones was measured as a proxy for subjective loudness in a Tursiops truncatus and Zalophus californianus. Contours fit to equal reaction-time curves were then used to estimate the shapes of auditory weighting functions.


Long-term outcomes after circular stapled hemorrhoidopexy versus Ferguson hemorrhoidectomy.
We aimed to compare long-term outcomes and quality of life in patients undergoing circular stapled hemorrhoidopexy to those who had Ferguson hemorrhoidectomy. Patients who underwent Ferguson hemorrhoidectomy and circular stapled hemorrhoidopexy between 2000 and 2010 were reviewed. Long-term follow-up was assessed with questionnaires. Two hundred seventeen patients completed the questionnaires. Mean follow-up was longer in the Ferguson hemorrhoidectomy subgroups (7.7 ± 3.4 vs. 6.3 ± 2.9 years, p = 0.003). Long-term need for additional surgical or medical treatment was similar in the Ferguson hemorrhoidectomy and circular stapled hemorrhoidopexy groups (3 vs. 5%, p = 0.47 and 3% in both groups, p > 0.99, respectively). Eighty-one percentage of Ferguson hemorrhoidectomy and 83% of circular stapled hemorrhoidopexy patients stated that they would undergo hemorrhoid surgery again if needed (p = 0.86). The symptoms were greatly improved in the majority of patients (p = 0.06), and there was no difference between the groups as regards long-term anorectal pain (p = 0.16). The Cleveland global quality of life, fecal incontinence severity index, and fecal incontinence quality of life scores were similar (p > 0.05). This is one of the longest follow-up studies comparing the outcomes after circular stapled hemorrhoidopexy and Ferguson hemorrhoidectomy. Patient satisfaction, resolution of symptoms, quality of life, and functional outcome appear similar after circular stapled hemorrhoidopexy and Ferguson hemorrhoidectomy in long term.


The metabolic response to operative stress in infants.
The aim of this study was to characterize energy metabolism and substrate utilization in infants following an operation. Nineteen infants (weight 3.2 +/- 0.2 kg) who had an operation were studied. Anesthesia was standardized and operative stress score (OSS) was recorded. Five infants had a minor operation (OSS < 7), and 14 infants had a major operation (OSS > or = 7). Energy and nitrogen intake were constant during the 48-hour study period. Respiratory gas exchange was measured by indirect calorimetry preoperatively, and postoperatively for the first 12 hours continuously and at 24 hours, 48 hours, and 5 days. Urinary nitrogen excretion rate was measured for the first 48 hours following the operation. Physical activity was scored. Resting energy expenditure (REE) and nonprotein respiratory quotient (NPRQ) were calculated. REE increased postoperatively, peaking at 2 to 4 hours, and returned to baseline levels by 12 to 24 hours. Peak REE was significantly higher than baseline REE (P < .001). Substrate utilization was not altered by operation. The increase in REE was significantly greater in infants having a major operation than in infants having a minor operation (P < .05). Among infants having a major operation, the increase in REE was significantly greater in those infants more than 48 hours old, than in those infants less than 48 hours old (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Cell-surface enzymes in control of leukocyte trafficking.
Leukocyte trafficking between the blood and the tissues is pivotal for normal immune responses. Cell-adhesion molecules (such as selectins and leukocyte integrins) and chemoattractants (such as chemokines) have well-established roles in supporting leukocyte exit from the blood. Emerging data now show that, for both leukocytes and endothelial cells, enzymatic reactions that are catalysed by cell-surface-expressed enzymes with catalytic domains outside the plasma membrane (known as ectoenzymes) also make crucial contributions to this process. Ectoenzymes can function physically as adhesion receptors and can regulate the recruitment of cells through their catalytic activities. Here, we provide new insights into how ectoenzymes--including nucleotidases, cyclases, ADP-ribosyltransferases, peptidases, proteases and oxidases--guide leukocyte traffic.


A change of threonine 266 to isoleucine in the lac permease of Escherichia coli diminishes the transport of lactose and increases the transport of maltose.
The DNA sequence of several functionally interesting lac permease mutants of Escherichia coli has been determined. The phenotypes of the mutant permeases were described by Mieschendahl et al. (1981). The following exchanges are noteworthy: tyr to asp in codon 26 in Y-K MUB 7; thr to ile in codon 266 in Y-K AJ 33; gly to asp in codon 262 in Y-D 3 and in Y-D 4.


Relationship of smoking and/or passive exposure to tobacco smoke on the association between serum thyrotropin and body mass index in large groups of adolescents and children.
Hypothyroidism may be a risk factor for obesity, because metabolic rates tend to be decreased in this disorder. Currently, it is under debate whether smoking may modify the association between hypothyroidism and obesity. Against this background, the aims of our study were to investigate whether there is an association between serum thyrotropin (TSH) and body mass index (BMI) in children and adolescents and whether smoking mediates this association. Data from 6435 children (ages 3-10) and 5918 adolescents (ages 11-17) from the "The German Health Interview and Examination Survey for Children and Adolescents" (KiGGS) were analyzed. Smoking status was classified into two categories: smokers and nonsmokers. A subject was classified as being exposed to environmental tobacco smoke (ETS) if someone in the parental home smoked more than 1 day a week. Serum TSH levels were measured with an ELISA method. Serum TSH levels were associated with BMI and obesity by multivariable linear regression stratified by smoking status and exposure to ETS. In adolescents, there was an association between serum TSH levels and BMI, and it was stronger in smokers (β=0.62; 95% confidence interval [CI 0.38-0.85]) than in nonsmokers (β=0.18 [CI 0.09-0.28]). Likewise, it was stronger in adolescents exposed to ETS and adolescents not exposed to ETS. In children, who were either exposed or not exposed to ETS, there was an association between serum TSH levels and BMI. In them, however, the strength of this association was similar in those exposed and those not exposed to ETS. Active and passive smoking may mediate the association between thyroid function and BMI in adolescents. In smoking adolescents, hypothyroidism may lead to an increase of the BMI, whereas this is not the case in nonsmoking adolescents.


Quantitative dataset of shallow water reef in Pulau Bidong, Southern of South China sea during pre and post of tropical storm (Pabuk - January 2019).
This article provides raw datasets of the coral reefs status in Pulau Bidong, southern of South China Sea before and after being strike by the tropical storm Pabuk on January 2019. Data were collected using a rapid coral survey method called Coral Video Transect (CVT) technique. The data were collected along a 100 m transect line set up parallel to the shoreline and at a constant depth. In total, eight transects were surveyed during both periods (pre - August 2016, post - March 2019). Back in laboratory, the footage was then extracted into non-overlapping frames or still images prior to image analysis using Coral Point Count with Excel Extension (CPCe) software. The benthic coral reefs relative percentage cover was automatically generated after the image analysis and represented by five major categories; live coral (C), algae (ALG), other invertebrates (OT), dead coral (DC), and sand silt and rock (SR). Live coral cover was identified up to the genus level. This raw dataset was used in this article. The data provided in this article could be of significant use for future studies especially on coral recovery after the natural disturbances. It can provide a baseline assessment especially for coral reefs management as well as to comprehend changes in coral health status in the face of natural and anthropogenic disturbances. The data presented here support the information in the article Safuan et al. (2020).


The effect of orexin-A and -B on the histamine release in the anterior hypothalamus in rats.
The neuropeptides orexin-A and -B have been reported to be appetite-stimulating peptides, but they are also known as important factors that control arousal state. We studied the effects of orexin-A and -B on the hypothalamic histamine release using in vivo microdialysis. A significant and sustained increase in histamine release was observed by intracerebroventricular injection of 1 nmol of orexin-A, but not by the same dose of orexin-B. An increased dose of orexin-B to 5 nmol facilitated histamine release, although this effect was much less potent than orexin-A. These findings suggest that both of the orexins play important roles in the regulation of waking through the activation of histaminergic system.


Microbiological diagnosis of catheter-related infections.
This revision describes in detail the different diagnostic techniques of catheter-related infection, both in terms of catheter removal and preservation. Culture techniques based on catheter withdrawal are classified depending on the detection of extraluminal and/or intraluminal colonization, and new methodologies are described. In general, the most important recommendations are: (a) do not send for culture catheter tips without suspicion of infection, (b) Maki's technique is the standard for detecting extraluminal colonization, (c) take 2 pairs of peripheral blood cultures before starting antibiotic treatment, (d) use skin and connections/connectors cultures for the conservative diagnosis due to their high negative predictive value (Gram and culture), and (e) take differential quantitative blood cultures though all catheter lumens and through a peripheral vein.


Immunization of sheep against modified peptides of gonadotropin releasing hormone conjugated to carriers.
The efficacy of antigens based on modified GnRH peptides in stimulating the production of antibodies against GnRH in sheep was tested. In the first study cysteine-containing GnRH peptides were conjugated to keyhold limpet haemocyanin (KLH) in 3 different orientations. The 3 conjugates were prepared in an emulsion of Freund's complete adjuvant (FCA) and were injected into 3 groups of 6 castrated male lambs. The 3 vaccines efficiently induced anti-GnRH titers in all the animals treated. The specificity of the GnRH antisera raised varied depending on the orientation of the GnRH molecule in the antigen and on the individual animal. In a second trial designed to evaluate carrier molecules, a cysteine-containing GnRH peptide was conjugated to either KLH, equine serum albumin, ovalbumin or tetanus toxoid. The conjugates were prepared with FCA and injected into intact male lambs. All 4 vaccines stimulated the production of antibodies against GnRH in all the animals treated. The conjugates prepared with equine serum albumin or ovalbumin were the most effective in raising high anti-GnRH titers. In 18 of 20 lambs treated, anti-GnRH titers resulted in a marked atrophy of the testes. We conclude that: 1) the different epitopes of the GnRH molecule are equally immunogenic in sheep; 2) the GnRH antibody response is affected by the carrier used; and, 3) anti-GnRH vaccines based on cysteine-substituted GnRH analogues show potential for use in immunocastration of livestock.


Hypothermia for acute brain injury--mechanisms and practical aspects.
Hypothermia is widely accepted as the gold-standard method by which the body can protect the brain. Therapeutic cooling--or targeted temperature management (TTM)--is increasingly being used to prevent secondary brain injury in patients admitted to the emergency department and intensive care unit. Rapid cooling to 33 °C for 24 h is considered the standard of care for minimizing neurological injury after cardiac arrest, mild-to-moderate hypothermia (33-35 °C) can be used as an effective component of multimodal therapy for patients with elevated intracranial pressure, and advanced cooling technology can control fever in patients who have experienced trauma, haemorrhagic stroke, or other forms of severe brain injury. However, the practical application of therapeutic hypothermia is not trivial, and the treatment carries risks. Development of clinical management protocols that focus on detection and control of shivering and minimize the risk of other potential complications of TTM will be essential to maximize the benefits of this emerging therapeutic modality. This Review provides an overview of the potential neuroprotective mechanisms of hypothermia, practical considerations for the application of TTM, and disease-specific evidence for the use of this therapy in patients with acute brain injuries.


Low-Pressure Pneumoperitoneum During Laparoscopic Sleeve Gastrectomy: a Safety and Feasibility Analysis.
Laparoscopy is advised under the lowest possible intra-peritoneal pressure. The aim of this study is to analyze the safety/feasibility of low pneumoperitoneum pressure (LPP) during laparoscopic sleeve gastrectomy (LSG). All primary LSGs who completed a 3-month follow-up were included. Re-do operations and LSGs performed with concomitant procedures were excluded. All LSGs were performed by the senior author. Upon trocar insertions, pressure was set to 10 mmHg, and the procedure was started. The pressure was increased step-wise, according to the senior author's assessment of the quality of exposure. Doing so, three pressure groups were formed: groups 1 (10 mmHg), 2 (11-13 mmHg), and 3 (14 mmHg). All data was retrieved from our database. Statistical analysis was performed using one-way ANOVA/Tukey's HSD test/Chi-square test. P values < 0.05 were regarded as significant. Between February 2018 and October 2022, 708 consecutive/primary LSGs were studied. No mortality/conversion/thromboembolic event was observed. Groups 1, 2, and 3 comprised 376 (53.1%), 243 (34.3%), and 89 (12.6%) patients, respectively. Demographics, initial weight, duration of surgery, history for abdominoplasty, drain output, length of stay, and %total weight loss were evenly distributed among groups. Among 16 bleeding episodes, 14 occurred in the LPP group (p = 0.019). Including the only leak and stenosis, 8/9 of Clavien-Dindo 3b + 4 complications were observed in the LPP group (p = 0.092). LSG with LPP is feasible in about half of the patients. However, almost all potentially life-threatening complications occurred in the LPP group where a significantly higher rate of bleeding was observed. Our findings suggest caution for routinely using LPP during LSG.


Effect of lithium administration on brain activity under an emotion regulation paradigm in healthy participants: a functional magnetic resonance imaging study.
Emotion regulation (ER) difficulties have been previously described in bipolar disorder (BD). Whilst lithium has been shown to be effective in the treatment of BD, the mechanisms underlying lithium's effect on mood stabilisation remain unclear. Unravelling lithium's effect on psychological processes impaired in BD, such as ER, could address this translational gap and inform the development of new treatments. This study investigated the neural effects of lithium (800mg) on ER in 33 healthy volunteers in a double-blind between-groups design, randomised to lithium (n=17) or placebo (n=16) for 11 days. At treatment completion, participants underwent 3-Tesla fMRI scan whilst performing an ER task. Reappraisal reduced negative affect across groups and led to the expected increase in frontal brain activity. Participants receiving lithium showed (1) decreased activation in prefrontal and posterior parietal cortices and connectivity between the fronto-limbic network (Z>2.3, p<0.05 corrected); and (2) increased activity in the right superior temporal gyrus (Z>3.1, p<0.05 corrected) and connectivity between the right medial temporal gyrus (MTG) and left middle frontal gyrus (Z>2.3, p<0.05 corrected) during reappraisal. Further effects of lithium were found in response to negative picture presentation, whereby an anticorrelation was found between the left amygdala and the frontal cortex, and greater connectivity between the right MTG and the bilateral medial prefrontal cortex extending into the paracingulate gyrus, compared to placebo (Z>2.3, p < 0.05 corrected). These results show a potential effect of lithium on ER through its effects on activity and connectivity, and further elaborate the neural underpinnings of cognitive reappraisal. Future work should investigate longer term effects of lithium on ER in BD, ultimately benefitting the development of novel and more effective treatments.


Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and modifies location of late endosomal compartments.
CLN3 is an endosomal/lysosomal transmembrane protein mutated in classical juvenile onset neuronal ceroid lipofuscinosis, a fatal inherited neurodegenerative lysosomal storage disorder. The function of CLN3 in endosomal/lysosomal events has remained elusive due to poor understanding of its interactions in these compartments. It has previously been shown that the localisation of late endosomal/lysosomal compartments is disturbed in cells expressing the most common disease-associated CLN3 mutant, CLN3∆ex7-8 (c.462-677del). We report here that a protracted disease causing mutant, CLN3E295K, affects the properties of late endocytic compartments, since over-expression of the CLN3E295K mutant protein in HeLa cells induced relocalisation of Rab7 and a perinuclear clustering of late endosomes/lysosomes. In addition to the previously reported disturbances in the endocytic pathway, we now show that the anterograde transport of late endosomal/lysosomal compartments is affected in CLN3 deficiency. CLN3 interacted with motor components driving both plus and minus end microtubular trafficking: tubulin, dynactin, dynein and kinesin-2. Most importantly, CLN3 was found to interact directly with active, guanosine-5'-triphosphate (GTP)-bound Rab7 and with the Rab7-interacting lysosomal protein (RILP) that anchors the dynein motor. The data presented in this study provide novel insights into the role of CLN3 in late endosomal/lysosomal membrane transport.


Clinicopathological Study of Primary Pediatric Gastrointestinal Lymphomas.
Primary gastrointestinal lymphomas (PGIL) are uncommon in children and account for <5% of all pediatric malignancies. The objective of our study was to analyze the prognostic factors of pediatric PGILs with reference to its histological subtypes, stage, and outcomes using immunohistochemistry. Twenty cases were studied over 11 years. Clinicopathological profiles, histological details, and immunohistochemical (IHC) profiles were analyzed. The mean age at the presentation was 6 years. Using IHC stains (CD CD10, CD19, CD20, CD3, terminal deoxynucleotidyl transferase, BCL 2 and 6, PAX 5, and MUM1), diffuse large B-cell lymphoma (DLBCL) was most prevalent (45%), followed by Burkitt lymphoma (35%) and lymphoblastic lymphoma (20%). DLBCLs (9) were classified using the Han's algorithm. Six were activated B-cell and 3 were germinal center B-cell subtypes. The cases of lymphoblastic lymphoma and those in Stage I disease had the best prognosis. Pediatric PGILs have variable presentation, outcomes, and diverse treatment modalities depending on the histological subtypes. A panel of IHC stains can be a useful adjunct for the categorization and prognosis of pediatric PGILs.


Safety of biologic therapy in rheumatoid arthritis and other autoimmune diseases: focus on rituximab.
To review the safety of biologic agents used to treat rheumatoid arthritis (RA) and other autoimmune diseases, with a focus on rituximab. Information was gathered from a search of the PubMed database and from major congress abstract listings through June 2007. Rituximab is approved for treating RA in patients with an inadequate response to TNF inhibitors and is under study in other indications for RA and other autoimmune disorders. The current safety profile of rituximab in RA is known from Phase II and III studies conducted preapproval, treating approximately 750 patients, as well as from long-term extension studies with repeated therapy. Clinical trials have established that the most common adverse events are infusion-associated reactions, seen in 29 to 40% of patients, most of which are mild to moderate and occur following the first rituximab infusion, with incidence and severity decreasing with subsequent infusions. Rates of infections and serious infections to date are within the range expected for RA patients treated with other biologic agents, but the longer term effects of B-cell depletion and the effects of repeated treatment on the risk of infections are uncertain. Information is limited for rituximab safety in other autoimmune disorders but current data do not suggest that there is a significant difference in adverse events from that previously reported. Rituximab is an important addition to the rheumatologist's armamentarium for the treatment of difficult RA and ongoing trials will determine its utility in other indications for RA and other autoimmune conditions. The true safety profile of rituximab will emerge as larger numbers of patients are treated in routine clinical practice.


PES1 regulates sensitivity of colorectal cancer cells to anticancer drugs.
PES1 (also known as Pescadillo), a nucleolar protein, was involved in biogenesis of ribosomal RNA. Up-regulation of PES1 has been documented in some human cancers, indicating that PES1 may play some crucial roles in tumorigenesis. In our previous study, it was found that silencing of PES1 resulted in decreased proliferation of colorectal cancer cells. We also noticed that depletion of PES1 altered expression profiles of diverse genes. In the present study, we validated the expression changes of a subset of genotoxic stress-related genes in PES1-silenced HCT116 cells by quantitative RT-PCR. The steady and etoposide-induced phosphorylated H2AX (γ-H2AX) were higher in PES1-silenced cells than in control cells. Besides, etoposide-induced γ-H2AX persisted longer in PES1-silenced cells after removing the etoposide. Next, results of comet assay revealed decreased DNA repair after PES1-ablation. PES1-ablated cells were more sensitive to chemotherapeutic agents, which could be reversed by reconstitution with exogenous PES1. Furthermore, deletion of PES1 diminished steady and DNA damage-induced levels of nuclear RAD51. Our results uncover a potential role of PES1 in chemoresistance by regulating DNA damage response in colorectal cancer cells.


Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degeneration.
Disordered immune responses and cholesterol metabolism have been implicated in age-related macular degeneration (AMD), the leading cause of blindness in elderly individuals. SULT2B1, the key enzyme of sterol sulfonation, plays important roles in inflammation and cholesterol metabolism. However, the role and underlying mechanism of SULT2B1 in AMD have not been investigated thus far. Here, we report that SULT2B1 is specifically expressed in macrophages in choroidal neovascularization lesions. Sutl2b1 deficiency significantly reduced leakage areas and inhibited pathological angiogenesis by inhibiting M2 macrophage activation in vivo and in vitro. Mechanistically, loss of Sult2b1 activated LXRs and subsequently increased ABCA1 and ABCG1 (ABCA1/G1)-mediated cholesterol efflux from M2 macrophages. LXR inhibition (GSK2033 treatment) in Sult2b1 -/- macrophages reversed M2 polarization and decreased intracellular cholesterol capacity to promote pathological angiogenesis. In contrast to SULT2B1, STS, an enzyme of sterol desulfonation, protected against choroidal neovascularization development by activating LXR-ABCA1/G1 signalling to block M2 polarization. Collectively, these data reveal a cholesterol metabolism axis related to macrophage polarization in neovascular AMD.


Accidental latissimus dorsi flap pedicle avulsion during immediate breast reconstruction: salvage by conversion to free flap.
Pedicle damage is a rare complication of latissimus dorsi (LD) flap breast reconstruction. We report a case of accidental avulsion of the vascular pedicle of a totally autologous (extended) LD flap during immediate breast reconstruction in a patient who had previously undergone contralateral breast reconstruction with a pedicled TRAM flap based on the opposite superior epigastric vessels. The intra-operative strategy to salvage the avulsed LD flap by conversion to a free flap while not compromising the contralateral breast reconstruction is discussed.


Sensory processing sensitivity and culturally modified resilience education: Differential susceptibility in Japanese adolescents.
This study investigated the efficacy of a culturally modified resilience education program on Japanese adolescents' well-being from a differential susceptibility perspective. First, a culturally modified resilience education intervention was developed by employing the SPARK resilience program and implemented with 407 Japanese high school students in Tokyo (age = 15-16, M = 192, F = 215). To test intervention efficacy, students' level of resilience, self-esteem, self-efficacy, and depression were measured pre-, post-, and three months after intervention. Additionally, sensory processing sensitivity, using the Japanese version of the Highly Sensitive Child Scale for Adolescence, was measured as an index of individual sensitivity. Analysis of variance was used to examine the baseline differences and interaction effects of students' gender and level of sensory processing sensitivity. Latent growth curve models were used to assess the overall effects of the intervention and change over time. Results indicated that the intervention was effective in enhancing students' overall self-efficacy; and that highly sensitive students, who scored significantly lower in well-being than their counterparts at baseline, responded more positively to the intervention, and had a greater reduction in depression and promotion of self-esteem. These findings provided unique evidence in line with the differential susceptibility perspective and useful implications to develop personalized treatment interventions for adolescents in different cultural contexts.


MIQE précis: Practical implementation of minimum standard guidelines for fluorescence-based quantitative real-time PCR experiments.
The conclusions of thousands of peer-reviewed publications rely on data obtained using fluorescence-based quantitative real-time PCR technology. However, the inadequate reporting of experimental detail, combined with the frequent use of flawed protocols is leading to the publication of papers that may not be technically appropriate. We take the view that this problem requires the delineation of a more transparent and comprehensive reporting policy from scientific journals. This editorial aims to provide practical guidance for the incorporation of absolute minimum standards encompassing the key assay parameters for accurate design, documentation and reporting of qPCR experiments (MIQE précis) and guidance on the publication of pure 'reference gene' articles.


Oncogenic Ras upregulates NADPH oxidase 1 gene expression through MEK-ERK-dependent phosphorylation of GATA-6.
Ras oncogene upregulates the expression of nicotinamide adenine dinucleotide phosphate oxidase (Nox) 1 via the Raf/MEK/ERK pathway, leading to the elevated production of reactive oxygen species that is essential for maintenance of Ras-transformation phenotypes. However, the precise transcriptional control mechanism underlying Ras-induced Nox1 expression remains to be elucidated. Here we demonstrated that via the MEK/ERK pathway, Ras signaling enhances the activity of the functional Nox1 promoter (nt -321 to -1) in colon cancer CaCo-2 cells and thereby induces the formation of the specific protein-DNA complexes in the two GATA-binding site-containing regions (nt -161 to -136 and -125 to -100). Supershift assays with GATA antibodies, protein analyses and chromatin immunoprecipitation revealed that GATA-6 is a component of the specific protein-DNA complexes at the Nox1 promoter. GATA-6 was able to trans-activate the Nox1 promoter but not a promoter in which the GATA-binding sites are mutated. Moreover, GATA-6 was phosphorylated at serine residues by MEK-activated ERK, which increased GATA-6 DNA binding, correlating with suppression of the Nox1 promoter activity by an MEK inhibitor PD98059. Finally, the site-directed mutation of the consensus ERK phosphorylation site (PYS(120)P to PYA(120)P) of GATA-6 abolished its trans-activation activity, suppressing of the growth of CaCo-2 cells. On the basis of these results, we propose that oncogenic Ras signaling upregulates the transcription of Nox1 through MEK-ERK-dependent phosphorylation of GATA-6.


Efficient production of gamma-aminobutyric acid using Escherichia coli by co-localization of glutamate synthase, glutamate decarboxylase, and GABA transporter.
Gamma-aminobutyric acid (GABA) is an important bio-product, which is used in pharmaceutical formulations, nutritional supplements, and biopolymer monomer. The traditional GABA process involves the decarboxylation of glutamate. However, the direct production of GABA from glucose is a more efficient process. To construct the recombinant strains of Escherichia coli, a novel synthetic scaffold was introduced. By carrying out the co-localization of glutamate synthase, glutamate decarboxylase, and GABA transporter, we redirected the TCA cycle flux to GABA pathway. The genetically engineered E. coli strain produced 1.08 g/L of GABA from 10 g/L of initial glucose. Thus, with the introduction of a synthetic scaffold, we increased GABA production by 2.2-fold. The final GABA concentration was increased by 21.8% by inactivating competing pathways.


Stat3-Induced lncRNA Kcnq1ot1 Regulates the Apoptosis of Neuronal Cells in Spinal Cord Injury.
Emerging evidence validates the vital roles of long noncoding RNAs (lncRNAs) in spinal cord injury (SCI), which attracts great attention. In the present study, our study investigated the function and in-depth mechanism of lncRNA Kcnq1 overlapping transcript 1 (Kcnq1ot1) in SCI. Results indicated that lncRNA Kcnq1ot1 expression upregulated in the hypoxia-administered neuronal cells (PC12 cells) and SCI rat models. Moreover, transcription factor signal transducer and activator of transcription 3 (Stat3) accelerated the transcriptional enrichment of Kcnq1ot1 in SCI cellular model. Functional experiments demonstrated that Kcnq1ot1 knockdown repressed the apoptosis of neuronal cells. Mechanistically, Kcnq1ot1 recruited EZH2 to the promoter region of p27 to repress its transcription. Taken together, our results indicate that Stat3-induced lncRNA Kcnq1ot1 regulates the apoptosis in SCI through epigenetically silencing p27, contributing to novel therapeutic target for SCI.


Immunoblastic lymphoma following Hodgkin's disease: a case report with translocation t(8;14) in tumoral cells and sporadic t(7;14) in peripheral lymphocytes.
A non-Hodgkin's lymphoma was observed in a patient who had been treated for Hodgkin's disease (HD). The initial treatment consisted of radiotherapy alone, but following three subsequent relapses, both chemotherapy and radiotherapy were administered several times. Twenty years later, the biopsy of an isolated cervical lymph node revealed a non-Hodgkin's lymphoma. The histologic subtype was immunoblastic. Cytogenetic studies of the tumoral cells revealed a t(8;14)(q24;q32) translocation. At the same time, multiple chromosomal rearrangements were observed in peripheral blood lymphocytes, especially t(7;14)(q35;q12), which was noted in 6 of 53 mitoses. This anomaly, frequently observed in patients with ataxia telangiectasia or severe immunodeficiency, has not previously been described in such circumstances.


The effects of carbon nitrogen ratio and salinity on the treatment of swine digestion effluent simultaneously producing bioenergy by microalgae biofilm.
In order to remove high concentrations of ammonia nitrogen (NH4+-N) and refractory sulfamethazine (SM2) from swine digestion effluent, different carbon/nitrogen (C/N) ratios and salinity were used to determine the effects of pollutants removal in the microalgae biofilm system. Microalgae biofilm treatment under optimal environmental conditions in synthetic swine digestion effluent were C/N ratio of 20 and salinity of 140 mM. In order to make the actual swine digestion effluent discharge up to the standard, three different two-cycle treatments (suspended microalgae, microalgae biofilm, microalgae biofilm under the optimal conditions) were studied. The results showed that after two-cycle treatment with microalgae biofilm under the optimal conditions, the actual swine digestion effluent levels of total nitrogen (TN), NH4+-N, total phosphorus (TP), chemical oxygen demand (COD), SM2 were 22.65, 9.32, 4.11, 367.28, and 0.99 mg L-1, respectively, which could satisfy the discharge standards for livestock and poultry wastewater in China. At the same time, first-order kinetic simulation equations suggested a degradation half-life of 4.85 d for SM2 under optimal conditions in microalgae biofilm, and microbial community analysis indicated that the dominant genus was Halomonas. Furthermore, 35.66% of lipid, 32.56% of protein and 18.44% of polysaccharides were harvested after two-cycle in microalgae biofilm treatment under optimal environmental conditions. These results indicated that the regulation of C/N and salinity in microalgae biofilm for the treatment of swine digestion effluent was a high-efficiency strategy to simultaneously achieve wastewater treatment and bioenergy production.


O⁶-methylguanine-DNA methyltransferase promoter methylation in 45 primary central nervous system lymphomas: quantitative assessment of methylation and response to temozolomide treatment.
Favorable responses to temozolomide chemotherapy have recently been reported in primary central nervous system lymphoma (PCNSL) patients who are refractory to high-dose methotrexate therapy. The gene encoding the DNA repair enzyme O (6)-methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by promoter methylation in several human tumors, including gliomas and systemic lymphomas. MGMT promoter methylation is also a prognostic marker in glioblastoma patients treated with temozolomide. To validate temozolomide treatment in PCNSL, we applied methylation-sensitive high resolution melting (MS-HRM) analysis to quantitate MGMT methylation in PCNSL. MGMT promoter methylation was detected in tumors from 23 (51%) of 45 PCNSL patients, 11 of which were considered to have high (more than 70.0%) methylation status. Of the five recurrent PCNSLs treated with temozolomide, four cases responded, with three achieving complete response and one, a partial response. All four responsive PCNSLs had methylated MGMT promoters, whereas the non-responsive recurrent PCNSL did not. Thus, the use of quantitative MS-HRM analysis for the detection of MGMT promoter methylation has been suggested in PCNSL for the first time. The assay allows rapid and high-throughput evaluation of the MGMT methylation status, and seems to be promising in clinical settings. MGMT promoter methylation may become a useful marker for predicting the response of PCNSLs to temozolomide.


Effects of acetoacetate administration on glucose metabolism in mammary gland of fed lactating rats.
Administration of acetoactate to fed lactating rats rapidly decreases glucose uptake by the mammary gland, and causes an output of pyruvate, whereas lactate uptake remains unchanged. Similar changes, though not identical, occur in starved lactating rats, which suggests that the increased acetoacetate concentration in this situation may be one of the factors responsible for the alterations in glucose metabolism.


Association between Caregiver Role and Short- and Long-Term Functional Recovery after Hip Fracture: A Prospective Study.
After a hip fracture, 50% of senior patients are left with permanent functional decline and 30% lose their autonomy. The aim of this prospective study was to evaluate whether seniors who are in a caregiver role have better functional recovery after hip fracture compared with noncaregivers. Prospective observational study. A total of 107 Swiss patients with acute hip fracture age 65 years and older (84% women; 83.0 ± 6.9 years; 87% community-dwelling). At baseline, participants were asked if they were caregivers for a person, a pet, or a plant. Lower-extremity mobility was measured using the Timed Up and Go (TUG) test at baseline during acute care (day 1-12 after hip fracture surgery) and at 6 and 12 months follow-up. Subjective physical functioning (SPF) was rated for prefracture values and at 6 and 12 months follow-up using the Short Form 36 Health Survey questionnaire. Differences in TUG performance or SPF between caregivers and noncaregivers at 6 and 12 months were assessed using multivariable repeated-measures analysis adjusted for age, sex, body mass index, Charlson comorbidity index, Mini-Mental State Examination, living condition, baseline TUG, and treatment (vitamin D, home exercise program as part of the original trial). At baseline, adjusted TUG performance was better in caregivers of any kind compared with noncaregivers (40.9 vs 84.4 seconds, P < .0001). At 6 months, and after adjustment for baseline TUG performance and other covariates, TUG was better in caregivers of any kind (-6.4 seconds, P = .007) and caregivers of plants (-6.6 seconds, P = .003) compared with noncaregivers. At 12 months, only caregivers of persons had better TUG performance compared with noncaregivers (-7.3 seconds, P = .009). Moreover, at 12 months, SPF was better in caregivers of persons (58.9 vs 45.6, P = .01) and caregivers of any kind (50.8 vs 39.3, P = .02) compared with noncaregivers. Senior hip fracture patients who have a caregiver role of any kind, and especially of plants, had better short-term recovery after hip fracture assessed with the TUG. For long-term recovery, senior hip fracture patients who are caregivers for other persons appeared to have a significant benefit. These benefits were independent of baseline function and all other covariates.


A specific direct radioimmunoassay for oestriol-16alpha-glucuronide in pregnancy plasma.
A specific radioimmunoassay has been developed for measuring oestriol-16alpha glucuronide in pregnancy plasma using a highly specific antiserum. The specificity of this antiserum has been assessed by the 50% displacement method and by measuring oestriol-16alpha-glucuronide concentrations in pregnancy plasma samples, both with and without chromatography. The antiserum was found to have Ka of 1.3 X 10(10) M-1. The assay had a sensitivity of 5 pg (least quantity of oestriol-16alpha-glucuronide distinguishable from the zero point, p less than 0.05), an intra-assay variation of 6.07% and an inter-assay variation of 3.36%. The assay was used to measure plasma oestriol-16alpha-glucuronide concentrations throughout eight pregnancies, five of which were normal and three had some defined abnormality.


Self-report Pregnancy Physical Activity Questionnaire overestimates physical activity.
Physical activity (PA) research during pregnancy relies heavily on indirect/subjective measures of PA, which may be less accurate than directly measured PA. We tested whether the Pregnancy Physical Activity Questionnaire (PPAQ) could accurately estimate PA by comparing PPAQ results to directly measured PA. In a sample of 29 women who completed the PPAQ, PA was directly measured in the second trimester of pregnancy using Actical® accelerometers (valid day = 10+ hours; 4-7 valid days). Activity variables from the PPAQ were calculated using all questions, and also by only considering the leisure time section. Women were classified as 'active' or 'non-active' using Canadian PA guidelines for adults (150 minutes moderate to vigorous PA (MVPA)/ week, bouts of 10+ minutes). Bonferroni corrections were used to adjust for multiple comparisons. Data presented as mean ± standard deviation or median (interquartile range). The PPAQ overestimated MVPA by 12.12 (14.34) hours/week in the combined sample, and the difference remained substantial when investigating the non-active [overestimate = 11.54 (10.10) hrs/wk] and the active women [overestimate = 16 ± 11 hrs/wk] separately. PPAQ-measured PA variables did not correlate with any of their respective Actical®-measured variables (p > 0.008). The leisure time PPAQ questions overestimated MVPA by 1 ± 3 hrs/wk, with a positive correlation between PPAQ-leisure time MVPA and Actical®-measured MVPA (r = 0.565, p = 0.001). The PPAQ significantly overestimates MVPA and does not provide an accurate estimate of PA in pregnancy. While PPAQ leisure time questions may help distinguish trends in PA, data from subjective questionnaires may result in misinterpretation of relationships between prenatal PA and health outcomes.


A cross-over study comparing the kinetics of Tc-99m-labeled diisopropyl and p-butyl IDA analogs in patients.
Tc-99m-diisopropyl-IDA (DISIDA) and Tc-99m-p-butyl-IDA (BIDA) were compared in each of 33 patients who had serum bilirubins ranging from normal to 23.5 mg/dl. DISIDA exhibited quantitatively a higher liver uptake and faster rate of washout at all levels of bilirubinemia. There was a tendency for BIDA to have a slower blood clearance, particularly in hyperbilirubinemias exceeding 5 mg/dl. On visual comparison of the images, BIDA failed to identify the gallbladder in three icteric patients and dilated biliary tracts in two others.


[Quantitative analysis of survival during syngeneic and semisyngeneic bone marrow transplantation: relation of the protective effect and the ability to induce secondary disease as affected by differences in the major histocompatibility locus].
The protective effect of bone marrow (BM) with both syngeneic and semisyngeneic transplantation is an exponential function of the number of transplanted cells. The regression coefficient in the logarithmic equation represents a fraction of hemopoiesis repair units (HRU). The quantitative analysis of the remote death of recipients of the parents' BM shows that the secondary disease (SD) is caused by other than HRU cells which is in agreement with the data obtained by other methods. The fraction of BM cells that induces SD is lower than the fraction of HRU. This helps to find an optimum BM dose range within which the risk of the SD-induced death is minimized.


Molecular epidemiology of GII noroviruses in outpatients with acute gastroenteritis in Shandong Province, China.
Noroviruses have been recognized as the most important causative agents of acute gastroenteritis. The present study was carried out to investigate the molecular epidemiological features of genotype II (GII) norovirus in outpatients with acute gastroenteritis in Shandong province in China from July 2017 to June 2018. In total, 151 (10.30%) samples were positive for NoV GII strains by RT-PCR. Eight genotypes were detected: GII.2, GII.3, GII.4, GII.6, GII.7, GII.12, GII.13 and GII.17. GII.4 (43.71%) was the most prevalent genotype, and the dominant strains belonged to the group of Sydney-2012 strains. GII.17 (27.15%), which has become the main cause of outbreaks of acute gastroenteritis in China, also accounted for a high proportion. Meanwhile, three recombinant types (GII.P17-GII.7, GII.P3-GII.4 and GII.P12-GII.4) were observed and authenticated using Simplot software. The results showed that GII norovirus was the main cause of acute gastroenteritis in Shandong province. GII.4 and GII.17 were the dominant genotypes. Continuous observation and identification of emerging genotypes are necessary for understanding the evolution of the virus, control of infection, and development of vaccines.


Ten to fourteen year survival and functional analysis of the AGC total knee replacement system.
A study of 562 Anatomic Graduated Component (AGC) total knee arthroplasties that were performed in 402 patients between November 1986 and September 1990 is reported. All patients had implantation with a cemented posterior cruciate-retaining design, with resurfacing of the patella using all polyethylene patella components. Mean age at surgery was 71 years (range 41-92 years). Patients were followed for a minimum of 10 years (range 10-14 years). Nine knees were lost to follow-up (1.4%). The mean Knee Society Score for pain and function were analyzed by Charnley categories: Category A -- 97 (pain) and 89 (function); Category B -- 91 (pain) and 84 (function); and Category C -- 89 (pain) and 62 (function). The survival analysis at 14 years was 97% with revision for any reason as the endpoint and the authors continue to utilize this implant system.


Self-expanding metal ureteral stent for ureteral stricture: Experience of a large-scale prospective study from a high-volume center - Cross-sectional study.
The management of ureteral stricture is still a challenge for urologists. The aim of this prospective study was to assess the safety and effectiveness of self-expanding metal ureteral stents (URS) in ureteral strictures. We performed URS placement procedures for ureteral stricture from Jan 2019 to July 2020, and prospectively collect various data before and after the operation. A paired T test was used to compare continuous variables before and after surgery, binary logistic regression analysis was used to identify the independent risk predictors of surgical failure. A total of 147 patients with 157 renal units received successful placement of URS. The mean operative time was 70.0 min. After a median follow-up time of 15 months, 73.2% (115/157) of stents were kept in situ. The most common complication was hematuria (13, 8.8%), followed by urinary tract infection (11, 7.5%) and pain (8, 5.4%). The volume of hydronephrosis (67.9 ± 34.9 VS 34.9 ± 51.1 cm3, P = 0.0001), serum creatinine level (103.0 ± 54.5 VS 93.8 ± 45.1 μmol/L, P = 0.034) and blood urea nitrogen level (6.6 ± 6.7 VS 5.4 ± 2.4 mmol/L, P = 0.032) decreased significantly at last follow up when compared with baseline. Stricture of the distal ureter was an independent risk factor for stent failure (HR 1.77, 95% CI 1.15, 2.73, P = 0.009). URS was found to be safe and effective for ureteral strictures with a limited complications and good long-term results. For those who are not suitable for surgical reconstruction, the URS is an alternative management.


Arthroscopic Lunate Excision Provides Excellent Outcomes for Low-Demand Patients with Advanced Kienböck's Disease.
To examine the clinical outcomes of arthroscopic lunate excisions for advanced Kienböck's disease. Fifteen patients (six men and nine women; mean age: 65 years; range: 48-83 years) with advanced Kienböck's disease, who underwent arthroscopic lunate resection between April 2008 and March 2016, were reviewed clinically and radiographically after a follow-up of >2 years (mean: 29 months; range: 24-60 months). Clinical parameters, such as wrist range of motion, grip strength, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and patient-rated wrist evaluation (PRWE) score were evaluated. Radiographic parameters included radioscaphoid angle, scaphocapitate angle, carpal height ratio, ulnar-triquetrum distance, and the scaphoid-triquetrum distance. Wilcoxon's signed-rank test was used to compare measurement results. During the final follow-up, patients exhibited significant improvements, such as 42.9° in wrist range of motion (P = .009), 24.5% of the contralateral side in grip strength (P = .001), 26.2 points in DASH score (P = .002), and 37.8 points in PRWE score (P < .001), compared with the preoperative values. The radioscaphoid and scaphocapitate angles significantly increased by 4.8° (P = .0027) and 3.7° (P = .0012), respectively. The carpal height ratio, ulnar-triquetrum distance, and scaphoid-triquetrum distance significantly decreased by 0.05 (P < .001), 2.6 mm (P < .001), and 1.3 mm (P = .0012), respectively. Our results suggest that arthroscopic lunate excisions provided excellent postoperative pain relief and functional recovery within 2 years of follow-up. Changes in carpal alignment and stress concentration on the radial side of the carpal bones could occur in the long term; however, arthroscopic lunate excision can be a good surgical option for treating low-demand patients with advanced Kienböck's disease. Level IV, therapeutic case series.


Prophylactic pre-operative bilateral ureteric catheters for major gynaecological surgery.
The use of prophylactic pre-operative bilateral ureteric catheters for major gynaecological surgery is controversial. The aim of this study was to investigate the frequency of ureteric catheter-associated morbidity in our Unit, where systematic pre-operative ureteric catheterisation is performed. We conducted a retrospective casenote review of 337 gynaecology patients undergoing laparotomy at Salford Royal Hospital between January 2007 and September 2010. The mean age was 56.36 (range 17-89). Procedures included TAH BSO (n = 249, 74 %), BSO (n = 17, 5 %), radical hysterectomy (n = 36, 11 %), and other (n = 35, 10 %), for indications of ovarian (n = 189, 56 %), uterine (n = 88, 26 %) or cervical cancer (n = 18, 5.3 %), massive fibroids (n = 27, 8 %), severe endometriosis (n = 6, 1.78 %), or other (n = 9, 2.67 %). Bilateral ureteric catheters were attempted in most patients and successfully placed in 315/337 (93 %) patients. In 22 patients (7 %), either no ureteric catheters or a single ureteric catheter was placed due to pre-existing ureteric anomaly, technical difficulty, or surgeon choice. Bilateral ureteric catheterisation took an average of 5.4 min (SD 2.0, range 3.2-9.2) for an experienced consultant or 8.4 min (SD 3.9, range 6.4-18.6) for an SpR trainee to complete. There were no intra-operative ureteric complications. Post-operative complications included urinary tract infection (5/337 patients, 1.48 %), acute renal failure (2/337, 0.6 %), and uretero-vaginal fistulae (1/337 patients, 0.3 %). Prophylactic pre-operative ureteric catheters are quick and easy to insert and associated with low complication rates. Routine use before major gynaecological surgery can expedite intra-operative identification of the ureters and may reduce accidental ureteric injury.


Electric-field-induced local structural phenomena in relaxor ferroelectric PbSc(0.5)Nb(0.5)O3 near the intermediate temperature T* studied by Raman spectroscopy.
Raman spectroscopy at different temperatures and under an external electric field E was applied to PbSc0.5Nb0.5O3 single crystals in order to gain further insights into the mesoscopic-scale coupling processes in perovskite-type (ABO3) relaxor ferroelectrics. Parallel and cross-polarized Raman spectra were collected between 800-80 K with E applied along the cubic [1 0 0], [1 1 0] or [1 1 1] crystallographic directions. The analysis was focused on the field-induced changes in the temperature evolution of three low-energy phonon modes: the Pb-localized mode near 50 cm(-1), the Pb-BO3 translation mode near 150 cm(-1), and the B-cation-localized mode near 250 cm(-1). The results show that competitive ferroelectric (FE) and antiferroelectric (AFE) coupling exists within the system of off-centred Pb(2+) cations, within the system of off-centred B-site cations as well as between off-centred Pb(2+) and B-site cations. The strong AFE-type coupling between Pb(2+) cations along the cubic body diagonal significantly influences the coupling between the B-site cations via the Pb-BO3 mode and results in AFE-type behaviour of the 'microscopic' T* determined from the B-cation-localized mode near 250 cm(-1), which explains the previously reported non-trivial field dependence of the 'macroscopic' characteristic temperatures: the temperature of the dielectric-permittivity maximum Tm, T*, and the Burns temperature TB. The comparative analysis between PbSc0.5Nb0.5O3 and PbSc0.5Ta0.5O3 indicates that two major displacive order parameters couple to form a relaxor state in B-site complex perovskites: the FE order associated with polar shifts of B-site cations and the AFE order associated with polar shifts of A-site cations. The latter penetrates through both polar and non-polar regions, but it is highly frustrated due to the high density of translation-symmetry faults in the chemical NaCl-type B-site order. The frustrated AFE order of off-centred A-site cations might be the key factor for the existence of a relaxor state.


The effect of exercise on plasma somatomedin-C/insulinlike growth factor I concentrations.
Because inadequate intake of energy or protein causes reduction in the plasma concentrations of somatomedin-C/insulinlike growth factor I (Sm-C/IGF-I), we have completed studies to determine whether the energy deficit induced by vigorous exercise sustained for 1 week would also be associated with a reduction in this peptide. When six healthy, exercise-conditioned males were fed a diet consisting of 35 kcal/kg ideal body weight (IBW) and 1.0 g protein/kg and exercised so that 14.1 to 16.3 kcal/kg of energy was expended each day, their plasma Sm-C/IGF-I concentrations declined from a mean basal value of 1.15 +/- 0.78 U/mL (1 +/- SD) to 0.62 +/- 0.41 U/mL during the last two days of a seven-day exercise period (P less than .05). This decrease in Sm-C/IFG-I occurred almost entirely in the first four days of the study period. After 3 weeks for reacclimation, the calorie intake of each volunteer was reduced by the same number of calories as had been expended in the form of exercise during each day of the exercise week (mean of 15.1 kcal/kg IBW/d). On this regimen the mean plasma Sm-C/IGF-I declined from 1.12 +/- 0.57 U/mL, to 0.69 +/- 0.37 U/mL on the last two days of dietary restriction. The magnitude of fall with dietary restriction was not significantly different from that observed during exercise. During the last three days of the exercise period the mean daily nitrogen balance was -1.60 +/- 1.70 g/d, while this value was -3.50 +/- 1.73 g/d during the last three days of dietary restriction (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Nodal detection in malignant melanoma of the vagina using laparoscopic ultrasonography.
Primary malignant melanoma of the vagina is a rare variant of melanoma. It has worse prognosis compared to nongenital melanomas or other vaginal malignant neoplasms. A 40-year-old Chinese was diagnosed vaginal melanoma. Laparoscopic ultrasonography (USG) was used to search for abnormal pelvic and abdominal lymph nodes. Two metastatic pelvic lymph nodes were detected and excised. The vaginal tumour was removed by hysterectomy and partial vaginectomy. Despite a clear surgical margin and adjuvant radiotherapy, the patient died shortly after the operation. Patient with vaginal melanoma has grave prognosis, especially when metastatic disease presents. Radical surgery appears unjustified as a routine, it is essential to exclude lymphatic and distant metastases before embark to radical surgery. This report presents the first case of laparoscopic ultrasonographic detection of metastatic pelvic lymph nodes in patient with vaginal melanoma.


Hydration and N-acetylcysteine in acute renal failure caused by iodinated contrast medium: an experiment with rats.
The involvement of nephrotoxic agents in acute renal failure (ARF) has increased over the last few decades. Among the drugs associated with nephrotoxic ARF are the radiologic contrast media whose nephrotoxic effects have grown, following the increasing diagnostic use of these agents. We evaluated the effect of iodinated contrast (IC) medium, administered in combination, or not, with hyperhydration or N-acetylcysteine (NAC), on creatinine clearance, production of urinary peroxides and renal histology of rats. Adult Wistar rats treated for 5 days were divided into the following groups: control (saline, 3 ml/kg/day, intraperitoneally [i.p.]), IC (sodium iothalamate meglumine, 3 ml/kg/day i.p.), IC + water (12 mL water, orally + IC, 3 ml/kg/day i.p. after 1 hour), IC + NAC (NAC, 150 mg/kg/day, orally + IC, 3 ml/kg/day i.p. after 1 hour) and IC + water + NAC. IC medium reduced renal function, with maintenance of urinary flow. Hyperhydration did not reduce the nephrotoxic effect of the IC agent, which was observed in the group IC + NAC. The combination of hyperhydration and NAC had no superior protective effect compared with NAC alone. An increase in urinary peroxides was observed in the IC group, with NAC or water or the combination of both reducing this parameter. Histopathologic analysis revealed no significant alterations. In summary, given 5 days previously, NAC was found to be more effective than hyperhydration alone in the prevention of contrast-induced acute renal failure.


The isolation of a new compound from urine of humans with porphyria cutanea tarda.
A method is reported for the isolation of phyriaviolin, a new compound from human porphyria cutanea tarda urine. The substance has been crystallized and some of its properties are described.


Computed Tomography--Verified Leukoaraiosis Is a Risk Factor for Post-thrombolytic Hemorrhage.
Is computed tomography (CT)-verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage? (1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (tPA)-treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were excluded. (2) Pooled analysis with 1312 tPA-treated patients from literature. In all, 311 tPA-treated patients were included between April 2009 and July 2012. LA was present in 113 (36%). Twenty-three (7%) showed hemorrhagic transformation. LA positive patients had significantly higher hemorrhagic transformation frequency (11.5%, P = .04). LA doubled hemorrhagic transformation risk (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-5.8). Only 4 patients developed symptomatic intracerebral hemorrhage, 3 with LA. LA was not an independent risk factor for hemorrhagic transformation (P = .2). Pooled analysis of 1623 patients in total, hereof 479 LA positive patients, showed significantly higher symptomatic intracerebral hemorrhage frequency in 35 (7.3%) LA positive than that in 44 (3.8%) LA negative patients, (P = .005) and doubled symptomatic intracerebral hemorrhage risk in LA positives (OR, 1.97; 95% CI 1.22-3.19). LA doubles the risk of post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage; this finding does not support withholding thrombolysis from patients with LA.


The impact of Hydrogen peroxide on structure, stability and functional properties of Human R12C mutant αA-crystallin: The imperative insights into pathomechanism of the associated congenital cataract incidence.
The oxidative stress in eye lens which occurs during inflammation and under chronic hyperglycemia has been already indicated in the pathogenesis of cataract disorders. The aim of this study was to examine structural and functional properties of R12C mutant αA-Crystallin (αA-Cry) in the presence of hydrogen peroxide. The study was done using different spectroscopic techniques and gel mobility shift assay. According to results of our study, H2O2 oxidation strongly compromises the chaperone function of the R12C mutant but not of wild-type αA-Cry. Also, it affects the structural properties of both wild-type and mutant proteins, albeit to different degree. The H2O2 exposure promotes extensive disulfide mediated oligomerization of the R12C mutant but not of the wild-type as revealed by gel mobility shift assay and dynamic light scattering. Moreover, in the presence of hydrogen peroxide, the mutant protein demonstrates severe conformational and protease instability and increased amyloidogenic propensity. The obtained results suggest that incubation of R12C mutant recombinant αA-Cry with hydrogen peroxide accelerates the molecular events which have been already implicated in the pathomechanism of cataract development. Taken together these results suggest that individuals carrying the R12C mutation are at an increased risk to develop early-onset cataract under condition of oxidative stress.


Specific tricyclic antidepressant binding sites in rat brain.
The discovery of high-affinity binding sites for psychoactive drugs such as benzodiazepines, opiates and neuroleptics has opened up new approaches to the study of these drugs and their mechanisms of action. Although most tricyclic antidepressants inhibit neuronal uptake of noradrenaline and serotonin, their mechanism of action remains unclear. Changes in the sensitivity of the beta-receptor after chronic tricyclic antidepressant treatment suggest that they modulate noradrenergic neurotransmission. Tricyclic antidepressants also act directly on cholinergic, histaminergic, alpha-adrenergic and serotonergic receptors. It is not clear, however, which, if any, of these effects are related to the primary antidepressant effect or whether they are simply responsible for some of the side effects. We have thus investigated the possibility that specific binding sites for tricyclic antidepressants exist in the central nervous system. So far, binding studies using 3H-labelled tricyclic antidepressant drugs have only detected binding to histaminergic H2 and cholinergic muscarinic receptors and low-affinity binding. We demonstrate here a population of specific high-affinity binding sites for 3H-imipramine on brain membranes which may be responsible for the antidepressant effects of these drugs.


A 10-year follow up of ocular hypertensive patients within the Bolton Corneal Thickness Study. Can measured factors predict prognostic outcomes?
This is a case note review of a cohort of patients examining the effects of central corneal thickness (CCT), presenting intraocular pressure (IOP), age and gender on the risk of progression of ocular hypertension (OHT) to primary glaucoma (POAG) over a 10-year period. Cohort study with retrospective case note review. 58 case notes from a cohort at the Bolton Royal Infirmary initially assessed 10 years ago were reviewed again. Presenting CCT, IOP, age and gender were recorded. Development of POAG was assessed by visual field and/or optic disc changes being present. The effects of CCT, IOP, age and gender on the risk of progression of OHT to POAG were analysed in a multivariate logistic regression model following a preliminary univariate analysis. 50 out of 116 eyes developed primary open angle glaucoma over the 10-year period. Thinner CCT (odds ratio 0.985 associated with each 1mum increase in CCT), higher presenting IOP (odds ratio 1.131 associated with each 1mmHg increase in IOP) and increasing age (odds ratio 1.062 associated with each 1 year increase in age) were found to be associated with progression to POAG. Patients with a CCT of 579microm or more, a presenting intraocular pressure of 26mmHg or less and age 75 years or less had a lower risk of developing POAG within this cohort of patients.


Transient downregulation of protein O-N-acetylglucosaminylation by treatment of high-dose nicotinamide in human cells.
Nicotinamide at millimolar concentrations affects cell survival in various conditions, and is being utilized therapeutically in many human diseases. However, the effect of an acute treatment of nicotinamide at such high dose on gene expression and cellular metabolism has rarely been determined previously. In this study, we found that levels of O-N-acetylglucosamin(O-GlcNAc)ylated proteins including Sp1 acutely decreased upon treatment of 10 mM nicotinamide. Concomitantly, Sp1 protein level decreased rapidly through accelerated proteasome-mediated proteolysis. Cotreatment of glucosamine or 2-deoxyglucose, which inhibits protein deGlcNAcylation, effectively blocked the decrease induced by nicotinamide. Interestingly, the decline in the levels of Sp1 and protein O- GlcNAcylation was only transient lasting for two days post treatment, and this pattern matched closely the rapid fluctuation of the cellular [NAD+]. Our results suggest a possible link between cellular nicotinamide metabolism and protein O-GlcNAcylation, and an existence of cellular [NAD+] homeostasis.


Plastic ingestion by two cetacean groups: Ziphiidae and Delphinidae.
The presence of plastic in our environment is having a massive impact on today's marine biota. Whales and dolphins are becoming sentinels of litter pollution as plastic entanglement and ingestion affect them with unknown consequences. Although information exists about this anthropogenic interaction, the compilation of this data on metastudies is difficult due to the use of varied methodologies. A combination of our own data as well as a review of historical data was used to complete an extensive study of how cetaceans are interacting with macro and micro-litter at a global level. Here, we identify the plastic uptake by two cetacean families: Ziphiidae and Delphinidae, thus allowing for a better understanding in order to offer a global overview of their current status. Additionally, analysis was run on the plastic found in the digestive contents of stranded specimens of two Cuvier's beaked whales and fourteen striped dolphins in the Alboran Sea, in the Western Mediterranean, a hotspot for marine megafauna. Out of 623 stranded cetaceans from datasets, beaked whales displayed the highest concentration of macro, meso and microplastic in the Western Pacific Ocean. Regarding striped dolphins, Eastern Spain was the location with the highest plastic ingestion. Moreover, deep divers such as beaked whales ingested more plastic than striped dolphins which could be as a consequence of their feeding behavior or habitat. Thus, this overview provides useful information concerning conservation issues on how cetacean hotspots are highly affected by marine plastic ingestion.


Quantitative real-time polymerase chain reaction for determination of plasmid copy number in bacteria.
A method for determination of plasmid copy number (PCN) in bacteria by real-time quantitative polymerase chain reaction (QPCR) was developed as an alternative to current PCN assays. Conventional methods for PCN estimation are generally not of high throughput, laborious, have low reproducibility, require large amounts of biological samples and are applicable only for a narrow dynamic range. Real-time QPCR, using the ABI Prism 7000, was able to sensitively detect the quantity of the pUC ori based plasmid, NS3, transformed into Escherichia coli host, DH5alpha, to be 411+/-6.1. The PCN of pBR322 plasmid DNA in DH5alpha was estimated to be 40+/-0.6 which is within its previously reported PCN range of approximately 30 to 70. QPCR was found to show good reproducibility and high sensitivity in detecting a two fold difference in template concentration, and a wide linear dynamic range covering 0.5 pg to 50 ng of DNA. PCNs of DH5alpha bearing plasmids pBR322 and NS3 computed from real-time QPCR assay were validated by that of agarose gel assay, and a marginal difference of only 13.0% and 10.7% was found for the two plasmids respectively. The QPCR assay was able to detect changes in PCN of plasmid producing DH5alpha during the course of a 2 l batch fermentation.


Aeromonas hydrophila wound infection of the hand initially presenting as clostridial myonecrosis.
A traumatic hand laceration in a previously health 17-year-old boy resulted in a rapidly progressive palmar space infection, with gas formation, in the soft tissues caused by Aeromonas hydrophila. Typically associated with aquatic injuries, A. hydrophila was not initially suspected since the injury did not occur near water. Physicians treated trauma-related soft tissue infections, particularly when the initial Gram stain shows many polymorphonuclear leukocytes and gram-negative bacilli, must consider the possibility of an Aeromonas infection even if the injury occurred in a nonaquatic environment. Appropriate therapy, including vigorous wound debridement and an aminoglycoside antibiotic, will be curative in an immunologically normal host.


Exploring the antibacterial potential of magnetite/Quince seed mucilage/Ag nanocomposite: Synthesis, characterization, and activity assessment.
In this study, we present a novel core-shell antibacterial agent designed for water disinfection purposes. The nanocomposite is synthesized by combining quince seed mucilage (QSM) as the shell material and Fe3O4 as the core material. The integration of antibacterial silver nanoparticles (Ag NPs) onto the QSM shell effectively prevents agglomeration of the Ag NPs, resulting in a larger contact surface area with bacteria and consequently exhibiting enhanced antibacterial activity. The incorporation of magnetic Fe3O4 NPs with a saturation magnetization of 55.2 emu·g-1 as the core allows for easy retrieval of the nanocomposites from the medium using a strong magnetic field, enabling their reusability. The Fe3O4/QSM/Ag nanocomposite is extensively characterized using XRD, FT-IR, VSM, DLS, FE-SEM, and TEM techniques. The characterization results confirm the successful synthesis of the nanocomposites, with an average particle size of 73 nm and no contamination or impurities detected. The nanocomposites exhibit superparamagnetic properties, with a saturated magnetization of 22.69 emu·g-1, ensuring facile separation from water. The antibacterial activity of the synthesized nanocomposite is evaluated using the disk diffusion method against both Gram-positive and Gram-negative bacteria. The results reveal excellent antibacterial efficacy, with minimum inhibition concentrations (MIC) of 0.8 mg·mL-1 against E. coli and S. typhimurium. Furthermore, the measurement of released silver ions in water using ICP-OES indicates a low concentration of remaining silver ions in the medium, highlighting the controlled release of antimicrobial agents. Overall, this study provides valuable insights into the development of advanced antibacterial agents for water disinfection applications, offering potential solutions to combat microbial contamination effectively.


TiO2 nanoparticles modified graphitic carbon nitride with potential-resolved multicolor electrochemiluminescence and application for sensitive sensing of rutin.
Recently, nanocomposites with potential-resolved multicolor electrochemiluminescence (ECL) property have attracted new research interests. Herein, TiO2 nanoparticles modified graphitic carbon nitride (TiO2-NPs/g-C3N4) with inherent potential-resolved multicolor ECL emission was prepared via a simple synthesis method. The morphology and chemical composition of the synthesized TiO2-NPs/g-C3N4 were characterized. The obtained TiO2-NPs/g-C3N4 exhibited dual-peak multicolor ECL emission under cyclic voltammetry scanning by using K2S2O8 as co-reagent. The first ECL peak (ECL-1) is composed of turquoise blue ECL emission (471 nm) located at -1.3 V and olive green ECL emission (490 nm) ranging from -1.4 to -2.0 V. The second ECL peak (ECL-2) is composed of navy blue ECL emission (458 nm) located at -3.0 V. The ECL mechanism for the potential-resolved multicolor ECL emission was proposed. Furthermore, the first ECL imaging sensing method was fabricated for the sensitive quantitative detection of rutin based on the effective quenching effect of rutin on the ECL of TiO2-NPs/g-C3N4. The linear response range is 0.005-400 µM with detection limit as low as 2 nM. This work presents a simple way to prepare g-C3N4-based nanocomposites with potential-resolved multicolor ECL, which broadens the potential applications of g-C3N4-based nanocomposites for ECL imaging sensing and light-emitting devices.


Delivering the message: epimorphin and mammary epithelial morphogenesis.
The mammary gland consists of a highly branched tubular epithelium surrounded by a complex mesenchymal stroma. Epimorphin is an extracellular protein that is expressed by mammary mesenchymal cells that directs epithelial morphogenesis. Depending upon the context of presentation--polar versus apolar--epimorphin can selectively direct two key processes of tubulogenesis: branching morphogenesis (processes involved in tubule initiation and extension) and luminal morphogenesis (required for enlargement of tubule caliber). Here, we outline the fundamentals of mammary gland development and describe the function of epimorphin in these processes. We conclude with a review of recent studies that suggest similar morphogenic roles for epimorphin in other glandular organs.


Effect of N-bromosuccinimide modification on dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli. Activity, spectrophotometric, fluorescence and circular dichroism studies.
When dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli B, MB 1428, is treated with approximately a 5 mol ratio of N-bromosuccinimide (NBS) to enzyme at pH 7.2 and assayed at the same pH, there is a 40% loss of activity due to the modification of 1 histidine residue and possibly 1 methionine residue before oxidation of tryptophan occurs. The initial modification is accompanied by a shift of the pH for maximal enzymatic activity from pH 7.2 to pH 5.5 Upon further treatment with N-bromosuccinimide, the activity is gradually reduced from 60 to 0% as tryptophan residues become oxidized. An NBS to enzyme mole ratio of approximately 20 results in 90% inactivation of the enzyme. When the enzyme is titrated with NBS in 6 M guanidine HCl, 5 mol of tryptophan react per mol of enzyme, a result in agreement with the total tryptophan content as determined by magnetic circular dichroism. The 40% NBS-inactivated sample posses full binding capacity for methotrexate and reduced triphosphopyridine nucleotide, and the Km values for dihydrofolate and TPNH are the same as for the native enzyme. After 90% inactivation, only half of the enzyme molecules bind methotrexate, and the dissociation constant for methotrexate is 40 nM as compared to 4 nM for native enzyme in solutions of 0.1 M ionic strength, pH 7.2 Also, TPNH is not bound as tightly to the modified enzyme-methotrexate complex as to the unmodified enzyme-methotrexate complex. Circular dichroism studies indicate the 90% NBS-inactivated enzyme has the same alpha helix content as the native enzyme but less beta structure, while the 40% inactivated enzyme is essentially the same as the native enzyme. Protection experiments were complicated by the fact that NBS reacts with the substrates and cofactors of the enzyme. Although protection of specific residues was not determined, it was clear that TPNH was partially protected from NBS reaction when bound to the enzyme, and the enzyme, and the enzyme was not inactivated by NBS until the TPNH had reacted.


A modified incision closure for breast augmentation: remote-knot technique.
Closure techniques for breast augmentation incisions can affect wound healing with significant consequences if the incision does not heal properly. Suturing methods and materials include absorbable and nonabsorbable sutures and interrupted and continuous techniques. These choices can affect wound healing, wound strength, and wound integrity, and postoperative care. The goal of long-term incision support during wound healing, eliminating a suture knot within the incision, and decreased risk of compromise of wound healing are desired. A closure method called the "remote-knot" technique, which can be applied to other incision types, has been developed.


Interpretable AI-assisted clinical decision making (CDM) for dose prescription in radiosurgery of brain metastases.
AI modeling physicians' clinical decision-making (CDM) can improve the efficiency and accuracy of clinical practice or serve as a surrogate to provide initial consultations to patients seeking secondary opinions. In this study, we developed an interpretable AI model that predicts dose fractionation for patients receiving radiation therapy for brain metastases with an interpretation of its decision-making process. 152 patients with brain metastases treated by radiosurgery from 2017 to 2021 were obtained. CT images and target and organ-at-risk (OAR) contours were extracted. Eight non-image clinical parameters were also extracted and digitized, including age, the number of brain metastasis, ECOG performance status, presence of symptoms, sequencing with surgery (pre- or post-operative radiation therapy), de novo vs. re-treatment, primary cancer type, and metastasis to other sites. 3D convolutional neural networks (CNN) architectures with encoding paths were built based on the CT data and clinical parameters to capture three inputs: (1) Tumor size, shape, and location; (2) The spatial relationship between tumors and OARs; (3) The clinical parameters. The models fuse the features extracted from these three inputs at the decision-making level to learn the input independently to predict dose prescription. Models with different independent paths were developed, including models combining two independent paths (IM-2), three independent paths (IM-3), and ten independent paths (IM-10) at the decision-making level. A class activation score and relative weighting were calculated for each input path during the model prediction to represent the role of each input in the decision-making process, providing an interpretation of the model prediction. The actual prescription in the record was used as ground truth for model training. The model performance was assessed by 19-fold cross-validation, with each fold consisting of randomly selected 128 training, 16 validation, and 8 testing subjects. The dose prescriptions of 152 patient cases included 48 cases with 1 × 24 Gy, 48 cases with 1 × 20-22 Gy, 32 cases with 3 × 9 Gy, and 24 cases with 5 × 6 Gy prescribed by 8 physicians. IM-2 achieved slightly superior performance than IM-3 and IM-10, with 131 (86%) patients classified correctly and 21 (14%) patients misclassified. IM-10 provided the most interpretability with a relative weighting for each input: target (34%), the relationship between target and OAR (35%), ECOG (6%), re-treatment (6%), metastasis to other sites (6%), number of brain metastases (3%), symptomatic (3%), pre/post-surgery (3%), primary cancer type (2%), age (2%), reflecting the importance of the inputs in decision making. The importance ranking of inputs interpreted from the model also matched closely with a physician's own ranking in the decision process. Interpretable CNN models were successfully developed to use CT images and non-image clinical parameters to predict dose prescriptions for brain metastases patients treated by radiosurgery. Models showed high prediction accuracy while providing an interpretation of the decision process, which was validated by the physician. Such interpretability makes the model more transparent, which is crucial for the future clinical adoption of the models in routine practice for CDM assistance.


High N2O reduction potential by denitrification in the nearshore site of a riparian zone.
As a potent atmospheric greenhouse gas and a major source of ozone depletion, nitrous oxide (N2O) emission has been given increasing attention in aquatic systems, particularly at the aquatic-terrestrial interfaces, such as riparian zones. However, the microbial mechanisms regulating N2O emission in riparian zones remain unknown. Here, we measured the contributions of denitrification and ammonium oxidation to N2O emission along with the abundance and community structure of nirK-, nirS-, nosZ I- and nosZ II-harbouring bacteria in both surface sediments (0-10 cm) and overlying water along a lake riparian zone (including nearshore sites and offshore sites). Overall, the nearshore sites of the riparian zones emitted less N2O than the offshore sites. Nearshore N2O emission was dominated by denitrification with a high N2O reduction rate, whereas offshore N2O emission was driven by ammonium oxidation. Furthermore, N2O derived from ammonium oxidation was influenced by the NH4+-N content, and denitrification N2O was modulated by denitrifier communities. The N2O-producing community was dominated by nirS-harbouring bacteria, while the N2O-reducing community was dominated by nosZ I-harbouring bacteria. The relative abundance of Hydrogenophilales from nirS-denitrifiers and Chloroflexi unclassified from nosZ II-type communities influenced the N2O produced by denitrification, according to high-throughput sequencing analysis. Additionally, we also found lower levels of N2O production per unit volume in overlying water, which were 3-4 orders of magnitude less than in the surface sediment. Overall, we propose that using riparian zones can be an effective management tool for N2O mitigation by enhancing the N2O reduction process of denitrification and decreasing ammonium oxidation.


A cell-cycle-dependent protein of Physarum polycephalum revealed by two-dimensional gel electrophoresis.
Silver-stained two-dimensional polyacrylamide gels of Physarum polycephalum extracts have revealed no major changes in protein accumulation during the synchronous nuclear division cycle. However, one protein, or apparent Mr 32 000 and isoelectric point 4.9, shows a reproducible ten-fold increase in total amount between early G2 phase and metaphase. This protein represents about 0.005% of total plasmodial protein.


Different regulation of mid-size neurofilament and N-myc mRNA expression during neuroblastoma cell differentiation induced by retinoic acid.
1. Neuroblastoma (NB) is an unusual neuroectodermal tumor showing a high degree of spontaneous regression. NB cells can be induced to differentiate in vitro by various agents. Cell differentiation results in morphological changes characteristic of the mature neuronal phenotype, including outgrowth of neurite-like structures with several interconnections. 2. Recent experiments indicate that morphological differentiation of NB cells is associated with changes in expression of N-myc, c-myc, and c-myb oncogenes and synthesis of neurofilament proteins. However, little is known about the transcription of neurofilament genes during differentiation. 3. We have analyzed the expression of both the N-myc oncogene and mid-size neurofilament (NF) genes in the LAN-1 human NB cell line, cultured in the presence of retinoic acid (RA). Continuous treatment with RA induced morphological differentiation within 5-6 days. The transcription of N-myc was down-modulated within 24 hr of the initial exposure to RA. The mid-size NF mRNA was increased at this time. The expression of N-myc was not modified in serum-deprived LAN-1 cells, indicating that N-myc transcription is unaffected by the arrest of the cells in the G1 phase. 4. We conclude that new synthesis of mid-size NF mRNA and a decrease in N-myc transcription precede de novo formation of neurite-like processes and morphological cell differentiation of neuroblastoma cells.


The case for too little melatonin signalling in increased diabetes risk.
Genome-wide association studies have detected an association between type 2 diabetes risk and a non-coding SNP located in MTNR1B, the gene encoding melatonin receptor 2 (MT2). Melatonin regulates circadian rhythms and sleep and associates with metabolic disorders. However, the mechanisms underlying these actions are still unclear. Functional genomic, animal and clinical studies have not reached the same conclusions: while some studies have reported that decreased melatonin signalling increases type 2 diabetes risk, others have found the opposite. In this commentary, we have tried to provide an explanation for these contradictions and we suggest how the community may progress to reach a unified picture of the effect of melatonin and its signalling on type 2 diabetes.


[Hereditary angioedema. A clinical and immunologic contribution based on our 8 clinical cases under long-term treatment with androgens].
The literature on hereditary angioedema is reviewed and the case histories of 5 women and 3 men are reported. Special importance is attached to the results of therapy over 222 months of treatment with danazol and 40 months with stanozolol. The effects of androgen therapy on complement factor C4 and on C1-inhibitor are described.


Debunking the Neuromyth of Learning Style.
Neuromyths are an important issue in the context of the educational practice, as the misunderstanding of teachers about how the human brain works lead to educational interventions that can have a negative impact on learning. In this study, neuromyths and the problems leading to education are initially defined and identified. Then, following the presentation of the qualitative study, the findings of the case study conducted on high school students regarding the neuromyth of learning styles were highlighted. From the findings, it seems that although learners may indicate or argue that they fit a particular learning style, it is not shown that they learn better with the preferred learning style. In addition, it appears from the findings of the study that learning through multiple representations is an educational practice that contributes to learning. The above highlights the need to train in-service teachers and educate prospective teachers in the principles of educational neuroscience, so that their educational interventions can have a positive impact on students' learning.