Expression of MhcCyca class I and class II molecules in the early life history of the common carp (Cyprinus carpio L.)
In this study transcription of class I alpha chain (Cyca-UA), beta2-microglobulin (Cyca-B2m) and class II alpha (Cyca-DXA) and beta (Cyca-DAB) during the early stages of embryo development was investigated by semiquantitative PCR. No transcripts of the genes under investigation were detected in the unfertilized egg. The expression of the genes encoding for the class II molecules revealed to be synchronized starting at day 1, unlike those for the class I molecules. Transcription of Cyca-B2m was first detected at day 7, whereas Cyca-UA was already present on day 1. This discrepancy would suggest absence of class I molecules during early development. The transcription of the Mhc genes in lymphoid organs was well established on day 21, with the exception of the spleen. In later stages of ontogeny cell surface expression of class I molecules was studied using polyclonal antibodies to Cyca-UA and Cyca-B2m in conjunction with detection of surface Ig. In week 3-10 Cyca-B2m was found on a higher percentage of cells from pronephros, spleen and thymus compared to Cyca-UA, suggesting the use of an alternative class I alpha chain. In the thymus, unlike the other organs, this difference remained present in the adult stage. The most likely candidates are alpha chains encoded by non-classical class I genes.


Kunjin replicon-based simian immunodeficiency virus gag vaccines.
An RNA-based, non-cytopathic replicon vector system, based on the flavivirus Kunjin, has shown considerable promise as a new vaccine delivery system. Here we describe the testing in mice of four different SIVmac239 gag vaccines delivered by Kunjin replicon virus-like-particles. The four vaccines encoded the wild type gag gene, an RNA-optimised gag gene, a codon-optimised gag gene and a modified gag-pol gene construct. The vaccines behaved quite differently for induction of effector memory and central memory responses, for mediation of protection, and with respect to insert stability, with the SIV gag-pol vaccine providing the optimal performance. These results illustrate that for an RNA-based vector the RNA sequence of the antigen can have profound and unforeseen consequences on vaccine behaviour.


Splenosis presenting as occult gastrointestinal bleeding.
A 48-year-old man presented with recurrent gastrointestinal bleeding and anemia. Routine endoscopic evaluation was nondiagnostic. Angiography demonstrated multiple apparent arteriovenous malformations. Exploratory laparotomy revealed numerous splenic implants along the small and large bowels, some of which had apparently eroded through the bowel mucosa and bled. Excision of these penetrating lesions prevented further bleeding. An incidentally noted renal cell cancer was also resected. The patient's splenosis was the result of childhood trauma that caused splenic rupture and precipitated splenectomy. Splenosis develops frequently following traumatic splenic rupture. Experimental evidence suggests that the presence of an intact spleen suppresses the growth and development of splenic implants. Following splenectomy, splenules may replace some of the "housekeeping" and immunologic functions of the spleen, but even patients with documented splenosis should be considered functionally hyposplenic. While in most cases splenules cause no symptoms, splenosis must be considered in the differential diagnosis of previously splenectomized patients who present with unexplained masses or occult bleeding.


MRI analysis of cerebellar vermal abnormalities in bipolar disorder.
The authors sought to expand previous findings of vermal abnormalities in bipolar disorder patients. Magnetic resonance imaging (MRI) morphometry was used to quantify vermal subregion volumes in 18 subjects with first-episode bipolar disorder, 21 subjects with multiple-episode bipolar disorder, and 32 healthy subjects. Vermal subregion V2 volume was significantly smaller in multiple-episode bipolar disorder subjects than in first-episode patients and healthy subjects. Vermal subregion V3 was significantly smaller in multiple-episode bipolar disorder subjects than in healthy subjects. These results suggest that posterior-inferior cerebellar vermal abnormalities are present in patients with multiple-episode bipolar disorder.


Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665.
Therapy for gastrointestinal stromal tumors (GIST) has changed significantly with the use of imatinib mesylate (IM). Despite the success of this drug in metastatic GIST, disease progression remains a perplexing clinical issue suggesting the need for multimodality management. There have been no prospective studies either evaluating the neoadjuvant use of IM in primary GIST or as a preoperative cytoreduction agent for metastatic GIST. RTOG 0132/ACRIN 6665 was a prospective phase II study evaluating safety and efficacy of neoadjuvant IM (600 mg/day) for patients with primary GIST or the preop use of IM in patients with operable metastatic GIST. The trial continued postop IM for 2 years. Sixty-three patients were entered (52 analyzable), 30 patients with primary GIST (Group A) and 22 with recurrent metastatic GIST (Group B). Response (RECIST) in Group A was (7% partial, 83% stable, 10% unknown), in Group B (4.5% partial, 91% stable, 4.5% progression). Two-year progression free survival (Group A 83%, Group B 77%). Estimated overall survival (Group A 93%, Group B 91%). Complications of surgery and IM toxicity were minimal. This trial represents the first prospective report of preop IM in GIST. This approach is feasible, requires multidisciplinary consultations, and is not associated with notable postop complications.


Assessment of alkylimidazolium chloride ionic liquid formulations for cleaning and disinfection of environmental surfaces.
Surface disinfection is fundamental to good environmental hygiene and preventing infections. Development of newer formulations that can effectively kill and remove microorganisms from the surfaces is desired. Here, we assessed the efficacy of 1-hexadecyl-3-methylimidazolium chloride [C16MIM][Cl] ionic liquid (IL) and its formulation in ethanol for killing and removing bacteria from different environmental surfaces. Efficacy of IL and its formulation was determined on known monospecies bacterial cultures and unknown multispecies bacterial cultures on environmental surfaces. The surface disinfection efficacy of [C16MIM][Cl] was concentration dependent and achieved 41 to 100% reduction in total viable bacterial counts of Gram positive and Gram negative bacteria at varied concentrations. The treatment of wooden surface with 0.1% [C16MIM][Cl] caused 98% reduction in bacterial load within 20 s contact time as against mere 45% reduction (20 s) with 70% ethanol. Antibacterial and surface disinfection activities of [C16MIM][Cl] have increased markedly when prepared in 70% ethanol, suggesting synergistic activity. A formulation comprising of 0.01% [C16MIM][Cl] in 70% ethanol showed effective surface disinfection and achieved 95% to 98% reduction in bacterial load on different surfaces. Ionic liquids are potent candidates for disinfection of environmental surfaces.


Keratoacanthoma arising after site injection infection of cosmetic collagen filler.
Over one million treatments in more than 40 countries have been administered Zyplast implants. Infections at collagen implant sites have occurred in fewer than one per thousand treated patients. We present a case report of a 27-year-old man; he developed a severe granulomatous reaction in the site of resolvable collagen filler injection Zyplast, and one month later developed a cutaneous nodular lesion. Histological examination of the lesion revealed Keratoacanthoma (KA) with surgical margins free of tumor. We performed two surgical corrections within a period of six months on multiple hypertrophic skin scars of the face. Two years after the last excision, the patient continued to be free of any recurrence. Keratoacanthoma (KA) is a benign skin tumor with a quick growth pattern but may regress spontaneously. Though the exact etiology of KA is uncertain, it is found to be more frequent in elderly people, on photo-exposed skin areas and cutaneous infection site. Bovine collagen intradermal injections, though catabolized over the time in the patient, can raise several complications already described in technical literature, but we want underline that cutaneous infection near filler injection site can develope KA as described in our case report. KA must be considered as a new local unforeseeable complication of bovine collagen injection to fill facial soft tissue when occurred a face cutaneous infection. We believe that radical excision is the golden standard.


Chemoembolization of hepatocellular carcinomas. A study of the biodistribution and pharmacokinetics of doxorubicin.
This study evaluated the effects of an association of ethiodized oil (Lipiodol Ultra Fluide, Laboratoires Guerbet, Aulnay-sous-Bois, France), with or without gelatin sponge, with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) on the biodistribution and kinetics of doxorubicin during intraarterial injection. Eighteen patients with hepatocellular carcinoma on cirrhotic liver received a therapeutic injection into the hepatic artery of 50 mg of doxorubicin alone (Group 1; n = 4), or emulsified in 10 ml of ethiodized oil and 2.5 ml of ioxaglate (Hexabrix, Laboratoires Guerbet) with (Group 2; n = 7) or without (Group 3; n = 7) gelatin sponge embolization. Before treatment, the absence of intrahepatic shunts was verified by an injection of technetium-labeled albumin macroaggregates. The biodistribution of doxorubicin was studied on two fronts: (1) pharmacokinetic--by measurement of the doxorubicin blood level during the 48 hours after injection; and (2) scintigraphic (2 mg of doxorubicin were labeled with 2 mCi of iodine 131)--by examination of the scintigrams and calculation of the following parameters: tumours liver/nontumorous liver binding ratio (T/NT ratio), liver/liver+lungs+abdomen binding ratio, and doxorubicin half-life in tumorous tissue. Pharmacokinetics results showed the following: the peak plasma concentration was significantly higher in Group 1 as compared with Groups 2 or 3 (Group 1: 2.1 +/- 0.9 mg/ml; Group 2: 0.9 +/- 0.3 mg/ml; Group 3: 0.5 +/- 0.2 mg/ml); the area under curve calculated from time zero to 1 hour was lower in Groups 2 and 3 compared with Group 1. Examination of the scintigrams showed the following: diffuse activity throughout the organism (Group 1), diffuse activity with strong hepatic and tumorous binding (Group 2), and mostly hepatic and tumoral binding (Group 3). The liver/liver+lungs+abdomen binding ratio was 28% +/- 1% in Group 1, 36% +/- 5% in Group 2, and 63% +/- 7% in Group 3. The T/NT ratios were 1.0 +/- 0 (Group 1), 1.5 +/- 0.1 (Group 2), and 4.7 +/- 0.5 (Group 3). The doxorubicin half-lives in tumourous tissue were 0.7 +/- 0.1 days (Group 1), 1.8 +/- 0.2 days (Group 2), and 2.6 days (n = 1; Group 3). This study shows (1) that the association of ethiodized oil with doxorubicin lowers the peak concentration of doxorubicin and increases the intratumoral concentration and half-life of doxorubicin, and (2) that these kinetic ameliorations are even more pronounced after embolization. Therefore, from a kinetic standpoint, the doxorubicin-ethiodized oil-gelatin sponge association is the best.


Hedgehog-Gli signalling and the growth of the brain.
The development of the vertebrate brain involves the creation of many cell types in precise locations and at precise times, followed by the formation of functional connections. To generate its cells in the correct numbers, the brain has to produce many precursors during a limited period. How this is achieved remains unclear, although several cytokines have been implicated in the proliferation of neural precursors. Understanding this process will provide profound insights, not only into the formation of the mammalian brain during ontogeny, but also into brain evolution. Here we review the role of the Sonic hedgehog-Gli pathway in brain development. Specifically, we discuss the role of this pathway in the cerebellar and cerebral cortices, and address the implications of these findings for morphological plasticity. We also highlight future directions of research that could help to clarify the mechanisms and consequences of Sonic hedgehog signalling in the brain.


[Results of balloon kyphoplasty in the treatment of osteoporotic vertebral compression fractures].
The aim of this study was to evaluate the reduction of pain, improvement of sagittal alignment, complications and intermediate term results of balloon kyphoplasty in the treatment of osteoporotic vertebral compression fractures (VCF). The study group consisted of 87 patients with 145 VCFs which were not responsive to non-operative treatment. All data were collected prospectively. Improvement of sagittal alignment (Cobb and kyphotic angles, anterior, middle and posterior height) was determined from CT scans. Pain was evaluated by means of a visual analogue scale (VAS). Postoperative CT scans revealed a significant reduction of the mean kyphotic angle of 5.7 degrees (range 2-24 degrees ) and a significant reduction of pain from 7.8+/-2.4 to 2.0+/-1.5 in the VAS (improvement of pain in 95.5% of patients). An asymptomatic leakage of cement was observed in 28 out of 145 vertebrae (19.3%). The outcome of 35 patients with 51 VCFs was evaluated after a mean of 13 (range 12-70) months (CT and VAS) and there was a persisting reduction of pain and no loss of reduction. In this group of patients new symptomatic fractures were evident in 4 and clinically asymptomatic (only seen on CT) fractures were detected in 5 out of 35 patients, 7 fractures were adjacent to and 2 fractures were remote from the initially treated level. In two patients an asymptomatic moderate loss of reduction was detected. These intermediate term results indicate that kyphoplasty reduces pain and improves sagittal alignment in patients with VCF. However, in 26% of patients new fractures occurred, predominantly in adjacent levels but approximately 50% of these fractures were clinically asymptomatic.


FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.
FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis. We report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome. A total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150-380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1-1:32), while the median serum MOG antibody titer was 1:32 (1:10-1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike-slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses. FLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.


AHR-related activities in a creosote-adapted population of adult atlantic killifish, Fundulus heteroclitus, two decades post-EPA superfund status at the Atlantic Wood Site, Portsmouth, VA USA.
Atlantic killifish, Fundulus heteroclitus, are adapted to creosote-based PAHs at the US EPA Superfund site known as Atlantic Wood (AW) on the southern branch of the Elizabeth River, VA USA. Subsequent to the discovery of the AW population in the early 1990s, these fish were shown to be recalcitrant to CYP1A induction by PAHs under experimental conditions, and even to the time of this study, killifish embryos collected from the AW site are resistant to developmental deformities typically associated with exposure to PAHs in reference fish. Historically, however, 90 +% of the adult killifish at this site have proliferative hepatic lesions including cancer of varying severity. Several PAHs at this site are known to be ligands for the aryl hydrocarbon receptor (AHR). In this study, AHR-related activities in AW fish collected between 2011 and 2013 were re-examined nearly 2 decades after first discovery. This study shows that CYP1A mRNA expression is three-fold higher in intestines of AW killifish compared to a reference population. Using immunohistochemistry, CYP1A staining in intestines was uniformly positive compared to negative staining in reference fish. Livers of AW killifish were examined by IHC to show that CYP1A and AHR2 protein expression reflect lesions-specific patterns, probably representing differences in intrinsic cellular physiology of the spectrum of proliferative lesions comprising the hepatocarcinogenic process. We also found that COX2 mRNA expression levels were higher in AW fish livers compared to those in the reference population, suggesting a state of chronic inflammation. Overall, these findings suggest that adult AW fish are responsive to AHR signaling, and do express CYP1A and AHR2 proteins in intestines at a level above what was observed in the reference population.


An innovative safe anesthesia and analgesia package for emergency pediatric procedures and surgeries when no anesthetist is available.
Adequate pain control through sedation and anesthesia for emergency procedures is a crucial aspect of pediatric emergency care. Resources for administering such anesthesia are extremely limited in many low-income settings. Non-anesthetist providers in Western Kenya were trained in the use of a ketamine-based sedation and anesthesia package for non-anesthetists, Every Second Matters for Mothers and Babies-Ketamine™ (ESM-Ketamine). Data on use and safety of this package for emergent and urgent pediatric procedures was collected. Providers were surveyed as to what they would have done for similar procedures if the ESM-Ketamine package were unavailable. Ninety procedures were completed for 77 pediatric patients utilizing the ESM-Ketamine package. Of these, 29 (32.2 %) cases were orthopedic reductions, 19 (21.1 %) were incision and drainage, and 19 (21.1 %) were debridement and irrigation of burns. Remaining cases included cesarean section, repair of perineal tear, foreign body removal, arthrocentesis, laceration repair, exploratory laparotomy, excision of mass, paracentesis, and circumcision. There were no serious adverse events in any of the cases, 17 % experienced minor adverse events including hypersalivation, hallucinations, or brief, self-resolving, oxygen desaturations. Providers were surveyed for 80 of the 90 cases as to what they would have done in the absence of the ESM-Ketamine package: in 26 cases (32.5 %), they reported they would proceed with the procedure without any anesthesia or analgesia; in 15 (18.75 %), they reported they would significantly delay the procedure while waiting for an anesthetist; in 13 (16.25 %), they reported they would attempt referral to another facility; and in 26 (32.5 %), they reported they would try using an alternate form of analgesia, primarily acetaminophen, ibuprofen, diclofenac, and/or diazepam. All surveyed providers reported they would use the ESM-Ketamine package again in similar cases. The ESM-Ketamine package, through the use of a simplified protocol and checklist, allows for safe analgesia and anesthesia in children by non-anesthetists in a resource-limited setting for selected emergent and urgent procedures. This package addresses a significant gap in the availability of anesthesia services in low-income settings that would otherwise result in significant delays to procedures or proceeding with painful procedures with inadequate analgesia.


The fractal dimension as a measure for characterizing genetic variation of the human genome.
Motivated by the characteristics of highly clustered single nucleotide polymorphism (SNP) across the human genome, we propose a set of chromosome-wise fractal dimensions as a measure for identifying an individual for human polymorphism. The fractal dimension quantifies the degree of clustered distribution of SNPs and represents parsimoniously the genetic variation in a chromosome. In this sense, the proposed scheme projects the SNP genotype data into a new space which is simpler and lower in dimension. As an illustrative example, we estimate the chromosome-wise fractal dimensions of SNPs that are extracted from the HapMap of Phase III data set. To determine the validity of the proposed measure, we apply principal component analysis (PCA) to the set of estimated fractal dimensions and demonstrate that the set more or less described the population structure of 11 global populations. We also use multidimensional scaling to relate the genetic distances based on PCA to the geographical distances between global populations. This shows that, similar to the SNP genotype data, the fractal dimensions also has a role in genetic distance in the population structure. In addition, we apply the proposed measure to a signature for the classification of global populations by developing a support vector machine model. The selected feature model predicts the global population with a balanced accuracy of about 77%. These results support that the fractal dimension is an efficient way to describe the genetic variation of global populations.


A chromatin code for alternative splicing involving a putative association between CTCF and HP1α proteins.
Alternative splicing is primarily controlled by the activity of splicing factors and by the elongation of the RNA polymerase II (RNAPII). Recent experiments have suggested a new complex network of splicing regulation involving chromatin, transcription and multiple protein factors. In particular, the CCCTC-binding factor (CTCF), the Argonaute protein AGO1, and members of the heterochromatin protein 1 (HP1) family have been implicated in the regulation of splicing associated with chromatin and the elongation of RNAPII. These results raise the question of whether these proteins may associate at the chromatin level to modulate alternative splicing. Using chromatin immunoprecipitation sequencing (ChIP-Seq) data for CTCF, AGO1, HP1α, H3K27me3, H3K9me2, H3K36me3, RNAPII, total H3 and 5metC and alternative splicing arrays from two cell lines, we have analyzed the combinatorial code of their binding to chromatin in relation to the alternative splicing patterns between two cell lines, MCF7 and MCF10. Using Machine Learning techniques, we identified the changes in chromatin signals that are most significantly associated with splicing regulation between these two cell lines. Moreover, we have built a map of the chromatin signals on the pre-mRNA, that is, a chromatin-based RNA-map, which can explain 606 (68.55%) of the regulated events between MCF7 and MCF10. This chromatin code involves the presence of HP1α, CTCF, AGO1, RNAPII and histone marks around regulated exons and can differentiate patterns of skipping and inclusion. Additionally, we found a significant association of HP1α and CTCF activities around the regulated exons and a putative DNA binding site for HP1α. Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1α and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1α and AGO1 in chromatin-related splicing regulation.


Measurement of diffuse reflectance from combinatorial samples.
Using a luminescence spectrometer as a platform, a system of fibre-optic probes was created that allows full colour characterisation, fluorescence and phosphorescence spectra to be recorded in diffuse reflectance and in transmission from thick or thin film arrays of combinatorial samples of diameter down to 2 mm and from liquids. An integrating sphere is not required and the method is more versatile than the instrument's fibre-optic plate reader which has conjoined fibre bundles set at a fixed angle. Incident and detected light is routed via separate optical fibre bundles which remain stationary above or below a two-axis table. The validation and calibration are described. A library of 25 members was scanned for both diffuse reflectance (colour) and fluorescence in less than an hour. The method thus combines techniques that conventionally rely on different instruments and makes them amenable for high throughput libraries.


Bakke Redux - Affirmative Action and Physician Diversity in Peril.
This article examines the legal arguments that may lead the Supreme Court to overrule precedent and strike down affirmative action in university admissions. Given the critical importance of a diverse physician workforce for our Nation's health care system, the potential reversal of affirmative action admission programs in medical schools may have severe negative consequences. This article discusses the implications for health care should the Court issue an opinion restricting or eliminating affirmative action in higher education.


A method for the purification of placental protein 5 (PP5) from placental extracts.
We describe a method for the preparation of purified PP5 suitable for use as a tracer ligand in RIA. The method is based on the observation that PP5 will bind to heparin and employs a heparin-Sepharose column as a key step in the procedure.


Co-polymerization of penta-halogenated phenols in humic substances by catalytic oxidation using biomimetic catalysis.
A synthetic water-soluble meso-tetra(2,6-dichloro-3-sulfonatophenyl)porphyrinate of iron(III) chloride, Fe-(TDCPPS)Cl, was employed to catalyze the oxidative co-polymerization of penta-halogenated phenols in two humic materials of different origin. Co-polymerization of pentachlorophenol (PCP) was followed by high-performance size-exclusion chromatography (HPSEC), the unbound PCP recovered from reacting humic solutions was evaluated by gas-chromatography/electron capture detector, and the oxidative catalyzed coupling of pentafluorophenol (PFP) into humic matter was assessed by liquid-state (19)F-NMR spectroscopy. HPSEC showed that the catalyzed oxidative coupling between PCP and humic molecules increased the apparent weight-average molecular weight (M(w)) values in both humic substances. HPSEC further indicated that the co-polymerization reaction turned the loosely bound humic supramolecular structures into more stable conformations, which could no longer be disrupted by the disaggregating effect of acetic acid. The occurrence of covalent linkages established between PCP and humic molecules was also suggested by the very little amount of PCP found free in solution after the catalyzed co-polymerization. (19)F-NMR spectroscopy suggested that also PFP could be oxidatively coupled to humic materials. PFP-humic co-polymerization reaction produced (19)F-spectra with many more (19)F signals and wider chemical shifts spread than for PFP alone or PFP subjected to catalyzed coupling without humic matter. These findings show that biomimetic iron-porphyrin is an efficient catalyst for the covalent binding of polyhalogenated phenols to humic molecules, thereby suggesting that the co-polymerization reaction may become a useful technology to remediate soils and waters contaminated by polyhalogenated phenols and their analogues.


Data-Driven Pupil Response Profiles as Transdiagnostic Readouts for the Detection of Neurocognitive Functioning in Affective and Anxiety Disorders.
Neurocognitive functioning is a relevant transdiagnostic dimension in psychiatry. As pupil size dynamics track cognitive load during a working memory task, we aimed to explore if this parameter allows identification of psychophysiological subtypes in healthy participants and patients with affective and anxiety disorders. Our sample consisted of 226 participants who completed the n-back task during simultaneous functional magnetic resonance imaging and pupillometry measurements. We used latent class growth modeling to identify clusters based on pupil size in response to cognitive load. In a second step, these clusters were compared on affective and anxiety symptom levels, performance in neurocognitive tests, and functional magnetic resonance imaging activity. The clustering analysis resulted in two distinct pupil response profiles: one with a stepwise increasing pupil size with increasing cognitive load (reactive group) and one with a constant pupil size across conditions (nonreactive group). A larger increase in pupil size was significantly associated with better performance in neurocognitive tests in executive functioning and sustained attention. Statistical maps of parametric modulation of pupil size during the n-back task showed the frontoparietal network in the positive contrast and the default mode network in the negative contrast. The pupil response profile of the reactive group was associated with more thalamic activity, likely reflecting better arousal upregulation and less deactivation of the limbic system. Pupil measurements have the potential to serve as a highly sensitive psychophysiological readout for detection of neurocognitive deficits in the core domain of executive functioning, adding to the development of valid transdiagnostic constructs in psychiatry.


Mechanisms involved in gene electrotransfer using high- and low-voltage pulses--an in vitro study.
Gene electrotransfer is an established method for gene delivery which uses high-voltage pulses to increase permeability of cell membrane and thus enables transfer of genes. Currently, majority of research is focused on improving in vivo transfection efficiency, while mechanisms involved in gene electrotransfer are not completely understood. In this paper we analyze the mechanisms of gene electrotransfer by using combinations of high-voltage (HV) and low-voltage pulses (LV) in vitro. We applied different combinations of HV and LV pulses to CHO cells and determined the transfection efficiency. We obtained that short HV pulses alone were sufficient to deliver DNA into cells for optimal plasmid concentrations and that LV pulse did not increase transfection efficiency, in contrast to reported studies in vivo. However, for sub-optimal plasmid concentrations combining HV and LV pulses increased transfection rate. Our results suggest that low-voltage pulses increase transfection in conditions where plasmid concentration is low, typically in vivo where mobility of DNA is limited by the extracellular matrix. LV pulses provide additional electrophoretic force which drags DNA toward the cell membrane and consequently increase transfection efficiency, while for sufficiently high concentrations of the plasmid (usually used in vitro) electrophoretic LV pulses do not have an important role.


The optic nerve of the brush-tailed possum, Trichosurus vulpecula: fibre diameter spectrum and conduction latency groups.
The principal findings of this report on the morphology and electrophysiology of the possum optic nerve are: (i) There are about 230,000 fibres in the optic nerve. This fibre count, based on electron microscopy, is slightly less than a previously reported estimate of the total number of ganglion cells in the possum retina. (ii) The majority (greater than 98%) of the fibres of the optic nerve are myelinated axons of retinal ganglion cells. The diameters of these fibres range from 0.4--4.6 micrometer (axon diameter range: 0.3--3.8 micrometer) and the frequency distribution of the fibre diameters (and axon diameters) is positively skewed and unimodal. (iii) The antidromic compound action potential of the possum optic nerve shows four negative peaks following stimulation of the optic chiasm. These peaks are associated with four conduction latency groups of fibres which have been designated t1, t2, t3 and t4 in order of increasing conduction latency. (iv) The mean peak conduction velocities of the fibres in the conduction latency groups are 13.1 ms-1 (t1), 8.1 ms-1 (t2), 5.7 ms-1 (t3) and 3.1 ms-1 (t4). (v) There is no direct correlation between the frequency distribution of fibre (or axon) diameters as measured by electron microscopy of transverse sections of fixed optic nerve and the conduction latency groups. (vi) The reconstruction of the possum optic nerve compund action potential on the basis of either axon or fibre diameter frequency distribution does not provide an acceptable, indirect correlation between the morphology and the electrophysiology of this optic nerve.


Is Raman Optical Activity Spectroscopy Sensitive to β-Turns in Proteins? Secondary Structure and Side-Chain Dependence.
β-turns are essential for the structure and function of proteins. The spectroscopic technique Raman optical activity (ROA) has been suggested to be sensitive to such structural elements of proteins in solution. Three spectral features have been reported to mark β-turns in protein ROA spectra: being a negative band at 1220 cm-1 , positive intensity around 1290 cm-1 and negative intensity around 1340-1380 cm-1 . In this work, density functional theory calculations demonstrated that these assignments are inaccurate as these spectral regions are not robust and sense the exact secondary structure surrounding the β-turn as well. Furthermore, it was demonstrated that the amino acid side-chains affect the exact ROA patterns which can direct future research to perform a systematic analysis of the contributions of the side-chains.


A standardized block fabrication technique.
The accuracy of delivered dose is a primary goal in every radiation therapy department. Improved imaging techniques now enable the radiation therapist to define more precisely the area of interest, which helps the sparing of normal surrounding tissue. Tray-mounted customized blocks are routinely used to define this treatment portal accurately and reproducibly. However, the level of accuracy is dependent on the block fabrication technique and the skill of the block cutter. We at Moffitt Cancer Center have standardized our system in a way that minimizes some of the human errors, while keeping the procedure fast and accurate. This system uses a tray template that simulates our blocking trays. The function of this tray is to position the styrofoam (and therefore the cerrobend block) on the tray in such a way as to insure proper alignment with the treatment machine. We also feel this improves upon some common designs using random holes or hole patterns, which may interfere with the treatment area. This system is not overly sophisticated and can be easily implemented in most radiation therapy departments.


Cell Deformation by Single-beam Acoustic Trapping: A Promising Tool for Measurements of Cell Mechanics.
We demonstrate a noncontact single-beam acoustic trapping method for the quantification of the mechanical properties of a single suspended cell with label-free. Experimentally results show that the single-beam acoustic trapping force results in morphological deformation of a trapped cell. While a cancer cell was trapped in an acoustic beam focus, the morphological changes of the immobilized cell were monitored using bright-field imaging. The cell deformability was then compared with that of a trapped polystyrene microbead as a function of the applied acoustic pressure for a better understanding of the relationship between the pressure and degree of cell deformation. Cell deformation was found to become more pronounced as higher pressure levels were applied. Furthermore, to determine if this acoustic trapping method can be exploited in quantifying the cell mechanics in a suspension and in a non-contact manner, the deformability levels of breast cancer cells with different degrees of invasiveness due to acoustic trapping were compared. It was found that highly-invasive breast cancer cells exhibited greater deformability than weakly-invasive breast cancer cells. These results clearly demonstrate that the single-beam acoustic trapping technique is a promising tool for non-contact quantitative assessments of the mechanical properties of single cells in suspensions with label-free.


K-channel blockers attenuate the presynaptic effects of the D2/D3 agonist quinpirole in monkeys.
The present study investigated whether potassium channel blockade could modify the behavioral effects of the dopamine D2/D3 receptor agonist quinpirole in squirrel monkeys. The duration of immobility and/or unusual postures indicative of catalepsy-associated behavior or the duration of scratching, known to be related to the effects of low and high doses, respectively, of quinpirole, were scored during 5-min observation periods in three squirrel monkeys. Saline or incremental doses of quinpirole were administered 10 min before each observation period. Administration of saline did not increase the durations of catalepsy-associated behavior (8% of the observational period) or scratching (< 1% of the observational period). Low doses of quinpirole (0.003-0.03 mg/kg) dose dependently increased the duration of catalepsy-associated behavior to approximately 54% of the observational periods. Higher doses of quinpirole (0.1-0.3 mg/kg) did not increase the duration of catalepsy; rather, these doses increased the duration of scratching to approximately 57% of the observational periods. The differential induction of catalepsy-associated behavior or scratching is believed to be related to, respectively, pre- and postsynaptic activity of quinpirole on dopamine D2/D3 receptors. Pretreatment with the potassium channel blockers apamin, 4-aminopyridine, and amodiaquin attenuated the effects of quinpirole (0.03 mg/kg) on catalepsy-associated behavior, with cataleptic postures maintained for 27, 21, and 24% of the observational periods, respectively. In contrast, pretreatment with potassium channel blockers did not consistently affect the scratching induced by quinpirole. In addition, apamin did not attenuate the catalepsy-associated behavior induced by the postsynaptic D2 receptor antagonist haloperidol (0.01-0.1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)


Colloidal synthesis of monodisperse trimetallic Pt-Fe-Ni nanocrystals and their enhanced electrochemical performances.
Among the multi-metallic nanocatalysts, Pt-based alloy nanocrystals (NCs) have demonstrated promising performance in fuel cells and water electrolyzers. Herein, we demonstrate a facile colloidal synthesis of monodisperse trimetallic Pt-Fe-Ni alloy NCs through a co-reduction of metal precursors. The as-synthesized ternary NCs exhibit superior mass and specific activities toward oxygen reduction reaction (ORR), which are ∼2.8 and 5.6 times as high as those of the benchmark Pt/C catalyst, respectively. The ORR activity of the carbon-supported Pt-Fe-Ni nanocatalyst is persistently retained after the durability test. Owing to the incorporation of Fe and Ni atoms into the Pt lattice, the as-prepared trimetallic Pt-alloy electrocatalyst also manifestly enhances the electrochemical activity and durability toward the oxygen evolution reaction with a reduced overpotential when compared with that of the benchmark Pt/C (△η= 0.20 V, at 10 mA cm-2). This synthetic strategy paves the way for improving the reactivity for a broad range of electrocatalytic applications.


Watch out for the hazard! Blurring peripheral vision facilitates hazard perception in driving.
The objectives of this paper were to directly examine the roles of central and peripheral vision in hazard perception and to test whether perceptual training can enhance hazard perception. We also examined putative cortical mechanisms underpinning any effect of perceptual training on performance. To address these objectives, we used the gaze-contingent display paradigm to selectively present information to central and peripheral parts of the visual field. In Experiment 1, we compared hazard perception abilities of experienced and inexperienced drivers while watching video clips in three different viewing conditions (full vision; clear central and blurred peripheral vision; blurred central and clear peripheral vision). Participants' visual search behaviour and cortical activity were simultaneously recorded. In Experiment 2, we determined whether training with clear central and blurred peripheral vision could improve hazard perception among non-licensed drivers. Results demonstrated that (i) information from central vision is more important than information from peripheral vision in identifying hazard situations, for screen-based hazard perception tests, (ii) clear central and blurred peripheral vision viewing helps the alignment of line-of-gaze and attention, (iii) training with clear central and blurred peripheral vision can improve screen-based hazard perception. The findings have important implications for road safety and provide a new training paradigm to improve hazard perception.


Antro-pyloric canal values from early prematurity to full-term gestational age: an ultrasound study.
To evaluate antro-pyloric canal dimensions from early prematurity to full-term gestational age. Ninety infants with no signs of regurgitation or vomiting were studied 3-5 days after birth. Their gestational ages ranged from 26 to 41 weeks (mean 33.7 weeks) and the body weight from 670 to 4150 g (mean 2067 g). Antro-pyloric muscle thickness, canal length and canal width were measured. A positive correlation between gestational age, muscle thickness (R = 0.71, P < 0.001), length (R = 0.63, P < 0.001) and width (R = 0.42, P < 0.001) was found. Furthermore, a positive correlation between body weight, muscle thickness (R = 0.82, P < 0.001) length, (R = 0.67, P < 0.001) and width (R = 0.55, P < 0.001) was observed. This study shows that antro-pyloric canal dimensions increase with gestational age. Moreover, it provides normal values for muscle thickness, canal length and canal width from the early gestation to full term.


COVID-19, smoking, vaping and quitting: a representative population survey in England.
To estimate (1) associations between self-reported COVID-19, hand-washing, smoking status, e-cigarette use and nicotine replacement therapy (NRT) use and (2) the extent to which COVID-19 has prompted smoking and vaping quit attempts and more smoking inside the home. Cross-sectional household surveys. A representative sample of the population in England from April to May 2020. The sample included 3179 adults aged ≥ 18 years. Participants who reported that they definitely or thought they had coronavirus were classified as having self-reported COVID-19. Participants were asked how often they wash their hands after returning home, before preparing foods, before eating or before touching their face. They were also asked whether, due to COVID-19, they had (i) attempted to quit smoking, (ii) attempted to quit vaping and (iii) changed the amount they smoke inside the home. Odds of self-reported COVID-19 were significantly greater among current smokers [20.9%, adjusted odds ratio (aOR) = 1.34, 95% confidence interval (CI) = 1.04-1.73] and long-term (> 1-year) ex-smokers (16.1%, aOR = 1.33, 95% CI = 1.05-1.68) compared with never smokers (14.5%). Recent (< 1-year) ex-smokers had non-significantly greater odds of self-reported COVID-19 (22.2%, aOR = 1.50, 95% CI = 0.85-2.53). Bayes factors indicated there was sufficient evidence to rule out large differences in self-reported COVID-19 by NRT use and medium differences by e-cigarette use. With the exception of hand-washing before face-touching, engagement in hand-washing behaviours was high (> 85%), regardless of nicotine use. A minority (12.2%) of quit attempts in the past 3 months were reportedly triggered by COVID-19, and approximately one in 10 current e-cigarette users reported attempting to quit vaping because of COVID-19. In England, current smokers and long-term ex-smokers appear to have higher odds of self-reported COVID-19 compared with never smokers in adjusted analyses, but there were no large differences between people who used nicotine replacement therapy or e-cigarettes. Engagement in hand-washing appears to be high, regardless of nicotine or tobacco use. A minority of past-year smokers and current e-cigarette users, respectively, report attempting to quit smoking/vaping due to COVID-19.


Human-driven spatiotemporal distribution of phosphorus flux in the environment of a mega river basin.
Large river basins transport considerable nutrients to the ocean every year. However, phosphorus (P) generated by human activities not only threatens aquatic ecosystem health in the river basin, but also has a negative effect on the estuary water environment. To better understand the environmental effects of anthropogenic P in a mega basin, we examined its inputs and distribution characteristics, and analyzed the factors driving it in the Yangtze River Basin (YRB) and sub-catchments. Anthropogenic P flux in the sub-catchments gradually increased from upper to lower reaches, and hotspots were primarily concentrated in traditional agricultural areas such as the Sichuan Basin and the Middle-Lower Yangtze plains. Agricultural sources were the main anthropogenic P inputs, of which fertilizer P was the leading contributor and driver of P changes, but livestock manure also accounted for a high proportion. Presently, anthropogenic P inputs in the YRB are considerably higher than in other parts of the world. Although long-distance transportation allows some P from the entire basin to be deposited in freshwater, a large amount of P still reaches the estuary and has a negative effect on water quality, outweighing the influence of local coastal inputs. To maintain the ecological health of the river basin and estuary, it will be necessary to further improve P utilization efficiency and encourage greater cooperation between different regions in the river basin.


Efficacy of occupational therapy for patients with Parkinson's disease: a randomised controlled trial.
There is insufficient evidence to support use of occupational therapy interventions for patients with Parkinson's disease. We aimed to assess the efficacy of occupational therapy in improving daily activities of patients with Parkinson's disease. We did a multicentre, assessor-masked, randomised controlled clinical trial in ten hospitals in nine Dutch regional networks of specialised health-care professionals (ParkinsonNet), with assessment at 3 months and 6 months. Patients with Parkinson's disease with self-reported difficulties in daily activities were included, along with their primary caregivers. Patients were randomly assigned (2:1) to the intervention or control group by a computer-generated minimisation algorithm. The intervention consisted of 10 weeks of home-based occupational therapy according to national practice guidelines; control individuals received usual care with no occupational therapy. The primary outcome was self-perceived performance in daily activities at 3 months, assessed with the Canadian Occupational Performance Measure (score 1-10). Data were analysed using linear mixed models for repeated measures (intention-to-treat principle). Assessors monitored safety by asking patients about any unusual health events during the preceding 3 months. This trial is registered with ClinicalTrials.gov, NCT01336127. Between April 14, 2011, and Nov 2, 2012, 191 patients were randomly assigned to the intervention group (n=124) or the control group (n=67). 117 (94%) of 124 patients in the intervention group and 63 (94%) of 67 in the control group had a participating caregiver. At baseline, the median score on the Canadian Occupational Performance Measure was 4·3 (IQR 3·5-5·0) in the intervention group and 4·4 (3·8-5·0) in the control group. At 3 months, these scores were 5·8 (5·0-6·4) and 4·6 (4·6-6·6), respectively. The adjusted mean difference in score between groups at 3 months was in favour of the intervention group (1·2; 95% CI 0·8-1·6; p<0·0001). There were no adverse events associated with the study. Home-based, individualised occupational therapy led to an improvement in self-perceived performance in daily activities in patients with Parkinson's disease. Further work should identify which factors related to the patient, environmental context, or therapist might predict which patients are most likely to benefit from occupational therapy. Prinses Beatrix Spierfonds and Parkinson Vereniging.


PCy3-catalyzed ring expansion of aziridinofullerenes with CO2 and aryl isocyanates: evidence for a two consecutive nucleophilic substitution pathway on the fullerene cage.
A PCy3-catalyzed ring-expansion reaction of aziridine-fused fullerenes (aziridinofullerenes) through the insertion of CO2 and aryl isocyanates is disclosed. The reaction allows for CO2 fixation by aziridinofullerenes, producing oxazolidinone-fused fullerenes (oxazolidinofullerenes) in high yields, whereas treatment with aryl isocyanates led to a new fullerene family-imidazolidinone-fused fullerenes (imidazolidinofullerenes)-in good to high yields. Furthermore, a mechanistically related unprecedented fullerenyl phosphonium salt was successfully isolated. Using the isolated salt, mechanistic studies were also investigated.


Control of lower-esophageal-sphincter contractile activity by motilin in conscious dogs.
The effect of synthetic motilin on contractile activity in the lower esophageal sphincter (LES) and the stomach has been studied in 5 healthy dogs by means of chronically implanted strain gage force transducers. Motilin produced strong contractions in the LES and the stomach simultaneously after intravenous doses ranging from 0.3 to 2.7 microgram/kg hr, which were similar to the naturally occurring interdigestive contractions in the LES and the stomach. However, these contractions could be induced only in the interdigestive state; infusion of motilin into dogs in the digestive state brought about no significant effect on either the LES or the stomach. Motilin-induced contractions in the LES and the stomach were instantly abolished by ingestion of food. It is considered that the contractions induced by motilin are identical with the naturally occurring interdigestive contractions in the LES and these contractions are the most orad component of the interdigestive cyclic recurring caudad-moving bands of strong contractions in the dogs.


Rich spectrum of neural field dynamics in the presence of short-term synaptic depression.
In continuous attractor neural networks (CANNs), spatially continuous information such as orientation, head direction, and spatial location is represented by Gaussian-like tuning curves that can be displaced continuously in the space of the preferred stimuli of the neurons. We investigate how short-term synaptic depression (STD) can reshape the intrinsic dynamics of the CANN model and its responses to a single static input. In particular, CANNs with STD can support various complex firing patterns and chaotic behaviors. These chaotic behaviors have the potential to encode various stimuli in the neuronal system.


Comparison of Modified Triple Antibiotic Paste in Two Concentrations for Lesion Sterilization and Tissue Repair in Primary Molars: An In Vivo Interventional Randomized Clinical Trial.
"Lesion sterilization and tissue repair" (LSTR) is a non-instrumentation endodontic treatment modality that has recently gained popularity with promising results in several clinical trials. However, there is a dearth of evidence regarding the concentration of modified triple antibiotic paste (MTAP) to be used for the procedure. To compare the clinical and radiographic efficacy of 1 mg/mL and 1 g/mL concentrations of MTAP (ciprofloxacin, metronidazole, and clindamycin) used in LSTR of primary molars. Sixty-four infected primary molars in children between 4 years and 10 years of age were randomly allocated to two groups. Lesion sterilization and tissue repair at 1 mg/mL concentration of MTAP (group I) and 1 g/mL concentration of MTAP (group II) was performed. Clinical and radiographic outcomes were evaluated using Coll and Sadrian's criteria at 10 days, 1 month, and 3 months and the results were tabulated. The data obtained were subjected to statistical analysis with IBM. SPSS statistics software 23.0 Version. To test the significance in categorical data, a Chi-square test was used. The probability value of 0.05 was considered significant. At the end of 3 months review, clinical success rates of group I and group II were 84.4 and 90.6%, respectively, and radiographic evaluation showed group I-78.1% and group II-90.6%. Both 1 mg/mL and 1 g/mL concentrations of MTAP used in LSTR of primary molars had similar success rates with no statistically significant difference. Lesion sterilization and tissue repair when found to be equally effective in less concentration may aid in achieving adequate infection control with the least detrimental effect on the remaining vital pulp and periradicular structures. In addition, this circumvents the systemic administration of potent antibiotics thus combating antibiotic resistance. Shankar K, Ramkumar H, Dhakshinamoorthy S, et al. Comparison of Modified Triple Antibiotic Paste in Two Concentrations for Lesion Sterilization and Tissue Repair in Primary Molars: An In Vivo Interventional Randomized Clinical Trial. Int J Clin Pediatr Dent 2021;14(3):388-392.


Diagnostic utility of p57 immunohistochemistry and DNA ploidy analysis by fluorescence in situ hybridisation in hydatidiform moles.
Hydatidiform moles (HMs) include complete and partial moles, are the result of abnormal fertilisation. The accurate classification of HMs and its distinction from non-molar specimens is utmost important for clinical management and risk assessment. It is diagnostically challenging if the distinction is based solely on histomorphology with poor interobserver reproducibility, especially in early gestations. This study aimed to investigate the diagnostic ability of combined p57 immunohistochemistry and DNA ploidy analysis to distinguish between complete moles, partial moles and non-molar abortus. We included all HMs cases diagnosed in our centre over a six-year period. p57 immunohistochemistry stain was performed. Only nuclear immunoreactivity in >50% of cytotrophoblasts and villous stromal cells was regarded as positive for p57. DNA ploidy status was determined by fluorescence in situ hybridisation. A total of 250 cells from five chorionic villi were counted and were scored as diploid or triploid if more than 10% of nuclei demonstrated two or three signals, respectively. A total of 51 cases originally diagnosed by histomorphology as complete mole (n = 18), partial mole (n = 24) and non-molar abortus (n = 9) were recruited. The cases were reclassified based on the p57 immunostaining pattern and DNA ploidy status, into 27 complete moles (p57-/diploid), 9 partial moles (p57+/triploid) and 15 non-molar abortus (p57+/diploid). The diagnostic accuracy by histomorphological features alone in each category: complete moles, partial moles and non-molar abortus was 78.4%, 70.6% and 88.2% respectively. This study highlighted the importance of the utility of combined p57 immunostain and DNA ploidy analysis in arriving at an accurate diagnosis in HMs. An algorithmic approach utilising these ancillary techniques is advocated in routine diagnostic workup for a more refined diagnostic approach to HMs.


A select set of opioid ligands induce up-regulation by promoting the maturation and stability of the rat kappa-opioid receptor in human embryonic kidney 293 cells.
Ligand-induced regulation of the rat kappa-opioid receptor (rKOR) was investigated in human embryonic kidney 293 cells stably expressing the FLAG-tagged rKOR. Incubation of rKOR cells with naltrexone for 24 h increased the B(max) >3-fold, with no change in the affinity of [(3)H]diprenorphine. Two immunoreactive receptor species were present in cell lysates: naltrexone treatment caused a >3-fold increase in the 52-kDa species while decreasing the level of the 42-kDa species. Dynorphin(1-13), U69,593 [(5alpha,7alpha,8beta)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4,5]dec-8-yl)benzeneacetamide], or salvinorin A [2S,4aR,6aR,7R,9S,10aS, 10bR)-9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1c]pyran-7-carboxylic acid methyl ester] treatment did not alter the level of immunoreactive rKOR protein, whereas etorphine, cyclazocine, naloxone, and naloxone methiodide increased the 52-kDa and decreased the 42-kDa rKOR bands. Receptor up-regulation was associated with an increase in the number of cell surface receptors and a 2-fold increase in the E(max) for guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. Glycosidase digestion indicated that the 52- and 42-kDa receptors contained complex and high-mannose N-glycans, respectively, Pulse-chase analysis and glycosidase digestion sensitivities suggested that the 42-kDa rKOR species was a precursor of the 52-kDa species. Naltrexone did not alter rKOR mRNA levels or translational efficiency, and rKOR up-regulation was not inhibited by cycloheximide. Brefeldin A caused accumulation of intracellular rKOR intermediates, and coincubation with naltrexone increased the levels of the brefeldin-induced species significantly. These results suggest that select opioid ligands up-regulate rKOR by enhancing the rate of receptor folding and maturation and by protecting the receptor from degradation, resulting in an increase in the number of rKOR binding sites, immunoreactive protein, and functional receptors.


The pneumatic syringe: a simple apparatus for self-administration of drugs by rats.
Drug solution is delivered by a syringe operated by a pneumatic cylinder. Recommended delivery volumes are from 10 to 200 microliter. A solid-state control unit is described which can operate two syringes (drug injection and flush), has outputs for recording responses and injections, and can be programmed to provide several schedules of reinforcement. All components are readily commercially available.


Mixed pleomorphic lobular and apocrine carcinoma of the breast: A case report suggesting pathogenesis.
Pleomorphic lobular carcinoma (PLC) of the breast is a variant of lobular carcinoma, characterized by loss of E-cadherin expression and high-grade morphologies. Whether the pathogenesis of PLC is in the ductal or the lobular lineage has been discussed. In this report, a case of PLC combined with apocrine carcinoma is presented. Histologically, the tumor showed two distinct carcinoma components: one was a typical apocrine carcinoma, and the other was a pleomorphic invasive lobular carcinoma. The former showed complete membranous expression of E-cadherin, whereas the latter aberrantly expressed it not on the cell membrane, but in the cytoplasm. Both components were triple-negative and strongly positive for GCDFP-15, suggesting apocrine differentiation. The intraductal component showed only a feature of apocrine ductal carcinoma in situ. This case suggests that apocrine carcinoma could be an origin of PLC.


The environment quality of heavy metals in sediments from the central Bohai Sea.
The heavy metals (Cu, Co, Ni, Zn, Cr, Pb, Cd) in surface and core sediments from the central Bohai Sea were analyzed to evaluate the temporal/spatial distribution and pollution status. Cd exhibited gradual increase vertically, while others were stable or declined slightly in core sediments. In surface sediments, metals showed higher values in 'central mud area of the Bohai Sea' and the coastal area of the Bohai Bay. Cd and Pb also had high levels in the northeastern part of Bohai Sea. Both the contamination factors (CFs) and the geo-accumulation index (Igeo) indicated that Cu, Co, Ni, and Cr were not at pollution levels, while Pb, Zn, and Cd indicated moderate contamination. Compared with sediment quality guidelines (SQGs), Cu, Zn, Cr, Pb, and Cd were likely to produce occasional adverse biological effects, while Ni showed possible ecotoxicological risks. The combined levels of the metals have a 21% probability of being toxic.


Effective dermatomal blockade after subcostal transversus abdominis plane block.
The ultrasound-guided transversus abdominis plane (TAP) block is used to treat postoperative pain after abdominal surgery. Abdominal wall sensory nerves are anaesthetised by injecting local anaesthetics into the neurofascial plane between the internal oblique and the transversus abdominis muscles. Sensory assessment of a TAP block may guide the decision on the extent of the block. The purpose of this study was to investigate if the dermatomal extent of sensory blockade after injection of 20 ml 0.5% ropivacaine bilaterally into the TAP can be assessed using cold and pinprick sensation. Subcostal TAP block was performed bilaterally in 20 awake patients scheduled for elective abdominal surgery. Sensory change in dermatomes T4-L4 was tested with pinprick using a blunt needle and cold disinfectant swabs after 10, 20 and 30 minutes. Data from 20 patients (40 blocks) were analysed. Eighteen patients registered sensory change after subcostal TAP block, and dermatomes T10-T12 were blocked after 30 minutes in all of these patients. Spread of sensory change to dermatomes T5-L3 was variable. This study confirmed that the dermatomal extent of a sensory blockade after a single-shot subcostal TAP block can be assessed using cold and pinprick sensation. not relevant. The study was registered at clinicaltrials.gov with the registration number NCT01024868.


Basic primary rhinoplasty.
This article presents the guest editor's views on basic primary rhinoplasty at this time, and explains changes in techniques during the past 30 years of his practice.


Portable hydrogel test kit integrated dual-emission coordination polymer nanocomposite for on-site detection of organophosphate pesticides.
It is of great significance to on-site detection of organophosphate pesticides (OPs) for pollution monitoring and poisoning estimation. Herein, we developed a portable hydrogel test kit for on-site detection of OPs, which is based on the integration of agarose hydrogel with dual-emission coordination polymers (CPs) nanocomposite comprised of Ru(bpy)32+ and zinc (II)-based CPs (ZnCPs) loaded with thioflavin T (ThT). Different from Ru(bpy)32+ with stable fluorescence in acidic environment, ThT@ZnCPs is highly sensitive to H+, which destroys the structure of ZnCPs as a host and quenches ThT@ZnCPs fluorescence. The distinct fluorescence behaviors of Ru(bpy)32+ and ThT@ZnCPs in acidic environment enable the hydrogel test kit to exhibit ratiometric fluorescence responses to acetylcholinesterase (AChE), which hydrolyzes acetylcholine to acetic acid and provides H+. On this basis, combining the inhibition effect of OPs to AChE activity, a ratiometric fluorescence method for OPs detection was established with the hydrogel test kit, and satisfactory results have been achieved in buffered aqueous solutions and apple juice samples. Attractively, by employing smartphone as a signal readout, on-site quantitation of OPs was accomplished with the features of easy to use, portability and low cost, demonstrating a great promising for point-of-care testing in food safety monitoring.


The cGMP system in normal and degenerating mouse neuroretina: New proteins with cGMP interaction potential identified by a proteomics approach.
The hereditary disease Retinitis pigmentosa results in severe vision loss due to photoreceptor degeneration by unclear mechanisms. In several disease models, the second messenger cGMP accumulates in the degenerating photoreceptors, where it may over-activate specific cGMP-interacting proteins, like cGMP-dependent protein kinase. Moreover, interventions that counteract the activity of these proteins lead to reduced photoreceptor cell death. Yet there is little or no information whether other than such regular cGMP-interactors are present in the retina, which we, therefore, investigated in wild-type and retinal degeneration (rd1, rd10, and rd2) mouse models. An affinity chromatography based proteomics approach that utilized immobilized cGMP analogs was applied to enrich and select for regular and potentially new cGMP-interacting proteins as identified by mass spectrometry. This approach revealed 12 regular and 10 potentially new retinal cGMP-interacting proteins (e.g., EPAC2 and CaMKIIα). Several of the latter were found to be expressed in the photoreceptors and to have proximity to cGMP and may thus be of interest when defining prospective therapeutic targets or biomarkers for retinal degeneration.


Mapping of the snuffbox and cubital vessels for percutaneous arterial venous fistula (pAVF) in dialysis patients.
Report on the anatomic qualification of the snuffbox radial artery (SBRA) and proximal radial artery (PRA) for pAVF. Retrospective analysis of upper extremity mapping in 64 limbs in 55 dialysis patients was performed. The radial artery was assessed for diameter, patency, flow and proximity to the adjacent vein to SBRA and PRA. Sites qualified for pAVF on a binary basis when the in situ radial artery and adjacent vein were straight, parallel, greater than 2 mm in diameter and within 1.5 mm of each other. Effect of age, sex, diabetes, systolic blood pressure and obesity were assessed with logistic regression. Mean, median and frequency distribution of vessel diameter and distance were analyzed. Radial artery sites were qualified for pAVF in 47.6% (30/63) at the SBRA and 87.9% (29/33) at the PRA. SBRA sites were disqualified for vessel size in 36.4% (12/33 overall, usually vein 11/12), distance in 24% (8/33) and both 36.4% (12/33). All (4/4) PRA sites were disqualified for vessel size alone. The adjacent vein was the median vein or cephalic vein for the SBRA, and the perforating vein or vena comitans for the PRA. Effects of age, sex, diabetes, systolic blood pressure, obesity and prior fistula did not attain statistical significance. Most dialysis patients meet the anatomic requirements for pAVF in the SBRA or PRA. Vessel size is the most common limiting variable followed by distance between vessels.


Fear signals vulnerability and appeasement, not threat.
Humans are not only fearful apes, but we also communicate our fear using social cues. Social fear displays typically elicit care and assistance in the real world and the lab. But in the psychology and neuroscience literature fearful expressions are commonly interpreted as "threat cues." The fearful ape hypothesis suggests that fearful expressions should be instead considered appeasement and vulnerability cues.


Poly-Phthalocyanine-Doped Graphene Oxide Nanosheet Conjugates for Electrocatalytic Oxidation of Drug Residues.
Donor and acceptor phthalocyanine molecules were copolymerized and linked to graphene oxide nanosheets through amidation to yield electrocatalytic platforms on glassy carbon electrodes. The platforms were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, UV/Vis spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The fabricated electrochemical catalytic surfaces were then evaluated toward electrocatalytic detection of ascorbic acid and tryptophan. These were characterized by a wide linear dynamic range and low limits of detection and quantification of 2.13 and 7.12 µM for ascorbic acid and 1.65 and 5.5 µM for tryptophan, respectively. The catalytic rate constant was 1.86 × 104 and 1.51 × 104 M-1s-1 for ascorbic acid and tryptophan, respectively. The Gibbs energy for catalytic reactions was -17.45 and -14.83 kJ mol-1 depicting a spontaneous reaction on the electrode surface. The sensor platform showed an impressive recovery when applied in real samples such as fresh cow milk, in the range 91.71-106.73% for both samples. The developed sensor therefore shows high potential for applicability for minute quantities of the analytes in real biological samples.


Warning! Schools can damage your health: alienation from school and its impact on health behaviour.
An international study of health behaviour among school-age children was co-ordinated by the World Health Organization (WHO). The data were obtained from a self-completion questionnaire examining key health behaviours and associated psycho-social variables obtained from representative samples of young people in school aged 11.5, 13.5, and 15.5 years. The analysis focuses on the relationship between older (15.5 years) students' attitudes towards school and health behaviours such as regular smoking, alcohol use, physical activity and food choices. The data show a strong and progressive relationship between indicators of 'alienation' from school, and health compromising behaviours among school students from Australia and Wales. This relationship is most obvious with the 'abusive' behaviours of smoking and alcohol misuse. Summary data for nine other countries in the WHO study indicate that this relationship is found consistently across all countries in the study. This substantial minority of students (approximately 30% varying between countries) represents an important target population for efforts to promote healthy lifestyles. Traditional school health education is seen as insufficient to tackle this task and recommendations are made concerning change to the school environment and ethos, and the need to reach young people in their home and community settings.


Detection of micrometastases in histologically negative lymph nodes in esophageal cancer.
New molecular techniques may identify micrometastases in histologically negative lymph nodes and have an impact on the staging of esophageal cancer. We investigated the role of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay to identify micrometastases in esophageal cancer. The RT-PCR assay to detect carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) was performed on lymph nodes from patients with esophageal cancer and benign esophageal disorders. The presence of CEA mRNA in lymph nodes was considered evidence of metastases. Histopathologic study revealed metastases in 50 (41%) of 123 lymph nodes from 30 patients with esophageal cancer. All histologically positive lymph nodes contained CEA mRNA by RT-PCR. Of 73 histologically negative lymph nodes, 36 (49%) contained CEA mRNA, a significant increase compared with the histopathologic diagnosis (p < 0.001). Lymph nodes in patients with benign disease contained no CEA mRNA. In 10 patients, histologic stage was NO. Five of them were also negative by RT-PCR, and all are alive with only one recurrence. In the remaining 5 patients, RT-PCR was positive for occult lymph node metastases; 2 have died of disease, and 1 is alive with recurrent disease. In patients with esophageal cancer, RT-PCR detects more lymph node metastases than does histopathology. Initial follow-up suggests a positive RT-PCR with negative histologic findings may have poor prognostic implications. Further studies will be needed to confirm any clinical implications.


Obesity in women: a life cycle of medical risk.
Obesity can have an adverse impact on health at each stage of a woman's life cycle. In young women, obesity has an impact on psychosocial health and, as they grow older and become parents, on their reproductive health. Obesity also imposes a number of serious risks during pregnancy. In older women, obesity is associated with the emergence of a number of related chronic diseases, such as type 2 diabetes and cardiovascular disease, and increased risk for almost all types of cancer. Of concern in the elderly is the increasing evidence that obesity is an independent risk factor for dementia and Alzheimer's disease. Obesity also has a marked impact on life expectancy. The medical risks associated with obesity in women are also important for the woman's children and future generations. There is emerging evidence that nutrition during fetal and early life can influence risk for obesity and chronic diseases for both sexes.


Mechanism of synergistic action of all-trans- or 9-cis-retinoic acid and interferons in breast cancer cells.
Combination of all-trans-retinoic acid (RA) with either interferon-alpha or -gamma resulted in a synergistic amplification of the anti-proliferative effect on cultured breast cancer cells. RA could be replaced by other biologically active retinoids. The synergism was also observed for the induction of 2'-5'-oligoadenylate synthetase, an enzyme which is involved in anti-viral activity of interferons and possibly in growth regulation of tumor cells. Combination of RA with interferon-gamma increased the down-regulation of specific binding sites for [125I]interferon-gamma. On the other hand interferons had no effect on the cytoplasmic binding protein for RA. Comparing all-trans- with 9-cis-RA, the latter was more effective in inhibiting tumor cell growth and in inducing synergism with interferon-gamma. This would indicate that retinoic X receptors are more important in mediating these effects than the RA receptors (RARs). This assumption is also supported by the failure of Ro-415253, a specific RAR-alpha antagonist, to reduce the synergistic interaction of RA with interferon with respect to growth inhibition.


Relationship between distention and absorption in rat intestine. I. Effect of luminal volume on the morphology of the absorbing surface.
Previous studies in vivo have suggested that distention of the intestinal lumen may enhance intestinal absorption by augmenting absorptive surface area. The precise anatomic mechanism for this increase in surface area, however, has not been explored in detail. We developed methods for rapidly freezing and fixing intestinal segments in situ in the nondistended or distended state. Distention led to a reduction in villus height (309.2 +/- 9.9 to 230.7 +/- 11.8 micron) and a marked increase in the width of intervillus space in both the transverse (50.4 +/- 4.8 to 298.0 +/- 24.8 micron) and longitudinal (15.2 +/- 3.4 to 76.0 +/- 10.6 micron) dimensions. There was, however, no absolute change in total mucosal surface area. The changes in morphology occurred instantaneously, were entirely reversible, and were demonstrated at pressures that occur spontaneously in the mammalian intestine. These studies demonstrate that luminal distention results in marked alterations in intestinal histology that promote increased access of luminal contents to intervillus transport sites in the intestine in vivo. The resulting alterations could lead to an increase in functional rather than absolute absorptive surface area.


Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans.
The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3-hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss.


Neuronal correlates of eyeblinks are an expression of primary consciousness phenomena.
The blinking rate far exceeds that required for moistening the cornea and changes depending on whether a person is resting or engaged in cognitive tasks. During ecological cognitive tasks (such as speaking, reading, and watching videos), blinks occur at breakpoints of attention suggesting a role in information segmentation, but the close relationship between cognition dynamics and blink timing still escapes a full understanding. The aim of the present study is to seek (1) if there is a temporal relationship between blink events and the consecutive steps of cognitive processing, and (2) if blink timing and the intensity of blink-related EEG responses are affected by task-relevance of stimuli. Our results show that, in a classical visual oddball task, (i) the occurrence of blinks is influenced by stimuli, irrespective of their relevance, (ii) blinks following relevant stimuli are only apparently delayed due to the need of finalizing a behavioural response, and (iii) stimulus relevance does not affect the intensity of the blink-related EEG response. This evidence reinforce the idea that blinks are not emitted until the last step of the processing sequence has been completed and suggests that blink-related EEG responses are generated by primary consciousness phenomena which are considered by their nature non-modulable (all-or-nothing) phenomena.


Histological examination of choroid plexus epithelia changes in schizophrenia.
The choroid plexus (CP) produces and secretes most of the cerebrospinal fluid (CSF) of the central nervous system. The CP is suggested to be regulated by descending neurons and by circulating factors and is involved in the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP changes in psychosis, schizophrenia and depression. This study histologically examines CP epithelial cell morphology in these illnesses to identify the biological source of such volumetric changes. Formalin-fixed paraffin-embedded (FFPE) blocks were obtained bilaterally from the lateral ventricles of 13 cases of sex- and age-matched brains from each of schizophrenia (SZ) with psychosis, major depressive disorder (MDD) and matched controls (NPD). FFPE blocks were sectioned at 7 μm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected at x600 magnification. Calcification was assessed in all CP regions manually. Analysis with a General Linear Model demonstrated a significant effect of diagnosis on somal width (p = 0.006, R2 = 0.33 R2(adj) = 0.25) demonstrating increased somal width in SZ without psychotic medication versus controls (p = 0.032), but not in medicated SZ cases. No effects were observed in calcification. The epithelial cells that were examined were attached to the CP fibrous surface, so width expansion describes the primary methods for these cells to expand with adherence to this surface in SZ. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness-specific change mediated through the DA-system with likely neuronal origin. CP alterations were not found in MDD where they are instead generally associated with heightened allostatic load that was unknown in this cohort.


The transfer of circulating 131I IgG1 and 125I IgG2 to the nasal secretions of sheep.
Ovine IgG1 and IgG2 labelled with 131I and 125I respectively were injected intravenously into four sheep. Serum and nasal secretion samples were collected and fractionated by gel filtration on columns of Sephadex G100. Results showed that in serum more than 95 per cent of the radioactivity was associated with intact IgG molecules whereas in nasal secretion samples the percentage varied from five to 47. It was found that the concentrations of IgG1 and IgG2 in the nasal secretions were similar and were approximately 2 per cent of the serum concentrations. This finding indicates a lack of selective transfer of either IgG1 or IgG2 from blood to nasal secretions in sheep.


Predictors of Condom Use Among Iranian Women at Risk of HIV.
Sexual transmission of HIV/AIDS is increasing in Iran and is the main route of infection among women. In order to foster the development of future HIV prevention interventions for women, researchers need to understand the factors that influence sexual risk reduction behaviors in this group. The aim of this study was to explore the predictors of condom use among women at risk of HIV and develop a model of condom use in a sample of women at risk of HIV. We cross-sectionally examined predictors of condom use among 200 women at risk of HIV. Women were recruited from drop-in centers and voluntary counseling and testing centers in Tehran. Condom use among women at risk of HIV was examined using path analysis, and fit indices showed a good fit for the model. Condom use self-efficacy, social support, and less stereotypic gender roles influenced sexually protective behaviors of women at risk of HIV. Our results can provide a basis for future gender-specific intervention programs among women at risk of HIV. Researchers, practitioners, and organizations that play a central role in protecting the health of this population can make use of these results for the benefit of sexual and reproductive health programs.


Microbiota regulates the turnover kinetics of gut macrophages in health and inflammation.
The gut immune system has evolved to co-exist in a mutually beneficial symbiotic relationship with its microflora. Here, using a germ-free fate-mapping mouse model, we provide clear insight into how the enteric commensals determine the kinetics of macrophage turnover. The microbiome density along the gastrointestinal tract defines the persistence of ontogenically diverse macrophages, with the highest numbers of the long-lived F4/80hiTim4+ macrophage subset in the less densely colonized small intestine. Furthermore, the microbiome contributes to a tightly regulated monocyte-dependent replenishment of both long- and short-lived F4/80hi macrophages under homeostatic and inflammatory conditions. In the latter situation, the commensals regulate rapid replenishment of the depleted macrophage niche caused by the intestinal inflammation. The microbial ecosystem imprints a favorable cytokine microenvironment in the intestine to support macrophage survival and monocyte-dependent replenishment. Therefore, the host immune system-commensal cross-talk provides an efficient strategy to assure intestinal homeostasis.


Prevention of travel-related infectious diseases in families of internationally adopted children.
Pretravel consultation before international adoption must encompass standard advice for those who travel, advice for those who are exposed to the newly adopted child, and information about caring for a new child during travel. Children who travel to meet siblings may need special accommodations before and during travel. Data on the health of internationally adopted children illustrate the risk of exposing family members and close contacts to some infectious diseases during or after international adoption. Parents, family members, and close contacts of the newly adopted child should be given advice to reduce their own and their child's risk. Targeted preadoption counseling, close attention to hygiene and safety advice, and prompt identification and treatment of infections lead to the safest and most trouble-free adoption travel experience.


Emotion recognition and theory of mind after temporal lobe epilepsy surgery: A systematic review.
In order to navigate in our complex social world successfully, it is crucial to maintain and practice cognitive skills that are dedicated to adaptive social functioning. Emerging evidence suggests that besides deficits in declarative memory, executive functions, and language, impairments in social cognition (SC, e.g., emotion recognition, theory of mind) are also present in temporal lobe epilepsy (TLE). The organic and psycho-social consequences of epilepsy surgery might have additional implications regarding this deficit. Here we qualitatively synthesize longitudinal and cross-sectional findings on SC after TLE surgery. A literature search using PubMed and Scopus identified 275 potential articles. Studies were eligible if they (1) included patients with a diagnosis of TLE, (2) included a healthy comparison group, (3) reported original research, (4) were published in peer-reviewed journals and in English language, (5) reported the intervention of epilepsy surgery. Articles that (1) were case studies, (2) did not focus on SC abilities, (3) used interviews or self-report questionnaires to examine SC functions were excluded. A total of 16 original studies assessing emotion recognition (ER) and/or theory of mind (ToM) matched our criteria. The literature suggests that neither ER nor ToM abilities change after surgery: post-surgery patients show similar impairment patterns to pre-surgery patients. Nevertheless, individual improvement or decline could be masked by group comparisons and results should be considered in light of methodological heterogeneity among studies.


Isotopomer-based metabolomic analysis by NMR and mass spectrometry.
Nuclear magnetic resonance (NMR) and mass spectrometry (MS) together are synergistic in their ability to profile comprehensively the metabolome of cells and tissues. In addition to identification and quantification of metabolites, changes in metabolic pathways and fluxes in response to external perturbations can be reliably determined by using stable isotope tracer methodologies. NMR and MS together are able to define both positional isotopomer distribution in product metabolites that derive from a given stable isotope-labeled precursor molecule and the degree of enrichment at each site with good precision. Together with modeling tools, this information provides a rich functional biochemical readout of cellular activity and how it responds to external influences. In this chapter, we describe NMR- and MS-based methodologies for isotopomer analysis in metabolomics and its applications for different biological systems.


Perioperative nutritional support: a randomised clinical trial.
Ever since methods of artificial nutritional support became available, attempts have been made using this form of treatment to reduce mortality and morbidity in surgical patients. Many trials have addressed this question, but very few have given a meaningful answer because of conceptual and methodological flaws. We therefore undertook a prospective randomised trial investigating the effects of at least 10 days pre-operative total parenteral nutrition (TPN) (n = 51) or total enteral nutrition (TEN) (n = 50) providing 150% basal energy expenditure (BEE) non-protein energy, to reduce major postoperative complications and mortality in a homogeneous patient group with signs of depletion. 50 patients served as a depleted control group (D) and 49 patients served as a non-depleted reference group (ND) and were operated upon without delay. Depleted control patients suffered significantly more septic complications than did patients in the non-depleted reference group (p < 0.05). There was no significant difference, however, in septic complications between either of the nutritional support groups and the non-depleted control group. In high risk patients, with weight loss >10% of body weight and over 500 ml blood loss during operation, a significant decrease in major complications was observed (p < 0.05) as a result of nutritional support. We conclude that pre-operative nutritional support, in patients with severe depletion, results in a reduction in major complications to a degree that justifies its routine use in this selected group of patients.


Ambulatory arterial stiffness in chronic kidney disease: a methodological review.
Cardiovascular mortality is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). This can be explained in part by an increased and progressive calcification of the medial layer of the large arteries leading to arterial stiffening. The prognostic value of measurements of arterial stiffness, especially pulse wave velocity (PWV), in the general population and in CKD and ESRD patients is high, and is above that of traditional risk factors with respect to cardiovascular outcome. In recent years, as an alternative to office measurements, methods for monitoring ambulatory arterial stiffness have been developed. The ambulatory arterial stiffness index (AASI) allows derivation of a parameter from ambulatory blood pressure measurements; however, doubts have emerged about the usefulness of this parameter. Recently, new oscillometric methodologies using simple brachial cuffs, such as Mobil-O-Graph, Vasotens or Arteriograph 24, have been introduced. They measure parameters of 24-h arterial stiffness including PWV, augmentation index and central blood pressure. This enables study of the 24-h variability of these parameters, which will hopefully lead to better cardiovascular risk stratification and improved cardiovascular outcomes of patients. Our review summarizes the present data and future directions of AASI and the methods for monitoring oscillometric 24-h stiffness in different patient populations and especially in CKD.


New Insights into the Functions of Cytokinins in Plant Development.
Recent breakthroughs in cytokinin research have shed new light on the role of cytokinin in plant development. Loss-of-function mutants of a cytokinin receptor reveal a role for the hormone in establishment of the vasculature during embryonic development. Cytokinin controls the number of early cell divisions via a two-component signaling system. Genetically engineered plants that have a reduced cytokinin content demonstrate the regulatory role of the hormone in control of meristem activity and organ growth during postembryonic development, with opposite roles in roots and shoots. There is increasing evidence from work with transgenic plants and mutant analysis that cytokinins do not perform the previously proposed function as a root-derived signal for the regulation of shoot branching. Root-borne cytokinins might serve as a long-range signal controling other processes at distant sites, such as responding to nutritional status, particularly nitrogen availability.


Assessment of serum adiponectin in Egyptian patients with HCV-related cirrhosis and hepatocellular carcinoma.
Hepatitis C-associated insulin resistance is involved in the development of various complications including hepatocarcinogenesis. Low plasma levels of adiponectin contribute to the pathogenesis of insulin resistance and type II diabetes mellitus. The aim of this study was to determine the value of serum adiponectin in Egyptian patients with hepatitis C-related cirrhosis and hepatocellular carcinoma. 90 Egyptian patients with hepatitis C-related liver cirrhosis were enrolled in this study. Patients were divided into two groups as follows: group I: 61 patients with hepatitis C-related cirrhosis and hepatocellular carcinoma, group II: 29 patients with hepatitis C-related cirrhosis (hepatocellular carcinoma was excluded in these patients at the time of recruitment in the study). Serum adiponectin level was measured and correlated with all other studied parameters. Serum adiponectin was significantly lower in patients with hepatocellular carcinoma and it had significant negative correlations with both the overall tumor size and the number of tumor foci. Highly significant negative correlations were found between adiponectin and all markers of insulin resistance in both groups. At a cut-off value ≤5.4 μg/ml, adiponectin had a sensitivity of 60.7%, a specificity of 93.1%, a positive predictive value of 94.9%, and a negative predictive value of 52.9% for detection of hepatocellular carcinoma (with an overall accuracy of 77.6%). An independent association exists between serum adiponectin and hepatocellular carcinoma in Egyptian patients with hepatitis C-related cirrhosis. Therapy to increase circulating adiponectin concentration might represent a novel strategy to prevent hepatitis C-related hepatic complications.


Design and synthesis of new templates derived from pyrrolopyrimidine as selective multidrug-resistance-associated protein inhibitors in multidrug resistance.
In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.


Reducing sodium levels in frankfurters using naturally brewed soy sauce.
Sodium chloride (NaCl; salt) serves important functions in processed meats, contributing to desirable quality and food safety characteristics; however, renewed interest exists in reducing sodium in the human diet despite sodium being a required component of the diet for physiological regulation. This study investigated consumer sensory and quality impacts from replacement of normally added NaCl (flake salt) with naturally brewed soy sauce (SS). Varying levels of SS were used with NaCl and/or potassium chloride (KCl) to comprise treatments (TRT) which investigated flake salt replacement (Phase I) and sodium reduction (Phases II and III). Phase I identified a 50% replacement of NaCl with SS as the baseline for subsequent phases. Phase II indicated that the inclusion of SS could allow for a 20% NaCl reduction without adverse effects on quality or sensory attributes. Phase III results demonstrated that it was feasible to reduce NaCl by 35% via the inclusion of KCl in SS containing frankfurters without major quality or sensory changes.


An approach towards (+)-allokainic acid via diphenylprolinol-catalyzed direct cross-aldol reaction.
This article describes an enantioselective strategy for the synthesis of the kainoid component, (+)-allokainic acid using an organocatalytic approach. A cross-aldol reaction catalyzed by diphenylprolinol yielded a highly functionalized γ-lactam with excellent enantio- and diastereoselectivity, and the resulting hydroxy pyrrolidone was then utilized to synthesize Ganem's intermediate of (+)-allokainic acid. Krapcho decarboxylation and Wittig olefination were pivotal transformations towards the final trans-substituted Ganem's intermediate.


Differences Between the 2016 and 2022 Editions of the Enhanced Recovery After Bariatric Surgery (ERABS) Guidelines: Call to Action of FAIR Data and the Creation of a Global Consortium of Bariatric Care and Research.
In 2016, the Enhanced Recovery After Bariatric Surgery guidelines (G16) was published, and in 2022, an update to it was released (G22). Grading of recommendations, assessment, development, and evaluations (GRADE), emphasizing the level of evidence (LoE) of both the guidelines, was performed. An overview of methodology was also performed, considering the following questions: how can research be improved, what can be done in the future using data, and how to collaborate more? Both guidelines did not explain how the LoE conclusions were derived regarding the risk of bias. There is also potential for forming a global consortium that deals with bariatric research, which can serve as a repository for all relevant data. Ensuring that this data is FAIR (findability, accessibility, interoperability, reusability) compliant and using this data to formulate future guidelines will benefit clinicians and patients alike.


T cells in health and disease.
T cells are crucial for immune functions to maintain health and prevent disease. T cell development occurs in a stepwise process in the thymus and mainly generates CD4+ and CD8+ T cell subsets. Upon antigen stimulation, naïve T cells differentiate into CD4+ helper and CD8+ cytotoxic effector and memory cells, mediating direct killing, diverse immune regulatory function, and long-term protection. In response to acute and chronic infections and tumors, T cells adopt distinct differentiation trajectories and develop into a range of heterogeneous populations with various phenotype, differentiation potential, and functionality under precise and elaborate regulations of transcriptional and epigenetic programs. Abnormal T-cell immunity can initiate and promote the pathogenesis of autoimmune diseases. In this review, we summarize the current understanding of T cell development, CD4+ and CD8+ T cell classification, and differentiation in physiological settings. We further elaborate the heterogeneity, differentiation, functionality, and regulation network of CD4+ and CD8+ T cells in infectious disease, chronic infection and tumor, and autoimmune disease, highlighting the exhausted CD8+ T cell differentiation trajectory, CD4+ T cell helper function, T cell contributions to immunotherapy and autoimmune pathogenesis. We also discuss the development and function of γδ T cells in tissue surveillance, infection, and tumor immunity. Finally, we summarized current T-cell-based immunotherapies in both cancer and autoimmune diseases, with an emphasis on their clinical applications. A better understanding of T cell immunity provides insight into developing novel prophylactic and therapeutic strategies in human diseases.