Effect of charged residues in the N-domain of Sup35 protein on prion [PSI+] stability and propagation.
Recent studies have shown that Sup35p prion fibrils probably have a parallel in-register β-structure. However, the part(s) of the N-domain critical for fibril formation and maintenance of the [PSI(+)] phenotype remains unclear. Here we designed a set of five SUP35 mutant alleles (sup35(KK)) with lysine substitutions in each of five N-domain repeats, and investigated their effect on infectivity and ability of corresponding proteins to aggregate and coaggregate with wild type Sup35p in the [PSI(+)] strain. Alleles sup35-M1 (Y46K/Q47K) and sup35-M2 (Q61K/Q62K) led to prion loss, whereas sup35-M3 (Q70K/Q71K), sup35-M4 (Q80K/Q81K), and sup35-M5 (Q89K/Q90K) were able to maintain the [PSI(+)] prion. This suggests that the critical part of the parallel in-register β-structure for the studied [PSI(+)] prion variant lies in the first 63-69 residues. Our study also reveals an unexpected interplay between the wild type Sup35p and proteins expressed from the sup35(KK) alleles during prionization. Both Sup35-M1p and Sup35-M2p coaggregated with Sup35p, but only sup35-M2 led to prion loss in a dominant manner. We suggest that in the fibrils, Sup35p can bind to Sup35-M1p in the same conformation, whereas Sup35-M2p only allowed the Sup35p conformation that leads to the non-heritable fold. Mutations sup35-M4 and sup35-M5 influence the structure of the prion forming region to a lesser extent, and can lead to the formation of new prion variants.


Diseases of the peripheral nerves.
This chapter reviews the diseases of the peripheral nerves from a neuropathologic point of view, with a special focus on specific morphologic changes, and includes a summary of the histopathologic methods available for their diagnosis. As the rate of obesity and the prevalence of type 2 diabetes increase, diabetic neuropathy is the most common cause of peripheral neuropathy. Many systemic disorders with metabolic origin, like amyloidosis, hepatic failure, vitamin deficiencies, uremia, lipid metabolism disorders, and others, can also cause axonal or myelin alterations in the peripheral nervous system. The most notable causes of toxic neuropathies are chemotherapeutic agents, alcohol consumption, and exposure to heavy metals and other environmental or biologic toxins. Inflammatory neuropathies cover infectious neuropathies (Lyme disease, human immunodeficiency virus, leprosy, hepatitis) and neuropathies of autoimmune origin (sarcoidosis, Guillain-Barré syndrome/acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, and diverse forms of vasculitis. The increasing number of known diseases causing gene mutations in hereditary peripheral neuropathies requires precise characterization, which includes histopathology.


Aberrant epididymal tissue: a significant clinical entity.
Epididymal anomalies are relatively rare and usually they are associated with an undescended testis. A 33 to 66 per cent incidence of epididymal anomalies has been noted in male subjects with cryptorchidism. An increased incidence of epididymal anomalies also has been noted in association with cystic fibrosis, von Hippel-Lindau's syndrome and in male offspring of women treated with diethylstilbestrol. The frequency and anatomical spectrum of epididymal anomalies among men with normal descended testes are not known. We describe 3 patients with bilaterally descended testes, who were found to have aberrant epididymal tissue at scrotal or inguinal exploration. The variable presentations of aberrant epididymal tissue in these 3 patients can be explained best by understanding the embryology and anatomy of the epididymis and its associated vestigial structures. In all likelihood the structures encountered in our patients were the ductus aberrans inferior and the paradidymis. These structures, which rarely are included in urological anatomical descriptions of the epididymis, can be significant clinically. Therefore, it is important that the urologist be aware of their existence and their means of presentation.


The N-linked oligosaccharide at Fc gamma RIIIa Asn-45: an inhibitory element for high Fc gamma RIIIa binding affinity to IgG glycoforms lacking core fucosylation.
Human leukocyte receptor IIIa (Fc gamma RIIIa) plays an important role in mediating therapeutic antibodies' antibody-dependent cellular cytotoxicity (ADCC), which is closely related to the clinical efficacy of anticancer processes in humans in vivo. The removal of the core fucose from oligosaccharides attached to the Fc region of antibodies improves Fc gamma RIIIa binding, allowing the antibodies to enhance dramatically the antibody effector functions of ADCC. In this study, the contribution of Fc gamma RIIIa oligosaccharides to the strength of the Fc gamma RIIIa/antibody complex was analyzed using a serial set of soluble human recombinant Fc gamma RIIIa lacking the oligosaccharides. A nonfucosylated antibody IgG1 appeared to have a significantly higher affinity to the wild-type Fc gamma RIIIa fully glycosylated at its five N-linked oligosaccharide sites than did the fucosylated IgG1, and this increased binding was almost abolished once all of the Fc gamma RIIIa glycosylation was removed. Our gain-of-function analysis in the Fc gamma RIIIa oligosaccharide at Asn-162 (N-162) confirmed that N-162 is the element required for the high binding affinity to nonfucosylated antibodies, as previously revealed by loss-of-function analyses. Interestingly, beyond our expectation, the Fc gamma RIIIa modified by N-162 alone showed a significantly higher binding affinity to nonfucosylated IgG1 than did the wild-type Fc gamma RIIIa. Attachment of the other four oligosaccharides, especially the Fc gamma RIIIa oligosaccharide at Asn-45 (N-45), hindered the high binding affinity of Fc gamma RIIIa to nonfucosylated IgG1. Our data clearly demonstrated that N-45 is an inhibitory element for the high Fc gamma RIIIa binding affinity mediated by N-162 to nonfucosylated antibodies. This information can be exploited for the structural-based functional study of Fc gamma RIIIa.


Multi-Omic Analysis of CIC's Functional Networks Reveals Novel Interaction Partners and a Potential Role in Mitotic Fidelity.
CIC encodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CIC's interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, as well as novel interactions between CIC and cell cycle regulators and RNA processing factors. We found that CIC loss is associated with an increased frequency of mitotic defects in human cell lines and an in vivo mouse model and with dysregulated expression of mitotic regulators. We also observed aberrant splicing in CIC-deficient cell lines, predominantly at 3' and 5' untranslated regions of genes, including genes involved in MAPK signalling, DNA repair, and cell cycle regulation. Our study thus characterises the complexity of CIC's functional network and describes the effect of its loss on cell cycle regulation, mitotic integrity, and transcriptional splicing, thereby expanding our understanding of CIC's potential roles in cancer. In addition, our work exemplifies how multi-omic, network-based analyses can be used to uncover novel insights into the interconnected functions of pleiotropic genes/proteins across cellular contexts.


Patients' perspective of pathology specimens. A prospective study.
To determine the degree of patients' interest in surgical pathology specimens. To assess the impact of patients' involvement in surgical pathology on their understanding of (and confidence in) the storage and use of pathology specimens. Forty seven patients were invited to visit the pathology department and view their specimens postoperatively. Those who visited were asked to complete a questionnaire to assess the effect of the visit. Thirty three of the 47 patients wished to view their specimens, but only 14 actually made the visit. All those who visited indicated that it made them better able to understand the reason for surgery and tissue retention issues, and more likely to consent to the use of excess tissue for research. In general, patients are keen to know what happens to and what is wrong with the organs removed at surgery, and their involvement in surgical pathology can have positive and beneficial effects both for themselves and the profession.


Stratified glucocorticoid monotherapy is safe and effective for most cases of giant cell arteritis.
High-dose glucocorticoids anchor standard care in GCA but are associated with significant toxicity. We aimed to evaluate the safety and effectiveness of a stratified approach to glucocorticoid tapering. The strategy aggressively reduced glucocorticoid doses in those manifesting an adequate early response to treatment, with a view to minimizing glucocorticoid complications. A retrospective, population-based study of GCA was performed. All cases were confirmed by temporal artery biopsy between November 2010 and November 2015. Baseline and outcome data were extracted from secondary and primary care records at diagnosis and 1 year follow-up. The primary outcome was loss of vision. Secondary outcomes included remission and relapse rates and CS-related complications. The cohort consisted of 73 patients (76% female; mean age 73.5 years, s.d. 7.6 years). At presentation, a reduction in visual acuity was recorded in 17 patients (22.3%). The median CRP at diagnosis was 69.5 mg/l [interquartile range (IQR) 40.5-101 mg/l], with a median ESR of 80 mm/h (IQR 60-91 mm/h). At 1 year, remission was achieved in 64 patients (87.7%), whereas 10 patients (13.7%) relapsed. A single patient sustained visual loss after initiation of therapy. The median CRP at 1 year was 4 mg/l (IQR 4-9.5 mg/l) and the mean prednisolone dose was 5.4 mg (0-15 mg). CS-related complications were observed in 10 patients (13.7%). A stratified approach to CS tapering appeared safe and effective in GCA. It was associated with a high rate of remission and promisingly low rates of relapse at 1 year follow-up. These real-world data indicate that glucocorticoid exposure can be minimized safely in some patients with GCA.


The overbite and intraoral mandibular distraction osteogenesis.
The purpose of this study was to quantify the overbite reduction in skeletal Angle Class II malocclusions and discuss the management of the overbite during and after intraoral distraction of the mandible, and during orthodontic treatment with fixed appliances. Cephalograms of 26 patients with an Angle Class II malocclusion and orthodontic appliances and distraction osteogenesis of the horizontal part of the mandible before (T0) and at least 1 year after treatment (T1) were evaluated. Mean age of the patients at the time of distraction was 14.6 years (range 12.8-15.9 years) and at the final registration 17.3 years (range 14.6-20.4 years). The overbite decreased significantly and the SpP/MP value increased significantly. The increase in the value of the Y-axis and the MP/SN angle before and after treatment was statistically insignificant. Opening of the bite during distraction of the mandible can be expected. The use of the 'floating bone' technique did not correct the overbite permanently. The patients in whom an open bite has already been treated are not ideal for mandibular lengthening by means of distraction osteogenesis.


Measurement of lithium transport in RBC from psychiatric patients receiving lithium carbonate and normal individuals by 7Li NMR spectroscopy.
A reproducible 7Li nuclear magnetic resonance (NMR) method, based on a modified inversion recovery (MIR) pulse sequence, was used to discriminate between intra- and extracellular lithium concentrations in red blood cell (RBC) suspensions. The rates of Na(+)-Li+ countertransport determined by the 7Li NMR method were significantly correlated with the measurements made by atomic absorption (AA) for 14 psychiatric patients receiving lithium carbonate (r = 0.937) and 14 normal individuals (r = 0.931). As expected, the rates of Na(+)-Li+ countertransport measured by MIR were significantly lower for the psychiatric patients receiving lithium carbonate than for normal individuals. The 7Li NMR method provides RBC Li+ countertransport information comparable to AA for psychiatric patients and normal individuals. A description of the advantages of the 7Li NMR method in contrast to the AA method, including the study of Li+ interactions with RBC components such as membrane proteins and anionic phospholipids, is included.


Radiofrequency ablation in patients with primary and secondary hepatic malignancies.
The aims of this study were to assess the technical effectiveness of radiofrequency (RF) ablation in patients with primary or secondary hepatic malignancies and to determine survival and complication rates. This was a retrospective analysis of prospectively collected data of patients treated with RF ablation and controlled for recurrence every 3 months by contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The outcome is compared with a comprehensive review of data published in recent literature. Forty-seven patients underwent 50 RF sessions for the ablation of 73 tumors. Local tumor progression was observed in 11 patients (23%). A tumor sized larger than 30 mm, a tumor load larger than 14 cm3, and a percutaneous approach were associated with a faster time to local tumor progression. At the end of a mean (+/- SD) follow-up period of 11.4 +/- 7.5 months, 39 patients (83%) were alive, including eight patients with recurrent disease. The overall cumulative survival rates at 12 and 24 months were 87% and 70%, respectively. In our center, RF ablation can be safely performed to achieve adequate local control and survival rates. Time to local tumor progression was significantly related to initial size of the tumor and tumor load.


ESIPT-based fluorescent enhanced probes prompted by methylated β-cyclodextrin for the detection of thiophenols.
Thiophenol and its derivatives are compounds with high toxicity to organisms and environmental pollution, so it is necessary to detect the level of thiophenols in the environment and biological samples. The probes 1a-b were obtained by introducing the 2,4-dinitrophenyl ether group into diethylcoumarin-salicylaldehyde based compounds. And they can form host-guest compounds with methylated β-cyclodextrin (M-β-CD), the association constants of inclusion complexes are 49.2 M-1, 125 M-1 respectively. The fluorescence intensities of probes 1a-b at 600 nm (1a) and 670 nm (1b) increased significantly in thiophenols detection. Meanwhile, with the addition of M-β-CD, the hydrophobic cavity of M-β-CD significantly increased the fluorescence intensity of probes 1a-b, thus the detection limits of probes 1a-b to thiophenols were reduced from 410 nM, 365 nM to 62 nM, 33 nM respectively. Whereas, the good selectivity and short response time of probes 1a-b towards thiophenols was not affected in the presence of M-β-CD. Moreover, probes 1a-b were used for further water sample detection and HeLa cell imaging experiments due to their good response to thiophenols and the results suggested that probes 1a-b had the potential to detect the content of thiophenols in water samples and living cells.


Kindlin-2 (Mig-2): a co-activator of beta3 integrins.
Integrin activation is essential for dynamically linking the extracellular environment and cytoskeletal/signaling networks. Activation is controlled by integrins' short cytoplasmic tails (CTs). It is widely accepted that the head domain of talin (talin-H) can mediate integrin activation by binding to two sites in integrin beta's CT; in integrin beta(3) this is an NPLY(747) motif and the membrane-proximal region. Here, we show that the C-terminal region of integrin beta(3) CT, composed of a conserved TS(752)T region and NITY(759) motif, supports integrin activation by binding to a cytosolic binding partner, kindlin-2, a widely distributed PTB domain protein. Co-transfection of kindlin-2 with talin-H results in a synergistic enhancement of integrin alpha(IIb)beta(3) activation. Furthermore, siRNA knockdown of endogenous kindlin-2 impairs talin-induced alpha(IIb)beta(3) activation in transfected CHO cells and blunts alpha(v)beta(3)-mediated adhesion and migration of endothelial cells. Our results thus identify kindlin-2 as a novel regulator of integrin activation; it functions as a coactivator.


In vitro fertilizing ability of testicular, epididymal, and ejaculated rabbit spermatozoa.
The fertilizing ability of testicular, epididymal, and ejaculated rabbit spermatozoa was evaluated in vitro following in vitro capacitation by high ionic strength treatment. Fewer than 11% of inseminated ova were apparently fertilized (i.e., in pronuclear, two-, and four-cell stages as determined by light microscopy) when testicular sperm treated with caffeine, caput epididymal, or corpus epididymal sperm samples were tested. A greater fertilizing ability, reflected by the percentage of ova fertilized and more normal progression of embryonic development, was exhibited by cauda epididymal sperm. Of 93 ova, 68 (73.1%) were fertilized by cauda sperm, whereas ejaculated sperm from the same 10 bucks fertilized 34 (36.6%) of 93 ova (P is less than 0.005). Ultrastructural examination of selected ova apparently fertilized by sperm from levels of the male reproductive tract proximal to the cauda epididymidis revealed abnormal activation. Authentic fertilization occurred when ova were inseminated with cauda epididymal and ejaculated sperm. An unusual and infrequent form of activation involving failure of cortical granule breakdown in ova penetrated by cauda epididymal and ejaculated sperm was seen. A comparison of fertilizing ability of sperm from first, second, and third ejaculates revealed a significant decrease with the third ejaculate (P is less than 0.01).


Membrane labeling and immobilization via copper-free click chemistry.
Copper-free click chemistry was employed to derivatize membrane bilayers. This approach uses an azido-lipid conjugate presented on liposomes, which can be labeled in bioorthogonal fashion via cyclooctyne-tagged reagents. An immobilization-based approach using streptavidin-coated microplates was exploited to evaluate membrane derivatization.


Identification and characterization of a JC virus pentanucleotide repeat element binding protein: cellular nucleic acid binding protein.
The JC virus (JCV) control region contains AGGGAAGGGA, the tandem pentanucleotide repeat element (Pnt2). Several proteins specifically interacted via Pnt2 to regulate the expression of JCV early promoter-enhancer (JCV(E)) or late promoter-enhancer (JCV(L)). In this study, a JCV Pnt2 oligonucleotide probe was used to screen a cDNA expression library from glial P19 mouse embryonal carcinoma cells. A cDNA clone was isolated by Southwestern blot assay and it produced a protein that reproducibly and specifically bound to Pnt2. This cDNA had 100% homology to one of three previously identified mouse cDNAs called cellular nucleic acid binding proteins (Cnbps). Cnbps are a highly homologous family of eukaryotic genes implicated in functional interactions with cytoplasmic RNA and regulatory DNA elements. An mRNA of 2.2 kb of Pnt2-interacting Cnbp (PCnbp) was seen in undifferentiated, muscle or glial P19 cells. When expressed from a cDNA expression vector as a fusion protein that also contained 115 kDa from beta-galactosidase, a Pnt2 binding protein (PCNBP) specifically bound to Pnt2 in Southwestern blots as a 30 kDa component of the 145 kDa fusion protein. Furthermore, JCV(E) expression was negatively regulated by PCnbp produced in vivo from the cDNA expression vector. Regulation of JCV(L) was unaffected. We suggest a novel role for CNBP as a PCNBP that interacts with Pnt2 in the negative transcriptional regulation of JCV(E).


Outcome analysis of free flap reconstruction for head and neck cancer with intraoperative indocyanine green angiography.
Intraoperative indocyanine green (ICG) angiography is used in free flap surgery to evaluate the patency of vessel anastomosis. This study evaluated the outcomes of intraoperative ICG angiography in free flap surgery for head and neck cancer. This was a retrospective study of free flap reconstruction for head and neck cancer performed between 2015 and 2021. The outcomes analyzed were the total flap failure rate, re-exploration rate, and flap salvage rate. Differences in outcomes were compared in patients treated using intraoperative ICG angiography and those treated without. Of the 520 free flap surgeries in the 486 enrolled patients, 259 cases underwent intraoperative ICG angiography. In this group, there were 10 (3.9%) cases of total flap failure. In the non-ICG group, there were 22 cases (8.4%). There were 35 (13.5%) cases requiring re-exploration in the ICG group and 40 (15.3%) in the non-ICG group. The difference was not statistically significant. The flap salvage rate was 75.8% (25/33) in the ICG group and 51.4% (18/35) in the non-ICG group, which was a significant difference. We found that free flap surgery with intraoperative ICG angiography significantly decreased total flap failure rate and significantly increased salvage rate but did not significantly affect the re-exploration rate.


Preliminary investigation of effects of copper on a terrestrial population of the antarctic rotifer Philodina sp.
Terrestrial microinvertebrates in Antarctica are potentially exposed to contaminants due to the concentration of human activity on ice-free areas of the continent. As such, knowledge of the response of Antarctic microinvertebrates to contaminants is important to determine the extent of anthropogenic impacts. Antarctic Philodina sp. were extracted from soils and mosses at Casey station, East Antarctica and exposed to aqueous Cu for 96 h. The Philodina sp. was sensitive to excess Cu, with concentrations of 36 μg L-1 Cu (48 h) and 24 μg L-1 Cu (96 h) inhibiting activity by 50%. This is the first study to be published describing the ecotoxicologically derived sensitivity of a rotifer from a terrestrial population to metals, and an Antarctic rotifer to contaminants. It is also the first study to utilise bdelloid rotifer cryptobiosis (chemobiosis) as a sublethal ecotoxicological endpoint. This preliminary investigation highlights the need for further research into the responses of terrestrial Antarctic microinvertebrates to contaminants.


Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis.
The l-tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the "magic" mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)-dependent decarboxylases for natural product biosyntheses, PsiD is PLP-independent and resembles type II phosphatidylserine decarboxylases. Here, we report on the in vitro biochemical characterization of Psilocybe cubensis PsiD along with in silico modeling of the PsiD structure. A non-canonical serine protease triad for autocatalytic cleavage of the pro-protein was predicted and experimentally verified by site-directed mutagenesis.


Psychological distress and its effect on tuberculosis treatment outcomes in Ethiopia.
Psychological distress is the major comorbidity among tuberculosis (TB) patients. However, its magnitude, associated factors, and effect on treatment outcome have not been adequately studied in low-income countries. This study aimed to determine the magnitude of psychological distress and its effect on treatment outcome among TB patients on treatment. A follow-up study was conducted in Addis Ababa, Ethiopia, from May to December 2014. Patients (N=330) diagnosed with all types of TB who had been on treatment for 1-2 months were enrolled consecutively from 15 randomly selected health centers and one TB specialized hospital. Data on sociodemographic variables and economic status were collected using a structured questionnaire. The presence of psychological distress was assessed at baseline (within 1-2 months after treatment initiation) and end point (6 months after treatment initiation) using the 10-item Kessler (K-10) scale. Alcohol use and tobacco smoking history were assessed using WHO Alcohol Use Disorder Identification Test and Australian Smoking Assessment Checklist, respectively. The current WHO TB treatment outcome definition was used to differentiate the end result of each patient at completion of the treatment. The overall psychological distress was 67.6% at 1-2 months and 48.5% at 6 months after treatment initiation. Multiple logistic regression analysis revealed that past TB treatment history [adjusted odds ratio (AOR): 3.76; 95% confidence interval (CI): 1.67-8.45], being on anti-TB and anti-HIV treatments (AOR: 5.35; 95% CI: 1.83-15.65), being unmarried (AOR: 4.29; 95% CI: 2.45-7.53), having alcohol use disorder (AOR: 2.95; 95% CI: 1.25-6.99), and having low economic status (AOR: 4.41; 95% CI: 2.44-7.97) were significantly associated with psychological distress at baseline. However, at 6 months after treatment initiation, only being a multidrug-resistant tuberculosis (MDR-TB) patient (AOR: 3.02; 95% CI: 1.17-7.75) and having low economic status (AOR: 3.75; 95% CI: 2.08-6.74) were able to predict psychological distress significantly. Past TB treatment history (AOR: 2.13; 95% CI: 1.10-4.12), employment status (AOR: 2.06; 95% CI: 1.06-7.00), and existence of psychological distress symptoms at 6 months after treatment initiation (AOR: 2.87; 95% CI: 1.05-7.81) were found to be associated with treatment outcome. The overall magnitude of psychological distress was high across the follow-up period; this was more pronounced at baseline. At baseline, past TB treatment history, being on anti-TB and anti-HIV treatments, being unmarried, and having symptoms of alcohol use disorder were associated with psychological distress. However, both at baseline and end point, low economic status was associated with psychological distress. Screening and treatment of psychological distress among TB patients across the whole treatment period is needed, and focusing more on patients who have been economically deprived, previously treated for TB, and on MDR-TB treatment are important.


The effects of dissolved oxygen levels on the metabolic interaction between digestion and locomotion in Cyprinid fishes with different locomotive and digestive performances.
To test whether the effects of water oxygen concentration ([O(2)]) on the metabolic interaction between locomotion and digestion differ between fish species with different locomotive and digestive behaviours in normoxia, we investigated the swimming performance of fasted and fed fish at water [O(2)] of 1, 2 and 8 (normoxia) mg L(-1) (2.5, 5 and 20 kPa) at 25°C in three juvenile Cyprinidae fish species: goldfish (Carassius auratus), common carp (Cyprinus carpio) and qingbo (Spinibarbus sinensis). Digestion, taxon and water [O(2)] all had significant effects on the pre-exercise oxygen consumption rate [Formula: see text] and the swimming performance (P < 0.05). Among the three fishes, qingbo showed the highest swimming performance and the lowest feeding [Formula: see text] at the saturated water [O(2)], and its active oxygen consumption rate [Formula: see text] and critical swimming speed (U (crit)) decreased the most with decreases in water [O(2)]. Qingbo exhibited a locomotion-priority metabolic mode at all three water [O(2)]. Digestion was sacrificed to locomotion in a postprandial swimming situation, but fed qingbo could not maintain their U (crit) at water [O(2)] of 2 and 1 mg L(-1). Goldfish showed the lowest swimming performance and the highest feeding [Formula: see text] at the saturated water [O(2)]. They exhibited a digestion-priority metabolic mode at high water [O(2)]. However, with a decrease in water [O(2)], the feeding [Formula: see text] decreased more acutely than the respiratory capacity; thus, digestion and locomotion performed independently in a postprandial swimming situation (i.e., an additive metabolic mode) at a water [O(2)] of 1 mg L(-1). The common carp showed moderate and balanced swimming performance and feeding [Formula: see text] at the saturated water [O(2)], and exhibited an additive metabolic mode at all 3 water [O(2)], because digestion, swimming and respiratory capacities decreased in parallel with the decrease in water [O(2)].


Oligoclonality of rheumatoid factors arising spontaneously in lpr/lpr mice.
Rheumatoid factors (RF) from individual mice of the MRL/lpr and C3H/lpr strains were examined with regard to target specificity and heavy chain class expression. It was found that MRL/lpr-derived RF preferentially recognize IgG2a target antibodies while C3H/lpr-derived RF exhibit a broader range of cross-reactivity. IgM RF represent only a minor proportion of the RF response in both strains. The IgG2a-specific RF produced by the lpr strains were found to consist of relatively equal proportions of IgG1, IgG2b, IgG3, and IgA antibodies. However, most of the RF produced by a single individual expressed the same heavy chain class and antigen-binding specificity. These results indicate that within an individual lpr mouse, circulating RF are derived from extensive expansion of a limited number of antigen-activated precursors.


Cre/loxP-mediated in vivo excision of large segments from yeast genome and their amplification based on the 2microm plasmid-derived system.
In vivo excision and amplification of pre-determined, large genomic segments, directly from the genome of a natural host, provides an alternative to conventional cloning in foreign vectors. Using this approach, we have devised an in vivo procedure for excising large segments of Saccharomyces cerevisiae genome using Cre/loxP system of bacteriophage P1, followed by amplification of excised circles, as based on the yeast 2microm plasmid-derived ori and Flp/FRT machinery. To provide the excision and replication enzymes, trans-acting genes cre and FLP, which were under a very tight control of GAL1 and GAL10 promoters, respectively, were inserted by homologous recombination into the URA3 gene on chromosome V. Two parallel loxP sequences, which serve as the recognition sites for the Cre recombinase, were also integrated into the genome at pre-determined sites that are 50-100kb apart. Moreover, 2microm ori, REP3 and two inverted FRTs, which serve as a conditional replication system, were also integrated between the loxP sites. The strain carrying all these inserted elements was perfectly stable. Only after the induction by galactose of the Cre excision function, the genomic segment flanked by two loxP sites was excised and circularized. Applying this procedure, the 50-kb LEU2-YCR011c and 100-kb LEU2-YCR035c regions of chromosome III were successfully excised from the S. cerevisiae genome, whereas the 2microm ori, as aided by FRT/Flp, provided the amplification function. Such excised and amplified genomic segments can be used for the sequencing and functional analysis of any yeast genes.


When pregnancy is a research risk.
A published study reported by Munné using uterine lavage to retrieve in vivo blastocysts for preimplantation genetic testing has been the subject of several technical and ethical critiques. None of these critiques has been based on a review of the study's IRB-approved informed consent. This commentary seeks to do that, examining the Munné (and related Nadal) consent forms for their conformity to existing requirements for a full and informed consent.


Prognostic implication of tumor spread through air spaces in patients with pathologic N0 lung adenocarcinoma.
Tumor spread through air spaces (STAS) has been identified as an invasive pattern in lung adenocarcinoma (ADC), but the prognostic implication of STAS has not been well studied in patients with pathologic N0 lung ADC. The purpose of this study was to evaluate the prognostic implication of STAS in pathologic N0 lung ADC patients after radical surgery. Between January 2017 and December 2018, 796 patients with completely resected pathologic N0 lung ADC were reviewed. Pearson's chi-square test or Fisher exact test was used for comparing the relationship between STAS and clinicopathological features. The log-rank test and multivariate Cox regression models were used to explore prognostic factors. Among the 796 patients, STAS was positive in 201 patients (25.3%). The presence of STAS was significantly associated with patients with solid nodules (P < 0.001), micropapillary pattern-predominant adenocarcinoma/solid pattern-predominant adenocarcinoma (P < 0.001), larger tumor size (P < 0.001), visceral pleural invasion (P < 0.001) and lymphovascular invasion (P < 0.001). Multivariable analysis showed that STAS was an independent prognostic factor for recurrence-free survival (RFS) in pathologic N0 lung ADC patients (P = 0.014). For patients with acinar pattern-predominant adenocarcinoma (APA) / papillary pattern-predominant adenocarcinoma (PPA) / invasive mucinous adenocarcinoma (IMA) and patients who underwent lobectomy, STAS was an independent prognostic factor for RFS (P = 0.015, P = 0.011; respectively) and overall survival (OS) (P = 0.038, P = 0.020; respectively). In this study, STAS was an independent prognostic factor for RFS in pathologic N0 lung adenocarcinomas, and it was also an independent prognostic factor for RFS and OS in patients with APA/PPA/IMA and those who received lobectomy.


Modeling the binding specificity of the RNA-binding protein GLD-1 suggests a function of coding region-located sites in translational repression.
To understand the function of the hundreds of RNA-binding proteins (RBPs) that are encoded in animal genomes it is important to identify their target RNAs. Although it is generally accepted that the binding specificity of an RBP is well described in terms of the nucleotide sequence of its binding sites, other factors such as the structural accessibility of binding sites or their clustering, to enable binding of RBP multimers, are also believed to play a role. Here we focus on GLD-1, a translational regulator of Caenorhabditis elegans, whose binding specificity and targets have been studied with a variety of methods such as CLIP (cross-linking and immunoprecipitation), RIP-Chip (microarray measurement of RNAs associated with an immunoprecipitated protein), profiling of polysome-associated mRNAs and biophysical determination of binding affinities of GLD-1 for short nucleotide sequences. We show that a simple biophysical model explains the binding of GLD-1 to mRNA targets to a large extent, and that taking into account the accessibility of putative target sites significantly improves the prediction of GLD-1 binding, particularly due to a more accurate prediction of binding in transcript coding regions. Relating GLD-1 binding to translational repression and stabilization of its target transcripts we find that binding sites along the entire transcripts contribute to functional responses, and that CDS-located sites contribute most to translational repression. Finally, biophysical measurements of GLD-1 affinity for a small number of oligonucleotides appear to allow an accurate reconstruction of the sequence specificity of the protein. This approach can be applied to uncover the specificity and function of other RBPs.


Spectrin-actin associations studied by electron microscopy of shadowed preparations.
By shadowing specimens dried onto mice sheets we have obtained clear images of actin crosslinked by spectrin, an actin-binding protein found in erythrocytes. We conclude that spectrin dimers possess a single binding site for F actin. Tetramers formed by head-to-head association of two dimers possess two actin binding sites, one at each tail. Polymerizing G actin in the presence of spectrin tetramers or mixing preformed F actin with spectrin tetramer plus bad 4.1 results in an extensively crosslinked network of actin filaments. When G actin is polymerized in the presence of spectrin at spectrin:actin mole ratios close to that present on the erythrocyte membrane, large amorphous protein networks are formed. These networks are clusters of spectrin around 25 nm diameter structures which may be actin protofilaments. These networks are similar to the cytoskeletal network seen after erythrocyte membranes are extracted with detergent, and may represent the first in vitro assembly of a cytoskeletal complex resembling that of the native cell both biochemically and structurally.


Outcome of a new patient pathway for managing B3 breast lesions by vacuum-assisted biopsy: time to change current UK practice?
B3 lesions of the breast represent a difficult management dilemma. The umbrella term 'B3' incorporates lesions with little associated malignancy risk as well as lesions with significant risk of concurrent neoplasia. Diagnosis of B3 lesions in screening populations is largely made on needle core biopsy, which provides little tissue to adequately diagnose pathologically diverse lesions. The advent of vacuum-assisted biopsy (VAB) provides the multidisciplinary team with a more representative pathology sample to direct management. In this unit, in 2009, a pathway to guide management of B3 lesions detected on needle core biopsy in screening patients was implemented to assess whether VAB was a safe and viable alternative to surgery in selected cases.Here we present the 5-year follow-up results of this pathway. 398 patients with B3 lesions were suitable for this pathway, of which 321 went on to have second-line VAB. 24% of these patients subsequently required surgery for malignancy or ongoing concerns, and thus 245 avoided surgery being subsequently referred for 5-year mammographic surveillance or back to screening. Median follow-up was 3 years (IQR 2), and no cancers were detected at the original B3 site during follow-up. We have demonstrated here that with large volume tissue sampling for indeterminate lesions of the breast surgery can be safely avoided in selected B3 lesions with and without atypia.


[A epidemiological survey and management analysis of asthma among employees of 6 chemical plants in Beijing area].
To estimate the prevalence and to evaluate the current status for management of asthma among employees in chemical plants in Beijing area. A general survey was conducted among 12694 employees in 6 large chemical plants in Beijing area by face to face interview and physical examination. The prevalence of asthma was 1.13% (143/12694), 1.09% (78/7164) for male and 1.18% (65/5530) for female. The incidence of asthma was different among various chemical plants. 91.61% of the patients had received drug therapy in acute exacerbation stage, however, only 8.39% of them persevered drug therapy in remission stage. Atopy and exposure to some chemical substances are risk factors for asthma. Treatment of asthma among this population by far fails to accord with the demands of the recommeded regimen for asthma.


Absorption characteristics of a new valproate formulation: divalproex sodium-coated particles in capsules (Depakote Sprinkle).
To determine the absorption characteristics of a new dosage form of divalproex sodium consisting of coated particles in a pull-apart capsule (Depakote Sprinkle, Abbott Laboratories, North Chicago, IL), two absorption studies were conducted in adult volunteers. Ten fasting men participated in a single-dose, crossover study comparing absorption from Sprinkle capsules versus enteric-coated tablets (study 1). Eleven men participated in a multidose study (study 2) in which Sprinkle capsules or enteric-coated tablets were given once every 24 hours for three doses under fasting and nonfasting conditions. In study 1, the extent of absorption from Sprinkle capsules equalled that from enteric-coated tablets. Compared to enteric-coated tablets, Sprinkle capsules had earlier absorption onset, 1 versus 2.6 hours (P less than .05), slightly slower absorption rate, time to reach peak (tmax) of 4.0 versus 3.4 hours (P less than .1), and lower maximum peak plasma drug concentration (Cmax), 20.7 versus 25.9 mcg/mL (P less than .05). In study 2, food intake did not affect onset or extent of absorption nor maximum concentration, but did slow rate of absorption. Time to reach peak concentration was 2.7 hours for tablet (fasting), 3.3 hours for capsule (fasting), and 4.8 hours for capsule (nonfasting) (P less than .05). Intrasubject absorption performance from the three doses was highly consistent, regardless of food intake. These data indicate that Sprinkle capsules possess desirable absorption characteristics in a form that makes ingestion easier for patients who have difficulty taking other valproate dosage forms.


Differences in the T lope in males and females with angina pectoris.
In cases with angina pectoris, the location and configuration of the T loop in a male group and a female group were compared. In the male group, the types of abnormal T loop were mainly an anterior displacement type (the AD type) and an abnormal shape type (the AS type). On the contrary, a posterior displacement type (the PD type) was found in most cases in the female group. The movement of the T loop after exercise test or exacerbation was also different in the two groups. In the male group, an anterior displacement or increase of W/L of the T loop was observed, but in the female group, the T loop was dislocated more to the left and posteriorly. The reason for these differences in the T loop in both groups is discussed.


Identification of a transcriptional regulatory region for germline-specific expression of vasa gene in Drosophila melanogaster.
The vasa gene (vas) is essential for germline development in Drosophila melanogaster. Zygotic vas is expressed in pole cells earlier than any other pole cell-expressing genes thus far identified, and VAS protein is continuously present in germline cells throughout development. Here, we report the identification of a regulatory region that directs germline-specific vas expression. A genomic fragment containing the vas locus was linked to enhanced green fluorescent protein (egfp)-vas fusion gene, and the resulting gene was introduced into fly genome. Developmental vas expression was assessed by monitoring the expression of EGFP-VAS in these transformants. The spatio-temporal expression pattern of EGFP-VAS is essentially identical to that of endogenous VAS throughout germline development. By dissecting the vas promoter, we identified a 40-bp regulatory element, which is necessary and sufficient for germline-specific expression during oogenesis. This region interacts specifically with ovarian protein(s). Furthermore, this region is also required for vas expression in pole cells during embryogenesis. These results suggest that a similar mechanism regulates vas expression both in oogenesis and embryogenesis.


Entorhinal transplants and spatial memory abilities in rats.
Transplants of embryonic entorhinal tissues, placed into the angular bundle region of adult rats, innervate appropriate areas of the host hippocampal formation and amygdala, provided that native entorhinal connections have been destroyed. In the present study, transplants were examined for their ability to restore spatial memory abilities which are lost following the bilateral destruction of native entorhinal connections. Animals were tested for their ability to perform an 8-arm radial maze task, for spontaneous alternation in a T-maze, and for their ability to learn to alternate in a T-maze for a food reward. Animals with lesions, and those with lesions + implants, remained impaired on all 3 tasks examined for as long as 6 months postimplantation. During this time, no transplant-induced behavioral recovery was observed, although behavioral stabilization was observed on the spontaneous alternation task at 6 months post-transplantation. The data suggest that these transplants may be limited in their ability to restore functions which are highly dependent upon the anatomical integrity of the damaged circuits and the precise organization of information flow through the damaged area.


Effect of patient history data on the prediction of breast cancer from mammographic findings with artificial neural networks.
The authors evaluated the contribution of medical history data to the prediction of breast cancer with artificial neural network (ANN) models based on mammographic findings. Three ANNs were developed: The first used 10 Breast Imaging Reporting and Data System (BI-RADS) variables; the second, the BI-RADS variables plus patient age; the third, the BI-RADS variables, patient age, and seven other history variables, for a total of 18 inputs. Performance of the ANNs and the original radiologist's impression were evaluated with five metrics: receiver operating characteristic area index (Az); specificity at given sensitivities of 100%, 98%, and 95%; and positive predictive value. All three ANNs consistently outperformed the radiologist's impression over all five performance metrics. The patient-age variable was particularly valuable. Adding the age variable to the basic ANN model, which used only the BI-RADS findings, significantly improved Az (P = .028). In fact, replacing all history data with just the age variable resulted in virtually no changes for Az or specificity at 98% sensitivity (P = .324 and P = .410, respectively). Patient age was an important variable for the prediction of breast cancer from mammographic findings with the ANNs. For this data set, all history data could be replaced with age alone.


Clinical indications for pulmonary artery catheterization in the patient with severe preeclampsia.
The obstetric literature reflects an increased interest in invasive hemodynamic monitoring during the past decade. While much of this interest has focused on research applications, the patient with severe preeclampsia may benefit clinically from pulmonary artery catheterization under several circumstances. These conditions include severe hypertension unresponsive to conventional antihypertensive therapy, pulmonary edema, persistent oliguria unresponsive to fluid challenge, and in induction of conduction anesthesia in select patients. Theoretical and clinical evidence to support this contention is presented.


Ketosteroid Standardized Cissus quadrangularis L. Extract and its Anabolic Activity: Time to Look Beyond Ketosteroid?
Cissus quadrangularis (CQ) L. reported to contain 3-ketosteroids and have bone health benefits. This study aimed at establishing the relationship between the ketosteroid content and anabolic as well as bone health-promoting activities of various Cissus extracts in well-established orchidectomized (ORX) rat model. Supercritical carbon dioxide, ethyl acetate, and aqueous extracts (AE) of CQ L. were prepared and standardized for ketosteroid content by two methods used in commerce. Moreover, ketosteroid standardized extracts of this plant were evaluated for anabolic activity in rats in well-established ORX rat model. The increase in the absolute weight was appreciable in the CQ-AE treated group. Similarly, with respect to bone parameters, a similar trend was seen. The mean bone density, strength, and calcium content were found to be highest in the group treated with CQ-AE compared to groups treated with other extracts. This study reveals for the first time that 3-ketosteroids are not linked to the beneficial activities on bone and highlights the need for extensive characterization of biological active principles from CQ L. In light of the above estimation studies, we believe that current standardization of Cissus extraction "3-ketosteroids" is incorrect. We also did not find any report suggesting the presence of androgenic steroids in this plant and hence the characterization based on "3-ketosteroids" is scientifically incorrect. This study highlights the insufficient understanding of biological active principles from CQ L. and underlines the need for extensive bioactivity guided studies. Cissus quadrangularis (CQ) L. reported to contain 3.ketosteroids and have bone health benefitsWe did not find correlation between ketosteroid content obtained by conventional methods and its biological effectStudies indicate that claims of ketosteroid content need not necessarily correlate to biological effects and hence warrants extensive phytochemical characterization of biological active principles from CQ L. Abbreviations used: CQ: Cissus quadrangularis, ORX: Orchidectomized, AE: Aqueous extract, EE: Ethyl acetate extract, SFE: Supercritical fluid extract.


Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis.
Different data show an association between human herpesvirus 6 (HHV-6) and multiple sclerosis (MS). Intrathecal anti-HHV-6 immunoglobulin G (IgG) was detected in MS patients, but the antigen recognized by cerebrospinal fluid (CSF) IgG has not been characterized yet. Our objective was to identify the HHV-6 antigens recognized by IgG present in the CSF of patients with MS. Cerebrospinal fluid IgG of 15 MS patients and eight patients with other neurological diseases was purified on protein G Sepharose columns. Purified IgG from every patient was linked to a CNBr-activated Sepharose 4B column. Fifty micrograms of viral extract was applied to each column. Bound proteins were eluted and analysed by SDS-PAGE and silver staining. The viral protein was characterized by mass spectrometry. A protein of 150 kD was eluted from CSF IgG columns of three of eight patients with primary progressive MS and one of seven with relapsing-remitting MS. After digestion and mass spectrometry analysis 10 peptides were found with 100% homology with the major capsid protein of the HHV-6A. These findings confirm the presence of anti-HHV-6 IgG in CSF of MS patients, particularly in progressive forms, and identify major capsid protein as the major antigen recognized by CSF IgG from MS patients.


Suppression mechanism of the calcium sensitivity in Saccharomyces cerevisiae ptp2Δmsg5Δ double disruptant involves a novel HOG-independent function of Ssk2, transcription factor Msn2 and the protein kinase A component Bcy1.
In Saccharomyces cerevisiae, disruption of both protein phosphatase genes, PTP2 and MSG5, causes calcium sensitivity while additional disruption of protein kinase genes BCK1, MKK1, SLT2, MCK1, YAK1 and SSK2 confers calcium tolerance. Although the roles of BCK1, MKK1 and SLT2 have been characterized recently, the mechanism of suppression of the calcium sensitivity by SSK2 disruption is poorly understood. In this study, genetic analysis revealed a novel, high osmolarity glycerol (HOG)-independent suppressor function of Ssk2 in relation to the Ptp2 and Msg5-mediated calcium signaling. Through microarray analysis, we identified 19 genes with distinct pattern of expression that is likely involved in the calcium sensitive phenotype of the ptp2Δmsg5Δ double disruptant. Furthermore, we found msn2Δ and bcy1Δ as suppressors of the calcium sensitive phenotype. Our results suggest the interrelationship of a HOG-independent function of Ssk2, transcription factor Msn2, protein kinase A-related protein Bcy1 and 19 rise and fall genes as responsible for the suppression mechanism of the ptp2Δmsg5Δ double disruptant by ssk2Δ disruption.


Effectiveness of an insurance enrollment support tool on insurance rates and cancer prevention in community health centers: a quasi-experimental study.
Following the ACA, millions of people gained Medicaid insurance. Most electronic health record (EHR) tools to date provide clinical-decision support and tracking of clinical biomarkers, we developed an EHR tool to support community health center (CHC) staff in assisting patients with health insurance enrollment documents and tracking insurance application steps. The objective of this study was to test the effectiveness of the health insurance support tool in (1) assisting uninsured patients gaining insurance coverage, (2) ensuring insurance continuity for patients with Medicaid insurance (preventing coverage gaps between visits); and (3) improving receipt of cancer preventive care. In this quasi-experimental study, twenty-three clinics received the intervention (EHR-based insurance support tool) and were matched to 23 comparison clinics. CHCs were recruited from the OCHIN network. EHR data were linked to Medicaid enrollment data. The primary outcomes were rates of uninsured and Medicaid visits. The secondary outcomes were receipt of recommended breast, cervical, and colorectal cancer screenings. A comparative interrupted time-series using Poisson generalized estimated equation (GEE) modeling was performed to evaluate the effectiveness of the EHR-based tool on the primary and secondary outcomes. Immediately following implementation of the enrollment tool, the uninsured visit rate decreased by 21.0% (Adjusted Rate Ratio [RR] = 0.790, 95% CI = 0.621-1.005, p = .055) while Medicaid-insured visits increased by 4.5% (ARR = 1.045, 95% CI = 1.013-1.079) in the intervention group relative to comparison group. Cervical cancer preventive ratio increased 5.0% (ARR = 1.050, 95% CI = 1.009-1.093) immediately following implementation of the enrollment tool in the intervention group relative to comparison group. Among patients with a tool use, 81% were enrolled in Medicaid 12 months after tool use. For the 19% who were never enrolled in Medicaid following tool use, most were uninsured (44%) at the time of tool use. A health insurance support tool embedded within the EHR can effectively support clinic staff in assisting patients in maintaining their Medicaid coverage. Such tools may also have an indirect impact on evidence-based practice interventions, such as cancer screening. This study was retrospectively registered on February 4th, 2015 with Clinicaltrials.gov (#NCT02355262). The registry record can be found at https://www.clinicaltrials.gov/ct2/show/NCT02355262 .


Salt in the soul, steel in the eye and caution towards the winds: a mariner's guide for navigating a new academic psychiatry department.
This paper describes principles and advice regarding the development of a new academic psychiatry department within a medical school for aspiring academic psychiatrists. We describe general principles based on the experience of the foundation of the Academic Unit of Psychiatry and Addiction Medicine at the Australian National University Medical School. Perspicacious leadership and organisation are the foundation for an academic psychiatry department which delivers teaching, research and broader intellectual engagement with the medical and broader community.


Intrapericardial immature teratoma with successful treatment in a neonate.
Intra-pericardial teratoma, most often a benign tumor, is an extremely rare condition in a newborn. It can be a diagnostic and therapeutic challenge if it presents with massive pericardial effusion. Complete surgical excision of the tumor is necessary because of its association with tissues of malignant potential. A 16-d-old newborn was diagnosed with intra pericardial immature teratoma (IT) and managed successfully with multidisciplinary team approach by prompt referral for complete surgical resection followed by adjuvant chemotherapy with carboplatin, etoposide and bleomycin (JEB) to prevent recurrence. The infant is now on close follow up with monitoring of serum alpha fetoprotein (AFP) levels and imaging studies for early diagnosis of recurrence of tumor and chemotherapy related complications.


Myopathy in acquired partial lipodystrophy.
We describe two women with acquired partial lipodystrophy, one with significant myopathic symptoms and signs. Muscle biopsy of deltoid and quadriceps was performed in each case. The light microscopy findings were of type 1 and type 2 fibre hypertrophy, with an increase in intracytoplasmic fat in both cases. Electron microscopy showed normal fibres, with accumulations of electron-lucent fat droplets between the myofibrils. The cause of the lipodystrophies is uncertain, but myopathy may be a feature, and muscle biopsy studies may help in further defining the syndrome.


Significance of incidental desmoids identified during surgery for familial adenomatous polyposis.
The behavior of intra-abdominal desmoids in familial adenomatous polyposis is incompletely understood. Findings range from typical mass lesions to flat sheets, termed the desmoid reaction or desmoid precursor lesion. The latter often are incidental findings of uncertain significance. The study was designed to describe the natural history of incidental intra-abdominal desmoid tumors with particular reference to the desmoid reaction. Patients who underwent laparotomy for familial adenomatous polyposis at the Cleveland Clinic Foundation were identified. The incidence of incidental intra-abdominal desmoid tumors was determined by review of operative records. Intra-abdominal desmoid tumors were classified as mass lesions if three-dimensional or desmoid reaction if two-dimensional. The incidence of clinically apparent intra-abdominal desmoid tumors (typical mass lesions on physical examination or cross-sectional imaging in symptomatic patients) was determined by chart review. The incidence of clinical intra-abdominal desmoid tumors between groups was compared by Fisher's exact test. A total of 266 patients (153 females; median age, 26 (range, 9-63) years) underwent abdominal surgery for familial adenomatous polyposis. Incidental intra-abdominal desmoid tumors were identified in 34 patients: 8 at the index surgery and 26 at relaparotomy. These lesions influenced the planned procedure in eight cases (26 percent), including preventing ileoanal pouch in 3 of 19 patients in whom this was intended. The median follow-up from the time of identification of intra-abdominal desmoids was 42 (range, 2-178) months at which point four patients (11 percent) had developed clinical intra-abdominal desmoid tumors. There was no significant difference in incidence of clinical intra-abdominal desmoid tumors between mass and desmoid reaction groups ( P = 0.27). Incidental intra-abdominal desmoid tumors are a common finding at relaparotomy in patients with familial adenomatous polyposis. These lesions influence planned surgery in a minority of cases. Desmoid reaction may have little bearing on the subsequent development of clinically significant intra-abdominal desmoid tumors.


Effects of phenylpropanolamine on withdrawal symptoms.
A prior report (Klesges et al. 1990) suggested that phenylpropanolamine (PPA) was successful in reducing the smoking withdrawal symptom of weight gain in a sample of women. The current investigation evaluates whether the effects of phenylpropanolamine (PPA; up to 10/day PPA gums) on withdrawal symptoms associated with smoking cessation are specific to weight and weight-related symptoms or whether PPA alleviates withdrawal in general. One hundred and seven adult smokers (56 men, 51 women) were randomly assigned, in this double-blind trial, to chew either 8.33 mg phenylpropanolamine gum or a placebo gum. Subjects were then aided to quit smoking for 4 weeks. PPA did not enhance cessation rates. Results from the 47 subjects who successfully quit smoking indicated that postcessation weight gain and ratings of hunger were significantly reduced in both men and women for those assigned to the PPA group relative to the placebo group. Overall, no effects of PPA relative to placebo were observed for other smoking-related withdrawal symptoms. Thus, although PPA appears to reduce weight gain and alleviate weight-related symptoms, no effects on other withdrawal symptoms were observed. Future research directions are suggested.


Multicore-shell MnO2@Ppy@N-doped porous carbon nanofiber ternary composites as electrode materials for high-performance supercapacitors.
In this study, a multicore-shell ternary composite electrode material (MnO2@Ppy@NPCNFs) with excellent electrochemical performances was prepared by using surface modification, in which core-shell Ppy@N-doped porous carbon nanofibers (Ppy@NPCNFs) with large specific surface area and high conductivity were used as the substrate (a multicore layer), and MnO2 was loaded on the substrate by hydrothermal synthesis to form a shell layer, further improving the SC of electrode material. The parameters of hydrothermal growth of MnO2 on Ppy@NPCNFs were explored by means of the control variable method and response surface methodology, and the optimal parameters were predicted and verified. Electrochemical test results showed that the SC of MnO2@Ppy@NPCNFs prepared under the optimal reaction parameters was as high as 595.77 F g-1, and its capacitance retention was 96.2 % after 1000 cycles. Moreover, a symmetric supercapacitor prepared with the optimal multicore-shell electrode showed an energy density of 9.36 Wh kg-1 at a power density of 1000 W kg-1 and a retention rate of 92.46 % after 1000 cycles, indicating the promising application of multicore-shell ternary composite electrode material in high-performance supercapacitors.


[Red blood cell production for transfusion purposes. A stem cell ex vivo fate].
In vitro generation of red blood cells (RBC) makes sense in a context of recurrent shortage. It could be an interesting complementary source for "classic" transfusion products by combining the sufficiency of supply, homemade production of a particular phenotype of interest and reduced risk of infection. The question that arises is how to produce in vitro RBC? Here we retrace the steps that led to the production of functional RBC, from basic knowledge of in vivo erythropoiesis to in vitro generation of RBC from different sources of stem cells. Regarding the adults HSC, the major finding lies in the recent establishment of proof of concept of their transfusion in humans. Because the induced pluripotent stem cells (IPS) can proliferate indefinitely and be selected for a phenotype of interest, they are obviously the best source of stem cells. Proof of concept of generation of RBC from IPS has been made, but still has to be optimized. We also discuss the key points that need to be solved to achieve clinical transfusion application.


Traumatic brain injury and bone healing: radiographic and biomechanical analyses of bone formation and stability in a combined murine trauma model.
The combination of traumatic brain injury (TBI) and long-bone fractures has previously been reported to lead to exuberant callus formation. The aim of this experimental study was to radiographically and biomechanically study the effect of TBI on bone healing in a mouse model. 138 female C57/Black6N mice were assigned to four groups (fracture (Fx) / TBI / combined trauma (Fx/TBI) / controls). Femoral osteotomy and TBI served as variables: osteotomies were stabilized with external fixators, TBI was induced with controlled cortical impact injury. During an observation period of four weeks, in vivo micro-CT scans of femora were performed on a weekly basis. Biomechanical testing of femora was performed ex vivo. The combined-trauma group showed increased bone volume, higher mineral density, and a higher rate of gap bridging compared to the fracture group. The combined-trauma group showed increased torsional strength at four weeks. TBI results in an increased formation of callus and mineral density compared to normal bone healing in mice. This fact combined with a tendency towards accelerated gap bridging leads to increased torsional strength. The present study underscores the empirical clinical evidence that TBI stimulates bone healing. Identification of underlying pathways could lead to new strategies for bone-stimulating approaches in fracture care.


Germline Variants Incidentally Detected via Tumor-Only Genomic Profiling of Patients With Mesothelioma.
Patients with mesothelioma often have next-generation sequencing (NGS) of their tumor performed; tumor-only NGS may incidentally identify germline pathogenic or likely pathogenic (P/LP) variants despite not being designed for this purpose. It is unknown how frequently patients with mesothelioma have germline P/LP variants incidentally detected via tumor-only NGS. To determine the prevalence of incidental germline P/LP variants detected via tumor-only NGS of mesothelioma. A series of 161 unrelated patients with mesothelioma from a high-volume mesothelioma program had tumor-only and germline NGS performed during April 2016 to October 2021. Follow-up ranged from 18 months to 7 years. Tumor and germline assays were compared to determine which P/LP variants identified via tumor-only NGS were of germline origin. Data were analyzed from January to March 2023. The proportion of patients with mesothelioma who had P/LP germline variants incidentally detected via tumor-only NGS. Of 161 patients with mesothelioma, 105 were male (65%), the mean (SD) age was 64.7 (11.2) years, and 156 patients (97%) self-identified as non-Hispanic White. Most (126 patients [78%]) had at least 1 potentially incidental P/LP germline variant. The positive predictive value of a potentially incidental germline P/LP variant on tumor-only NGS was 20%. Overall, 26 patients (16%) carried a P/LP germline variant. Germline P/LP variants were identified in ATM, ATR, BAP1, CHEK2, DDX41, FANCM, HAX1, MRE11A, MSH6, MUTYH, NF1, SAMD9L, and TMEM127. In this case series of 161 patients with mesothelioma, 16% had confirmed germline P/LP variants. Given the implications of a hereditary cancer syndrome diagnosis for preventive care and familial counseling, clinical approaches for addressing incidental P/LP germline variants in tumor-only NGS are needed. Tumor-only sequencing should not replace dedicated germline testing. Universal germline testing is likely needed for patients with mesothelioma.


Exercise-induced changes in hippocampal brain-derived neurotrophic factor and neurotrophin-3: effects of rat strain.
We tested the hypothesis that exercise-induced changes in hippocampal brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) differ among rat strains exhibiting a range of voluntary wheel running activity. Four strains (Sprague-Dawley, Brown Norway, Dark Agouti and PVG) were given access to running wheels (1 or 7 nights). Over 7 nights, the average distance run per night was higher in PVG versus other strains, and higher in Brown Norway versus Sprague-Dawley rats. Hippocampal BDNF concentrations in sedentary rats were higher in PVG versus Sprague-Dawley rats. When data from all strains were combined, BDNF levels increased with 7 nights of wheel running and were positively correlated to the previous night distance run. Sedentary hippocampal NT-3 levels were not different between rat strains, but decreased with 7 nights of wheel access; NT-3 was negatively correlated with previous night distance run. There were no differences between strains in the correlation between distance run and BDNF or NT-3 levels. Although exercise decreases hippocampal NT-3, strain does not alter NT-3 levels. In contrast, BDNF levels increase with exercise and basal levels differ between strains, possibly due to strain differences in spontaneous activity.


Barriers to Patient Portal Access and Use: Evidence from the Health Information National Trends Survey.
Patient access to their medical records through patient portals (PPs) facilitates information exchange and provision of quality health care. Understanding factors that characterize patients with limited access to and use of PPs is needed. Data were from the 2017-2018 Health Information National Trends Survey 5, Cycles 1 and 2, a nationally representative survey of US adults ≥ 18 years old (n = 6789). Weighted multivariate logistic regressions modeled the associations between patient characteristics and access to, facilitators of use, and use of PPs and their functions. Individuals without (vs with) a regular doctor (adjusted odds ratio [aOR], 0.4; CI, 0.3-0.5) or health insurance (aOR, 0.4; CI, 0.2-0.7), those with high school (aOR 0.4; CI, 0.3-0.5) or with vocational/some college (aOR, 0.5; CI, 04.-0.7) education (vs college/postgraduate), or those with limited English proficiency (vs those who speak English very well) (aOR, 0.7; CI, 0.5-0.9) were less likely to report accessing their personal medical records. Women (vs men) were more likely to report accessing their medical records (aOR, 1.5; CI, 1.2-1.8). Similar patterns were found for PPs access and facilitators of use. Less consistent associations emerged between patient characteristics and use of PP functionalities. PP access and use are low. Having a primary care clinician, patient's educational attainment, and being a woman were factors associated with PP access and use, but not race/ethnicity. Once access was achieved, use of PP functionalities was generally uniform across demographic segments. Facilitating PP access and use among all patient populations is warranted.


IL1A-889 C/T gene polymorphism in irritant contact dermatitis.
Upon skin contact to irritants, interleukin-1 alpha (IL-1α) is released in the stratum corneum as a primary step of skin inflammation. Variations in the IL-1A gene have been shown to alter the expression of IL-1α. This may influence the susceptibility to skin inflammation and the development of irritant contact dermatitis (ICD). To determine effects of an IL1A-889 C/T polymorphism in view of susceptibility to develop irritant contact dermatitis. In a case-control study, 478 Caucasian patients with occupational ICD of the hands were genotyped for an IL1A-889 C/T polymorphism. Results were compared to 393 apprentices from the same high risk occupations (controls). Trends of a protective effect of the C → T transition at position IL1A-889 were seen (OR = 0.81; 95% CI: 0.65-1.00). The genotype distribution for IL1A-889 was 52.2% wild type (C/C), 39.2% heterozygous (C/T) and 8.6% homozygous for variant allele (T/T) in patients and 46.0%, 42.7% and 11.4% in controls. Subgroup analysis, which took into account atopy status and exposure, did not reveal a significant effect of this polymorphism for an aberrant risk to acquire for ICD. Our study indicates a possible protective effect of the IL1A-889 C/T polymorphism regarding the development of ICD.


LncRNAs in Kawasaki disease and Henoch-Schönlein purpura: mechanisms and clinical applications.
Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the two most predominant types of childhood vasculitis. In childhood vasculitis, factors such as lack of sensitive diagnostic indicators and adverse effects of drug therapy may cause multiorgan system involvement and complications and even death. Many studies suggest that long noncoding RNAs (lncRNAs) are involved in the mechanism of vasculitis development in children and can be used to diagnose or predict prognosis by lncRNAs. In existing drug therapies, lncRNAs are also involved in drug-mediated treatment mechanisms and are expected to improve drug toxicity. The aim of this review is to summarize the link between lncRNAs and the pathogenesis of KD and HSP. In addition, we review the potential applications of lncRNAs in multiple dimensions, such as diagnosis, treatment, and prognosis prediction. This review highlights that targeting lncRNAs may be a novel therapeutic strategy to improve and treat KD and HSP.


PnpB involvement in the regulation of temperature-sensitive para-nitrophenol degradation in Pseudomonas putida MT54 via PnpA.
Pseudomonas putida DLL-E4 can efficiently degrade para-nitrophenol and its intermediate metabolite hydroquinone at 37 °C and 30 °C. However, mutant strain Pseudomonas putida MT54, obtained by transposon mutagenesis from P. putida DLL-E4, could not degrade para-nitrophenol at 37 °C. The mutant genes including DW66_0143, DW66_0153 and pnpB were discovered in strain MT54 by whole genome resequencing. Gene knockout and complementation confirmed the necessity of PnpB in PNP degradation by temperature-sensitive strain MT54. PnpA catalyzes the first step in complete degradation of PNP, and we found its activity was significantly enhanced by PnpB. The measurement of bacterial two-hybrid system indicated that the effect was not mediated by the direct interaction between PnpA and PnpB, but caused by the elimination of product inhibition of PnpA. Furthermore, PnpA was characterized as a psychrophilic enzyme with optimum temperature of 20 °C. We concluded that the lowered activity of PnpA resulted from inactivation of PnpB at the restrictive temperature induced the temperature-sensitive characteristic of P. putida MT54.


[Ocular trauma in the Pediatric Emergency Departments, characteristics and risk factors of immediate sequelae].
This study assesses the clinical characteristics and epidemiology of children with eye trauma presenting to the Emergency Department in Spain and analyze the risk factors associated with immediate sequelae. A multicentric prospective case series study conducted during 24 months of patients presenting to the Pediatric Emergency Departments in five hospitals collaborating with the Spanish Pediatric Emergency Research Group. Data were collected from October 2016 through September 2018, including all patients up to the age of 16 years old presenting to the Emergency Department with an ocular trauma. All injuries were classified by Birmingham Eye Trauma Terminology. A total of 242,134 visits to the Emergency Departments took place during the study period, being 1,007 ocular traumas (0.42%; IC 95% 0.40-0.45) and 858 were included in the study. Most commonly, injuries occurred while playing (54.7%), except in the 15 or more-age group, in which sports activities were more common (23.1%). The place of the trauma varied depending on the age group, being home (34.7%) and schools or sports areas (34.3%) the most recurrent. Blunt objects were the most frequent mechanism of trauma (48.6%). Most of the injuries were classified as closed globe (85.5%), mainly contusions (52.7%). Fifty-eight patients (6.8%) presented with immediate sequelae, being the impairment of visual acuity the most common (70.7%). The risk factors associated with immediate sequelae were the 10 or more-age group, the preexisting refractive errors, the open globe injuries and the injuries with blunt objects. Ocular trauma is a frequent chief complaint in the Pediatric Emergency Departments in Spain. Increasing awareness of the serious nature of ocular injuries and the study of the risk factors will help to develop a comprehensive plan for educating both parents and children to minimize preventable eye injuries sequelae.


Peripheral signals modifying food reward.
The pleasure derived from eating may feel like a simple emotion, but the decision to eat, and perhaps more importantly what to eat, involves central pathways linking energy homeostasis and reward and their regulation by metabolic and endocrine factors. Evidence is mounting that modulation of the hedonic aspects of energy balance is under the control of peripheral neuropeptides conventionally associated with homeostatic appetite control. Here, we describe the significance of reward in feeding, the neural substrates underlying the reward pathway and their modification by peptides released into the circulation from peripheral tissues.


Association between vitiligo and hearing loss.
Vitiligo is a common depigmenting disorder caused by the autoimmune destruction of melanocytes. Some evidence suggests the involvement of melanocytes in the auditory system in the disease process. However, the relationship between vitiligo and sensorineural hearing loss (SNHL) remains uncertain. We investigated the association between vitiligo and SNHL. In this systematic review and meta-analysis, EMBASE, MEDLINE, PubMed, and the Cochrane database were searched for studies examining the association between SNHL and vitiligo from inception to June 28, 2020. A total of 14 case-control studies with 938 patients with vitiligo were included. The meta-analysis showed a significant association of SNHL with vitiligo (odds ratio [OR] 6.02 [95% confidence interval {CI} 3.41-10.62]). The association remained significant after adjustment of study quality and publication bias, with ORs of 5.30 (95% CI 1.53-18.35), and 3.45 (95% CI 1.75-6.81), respectively. Heterogenous definition and measurement of hearing loss and racial differences are potential sources of bias. The evidence to date supports an association of SNHL with vitiligo. These results suggest audiologic assessment for early recognition and management of hearing loss in patients with vitiligo.


Prognostic Value of Troponin in Patients with Atrial Fibrillation Admitted to an Emergency Department: Review and Meta-Analysis.
Elevated levels of cardiac troponin (cTn) indicate underlying heart disease and is known to predict adverse events in multiple conditions. Its role in atrial fibrillation (AF) in the acute setting is still not conclusive. We aimed to assess the prognostic value of c-Tn in patients with AF admitted to an emergency department (ED). Systematic searches were conducted using PubMed and the Cochrane Library and the International Clinical Trials Registry Platform to identify studies from year 2009 to October 2019 reporting on the prognostic value of cTn on all-cause mortality or major adverse cardiac events (MACE) in adult patients with AF in the ED. We pooled hazard ratio (HR) and 95% confidence interval (CI) using fixed and random effects models according the heterogeneity. We planned to conduct a sensitivity and subgroup analyses. Five studies involving 5750 patients were identified. The mean follow-up ranged from 12 to 35 months. An increase in mortality was observed in the elevated cTn group compared to the controls, HR=2.7 (95% CI 1.55-4.72), P for effect<0.001, I2=80%). For MACE, the pooled HR was 2.17 (95%CI 1.60-2.94), P for effect<0.001, I2=0%). In the subgroup analysis we found no significant difference in type of troponin used and study design. The elevation of cardiac troponin was significantly associated with higher mortality and major adverse cardiac events in patients with AF admitted to an ED. In this setting the use of c-Tn could provide prognostic information.


Bioinformatics analysis of amino acid decarboxylases related to four major biogenic amines in pickles.
Microbial amino acid decarboxylases (AADs) produce biogenic amines (BAs) in fermented food. However, a systematic comparison of the AADs' properties from different microorganisms in pickle fermentation remains unexplored. Here, we bioinformatically analyzed the amino acid sequences of AADs corresponding to four major BAs for common microorganisms in pickle fermentation. We showed that their sequences, besides tyrosine decarboxylase, differed among microorganisms. Overall, the AAD sequences varied lesser among bacterial species than between bacteria and fungi, with those in Lactobacillus sharing occasionally high similarity with other bacteria. Most AADs were predicted as stable cytosolic endoenzymes. Molecular docking showed that most commonly used spice components in pickle production, especially pepper, chili, and ginger, strongly bind to the AAD active sites, thus may inhibit the enzymes and reduce the BA accumulation. This study provides insights for deeply understanding the different microbial AAD properties in pickle fermentation and reducing BAs by appropriately using spices.


Access and latency to first antipsychotic treatment in Italian patients with schizophrenia and other schizophrenic spectrum disorders across different epochs.
The duration of untreated illness (DUI) is a measure to express the latency to first psychopharmacological treatment: it differs among psychiatric disorders, being influenced by several illness-intrinsic and environmental factors. The present study aimed to assess differences in DUI and related variables in patients with schizophrenia (SKZ) versus other schizophrenic spectrum disorders (SSDs) across different epochs. 101 SKZ or SSD patients were assessed with respect to DUI and related variables through clinical interview and questionnaire. Patients with SKZ showed earlier ages of onset, first diagnosis and first antipsychotic treatment compared with patients with other SSDs (F = 11.02, p < 0.001; F = 12.68, p < 0.001; F = 13.74, p < 0.001, respectively) who showed an earlier access to benzodiazepines than SKZ patients (F = 6.547; p < 0.05). Dividing the total sample by the epoch of onset (before 1978; between 1978-2000; after 2000) showed a significantly later age of onset in patients with onset within the two most recent epochs (F = 7.46; p < 0.001) and a reduced DUI across epochs (from 144 to 41 to 20 months, on average; F = 11.78, p < 0.001). Schizophrenic patients showed earlier onset and longer DUI compared with patients with other SSDs. Data on the total sample showed a later age of onset and a reduced DUI across epochs.


Concomitant Malnutrition and Frailty Are Uncommon, but Significant Risk Factors for Mortality and Complication Following Primary Total Knee Arthroplasty.
Total knee arthroplasty (TKA) demand continues to rise, but we are also gaining greater insight into patient risk factors for postoperative complications and excess resource utilization. There has been growing interest in frailty and malnutrition as risk factors, although they are often mistakenly used interchangeably. We aimed at identifying the incidence of their coexistence, and the magnitude of risk they confer to TKA patients. We queried the American College of Surgeons-National Surgery Quality Improvement Program database to identify 4 patient cohorts: healthy/normal serum albumin, healthy/hypoalbuminemic patients, normoalbuminemic/medically frail patients (defined by modified frailty index), and hypoalbuminemic/frail patients. We performed both univariate and multivariate analyses to quantify the risk conferred by each condition in isolation, and in coexistence. Of 179,702 elective TKA cases from 2006 to 2018, 18.6% of patients were frail only, 3.0% were hypoalbuminemic -only, and just 1.2% were both frail and hypoalbuminemic. The raw rate of any complication was highest in frail/hypoalbuminemic patients (8.7%), 5.2% in hypoalbuminemic patients, 4.8% in frail patients, and just 3.4% in healthy patients (P < .001); the multivariate model revealed odds ratio of a complication in frail/hypoalbuminemic group of 2.40 (95% confidence interval = 1.27-1.63; P < .001). Mortality within 30 days was highest in the frail/hypoalbuminemic cohort (1.0%), and just 0.1% in healthy patients, and the multivariate model noted an odds ratio of 9.43 for these patients (95% confidence interval = 5.92-14.93; P < .001). The odds of all studied complications were highest in the frail/hypoalbuminemic group. Frailty and hypoalbuminemia represent distinct conditions and are independent risk factors for a complication after TKA. Their coexistence imparts a synergistic association with the risk of post-TKA complications.


Inflammatory cell changes in haversian canals. A possible cause of osteoporosis in rheumatoid arthritis.
We studied the morphology of the haversian canals in the osteopenic cortical bone of the medial femoral neck from patients with rheumatoid arthritis and compared the findings with those in patients with osteoarthritis and with uncomplicated coxa valga. In the rheumatoid bone, the diameters of the canals were larger and many more contained osteoclasts. Fewer haversian canals showed only lining cells than in the osteoarthritic or coxa valga patients. In bone from rheumatoid patients, especially in canals with osteoclasts, small blood vessels were frequently lined by tall endothelial cells with an infiltration of mononuclear cells. These morphological differences are discussed with reference to the possible mechanisms of loss of cortical bone in rheumatoid arthritis and other conditions.


Sex-differences in relation to the association between patterns of physical activity and sedentary behavior with frailty.
To investigate the sex-difference in relation to the association between moderate-vigorous physical activity (MVPA) and sedentary time (ST) patterns with frailty. Accelerometry from ≥50 year olds from the National Health and Nutrition Examination Survey (2003-04/2005-06 cycles) were included. Bouted and sporadic MVPA were defined as MVPA in ≥10 min or <10 min durations, respectively. MVPA was analyzed based on meeting 0 %, 1-49 %, 50-99 %, and ≥100 % of the physical activity guidelines of 150 min/week. A duration of ≥30 minutes defined prolonged ST. The frequency (≥1 min interruption in ST), intensity and duration of breaks from ST were calculated. A 46-item frailty index (FI) quantified frailty. Multivariable linear regression models adjusted for demographics, total sedentary time, and accelerometer wear time. There were 1143 females and 1174 males available for analysis. Bouted MVPA was associated with lower frailty levels; the association peaked at meeting 50-99 % of the guidelines in females and ≥1.0 % in males (p = NS for sex-interaction). Meeting a higher proportion of the guidelines through sporadic MVPA was significantly associated with a lower FI in males only (p = NS for sex-interaction). Prolonged ST bouts were associated with worse frailty in females but not males (p < 0.05 sex-interaction). Average break intensity was associated with a lower FI in both sexes, whereas, total sedentary breaks were not (p = NS for sex-interaction). Average break duration was associated with frailty in males (p = NS for sex-interaction). Prolonged ST was more detrimentally associated with frailty in females than males, which could influence tailored movement prescriptions and guidelines.


The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy.
Severe congenital neutropenia as well as primary myelofibrosis are rare in infancy. Elucidation of the underlying mechanism is important because it extends our understanding of the more common adult forms of these disorders. Using homozygosity mapping followed by exome sequencing, we identified a Thr224Asn mutation in the VPS45 gene in infants from consanguineous families who suffered from life-threatening neutropenia, which was refractory to granulocyte CSF, from defective platelet aggregation and myelofibrosis. The mutation segregated in the families, was not present in controls, affected a highly conserved codon, and apparently destabilized the Vps45 protein, which was reduced in the patients' leukocytes. Introduction of the corresponding mutation into yeast resulted in reduced cellular levels of Vps45 and also of the cognate syntaxin Tlg2, which is required for membrane traffic through the endosomal system. A defect in the endosomal-lysosomal pathway, the homologous system in humans, was suggested by the absence of lysosomes in the patients' fibroblasts and by the depletion of α granules in their platelets. Importantly, accelerated apoptosis was observed in the patients' neutrophils and bone marrow. This is the first report of a Vps45-related disease in humans, manifesting by neutropenia, thrombasthenia, myelofibrosis, and progressive bone marrow failure.


Antioxidant analysis of ultra-fast selectively recovered 4-hydroxy benzoic acid from fruits and vegetable peel waste using graphene oxide based molecularly imprinted composite.
Food processing industries generate 25-30% of fruit and vegetable peel (F&VP) waste of the total produce, which are rich in polyphenolic antioxidants (PA). Sustainable solution for the above waste can be its valorization for the recovery of PA, often used as natural preservative. Present work reports rationally designed graphene oxide-based molecularly imprinted composites (GOMIPs) using ionic liquid 1-allyl-3-octylimidazolium chloride (A) as a green functional monomer for selective recovery of PA 4-Hydroxy benzoic acid (4HA) from F&VP/pomegranate peel (PGP) waste. GOMIP-A and GOMIP-V were characterized using various techniques for its successful synthesis. GOMIP-A attained equilibrium within 10 min with adsorption capacity of 190.56 μmol g-1 for 4HA. Developed HPLC method depicted selective recovery of 77.23% and 62.83% 4HA from F&VP and PGP waste respectively by GOMIP-A. Subsequently, desorbed 4HA from GOMIP-A matrices exhibited the antioxidant potential of 33.53% (F&VP extract) and 47.97% (PGP extract) for DPPH radical.


Bacteria can promote calcium oxalate crystal growth and aggregation.
Our previous report showed that uropathogenic bacteria, e.g., Escherichia coli, are commonly found inside the nidus of calcium oxalate (CaOx) kidney stones and may play pivotal roles in stone genesis. The present study aimed to prove this new hypothesis by direct examining CaOx lithogenic activities of both Gram-negative and Gram-positive bacteria. CaOx was crystallized in the absence (blank control) or presence of 10(5) CFU/ml E. coli, Klebsiella pneumoniae, Staphylococcus aureus, or Streptococcus pneumoniae. Fragmented red blood cell membranes and intact red blood cells were used as positive and negative controls, respectively. The crystal area and the number of aggregates were measured to initially screen for effects of bacteria on CaOx crystal growth and aggregation. The data revealed that all the bacteria tested dramatically increased the crystal area and number of crystal aggregates. Validation assays (spectrophotometric oxalate-depletion assay and an aggregation-sedimentation study) confirmed their promoting effects on both growth (20.17 ± 3.42, 17.55 ± 2.27, 16.37 ± 1.38, and 21.87 ± 0.85 % increase, respectively) and aggregation (57.45 ± 2.08, 51.06 ± 5.51, 55.32 ± 2.08, and 46.81 ± 3.61 % increase, respectively) of CaOx crystals. Also, these bacteria significantly enlarged CaOx aggregates, with the diameter greater than the luminal size of distal tubules, implying that tubular occlusion might occur. Moreover, these bacterial effects were dose-dependent and specific to intact viable bacteria, not intact dead or fragmented bacteria. In summary, intact viable E. coli, K. pneumoniae, S. aureus, and S. pneumoniae had significant promoting effects on CaOx crystal growth and aggregation. This functional evidence supported the hypothesis that various types of bacteria can induce or aggravate metabolic stone disease, particularly the CaOx type.


Clinical analysis of 40 cases of uterine rupture at Durgapur Subdivisional Hospital: an observational study.
Forty cases of uterine rupture that occurred at Durgapur Subdivisional Hospital during 5 years period from January, 1995 to December, 1999 were analysed for clinical observations. The incidence was 1:273; 77.5% were spontaneous, 15% were traumatic, and 7.5% had scar rupture. It was complete in 92.5% cases. Disproportion was responsible in 40% cases and malpresentation in 27.5% cases. Total hysterectomy was done in 30% cases, subtotal in 27.5% cases and rent repair in 42.5% of cases. Overall maternal mortality was 30% of which highest (41.2%) found in rent repair and lowest (16.6%) in total hysterectomy.


Inclusion of vein traits improves predictive power for the leaf economic spectrum: a response to Sack et al. (2013).
Our model for the worldwide leaf economics spectrum (LES) based on venation networks (Blonder et al., 2011, 2013) was strongly criticized by Sack et al. (2013) in this journal. Here, we show that the majority of criticisms by Sack et al. are based on mathematical and conceptual misunderstandings. Using empirical data from both our original study as well as others in the literature, we show support for our original hypothesis, that venation networks provide predictive power and conceptual unification for the LES. In an effort to reconcile differing viewpoints related to the role of leaf venation traits for the LES, we highlight several lines of further investigation.


Influence of deep dry cryogenic treatment on cutting efficiency and wear resistance of nickel-titanium rotary endodontic instruments.
This study tested the effect of cryogenic treatment on nickel-titanium (NiTi) endodontic instruments. Ten rotary NiTi instruments (ProFile 30, 0.06; Dentsply Maillefer Instruments SA, Baillegues, Switzerland)) were subjected to deep dry cryogenic treatment at liquid nitrogen temperature (-185 degrees C) (group A) and compared with that of nontreated instruments (group B). Root canals of 30 extracted permanent mandibular premolars were prepared to size 25 using ProFile 0.04 taper rotary NiTi instruments. Each instrument was used in 4 root canals for a total of 240 seconds. Cutting efficiency in rotary motion was assessed from weight loss of tooth samples after instrumentation. Wear resistance was assessed from surface defects on cutting heads pre- and postinstrumentation using scanning electron microscope. The weight loss was significantly higher in group A (p < 0.05, Student t test). The presence of surface defects after use was higher in group B. Deep dry cryogenic treatment increases the cutting efficiency significantly but not the wear resistance.


The immunity and lysis genes of ColN plasmid pCHAP4.
Nucleotide sequencing of part of the plasmid pCHAP4, which encodes the ca. 42,000 Da putative poreforming colicin N, confirmed previous results indicating that the colicin N immunity gene (cni) and the colicin release or lysis gene (cnl) are located immediately downstream from the colicin N structural gene (cna) in the order cna-cni-cnl. The cni gene is transcribed in the opposite direction to cna and probably encodes an Mr 15239 Da protein. The putative immunity protein was detected among the [35S]methionine-labelled proteins produced by minicells carrying cni cloned under lac promoter control, and when the gene was subcloned into expression vectors under the control of a bacteriophage T7 promoter. Deletion of the region immediately upstream from cni completely abolished colicin N immunity, presumably because the natural promoter had been deleted. cnl is in the same operon as cna, and encodes a typical Col plasmid pro-lysis protein comprising a signal peptide and a 34 residue mature polypeptide with high homology to all but one of the other known Col lysis proteins, including the fatty acylated amino-terminal cysteine residue which was specifically labelled with 3H-palmitate. Cell fractionation studies indicated that the cnl gene product was located predominantly in the outer membrane.


Threats to epistemic agency in young people with unusual experiences and beliefs.
A good therapeutic relationship in mental health services is a predictor of positive clinical outcomes for people who seek help for distressing experiences, such as voice hearing and paranoia. One factor that may affect the quality of the therapeutic relationship and raises further ethical issues is the impact of the clinical encounter on users' sense of self, and in particular on their sense of agency. In the paper, we discuss some of the reasons why the sense of epistemic agency may be especially fragile in young people with unusual experiences and beliefs. We argue that it is important to identify and avoid behaviours that can undermine young people's contributions as epistemic agents in the clinical encounter.


[Short Stem, Straight Stem or Anatomical Stem: Free Decision or Recommendations?]
The main goal of total hip arthroplasty is to reduce pain. But function, stability, and longevity are also of major importance. Since the inauguration of modern total hip arthroplasty by Charnley, the designs of stems has undergone many changes. The following paper concerns the straight stem, the anatomical stem and the short stem in total hip arthroplasty. It attempts to answer the question as to whether there is a recommendation for the use of a special stem. The straight stem is the oldest of these stem types. Depending on the particular design, the anchorage of these stems may lie in the metaphyseal or the diaphyseal parts of the femur. The closer the contact of the stem is to the diaphyseal part, the greater is the risk of stress shielding. The anatomical stem attempts to match the geometry of the proximal femoral endosteal. This can be helpful to reconstruct the natural load bearing but has also limitations in fitting. The short stem was designed to achieve an anatomical pattern of stress distribution, resection of less bone and reduction in thigh pain. There are additional differences between the designs. But not only the stem design has to be considered. The proximal part of the femur exhibits a great variety of morphologies. Whereas younger patients mostly have secondary osteoarthritis due to deformities, elderly patients may have changes in morphology due e.g. osteoporosis. Depending on these patient-specific factors and bearing biomechanical aspects in mind, the surgeon must choose the stem design. This may require different stem designs with different mechanisms of fixation.


Evidence for differentiation of NK1+ cells into cytotoxic T cells during acute rejection of allogeneic bone marrow grafts.
The ability of lethally irradiated C57BL/6 mice to acutely reject H-2d bone marrow is due to a lymphocyte population that is NK1+, ASGM1+, CD4-, CD8-, CD3+. Transfer of spleen cells from C57BL/6 mice expressing these antigens into nonresponder 129 mice adoptively transfers the ability to reject H-2d marrow grafts. The specificity of this rejection maps to the H-2D major histocompatibility complex (MHC) region. Transplantation of high doses of H-2d marrow into C57BL/6 overrides the acute rejection mechanism leading to graft survival. During growth of the graft, a cytolytic activity develops that is due to ASGM1+, CD8+ cytolytic T lymphocytes (CTLs) with H-2Ld specificity. The possibility that the ASGM1+, CD8+ CTLs are descendents of the CD3+, NK1+, ASGM1+, CD8- cells responsible for acute rejection is investigated by adoptive cell transfer experiments. We show that beige mice that lack NK1+ cells as well as the ability to acutely reject H-2d marrow fail to generate specific CTLs after transplantation with a high dose of H-2d marrow. Transfer of highly purified NK1+ cells from B6.PL-Ly-2a/Ly-3a (Lyt-2.1) into beige mice together with H-2d marrow leads to generation of Lyt-2.1 CTLs from donor NK1+ cells. These results show that specific CTLs are generated from NK1+ cells during acute marrow graft rejection.