Time from submission to publication in plastic surgery journals: The story of accepted manuscripts.
Publication of research in highly regarded journals is a laborious journey that requires a considerable amount of effort and time. The objective of this article is to obtain insight into the time required for articles to be accepted and published in the top six plastic surgery journals and to study the effects of article characteristics on their publication time. A comprehensive review of all articles published by six scientific plastic surgery journals during a one-year period (2018) was performed. Time taken from submission to acceptance, online, and in-print publication was abstracted and analyzed. A total of 1141 articles were reviewed. The median total time (TT) from submission to in-print publication was 10.3 months (IQR 8-12.6), with a median time of 4.6 months (3-6.8) from submission to acceptance and 5.4 months (4.2-6.3) from acceptance to publication. TT varied among journals, ranging from 7.2 months for Aesthetic Plastic Surgery to 16.1 months for Microsurgery. The articles were available online after a median of 21 days from their acceptance date. When comparing our results to publication times in 2005, most journals showed a decrease in their total publication time. Our study highlights the time taken for publication and the differences between plastic surgery journals and study characteristics. Most journals have demonstrated a quicker turnaround time during the last 13 years. Online publication has greatly decreased the time between acceptance and in-print publication. We advocate for improving certain areas of this timeline, but this improvement should not be at the expense of review quality.


Cosubstrate-induced dynamics of D-3-hydroxybutyrate dehydrogenase from Pseudomonas putida.
D-3-Hydroxybutyrate dehydrogenase from Pseudomonas putida belongs to the family of short-chain dehydrogenases/reductases. We have determined X-ray structures of the D-3-hydroxybutyrate dehydrogenase from Pseudomonas putida, which was recombinantly expressed in Escherichia coli, in three different crystal forms to resolutions between 1.9 and 2.1 A. The so-called substrate-binding loop (residues 187-210) was partially disordered in several subunits, in both the presence and absence of NAD(+). However, in two subunits, this loop was completely defined in an open conformation in the apoenzyme and in a closed conformation in the complex structure with NAD(+). Structural comparisons indicated that the loop moves as a rigid body by about 46 degrees . However, the two small alpha-helices (alphaFG1 and alphaFG2) of the loop also re-orientated slightly during the conformational change. Probably, the interactions of Val185, Thr187 and Leu189 with the cosubstrate induced the conformational change. A model of the binding mode of the substrate D-3-hydroxybutyrate indicated that the loop in the closed conformation, as a result of NAD(+) binding, is positioned competent for catalysis. Gln193 is the only residue of the substrate-binding loop that interacts directly with the substrate. A translation, libration and screw (TLS) analysis of the rigid body movement of the loop in the crystal showed significant librational displacements, describing the coordinated movement of the substrate-binding loop in the crystal. NAD(+) binding increased the flexibility of the substrate-binding loop and shifted the equilibrium between the open and closed forms towards the closed form. The finding that all NAD(+) -bound subunits are present in the closed form and all NAD(+) -free subunits in the open form indicates that the loop closure is induced by cosubstrate binding alone. This mechanism may contribute to the sequential binding of cosubstrate followed by substrate.


Characterization of 58 STRs and 94 SNPs with the ForenSeq™ DNA signature prep kit in Mexican-Mestizos from the Monterrey city (Northeast, Mexico).
STR allele frequency databases from populations are necessary to take full advantage of the increased power of discrimination offered by massively parallel sequencing (MPS) platforms. For this reason, we sequenced 58 STRs (aSTRs, X-STRs, and Y-STRs) and 94 identity informative SNPs (iiSNPs) on 105 Mestizo (admixed) individuals from Monterrey City (Northeast, Mexico), with the Primer Set-A of the ForenSeq™ DNA Signature Prep Kit. Most of the STR markers were in Hardy Weinberg equilibrium, with a few exceptions. We found 346 different length-based alleles for these 58 STRs; nevertheless, they became 528 alleles when the sequence was assessed. The combined power of discrimination from autosomal STRs (aSTRs) was -virtually- 100% in both length and sequence-based alleles, while the power of exclusion was 99.9999999976065 and 99.9999999999494%, respectively. Haplotypes based on X-STRs and Y-STRs showed 100% of discriminatory capacity. These results provide -for the first time- forensic genomic population data from Mexico necessary for interpretation in kinship and criminal analyses.


Ovarian tumour xenografts in the study of the biology of human epithelial ovarian cancer.
Human epithelial ovarian tumours were successfully established as xenografts in nude mice in 54% of cases. An evaluation of the biological characteristics of tumours propagated in nude mice was carried out and the functions investigated included morphology, growth kinetics, cellular DNA content, cell surface antigen expression and sensitivity to chemotherapy. To allow a more detailed study of the influence of ploidy on biological behaviour, xenografted tumour with varying degrees of aneuploidy and tumours with a common ancestry but different ploidies were also established. Although this is a highly selective model system favouring the growth of biologically aggressive tumours the xenografts, in general, reflect many of the characteristics of the tumours from which they were derived and are likely to provide a useful model for investigating the biology of ovarian cancer.


Compression complexity with ordinal patterns for robust causal inference in irregularly sampled time series.
Distinguishing cause from effect is a scientific challenge resisting solutions from mathematics, statistics, information theory and computer science. Compression-Complexity Causality (CCC) is a recently proposed interventional measure of causality, inspired by Wiener-Granger's idea. It estimates causality based on change in dynamical compression-complexity (or compressibility) of the effect variable, given the cause variable. CCC works with minimal assumptions on given data and is robust to irregular-sampling, missing-data and finite-length effects. However, it only works for one-dimensional time series. We propose an ordinal pattern symbolization scheme to encode multidimensional patterns into one-dimensional symbolic sequences, and thus introduce the Permutation CCC (PCCC). We demonstrate that PCCC retains all advantages of the original CCC and can be applied to data from multidimensional systems with potentially unobserved variables which can be reconstructed using the embedding theorem. PCCC is tested on numerical simulations and applied to paleoclimate data characterized by irregular and uncertain sampling and limited numbers of samples.


Proteomic analysis of rat retina after methanol intoxication.
In order to investigate markers of toxic injury and elucidate the mechanisms underlying methanol intoxication at the protein level, proteomics technology was applied to study variations in retinal protein expression between normal rats and rat models of methanol intoxication. Seven rats were administered saline and methanol respectively by gavage. After seven days, retinal function was assessed by electroretinography and retinal proteins were extracted and separated by two-dimensional gel electrophoresis. The gels were then stained with AgNO₃ and analyzed with Pdquest software. The differential expression of proteins was analyzed by MALDI-TOF-TOF MS, and related proteins were searched in a protein database. Twenty-eight spots with significant differences were found, 24 of which were successfully identified. Specifically, there were 14 increased expression proteins, such as aldehyde dehydrogenase, tropomyosin alpha-1 chain, myosin light chain, and crystallin family proteins. There were 10 decreased expression ones, such as glyceraldehyde-3-phosphate dehydrogenase, recoverin, ATP synthase alpha subunit in rats with methanol toxicity. Retinal function was greatly destroyed upon methanol intoxication. Several key proteins were up- or down-regulated upon induced retinal toxicity, indicating that there are other mechanisms underlying methanol poisoning besides oxidative injury. Together, this data provides insight and knowledge for future studies in this field.


Tolerability of statin-fibrate and statin-niacin combination therapy in dyslipidemic patients at high risk for cardiovascular events.
Achieving recommended cholesterol and triglyceride targets for the prevention of cardiovascular events is difficult and frequently requires the use of >1 lipid-lowering medication. This study evaluated the tolerability and effectiveness of combination regimens in high-risk dyslipidemic patients resistant to monotherapy. A retrospective chart review of all patients referred to a cardiovascular risk reduction clinic over a 7.5-year period identified 136 patients who received combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus fibrate (n = 106) or a statin plus niacin (n = 30) regimen. During follow-up (mean 18.5 months), 28 patients (20.6%) discontinued combination therapy: 11 (8.1%) experienced myalgia with or without elevated creatine kinase, 3 had gastrointestinal upset, and 1 had asymptomatic creatine kinase elevation. No patient had combination therapy discontinued due to elevated liver enzymes. Medications were stopped in 8 patients for reasons other than reported adverse effects or biochemical abnormalities, and 5 patients were switched to alternate monotherapy. Mean percent change from baseline to treatment with combination therapy for total cholesterol (-35%), low-density lipoprotein cholesterol (-37%), high-density lipoprotein cholesterol (+23%), triglycerides (-62%), and total cholesterol/high-density lipoprotein cholesterol ratio (-41%) were all statistically significant (p <0.01). These results demonstrate that combination statin-fibrate and statin-niacin regimens are safe and effective in managing dyslipidemias in most patients at risk for cardiovascular events who are inadequately treated with one of these agents alone.


[Lipectomy of the abdominal region (author's transl)].
Indications and operative techniques for dermolipectomies in the abdominal and lumbar region are discussed including resections of excess skin after weight reduction, intestinal bypass, and pregnancy. Dangers and complications are discussed.


Pattern and frequency of neurological and neurosurgical care of adult inpatients and outpatients at a tertiary referral hospital in Kenya.
To describe the patterns and burden of neurological and neurosurgical disorders at a national tertiary level referral hospital in western Kenya. We conducted a three-month period prevalence study. We recruited consecutive adult patients seeking neurological-neurosurgical care in both inpatient and outpatient settings at Moi Teaching and Referral Hospital. 833 participants were included. The age range was between 19 year and 99 years (mean age = 45.3 years). The most common diagnoses among neurology inpatients were meningitis (12%), ischemic stroke (11.0%) and epilepsy/seizure (6.7%). Among neurology outpatients, epilepsy (35.1%) and ischemic stroke (18.8%) were the most common diagnoses. The most common neurosurgery inpatient diagnosis was hemorrhagic stroke (16.3%) and among outpatients, the most common diagnoses were traumatic brain injury (17.4%) and hemorrhagic stroke (16.3%). Overall, 471 (56.5%) patients underwent HIV testing, of which, 89 (18.9%) were HIV positive and 382 (81.1%) were HIV negative. Thirty-one inpatient deaths (male 58%), attributable to neurological and neurosurgical disorders, occurred during the study period. Meningitis was the most common cause of death. The findings suggest that meningitis, stroke, epilepsy, and traumatic brain injury were the most common diagnosis. More resources and efforts should be directed towards prevention, diagnosis and management of these conditions in the region.


Examination of n=2 reaction mechanisms that reproduce pH-dependent reduction potentials.
Flavo- and quinoproteins often exhibit trends in reduction potentials that approximate -30 mV per pH unit. At least five different reaction mechanisms can model the behavior described by the following Nernst equation: E(observed)=E0'+(0.059/2) log [H+]. The pH-reduction potential profile described by this equation can be reproduced by various models using different reaction mechanisms, and these mechanisms yield different reduction potentials and acid dissociation constants. In order to understand these discrepancies, this article discusses how the various methods reproduce this pH-dependent Nernst equation.


Dominant rearrangements among human tumor-infiltrating lymphocytes. Analysis of T-cells derived from 32 patients with melanoma, lung, and renal cell carcinoma.
Dominant rearrangements of T-cell receptor (TCR) beta-chain genes are reported among tumor-infiltrating lymphocytes (TIL). After interleukin-2 expansion of TIL from renal and lung carcinoma and melanoma biopsy tissues, rearrangements of TCR beta-chain genes were analyzed by Southern blotting. Nongermline restriction fragments, indicating dominant rearrangements, were detected among the TIL from all 6 patients with renal cell carcinoma, 17 of 20 patients with melanoma, and 3 of 6 patients with lung tumors. The restriction-fragment sizes of these dominant rearrangements were heterogeneous among the various patients. Rearrangements into C beta 1 were more common than C beta 2 rearrangements. Phenotypic analyses indicated that dominant rearrangements occurred in both CD4 and CD8 predominant TIL populations. The TIL populations that were extracted were expanded to derive large cell numbers suitable for in vivo transfer in an interleukin-2 and TIL immunotherapy program. The data indicated that the cells delivered to these patients usually were characterized by dominant populations of T-cells with selective TCR gene rearrangements. The significance of selective TCR use requires evaluation of the function and specificity of the TIL comprising these dominant populations both in their native in vivo setting and in the context of therapeutic transfer.


Epigenetic interaction of microbes with their mammalian hosts.
The interaction of microbiota with its host has the ability to alter the cellular functions of both, through several mechanisms. Recent work, from many laboratories including our own, has shown that epigenetic mechanisms play an important role in the alteration of these cellular functions. Epigenetics broadly refers to change in the phenotype without a corresponding change in the DNA sequence. This change is usually brought by epigenetic modifications of the DNA itself, the histone proteins associated with the DNA in the chromatin, non-coding RNA or the modifications of the transcribed RNA. These modifications, also known as epigenetic code, do not change the DNA sequence but alter the expression level of specific genes. Microorganisms seem to have learned how to modify the host epigenetic code and modulate the host transcriptome in their favour. In this review, we explore the literature that describes the epigenetic interaction of bacteria, fungi and viruses, with their mammalian hosts.


Gas chromatographic-mass spectrometric determination of macrolide antibiotics in beef and pork using single ion monitoring.
A gas chromatographic-mass spectrometric (GC-MS) method using single ion monitoring (SIM) is described for the determination of residual macrolide antibiotics, oleandomycin, kitasamycin, spiramycin and tylosin, in beef and pork. For GC-MS determination, oleandomycin is acid hydrolysed to desoleandomycin and acetylated, in the same way as erythromycin. However, for elution from a GC column, the carbon-carbon double bonds in the antibiotics must be hydrogenated to single bonds before acid hydrolysis. Kitasamycin and spiramycin are therefore converted into hydroforocidine acetate and tylosin into hydro-O-mycaminosyl tylonolide acetate, which are determined by GC-MS with SIM.


Spatiotemporal expression of proprotein convertase subtilisin/kexin type 5 in the development of anorectal malformations in fetal rats.
This study examined the expression patterns of proprotein convertase subtilisin/kexin type 5 (Pcsk5) during anorectal development in normal and anorectal malformations (ARM) rat embryos, determine the possible role of Pcsk5 in the pathogenesis of ARM. An ARM rat model was developed by the administration of ethylenethiourea gestational day 10 (GD10). Embryos were harvested by surgical excision from GD13 to GD16, and the spatiotemporal expression of Pcsk5 was evaluated, using immunohistochemistry staining, Western blotting and real time RT-PCR. Immunohistochemistry staining in normal embryos revealed that Pcsk5 was abundantly expressed on the epithelium of the cloaca (CL) on GD13. On GD14 and GD15, positive cells were noted on the urorectal septum and the thin anal membrane. However, the epithelium of the CL of ARM embryos only faintly expressed Pcsk5 from GD13 to GD15. Western blotting and real time RT-PCR showed time-dependent increase of Pcsk5 expression in the developing hindgut. Pcsk5 expression levels were lower in the ARM group from GD14 to GD16 (p ≤ 0.05). These results indicate that downregulation of Pcsk5 during cloaca development into the rectum and urethra might be related to the formation of ARMs.


Protective effect of HIF-1α against hippocampal apoptosis and cognitive dysfunction in an experimental rat model of subarachnoid hemorrhage.
Hypoxia-inducible factor 1α (HIF-1α) is a master regulator of cellular adaptation to hypoxia and has been proposed as a potent therapeutic target for cerebral ischemia. However, research on the expression and effects of HIF-1α in subarachnoid hemorrhage (SAH) is limited. The aim of the present study was to investigate the expression of HIF-1α in the hippocampus and its possible protective effect against hippocampal apoptosis and cognitive dysfunction in a rat model of SAH. Seventy-two Sprague-Dawley (SD) rats were randomly divided into the sham group, the SAH+vehicle group, and the SAH+YC-1 group. Immunohistochemical staining and western blotting analyses revealed that the expression of HIF-1α and its downstream effectors, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and glucose transporter 1 (GLUT1), increased in the hippocampus 48h after the induction of SAH. YC-1 blocked this upregulation. The number of active caspase-3-positive cells and the expression of active caspase-3 in the hippocampus significantly increased in the YC-1 group relative to the vehicle group. A cell death assay further revealed that DNA fragmentation was significantly increased at 48h in the YC-1 group compared with the vehicle group. In Morris water maze (MWM) tests, the YC-1 group showed increased escape latency times and distances as well as reduced time spent and distance traveled in the target quadrant. These results indicate that hippocampal apoptosis increased and cognitive function deteriorated when HIF-1α was inhibited, suggesting that HIF-1α has a neuroprotective effect in SAH and may represent an effective therapeutic target.


A Comparative Study of the Efficacy of Fat Plug Myringoplasty and Conventional Myringoplasty in Chronic Suppurative Otitis Media with Small Central Perforation.
Chronic Otitis Media (COM) is a major cause of acquired hearing impairment especially in developing countries. Persistent perforations occur either due to improper treatment of recurrent otitis media or infected traumatic perforation. Myringoplasty, repair of the Tympanic membrane using autologous temporalis fascia, is the standard procedure for COM. Other graft materials commonly used include tragal perichondrium, tragal cartilage and adipose tissue. This prospective study aims to compare the surgical and audiological outcome of fat plug myringoplasty [FPM] and conventional myringoplasty using temporalis fascia [CM-TF] in COM with small dry central perforation. A total of 60 patients of COM with small dry central perforation, aged 16-60 years, during the study period of October 2013 to August 2015 were divided into two groups of 30 cases each. The first group underwent FPM while the second group underwent CM-TF. The graft uptake and hearing outcome [pre operative and 3 months post operative PTA] were assessed. The surgical outcome of FPM with graft uptake of 86.7% was comparable to CM-TF with a graft uptake of 90%. The mean post operative hearing gain in FPM was 3.43 ± 2.81 dB which correlated well with that of CM-TF with 3.85 ± 3.05 dB. The duration of hospital stay and operative time was significantly lower in FPM group. FPM can be safely performed in cases with dry, small central perforations of the tympanic membrane with outcomes comparable to CM-TF.


A tyrosine-tryptophan dyad and radical-based charge transfer in a ribonucleotide reductase-inspired maquette.
In class 1a ribonucleotide reductase (RNR), a substrate-based radical is generated in the α2 subunit by long-distance electron transfer involving an essential tyrosyl radical (Y122O·) in the β2 subunit. The conserved W48 β2 is ∼10 Å from Y122OH; mutations at W48 inactivate RNR. Here, we design a beta hairpin peptide, which contains such an interacting tyrosine-tryptophan dyad. The NMR structure of the peptide establishes that there is no direct hydrogen bond between the phenol and the indole rings. However, electronic coupling between the tyrosine and tryptophan occurs in the peptide. In addition, downshifted ultraviolet resonance Raman (UVRR) frequencies are observed for the radical state, reproducing spectral downshifts observed for β2. The frequency downshifts of the ring and CO bands are consistent with charge transfer from YO· to W or another residue. Such a charge transfer mechanism implies a role for the β2 Y-W dyad in electron transfer.


Efficacy and Safety of Vinpocetine as Part of Treatment for Acute Cerebral Infarction: A Randomized, Open-Label, Controlled, Multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial.
The objective of this study was to evaluate the efficacy and safety of intravenous vinpocetine administration as part of a comprehensive treatment for acute cerebral infarction in a Chinese population. 610 acute cerebral infarction patients were randomized into two groups: the vinpocetine group (469 patients) received cytidine disphosphate choline 0.4-0.5 g in combination with aspirin 75-100 mg or clopidogrel 75 mg once daily, plus vinpocetine 30 mg intravenously once daily for 7 days, while the control group (141 patients) received cytidine disphosphate choline 0.4-0.5 g in combination with aspirin 75-100 mg or clopidogrel 75 mg once daily for 7 days. Additionally, patients received medications for symptoms such as hypertension, hyperglycemia, hyperlipidemia, and intracranial hypertension when necessary. Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale, and Barthel Index (BI) scores and transcranial doppler (TCD) were assessed at baseline, 7, 14, and 90 days after treatment. Adverse events (AEs) and abnormalities in blood, urine, liver, and kidney function were monitored. MMSE, NIHSS, and BI scores were significantly higher in the vinpocetine group than in the control group 90 days after treatment, indicating significantly improved cognitive skill, neurological function, and quality of life (QOL) in the vinpocetine group versus the control group. Importantly, such effects of vinpocetine were maintained over time. In addition, TCD monitoring showed significantly increased cerebral blood flow associated with vinpocetine versus control. No significant difference in safety was noted between the two groups. When used as part of treatment for acute cerebral infarction, vinpocetine improves patients' cerebral blood flow, cognitive quality, neurological functions, and QOL. Vinpocetine could be an effective and safe component of treatment regimen for acute cerebral infarction.


Monocyte count is an underlying marker of lacunar subtype of hypertensive small vessel disease.
In the hypertensive small vessel disease (HSVD), it remains unclear why some patients develop lacunar infarcts (LIs) whilst others develop deep intracerebral hemorrhages (dICHs). Inflammation might be related to LI, and leukocyte and monocyte counts are regarded as an inflammatory marker of ischemic stroke. We investigated the relationship between leukocyte and monocyte counts determined in the first 24 h after stroke onset in HSVD patients. We prospectively studied 236 patients with first acute stroke because of HSVD (129 LI and 107 dICH). We analyzed demographic data, vascular risk factors, and white blood cell count subtypes obtained in the first 24 h after stroke. The multivariate analysis showed that LI subtype of HSVD was correlated with hyperlipidemia (P < 0.0001), a higher monocyte count (P = 0.002), and showed a trend with current smoking (P = 0.051), whereas dICH subtype was correlated with low serum total cholesterol (P = 0.003), low serum triglycerides (P < 0.0001), and high neutrophil count (P = 0.050). In patients who developed HSVD-related stroke, high monocyte count, current smoking, and hyperlipidemia are prothrombotic factors related to LI, whereas low cholesterol and triglyceride values are related to dICH. Monocyte count might be an inflammatory risk marker for the occlusion of small vessels in hypertensive patients.


Synthesis and coordination behaviors of P-stereogenic polymers.
Optically active polymers containing P-stereogenic bisphosphine and 1,2,3-triazole units in the main chain were obtained by copper-catalyzed Huisgen cycloaddition. The repeating unit of the polymer adopted bidentate as well as tetradentate coordination, leading to the change in the conformations of the polymer via complexation with transition metals.


Identification of Carboxypeptidase Substrates by C-Terminal COFRADIC.
We here present a detailed procedure for studying protein C-termini and their posttranslational modifications by C-terminal COFRADIC. In fact, this procedure can enrich for both C-terminal and N-terminal peptides through a combination of a strong cation exchange fractionation step at low pH, which removes the majority of nonterminal peptides in whole-proteome digests, while the actual COFRADIC step segregates C-terminal peptides from N-terminal peptides. When used in a differential mode, C-terminal COFRADIC allows for the identification of neo-C-termini generated by the action of proteases, which in turn leads to the identification of protease substrates. More specifically, this technology can be applied to determine the natural substrate repertoire of carboxypeptidases on a proteome-wide scale.


No evidence for a major effect of three common polymorphisms of the GPx1, MnSOD, and CAT genes on PCOS susceptibility.
Polycystic ovary syndrome (PCOS) is one of the prevalent endocrine-metabolic disorders. It is proposed that oxidative stress contributes to PCOS susceptibility and its metabolic associations. The current study aimed to investigate the influence of GPx1 (rs1050450), MnSOD (rs4880), and Catalase (rs1001179) variants with PCOS susceptibility, for the first time. In a case-control study, 350 Kurdish female volunteers (175 PCOS patients and 175 healthy controls) from Western Iran were studied. Genotyping for GPx1 and MnSOD were done using PCR-RFLP and for CAT the allele-specific PCR method was used. The percentage of patients suffering from hirsutism, acne, and acanthosis among patients with PCOS were 44.6%, 30.3%, and 14.9%, respectively. Distribution of alleles among patients suffering from PCOS versus healthy women was 'Pro' (69.1% vs 68.8%) and 'Leu' (31.4% vs 31.2%) for Gpx1, 'Ala' (61.43% vs 56.57%) and 'Val' (38.57% vs 43.43%) for MnSOD, and 'C' (83.43% vs 84.57%) and 'T' (16.57% vs 15.43%) for CAT. GPx1 (rs1050450), MnSOD (rs4880), and CAT (rs1001179) variants might not be a risk factor for PCOS.


Supporting effects of myoepithelial cells in submandibular glands of dogs when acting against increased intraluminal pressure.
1. In dogs under chloralose-urethane anaesthesia secretion from the submandibular gland was recorded with the outflow at gland level and at heights of up to 50 cm above the gland.2. With the outflow level increased, secretion elicited by sympathetic nerve stimulation was far better maintained before than after injection of the alpha-adrenoceptor blocking agent dihydroergotamine.3. When the outflow level was raised while no secretion occurred, fluid flowed into the gland. Part of this amount was returned on lowering the outflow to gland level. This volume was assumed to have been accommodated in the distended luminal system, whereas some fluid was obviously lost into the gland tissues.4. Both these fractions of the fluid flowing into the gland when the outflow level was high could be reduced by injecting the alpha-receptor agonist phenylephrine. Bradykinin, which like phenylephrine is known to contract salivary myoepithelial cells, had the same effect on the two inflow volumes.5. It is concluded that myoepithelial contraction reduced the distensibility of the luminal system and in addition supported the acini, thereby diminishing backflow into the glandular tissues and enabling the gland to discharge saliva against a high pressure.6. Morphologically it was found that in resting glands PAS-positive saliva was displaced from the ductal system when the outflow cannula was raised, but it was preserved in the lumina under similar conditions when the myoepithelial cells were being stimulated by phenylephrine or bradykinin.7. Although sympathetic secretion could be maintained against a head of pressure, so long as it was accompanied by myoepithelial contraction, the increased force caused by the secretion led to disruptive damage of striated ducts which are the first part of the luminal system not supported by myoepithelial cells.8. The morphological findings reinforce the belief that contraction of myoepithelial cells gives active support to the underlying parenchyma.


Open reduction-internal fixation versus intramedullary nailing for humeral shaft fractures: an expected value decision analysis.
Previous randomized controlled studies and meta-analyses have failed to collectively favor either open reduction-internal fixation (ORIF) or intramedullary nailing (IMN) fixation. The purpose of our investigation was to elucidate the optimal decision between ORIF and IMN for acute traumatic operative humeral shaft fractures through an expected value decision analysis. We performed an expected value decision analysis and sensitivity analysis to elucidate the difference between ORIF and IMN fixation for patients with acute traumatic humeral shaft fractures. We surveyed 100 consecutive, randomly selected volunteers for their outcome preferences. Outcomes included union, delayed union, major complications, minor complications, and infection. A literature review was used to establish probabilities for each of these respective outcomes. A decision tree was constructed and a fold-back analysis was performed to find an expected patient value for each treatment option. The overall patient expected values for ORIF and IMN were 12.7 and 11.2, respectively. Despite artificially decreasing the rates of major complications, infection, delayed union, and nonunion each to 0% for IMN fixation (sensitivity analysis), ORIF continued to maintain a greater overall patient expected value (12.7 vs. 11.4, 11.2, 11.2, and 12.1, respectively). Only if the rate of nonunion after ORIF was increased from 6.1% to 16.8% did the overall expected outcome after ORIF equal that of IMN (11.2). Our expected value decision analysis demonstrates that patients favor ORIF over IMN as the optimal treatment decision for an acute traumatic humeral shaft fracture.


Shift in bacterioplankton diversity and structure: Influence of anthropogenic disturbances along the Yarlung Tsangpo River on the Tibetan Plateau, China.
River systems have critical roles in the natural water environment and the transportation of nutrients. Anthropogenic activities, including wastewater discharge and river damming, raise adverse impacts on ecosystem and continuum of rivers. An increasing amount of attention has been paid to riverine bacterioplankton as they make vital contributions to biogeochemical nutrient cycle. A comprehensive study was conducted on the bacterioplankton community along the Yarlung Tsangpo River, which is the longest plateau river in China and is suffering from various anthropogenic impacts. The results indicated that nutrient variations corresponded to anthropogenic activities, and silica, nitrogen and phosphorus were retained by the dam. River damming influenced the biomass and diversity of the bacterioplankton, but significant alterations in the community structure were not observed between upstream and downstream of the dam. Moreover, the spatial distribution of the bacterioplankton community changed gradually along the river, and the dominant bacterioplankton in the upstream, midstream and downstream portions of the river were Firmicutes, Bacteroidetes and Proteobacteria, respectively. Soluble reactive phosphorus, elevation, ammonium nitrogen, velocity and turbidity were the main environmental factors that shape the bacterioplankton community. Our study offers the first insights into the variation of a bacterioplankton community of a large river in plateau region.


A Computational Framework for Determining the Breadth of Antibodies Against Highly Mutable Pathogens.
Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies. To overcome these limitations, design of antibodies with a larger neutralizing breadth can be pursued. Such broadly neutralizing antibodies (bnAbs) should remain targeted to a specific epitope, yet show robustness against pathogen mutability, thereby neutralizing a higher number of antigens. This is particularly important for highly mutable pathogens, like the influenza virus and the human immunodeficiency virus (HIV). The protocol describes a method for computing the "breadth" of a given antibody, an essential aspect of antibody design.


Expression of GPCRs in Pichia pastoris for structural studies.
Recent success in obtaining high-resolution structural data for the first several G protein-coupled receptors (GPCRs) has highlighted the feasibility of structural membrane proteomics approaches for obtaining molecular models of additional GPCRs from among the nearly 800 encoded by the human genome. Yet, production of functional receptors, in general, has proven to be difficult, typically requiring considerable time and cost investments. Here we describe screening, optimization, and scale-up methods we successfully used to produce milligram amounts of functional GPCRs in Pichia pastoris. When we surveyed a large number of receptors recombinantly produced in Pichia, 85% exhibited specific ligand binding, strongly suggesting that this expression system is excellent for producing functional GPCRs. Of the latter group, 20 were optimized according to our protocol. Of these, we produced 10 as milligram amounts of functional receptors using large-scale shaker culture. Cost and time expenditures were considerably lower using the Pichia system than for other successfully employed cell culture systems.


Maturation of the European sardine Sardina pilchardus under experimental conditions strengthens bioenergetic estimate.
This study aims at (1) experimentally estimating first sexual maturation of the European sardine S. pilchardus, (2) using the results to calibrate existing bioenergetic models. During the 183 days-experiment, fish growth and body condition were assessed by biometry, and gonads were weighed when present. Age, wet weight and total length at first maturity were estimated at 262 days, 10.79 ± 0.75 g, and 11.26 ± 0.21 cm, respectively. Including these traits in biphasic Von Bertalanffy models did not significantly improve simulations for either length or weight data, meaning that energy allocation was not impacted by these traits. The implementation of the results in the Dynamic Energy Budget (DEB) calibration procedure strengthened the parameter set of the existing model, but resulted in significant changes in the energy allocation. Our results are a first step that will allow the design of new experiments to further quantify maturation and reproduction rates in diverse environmental conditions, consolidating DEB model calibration.


Making disjunctions exclusive.
This work examines how people interpret the sentential connective "or", which can be viewed either inclusively (A or B or both) or exclusively (A or B but not both). Following up on prior work concerning quantifiers (Bott & Noveck, 2004; Noveck, 2001; Noveck & Posada, 2003), which shows that the common pragmatic interpretation of "some", some but not all, is conveyed as part of an effortful step, we investigate how extra effort applied to disjunctive statements leads to a pragmatic interpretation of "or", or but not both. Experiment 1 compelled participants to wait for three seconds before answering, hence giving them the opportunity to process the utterance more deeply. Experiments 2 and 3 emphasized "or", either by visual means ("OR") or by prosodic means (contrastive stress) as another way to encourage participants to apply more effort. Following a relevance-theoretic line of argument, we hypothesized that conditions encouraging more processing effort would give rise to more pragmatic inferences and hence to more exclusive interpretations of the disjunction. This prediction was confirmed in the three experiments.


Increased expression of enzymes of triglyceride synthesis is essential for the development of hepatic steatosis.
Molecular mechanisms underpinning nonalcoholic fatty liver disease (NAFLD) are not well understood. The earliest step of NAFLD is hepatic steatosis, which is one of the main characteristics of aging liver. Here, we present a molecular scenario of age-related liver steatosis. We show that C/EBPα-S193D knockin mice have age-associated epigenetic changes and develop hepatic steatosis at 2 months of age. The underlying mechanism of the hepatic steatosis in old wild-type (WT) mice and in young S193D mice includes increased amounts of tripartite p300-C/EBPα/β complexes that activate promoters of five genes that drive triglyceride synthesis. Knockdown of p300 in old WT mice inhibits hepatic steatosis. Indeed, transgenic mice expressing dominant-negative p300 have fewer C/EBPα/β-p300 complexes and do not develop age-dependent hepatic steatosis. Notably, the p300-C/EBPα/β pathway is activated in the livers of patients with NAFLD. Thus, our results show that p300 and C/EBP proteins are essential participants in hepatic steatosis.


Fluoro-modified chemotactic peptides: fMLF analogues.
A small library of peptide analogues of the chemotactic tripeptide For-Met-Leu-Phe-NH2 modified by substitution of Leu at position 2 by three different fluorinated amino acids varying in content of fluorine, length of the fluorinated side chain, and alkylation degree at the alpha-carbon atom was synthesized. The influence of the fluorine substitution on the biological activity was investigated by measuring the oxidative activity of neutrophils using a luminol-dependent chemiluminescence assay.


Impact of Frailty on Postoperative Dysphagia in Patients Undergoing Elective Cardiovascular Surgery.
Postextubation dysphagia (PED) is a serious postoperative complication following cardiovascular surgery that can lead to a worse prognosis. On the other hand, frailty is a prognostic factor in patients who undergo cardiac surgery. This study investigated the effect of frailty status on PED and impact of PED on postoperative complications. This single-center retrospective cohort study included 644 consecutive patients who underwent elective cardiovascular surgery between May 1, 2014, and December 31, 2020; they were assigned to the PED or non-PED group based on postoperative swallowing status, and postoperative complications were investigated. Frailty status and physical functions, including walking speed, grip strength, Short Physical Performance Battery, and 6-minute walking distance, were preoperatively assessed; the frailty-status cutoff for predicting PED was determined from the receiver-operating characteristic curve. In this study cohort (mean age 67.7 years), the overall PED prevalence was 14.8%; preoperative frailty had a significantly higher prevalence in the PED group (50.0%) than in the non-PED group (20.3%; P < 0.001). PED correlated with a higher incidence of postoperative pneumonia and prolonged intensive care unit or hospital stay (P < 0.05 for all). After adjustment for confounders, multiple regression analysis revealed that preoperative frailty was independently associated with PED (P < 0.001). PED occurred commonly after cardiovascular surgery and increased the risk of postoperative complications. Preoperative frailty was independently associated with PED. The 6-minute walking distance was the most powerful predictor of PED. Evaluation of preoperative frailty status is important for risk stratification and prevention of postoperative morbidity in patients undergoing surgery.


Ventral pallidum roles in reward and motivation.
In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that (1) an intact ventral pallidum is necessary for normal reward and motivation, (2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and (3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important 'limbic final common pathway' for mesocorticolimbic processing of many rewards.


High insertion of conjoint tendon is associated with inguinal-related groin pain: a MRI study.
To compare the insertions of the conjoint tendon (CT) on MRI in athletes with and without symptoms and to assess their relationship to groin pain with surgery as a reference. Between January and May 2017, patients with inguinal-related groin pain undergoing Shouldice repair were prospectively enrolled and underwent MRI. Exams were independently reviewed by two radiologists blinded to surgical results to assess types of CT insertion as high muscular without (type 1) or with tendinous expansion (type 2) or low muscular (type 3). Radiological and surgical results were compared. Patients were compared with a gender- and age-matched control group of asymptomatic athletes. One hundred twenty-eight walls (64 in patients, 64 in controls) in 64 subjects (32 patients and 32 controls, only men; mean age, 31.7 ± 10 years; range, 15.0-54.8) were analyzed. CT insertion was defined as types 1, 2, and 3 in 32/128 (25%), 35/128 (27%), and 61/128 (48%) walls, respectively, with 22/64 (34%), 27/64 (42%), and 15/64 (23%) in patients and 10/64 (16%), 8/64 (12.5%), and 46/64 (72%) in controls. Type s1+2 were significantly more frequent in patients compared with that in controls (p < 0.01). MRI predicted a high CT insertion with a sensitivity and specificity of 97% (95%CI 85-99) and 62% (95%CI 36-82). The intra- and inter-reader agreement for the prediction of the type of insertion was excellent (k > 0.75). A high CT insertion is more frequent in athletes with groin pain and may be a predisposing factor. MRI could help predict the type of CT insertion. • MR imaging should be included in the initial workup of patients with inguinal-related groin pain. • MR imaging can be used to visualize the type of insertion with acceptable results. • High insertion of the conjoint tendon may be a predisposing factor for inguinal-related groin pain.