Footshock-induced analgesia: neurochemical correlates and pharmacological profile.
The administration of electric shock to the feet of rats can produce either opioid, naloxone-sensitive analgesia or non-opioid, naloxone-insensitive analgesia. In our hands opioid analgesia could be elicited in young Sabra rats (75 days of age) by all analgesia induction methods while older rats of the same strain and rats of the Charles River-derived strain (CR) showed only naloxone-resistant analgesia. We therefore compared the effects of 2 different footshock parameters, 3 min continuous shock (3 mA) and 30 min intermittent shock (30 min, 1 s on 5 s off) on the responsiveness to noxious stimuli and on brain enkephalins and humoral (H-) endorphin content in these strains of rats. As previously reported, only young Sabra rats showed opioid analgesia whereas all other animals displayed naloxone-resistant effects. In contrast, no differential effects on brain opioids could be seen in these species. Thus, 30 min of shock produced a significant increase in brain enkephalins and a noticeable albeit non-significant increase in brain H-endorphin. A slight non-significant increase was seen following brief footshock. To assess the nature of non-opioid analgesia further we examined the effects of both reserpine and a series of antagonists on the analgesia produced by 3 and 30 min of either brief or prolonged shock. Pretreatment with reserpine caused a significant attenuation of non-opioid analgesia with both shock parameters while none of the antagonists administered (methysergide, phentolamine, phenoxybenzamine, yohimbine, theophylline, diphenhydramine and scopolamine) were effective.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamic 13C NMR analysis of oxidative metabolism in the in vivo canine myocardium.
Oxidative metabolism in the in vivo canine myocardium was studied noninvasively using 13C-enriched acetate and non-steady state 13C NMR techniques. Under low workload conditions, the myocardium oxidized the infused [2-13C]acetate and incorporated the labeled carbon into the glutamate pool as expected. This conclusion stems from the rapid enrichment of the C-2, C-3, and C-4 carbons of glutamic acid both under in vivo conditions and in extracts. Surprisingly, [2-13C]acetate uptake was not observed at high workloads as reflected by an absence of glutamate pool enrichment at these rate pressure products. Rather, the myocardium selected its substrate from an endogenous pool. Since free acetate can directly cross the inner mitochondrial membrane and be converted to acetyl-CoA through acetyl-CoA synthetase, these results support workload-dependent regulation of substrate access to the mitochondrial CoASH pool. As such, we advance the hypothesis that the selection of substrate for condensation with CoASH and subsequent oxidation in the tricarboxylic acid cycle is regulated kinetically through the Km values of the appropriate condensation enzymes and through the absolute levels of free CoASH in the mitochondria.


Characterization of the 80,000 molecular weight form of neurophysin isolated from bovine neurohypophysis.
Partially purified immunoreactive species extracted from bovine posterior pituitary have been labeled with 125I and analyzed by immunoprecipitation with antineurophysin antibodies followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under denaturing, but nonreducing conditions, a band of Mr = 80,000 was observed. This band corresponded to immunoreactive species detected by radioimmunoassay after chromatography of unlabeled material on a Sepharose CL-4B gel filtration column run in the presence of 6 M guanidine hydrochloride. Under nondenaturing conditions, this species behaved like molecules with an apparent Mr of 140,000 to 160,000. Electrophoretic analysis of the immunoprecipitated material showed that it contained an immunoreactive, single polypeptide chain of Mr = 80,000. Another immunoreactive species of similar molecular weight was also detected, apparently derived from the first one by peptide bond cleavage yielding two fragments of Mr = 68,000 and 10,000, respectively, held together by disulfide bridges. The Mr = 68,000 fragment had lost immunoprecipitability, although its peptide map was largely homologous to that or Mr = 80,000 polypeptide. The 10,000 piece was shown by radioimmunoassay and peptide analysis to be homologous to neurophysin.


Structural change of a cofactor binding site of flavoprotein detected by single-protein fluorescence spectroscopy at 1.5 k.
The visible fluorescence spectrum of single flavoprotein at a temperature of 1.5 K has been measured by one-photon excitation. The flavoprotein studied was a photoswitchable enzyme, photoactivated adenylyl cyclase. The time course of the spectrum revealed a structural change occurring at a rate of 10(-3) s(-1) around hydrogen bonds at the flavin cofactor binding site.


Targeting O-GlcNAcylation to develop novel therapeutics.
O-linked β-D-N-acetylglucosamine (O-GlcNAc) is an abundant post-translational modification (PTM) that modifies the serine or threonine residues of thousands of proteins in the nucleus, cytoplasm and mitochondria. Being a major "nutrient sensor" in cells, the O-GlcNAc pathway is sensitive to cellular metabolic states. Extensive crosstalk is observed between O-GlcNAcylation and protein phosphorylation. O-GlcNAc regulates protein functions at multiple levels, including enzymatic activity, transcriptional activity, subcellular localization, intermolecular interactions and degradation. Abnormal O-GlcNAcylation is associated with many human diseases including cancer, diabetes and neurodegenerative diseases. Though research on O-GlcNAc is still in its infantry, accumulating evidence suggest O-GlcNAcylation to be a promising therapeutic target. In this review, we briefly discuss the basic features of this PTM, the O-GlcNAc signaling pathway, its regulatory functions on different proteins, and its involvement in human diseases. We hope this review will provide insights to researchers who study human disease, as well as researchers who are interested in the fundamental roles of O-GlcNAcylation in all cells.


Bladder neck stenosis after transurethral resection of prostate: does size matter?
To understand the risk factors associated with the incidence of bladder neck stenosis (BNS) after transurethral prostate surgery. We retrospectively reviewed 900 patients who underwent transurethral prostate surgery over a 4-year period. The mean age of the men was 72.3 (47-94) years. The specific outcome data assessed related to BNS, including type of operation performed, resected tissue weight and history of previous surgery in the lower urinary tract. 29 (3.4%) patients developed BNS at a mean of 10.3 (3-33) months, with a mean resected prostatic tissue weight of 11+/-3.7 g. Four of the 29 patients with BNS were treated with bladder neck resection and re-stenosed. Fifty-four men underwent bladder neck incision for small prostates with a high bladder neck, measured by digital rectal examination and assessed cystoscopically, with no BNS. All the remaining patients from our series did not have a BNS, with a mean resected weight of 28+/-8.9 g, which is statistically greater than in the BNS group (p<0.05, unpaired t test). BNS after transurethral prostate surgery is a significant problem. It is clear from our study that resection in small prostates with no sign of a high bladder neck will increase the development of BNS. Thus, small prostates should be managed by an initial bladder neck incision, even if the bladder neck is not high.


Genome-wide association study of the candidate genes for grape berry shape-related traits.
In the breeding of new horticultural crops, fruit shape is an important selection characteristic. A variety of fruit shapes appeared during the gradual process of selection and domestication. However, few studies have been conducted on grape berry shape, especially studies related to mining candidate genes. To discover candidate genes related to grape berry shape, the present study first took the berry shape parameters analyzed by Tomato Analyzer as the target traits and used a genome-wide association analysis to analyze candidate genes. In total, 122 single-nucleotide polymorphism (SNP) loci had significant correlations with multiple berry shape traits in both years, and some candidate genes were further mined. These genes were mainly related to LRR receptor-like serine/threonine-protein kinase (At1g05700 and At1g07650), transcription factors (GATA transcription factor 23-like, transcription factor VIP1, transcription initiation factor TFIID, and MADS-box transcription factor 6), ubiquitin ligases (F-box protein SKIP19 and RING finger protein 44), and plant hormones (indole-3-acetic acid-amido synthetase GH3.6 and ethylene-responsive transcription factor ERF061). In addition, some important SNP loci were associated with multiple berry-shape traits. The study further revealed some genes that control multiple traits simultaneously, indicating that these berry shape traits are subject to the coordinated regulation of some genes in controlling berry shape. In the present work, we identified interesting genetic determinants of grape berry shape-related traits. The identification of molecular markers that are closely related to these berry-shape traits is of great significance for breeding specific berry-shaped grape varieties.


Adenosine as inhibitor of myocardial effects of catecholamines.
Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of dP/dtmax caused by bolus injections of isoproterenol (4 X 10(-11) moles). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) occurred at 10(-5) M. Coronary dilation induced by papaverine did not influence the contractile response to catecholamines. In addition to its influence on cardiac performance, adenosine (10(-5) M) effectively inhibited the isoproterenol (10(-7)M) induced initial rise in myocardial levels of cyclic 3'5'-AMP, glucose-1-phosphate and glucose-6-phosphate. Adenosine also antagonized the effect of isoproterenol on adenylate cyclase activity in a crude membrane preparation from guinea pig ventricles; it was without effect on the activity of the membrane phosphodiesterase. Theophylline inhibited the actions of adenosine both on adenylate cyclase activity and on contractile force development. Upon infusion of isoproterenol (3 X 10(-7)M) into the coronary arteries of the isolated heart (perfusion at constant pressure), the adenosine concentration in the effluent perfusate increased within 45 s from 10(-8) M to about 10(-6) M. It thus appears conceivable that in ventricular myocardium endogenously formed adenosine may serve 2 functions: dilation of the coronary arteries and limitation of the inotropic and metabolic effects of catecholamines.


S.Typhi derived OmpC peptide conjugated with Vi-polysaccharide evokes better immune response than free Vi-polysaccharide in mice.
Salmonella typhi is a causative organism for typhoid fever. Free Vi capsular polysaccharide (Vi) is licensed for use as vaccine for typhoid fever in individuals 2 years of age and older, which has limited memory response. There is dire need of protein or peptide as conjugate partner with Vi polysaccharide to improve shortcomings of Vi vaccine. Prediction of immunogenic peptide was deduced by program T sites. Carbodiimide mediated conjugation of Vi polysaccharide with OmpCp was performed utilizing ADH as linker. Immune response of Vi-conjugates along with control group was tested in mice. Ig and IgG antibodies against Vi polysaccharide was measured by ELISA. Two immunodominant regions (loop number 3a and 7) with high content of T-cell epitopes from OmpC was selected and synthesized. Vi poly/OmpCp ratios in Vi-conjugates were ~0.43-0.65. Vi polysaccharide alone elicited very low levels of Vi antibody without any booster effect. Vi-conjugate evoked 20-fold higher immune response compared to free Vi. Further, adequate levels of IgG antibodies were induced only by the Vi-conjugate suggesting that T-helper cells had been induced. Our data suggest that selected short peptide (OmpCp)as a carrier with Vi polysaccharide is assumed to be a promising molecule for candidate vaccine for typhoid fever.


Synthesis of a hybrid assembly composed of titanium dioxide nanoparticles and thin multi-walled carbon nanotubes using "click chemistry".
A hybrid assembly composed of thin multi-walled carbon nanotubes (t-MWCNT) and titanium dioxide (TiO(2)) has been prepared by using "click" chemistry for photocatalytic applications. TiO(2)-decorated t-MWCNT hybrids with anatase phase TiO(2) were obtained from the reaction of an azide moiety-containing TiO(2) with alkyne-functionalized t-MWCNTs. The hybrids were systematically characterized using Fourier transform infrared spectroscopic (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectrum (EDX), and X-ray diffraction (XRD) measurements. The nanohybrid has been proved to be highly active and robust for photocatalytic degradation of methyl orange. The click coupling approach is a simple and convenient route to efficiently assemble TiO(2) on the surface of carbon nanotubes, and can be extended to obtain many other nanoparticle hybrids based on carbon nanotubes.


A randomized, double-blind, single-dose, single-center, parallel phase I clinical study comparing the pharmacokinetics, immunogenicity, safety, and tolerance of pertuzumab injection and Perjeta® in healthy Chinese male subjects.
Perjeta® is a recombinant, humanized monoclonal antibody that has been marketed and approved for the targeted therapy of human epidermal growth factor receptor (HER2) positive breast cancer in the United States. This study compared the bioequivalence, immunogenicity, and safety of pertuzumab injection (a biosimilar of Perjeta® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Perjeta® (produced by Roche Pharma AG) in healthy Chinese males. Healthy Chinese male subjects (N = 87) were randomly given intravenous injection of 5 mg/kg pertuzumab or Perjeta® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay, and primary pharmacokinetic parameters were statistically analyzed. We detected the levels of anti-drug antibody (ADA) and neutralizing antibody (nAb) to evaluate drug immunogenicity and safety of the drugs throughout the study. The geometric mean ratios of AUC0-t, Cmax, and AUC0-∞ for pertuzumab and Perjeta® were 100.42%, 96.71%, and 101.47%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. The levels of ADA and nAb were similar. In addition, both had good safety in the study. The study shows that pertuzumab injection and Perjeta® had similar bioequivalence, immunogenicity, and safety.


Factitial bleeding: successful management with psychotherapy.
A young female nurse presented with unusual upper and lower-gastrointestinal bleeding, shown to be factitial. Following detection, she was successfully confronted and treated with psychotherapy. A plan for successful management of the Munchausen syndrome is discussed.


Refractive corneal inlay implantation outcomes: a preliminary systematic review.
To review all case series of refractive corneal inlay implantation: Flexivue (Presbia, Netherlands), Invue (BioVision, Brügg, Switzerland) and Icolens (Neoptics, Hünenberg, Switzerland) performed in presbyopia patients and to evaluate the reported visual outcomes. In addition, our aim is to provide assessment for complications and to report the satisfaction rates. PubMed, Web of Science and Scopus databases were consulted using "refractive corneal inlay", "Flexivue Inlay", "Invue Inlay" and "Icolens inlay" as keywords. 147 articles were found, and they were assessed considering the inclusion and exclusion criteria. After filtering, this systemic review included ten articles, published between 2011 and 2020. 308 eyes from 308 participants were enrolled in this systematic review. Mean maximum follow-up was 13.9 months. Nine of the ten case series included used femtosecond laser for the corneal pocket creation. Mean pocket depth was 293.75 µm. 77.5% of the eyes reported a postoperative uncorrected near visual acuity of 20/32 or better, and 19.20% of the inlay-implanted eyes achieved an uncorrected distance visual acuity of 20/20 or better. The most prominent complications were halos, pain, photophobia, and poor distance visual acuity. 27 eyes (8.7%) had to be explanted due to complications, such as near-distance spectacle dependence or blurred distance vision. Refractive corneal inlay outcomes demonstrated high efficacy, safety, and satisfaction rates. Furthermore, it is a reversible technique. However, the findings must be viewed with caution due potential conflict of interest. Further research with higher sample size is needed to validate these findings.


Structure-activity relationships of a peptidic antagonist of Id1 studied by biosensor method, circular dichroism spectroscopy, and bioassay.
Id1 proteins, inhibitors of differentiation or DNA binding, act as dominant negative antagonists of the bHLH family of transcription factors, which play an important role in cellular development, proliferation, and differentiation. The mechanism of Id proteins is to antagonize bHLH proteins by forming high-affinity heterodimers with other bHLH proteins, thereby preventing them from binding to DNA and inhibiting transcription of differentiation-associated genes. Our goal is to study the SARs of a peptidic antagonist of Id1, peptide 3C, which exhibits high affinity for Id1 and inhibitory effect on the proliferation of cancer cells. A series of N-terminal- and C-terminal-deleted analogs of peptide 3C were designed, synthesized, and characterized. Affinity of each peptide for Id1 or Id1-HLH domain was determined by SPR-based biosensor. The secondary structure of each peptide was studied by CD spectroscopy. Biological effect of each peptide in breast cancer cell (MCF-7) was analyzed by the MTT cell viability assay. Results demonstrated that peptide 3C and peptide 3C-CtD4 exhibited higher affinity for Id1-HLH and the equilibrium dissociation constants (K(D) ) were 3.16 and 2.77 µM, respectively. CD results indicated that the percentage of α-helix (%) in the secondary structure of deleted peptides were different, ranging from 7.93 to 10.45%. Although MTT results showed that treatment of MCF-7 with these peptides did not cause antiproliferative effects in cancer cells, SPR results demonstrated that the high-affinity peptides 3C and 3C-CtD4 are promising for further modifications to enhance their affinity for Id1-HLH and antiproliferative effects in cancer cells and for the development of peptidic antagonists as anticancer agents.


Allopurinol can act as an electron transfer agent. Is this relevant during reperfusion injury?
The xanthine oxidase inhibitor allopurinol markedly enhances myocardial function and decreases ventricular irritability during myocardial reperfusion. In the present report, we have evaluated the molecular mechanism of allopurinol action. First, allopurinol was shown to be a weak radical scavenger. Second, allopurinol was found to act as an electron transfer agent from ferrous iron to ferric cytochrome c. The results suggest that the beneficial effect of allopurinol might partially result from its facilitated electron transport during reperfusion when the lipid components of the chain can be expected to be disordered.


A survey of formal methods for determining the centre of rotation of ball joints.
The determination of an accurate centre of rotation (CoR) from segment marker positions is of interest across a wide range of applications, but particularly for clinical gait analysis and for estimating the hip joint centre during surgical intervention of the knee, for limb alignment purposes. For the first time in this survey of formal methods, we classify, analyse and compare different methods (geometric, algebraic, bias compensated algebraic, and Pratt sphere fit methods, as well as the centre transformation technique, the Holzreiter approach, the helical pivot technique, the Schwartz transformation techniques, the minimal amplitude point method and the Stoddart approach) for the determination of spherical joint centres from marker position data. In addition, we propose a new method, the symmetrical CoR estimation or SCoRE, in which the coordinates of the joint centre must only remain constant relative to each segment, thus not requiring the assumption that one segment should remain at rest. For each method, 1000 CoR estimations were analysed with the application of isotropic, independent and identically distributed Gaussian noise (standard deviation 0.1cm) to each of the marker positions, to all markers on the segment simultaneously and the two in combination. For the test conditions used here, most techniques were capable of determining the CoR to within 0.3 cm, as long as the spherical range of motion (RoM) of the joint was 45 degrees or more. Under the most stringent conditions tested, however, the SCoRE was capable of best determining the CoR, to within approximately 1.2mm with a RoM of 20 degrees . The correct selection and application of these methodologies should help improve the accuracy of surgical navigation and clinical kinematic measurement.


Hereditary and non-hereditary branches of family eligible for BRCA test: cancers in other sites.
The analysis of relationships of BRCA alterations with cancer at sites other than breast/ovary may provide innovative information concerning BRCA pathogenic role and support additional clinical decisions. Aim of this study is to compare presence of cancers in other sites in members of hereditary (H) and not-hereditary (nH) branches of families of patients eligible to BRCA test. We retrospectively analyzed the incidence of cancer in other sites in members of 136 families eligible for hereditary breast/ovarian cancer genetic counseling at Centro Studi Tumori Eredo-familiari of our Institute; we compared the frequency of other cancer types in 1156 members of the H-branch with respect to 1062 members of nH-Branch. The families belonging to a proband case and with informative members in at least three generation entered the present study. The frequency of other Cancers in members of H-branch was significantly higher than that in members of nH-branch (161 vs 75 cancers; p < 0.0001). In specific, members of H-branch had a significantly higher probability to have more lung cancer (38 vs 9;p < 0.0006), kidney cancer (23 vs 5;p < 0.0005), liver cancer (13 vs 3;p < 0.02) and larynx cancer (14 vs 4;p < 0.03). Interestingly, to belong to H-branch resulted significantly associated with a higher probability of lung cancer (OR 4.5; 2.15-9.38 95%C.I.), liver cancer (OR: 4.02; 1.14-14.15 95% C.I.) and larynx cancer (OR:3.4; 1.12-10.39 95%C.I.) independently from Gender and Age. Members belonging to the H-branch of families of patients eligible to BRCA test have a higher risk of tumors in lung, larynx and liver. Clinicians should consider the increased risk for these cancers to activate prevention/early diagnosis practices in members of families with breast/ovarian familial cancer syndrome.


Infectious sacroiliitis: Retrospective analysis of 18 case patients.
Few infectious sacroiliitis reports are available in the literature. There is no standard clinical presentation, and diagnosis and treatments are therefore usually delayed. We aimed to describe this infection. We performed a single-center retrospective study of patients hospitalized in the infectious diseases unit of the Limoges University Hospital from January 1, 2006 to January 31, 2016. We included all patients presenting with infectious monoarthritis of native sacroiliac joint. Clinical, biological, bacteriological, radiological, and therapeutic characteristics were collected. A total of 18 patients were enrolled. The sex ratio was 1.25. Mean age was 39.6years (17-69years). The average progression time at diagnosis was 17.9days (1-110days). The mean hospital stay was 16.2days (3-35days). Temperature at admission was 38.8°C (37-40°C). Identified bacteria were methicillin-susceptible Staphylococcus aureus in 83.3% of cases (n=15), Proteus mirabilis (n=1), and Streptococcus dysgalactiae (n=1). Thirty-two (88.9%) of the 36 imaging examinations were consistent with the diagnosis. The survival rate was 100% at the end of the six-month follow-up. Infectious sacroiliitis is a complex pathology requiring precise clinical examination for a rapid diagnosis. The outcome is usually favorable.


A Monocentric Randomized Controlled Clinical Trial to Compare Single- and Double-Lumen Needles in Oocyte Retrieval Procedure in Assisted Reproductive Technologies.
The purpose was to determine any difference in outcomes, primarily in terms of number of retrieved oocytes per procedure, between two different needles used for oocytes retrieval procedure in Assisted Reproductive Technologies: the single-lumen needle (SLN) versus the double-lumen needle (DLN) with follicle flushing after aspiration. This randomized controlled trial included oocyte retrieval (OR) cycles for IVF and ICSI performed in 18 to 42-year-old women between March 2019 and January 2021 at a tertiary-care Fertility Center. A total of 200 ORs were randomized, 100 in each group. The mean number of retrieved oocytes was not different between groups (10.2 ± 6.5 for DLNs vs. 10.7 ± 7.0 for SLNs, p = 0.810). No significant differences were observed also in terms of number of retrieved oocytes/punctured follicles (83.0% ± 27.0% vs. 81.0% ± 22.0%, p = 0.916), number of retrieved oocytes/follicles at trigger (78.0% ± 29.0% vs. 78.0% ± 27.0%, p = 0.881), number of mature oocytes (7.6 ± 5.3 vs. 8.0 ± 5.1, p = 0.519), and pregnancy rate (27% vs. 23%, p = 0.514). However, the time required to retrieve each oocyte was longer using the DLN (1.5 ± 1.3 vs. 1.1 ± 0.9 minutes, p = 0.002). The present study confirmed the new perspectives on the sole use of SLNs in terms of saving time, without affecting the number of retrieved oocytes. Trial registration number and date of registration NCT03611907; July 26, 2018.


Hippocampal and lateral entorhinal cortex physiological activity during trace conditioning under urethane anesthesia.
Significant evidence shows that the acquisition of delay conditioning can occur in out-of-awareness states, such as under anesthesia. However, it is unclear to what extent and what type of conditioning animals may achieve during nonawake states. Trace conditioning is an appealing protocol to study under anesthesia, given the long empty gap separating the conditioned and unconditioned stimuli, which must be bridged for acquisition to happen. Here, we show evidence that rats develop physiological responses during the trace conditioning paradigm under anesthesia. We recorded the activity of the hippocampus (HPC) and lateral entorhinal cortex (LEC) in urethane-anesthetized rats, along with an electromyogram and an electrocardiogram. The protocol consisted of randomly presenting two distinct sound stimuli (CS- and CS+), where only one stimulus (CS+) was assigned to be trace-paired with a footshock. A trial-average analysis revealed that animals developed significant climbing heart rate activity initiating at the CS onset and persisting during the trace period. Such climbing arose for both CS- and CS+ with similar slopes but different intercepts, suggesting CS+ heart rates were typically above CS-. The power and coherence of HPC and LEC high-frequency bands (>100 Hz) significantly increased during CS presentation and trace, similarly to CS- and CS+ and insensitive to either activated or deactivated states. To the best of our knowledge, this is the first attempt to perform a trace conditioning protocol under anesthesia. Confirmation of this procedure acquisition can allow a new preparation for the exploration of brain mechanisms that bind time-discontinuous events.NEW & NOTEWORTHY Some forms of learning, such as some types of conditioning, can occur in anesthetized states. However, the extent to which memories can be formed in these states is still an open question. Here, we investigated the trace conditioning under urethane anesthesia and found heart rate, hippocampus, and lateral entorhinal cortex physiological changes to stimuli presentation. This new preparation may allow for exploration of memory acquisition of time-discontinuous events in the nonawake brain.


Hypoxia-dependent accumulation of hypoxia-inducible factor-1 alpha induces transient cell cycle arrest in porcine trophectoderm cells.
In the uterine environment, the pre-implantation embryo adapts to low oxygen concentrations through intracellular responses including modification of gene expression, progression via the cell cycle and metabolism. In this study, we determined mechanisms underlying the adaptation of pig embryos to oxygen deficiency in the maternal-conceptus microenvironment in in vitro experiments using our established porcine trophectoderm (pTr) cells in culture. The transition from G1 to S phase in pTr cells was reduced in response to 2% oxygen during a short period (<24 h), and the hypoxia-induced G1 arrest was reversible during prolonged hypoxia exposure. Acute hypoxia up-regulated expression of transcription factors p21 and p27 and down-regulated cell cycle regulators associated with the G1/S phase transition including cyclin D1, cyclin E1 and E2F1 mRNAs and proteins. Furthermore, hypoxia exposure for 24 h markedly increased the abundance of HIF-1α protein. Even under acute hypoxia, by HIF-1α silencing reduced the hypoxia-induced transient G1 arrest and expression of p21 and p27 genes was restored. Contrary to acute hypoxia, the accumulation of HIF-1α protein decreased as the length of the hypoxic period increased. Overall results of the present study suggest that increases in HIF-1α are responsible for initial response to hypoxia that results in a transient cell cycle arrest in pTr cells and cell cycle progression is restored by increasing degradation of HIF-1α during prolonged hypoxia. These findings advance understating of cellular adaptation of developing pre-implantation porcine conceptuses to hypoxic stress.


A3-A3 anastomosis and superficial temporal artery-radial artery graft-A3 bypass to treat bilateral ACA steno-occlusive hemodynamic ischemia with cognitive and executive dysfunction: a technical note.
Executive functions are complex cognitive control functions that include cognitive flexibility, inhibition (self-control, self-regulation), and working memory. Bilateral frontal lobe ischemia is associated with cognitive impairment, especially in the context of dysexecutive syndrome. This report describes two patients who underwent bilateral anterior cerebral artery (ACA) reconstruction by A3-A3 anastomosis in conjunction with superficial temporal artery (STA)-radial artery (RA) graft-A3 bypass to treat bilateral ACA steno-occlusive hemodynamic ischemia accompanying cognitive and executive dysfunction. A 74-year-old woman and a 73-year-old woman were admitted to our hospital for unilateral cerebral infarction in the frontal lobe. Magnetic resonance angiogram (MRA) demonstrated severe bilateral ACA steno-occlusive pathology in both patients. Considering the presence of impaired cognitive function with dysexecutive syndrome as well as hemodynamic compromise shown by single photon emission computed tomography (SPECT), we proceeded with A3-A3 anastomosis in conjunction with STA-RA-A3 bypass. Various neuropsychiatric tests were performed before and after the surgery. We confirmed good bypass patency without periprocedural complications. One patient recovered from apallic and bedridden status and regained ambulatory condition and ability to take in an oral diet. Another patient demonstrated improved scores in several cognitive tests with some persistent executive dysfunction. Bilateral ACA revascularization was technically feasible in two patients. This bypass surgery could have some positive effects in some basic cognitive function, such as memory, attention, and concentration by bilateral ACA hemodynamic improvement, although executive function, which is specific to prefrontal function, might not be reversible.


Structural and functional characterization of a synthetically modified OmpG.
Chemical modification of ion channels has recently attracted attention due to their potential use in stochastic sensing and neurobiology. Among the available channel templates stable β-barrel proteins have shown their potential for large scale chemical modifications due to their wide pore lumen. Ion-channel hybrids using the outer membrane protein OmpG were generated by S-alkylation with a synthetic modulator and functionally as well as structurally characterized. The dansyl moiety of the used modulator resulted in partial blockage of current though the OmpG channel with its gating characteristics mainly unaffected. The crystal structure of an OmpG-dansyl hybrid at 2.4Å resolution correlates this finding by showing that the modulator lines the inner walling of the OmpG pore. These results underline the suitability of OmpG as a structural base for the construction of stochastic sensors.


Cytotoxicity and growth-inhibiting activity of Astragalus polysaccharides against breast cancer via the regulation of EGFR and ANXA1.
Astragalus polysaccharide (APS) has been frequently used as an adjuvant agent responsible for its immunoregulatory activity to enhance efficacy and reduce toxicity of chemotherapy used in the management of breast cancer. However, the other synergism mechanism of APS remains unclear. This study was performed to evaluate the potential targets and possible mechanism behind APS in vivo direct anti-tumor activity on breast cancer. Multiple biological detections were conducted to investigate the protein and mRNA expression levels of key targets. In total, 116 down-regulated and 73 up-regulated differential expressed genes (DEGs) were examined from 7 gene expression datasets. Top ten hub genes were obtained in four typical protein-protein interaction (PPI) network of DEGs involved in each specific biological process (BP, cell cycle, cell proliferation, cell apoptosis and death) that was related to inhibitory activity of APS in vitro against breast cancer cell lines. Four common DEGs (EGFR, ANXA1, KIF14 and IGF1) were further identified in the above four BP-PPI networks, among which EGFR and ANXA1 were the hub genes that were potentially linked to the progression of breast cancer. The results of biological detections indicated that the expression of EGFR in breast cancer cells was down-regulated, while the expression of ANXA1 was markedly increased in response to APS. In conclusion, the present study may provide potential molecular therapeutic targets and a new insight into the mechanism of APS against breast cancer.


Transcatheter Valve SELECTion in Patients With Right Bundle Branch Block and Impact on Pacemaker Implantations.
This study sought to evaluate the impact of the ACURATE neo (NEO) (Boston Scientific, Marlborough, Massachusetts) versus SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California) on permanent pacemaker implantation (PPI) in patients with pre-existing right bundle branch block (RBBB) after transcatheter aortic valve replacement. Pre-existing RBBB is the strongest patient-related predictor for PPI after transcatheter aortic valve replacement. No comparison of newer-generation transcatheter heart valves with regard to PPI in these patients exists. This multicenter registry includes 4,305 patients; 296 (6.9%) had pre-existent RBBB and no pacemaker at baseline and formed the study population. The primary endpoint was new PPI at 30 days. The association of NEO versus S3 with PPI was assessed using binary logistic regression analyses and inverse probability treatment weighting in a propensity-matched population. The 30-day PPI rate was 39.2%. The S3 and NEO were used in 66.9% and 33.1%, respectively. The NEO was associated with lower rates of PPI compared with the S3 (29.6% vs. 43.9%; p = 0.025; odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.32 to 0.89; p = 0.018), after multivariable adjustment (OR: 0.48; 95% CI: 0.26 to 0.86; p = 0.014), and in the inverse probability treatment weighting analysis (OR: 0.37; 95% CI: 0.25 to 0.55; p < 0.001). There was no difference in device failure (8.2% vs. 6.6%; p = 0.792) or in-hospital course. In the propensity-matched population, PPI rate was also lower in the NEO versus S3 (23.1% vs. 44.6%; p = 0.016; OR: 0.37; 95% CI: 0.17 to 0.78; p = 0.010), with no difference in device failure (9.2% vs. 6.2%; p = 0.742). In patients with RBBB, risk of PPI was significantly lower with the NEO compared with the S3, suggesting the possibility of a patient tailored transcatheter heart valve therapy.


Addressing the challenge of cold stress resilience with the synergistic effect of Rhizobium inoculation and exogenous melatonin application in Medicago truncatula.
Cold stress is an adverse environmental condition that limits the growth and yield of leguminous plants. Thus, discovering an effective way of ameliorating cold-mediated damage is important for sustainable legume production. In this study, the combined use of Rhizobium inoculation (RI) and melatonin (MT) pretreatment was investigated in Medicago truncatula plants under cold stress. Eight-week-old seedlings were divided into eight groups: (i) CK (no stress, noninoculated, no MT), (ii) RI (Rhizobium inoculated), (iii) MT (75 μM melatonin), (iv) RI+MT, (v) CS (cold stress at 4 °C without Rhizobium inoculation and melatonin), (vi) CS+RI, (vii) CS+MT, and (viii) CS+RI+MT. Plants were exposed to cold stress for 24 hrs. Cold stress decreased photosynthetic pigments and increased oxidative stress. Pretreatment with RI and MT alone or combined significantly improved root activity and plant biomass production under cold stress. Interestingly, chlorophyll contents increased by 242.81% and MDA levels dramatically decreased by 34.22% in the CS+RI+MT treatment compared to the CS treatment. Moreover, RI+MT pretreatment improved the antioxidative ability by increasing the activities of peroxidase (POD; 8.45%), superoxide dismutase (SOD; 50.36%), catalase (CAT; 140.26%), and ascorbate peroxidase (APX; 42.63%) over CS treated plants. Additionally, increased osmolyte accumulation, nutrient uptake, and nitrate reductase activity due to the combined use of RI and MT helped the plants counteract cold-mediated damage by strengthening the nonenzymatic antioxidant system. These data indicate that pretreatment with a combined application of RI and MT can attenuate cold damage by enhancing the antioxidation ability of legumes.


Colloid infusion in the perinatal period and abnormal neurodevelopmental outcome in very low birth weight infants.
In very low birth weight (VLBW) infants, colloid infusion is associated with impaired perinatal lung function and increased oxygen dependency duration. The aim of this study was to determine whether perinatal colloid infusion was associated with abnormal neurodevelopmental outcome. All perinatal fluid input (crystalloid and colloid) given to VLBW infants entered into a randomised trial was recorded. At 1 and/or 2 years, the neurodevelopmental status of VLBW infants was routinely assessed. Of 131 survivors, median gestational age 27 weeks (range 23-33 weeks), 95 were seen at follow-up. Nineteen had abnormal neurodevelopmental outcome and differed significantly from the rest of the cohort with regard to their birth weight, magnitude of colloid infusion received and the proportions who had received postnatal steroids, suffered prolonged oxygen dependency or having had intracerebral haemorrhage/periventricular leucomalacia development. Regression analysis demonstrated that only colloid infusion related significantly to abnormal neurodevelopmental outcome independent of other variables. These data suggest that colloid infusion should be used with caution in the perinatal period.


Classification of extrachromosomal circular DNA with a focus on the role of extrachromosomal DNA (ecDNA) in tumor heterogeneity and progression.
Although the eukaryotic genome is mainly comprised of linear chromosomal DNA, genes can also be found outside of chromosomes. The unconventional presence of extrachromosomal genes is usually found to be circular, and these structures are named extrachromosomal circular DNA (eccDNA), which are often observed in cancer cells. Various types of eccDNA including small polydispersed DNA (spcDNA), telomeric cirlces, microDNA, etc. have been discovered. Among these eccDNA, extrachromosomal DNA (ecDNA), which encompasses the full spectrum of large, gene-containing extrachromosomal particles, has regained great research interest due to recent technological advances such as next-generation sequencing and super-resolution microscopy. In this review, we summarize the different types of eccDNA and discuss the role of eccDNA, especially ecDNA in tumor heterogeneity and progression. Additionally, we discuss some possible future investigative directions related to ecDNA biogenesis and its clinical application.


Virtual Care Takes Off During COVID-19 Pandemic.
Studies of safety and quality will determine the optimum use of this option.


Minimally invasive transforaminal lumbar interbody fusion using the biportal endoscopic techniques versus microscopic tubular technique.
Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) with microscopic tubular technique is an established surgical procedure with several potential advantages, including decreased surgical-related morbidity, reduced length of hospital stay, and accelerated early rehabilitation. A recently introduced biportal endoscopic technique for spine surgery presents familiar surgical anatomy and can be conducted using a conventional approach with a minimal footprint; it is also applicable to TLIF. To compare the clinical and radiological outcomes of biportal endoscopic technique transforaminal lumbar interbody fusion (BE-TLIF) and microscopic tubular technique transforaminal lumbar interbody (MT-TLIF) in patients with single- or two-segment lumbar spinal stenosis with or without spondylolisthesis. A retrospective cohort study. One hundred two participants with neurogenic intermittent claudication or lumbar radiculopathy with single- or two-level lumbar spinal stenosis with or without spondylolisthesis. Clinical outcomes were assessed using the visual analog scale (VAS) score for the back and leg pain, Oswestry Disability Index (ODI), and the Short Form-36 health survey Questionnaire (SF-36). Demographic data, operative data (total operation time, estimated blood loss, amount of surgical drain, postoperative transfusion, and length of hospital stay), and laboratory results (plasma hemoglobin, serum creatine phosphokinase, and C-reactive protein) were also evaluated. The fusion rate was assessed using the Bridwell interbody fusion grading system. Postoperative complications were also noted. Patients were divided into two groups: group A (BE-TLIF) and group B (MT-TLIF). The clinical outcomes, including VAS-Back and VAS-Leg, ODI, and SF-36 scores, were evaluated at 1 month, 6 months, and 1 year after surgery. Differences in demographics, operative data, and the laboratory and radiological results were assessed between the two groups. The fusion rate was assessed using standard standing lumbar radiographs and computed tomography scans conducted 1 year after surgery. Seventy-nine patients were analyzed in this study, 47 from group A and 32 from group B. Demographic and operative data were comparable for both the groups. The VAS-Back and SF-36 scores were more significantly improved in group A than in group B at 1 month after surgery. However, there were no significant differences between groups for the mean VAS-Back, VAS-Leg, ODI, and SF-36 scores at 1year after the surgery. Although the total operation time was significantly longer in group A, the estimated blood loss and the amount of surgical drainage was significantly higher in group B (p < .001). There were no between-group differences for the fusion rate and postoperative complications. Both BE-TLIF and MT-TLIF provided equivalent and favorable clinical outcomes and fusion rates. Further large-scale, randomized, controlled trials with long-term follow-ups are warranted.


Decidua mesenchymal stem cells migrated toward mammary tumors in vitro and in vivo affecting tumor growth and tumor development.
Mesenchymal stem cells (MSCs) have affinity to tumor sites where they home, affecting their biology and growth. Previously, we have isolated mesenchymal cells from the decidua of the human placenta named as decidua-derived MSCs (DMSCs). The aims of the present study were to investigate the migration capacity of DMSCs in vitro, and in vivo in a preclinical model of mammary tumors induced by N-nitroso-N-methylurea (NMU). Additionally, we assessed the safety of DMSC administration in vivo and their effect on tumor growth. In vitro studies showed that DMSCs significantly migrate toward both, healthy human breast tissue and breast adenocarcinoma. Nevertheless, the effect on DMSC migration was significantly higher in the presence of tumor tissue. DMSCs also significantly migrated in vitro in the presence of NMU-mammary tumor homogenate when compared with control media alone. In vivo studies showed both migration and engraftment of DMSCs into NMU-induced tumors. Interestingly, DMSCs showed an inhibitory effect on the growth of primary tumors and in the development of new tumors. DMSCs did not affect the growth of secondary tumors, although secondary tumors appeared 2 weeks later, and the number of secondary tumors was lower in the DMSC-treated rats as compared with vehicle-treated rats. To our knowledge, this is the first report showing placental MSCs effect on tumor growth. In conclusion, DMSCs could serve as a therapeutic agent themselves and as a cellular vehicle of anticancer drugs.


How genomic studies have improved our understanding of the mechanisms of transcriptional regulation by NR5A nuclear receptors.
SF-1 and LRH-1 are transcription factors that belong to the NR5A family of nuclear receptors that both have an essential role during development. Recent studies at the genome-wide scale have enabled the characterization of the cistrome and transcriptome regulated by SF-1 and LRH-1 in different cell lines and tissues. Those studies have allowed us to make a significant leap forward in our understanding of the mechanisms of transcriptional regulation of NR5A nuclear receptors in stem cells and cancer.


[Reduction of germ cell number induced in vitro by the testis in fetal rat ovary may be caused by factors other than anti-Müllerian hormone].
Fetal testes explanted at 16.5 days and cultured with female genital tracts from 13.5-day-old rat fetuses strongly inhibited the Müllerian ducts and reduced the number of ovarian germ cells. Such a reduction was not obtained during cultures with testes from 13.5 days, even though they clearly inhibited Müllerian ducts. When testes from 16.5 days were cultured at distance from the female tracts only the loss of germ cells was observed. These results suggest that testes from 16.5 days produce a diffusible factor distinct from AMH and which reduces the number of germ cells in cultured ovaries.


Neighborhood environment profiles for physical activity among older adults.
To explore among older adults whether multivariate neighborhood profiles were associated with physical activity (PA) and BMI. Adults (66-97 years) were recruited from Baltimore-Washington, DC (n=360), and Seattle-King County, Washington (n=368), regions. Latent profile analyses were conducted using the Neighborhood Environment Walkability Scale. ANCOVA models tested for criterion validity of profiles by examining relationships to PA and BMI. Neighborhood profiles differed significantly by as much as 10 minutes/day for moderate-to-vigorous PA, 1.1 hours/week for walking for errands, and almost 50 minutes/week for leisure PA. Environmental variables resulted in meaningful neighborhood patterns that explained large differences in seniors' health outcomes.


Roles of Ambient Temperature and PM2.5 on Childhood Acute Bronchitis and Bronchiolitis from Viral Infection.
Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006−2016. The monthly average incident CABs increased with increasing PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June−August). The highest incidence was 698 cases/day at <20 °C with PM2.5 > 37.0 μg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97−1.04) compared to 568 cases/day at <20 °C with PM2.5 < 15.0 μg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85−1.06) with PM2.5 > 37.0 μg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58−0.65) when PM2.5 was <15.0 μg/m3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.


Y-Stent Technique for Treatment of Wide-Necked Posterior Communicating Artery Aneurysm Associated with Fetal Posterior Cerebral Artery: Technical Report.
Despite a variety of technologies that are available for treatment of complex intracranial aneurysms, certain anatomic configurations remain challenging to address endovascularly. A patient was found to have an incidental 12 mm × 11 mm × 10 mm, wide-necked right posterior communicating artery aneurysm with a fetal origin of the posterior cerebral artery arising directly from the aneurysm dome. After multidisciplinary discussion, a staged endovascular treatment approach was undertaken in 2 stages. First, a Y-stent construct using 2 overlapping Neuroform Atlas stents was placed into the M1 and fetal posterior cerebral artery segments. Two months later, after endothelialization of the stent construct, coil embolization of the aneurysm was performed. The patient tolerated both stages of the procedure well and was discharged the following day in each case. She remained neurologically intact, and at follow-up 5 months later had no evidence of residual or recurrent aneurysm. This case illustrates a number of important considerations in the management approach for wide-necked intracranial aneurysms.


Let-7 microRNA and HMGA2 levels of expression are not inversely linked in adipocytic tumors: analysis of 56 lipomas and liposarcomas with molecular cytogenetic data.
The aim of our study was first to assess the role of HMGA2 expression in the pathogenesis of adipocytic tumors (AT) and, second, to seek a potential correlation between overexpression of HMGA2 and let-7 expression inhibition by analyzing a series of 56 benign and malignant AT with molecular cytogenetic data. We measured the levels of expression of HMGA2 mRNA and of eight members of the let-7 microRNA family using quantitative RT-PCR and expression of HMGA2 protein using immunohistochemistry. HMGA2 was highly overexpressed in 100% of well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS), all with HMGA2 amplification, and 100% of lipomas with HMGA2 rearrangement. Overexpression of HMGA2 mRNA was detected in 76% of lipomas without HMGA2 rearrangement. HMGA2 protein expression was detected in 100% of lipomas with HMGA2 rearrangement and 48% of lipomas without HMGA2 rearrangement. We detected decreased expression levels of some let-7 members in a significant proportion of AT. Notably, let-7b and let-7g were inhibited in 61% of WDLPS/DDLPS. In lipomas, each type of let-7 was inhibited in approximately one-third of the cases. Although overexpression of both HMGA2 mRNA and protein in a majority of ordinary lipomas without HMGA2 structural rearrangement may have suggested a potential role for let-7 microRNAs, we did not observe a significant link with let-7 inhibition in such cases. Our results indicate that inhibition of let-7 microRNA expression may participate in the deregulation of HMGA2 in AT but that this inhibition is neither a prominent stimulator for HMGA2 overexpression nor a surrogate to genomic HMGA2 rearrangements.


Amino acid composition, relative nutritive value and in vitro protein digestibility of several Philippine indigenous legumes.
This study demonstrates variability in amino acid composition among accessions of several Philippine indigenous legumes. Moreover, two accessions of D. lablab were identified to have high level of methionine (greater than 2%). Methionine was identified as the first limiting amino acid with leucine, and threonine as the second limiting amino acids for most legumes studies. The IVPDs of the legumes under study ranged from greater than 70 to 79%. Raw mature seeds had relatively low RNVs of 11 to 68% which increased to 68 to 94% and 51 to 89% after boiling and roasting, respectively.


Nonproteinogenic deep mutational scanning of linear and cyclic peptides.
High-resolution structure-activity analysis of polypeptides requires amino acid structures that are not present in the universal genetic code. Examination of peptide and protein interactions with this resolution has been limited by the need to individually synthesize and test peptides containing nonproteinogenic amino acids. We describe a method to scan entire peptide sequences with multiple nonproteinogenic amino acids and, in parallel, determine the thermodynamics of binding to a partner protein. By coupling genetic code reprogramming to deep mutational scanning, any number of amino acids can be exhaustively substituted into peptides, and single experiments can return all free energy changes of binding. We validate this approach by scanning two model protein-binding peptides with 21 diverse nonproteinogenic amino acids. Dense structure-activity maps were produced at the resolution of single aliphatic atom insertions and deletions. This permits rapid interrogation of interaction interfaces, as well as optimization of affinity, fine-tuning of physical properties, and systematic assessment of nonproteinogenic amino acids in binding and folding.


Stress shielding effect of rigid internal fixation plates on mandibular bone grafts. A photon absorption densitometry and quantitative computerized tomographic evaluation.
The use of rigid internal fixation reconstruction plates in combination with bone grafts provides many advantages in mandibular reconstruction. These advantages include ease of adaptability at the time of surgery as well as immediate postoperative function for the patient. Disadvantages may include a "stress shielding" or disuse osteoporosis effect on the underlying bone graft as a result of the rigidity of the reconstruction plate. This study evaluated the stress shielding effects on bone grafts in primate mandibles. Bilateral bone grafts stabilized with rigid fixation plates were performed in 4 Macaca fascicularis monkeys. Three months after the bone grafting procedure one plate was removed from each monkey. The monkeys were then killed 1, 4, 6 and 8 months after plate removal. Photon absorption densitometry and computerized tomography were used to evaluate stress shielding. The results of this study indicate that the stress shielding effect occurs if the plate is not removed from the area of bone grafting postoperatively.


Alloimmunization against Iy, a low-frequency antigen on platelet glycoprotein Ib/IX as a cause of severe neonatal alloimmune thrombocytopenic purpura.
Neonatal alloimmune thrombocytopenia (NAIT) is usually induced by platelet-specific antibodies against HPA-1a (Zwa) or HPA-5b (Bra). Recently, low-frequency alloantigens on the platelet glycoprotein (GP) IIb/IIIa complex have been discovered as a cause for NAIT. In this report, a new low-frequency platelet-specific alloantigen, Iy, is described which induced severe NAIT. The corresponding antigen was detected in 1/249 unrelated German blood donors. Antibody binding assays with trypsin-digested platelets (ELISA, immunoprecipitation with biotin-labelled platelets) indicate that the antigen is not localized on the glycocalicin moiety of GP Ib alpha, but may be situated on the remnant moiety of GP Ib alpha, GP IX or GPIb beta. Apparently, Iy is not related to the HPA-2 (Ko) antigen system.


Morphological, biochemical and molecular identification of petroleum hydrocarbons biodegradation bacteria isolated from oil polluted soil in Dhahran, Saud Arabia.
Accumulation of petroleum hydrocarbon residual considered a major environmental problem in the kingdom of Saudi Arabia cause of intensive efforts for oil detecting. Until now, In situ biodegradation considered the most effective method for petroleum hydrocarbon residual biodegradation. The aim of this study is isolation and identification biodegradable capability bacteria from contaminated sites in Khurais oil field, Dhahran, Saud Arabia via Different morphological and biochemical and molecular methods. Furthermore, degradation level in contaminated liquid medium and soil were evaluated. Three bacterial strains were selected from petroleum-contaminated soils of Khurais oil field depending on their capacity to grow in the existence of hydrocarbon components and identified according to morphological, biochemical. Interestingly, 16S rDNA sequencing fingerprinting results confirmed our bacterial identification as Bacillus subtilis, Pseudomonas aeruginosa and Bacillus cereu. Phyllogenetic tree was constructed and genetic similarity was calculated according to alignments results. Biodegradation patterns for different three isolates were reflected varied degradation ability for three isolates regarding incubation time. Different features were studied for three biodegrading bacterial strains and identified as Bacillus subtilis, Pseudomonas aeruginosa and Bacillus cereus. Remarkable degradation rate % patterns for hydrocarbons residual were recorded for all three isolates with varied.


Comparison of withdrawing antihypertensive therapy between diuretics and angiotensin converting enzyme inhibitors in essential hypertensives.
One hundred thirteen patients with essential hypertension receiving single or multiple antihypertensive agents were enrolled in the study. All had had mild to severe hypertension before treatment, but their diastolic blood pressure (DBP) at study entry was lower than 90 mm Hg for all measurements. In half of the subjects, non-thiazide diuretics (n = 35) or angiotensin-converting enzyme inhibitors (ACEI, n = 37) were discontinued, and their remaining drugs were maintained throughout the study. The other patients (n = 41) continued all their medications. Forty-one percent of subjects remained normotensive for 12 months after withdrawal of diuretics, and 37% of patients with ACEI discontinuation remained normotensive, although the recurrence of hypertension after withdrawal of ACEI tended to be earlier than its recurrence after withdrawal of diuretics. Serum uric acid and creatinine concentration decreased after diuretic withdrawal, but not after ACEI withdrawal. Diuretic withdrawal resulted in an increase in serum potassium, but ACEI withdrawal induced a decrease in serum potassium. Withdrawal of diuretics or ACEI both significantly reduced plasma renin activity. The present study may be indicative of the ability to withdraw some medications in many patients being treated with multiple antihypertensive agents.


Numerical simulation of tropical cyclone generated waves in South China Sea during winter monsoon surge.
The South China Sea (SCS) is a highly semi-enclosed marginal sea located in the East Asian monsoon region. This paper proposes interesting aspects of the unique feature of the SCS waves in response to tropical cyclone's passage when large-scale winter monsoon winds prevail. We use the wave model WaveWatch III to study the wave characteristics of typhoon Durian (2006) passing over the middle of SCS in early December 2006, and state the new understanding acquired in the aspects of the tropical cyclone generated waves in the SCS during winter monsoon surge. In light of this, the role of the large-scale NE monsoon winds on winter typhoon wave field characteristics in the SCS are highlighted by conducting sensitivity experiments with and without the NE monsoon winds. The NE monsoon winds weakly affect the SWH field near the typhoon track and strongly away from the track, especially in the deep water area of the northern SCS where the NE monsoon winds produce high waves. Comparisons between the two experiments show the effect of the NE monsoon winds on the directional wave spectra in the SCS, suggesting that the monsoon-generated swells do not decay and remain throughout the typhoon period.


Intra-articular injections for joint disease in horses.
Lameness remains an important source of reduced performance in many types of horses. Pain referable to joints is among the most common causes, and intra-articular injections remain a common and important means of addressing lameness referable to joints in horses.


Calcified obstructive disease of the aortic isthmus.
A 52-year-old man presented with a calcified thrombus measuring 5 cm in length, which was responsible for obstruction of two-thirds of the aortic isthmus lumen. At operation the thrombus was seen to stem from an ulcerated plaque in the aortic wall, 4 mm in diameter. Six years later, his aortograms were normal. We believe the thrombus had an atheromatous origin.


Older Age and High α-Fetoprotein Predict Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis-B-Related Cirrhotic Patients Receiving Long-Term Nucleos(t)ide Analogue Therapy.
Background: Nucleos(t)ide analogues (NUCs) were proved to reduce hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients, but data were limited on their efficacy in cirrhotic CHB patients. Methods: A total of 447 cirrhotic CHB patients treated with tenofovir/entecavir were retrospectively analyzed and divided into HCC (n = 48) and non-HCC (n = 399) groups. The median follow-up period was 62.1 months. Results: A total of 48 patients (10.7%) developed HCC during surveillance. The annual incidence rate of HCC was 2.04 per 100 person-years. The cumulative incidence of HCC was 0.9%, 9.8%, and 22.1% at 1, 5, and 10 years, respectively. Significant predictors for HCC identified using a multiple Cox regression analysis were age ≥50 years (hazard ratio (HR): 2.34) and α-fetoprotein (AFP) ≥8 ng/mL (HR: 2.05). The incidence rate of HCC was 8.67-fold higher in patients with age ≥50 years and AFP ≥8 ng/mL (3.14 per 100 person-years) than those with age <50 years and AFP <8 ng/mL (0.36 per 100 person-years). Conclusions: Cirrhotic CHB patients with age <50 years and AFP <8 ng/mL had the lowest annual incidence of HCC. However, those with age ≥50 years or/and AFP ≥8 ng/mL had a significantly higher risk for HCC development and warrant a careful surveillance schedule.


Comparison of thyroid hormone levels between normal and preeclamptic pregnancies.
To investigate thyroid function in preeclamptic patients in comparison with normal pregnant women. In this analytical cross-sectional study free Thyroxine (T4), and Thyroid Stimulating Hormone (TSH) levels were measured in 100 preeclamptic patients and were compared with Free T4 and TSH levels in 101 normal pregnant women in their third trimester of pregnancy. Patients with thyroid or other systemic disorders were excluded from this study. A significant difference in concentration of free T4 levels (0.729 ±0.324 ng/ dl versus 0.929± 0.314 ng/dl, p <0.001) was observed in the preeclamptic group compared with the normotensive group, but the mean TSH level was not significantly different (2.935±1.16 mIU/L versus 2.339±1/15 mIU/L, p = 0.170). Women who develop preeclampsia are more likely to have lower normal limits of thyroid function during their final weeks of pregnancy.


Anti-epileptogenic effects of synaptic vesicle protein 2A modulation in a mouse model of Alzheimer's disease.
To assess the effects of synaptic vesicle protein 2A (SV2A) modulators brivaracetam and levetiracetam on amygdala kindling epileptogenesis in Tg2576 mice, a model of Alzheimer's disease which exhibits sensitivity to seizures. First, aged Tg2576 mice (13-25 months; n = 17) were treated subcutaneously with either brivaracetam (10 mg/kg/day), levetiracetam (150 mg/kg/day) or vehicle via osmotic pumps for 28 days prior to, and during electrical amygdala kindling epileptogenesis. Next, we treated young (4-6 months; n = 24) Tg2576 mice with brivaracetam (10 mg/kg/day) or vehicle for 28 days and allowed one week's 'washout' before commencing kindling. Progression of seizure severity and duration were compared between treatment groups and wildtype mice (WT). In older Tg2576 mice, treatment with brivaracetam (p < 0.001) and levetiracetam (p < 0.05) before and during kindling significantly delayed the progression of seizure severity, compared to vehicle. Animals treated with brivaracetam required significantly more stimulations to reach the first class V (convulsive) seizure and had a lower mortality rate (p < 0.05) compared to those treated with vehicle. Young Tg2576 mice also exhibited increased susceptibility to kindling epileptogenesis compared to WT. Treatment with brivaracetam in younger animals only prior to kindling also delayed kindling acquisition compared to vehicle treatment, increasing the number of stimulations required to experience class V seizures (p < 0.05). Brivaracetam treatment displayed marked anti-epileptogenic effects in both aged and young Tg2576 mice, including when treatment is ceased prior to initiating kindling. Targeting SV2A might represent a strategy for prevention of epilepsy in patients with Alzheimer's disease.


[Radical lung surgery interventions with special reference to lymphadenectomy].
Intraoperative lymph node staging plays an essential part in the surgical treatment of lung cancer. The mean number of resected lymph nodes in 237 patients was 17, with a minimum of 1 and a maximum of 60. The largest number was found in N1 regions as expected. The number of resected nodes in the paratracheal, tracheobronchial and subcarinal region was 4, in the paraoesophageal and ligament region 1.2. Twenty-two percent of the whole group showed an N2 situation. In 45% of the patients with N2 invasion, we found a lymph node skipping and in 25% only one positive N2 node. Thus, it is obvious that without a systematic lymph node dissection an exact staging is not possible.


Calcium Channel Blockers Induced Gingival Overgrowth: A Comprehensive Review from a Dental Perspective.
Gingival overgrowth (GO) as a manifestation of calcium channel blockers (CCBs) was first introduced in the literature by Ramon et al. in 1984. Since then, the use of CCBs as a treatment modality for hypertension has been recorded extensively in the literature for its association with GO. The aim of our study is to evaluate histopathology, treatment, and follow-up for the cases detailed in various studies and also to highlight the protocol mentioned to identify these presentations. A broad search was conducted from the period 1980 to 2021 using electronic databases PubMed Central, Scopus, Cochrane, and SciELO databases. About 293 articles were initially chosen. The articles further excluded did not fit the criteria for the study and eventually 50 articles which met the inclusion criteria were chosen as part of this literature review. A comparative analysis was carried out regarding histopathology, treatment modalities, drug dosage, and duration to evaluate the differences in cases between 1980 and 2021. From the available studies, it was found that the histopathological and clinical findings were varied. Treatment strategies employed were different, though follow-ups in most cases were uniform. CCBs and their relationship with GO have been widely reported in the literature. Dentists should approach this condition by taking appropriate medical and dental history and follow evidence-based treatment guidelines to provide more relevant and judicious management of this condition. Inter-disciplinary treatment approaches would provide better outcomes.


Comparative Effectiveness and Safety of Allografts and Autografts in Posterior Cruciate Ligament Reconstruction Surgery: A Systematic Review.
To evaluate the evidence of the effectiveness and safety of allografts compared to autografts in posterior cruciate ligament reconstruction. Four electronic databases were systematically searched for eligible randomized controlled studies. Crucial effectiveness outcomes included patient-reported function, activity level and symptoms, clinical knee stability, health-related quality of life, and patient satisfaction. Safety was evaluated through graft failures, revisions, reruptures and complications. The internal validity of the studies was assessed by the Cochrane risk of bias tool, and the strength of the evidence was judged according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Two randomized controlled studies were included: 50 patients were analyzed in the allograft group and 58 in the autograft group. No statistically significant postoperative differences were reported between the groups for patient-reported function, activity levels or symptoms. One study reported a statistically significant difference in instrumented postoperative anteroposterior knee laxity favoring stability in autografts. This difference is, however, not relevant in the clinical setting. Insufficient evidence was found to judge safety outcomes and because complications were poorly measured, and none of the studies reported on graft failure, revision or rerupture rates. The studies were judged with unclear to high risk of bias. The strength of the evidence for effectiveness and safety was judged to be low to very low, according to GRADE. Allografts may be comparable to autografts for crucial effectiveness outcomes, but insufficient evidence was found to judge crucial safety outcomes due to poor reporting of safety measures and outcomes. Results should be interpreted with caution because there is lack of good-quality evidence to support the superiority of allografts over autografts due to the high risk of bias in the primary studies and overall very low strength of the body of evidence according to GRADE. Systematic review of Level II studies.


Management of the neck in patients with T1 and T2 cancer in the mouth.
Our aim in this retrospective study was to evaluate the extent of control of metastatic disease in the neck and the survival of patients with T1 and T2 oral cancer. All 171 patients with T1 and T2 squamous cell carcinoma (SCC) in the mouth were identified from our computerised database. All had had primary tumours resected and 21 patients with palpable neck nodes had therapeutic neck dissections. Among 150 patients with no palpable nodes, 75 had elective neck dissections, and 75 were observed. The decision to do an elective neck dissection was based on clinical criteria and was not randomised. Cervical nodes contained metastases in 17 of 21 patients who had therapeutic, and 27 of 75 who had elective, neck dissections. Neck metastases developed subsequently in 15 of 75 patients in the observed group, and 9 of these were salvaged by therapeutic neck dissection. The 5-year disease free survival was 19/21 after therapeutic dissection, 72/75 after elective dissection, and 69/75 in the observed group. Patients with cervical nodal metastases had significantly reduced 5-year survival compared with those without (63% and 91%, P = 0.003).


Zero-valent iron enhanced anaerobic digestion of pre-concentrated domestic wastewater for bioenergy recovery: Characteristics and mechanisms.
Pre-concentrated domestic wastewater (PDWW) rich in organic matters can be a suitable substrate for anaerobic digestion (AD) towards holistic resource and bioenergy recovery. Micron zero-valent iron (ZVI) was applied in designed batch experiments during anaerobic treatment of PDWW to verify its roles in performance enhancement and associated mechanisms. In the selected range of food to microorganism (F/M) ratio, 0.5 gCOD/gMLVSS was most appropriate as biomethane production potential (BMP) of 0.275 L CH4/gCOD was obtained. The optimal ZVI dosage at fixed F/M of 0.5 was 6 g/L, further enhancing the BMP by 15.2%. Furthermore, ZVI improved the hydrolysis process (producing more soluble organics) and regulated acidification process (affecting volatile fatty acids distribution). No obvious impact on acetoclastic and hydrogenotrophic methanogenesis processes was noted with ZVI addition. ZVI based AD of the PDWW is promising for promoting the practical application of advanced domestic wastewater treatment strategy (pre-concentration plus anaerobic digestion).


Inflammatory response and bacterial dissemination after laparotomy and abdominal CO2 insufflation in a murine model of peritonitis.
The immunologic repercussions due to cavity insufflation are the focus of great discussion. The aim of this study was to compare the inflammatory response and bacterial dissemination after laparotomy and abdominal CO2 insufflation in a murine model of peritonitis. Swiss mice were inoculated intraperitoneally with 0.5 ml of a solution containing 1 x 10(8) colony-forming units (CFU)/ml of Escherichia coli and were divided into three groups as follow: control (anesthesia for 30 min), laparotomy (2.5-cm midline incision for 30 min), and CO2 pneumoperitoneum (CO2 cavity insufflation for 30 min). The number of leukocytes, CFU/ml counting, and the levels of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-10 were evaluated in blood, peritoneal, and pleural fluid samples obtained at 90 min and 18 h after the procedures. The laparotomy group showed a greater bacterial dissemination to the blood, peritoneum, and pleural cavity and also greater neutrophil migration to the peritoneal cavity compared to the CO2 insufflated and control groups. The 24-h mortality was also significantly higher in the laparotomy group. The IL-6 levels showed a precocious rise in all groups submitted to bacterial inoculation at the 90-min time point. At the 18-h time point, IL-6 levels in the peritoneum were significantly higher in the laparotomy group than in the control or CO2 insufflated groups. At the same time, TNF-alpha levels were higher in the laparotomy and CO2 insufflated groups than in controls; IL-10 levels showed no differences among the groups. Our results suggest that cavity insufflation with CO2 is a more effective method of access, inducing less bacterial dissemination and also a less intense inflammatory response. Cavity insufflation with CO2 may present a good option for the surgical treatment of patients with bacterial peritonitis.


Fenoprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases.
Fenoprofen1 (dl-2-[3-phenoxyphenyl]propionic acid) is a new non-steroidal anti-inflammatory, antipyretic, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Published data suggest that in rheumatoid arthritis, fenoprofen 2.4 g daily is comparable in effectiveness with moderate doses of aspirin (3.6 to 4 g daily), but generally causes fewer and milder side-effects at the dosages used. In published comparisons with other non-steroidal anti-inflammatory agents of the same chemical group, it is closely comparable with naproxen in effectiveness but tends to cause more minor side-effects than naproxen. However, as no one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, fenoprofen should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Fenoprofen has compared favourably with phenylbutazone in osteoarthrosis of the hips and with aspirin in osteoarthrosis of the shoulders, hips, knees and spine. Its exact place in the management of gout and ankylosing spondylitis remains to be determined.


Differences in blood vessels between species: relation to differences in blood vessels of varying type within the same species.
1. Major differences in physiological and pharmacological responsiveness may be observed between blood vessels that differ either in anatomical type or in that they serve different organs or tissues. 2. The intrinsic properties of the vascular smooth muscle appears to differ little between species. No important differences in noradrenergic innervation have been observed, but major differences may exist in neural dilator systems. A few differences have been demonstrated that can be attributed to variations in the receptor population. No clear differences in local humoral mechanisms are known. There is, however, an insufficient number of strictly comparable studies in different species and it is likely that more differences will be found as our knowledge of vascular responsiveness is extended.


The effect of occupational exposure to petrol on pulmonary function parameters: a review and meta-analysis.
Introduction Exposure to petrol and gasoline can have harmful effects on the lungs. This review aimed to summarize the reported effects of this exposure on pulmonary function parameters. Methods Relevant studies were identified by a comprehensive search in PubMed, Scopus, Science Direct and Google Scholar databases. Irrelevant studies were excluded. Quality assessment was performed using the Newcastle-Ottawa score (NOS). The standard mean difference of pulmonary parameters between exposed and unexposed petrol station attendants was pooled using random effects. Meta-regression was used to investigate factors probably related to heterogeneity. Studies affecting the total estimates were assessed during sensitivity analysis. The Egger test was performed to investigate any evidence of publication bias. Results Eventually, 26 studies entered the meta-analysis, and the pooled standard difference [95% confidence interval (CI)] of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, vital capacity (VC), peak expiratory flow (PEF), forced expiratory flow (FEF25-75) and maximum voluntary ventilation (MVV) in the exposed minus unexposed groups was -1.08 L (95% CI: -1.38, -0.78), -0.92 L (-1.15, -0.69), -0.65 (-1.01, -0.30), -0.51 L (-0.96, -0.06), -0.96 L/s (-1.21, -0.69), -0.78 L/s (1.14, -0.42) and -0.58 L/min (-0.90, -0.27), respectively, and showed a decrease in all pulmonary parameters in the exposed group. Conclusion Occupational exposure to petrol fumes is a risk factor for lung function and there is a reverse relation between lung function and the duration of exposure.


Suicidality and depression disparities between sexual minority and heterosexual youth: a meta-analytic review.
To examine disparities between sexual minority youth (SMY) and heterosexual youth in rates of suicidality and depression symptoms. Separate meta-analyses were conducted to examine suicidality and depression disparities. Studies were included if the average age of the participants was <18 years, and if suicidality or depression symptoms were compared across SMY and heterosexual youth. SMY reported significantly higher rates of suicidality (odds ratio [OR] = 2.92) and depression symptoms (standardized mean difference, d = .33) as compared with the heterosexual youth. Disparities increased with the increase in the severity of suicidality (ideation [OR = 1.96], intent/plans [OR = 2.20], suicide attempts [OR = 3.18], suicide attempts requiring medical attention [OR = 4.17]). Effects did not vary across gender, recruitment source, and sexual orientation definition. Disparities in suicidality and depression may be influenced by negative experiences including discrimination and victimization. Clinicians should assess sexual orientation, analyze psychosocial histories to identify associated risk factors, and promote prevention and intervention opportunities for SMY and their families.


Fractionation of RNA polymerase II transcription factors from HeLa cell nuclear extracts by affinity chromatography on "DNA-like" phosphorylated polystyrene.
It was previously shown that phosphorylated cross-linked polystyrene derivatives specifically interacted with anti-DNA antibodies and anti-phospholipid antibodies present in the sera of systemic lupus erythematosus patients. These resins are potential candidates as stationary phases in affinity chromatography. We wondered whether these biospecific resins might allow the fractionation of DNA binding proteins such as RNA polymerase II transcription factors from HeLa cell nuclear extracts. Indeed, these proteins play a major role in gene regulation in mammalian cells and their purification still requires numerous steps. To study the biospecificity of DNA-like phosphorylated polystyrene derivatives, ethanolamine sulfamide crosslinked polystyrene derivatives were phosphorylated at various rates and HeLa cell nuclear extracts were adsorbed on these resins. Adsorbed proteins were eluted with increasing concentrations of aqueous potassium chloride. Collected fractions were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and the biological activities of the eluted transcription factors were tested by in vitro transcription assay. Results showed that the elution of transcription factors depended on the substitution rate in phosphoester groups of the resins. It appears that specific interactions were developed between the polymers and the transcription factors. Moreover, the eluted transcription factors kept their biological activity. These results lead us to propose the purification of RNA polymerase II transcription factors using the phosphorylated polystyrene resins as stationary phases.


Membrane trafficking and positioning of mGluRs at presynaptic and postsynaptic sites of excitatory synapses.
The plethora of functions of glutamate in the brain are mediated by the complementary actions of ionotropic and metabotropic glutamate receptors (mGluRs). The ionotropic glutamate receptors carry most of the fast excitatory transmission, while mGluRs modulate transmission on longer timescales by triggering multiple intracellular signaling pathways. As such, mGluRs mediate critical aspects of synaptic transmission and plasticity. Interestingly, at synapses, mGluRs operate at both sides of the cleft, and thus bidirectionally exert the effects of glutamate. At postsynaptic sites, group I mGluRs act to modulate excitability and plasticity. At presynaptic sites, group II and III mGluRs act as auto-receptors, modulating release properties in an activity-dependent manner. Thus, synaptic mGluRs are essential signal integrators that functionally couple presynaptic and postsynaptic mechanisms of transmission and plasticity. Understanding how these receptors reach the membrane and are positioned relative to the presynaptic glutamate release site are therefore important aspects of synapse biology. In this review, we will discuss the currently known mechanisms underlying the trafficking and positioning of mGluRs at and around synapses, and how these mechanisms contribute to synaptic functioning. We will highlight outstanding questions and present an outlook on how recent technological developments will move this exciting research field forward.


Incorporating New Technologies to Overcome the Limitations of Endoscopic Spine Surgery: Navigation, Robotics, and Visualization.
Recently, spine surgery has gradually evolved from conventional open surgery to minimally invasive surgery, and endoscopic spine surgery (ESS) has become an important procedure in minimally invasive spine surgery. With improvements in the optics, spine endoscope, endoscopic burr, and irrigation pump, the indications of ESS are gradually widening from lumbar to cervical and thoracic spine. ESS was not only used previously for disc herniations that were contained without migration but is also used currently for highly migrated disc herniations and spinal stenosis; thus, the indications of ESS will be further expanded. Although ESS has certain advantages such as less soft tissue dissection and muscle trauma, reduced blood loss, less damage to the epidural blood supply and consequent less epidural fibrosis and scarring, reduced hospital stay, early functional recovery, and improvement of quality of life as well as better cosmesis, several obstacles remain for ESS to be widespread because it has a steep learning curve and surgical outcome is strongly dependent on the surgeon's skillfulness. A solid surgical technique requires reproducibility and ensured safety in addition to surgical outcomes. In this review article, how to improve ESS was investigated by grafting novel technologies such as navigation, robotics, and 3-dimensional and ultraresolution visualization.


A low prognostic nutritional index is associated with increased remote infections within 30 days of colorectal surgery: A retrospective cohort study.
This study aimed to identify risk factors for remote infection (RI) within 30 days after colorectal surgery. This retrospective study included 660 patients who underwent colorectal surgery at Yamaguchi University Hospital or Ube Kosan Central Hospital between April 2015 and March 2019. Using electronic medical records, we identified the incidence of surgical site infection and RI within 30 days after surgery and obtained information on associated factors. Univariate and multivariable analyses were performed to identify significant risk factors in 607 (median age, 71 years) patients. Seventy-eight (13%) and 38 (6.3%) patients had surgical site infection and RI, respectively. Of the 38 patients diagnosed with RI, 14 (36.8%) had a bloodstream infection, 13 (34.2%) had a urinary tract infection, 8 (21.1%) had a Clostridioides difficile infection, and 7 (18.4%) had respiratory tract infections. Multivariable analysis showed that a preoperative prognostic nutritional index of ≤40 (OR, 2.30; 95% CI, 1.07-4.92; P = .032), intraoperative blood transfusion (OR (odds ratio), 3.06; 95% CI, 1.25-7.47; P = .014), and concomitant stoma creation (OR, 4.13; 95% CI, 1.93-8.83; P = .0002) were significant RI predictors. Nutritional interventions prompted by low preoperative prognostic nutritional index in colorectal surgery may lead to decreases in postoperative RI.


3-Cyano-N-(2-hy-droxy-benz-yl)anilinium nitrate.
In the crystal structure of the title compound, C(14)H(13)N(2)O(+)·NO(3) (-), N-H⋯O and O-H⋯O hydrogen bonds link cations and anions into a two-dimensional network parallel to (100). The dihedral angle between the rings is 9.48 (2)°.


Surface Grafting "Band-Aid" for "Everyone": Filter Paper-Assisted Surface-Initiated Polymerization in the Presence of Air.
We report herein a facile and generalized approach to the modification of solid surfaces with polymer brushes under ambient conditions: filter paper-assisted surface-initiated Cu0 -mediated controlled radical polymerization (PSI-CuCRP). The polymerization solution wetted filter paper is sandwiched between a copper plate and an initiator-modified substrate, which allows the creation of a surface-initiated polymerization (SIP) "band-aid" so that everyone can perform the surface grafting selectively with good control over the quality of the polymer brushes employing low concentration and microliter amounts of the monomer solution. The versatility of this method is demonstrated by grafting different homo-, block-, and multicomponent polymer brushes by using the same activation system and reaction conditions, the polymerization process can be precisely controlled to yield uniform polymers and show high chain-end functionality which is exemplified by in situ tetra-copolymerization. The combination of photolithography and paper cutting enables to prepare arbitrary three-dimensional patterned polymer brushes on the surface.


Can hypertonic saline inhalation influence preformed chemokine and mediator release in induced sputum of chronic obstructive pulmonary disease patients? Comparison with isotonic saline.
Hypertonic saline (HS) has been shown to modulate in vitro cell functions according to the state of cell activation; however, few studies have evaluated the effect of HS in vivo. Chronic airway inflammation, a major feature of chronic obstructive pulmonary disease (COPD), is associated with an activation of inflammatory and resident cells, which in turn makes them more prompt to respond to further stimuli. To evaluate whether HS might modulate, also in vivo, the release of preformed mediators and intracellular chemokines from airway cells of COPD patients. Sputum was induced by inhalation of either HS (4.5% w/v) or isotonic saline (IS 0.9% w/v) solution and processed by plug selection. We measured eosinophil cationic protein (ECP), neutrophil elastase (NE), IL-8 and monocyte chemoattractant protein-1 (MCP-1) in sputum samples obtained by either HS or IS inhalation in 24 COPD patients. No significant difference in mediators measured in sputum samples obtained by the two different inductions was observed; also, there was no significant difference in sputum sample volumes, cell viability, total and differential cell counts. Repeatability between the two tests was high for ECP, NE, macrophages, neutrophils and eosinophils, and satisfactory for IL-8 and MCP-1. Hyperosmolarity does not affect the levels of the inflammatory mediators and chemokines examined or the cell counts measured in induced sputum obtained from COPD patients. This study does not support the hypothesis that HS can stimulate chemokine and mediator release from airway cells of COPD patients. Therefore, HS and IS can be interchangeably used to measure inflammatory mediators in the sputum supernatant of COPD patients.


An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions.
1. Frog neuromuscular junctions were viewed with Nomarski optics and voltage clamped. Agonist was applied ionophoretically and agonist concentrations were measured using a micro-electrode sensitive to quaternary amines. 2. The dose-response relationship was studied using the agonists carbamylcholine, suberyldicholine and hydroxyphenyl-propyltrimethylammonium. 3. With all of these agonists, it appeared that the ACh receptor could be active when either one or two agonist binding sites were occupied. The receptor was much more likely to be active when both sites were occupied. Agonist dissociation constants and receptor activation probabilities were estimated by non-linear regression techniques for several possible receptor activation schemes.


Acute testosterone deprivation reduces insulin sensitivity in men.
In men with prostate cancer, androgen deprivation reduces insulin sensitivity; however, the relative roles played by testosterone and estradiol are unknown. To investigate the respective effects of these hormones on insulin sensitivity in men, we employed a model of experimental hypogonadism with or without hormone replacement. Placebo-controlled, randomized trial. Twenty-two healthy male volunteers, 18-55 years old. Following screening, subjects received the gonadotrophin-releasing hormone antagonist acyline plus one of the following for 28 days: Group 1, placebo transdermal gel and placebo pills; Group 2, transdermal testosterone gel 10 g/day plus placebo pills; Group 3, transdermal testosterone gel 10 g/day plus the aromatase inhibitor anastrozole 1 mg/day to normalize testosterone while selectively reducing serum estradiol. Fasting insulin, glucose, adipokines and hormones were measured bi-weekly. With acyline administration, serum testosterone was reduced by >90% in all subjects in Group 1. In these men, mean fasting insulin concentrations were significantly increased compared with baseline (P = 0·02) at 28 days, despite stable body weight and no changes in fasting glucose concentrations. Decreased insulin sensitivity was also apparent in the insulin sensitivity indices homeostasis model of insulin resistance (P = 0·03) and quantitative insulin sensitivity check index (P = 0·04). In contrast, in Groups 2 and 3, testosterone concentrations remained in the physiologic range, despite significant reduction in mean estradiol in Group 3. In these groups, no significant changes in insulin sensitivity were observed. Acute testosterone withdrawal reduces insulin sensitivity in men independent of changes in body weight, whereas estradiol withdrawal has no effect. Testosterone appears to maintain insulin sensitivity in normal men.


Perioperative peripheral parenteral nutrition to support major gastrointestinal surgery: Expert opinion on treating the right patients at the right time.
Patients undergoing major gastrointestinal surgery may be in particular need of nutritional therapy due to potential pre-existing disease-related malnutrition and the impact of surgical procedures. Peripheral parenteral nutrition (PPN), delivered via a peripheral catheter, is aligned with the Enhanced Recovery After Surgery (ERAS) concept of minimally invasive interventions where possible. However, uncertainties regarding perioperative PPN for patients undergoing major gastrointestinal surgery arise, in part, due to lack of clinical guidelines. This paper aims to provide practical guidance on perioperative PPN, within the framework of ERAS. A panel of surgeons and nurses convened to identify knowledge gaps and share their best practice experience regarding PPN provision for patients undergoing major gastrointestinal surgery. Clinical needs were identified and addressed based on the panel's experience and a narrative review. Key topics addressed include how PPN can support ERAS nutritional recommendations, identifying gastrointestinal surgery patient subgroups who are likely to benefit from PPN, perioperative timepoints when PPN may be required, and optimizing the delivery of PPN. An algorithm to support the identification and management of patients' perioperative nutritional needs was developed. This paper aims to assist healthcare providers by addressing best practice questions related to the use of PPN during the critical perioperative period within the ERAS concept. This may facilitate timely nutritional intervention to help improve postoperative clinical outcomes and quality of life for patients undergoing major gastrointestinal surgery.


Modeling of permeabilization process in Pseudomonas putida G7 for enhanced limonin bioconversion.
A facile process of enhanced whole cell biotransformation to debitter the triterpenoid limonin in citrus juices was optimized in this work. To maximize bioconversion, permeabilization conditions were modeled using response surface methodology. A central composite rotatable design with four significant variables (concentration, temperature, pH, and treatment time) was employed. The second order polynomial equations with R² values above 0.9 showed good correspondence between experimental and predicted values. The concentration, temperature, pH, and treatment time as well as their interactions had significant effects (p < 0.001) on limonin bioconversion. The optimum operating conditions for permeabilization were observed at a Na₂EDTA concentration of 1.5 μM, treatment time of 15 min, temperature of 28 °C, and pH 8. A maximum reduction of 76.71% in the limonin content was achieved within 150 min under selected conditions. The results are promising for refining permeabilization technique for whole cell biocatalysts thereby improving the debittering of citrus juices significantly.


Effect of low levels of dietary fish oil on fatty acid desaturation and tissue fatty acids in obese and lean rats.
The effect of very low levels of dietary long-chain n-3 fatty acids on delta 6 desaturation of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), and on delta 5 desaturation of dihomo-gamma-linolenic acid (20:3n-6), in liver microsomes and its influence on tissue fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing ca. 200 mg of long-chain polyunsaturated n-3 fatty acids per 100 g of diet were compared to those fed the same amount of alpha-linolenic acid. Low amounts of long-chain n-3 fatty acids greatly inhibited delta 6 desaturation of 18:2n-6 and delta 5 desaturation of 20:3n-6, while delta 6 desaturation of 18:3n-3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the biosynthesis of long-chain n-6 fatty acids was reflected in a decrease in arachidonic acid (20:4n-6) content of serum lipids when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids did not develop any decrease in 20:4n-6 during fish oil ingestion. Docosahexaenoic acid (22:6n-3), present in the dietary fish oil, was increased in serum lipids and in liver microsome, heart, and kidney phospholipids.