The plant lectin Bandeiraea simplicifolia I-B4 identifies a subpopulation of small diameter primary sensory neurones which innervate the skin in the rat.
In recent years a variety of glycoconjugates have been found associated with the plasma membrane of mammalian primary sensory neurones. The functional significance of these glycoconjugates remains obscure but their carbohydrate chains have been widely implicated in cell-cell recognition (or adhesion) during development. The plant lectin Bandeiraea simplicifolia I-B4 identifies a characteristic galactose-containing glycoconjugate associated with small diameter primary sensory neurones. In this study we have used a combination of lectin binding and retrograde tracing to examine the distribution of this glycoconjugate on sensory neurones which innervate different target tissues in the rat. The fluorescent tracer diamidino yellow was applied the cut end of peripheral nerves which selectively innervate either the skin, muscle or viscera. Retrogradely labelled neurones were then screened for lectin binding using a lectin-horseradish peroxidase conjugate. The results revealed that Bandeiraea simplicifolia I-B4 binding is associated with over one-third of neurones which innervate the skin, but only a small proportion of neurones innervating muscle or viscera.


Isolated anterior interosseous nerve palsy following herpes zoster infection: a case report and review of the literature.
A 64-year-old lady noticed weakness of her thumb within two weeks of having developed "shingles" causing vesicular lesions on her arm and hand. Clinical and neurophysiological testing confirmed a lesion of the anterior interosseous nerve. Although motor involvement after herpes zoster infection is recognised, this usually has a myotomal distribution; isolated involvement of a branch of a peripheral motor nerve has not previously been described.


Anesthesiologists and surgeons at Mount Sinai: a partnership in excellence.
Although anesthesia was available to patients when the doors of The Jews Hospital opened in 1855, "professional anesthetists" were not appointed to the staff until 1902. This article traces the history of the anesthesiology staff and department, and documents their accomplishments over the past century.


Percutaneous treatment of hepatic hydatid cysts: an alternative to surgery.
Percutaneous treatment of hydatid cysts is relatively new, and the data related to it are limited. The purpose of this study was to provide additional data to strengthen the proof of its effectiveness. One hundred sixty-eight hepatic cysts in 111 patients were treated using a percutaneous approach under sonographic and fluoroscopic guidance. Cysts smaller than 5 cm in diameter were treated with a one-stage procedure that consisted of puncture of the cyst, aspiration of fluid, and injection and reaspiration of hypertonic saline solution. Larger cysts were treated with a two-stage procedure that consisted of the one-stage procedure followed by catheterization and sclerotherapy with alcohol. The mean observation time was 19 months (range, 1-48 months). Follow-up examinations showed progressive shrinkage and solidification of the cysts. Early complications occurred in 32 (28.8%) of the 111 patients, including fatal anaphylaxis in one patient, biliary fistula in seven, infection of the cyst in four, persistent serous drainage from the cyst in two, intraperitoneal leakage of cyst fluid in two, urticaria in seven, fever without evidence of infection in seven, and pleural effusion in two. Late complications occurred in four (3.8%) of the 104 patients who underwent follow-up examinations, including local recurrence in three patients and intrabiliary rupture of a cyst in one patient. Our experience indicates that percutaneous treatment is efficient in the management of hepatic hydatid cysts and that this technique should be considered an alternative to surgery.


Executive functioning in depressed patients with suicidal ideation.
Suicidal thinking has been associated with cognitive rigidity, however, not all depressed patients contemplate suicide. Therefore, we hypothesized that compared with depressed subjects without suicidal ideation, depressed individuals with suicidal ideation would display poorer performance on measures of executive functioning that involve mental flexibility. In-patients with a current major depressive episode who had no current suicidal ideation (n=28) were compared with those who had current suicidal ideation (n=5) on measures of executive functioning and two neurocognitive tests that predominantly assess non-frontal regions. Compared with non-suicidal depressed patients, depressed suicidal patients performed significantly worse on several measures of executive functioning after controlling for age, IQ, severity of depression and prior suicide attempts. The two groups performed similarly on tests that predominantly assess non-frontal regions. Depressed individuals contemplating suicide have cognitive rigidity, which does not appear to be a global brain dysfunction. Suicidal mental states may result from dysfunctional executive decision-making that is associated with the frontal lobe.


Exploring the value of audiotapes for health literacy: a systematic review.
To evaluate the efficacy of audiotapes as a health information exchange intervention, specifically looking for use with the "hard-to-reach" population. Examined electronic databases and journals for articles that evaluated potential of audiotapes as an educational tool within diverse populations. The systematic review included randomized controlled trials, surveys and exploratory articles. Primary outcome variables analyzed were knowledge and recall, behavioral change, anxiety, self-care, and satisfaction. Audiotapes were used to record consultations and health-related information in specific health situations. No studies were found that targeted the needs of the "hard-to-reach" population. With the exception of positive patient satisfaction, the benefits of audio taped messages remain unclear. If even the average person is compromised in the context of information exchange, populations with communication barriers are at even greater risk. Research needs to be conducted, aimed at determining whether audiotapes enhance communication between the "hard-to-reach" population and health professionals.


Germline genetic factors influence the outcome of interferon-α therapy in polycythemia vera.
Interferon-α (IFN-α)-based treatments can induce hematologic and molecular responses (HRs and MRs, respectively) in polycythemia vera (PV); however, patients do not respond equally. Germline genetic factors have been implicated in differential drug responses. We addressed the effect of common germline polymorphisms on HR and MR after treatment of PV in the PROUD-PV and CONTINUATION-PV studies in a total of 122 patients who received ropeginterferon alfa-2b. Genome-wide association studies using longitudinal data on HR and MR over a 36-month follow-up did not reveal any associations at the level of genome-wide statistical significance. Furthermore, we performed targeted association analyses at the interferon lambda 4 (IFNL4) locus, well known for its role in hepatitis C viral clearance and recently reported to influence HR during treatment of myeloproliferative neoplasms. We did not observe any association of IFNL4 polymorphisms with HR in our study cohort; however, we demonstrated a statistically significant effect of the functionally causative IFNL4 diplotype (haplotype pair, including the protein-coding variants rs368234815/rs117648444) on MR (P = 3.91 × 10-4; odds ratio, 10.80; 95% confidence interval, 2.39-69.97) as reflected in differential JAK2V617F mutational burden changes according to IFNL4 diplotype status. Stratification of patients with PV based on IFNL4 functionality may allow for optimizing patient management during IFN-α-based therapy.


Endothelin Receptor-A Inhibition Decreases Ductular Reaction, Liver Fibrosis, and Angiogenesis in a Model of Cholangitis.
Primary sclerosing cholangitis (PSC) leads to ductular reaction and fibrosis and is complicated by vascular dysfunction. Cholangiocyte and endothelial cell crosstalk modulates their proliferation in cholestatic models. Endothelin (ET)-1 and ET-2 bind to their receptor, ET-A, and cholangiocytes are a key source of ET-1 after bile duct ligation. We aimed to evaluate the therapeutic potential of ET-A inhibition in PSC and biliary-endothelial crosstalk mediated by this pathway. Wild-type and multidrug resistance 2 knockout (Mdr2-/-) mice at 12 weeks of age were treated with vehicle or Ambrisentan (ET-A antagonist) for 1 week by daily intraperitoneal injections. Human control and PSC samples were used. Mdr2-/- mice at 4, 8, and 12 weeks displayed angiogenesis that peaked at 12 weeks. Mdr2-/- mice at 12 weeks had enhanced biliary ET-1/ET-2/ET-A expression and secretion, whereas human PSC had enhanced ET-1/ET-A expression and secretion. Ambrisentan reduced biliary damage, immune cell infiltration, and fibrosis in Mdr2-/- mice. Mdr2-/- mice had squamous cholangiocytes with blunted microvilli and dilated arterioles lacking cilia; however, Ambrisentan reversed these alterations. Ambrisentan decreased cholangiocyte expression of pro-angiogenic factors, specifically midkine, through the regulation of cFOS. In vitro, ET-1/ET-A caused cholangiocyte senescence, endothelial cell angiogenesis, and macrophage inflammation. In vitro, human PSC cholangiocyte supernatants increased endothelial cell migration, which was blocked with Ambrisentan treatment. ET-A inhibition reduced biliary and liver damage in Mdr2-/- mice. ET-A promotes biliary angiocrine signaling that may, in turn, enhance angiogenesis. Targeting ET-A may prove therapeutic for PSC, specifically patients displaying vascular dysfunction.


Role of BLACAT1 in IL-1β-Induced Human Articular Chondrocyte Apoptosis and Extracellular Matrix Degradation via the miR-149-5p/ HMGCR Axis.
Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development. In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA. Interleukin (IL)-1β was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1β-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing. In IL-1β-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR- 149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation. LncRNA BLACAT1 was overexpressed in IL-1β-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.


An examination of episodic future thinking in the emergency department among youth experiencing suicidal thoughts and behaviors.
Youth experiencing suicidal thoughts and/or behaviors (STBs) frequently present to emergency departments for acute psychiatric care. These settings offer a transitory yet pivotal opportunity to assess, intervene on, and plan continued care for STBs. This study examined a clinically relevant, understudied aspect of psychological functioning among youth experiencing STBs in the emergency department: episodic future thinking, or the ability to imagine discrete autobiographical future events. A sample of 167 youths (10-17 years) presenting to a pediatric psychiatric emergency department for STBs completed a performance-based measure of episodic future thinking assessing richness in detail and subjective characteristics of imagined future events. STB recurrence was assessed 6 months later. Immediately following a suicide-related crisis, youth demonstrated mixed abilities to imagine their future: they generated some concrete future event details but did not subjectively perceive these events as being very detailed or likely to occur. Older adolescents (i.e., 15-17) generated more episodic details than pre-/younger adolescents (i.e., 10-14), particularly those pertaining to actions or sensory perceptions. There was no evidence linking less detailed episodic future thinking and greater likelihood of STBs following the emergency department visit; instead, hopelessness was a more robust risk factor. Findings underscore the importance and clinical utility of better understanding the psychological state of youth during or immediately following a suicide-related crisis. In particular, assessing youths' future thinking abilities in the emergency department may directly inform approaches to acute care delivery.


A Pro/Ser substitution in nucleoside diphosphate kinase of Drosophila melanogaster (mutation killer of prune) affects stability but not catalytic efficiency of the enzyme.
Nucleoside diphosphate kinase of Drosophila, recently identified as the product of the awd gene, is essential for larval development. The conditional lethal mutation Killer of prune maps to the same gene. We purified the nucleoside diphosphate kinases from wild-type and mutant larvae by a simple procedure involving affinity chromatography on blue Sepharose. Both proteins are purified as hexamers in their native state. The mutant protein, which carries a serine instead of proline at position 97, has structural properties and catalytic efficiency that are very similar to the wild-type protein. However, the mutant protein has a much lower stability to denaturation by heat and urea. Following dilution of urea with buffer the urea-denaturated mutant nucleoside diphosphate kinase accumulates as folded monomers and cannot recover its quaternary structure and enzymatic activity. In contrast, the wild-type enzyme recovers hexameric structure and activity. This suggests that the mutation affects the folding/assembly pathway without affecting the function of the mature protein once folded and assembled into the mature hexameric structure.


Single-cell RNA sequencing reveals diverse intratumoral heterogeneities and gene signatures of two types of esophageal cancers.
Single-cell RNA sequencing and transcriptome analysis enable novel discovery and precise characterization of new cell types and states, which improves the understanding of the cellular context of tumorigenesis. Herein, we applied this powerful approach to analyze 368 single cells from three esophageal squamous cell carcinoma (ESCC) and two esophageal adenocarcinoma (EAC) tumors. Using inferred copy number variation analysis, we successfully distinguished carcinoma cells from heterogeneous cellular populations, identifying gene signatures and crucial cancer-related signaling pathways related to ESCC and EAC. In particular, we found that NOTCH signaling was exclusively activated in ESCC, but not in EAC. ESCC tumors with higher NOTCH activity were associated with significantly worse survival rates than those with lower NOTCH activity. Collectively, this study revealed that ESCC and EAC are distinct in terms of cellular transcriptome profiles, which leads to a wide range of intratumoral cellular heterogeneity. The findings suggest that different therapeutic strategies that target the differences between two types of esophageal cancers are required, guiding cancer-specific future drug development.


Proton-transfer kinetics of photoexcited 7-hydroxy-1-naphthalenesulfonic acid in aqueous formamide solutions.
The monoanion of 7-hydroxy-1-naphthalenesulfonic acid (HNS) undergoes pseudo-first order dissociation and its conjugate base, second order protonation in the lowest excited singlet state. The proton transfer kinetics in water containing formamide up to a mole fraction of about 0.95 have been evaluated as a function of formamide concentration. At mole fractions above 0.95 of formamide, proton-transfer does not measurably occur. At mole fractions below 0.95, steady state and pulsed-source fluorimetries show the rate constant for dissociation to decrease exponentially with increasing mole fraction of formamide. This is believed to be due to penetration and disruption of the aqueous solvent cage of the HNS by formamide, resulting in impairment of the Grotthus proton-transfer mechanism.


4D printing of biodegradable elastomers with tailorable thermal response at physiological temperature.
4D printing has a great potential for the manufacturing of soft robotics and medical devices. The alliance of digital light processing (DLP) 3D printing and novel shape-memory photopolymers allows for the fabrication of smart 4D-printed medical devices in high resolution and with tailorable functionalities. However, most of the reported 4D-printed materials are nondegradable, which limits their clinical applications. On the other hand, 4D printing of biodegradable shape-memory elastomers is highly challenging, especially when transition points close to physiological temperature and shape fixation under ambient conditions are required. Here, we report the 4D printing of biodegradable shape-memory elastomers with tailorable transition points covering physiological temperature, by using poly(D,L-lactide-co-trimethylene carbonate) methacrylates at various monomer feed ratios. After the programming step, the high-resolution DLP printed stents preserved their folded shape at room temperature, and showed efficient shape recovery at 37 °C. The materials were cytocompatible and readily degradable under physiological conditions. Furthermore, drug-loaded devices with tuneable release kinetics were realized by DLP-printing with resins containing polymers and levofloxacin or nintedanib. This study offers a new perspective for the development of next-generation 4D-printed medical devices.


Cu@Au alloy nanoparticle as oligonucleotides labels for electrochemical stripping detection of DNA hybridization.
Synthesis of the novel Cu@Au alloy nanoparticle and its application in an electrochemical DNA hybridization detection assay is described in this article. We report a low-temperature method for generating core-shell particles consisting of a core of Cu and a thin layer of Au shell that can be readily functionalized with oligonucleotides. Core-shell Cu@Au particles were successfully labeled to a 5'-alkanethiol capped oligonucleotides probe that is related to the colitoxin gene. The DNA genetic sensing assay relies on the electrostatic adsorption of target oligonucleotides onto conducting polypyrrole (PPy) surface at the glassy carbon electrode (GCE), and its hybridization to the alloy particle-oligonucleotides DNA probe. Hybridization events between probe and target were monitored by the release of the copper metal atoms anchored on the hybrids by oxidative metal dissolution and the indirectly determination of the solubilized Cu2+ ions by sensitive anodic stripping voltammetry (ASV). The detection limit is 5.0 pmol l(-1) of target oligonucleotides. The Cu@Au core-shell nanoparticles combining the surface modification properties of Au with the good electrochemical activity of Cu core shows their perspective application in the electrochemical DNA hybridization analysis assay.


Nanomechanical probing of microbubbles using the atomic force microscope.
Atomic force microscopy (AFM) is a versatile mechanical nanosensor that can be used to quantify the mechanical properties of microbubbles (MBs) and the adhesion mechanisms of targeted MBs. Mechanical properties were investigated using AFM tipless cantilevers to microcompress the MBs. The range of compressive stiffness for biSphere was found to be between 1 and 10Nm(-1) using a cantilever with a spring constant of 0.6 Nm(-1). This stiffness was shown to decrease with the MB size in a non-linear fashion. It is also possible to calculate a theoretical Young's modulus of the shell. The adhesion properties of targeted lipid based MBs that use avidin-biotin chemistry for the attachment of targeting ligands were also studied. The MBs were attached to poly-L-lysine treated tipless cantilevers with spring constants ranging from 0.03 to 0.1 Nm(-1). This system interrogated individual cells with pulling cantilever distance of 15 microm, and scan rate at 0.2 Hz. The depth of contact was not larger than 0.4 microm. The targeted MBs provided a significantly larger adhesion to the cells compared to control ones. Average adhesion force was dependent on depth of contact. Analysis of the data demonstrated a single distribution of adhesion events with median at 89 pN, which is in agreement with the literature for such interactions. The nanointerrogation of MBs using AFM provides new insight into their mechanical properties, and should be of assistance to MB design and manufacture.


A community-wide experience with jejunoileal bypass for obesity.
The records of seventy-nine patients who had jejunoileal bypass operations for morbid obesity were reviewed. The data represent the entire experience of surgeons in the Louisville, Kentucky metropolitan area for the period studied. Retrospective evaluations of criteria for selecting patients for bypass operation, type of shunt done, and clinical results were recorded. Sixty-eight patients (86 per cent) weighed more than 100 pounds over ideal weight. Operative mortality was 5 per cent. Only 31 patients (47 per cent) were judged as having satisfactory results. Two patients died of hepatic failure and five required restoration of intestinal continuity. Comparison of this community experience with published data supports the concept that these operations are best confined to those institutions where there is special interest in the full range of medical and surgical care of obese patients.


Current understanding of the role of the Brd4 protein in the papillomavirus lifecycle.
The Brd4 protein is an epigenetic reader that is central to regulation of cellular transcription and mitotic bookmarking. The transcription and replication proteins of many viruses interact with Brd4. We describe the multiple roles of Brd4 in the papillomavirus lifecycle.


Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2.
Epidemiological studies show that maternal diabetes is associated with an increased risk of autism spectrum disorders (ASDs), although the detailed mechanisms remain unclear. The present study aims to investigate the potential effect of maternal diabetes on autism-like behavior in offspring. The results of in vitro study showed that transient hyperglycemia induces persistent reactive oxygen species (ROS) generation with suppressed superoxide dismutase 2 (SOD2) expression. Additionally, we found that SOD2 suppression is due to oxidative stress-mediated histone methylation and the subsequent dissociation of early growth response 1 (Egr1) on the SOD2 promoter. Furthermore, in vivo rat experiments showed that maternal diabetes induces SOD2 suppression in the amygdala, resulting in autism-like behavior in offspring. SOD2 overexpression restores, while SOD2 knockdown mimics, this effect, indicating that oxidative stress and SOD2 expression play important roles in maternal diabetes-induced autism-like behavior in offspring, while prenatal and postnatal treatment using antioxidants permeable to the blood-brain barrier partly ameliorated this effect. We conclude that maternal diabetes induces autism-like behavior through hyperglycemia-mediated persistent oxidative stress and SOD2 suppression. Here we report a potential mechanism for maternal diabetes-induced ASD.


The central PPT of the yeast retrotransposon Ty1 is not essential for transposition.
The yeast retrotransposon Ty1 has structural and functional similarities to retroviruses. We report here that, as in retroviruses, the plus-strand DNA of Ty1 is synthesized as two segments. A central DNA flap is formed during reverse transcription consecutive to elongation (with strand displacement) of the upstream segment beyond the central polypurine tract (cPPT) until the replication machinery is stopped at the central termination sequence. Comparison of wild-type and cPPT-mutant Ty1 elements shows that the mutant element lacking the central DNA flap is only twofold defective in transposition.


Anti-inflammatory potential of native Australian herbs polyphenols.
The anti-inflammatory potential of hydrophilic polyphenolic-rich extracts obtained from native Australian herbs: anise myrtle, lemon myrtle and Tasmannia pepper leaf, and a reference sample bay leaf, was evaluated using the lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 model. Pretreatment with all herbal extracts at non-cytotoxic concentrations reduced the LPS-induced protein levels of pro-inflammatory enzymes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Concomitant decrease in accumulation of their products, prostaglandin E2 (PGE2) and nitric oxide (NO), respectively, was observed. A suppression of LPS-induced expression of COX-2 and iNOS and decrease of NO and PGE2 levels suggests potential anti-inflammatory properties of the extracts. Anise myrtle, lemon myrtle and bay leaf selectively inhibited COX-2 and iNOS enzymes, while Tasmannia pepper leaf extract exhibited a pronounced inhibitory activity toward COX-1 and was the least effective inhibitor of iNOS. Anise myrtle and lemon myrtle are potentially more efficient anti-inflammatory agents than Tasmannia pepper leaf.


Computer aided volumetric assessment of orbital structures in patients with Graves' orbitopathy: correlation with serum thyroid antiperoxidase antibodies and disease activity.
Graves' disease is an autoimmune disorder. Goiter and Graves' orbitopathy are frequently seen clinically. It would be helpful for the diagnosis, grading, prognosis, and treatment of this condition if it was possible to find serum biomarkers to establish a connection between the plasma levels of these compounds and orbital changes. A retrospective study was performed by revising the medical records of 44 patients with Graves' orbitopathy and 15 controls. The Osirix software (Pixmeo, Geneva, Switzerland) was used for manual orbital measurements. Plasma levels of Graves' orbitopathy substances were obtained in the analytical review of the patients. A greater muscle volume was observed in patients with Graves' orbitopathy in relation to the control group (p < 0.001). The clinical activity score (CAS) was associated to total muscle mass (p = 0.013) and retrorbital fat (p = 0.048). Our results indicated a direct relationship between serum concentrations of anti-thyroid peroxidase antibodies and inferior rectus thickening (p = 0.036); however, we did not observe a positive correlation between other muscle volumes and serum concentrations of various thyroid-related substances. This study is the first that uses Osirix measurement software to manually assess orbital features in patients with Graves' orbitopathy. These measurements were compared to the outcomes of tests performed in a laboratory. Among several serum biomarkers, anti-thyroid peroxidase appears to be a reliable biomarker that correlates positively with inferior rectus muscle thickness in patients with thyroid eye disease. This may help to improve the management of this disease.


The IFITMs Inhibit Zika Virus Replication.
Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.


Supramolecular organogels formed by monochain derivatives of succinic acid.
The monoalkyl chain derivatives of succinic acid self-assemble into ordered bilayer aggregates by forming dimers of hydrogen bonded carboxylic acid in a number of organic solvents and finally gelatinize the solvents. The gelation ability of each derivative was inspected. The morphologies of xerogels were investigated by scanning electron microscope (SEM). The microstructure of aggregates was studied by small angle X-ray diffraction (SA-XRD) and Fourier transform infrared spectroscopy (FT-IR). The results reveal that the intermolecular hydrogen bonds between neighboring molecules are critical factor in the process of organogelation.


Initial hematocrit values after birth and peri/intraventricular hemorrhage in extremely low birth weight infants.
Ischemia followed by reperfusion plays a significant role in the pathogenesis of peri/intraventricular hemorrhage (P/IVH). Delayed cord clamping promotes placental transfusion to newborn and is associated with decreased P/IVH. We hypothesized that extremely low birth weight (ELBW) infants with higher initial hematocrit (Hct) after birth are less likely to develop P/IVH. Pre- and postnatal data on inborn ELBW infants over 7 years were reviewed. We examined the relationship between P/IVH in the first week and initial Hct using logistic regression modeling. We studied 225 infants with a median gestational age (GA) 25.7 (22.4-31.7). Forty-one percent had grade I-IV P/IVH. In univariate analysis, cesarean section (CS) and higher GA, birth weight, 5-minute Apgar, and initial Hct were associated with decreased likelihood of P/IVH while higher maximum PCO2 in first 3 days and use of inotropes/vasopressors, postnatal steroid for hypotension, hypernatremia, transfusion, and use of insulin for hyperglycemia during the first week of life were associated with increased likelihood of P/IVH. In multiple regression analysis, only GA, CS, and initial Hct remained significantly associated with P/IVH. Adjusting for GA and CS, the odds of P/IVH was higher with Hct < 40% (OR 2.04, 95% CI [1.11, 3.76]) and Hct < 45% (2.38 [1.19, 4.76]). Higher initial Hct is associated with decreased P/IVH. Initial Hct < 45% was associated with a 2-fold increase in P/IVH. We speculate that lower initial Hct represents a lower intravascular volume status and promotes cerebral hypoperfusion preceding P/IVH.


Vascular endothelial growth factor polymorphisms (-460C/T, +405G/C, and 936C/T) and endometriosis: their influence on vascular endothelial growth factor expression.
To analyze three functional vascular endothelial growth factor (VEGF) polymorphisms (-460C/T, +405G/C, and 936C/T) in women with and without endometriosis and their correlation with VEGF expression in endometrial tissue and peritoneal fluid (PF). Case-control study. University-based hospital. One hundred eighty-six women with endometriosis and 180 controls without the disease. Endometrial biopsies were performed by aspiration and PF samples were obtained at laparoscopy. VEGF polymorphisms (-460C/T, +405G/C, and 936C/T) were determined using a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay. Quantitative real-time reverse transcriptase (RT)-PCR assay was used to quantify VEGF-A messenger RNA (mRNA) and VEGF-A antigen levels were quantified by ELISA. Patients with endometriosis showed a higher VEGF 936T allele frequency than controls. However, the distribution of genotypes and allele frequencies in the other two VEGF (-460C/T, +405G/C) polymorphisms was similar in the endometriosis and control groups. Endometrium and PF from women with endometriosis showed an increase in VEGF levels, but no association was found between the VEGF polymorphisms studied and VEGF expression in endometrial tissue and PF. These findings suggest that the VEGF 936C/T polymorphism may be associated with the risk of endometriosis in a Caucasian population, but the increased VEGF levels observed in endometriosis do not appear to be associated with this polymorphism.


A two-factor model of rotation-induced motion sickness syndrome in squirrel monkeys.
Nonrestrained squirrel monkeys were rotated repeatedly in the horizontal plane once per day for preset times or until a vomiting response occurred. Emesis latencies and frequencies were recorded. Some subjects were fed fresh banana immediately before and after each rotation. The amount consumed provided a measure of conditioned food aversion or feeding suppression. A two-factor model of the motion-sickness syndrome was formulated to account for the data. According to the model, appropriate stimulation of the semicircular canals accompanied by visual and proprioceptive stimulation generates two independent physiologic processes or states: an objective emesis and a subjective nausea process. The emesis process is revealed by vomiting responses and the nausea process is inferred from the appearance of conditioned food aversion. Susceptible monkeys (type I) and resistant monkeys (type II) have different emesis processes, but both have similar nausea processes. Refractory monkeys have no well-developed emesis or nausea processes. Time and order characteristics of the motion-sickness syndrome depend on specific interactions of emesis and nausea processes.


Hereditary sideroblastic anemia: pathophysiology and gene mutations.
Sideroblastic anemia is characterized by anemia with the emergence of ring sideroblasts in the bone marrow. Ring sideroblasts are erythroblasts characterized by iron accumulation in perinuclear mitochondria due to impaired iron utilization. There are two forms of sideroblastic anemia, i.e., inherited and acquired sideroblastic anemia. Inherited sideroblastic anemia is a rare and heterogeneous disease caused by mutations of genes involved in heme biosynthesis, iron-sulfur (Fe-S) cluster biogenesis, or Fe-S cluster transport, and mitochondrial metabolism. The most common inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutations of the erythroid-specific δ-aminolevulinate synthase gene (ALAS2), which is the first enzyme of heme biosynthesis in erythroid cells. Sideroblastic anemia due to SLC25A38 gene mutations, which is a mitochondrial transporter, is the next most common inherited sideroblastic anemia. Other forms of inherited sideroblastic anemia are very rare, and accompanied by impaired function of organs other than hematopoietic tissue, such as the nervous system, muscle, or exocrine glands due to impaired mitochondrial metabolism. Moreover, there are still significant numbers of cases with genetically undefined inherited sideroblastic anemia. Molecular analysis of these cases will contribute not only to the development of effective treatment, but also to the understanding of mitochondrial iron metabolism.


Emotional expressions of old faces are perceived as more positive and less negative than young faces in young adults.
Interpreting the emotions of others through their facial expressions can provide important social information, yet the way in which we judge an emotion is subject to psychosocial factors. We hypothesized that the age of a face would bias how the emotional expressions are judged, with older faces generally more likely to be viewed as having more positive and less negative expressions than younger faces. Using two-alternative forced-choice perceptual decision tasks, participants sorted young and old faces of which emotional expressions were gradually morphed into one of two categories-"neutral vs. happy" and "neutral vs. angry." The results indicated that old faces were more frequently perceived as having a happy expression at the lower emotional intensity levels, and less frequently perceived as having an angry expression at the higher emotional intensity levels than younger faces in young adults. Critically, the perceptual decision threshold at which old faces were judged as happy was lower than for young faces, and higher for angry old faces compared to young faces. These findings suggest that the age of the face influences how its emotional expression is interpreted in social interactions.


Simultaneous visualization of aortic and [3H]5-hydroxytryptamine-accumulating cell bodies in the nodose ganglion of the cat.
1. Single- and double-tracer experiments were performed in cats to investigate the relationship between the aortic cells and the cell bodies accumulating 5-hydroxytryptamine (5-HT) in the nodose ganglion. In one series of experiments, horseradish peroxidase (HRP) was applied to the central end of the aortic nerve, anterogradely transported and accumulated in ganglionar perikarya. The distribution of HRP-positive neurones was reconstructed in serial sections through the nodose ganglion. In a second series of experiments, the distribution of [(3)H]5-HT-accumulating cell bodies was assessed following incubation of the nodose ganglion in [(3)H]5-HT. The third series of experiments combined the treatments of the preceding ones: anterograde transport of HRP in the aortic nerve followed by incubation of the nodose ganglion in [(3)H]5-HT.2. The results from these experiments provide more information with regard to (i) the topographical relationship between the aortic and [(3)H]5-HT-accumulating cell bodies in the same ganglion and (ii) the distribution and number of double-labelled neurones, giving further indications about histochemical components of the aortic nerve.3. The HRP experiments demonstrated that HRP-positive cells show a preferential pattern of topographical organization. They were mostly located in the medial border of the ganglion where the laryngeal and aortic nerves enter. On the other hand, [(3)H]5-HT-accumulating neurones were scattered throughout the ganglion.4. In double-tracer experiments, three populations of labelled cell bodies were distinguished in the same nodose ganglion: (1) single HRP-cells; (2) single [(3)H]5-HT-accumulating cells and (3) double-labelled cells. The distribution of the latter population exhibited no preferential localization. Quantitative estimates indicated that double-labelled neurones constituted 65-85% of the population of HRP-positive cell bodies.5. These results show that most aortic neurones are able to take up exogenous serotonin and may be serotonergic neurones. They suggest that serotonin may be involved in physiological effects mediated via the aortic nerves.


The genetic polymorphisms of immune-related genes contribute to the susceptibility and survival of lymphoma.
Though immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear. We investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune-related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA. By comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK-STAT, NF-κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter-OS genotypes. We used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune-related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.


Genetic markers for stallion fertility--lessons from humans and mice.
Our knowledge on the many aspects of mammalian reproduction in general and equine reproduction in particular has greatly increased during the last 15 years. Advances in the understanding of the physiology, cell biology, and biochemistry of reproduction have facilitated genetic analyses of fertility. Currently, there are more than 200 genes known that are involved in the production of fertile sperm cells. The completion of a number of mammalian genome projects will aid in the investigation of these genes in different species. Great progress has been made in the understanding of genetic aberrations that lead to male infertility. Additionally, the first genetic mechanisms are being discovered that contribute to the quantitative variation of fertility traits in fertile male animals. As artificial insemination (AI) represents a widespread technology in horse breeding, semen quality traits may eventually become an additional selection criterion for breeding stallions. Current research activities try to identify genetic markers that correlate to these semen quality traits. Here, we will review the current state of genetic research in male fertility and offer some perspectives for future research in horses.


Gene transfer to the thymus. A means of abrogating the immune response to recombinant adenovirus.
The authors investigated whether adenoviral gene transfer to the thymus could be accomplished in vivo and whether immunologic unresponsiveness to recombinant adenovirus could be induced by intrathymic inoculation. A major barrier to the clinical application of adenovirus-mediated gene therapy for diseases requiring long-lasting gene expression is the immunogenicity of adenoviral vectors, which limits the duration of its effects. In other experimental models, intrathymic inoculation of foreign proteins or cells has proven to be an effective means to induce immunologic tolerance. The efficiency of gene transfer to the mouse thymus after direct inoculation of recombinant adenovirus was compared with that of several other vectors. Animals inoculated with adenovirus-infected pancreatic islets into the thymus were tested for unresponsiveness to the virus with a subsequent challenge of adenovirus administered into the liver by intravenous injection. Adenovirus accomplished highly efficient gene transfer to the thymus, unlike plasmid DNA, DNA-liposome complexes, retrovirus, and adeno-associated virus. Adenoviral transgene expression was transient in the thymus of immunocompetent mice but persistent in CD8+ T-cell-deficient and severe combined immunodeficiency (SCID) mice, implicating the role of cytotoxic T lymphocytes in viral clearance. Intrathymic transplantation of syngeneic pancreatic islet cells infected with adenovirus impaired the normal antiviral cytotoxic T-lymphocyte response and prolonged hepatic transgene expression after an intravenous challenge with adenovirus. Recombinant adenovirus accomplishes highly efficient gene transfer to the thymus in vivo. Intrathymic inoculation of adenovirus-infected islets can be used to induce immunologic unresponsiveness to the adenoviral vector and, potentially, to other proteins that it might be engineered to encode.


Lysis-free separation of hybridoma cells by continuous disc stack centrifugation.
The non-destructive removal of hybridoma cells from fermentation broth with an improved disc stack centrifuge (CSA1, Westfalia Separator AG, Oelde, Germany) was investigated. The centrifuge was equipped with a hydrohermetic feed system, which allowed a gentle, shearless acceleration of the cells inside the bowl. No significant cell damage was observed during the separation of hybridoma cells from repeated batch fermentation in 100 liter scale. In the clarified liquid phase there was no increase in Lactate-Dehydrogenase (LDH) activity. Consequently, there was no increased exposure of the product to intracellular components.Due to continuous operation with a periodic and automatic discharge of sediment, a high throughput was achieved without any considerable loss of product. The clarification for mammalian cells was in the range of 99% to 99.9%, depending on the operating conditions. The content of cell debris and other small particles decreased about 30 to 50%, depending on the particle load in the feed stream. The centrifuge was fully contained; cleaning and sterilizing in place possible. Therefore, the decice could be integrated easily into the fermentation process.


The septic brain.
Sepsis is a major disease entity with important clinical implications. Sepsis-induced multiple organ failure is associated with a high mortality rate in humans and is clinically characterized by pulmonary, cardiovascular, renal and gastrointestinal dysfunction. Recently, several studies have demonstrated that sepsis survivors present long-term cognitive impairment, including alterations in memory, attention, concentration and/or global loss of cognitive function. However, the pathogenesis and natural history of septic encephalopathy and cognitive impairment are still poorly known and further understanding of these processes is necessary for the development of effective preventive and therapeutic interventions. This review discusses the clinical presentation and underlying pathophysiology of the encephalopathy and cognitive impairment associated with sepsis.


IVIM-DWI and MRI-based radiomics in cervical cancer: Prediction of concurrent chemoradiotherapy sensitivity in combination with clinical prognostic factors.
To identify the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and magnetic resonance imaging (MRI)-based radiomics combined with clinical prognostic factors (CPF) in predicting concurrent chemoradiotherapy (CCRT) sensitivity of locally advanced cervical cancer (LACC). A retrospective analysis of 163 patients (assigned to training or test groups) who underwent conventional MRI and IVIM-DWI before CCRT were divided into sensitive and resistant groups according to their efficacy at 6 months after CCRT. Per-treatment IVIM-DWI parameters (ADC, D, D⁎ and f value), 3D texture features (from axial T2WI) and CPF were measured, analyzed and screened. The prediction model and its nomogram were developed by combining screened parameters and then validated internally and externally. Clinical stage, f value, D value, InverseVariance, SizeZoneNonUniformity, and Minimum were selected to construct prediction model. All parameters except D value showed independent diagnostic value in multivariate Logistic regression analysis and composed prediction model, with AUCs of 0.987 and 0.984 for training and test groups, respectively. The calibration curve (Brier score of 0.042, C-index of 0.987), decision curve and clinical impact curve further demonstrated the reliability and clinical value of prediction model. IVIM-DWI, MRI-based radiomics and CPF showed high clinical value in predicting CCRT sensitivity for LACC with better predictive performance when combined.


Quantitative Polymerase Chain Reaction Analysis of Cariogenic Streptococcus mutans in Saliva of Oral and Laryngeal Cancer Patients Undergoing Radiotherapy: A Clinical Study.
Radiotherapy leads to radiation-induced caries. There is limited knowledge about the quantification of cariogenic bacteria in the saliva of irradiated cancer patients. The aim of this study is to check salivary pH, flow rate, and the assessment of Streptococcus mutans in the saliva of irradiated oral and laryngeal cancer patients using quantitative real-time polymerase chain reaction (qRT-PCR). This was time-bound study which consisted of 26 cancer patients undergoing radiotherapy (13-oral cancer 13-laryngeal cancer). Resting saliva samples were gathered from oral (Group-I) and laryngeal (Group-II) cancer patients immediately before radiotherapy and after completion of radiotherapy (dose-60 Gy). pH of saliva and the salivary flow rate was measured. S. mutans were analyzed using qRT PCR. Data were analyzed using SPSS software 20. Paired t-test was used to evaluate salivary pH, flow rate, and amount of S. mutans pre- and post-radiotherapy for Group I and II. Independent t-test was used to compare salivary pH, flow rate, and S. mutans pre- and post-radiotherapy between Group I and II. Salivary pH and flow rate significantly reduced postradiotherapy in oral and laryngeal cancer patients (P < 0.001). The amount of S. mutans statistically increased postradiotherapy in oral cancer patients (P = 0.001). While S. mutans count was statistically insignificant in laryngeal cancer patients (P = 0.091). There was a significant increase in the amount of S. mutans in Group I when compared with Group II (P = 0.002). Amount of S. mutans increased postradiotherapy in oral cancer patients. While the salivary pH and salivary flow rate reduced postradiotherapy.


S100A expression and interleukin-10 polymorphisms are associated with ulcerative colitis and diarrhea predominant irritable bowel syndrome.
Both ulcerative colitis (UC) and diarrhea-predominant irritable bowel syndrome (IBS-D) are associated with alterations in enteric serotonin (5-HT) signaling. The purpose of this study was to compare the rectal and sigmoid colonic mucosal expression of S100A proteins and functional polymorphisms of the 5-HT transporter (5HTT) and interleukin-10 genes in patients with IBS-D or UC with healthy controls. mRNA expression of S100 proteins was measured in sigmoid and rectal biopsies and in rectal epithelium isolated by laser-captured microdissection. Leucocyte DNA was analyzed by PCR-based reaction fragment length polymorphisms and direct sequencing. Clinical symptoms were assessed by the self-rating depression scale and by the gastrointestinal symptom rating scale. Fifty patients with IBS-D, 56 with UC and 50 healthy controls were studied. Colonic mucosal expression of S100A8 and S100A9 in UC was significantly higher than in IBS or controls and correlated with the UC disease activity index (r = 0.65, p < 0.001). S100A10 expression in the rectal epithelium of the IBS patients was significantly higher (0.643 vs. 0.402, p = 0.01) than in controls and correlated with the SDS scores (r = 0.41, p = 0.002). The frequency of IL10-819 CC genotype was significantly higher in IBS-D (10.7 vs. 0 %, p = 0.047) and UC (16 vs. 0 %, p = 0.007) than that in controls. Overexpression of S100A10 in the rectum may play a role in IBS as it is involved in modulating 5-HT1B receptors. The IL10-819 CC is a candidate genotype for both IBS and UC in Japanese.


Body composition and short-term mortality in patients critically ill with acute-on-chronic liver failure.
Body composition is sex dependent and associated with an increased mortality risk in patients with cirrhosis. We evaluated whether it was also associated with short-term mortality in patients critically ill with acute-on-chronic liver failure (ACLF). We retrospectively included all patients with cirrhosis and ACLF hospitalised in the intensive care unit (ICU) of Lausanne University Hospital between 2010 and 2019 for whom an abdominal computed tomography (CT) scan performed ±7 days from admission was available. Patients from the ICU of Paul Brousse University Hospital admitted between 2017 and 2020 served as an external cohort. All body composition parameters at the third lumbar vertebral level (L3) were quantified using a deep learning-based method. In total, 192 patients from Lausanne were included. Median age was 62 years and 28-day survival rate was 58.2%. In males, variables independently associated with 28-day mortality on days 1 and 3 were Chronic Liver Failure Consortium (CLIF-C) ACLF-lactate and sarcopenia. In females, CLIF-C ACLF-lactate on days 1 and 3 was the only predictor of 28-day survival. We derived two scores combining sarcopenia and the CLIF-C ACLF-lactate score on days 1 and 3, with area under the receiver operating characteristic outperforming the CLIF-C ACLF-lactate score alone in male but not in female patients. Comparable results were found in the external cohort of 58 patients and supported the sex specificity of the performance of the model. Patients with sarcopenia had increased risks of invasive fungal infection and renal replacement therapy. Sarcopenia was associated with 28-day mortality in male but not in female patients critically ill with ACLF. Although screening for sarcopenia could impact the management of male patients, further studies are needed in female cohorts to investigate whether other body composition parameters are associated with outcomes. Body composition, easily assessed by CT, is altered in patients with cirrhosis and associated with outcome; it has never been investigated in patients critically ill with ACLF. The results of the present study, underlining the benefit of sarcopenia evaluation to improve prognosis prediction in males critically ill with ACLF, are of importance for physicians managing such patients to optimise the decision-making process toward continued treatment, liver transplantation, or limitation of care. In a wider sense, besides the number and course of organ failures, the results recall the weight of the general condition of males with ACLF at admission to ICU. In females critically ill with ACLF, in analyses limited by the sample size, none of the body composition parameters was associated with short-term mortality independently of organ failures; this suggests that the number and course of organ failures are the main determinant of mortality in these patients.


Intracranial and Extracranial Evaluation.
The vascular lab is an essential tool in diagnosing intracranial and extracranial disease including vasospasm from subarachnoid hemorrhage and carotid artery stenosis in the setting of stroke or transient ischemic attack. This article discusses the indications, protocol, and diagnostic criteria for transcranial doppler (TCD) and carotid artery duplex ultrasound. Intracranial and extracranial arterial testing by way of TCD and carotid imaging carries enormous implications and can provide life or death information. The learning curve for these techniques is steep but can be mastered with repetition and precise technique.


Intraoperative assessment of tibiofemoral contact stresses in total knee arthroplasty.
The production of polyethylene wear debris in total knee arthroplasty (TKA) is due to multiple factors. In particular, inadequate implant alignment and high bearing surface contact stresses are associated with polyethylene failure. Optimal implant placement and soft tissue balancing may contribute to reducing wear and the production of polyethylene particles. We present a case in which a quantitative technique was used to measure tibiofemoral contact stresses during implantation of a total knee prosthesis in vivo. In a knee with preoperative varus and fixed flexion deformity, medial compartment contact stresses after initial resection were reduced from 14.3 MPa to 11.3 MPa in neutral alignment by additional bone resection. Posterior cruciate release was required to reduce contact stresses further and to provide satisfactory balance between medial and lateral compartments, as determined by the operating surgeon, and was confirmed by the measurement system (3.8 MPa medially; 3.0 MPa laterally). This technique has potential to fine-tune implant positioning and ligament balancing during TKA.


Exploratory factor analysis of shared and specific genetic associations in depression and anxiety.
Previous genetic studies of anxiety and depression were mostly based on independent phenotypes. This study aims to investigate the shared and specific genetic structure between anxiety and depression. To identify the underlying factors of Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and their combined scale (joint scale), we employed exploratory factor analysis (EFA) using the eigenvalue of parallel analysis. Subsequently, we conducted a genome-wide association study (GWAS) for these factors. In addition, we utilized LD Score Regression (LDSC) to determine the genetic correlations between the identified factors and four common mental disorders, three sleep phenotypes, and other traits that have been previously linked to anxiety and depression. The EFA uncovered two factors for the GAD-7 scale, namely nervousness and disturbance, two factors for the PHQ-9 scale, namely negative affect and sleep/appetite disturbance, and four factors for the joint scale, specifically nervousness, anhedonia, sleep/appetite disturbance, and fidget. We identified two genome-wide significant genomic loci, with overlap across GAD-7 factor 1 and joint scale factor 1: rs148579586 (PGAD-7 = 1.365 × 10-09, PJoint scale = 1.434 × 10-09) and rs201074060 (PGAD-7 = 3.672 × 10-09, PJoint scale = 3.824 × 10-09). Genetic correlations in factors ranged from 0.722 to 1.000 (all p < 1.786 × 10-03) with 27 of 28 correlations being significantly smaller than one. The genetic correlations with external phenotypes showed small variation across the eight factors. Unidimensional structures can provide more precise scores, which can aid in identifying the shared and specific genetic associations between anxiety and depression. This is a crucial step in characterizing the genetic structure of these conditions and their co-occurrence.


The impact of baseline shifts towards the heart after image guidance on survival in lung SABR patients.
A recent study of NSCLC patients showed small residual shifts of the high dose region towards/away from the heart after image-guidance were significantly related to overall survival. This study investigates whether the effect is observed in a SABR cohort, who have significantly different baseline outlook and are treated using an imaging protocol matching on the tumour rather than bony-anatomy alone. 136 NSCLC patients treated with SABR were studied. The mean baseline shift of the tumour in the direction of the heart over the course of treatment was determined for each patient and used to categorise patients into risk groups. Kaplan-Meier survival curves were plotted and multivariable analysis performed to assess significance of the vector shift to the heart alongside common clinical variables. The vector shift to the heart was independent of all tested clinical variables. A significant difference was seen in patient survival, with patients with shifts towards the heart having significantly worse prognosis as compared to patients with shifts away. Multivariable analysis found a hazard ratio of 1.262 per mm (p = 0.013) for the vector shift to the heart, i.e. for every 1 mm shift of the high dose region towards the heart there is a 1.262 higher chance of death. Baseline shifts towards the heart significantly correlate with overall survival in a cohort of NSCLC SABR patients, with increased risk with increasing shifts towards the heart. These results provide further evidence for the use of stricter heart dose planning constraints for thoracic radiotherapy and suggest a heart planning organ at risk volume may be required for SABR treatments to account for baseline shifts.


Comparative sequence- and structure-inspired drug design for PilF protein of Neisseria meningitidis.
Serogroup A of Neisseria meningitidis is the organism responsible for causing epidemic diseases in developing countries by a pilus-mediated adhesion to human brain endothelial cells. Type IV pilus assembly protein (PilF) associated with bacterial adhesion, aggregation, invasion, host cell signaling, surface motility, and natural transformation can be considered as a candidate for effective anti-meningococcal drug development. Since the crystal structure of PilF was not available, in the present study, it was modeled after the Z2491 strain (CAM09255.1) using crystal structure of chain A of Vibrio cholerae putative Ntpase EpsE (Protein Data Bank (PDB) ID: 1P9R) and then we based this analysis on sequence comparisons and structural similarity using in silico methods and docking processes, to design a suitable inhibitor molecule. The ligand 3-{(4S)-5-{[(1R)-1-cyclohexylethyl]amino}-4-[(5S)-5-(prop-2-en-1-yl) cyclopent-1-en-1-yl]-1,4-dihydro-7H-pyrrolo[2,3-d] pyrimidin-7-yl}-1,2-dideoxy-b-L-erythro-hex-1-en-3-ulofuranosyl binds to the protein with a binding energy of -8.10 kcal and showed a drug likeness of 0.952 with no predicted health hazard. It can be utilized as a potent inhibitor of N. meningitidis pilus-mediated adhesion to human brain endothelial cells preventing meningeal colonization.


[Possibilities for preventing the epidemic spread of rotavirus infections on neonatal wards].
Rota viruses are the most frequent cause of acute gastroenteritis of infants and toddlers. Small epidemies occur enlarged in institutions for newborns and toddlers. The infection occurs normally via faeces. An aerogenes infection is in discussion. In case of a suspected Rota-Virus-Infection in an infant- or toddler care unit the patients have to be isolated immediately or quarantined. Further essential precautions preventing the spreading are mentioned. With this regime we could only see individual Rota-Virus-Infections in infant care units.


Enhancement of tensile toughness of poly(lactic acid) (PLA) through blending of a polydecalactone-grafted cellulose copolymer: The effect of mesophase transition on mechanical properties.
Increasing the toughness of poly(lactic acid) (PLA), i.e., simultaneously increasing both the tensile strength and ductility, remains a major challenge. In this study, fully bio-based PLA blends with polydecalactone (PDL)-grafted cellulose copolymer (CgPD) were prepared and comprehensively analyzed to enhance the toughness of the PLA matrix. The blends were found by FT-IR and solid-state 1H NMR to be physically intact and miscible at the sub-twenty-nanometer scale. The WXRD and DSC analyses indicated that the addition of the alkyl-branched CgPD imparts a more structurally disordered PLA mesophase state to the prepared PLA_CgPD bio-blends. UTM analysis was used to characterize the macroscopic mechanical properties of the PLA_CgPD bio-blends. Both the tensile strength and elongation properties were simultaneously improved with the addition of 1 wt% CgPD loading amount to PLA (PLA_CgPD1). This study experimentally demonstrates that the enhanced mechanical properties of PLA_CgPD1 are closely related to the existence of more ordered PLA mesophases induced by the introduction of an optimal amount of CgPD into the PLA matrix.


Can sepsis predict deep venous thrombosis in colorectal surgery?
Little data exist regarding the impact of sepsis on deep venous thrombosis (DVT) in colorectal surgery patients. We sought to elucidate this relationship. Current Procedural Terminology codes were used to identify patients who underwent colorectal surgery as reported to the National Surgical Quality Improvement Program in 2010. The relationship between DVT and sepsis was then explored in a matched population. Of the 26,554 patients who underwent colorectal surgery, 462 (1.7%) developed a DVT. The largest dependent correlations with DVT were malnutrition (33% vs 57%), emergency operation (15% vs 31%), open operation (58% vs 78%), and prolonged ventilator requirement (5% vs 24%; all P < .001). After propensity score matching, urosepsis (.5% vs 1.9%), organ/space sepsis (1.1% vs 4.8%), pneumosepsis (.5% vs 5.8%), and overall perioperative sepsis (18% vs 39%; all P ≤ .04) were associated with DVT. The strongest independent predictor of DVT was pneumosepsis (odds ratio 15.9, 95% confidence interval 3.7 to 67.2, P < .001). Perioperative sepsis is a significant risk factor for postoperative DVT in the colorectal surgery population.


The diagnostic value of miR-21 combined with CT in patients with liver cancer.
To explore the diagnostic value of miR-21 combined with computed tomography (CT) in patients with liver cancer. A total of 112 patients in our hospital were confirmed liver cancer by examination, and were collected as cancer group. Another 100 patients with hepatic focal nodular hyperplasia in the same period were collected as control group. The diagnostic value of miR-21 and CT on liver cancer was observed. The level of miR-21 in cancer group was significantly higher than that in control group, the difference was statistically significant (p < 0.05). The alpha-fetoprotein (AFP) level was tested. It was found that the AFP level in cancer group was significantly higher than that in control group (p < 0.001). The correlation between AFP and miR-21 levels in liver cancer patients was detected. It turned out that AFP and miR-21 had correlation. According to receiver operating curve (ROC) calculation results, the best cut-off value for miR-21 diagnosis was 4.142. The sensitivity, specificity and accuracy of diagnosis of miR-21 alone were 64.29%, 87.00% and 75.00%, respectively. The sensitivity, specificity and accuracy of diagnosis of CT alone were 91.07%, 62.00% and 77.36%, respectively. There were 108 cases of true positive and 80 cases of true negative after combined diagnosis in the two groups. The sensitivity, specificity and accuracy of combined diagnosis were 96.43%, 80.00% and 88.68%, respectively. Comparing the value of single diagnosis and combined diagnosis, we found that the accuracy, sensitivity and specificity of combined diagnosis were significantly higher than that of single diagnosis (p < 0.05). CT combined with miR-21 has great diagnostic value in liver cancer and may be a potential diagnostic indicator for liver cancer.


Presynaptic NK1 Receptor Activation by Substance P Suppresses EPSCs via Nitric Oxide Synthesis in the Rat Insular Cortex.
Substance P (SP) regulates inhibitory synaptic transmission mediated by GABAA receptors in the cerebral cortex; however, SP-mediated regulation of excitatory synaptic transmission remains poorly understood. We performed whole-cell patch-clamp recordings from pyramidal neurons to examine the effects of SP on excitatory postsynaptic currents (EPSCs) mediated via AMPA receptors in the insular cortex (IC), which is involved in nociceptive information processing. First, EPSCs evoked by minimal electrical stimulation (eEPSCs) including stepwise EPSCs and failure events, were examined. SP dose-dependently suppressed mean eEPSC amplitude, partially due to an increase in the failure rate of eEPSCs. The SP-induced suppression of eEPSCs was accompanied by an increase in the paired-pulse ratio and was inhibited by the preapplication of SR140333, an NK1 receptor antagonist. [Sar9,Met(O2)11]-substance P, an NK1 receptor-selective agonist, mimicked the effects of SP on eEPSCs and decreased the frequency of miniature EPSCs (mEPSCs) without changing the average mEPSC amplitude. Considering that most NK1 receptors in the cerebral cortex are expressed in nitric oxide synthase (NOS)-positive GABAergic neurons, the SP-induced suppressive effect on EPSCs may be mediated by nitric oxide (NO) in this subtype of GABAergic neurons. NO imaging using the fluorescent probe DAX-J2 Red supports this hypothesis: SP increased the fluorescence intensity of DAX-J2 Red in some GABAergic neurons. Furthermore, both L-NAME, an NOS inhibitor, and PTIO, an NO scavenger, diminished the SP-induced suppression of eEPSCs. These results suggest that the activation of presynaptic NK1 receptors contributes to SP-induced eEPSC suppression by activating the NO synthesis pathway in GABAergic neurons. (246 words).


Three-dimensional imaging of nerve tissue by x-ray phase-contrast microtomography.
We show that promising information about the three-dimensional (3D) structure of a peripheral nerve can be obtained by x-ray phase-contrast microtomography (p-microCT; Beckmann, F., U. Bonse, F. Busch, and O. Günnewig, 1997. J. Comp. Assist. Tomogr. 21:539-553). P-microCT measures electronic charge density, which for most substances is proportional to mass density in fairly good approximation. The true point-by-point variation of density is thus determined in 3D at presently 1 mg/cm3 standard error (SE). The intracranial part of the rat trigeminal nerve analyzed for the presence of early schwannoma "microtumors" displayed a detailed density structure on p-microCT density maps. The average density of brain and nerve tissue was measured to range from 0.990 to 0.994 g/cm3 and from 1.020 to 1.035 g/cm3, respectively. The brain-nerve interface was well delineated. Within the nerve tissue, a pattern of nerve fibers could be seen that followed the nerve axis and contrasted against the bulk by 7 to 10 mg/cm3 density modulation. Based on the fact that regions of tumor growth have an increased number density of cell nuclei, and hence of the higher z element phosphorus, it may become possible to detect very early neural "microtumors" through increases of average density on the order of 10 to 15 mg/cm3 by using this method.


Concentrated Aqueous Peroxodicarbonate: Efficient Electrosyn- thesis and Use as Oxidizer in Epoxidations, S-, and N-Oxidations.
Peroxodicarbonates are of substantial interest as potentially powerful and sustainable oxidizers but have so far been accessible only in low concentrations with unsatisfactory energy efficiency. Concentrated (> 0.9 mol L-1 ) peroxodicarbonate solutions have now been made accessible by the electrolysis of aqueous K2 CO3 /Na2 CO3 /KHCO3 solutions at high current density of 3.33 A cm-2 in an efficiently cooled circular flow reactor equipped with a boron-doped diamond anode and a stainless-steel cathode. Their synthetic potential as platform oxidizers was clearly demonstrated in transformations including sulfoxidation, N-oxidation, and epoxidation.


Limits of therapy for malignant chorioepithelioma.
Report on two cases of malignant chorio-epithelioma following hydatidiform mole, both decreased 4 years after inception of the disease despite initially successful therapy and repeated remissions. In the first case a solitary pulmonary metastasis showing obvious de-differentiation and extensive local reparative processes was removed operatively. Associations to cytostatic medication are discussed. The second case was characterized by unusually extensive chronic pulmonary embolism with highly regressive choriocardinomatous aggregates. Death resulted unexpectedly from chronic dextrocardial insufficiency. It is stressed that the treatment is subject ot limitations of not only relative (i.e., resistance to cytostatics, inadequate treatment etc.) but also of an absolute nature, as in case 2.


Iodine adequacy in reproductive age and pregnant women living in the Western region of Saudi Arabia.
Despite the serious maternal and foetal complications associated with iodine deficiency during pregnancy, surveys related to pregnant women in the Kingdom of Saudi Arabia (KSA) are lacking. This study, therefore, measured urine iodine concentrations (UIC) alongside the potential socioeconomic factors contributing towards iodine inadequacy in reproductive age and pregnant Saudi women from the Western province of KSA. Spot urine samples were collected from 1222 pregnant and 400 age-matched non-pregnant/non-lactating reproductive age women. The socioeconomic characteristics were obtained through a structured questionnaire. The WHO criteria for iodine sufficiency in non-pregnant (100-199 μg/L) and pregnant (150-249 μg/L) women were applied. The median UIC in the non-pregnant women (101.64 μg/L; IQR: 69.83-143.55) was at the lowermost WHO recommended cut-off, whereas the pregnant group was iodine deficient (112.99 μg/L; IQR: 81.01-185.57). Moreover, the median UIC was below adequacy across the different trimesters. The use of non-iodised salt significantly increased the risk of iodine deficiency in the non-pregnant (OR = 2.052; 95%CI: 1.118-3.766) and pregnant women (OR = 3.813; 95%CI: 1.992-7.297), whereas taking iodine supplements significantly lowered the risk in both groups (OR = 0.364; 95%CI: 0.172-0.771 and OR = 0.002; 95%CI: 0.001-0.005, respectively). Passive smoking was also an independent risk factor for iodine deficiency in the non-pregnant (OR = 1.818; 95%CI: 1.097-3.014) and pregnant (OR = 1.653; 95%CI: 1.043-2.618) groups. Additionally, BMI correlated independently and significantly with median UIC in the non-pregnant and pregnant populations. However, multiparity (OR = 3.091; 95%CI: 1.707-5.598) and earning below the minimum wage (2.520; 95%CI: 1.038-6.119) significantly increased the risk of iodine deficiency only in the non-pregnant women. This study is the first to show borderline iodine sufficiency in reproductive age Saudi women from the Western province, whereas mild iodine deficiency was observed in the pregnant population and could represent a serious public health problem. This study also advocates the necessity to establish routine iodine dietary advice services by the health authorities to foster adequate iodine intake in pregnant women to avoid the perilous consequences of iodine deficiency on maternal-foetal health.


Head orthesis therapy in infants with unilateral positional plagiocephaly: an interdisciplinary approach to broadening the range of orthodontic treatment.
Unilateral positional plagiocephaly is the most common deformity of the head in infants. As part of a prospective controlled clinical study, the pathomorphology of the positional plagiocephaly in early infancy was examined. The goal was to use noninvasive three-dimensional (3D) imaging to generate, for the first time ever, a standard database of infants without head deformities, to quantify the asymmetry of the positional plagiocephaly, and to evaluate the effectiveness of functional growth control using head orthesis. In the present study, 3D soft-tissue data of the entire head were collected from a total of 40 infants: 20 with positional plagiocephaly (6.0 ± 0.97 months) and 20 infants without a head deformity (6.4 ± 0.3 months). Functional growth was controlled using a custom-made head orthesis. To evaluate the therapy, pre- and posttherapeutic scans were evaluated in three dimensions. Compared with the control group, infants with positional plagiocephaly demonstrated a reduced maximum length of the head, an increased head height, a shift in the ear axis as well as asymmetric anterior and posterior volumes of the neurocranium in lateral comparisons. Therapy using head orthesis led to a significant improvement of the asymmetry, with a reduction of the diagonal difference and an adjustment of the posterior volumes. Conservative growth control of extrinsically deformed infant skulls represents an interdisciplinary medical expansion of the orthodontic therapeutic spectrum. To prevent potential effects of positional plagiocephaly on the viscerocranium, head orthesis therapy is advisable in infancy.


Psychological characteristics of volunteers in studies on gambling.
Advertisements were published in local newspapers asking for volunteers to participate in a study on gambling. A battery of eleven questionnaires was mailed to the subjects assessing pathological gambling behavior, sociodemographic characteristics, motivation to gamble, erroneous perceptions about gambling, superstitious beliefs, depressive symptoms, social anxiety and avoidance, alcohol and drug abuse, problem-solving skills, and marital satisfaction. Subjects received $10 when they returned the questionnaires fully completed. Response rate was over 95%. Surprisingly, 29% of the respondents met the criterion for probable pathological gambling (score of 5 or more on the SOGS) and a further 16% were identified as potential pathological gamblers (scores of 3 or 4). The potential and probable pathological gamblers showed significant differences on motivational and cognitive variables related to gambling compared to those subjects who showed no signs of pathological gambling. The probable pathological gamblers reported significantly more signs of poor psychosocial functioning than the other two groups, including depressive symptoms, poor problem orientation, drug and alcohol abuse, and interpersonal conflict. The practical and theoretical implications of these results are discussed.


Non-obstructive vesicoureteral reflux in adults: value of conservative treatment.
Chronic or recurrent non-obstructive urinary tract infection was investigated in 158 adult patients, 39 of whom had vesicoureteral reflux. Conservative, long-term chemotherapy did not eradicate the reflux in these patients. The characteristics of reflux in adults were studied with cystograms, excretory urograms, cystoscopic findings of the ureteral orifices or trigones and the clinical histories of the patients. These data were evaluated and compared to data obtained from adults with chronic or recurrent uncomplicated urinary tract infection and from children with vesicoureteral reflux who were referred to us during the same period. Non-obstructive vesicoureteral reflux in adults may be considered to be congenital in most cases, since the proportion of trigonal anomalies in adults with reflux is equal to that in children and the frequency of abnormalities at the ureteral orifice and trigonal region is significantly more than the frequency noted in control patients with uncomplicated pyelonephritis. Characteristically, excretory urography revealed caliceal scarring in adults with reflux in contrast to children, in whom a normal or dilated pattern of the upper tract was prominent. Recurring renal infection, for which this congenital defect of the ureterovesical valve must be responsible, produces progressive renal damage. Prolonged conservative treatment is of little use and is often destructive in adults with reflux.


Development and evaluation of multiplex PCR in rapid diagnosis of abdominal tuberculosis.
The clinical features of abdominal tuberculosis (TB) are non-specific and establishing a diagnosis remains a challenge. A delay in diagnosis is likely to increase the morbidity in these patients. We developed a multiplex polymerase chain reaction (PCR) using 16SrRNA, IS6110, and devR, and evaluated it in comparison with other conventional tests in clinical suspects of abdominal TB. A total of 183 patients with clinical suspicion of abdominal TB (96 patients with intestinal TB and 87 with peritoneal TB) were enrolled for the study. Endoscopic or intraoperative biopsies were collected from patients suspected of intestinal TB and ascitic fluid was collected from patients with a suspicion of peritoneal TB. Of the intestinal tuberculosis group, there were 40 confirmed cases and 56 controls, while of the peritoneal tuberculosis group there were 37 confirmed cases and 50 controls. Multiplex PCR showed a high sensitivity and specificity in both the intestinal TB and peritoneal TB groups. When combined with histopathology, multiplex PCR could detect 97.5% of all the cases in the intestinal tuberculosis group, while in combination adenosine deaminase levels (ADA) in cases of peritoneal tuberculosis it increased the specificity of diagnosis of peritoneal tuberculosis to 95%. In combination with histopathology in suspected intestinal TB cases, and ADA testing in suspected peritoneal TB cases, it can be used as a highly sensitive, specific, and rapid diagnostic tool with the ability to supplement the limitations of other diagnostic modalities.


Essential oils for treating anxiety: a systematic review of randomized controlled trials and network meta-analysis.
The findings of clinical studies exploring essential oils (EOs) for anxiety remain disputed, and no studies have yet clarified the differences in the efficacy of EOs. The purpose of the study was to directly or indirectly compare the efficacy of different types of EOs on anxiety by pooling the results of randomized controlled trials (RCTs). PubMed, Cochrane Library, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to November 2022. Only full texts of RCTs that investigated the effects of EOs on anxiety were included. The trial data were extracted and the risk of bias was assessed by two reviewers independently. Pairwise meta-analysis and network meta-analysis were performed by Stata 15.1 or R 4.1.2 software. Forty-four RCTs (fifty study arms) involving 10 kinds of EOs and 3419 anxiety patients (1815 patients in EOs group and 1604 patients in control group) were included. Pairwise meta-analyses showed that EOs were effective in reducing State Anxiety Inventory scores (SAIS) [WMD = -6.63, 95% CI-8.17, -5.08] and Trait Anxiety Inventory scores (TAIS) [WMD = -4.97, 95% CI-6.73, -3.20]. Additionally, EOs could decrease systolic blood pressure (SBP) [WMD = -6.83, (95% CI -10.53, -3.12), P < 0.001] and heart rate (HR) [WMD = -3.43, (95% CI -5.51, -1.36), P < 0.001]. Network meta-analyses demonstrated that regarding the outcome of SAIS, Jasminum sambac (L.)Ait. (jasmine) was the most effective with a weighted mean difference (WMD) of-13.61 (95% CrI-24.79, -2.48). Followed by Citrus (citrus aurantium L.), which had a WMD of-9.62 (95% CrI-13.32, -5.93). Moderate effect sizes were observed for Rosa rugosa Thunb. (damask rose) (WMD = -6.78, 95% CrI-10.14, -3.49) and Lavandula angustifolia Mill. (lavender) (WMD = -5.41, 95% CrI-7.86, -2.98). Regarding the results of TAIS, citrus aurantium L. was the best ranked intervention with a WMD of-9.62 (95% CrI-15.62, -3.7). Moderate-to-large effect sizes were observed for Citrus limon (L.) Burm. F. (lemon) (WMD:-8.48; 95% CrI-16.67, -0.33) and lavender (WMD:-5.5; 95% CrI-8.7, -2.46). According to the comprehensive analysis, EOs are effective in reducing both state anxiety and trait anxiety, and citrus aurantium L. essential oil seems to be the most recommended type of EO for treating anxiety because of its significant effects in reducing SAIS and TAIS. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022331319.


Factor analysis of serogroups botanica and aurisina of Leptospira biflexa.
Factor analysis is performed on serovars of Botanica and Aurisina serogroup of Leptospira biflexa. The results show the arrangement of main factors serovar and serogroup specific, as well as the antigens common with serovars of heterologous serogroups.


Effects of cyclohexanonic long-chain fatty alcohol, tCFA15 on amino acids in diabetic rat brain: a preliminary study.
The aim of this study was to evaluate the effects of streptozotocin-induced type 1diabetes and a subchronic treatment with cyclohexanonic long-chain fatty alcohol, 3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (tCFA15) on contents of amino acids including aspartate, glutamate, glutamine, GABA, glycine, taurine, alanine, serine, threonine, and arginine in the prefrontal cortex, hippocampus and striatum. Levels of glutamate, threonine, taurine, alanine, arginine, and the ratio of glutamate/glutamine were altered region-differently in the brain of diabetic rats. However, tCFA15 region-specifically antagonized the changes in taurine and arginine levels and the ratio of glutamate/glutamine. The alteration in glutamate/glutamine ratio may indicate that experimental models of type 1 diabetes have abnormalities of neuron-gria interaction in brain.


Dexamethasone implant in diabetic macular edema in real-life situations.
To report outcome of eyes with recalcitrant and naive eyes with diabetic macular edema (DME) treated with intravitreal dexamethasone implants (Ozurdex) injection. Retrospective multicenter data analysis of eyes with DME treated with Ozurdex implant and with minimum follow-up of at least one year after the first implant. Data collected included demographic details, history of presenting illness, past treatment history, clinical examination details including visual acuity at presentation, and follow-up with imaging and treatment details. Paired sample t-test was used to measure mean differences between pre- and post-implant values obtained at baseline and last follow-up. A total of 79 eyes (62 subjects) were included. Sixty-four eyes had been previously treated; 15 eyes were naive. Among the previously treated eyes, mean interval between first Ozurdex injection and any previous treatment was 7.69±8.2 months. In naive eyes, the visual acuity improved from baseline 0.58±0.25 to 0.44±0.33 logMAR at last follow-up (P=0.05). In eyes that had been previously treated, the improvement was from 0.65±0.34 at baseline to 0.48±0.35 logMAR (P=0.01). Mean treatment-free interval was 6.5±4.5 months. Nine eyes were steroid responder with controlled intraocular pressure (IOP), none showed any spike in IOP during the follow-up period. Ozurdex implant could be a good alternative for recalcitrant as well as naive eyes with DME. The visual gain after initial implant injection was fairly maintained, with additional treatment usually after 6 months in naive eyes. Ozurdex appeared safe even in steroid responders with good control of IOP with antiglaucoma medications.


Influence of the composition of in-vitro azo-reducing systems on the degradation kinetics of the model compound amaranth.
The purpose of this study was to investigate the influence of the composition of in-vitro azo-reducing systems on the degradation kinetics of the model compound amaranth. The degradation kinetics of amaranth were determined under anaerobic conditions both in rat caecal content (ex-vivo) and in a variety of in-vitro degradation media derived from rat caecal content. It was observed that the reducing activity was highly dependent on the preparation method and composition of the degradation medium. In pure rat caecal content, the degradation of amaranth was apparent first order (k = 0.044 +/- 0.002 min(-1)), while dilution of the rat caecal content resulted in an apparent zero-order degradation. Both apparent zero- and first-order degradations were also observed in media made up of diluted rat caecal content to which cofactors such as NADP, D-glucose-6-phosphate, glucose-6-phosphate dehydrogenase and Bz were added. This study demonstrates that in-vitro azo-reducing kinetics are dependent on the composition and mode of preparation of the in-vitro media used. This has to be taken into account when evaluating the degradability of azo-aromatic drug delivery systems in-vitro.


Osteosarcoma Overview.
Osteosarcoma (OS) is the most common primary malignancy of bone and patients with metastatic disease or recurrences continue to have very poor outcomes. Unfortunately, little prognostic improvement has been generated from the last 20 years of research and a new perspective is warranted. OS is extremely heterogeneous in both its origins and manifestations. Although multiple associations have been made between the development of osteosarcoma and race, gender, age, various genomic alterations, and exposure situations among others, the etiology remains unclear and controversial. Noninvasive diagnostic methods include serum markers like alkaline phosphatase and a growing variety of imaging techniques including X-ray, computed tomography, magnetic resonance imaging, and positron emission as well as combinations thereof. Still, biopsy and microscopic examination are required to confirm the diagnosis and carry additional prognostic implications such as subtype classification and histological response to neoadjuvant chemotherapy. The current standard of care combines surgical and chemotherapeutic techniques, with a multitude of experimental biologics and small molecules currently in development and some in clinical trial phases. In this review, in addition to summarizing the current understanding of OS etiology, diagnostic methods, and the current standard of care, our group describes various experimental therapeutics and provides evidence to encourage a potential paradigm shift toward the introduction of immunomodulation, which may offer a more comprehensive approach to battling cancer pleomorphism.


Iodide concentrations in matched maternal serum, cord serum, and amniotic fluid from preterm and term human pregnancies.
To characterize the matched maternal and cord plasma and the amniotic fluid concentrations of iodide in preterm and term human pregnancies. Specimens were collected at the delivery of 121 singleton pregnancies (92 at term, 29 preterm) with no pre-existing medical complications. Plasma unbound iodide concentrations were measured by the difference between the protein bound iodine and the total iodine measured spectrophotometrically. Total iodide was measured in amniotic fluid. Maternal plasma iodide concentrations were 1.6 +/- 0.4 mcg/dL (mean +/- S.D.) for preterm deliveries and 1.5+/ -0.5 mcg/dL for term deliveries. Cord plasma iodide concentrations were 1.4 +/- 0.5 mcg/dL for preterm deliveries and 1.7 +/- 0.7 mcg/dL for term deliveries. Cord plasma iodide concentrations at birth correlated highly with maternal levels (p < 0.001). The cord:maternal plasma iodide ratio for all pairs was 1.2+/- 0.7. The average cord:maternal plasma iodide ratio was not significantly different between the preterm (0.9+/- 0.4) and term (1.3+/- 0.8) deliveries. Amniotic fluid iodide concentrations did not correlate significantly with cord plasma concentrations. Cord plasma concentrations of iodide correlate with paired maternal levels, indicating that, unlike the rabbit and other species, the human conceptus does not highly concentrate iodide.


Dissociated cell culture for testing effects of carbon nanotubes on neuronal growth.
Cell culture has emerged as an important research method for studying the effects of carbon nanotubes (CNTs) on primary neurons. We describe the procedure for preparation of dissociated mixed cell culture from postnatal rat hippocampi. Based on morphological criteria and specific neuronal cell markers, neurons can be selected within this mixed cell culture and studied. We present the procedure for the assessment of neuronal cell morphology based on intracellular fluorescence of the vital dye calcein that accumulates in live neurons. This procedure encompasses fluorescence imaging and measurement of the following parameters: neurite number, total neurite length, mean neurite length, number of growth cones, number of branches, and number of branches per neurite. These combined cell culture and fluorescence microscopy approaches can be successfully used for assessment of the effects that CNTs, as water-soluble agents, have on neuronal cell growth and neurite outgrowth.


Pharmacological Treatment of Insomnia.
Up to 70 million U.S. adults have chronic sleep and wakefulness disorders. Therapies may include prescription medications approved by the Food and Drug Administration, off-label treatments, over-the-counter drugs, and herbal therapies.


Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain.
Irisin, a newly discovered muscle-derived hormone, acts in different organs and tissues, improving energy homeostasis. In this study, we assessed, for the first time, the effects of intraperitoneal irisin injections on circulating levels of leptin and ghrelin, mRNA expression of the major hypothalamic appetite regulators and brain neurotrophic factors, as well as feeding behaviour in healthy mice. Twelve male 6-week-old C57BL/6 mice were randomized into two groups and intraperitoneally injected daily with irisin (0.5 μg/g body weight) or vehicle (phosphate-buffered saline [PBS]) for 14 days. On the last day of observation, leptin and ghrelin levels were measured with an enzyme-linked immunosorbent assay (ELISA). mRNA levels of genes of interest were analysed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in brain extracts. Irisin administration did not change leptin or ghrelin serum concentrations. However, irisin injection increased CART, POMC, NPY, and BDNF mRNA levels, without affecting the mRNA expression of AgRP, orexin, PMCH, and UCP2. Finally, over the time frame of irisin treatment, body weight and feeding behaviour were unaltered. These results suggest that intraperitoneal injection of irisin, although without effects on feeding behaviour and body weight, can increase the expression of anorexigenic and neurotrophic genes in mouse brain.


Medical student evaluations of lectures attended in person or from rural sites via interactive videoconferencing.
Interactive videoconferencing may be an effective way for medical students on remote rotations to attend teaching sessions at the main campus. To compare medical student evaluations of lectures for those attending in person and those attending through interactive videoconferencing. Lecture evaluations were completed by medical students on University of Vermont College of Medicine clinical clerkship rotations. Students on clerkships at rural sites attended lectures using our telemedicine network. Responses from in-person and remote attendees were compared. Evaluation forms for 110 lectures were received from 648 in-person and 255 remote attendees. All evaluation items were rated "good" or "excellent" by at least 95% of in-person attendees. Over 90% of remote attendees rated nontelemedicine evaluation items, such as appropriateness of lecture topic for students, as good or excellent. Ratings of telemedicine-specific questions, such as ability to hear the lecturer, were lower. Level of satisfaction was high for most aspects of remote lecture attendance, although not quite as high as for in-person attendance. Improved technical reliability would likely increase remote attendee satisfaction. Overall, lecture attendance using videoconferencing was found to be an acceptable alternative to travel for medical students in rural clerkships.


Sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 1 pathway: A novel target of geniposide to inhibit angiogenesis.
Rheumatoid arthritis (RA) is a common inflammatory autoimmune disease characterized by the formation of joint synovitis and pannus. Sphingosine 1-phosphate (S1P) is an important mediator related to angiogenesis, inflammation and autoimmunity. As Geniposide (GE) has potent immuno-modulation function, we investigated the effects on the dynamic balance of angiogenesis-related factors and Sphingosine kinase 1 (SphK1)-S1P-S1P receptor 1 (S1PR1) signal transduction in adjuvant-induced arthritis (AA) rats. The model evaluation was performed from paw swelling degree, arthritis index and movement score. The immunohistochemistry and enzyme-linked immunosorbent assay were used to study the microvascular density (MVD) and pro/anti-angiogenic factors levels. The cell viability was examined by cell counting kit-8 assay. SphK1, S1PR1 mRNA and protein levels in fibroblast-like synoviocytes (FLSs) were detected by quantitative real-time polymerase chain reaction and Western blotting. The results showed that GE can apparently suppressed the inflammatory pathological status. The arthritis index, paw swelling and MVD of AA rats were decreased with dose dependence (⁎P < 0.05, ⁎⁎P < 0.01). In addition, GE can reduce the secretion of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), promote the secretion of endostatin (ES) and inhibit excessive proliferation of FLSs (⁎P < 0.05, ⁎⁎P < 0.01). Importantly, GE can significantly inhibit the activity of SphK1, the level of S1P and the expression of SphK1 and S1PR1 in FLSs (⁎P < 0.05, ⁎⁎P < 0.01). It indicated that GE reduces the activity of SphK1 by restoring the dynamic balance between pro/anti-angiogenic factors, thereby interfering with SphK1-S1P-S1PR1 signal transduction, reducing the formation of synovial microvessels and exerting anti-angiogenesis effect of RA.


The relative emphasis upon physician practice and organizational affairs of a consumer council in a prepaid group practice health plan.
This paper examines the topics of interest to a consumer advisory council in the Health Insurance Plan of Greater New York, a prepaid group practice. Data are derived from observations of consumer council meetings. Topics considered by the council dealt with (a) health plan services, (b) health plan structure, and (c) consumer council structure, process, and organizational role. The council was primarily interested in retaining and expanding existing services, facilitating utilization of services by enrollees, and achieving broader enrollee representation on the board of directors. These interests are directed toward the organizational context within which care is provided and do not relate to physician-patient encounters. Individual enrollees in prepaid group practice may be concerned with the physician-client relationship but consumer representatives are concerned only with the organization-client relationship.