Placement technique impacts gastrostomy tube-related complications amongst head and neck cancer patients.
Percutaneous endoscopic gastrostomy (PEG) placement is essential for the provision of enteral nutrition in select head and neck cancer (HNC) patients. Minimally invasive tube placement is facilitated through one of two techniques, push or pull, but there have been conflicting results regarding safety profiles of these procedures. The objectives of this study were to determine the association of PEG insertion technique with gastrostomy tube complications, including stomal metastases. A multi-institutional retrospective cohort study of patients with HNC undergoing PEG insertion by either the pull (gastroscope assisted) or push (fluoroscopy assisted) technique was performed. Tube-related complications included infection, dislodgement, deterioration, leak, and other. Adjusted analysis was performed via a multivariable logistic regression model. 1,575 patients were included across three institutions. Tube-related complications occurred in 36% of patients, the most common being peristomal leak (13%) and infection (16%). The push technique (OR 2.66, 95% CI: 1.42-4.97), and the presence of T4 disease (OR 4.62, 95% CI: 1.58-13.51), were associated with a greater risk of developing any tube-related complication. Infection rates were similar between pull and push cohorts. All detected stoma metastases occurred with the pull technique, with an overall prevalence of 0.32% amongst the cohort. The push technique is associated with a greater risk of developing any tube-related complication, but the rate of stomal metastases may be higher with the pull technique. There is potential for quality improvement measures to improve tube-related complications associated with either technique.


Characterization of Pasteurella spp. strains isolated from human infections.
This report describes the distribution of species and capsular groups in a collection of 143 strains of Pasteurella recovered from human patients. The organism isolated most frequently was Pasteurella multocida subsp. multocida. As in animals, most of the group A strains were recovered from the respiratory tract. The distribution of species in relation to the animal source suggests that P. multocida subsp. multocida is more infective than other Pasteurella species or subspecies for man.


Degradation of methyl and ethyl mercury into inorganic mercury by various phagocytic cells.
In connection with the dealkylation of methyl mercury (MeHg) and ethyl Hg (EtHg) with reactive oxygen-producing systems, we examined the ability of phagocytic cells to degrade MeHg or EtHg into inorganic mercury in vitro by collecting them from blood or peritoneal cavity of several species of animal. EtHg was readily degraded by human polymorphonuclear leukocytes (PMN), rat PMN, guinea-pig PMN, rabbit PMN, guinea-pig macrophages (M phi), human monocytes and guinea-pig eosinophils. In contrast, rat hepatocytes and the M phi hybridoma clone 39 cells were weaker in their degrading ability. Degradation of MeHg by these cells was always much weaker than EtHg, under identical conditions; however, by increasing the cell numbers, MeHg was appreciably degraded by human PMN, rat PMN and rabbit PMN. The reactive oxygen species mainly responsible for alkyl Hg degradation seemed to be hydroxyl radicals produced by M phi, and hypochlorous acid produced by PMN, monocytes and eosinophils. It was also suggested that the degradation of alkyl Hg by these cells might be an intraphagosomal event.


Mycotic aneurysm. Report of two cases.
Reference is made to two cases of mycotic aneurysm with different peripheral localizations, arising from a bacterial endocarditis. The cause, localizations, complications and histological findings are discussed.


Effects of levamisole on human natural killer and killer cell activity and production of interferons.
The effect of levamisole on natural killer (NK) and killer (K) cell activities and on interferon production was determined in both normal subjects and cancer patients. Levamisole had no effect on these cytolytic immune effector cells in vitro. It did not induce interferon production. Sequential determinations of NK cell activity and interferon plasma levels after single oral doses of levamisole failed to demonstrate an effect of levamisole on spontaneous cytotoxicity or interferon production.


Feeding electivity of two epiphytic chironomids in a subtropical lake.
Feeding electivity of two epiphytic orthoclad chironomid species, Psectrocladius sp. and Thienemanniella cf. fusca, was investigated using gut content analysis of larvae collected from Typha stems in Lake Padgett, Florida. Electivity values, computed using Strauss's Food Selection Index, were strongly positive for Cosmarium and negative for Oedogonium and Bulbochaete. Diatoms either were avoided or grazed in proportion to their abundance in the environment. Patterns of electivity were similar for both chrionomid species during all seasons studied. Pairwise food preference experiments were conducted in the laboratory using the algal species, Cosmarium impressulum, Navicula pelliculosa, Selenastrum capricornuatum, Oedogonium cardiacum, and Synedra sp. Preferences were hierarchical and consistent for both larval genera. Preference ranking for the algae offered were Cosmarium≥Synedra>Navicula>Oedogonium>Selenastrum. Larvae seemed to be feeding electively based upon algal genus, size, position in the epiphytic community, and possibly extracellular chemistry.


Shear bond strength of metallic orthodontic brackets to zirconium crowns treated by sandblasting compared to enamel using a universal adhesive: An in vitro study.
Orthodontic brackets are increasingly bonded to the surface of zirconium crowns due to the growing aesthetic demands in adults' restorations. Therefore, providing a reliable bond between these substrates is of great importance. This study aimed at investigating the shear bond strength (SBS) of orthodontic metal brackets bonded to zirconium treated by sandblasting. In addition, the value was compared with SBS between metal brackets and enamel. Samples were divided into three groups including first premolar enamel specimens (n=20), untreated zirconium blocks (n=20) and sandblasted zirconium blocks (n=20). Enamel specimens underwent etching and bonding procedures using 37% phosphoric acid and 3M™ Scotchbond™ Universal adhesive. Zirconium blocks were randomly allocated to two groups. The first group was prepared by sandblasting with 50μm aluminium oxide particles (Al2O3) under 4 bars pressure followed by bonding brackets with 3M™ Scotchbond™ Universal adhesive. Metal brackets were also bonded to the untreated zirconium group using the same adhesive. All samples underwent thermocycling, and SBS was calculated using a universal testing machine with a crosshead speed of 1mm/min. Data were analysed using One-way Anova and Tukey's tests. The highest SBS was recorded in sandblasted zirconium group (26.17±8.22MPa) followed by enamel group (23.667±7.00MPa) and untreated zirconium group (11.49±7.00MPa). There was a significant difference between the SBS of untreated zirconium and that of two other groups. Perfect SBS was achieved by sandblasting pre-treatment, comparable to that of enamel. Therefore, sandblasting of zirconium crowns is recommended prior to bonding orthodontic brackets.


Dynamics of beta-arrestin1 protein and mRNA levels elevation by antidepressants in mononuclear leukocytes of patients with depression.
Beta-arrestins interfere in G protein-receptor interaction leading to desensitization of G protein-mediated receptor signaling. G protein-receptor signaling and its desensitization were previously implicated in the pathophysiology, diagnosis and treatment of mood disorders. The present study aims at evaluating alterations in beta-arrestin1 protein and mRNA levels in mononuclear leukocytes of untreated patients with major depression and the effects and time course of antidepressant treatments on these alterations. Repeated beta-arrestin1 protein and mRNA measurements, through immunoblot analyses using monoclonal antibodies against beta-arrestin1 and reverse transcriptase polymerase chain reaction, respectively, were carried in mononuclear leukocytes of 18 patients with major depression and compared with 18 healthy subjects. Each patient was examined while untreated and after 1, 2, and 4 weeks of antidepressant treatment. Beta-arrestin1 protein and mRNA levels in mononuclear leukocytes of untreated patients with major depression were significantly lower than those of healthy subjects. The low beta-arrestin1 protein and mRNA levels were alleviated by antidepressant treatment. Normalization of beta-arrestin1 measures preceded, and thus predicted clinical improvement. These findings support the implication of beta-arrestin1 in the pathophysiology of major depression and in the mechanism underlying antidepressant-induced receptor down-regulation and therapeutic effects. Beta-arrestin1 measurements in patients with depression may potentially serve for biochemical diagnostic purposes and for monitoring and predicting response to antidepressants.


The activity of dental caries in students of the Faculty of Dentistry, the study with the use of microbiological and biochemical tests (Dentocult SM).
The aim of the paper is to answer the question whether the Dentocult SM tests could be used to study dental caries activity in the 20-25 age group. 66 students of the Faculty of Dentistry, Medical University of Lublin, were included in the study. In all cases dental state was assessed by using average numbers of DMF and DMFs Ds. In the microbiological examinations a ready-made medium from Dentocult SM set was used. The results revealed that the risk of dental caries in the population studied cannot be determined only on the basis of Streptococcus mutans values.


Decoupling the role of image size and calorie intake on gastric retention of swelling-based gastric retentive formulations: pre-screening in the dog model.
Gastric retention is postulated as an approach to improve bioavailability of compounds with narrow absorption windows. To elucidate the role of image size on gastric retention and pharmacokinetics, formulations with different image sizes and swelling kinetics but similar dissolution rates were designed and imaged in dogs. Diet had a clear effect, with increasing calorific intake prolonging retention in the dog model. In contrast to clinical observations, no obvious effect of image size on gastric retention was observed in the dog, with the larger gastric retentive (GR) and smaller controlled release (CR) formulations both demonstrating similar gastric emptying. Comparable pharmacokinetic profiles were observed for the two formulations, corroborating the imaging data and providing evidence of similar in vivo dissolution rates and dosage form integrity in the dog. Food, specifically meal composition, resulted in comparable enhancements in exposure in the dog and clinic due to prolonged gastric retention. However, differentiating retention based on image size in the dog was not feasible due to the smaller pyloric aperture compared to humans. This work illustrates that the dog is capable of determining the pharmacokinetic advantage of gastric retention relative to immediate release (IR) or CR formulations, however, has limited value in differentiating between CR and GR formulations.


A ring-reversed analog of atrial natriuretic peptide retains receptor binding, guanylate cyclase stimulation.
We have prepared an atrial natriuretic peptide analog, ANP[13-27][1-12], in which the connectivity of the disulfide-linked ring has been reversed by formally cleaving the ring and cyclizing the N- and C-terminal tails. This analog, which retains many of the spatial relationships of the native molecule, binds to both ANP-A and ANP-C receptor subtypes, and triggers the production of cyclic-GMP by ANP-A. ANP-C binding of ANP[13-27][1- 12] is roughly equipotent to that of ANP itself, although the ring cleavage falls within the putative ANP-C binding domain. ANP[13-27][1-8], a truncated analog in which much of this binding domain has been removed, surprisingly maintains a high affinity for ANP-C; however, this peptide has lost the ability to activate the ANP-A-linked guanylate cyclase.


Comparison of quantiferon test with tuberculin skin test for the detection of tuberculosis infection in children.
The efficacy of Quantiferon-TB gold test (QFT-GIT) remains to be documented in pediatric population. Tuberculin skin test (TST) is a conventional test available for the diagnosis of latent tuberculosis infection (LTBI). We aimed to investigate the concordance between QFT-GIT and TST in children with and without tuberculosis infection. Ninety-seven patients, aged 3 months-14 years, admitted to pediatric outpatient clinics of Dr. Sadi Konuk Training Hospital Bakırköy, Turkey between March 2008 and April 2009 were recruited. Demographic features, TST results, history of exposure to active tuberculosis (TB), chest X-ray findings, clinical history, presence of Bacillus Calmette Guerin (BCG) vaccination scar were recorded. Patients were categorized into four groups namely, active TB, LTBI, no TB and healthy. It was found that BCG scar positivity did not influence QFT-GIT results. There was a statistically significant agreement between QFT-GIT and TST results (κ = 0.486; p < 0.01). In patients ≥ 5 years of age, TST positivity and QFT positivity had a significant relationship (p < 0.01). In all patient groups, sensitivity and specificity was 65.85 % and 82.14 %, respectively. In active TB group, TST and QFT-GIT results demonstrated significant agreement ratio of 40.8 % (κ = 0.364; p < 0.01). Sensitivity and specificity was 100 % and 30 %, respectively. Utilization of QFT-GIT in the diagnosis of LTBI reduces false-positive results and prevents unnecessary treatment with INH and its adverse effects.


Growth regulation of A431 cells. Modulation of expression of transforming growth factor-alpha mRNA and 2',5'-oligoadenylate synthetase activity.
To explore bidirectional regulatory interactions between interferons and autocrine polypeptide factors, we examined the modulation of expression of transforming growth factor-alpha and 2',5'-oligoadenylate synthetase activity in A431 epidermoid carcinoma cells after treatment with interferon-gamma and transforming growth factor-alpha. Treatment of A431 cells with interferon-gamma increased steady state levels of transforming growth factor-alpha mRNA by 4-fold and increased the levels of transforming growth factor-alpha in the culture medium. There were additive growth inhibitory effects upon coaddition of exogenous transforming growth factor-alpha and interferon-gamma to the cultures. Addition of transforming growth factor-alpha to A431 cell cultures in the absence of interferon could stimulate the induction of 2',5'-oligoadenylate synthetase activity by more than 2-fold. These findings demonstrate that the induction of transforming growth factor-alpha in interferon-gamma-treated A431 cells could act to regulate interferon-induced gene(s), e.g. 2',5'-oligoadenylate synthetase, suggesting interactions between a potential autocrine growth factor and the interferon system in the growth regulation of A431 cells.


The association of serum uric acid levels in psoriasis patients: A systematic review and network meta-analysis.
Current research has proved that psoriasis is associated with serum uric acid (SUAC) levels. Our purpose is to clarify SUAC levels and the incidence of hyperuricemia in psoriasis patients, and to compare SUCA levels in different groups' psoriasis patients. We plan to search 7 electronic bibliographic databases (PubMed, Embase, Cochrane, and 4 Chinese databases) from inception to August 2019. Literatures selection and data collection will be performed independently by 2 authors. The Newcastle-Ottawa scale will be used to assess the methodologic quality and bias of included studies. Firstly, standard pairwise meta-analysis will be used to examine the considered data synthesis. Secondly, if the identified studies appear sufficiently similar within and across the different comparisons between different groups of psoriasis patients, we will estimate SUAC levels using network meta-analysis in different age and ethnicity psoriasis patients. Mean difference, risk ratio, and 95% confidence intervals will be used to assess the SUAC levels and the incidence of hyperuricemia in psoriasis patients. The software of Stata and WinBUGS will be used to calculations. The results will be published in a peer-reviewed journal. Our study will compare SUCA levels in different groups' psoriasis patients through network meta-analysis, and we believe our job is very meaningful. Our study is a secondary study of the existing literature. So, ethical and dissemination approval is not required.


Ketamine Use in the Intubation of Critically Ill Children with Neurological Indications: A Multicenter Retrospective Analysis.
Ketamine has traditionally been avoided for tracheal intubations (TIs) in patients with acute neurological conditions. We evaluate its current usage pattern in these patients and any associated adverse events. We conducted a retrospective observational cohort study of critically ill children undergoing TI for neurological indications in 53 international pediatric intensive care units and emergency departments. We screened all intubations from 2014 to 2020 entered into the multicenter National Emergency Airway Registry for Children (NEAR4KIDS) registry database. Patients were included if they were under the age of 18 years and underwent TI for a primary neurological indication. Usage patterns and reported periprocedural composite adverse outcomes (hypoxemia < 80%, hypotension/hypertension, cardiac arrest, and dysrhythmia) were noted. Of 21,562 TIs, 2,073 (9.6%) were performed for a primary neurological indication, including 190 for traumatic brain injury/trauma. Patients received ketamine in 495 TIs (23.9%), which increased from 10% in 2014 to 41% in 2020 (p < 0.001). Ketamine use was associated with a coindication of respiratory failure, difficult airway history, and use of vagolytic agents, apneic oxygenation, and video laryngoscopy. Composite adverse outcomes were reported in 289 (13.9%) Tis and were more common in the ketamine group (17.0% vs. 13.0%, p = 0.026). After adjusting for location, patient age and codiagnoses, the presence of respiratory failure and shock, difficult airway history, provider demographics, intubating device, and the use of apneic oxygenation, vagolytic agents, and neuromuscular blockade, ketamine use was not significantly associated with increased composite adverse outcomes (adjusted odds ratio 1.34, 95% confidence interval CI 0.99-1.81, p = 0.057). This paucity of association remained even when only neurotrauma intubations were considered (10.6% vs. 7.7%, p = 0.528). This retrospective cohort study did not demonstrate an association between procedural ketamine use and increased risk of peri-intubation hypoxemia and hemodynamic instability in patients intubated for neurological indications.


Investigation of the preliminary mechanism of action for the acute anti-inflammatory activity of the methanol extract of Smilax ornata Lem.
In folkloric medicine the dried rhizome of the Jamaican sarsaparilla (Smilax ornate Lem.), is given as a decoction to treat chronic rheumatism and rheumatoid arthritis. This particular claim has been scientifically validated; however, the mechanism for its anti-inflammatory activity is still unknown and hence, it forms the reason for this investigation. The objective of this study is to investigate the mechanism of the anti-inflammatory activity of the methanol extract of Smilax ornate Lem. The methanol extract was prepared using the soxhlet apparatus. The preliminary mechanism of action was investigated using models of oedema induced by histamine, bradykinin and prostaglandin E2. For the histamine-induced oedema model, the methanol extract (400 mg/kg) reduced the oedema formation, however, it was not significant (P > 0.05). For the bradykinin-induced oedema model, the methanol extract (400 mg/kg) exhibited significant (P < 0.05) anti-inflammatory activity when compared with that of the control (saline) group, with an onset on 60 min and a duration of 2 h. For the prostaglandin-induced oedema model, the methanol extract (400 mg/kg) exhibited significant (P < 0.05) anti-inflammatory activity when compared with that of its control group, with an onset on 120 min and a duration of 1.5 h. The methanol extract of Smilax ornata Lem. produced significant anti-inflammatory activity in the bradykinin-induced and prostaglandin-induced oedema models. It is possible that the mechanism by which it acts is by reducing the concentration or blocking the action of these mediators.


[Importance, especially in aeronautics, of color perception tests under dynamic conditions. Study of a suitable experimental apparatus].
Following a review of the most recent opinion on the physiology of colour vision, a device for examining it in dynamic, i.e. real-life conditions is described. The apparatus consist of two projectors which flash two absolutely identical pictures on to the screen, one of them is upside down. It appears at fixed but adjustable intervals so that the exposure time of the intelligible image can be varied. Subjects were also controlled with Ishihara charts and Nägel anomaloscope. The results are compared and point to the higher sensitivity of the dynamic test to even slight degrees of dyschromatopsia.


Psychotic-like experiences in general population: Psychiatric comorbidity and impact on quality of life across lifespan.
In this study, we aimed to determine the prevalence of Psychotics-Like Experiences according to age group and their association with psychiatric disorders through these different age-group, as well as their impact on quality of life. Using data from the second wave of the NESARC, a large general population study, we considered 6 mutually exclusive groups according to the age at the interview: 20-29 years; 30-39 years; 40-49 years; 50-59 years; 60-69 years; 70+ years. We determined the frequency of PLEs defined as positive, negative, depressive, mania and disorganization symptoms with reference to the PANSS, and the association between the presence of PLEs in the previous year and the presence of lifetime psychiatric disorders and quality of life across different age groups. The prevalence of PLEs decreased across age from a 34.7 % in the 20-29 years age group, to 19.7 % in the 70+ years age group. Across all age groups, individuals who reported PLEs in the previous year had higher risk of having any psychiatric disorder, (i.e any mood disorder, any anxiety disorder any substance abuse and any personality disorder) compared to individuals not reporting PLEs. All dimensions of quality of life on the SF12 scale were negatively associated with the presence of a PLE regardless of age group. We found that the frequency of PLEs decreased with age and that the presence of PLE is associated with psychiatric disorders and with impaired quality of life in all age groups.


On the specificity of antibody/antigen interactions: phosphocholine binding to McPC603 and the correlation of three-dimensional structure and sequence data.
Refined three-dimensional structures of McPC603 Fab and the complex with phosphocholine permit a detailed assessment of the residues crucial to determining the antibody specificity. Correlation with sequence data suggests that the structure of the binding site is highly conserved in immunoglobulins with phosphocholine-binding specificity. There is suggestive evidence that coupling of somatic mutations occurs to preserve antigen-binding specificity. The immune response is characterized by specificity and diversity. While each antibody appears to be specific for a single antigen, the immune response can generate up to 10(9) different specificities. In order to understand, at the molecular level, the nature of the interaction between antibody and antigen, it is necessary to have a high-resolution three-dimensional picture of the complex. Today it is possible to investigate antibody/antigen interactions directly by the crystallographic analysis of hybridoma products [5, 10]; in the past, structural studies were limited to myeloma proteins which, in some cases, could be shown to complex to certain haptens. Of the four Fab structures that have been determined by X-ray diffraction, only two have been demonstrated to bind hapten in the crystal. They are Fab NEW, which was shown to bind a vitamin K1 derivative [1] and McPC603, which binds to phosphocholine [6,9]. During the last few years, the McPC603 Fab structure has been refined at 2.7 A resolution and the complex of McPC603 Fab with phosphocholine has been refined independently at 3.1 A. In this communication, we make a comparative analysis of the sequences of a number of mouse phosphocholine-binding immunoglobulins based on the refined structure of the phosphocholine-binding site in McPC603.


Lifelong opioidergic vulnerability through early life separation: a recent extension of the false suffocation alarm theory of panic disorder.
The present paper is the edited version of our presentations at the "First World Symposium On Translational Models Of Panic Disorder", in Vitoria, E.S., Brazil, on November 16-18, 2012. We also review relevant work that appeared after the conference. Suffocation-False Alarm Theory (Klein, 1993) postulates the existence of an evolved physiologic suffocation alarm system that monitors information about potential suffocation. Panic attacks maladaptively occur when the alarm is erroneously triggered. The expanded Suffocation-False Alarm Theory (Preter and Klein, 2008) hypothesizes that endogenous opioidergic dysregulation may underlie the respiratory pathophysiology and suffocation sensitivity in panic disorder. Opioidergic dysregulation increases sensitivity to CO2, separation distress and panic attacks. That sudden loss, bereavement and childhood separation anxiety are also antecedents of "spontaneous" panic requires an integrative explanation. Our work unveiling the lifelong endogenous opioid system impairing effects of childhood parental loss (CPL) and parental separation in non-ill, normal adults opens a new experimental, investigatory area.


Nanoparticle transport phenomena in confined flows.
Nanoparticles submerged in confined flow fields occur in several technological applications involving heat and mass transfer in nanoscale systems. Describing the transport with nanoparticles in confined flows poses additional challenges due to the coupling between the thermal effects and fluid forces. Here, we focus on the relevant literature related to Brownian motion, hydrodynamic interactions and transport associated with nanoparticles in confined flows. We review the literature on the several techniques that are based on the principles of non-equilibrium statistical mechanics and computational fluid dynamics in order to simultaneously preserve the fluctuation-dissipation relationship and the prevailing hydrodynamic correlations. Through a review of select examples, we discuss the treatments of the temporal dynamics from the colloidal scales to the molecular scales pertaining to nanoscale fluid dynamics and heat transfer. As evident from this review, there, indeed has been little progress made in regard to the accurate modeling of heat transport in nanofluids flowing in confined geometries such as tubes. Therefore the associated mechanisms with such processes remain unexplained. This review has revealed that the information available in open literature on the transport properties of nanofluids is often contradictory and confusing. It has been very difficult to draw definitive conclusions. The quality of work reported on this topic is non-uniform. A significant portion of this review pertains to the treatment of the fluid dynamic aspects of the nanoparticle transport problem. By simultaneously treating the energy transport in ways discussed in this review as related to momentum transport, the ultimate goal of understanding nanoscale heat transport in confined flows may be achieved.


Low doses of eicosapentaenoic acid, docosahexaenoic acid, and hypolipidemic eicosapentaenoic acid derivatives have no effect on lipid peroxidation in plasma.
It was of interest to investigate the influence of both high doses of eicosapentaenoic acid (EPA) and low doses of 2- or 3-methylated EPA on the antioxidant status, as they all cause hypolipidemia, but the dose required is quite different. We fed low doses (250 mg/d/kg body wt) of different EPA derivatives or high doses (1500 mg/d/kg body wt) of EPA and DHA to rats for 5 and 7 d, respectively. The most potent hypolipidemic EPA derivative, 2,2-dimethyl-EPA, did not change the malondialdehyde content in liver or plasma. Plasma vitamin E decreased only after supplementation of those EPA derivatives that caused the greatest increase in the fatty acyl-CoA oxidase activity. Fatty acyl-CoA oxidase activity increased after administration of both EPA and DHA at high doses. High doses of EPA and DHA decreased plasma vitamin E content, whereas only DHA elevated lipid peroxidation. In liver, however, both EPA and DHA increased lipid peroxidation, but the hepatic level of vitamin E was unchanged. The glutathione-requiring enzymes and the glutathione level were unaffected, and no significant changes in the activities of xanthine oxidase and superoxide dismutase were observed in either low- or high-dose experiments. In conclusion, increased peroxisomal beta-oxidation in combination with high amounts of polyunsaturated fatty acids caused elevated lipid peroxidation. At low doses of polyunsaturated fatty acids, lipid peroxidation was unchanged, in spite of increased peroxisomal beta-oxidation, indicating that polyunsaturation is the most important factor for lipid peroxidation.


A Call for Transformation: Moving Away from Coercive Measures in Mental Health Care.
Coercion is common practice in mental health care [...].


Comparison-induced decoy effects.
Extant theories of decoy effects on evaluations of attribute values were assessed with respect to their ability to account for a one-dimensional analogue of the asymmetric dominance effect. Parducci's (1965, 1995) range-frequency theory, Krumhansl's (1978) distance-density model, Tversky's (1977) diagnosticity principle, and reference point theories (e.g., Holyoak & Mah, 1982) were unable to account for this effect. One version of Helson's (1964) adaptation-level theory and our comparison-induced distortion theory (Choplin & Hummel, 2002) were able to account for the qualitative effect. Quantitative fits revealed that comparison-induced distortion theory provides a better account of this effect than does adaptation-level theory. These results suggest that, in some cases, biases created by language-expressible magnitude comparisons mediate the effects of decoys on evaluation.


A chlorzoxazone-folic acid combination improves cognitive affective decline in SCA2-58Q mice.
Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder caused by a pathological expansion of CAG repeats in ATXN2 gene. SCA2 is accompanied by cerebellar degeneration and progressive motor decline. Cerebellar Purkinje cells (PCs) seem to be primarily affected in this disorder. The majority of the ataxia research is focused on the motor decline observed in ataxic patients and animal models of the disease. However, recent evidence from patients and ataxic mice suggests that SCA2 can also share the symptoms of the cerebellar cognitive affective syndrome. We previously reported that SCA2-58Q PC-specific transgenic mice exhibit anxiolytic behavior, decline in spatial memory, and a depressive-like state. Here we studied the effect of the activation of the small conductance calcium-activated potassium channels (SK channels) by chlorzoxazone (CHZ) combined with the folic acid (FA) on the PC firing and also motor, cognitive and affective symptoms in SCA2-58Q mice. We realized that CHZ-FA combination improved motor and cognitive decline as well as ameliorated mood alterations in SCA2-58Q mice without affecting the firing rate of their cerebellar PCs. Our results support the idea of the combination therapy for both ataxia and non-motor symptoms in ataxic mice without affecting the firing frequency of PCs.


Enzastaurin: A lesson in drug development.
Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. It was initially developed as an isozyme specific inhibitor of protein kinase Cβ (PKCβ), which is involved in both the AKT and MAPK signalling pathways that are active in many cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. In this review, we will discuss the development of enzastaurin from drug design to clinical testing, exploring target identification, validation and preclinical assessment. Finally, we will consider the clinical evaluation of enzastaurin as an example of the challenges associated with drug development. In particular, we discuss the poor translation of drug efficacy from preclinical animal models, inappropriate end point analysis, limited standards in phase I clinical trials, insufficient use of biomarker analysis and also patient stratification, all of which contributed to the failure to achieve approval of enzastaurin as an anticancer therapeutic.


[Computerized tomography in finding tumours in the orbit and in the base of the skull (author's transl)].
Two cases of tumours - a pleomorphic poorly differentiated malignant neoplasm and a juvenile angiofibroma - involving the orbit and extending to the base of the skull are reported. In both cases computerized tomography showed with great precision the localization and the extension of the tumours.


Spaced education and student learning: Results from a medical school.
It is critical for medical students to retain and apply their knowledge of basic sciences to become competent prescribing physicians. Poor long-term retention is a pervasive concern. We investigated the impact of 'spaced education' teaching modules to improve knowledge retention in medical students on a topic of public health: vitamin D and its role in health and disease. It is critical for medical students to retain and apply their knowledge of basic sciences to become competent prescribing physicians METHODS: In a self-matched design, 148 medical students were randomised and evaluated on vitamin D-related topics to assess reinforced and non-reinforced knowledge in a multiple-choice question format. Initial learning and long-term retention were assessed with an estimation of Cohen's effect size at 24 and 72 weeks, respectively. The administration of spaced educational material significantly improved composite formative test scores at 24 weeks (p < 0.001, effect size = 1.33). Although the scores dipped, there was a retention of knowledge at 72 weeks (effect size = 0.48). Spaced reinforcement and testing statistically improved knowledge retention among our medical students. Gaps in the present teaching could be bridged by motivating the students to extend their learning time by appropriate spacing intervals and to understand the relevance of course content in different scenarios as a physician. Further research could be instrumental in optimising interventions to enhance learning opportunities for medical students.


Computer-Generated Radiographic Measurements of Distal Radius Fractures: Does It Help With Decision Making?
Operative management of distal radius fractures (DRFs) has become increasingly common. Age, activity levels, and comorbid conditions are major factors influencing the treatment decision, although operative indications are still controversial. Radiographic parameters (RPs), such as radial inclination, dorsal tilt, and articular step-off, can provide objective support for effective decision making. However, manual measurement of RPs may be imprecise and subject to inconsistency. To address this problem, we developed custom software of an algorithm to automatically detect and compute 6 common RPs associated with DRF in anteroposterior and lateral radiographs. The aim in this study was to assess the effect of this software on radiographic interobserver variability among orthopedic surgeons. Our hypothesis was that precise and consistent measurement of RPs will improve radiographic interpretation variability among surgeons and, consequently, may aid in clinical decision making. Thirty-five radiograph series of DRFs were presented to 9 fellowship-trained hand and orthopedic trauma surgeons. Each case was presented with basic clinical information, together with plain anteroposterior and lateral radiographs. One of the 2 possible treatment options was selected: casting or open reduction with a locking plate. The survey was repeated 3 weeks later, this time with computer-generated RP measurements. Data were analyzed for interobserver and intraobserver variability for both surveys, and the interclass coefficient, kappa value, was calculated. The interobserver reliability (interclass coefficient value) improved from poor to moderate, 0.35 to 0.50, with the provided RP. The average intraobserver interclass coefficient was 0.68. When participants were assessed separately according to their subspecialties (trauma and hand), improved interobserver variability was found as well. Providing computed RPs to orthopedic surgeons may improve the consistency of the radiographic judgment and influence their clinical decision for the treatment of DRFs. Orthopedic surgeons' consistency in the radiographic judgment of DRFs slightly improved by providing automatically calculated radiographic measurements to them.


Are plant factors a missing link in the evolution of endemic Burkitt's lymphoma?
Burkitt's lymphoma, an Epstein-Barr virus (EBV)-associated non-Hodgkin's malignant lymphoma is endemic in an area of Africa known as the Lymphoma Belt. This zone is demarcated by climatic requirements of temperature and rainfall. EBV-activating plant factors are among several co-factors which have been proposed for the development of epidemic Burkitt's Lymphoma (eBL). The distribution of Euphorbia tirucalli, a plant which possesses EBV-activating substances and can induce the characteristic 8:14 translocation of eBL in EBV-infected lymphoblastic cell lines in vitro, conforms closely to the climatic requirements of the Lymphoma. This plant, other EBV-activating plants and plants of unknown EBV-activating status with medicinal uses, are found significantly more often at the homes of eBL patients in Malawi than in those of controls. The possible role of these plant factors in the pathogenesis of eBL and their routes of bodily access are discussed. It is postulated that the associations described in this paper provide support for the theory that EBV-activating plants are co-factors involved in the pathogenesis of some cases of eBL.


Recovery of Shoulder Rotational Muscle Strength After Arthroscopic Bankart Repair.
Shoulder rotational muscles act as dynamic stabilizers of the glenohumeral joint, and the recovery of muscle strength plays an important role in stabilizing the joint during postoperative rehabilitation. However, temporal changes in muscle strength after arthroscopic Bankart repair have not been clarified. To better understand the temporal recovery of shoulder rotational muscle strength after arthroscopic Bankart repair. Case series; Level of evidence, 4. Isokinetic concentric shoulder rotational muscle strength was evaluated in 50 patients who were diagnosed with recurrent dislocations of the glenohumeral joint and treated with arthroscopic Bankart repair. The mean peak torque/weight and total work were reduced significantly at 1.5 months after surgery (P < .0001) and returned to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation. The contralateral peak torque ratios reached preoperative levels by 6 months after surgery. The ipsilateral peak torque ratios were reduced between 1.5 and 3 months after surgery and returned to preoperative levels at 6 months for external rotation and 4.5 months for internal rotation. Isokinetic shoulder rotational muscle strength after arthroscopic Bankart repair recovered to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation.


Untapping host-targeting cross-protective efficacy of anticoagulants against SARS-CoV-2.
Responding quickly to emerging respiratory viruses, such as SARS-CoV-2 the causative agent of coronavirus disease 2019 (COVID-19) pandemic, is essential to stop uncontrolled spread of these pathogens and mitigate their socio-economic impact globally. This can be achieved through drug repurposing, which tackles inherent time- and resource-consuming processes associated with conventional drug discovery and development. In this review, we examine key preclinical and clinical therapeutic and prophylactic approaches that have been applied for treatment of SARS-CoV-2 infection. We break these strategies down into virus- versus host-targeting and discuss their reported efficacy, advantages, and disadvantages. Importantly, we highlight emerging evidence on application of host serine protease-inhibiting anticoagulants, such as nafamostat mesylate, as a potentially powerful therapy to inhibit virus activation and offer cross-protection against multiple strains of coronavirus, lower inflammatory response independent of its antiviral effect, and modulate clotting problems seen in COVID-19 pneumonia.


Thromboxane A2 analogue (U-46619) stimulates vascular PGI2 synthesis.
Since platelet release reaction products (e.g. serotonin, ADP) stimulate prostacyclin (PGI2) release in vitro, we have investigated whether thromboxane A2 (TXA2) also has a similar effect. An analogue, U-46619, was used for the experiments, since TXA2 is extremely unstable. U-46619 stimulated rat aortic PGI2 release; this stimulation was abolished by (a) EDTA and (b) verapamil. We conclude that TXA2 is a calcium-dependent stimulator of PGI2 release; this property may be relevant to the limitation of platelet aggregates in vivo and to vascular injury.


A bcl-xS adenovirus selectively induces apoptosis in transformed cells compared to normal mammary cells.
Oncogenes which drive the cell cycle, such as c-myc, can sensitize cells to apoptosis. This suggests the possibility that the expression of genes such as bcl-2 or bcl-xL is required to inhibit apoptosis induced by oncogene expression. We hypothesized that inhibition of Bcl-2/Bcl-xL by the pro-apoptotic Bcl-xS protein, would result in selective induction of apoptosis in mammary carcinoma cells compared to their nontransformed counterparts. Therefore, we compared the effects of Bcl-xS expression delivered by a bcl-xS adenovirus (bcl-xS-Adv) vector, on viability and apoptosis of nontransformed versus transformed mammary epithelial cells. We report that c-myc-transformed murine mammary cells are extremely sensitive to apoptosis induced by the bcl-xS adenovirus (bcl-xS-Adv) vector, whereas immortalized, nontransformed murine mammary cells are relatively resistant to apoptosis induced by this vector. Likewise, human mammary epithelial cells transduced with c-erbB-2 were more sensitive to apoptosis induced by the bcl-xS vector than the nontransformed parental cells. Similar results were obtained when we tested the effects of bcl-xS adenoviral infection on primary normal human mammary epithelial cells and SUM-190 PT cells, (a c-erbB-2 over-expressing human mammary carcinoma cell line) grown on Matrigel. These data are consistent with the hypothesis that inhibition of Bcl-2/Bcl-xL can result in selective killing of cancer cells compared to their nontransformed counterparts.


Evaluation of surgical strategy of conventional vs. percutaneous robot-assisted spinal trans-pedicular instrumentation in spondylodiscitis.
Robot-assisted percutaneous insertion of pedicle screws is a recent technique demonstrating high accuracy. The optimal treatment for spondylodiscitis is still a matter of debate. We performed a retrospective cohort study on surgical patients treated with pedicle screw/rod placement alone without the application of intervertebral cages. In this collective, we compare conventional open to a further minimalized percutaneous robot-assisted spinal instrumentation, avoiding a direct contact of implants and infectious focus. 90 records and CT scans of patients treated by dorsal transpedicular instrumentation of the infected segments with and without decompression and antibiotic therapy were analysed for clinical and radiological outcome parameters. 24 patients were treated by free-hand fluoroscopy-guided surgery (121 screws), and 66 patients were treated by percutaneous robot-assisted spinal instrumentation (341 screws). Accurate screw placement was confirmed in 90 % of robot-assisted and 73.5 % of free-hand placed screws. Implant revision due to misplacement was necessary in 4.95 % of the free-hand group compared to 0.58 % in the robot-assisted group. The average intraoperative X-ray exposure per case was 0.94 ± 1.04 min in the free-hand group vs. 0.4 ± 0.16 min in the percutaneous group (p = 0.000). Intraoperative adverse events were observed in 12.5 % of free-hand placed pedicle screws and 6.1 % of robot robot-assisted screws. The mean postoperative hospital stay in the free-hand group was 18.1 ± 12.9 days, and in percutaneous group, 13.8 ± 5.6 days (p = 0.012). This study demonstrates that the robot-guided insertion of pedicle screws is a safe and effective procedure in lumbar and thoracic spondylodiscitis with higher accuracy of implant placement, lower radiation dose, and decreased complication rates. Percutaneous spinal dorsal instrumentation seems to be sufficient to treat lumbar and thoracic spondylodiscitis.


Real-World Treatment Patterns and Economic Burden Following First-Line Trastuzumab in Patients with Metastatic Gastric Cancer in the USA.
Trastuzumab in combination with chemotherapy is the standard first-line (1L) treatment for HER2+ metastatic gastric cancer (mGC) in the USA. This study characterizes the real-world treatment patterns, healthcare resource use (HRU), and costs in patients with HER2+ mGC post-1L trastuzumab before approval of fam-trastuzumab deruxtecan-nxki. This retrospective study used the IQVIA PharMetrics® Plus Database (October 2014-September 2019) to identify adults with HER2+ mGC who discontinued trastuzumab-based regimens in 1L. Patient characteristics, second-line (2L) treatment patterns, and treatment duration were summarized. HRU and costs before and after discontinuation of 1L trastuzumab-based regimens as well as during 2L treatment were described. Of the 190 HER2+mGC patients who discontinued 1L trastuzumab-based regimens, 136 (71.58%) initiated 2L treatments. Trastuzumab-based regimens were the most common in 2L (50.74%), followed by ramucirumab + paclitaxel (19.85%). The median time to 2L discontinuation was 2.37 months. During a mean follow-up of 9.8 months, mean per-patient-per-month (PPPM) healthcare costs post-1L trastuzumab-based regimens were higher in patients receiving 2L treatment than those without subsequent treatment (US$25,178 vs. US$14,812). The mean PPPM cost during 2L treatment was US$30,838, primarily driven by outpatient infusion costs (US$22,262). The short duration of 2L treatment observed in this study is consistent with a lack of effective treatments post-1L trastuzumab prior to 2020. Re-use of trastuzumab treatment was common despite its limited efficacy and high treatment cost. The findings highlight the unmet medical needs and substantial burden faced by patients with HER2 +mGC previously treated with trastuzumab.


Human health risk assessment and geochemical mobility of rare earth elements in Amazon soils.
Rare earth elements (REEs) are a grouping of elements that encompasses lanthanides, yttrium and scandium due to their similar chemical properties and occurrence in ore deposits. Over the past few decades, economic interest in REEs has increased due to their use in several types of industries such as high-tech, medicine and agriculture. Extraction of REEs has been followed, in general, by incorrect disposal of tailing and waste, creating hazardous conditions in several countries. However, the magnitude of the possible impacts on ecosystem and human health are relatively unknown, especially in tropical systems. Thus, the objectives of this study were to assess the geochemical mobility and the bioaccessibility of REEs based on a series of chemical extractions and in vitro essay. We also tested two promising simple protocols (0.01 mol L-1 CaCl2 and 0.43 mol L-1 HNO3) for measuring REE bioaccessible fractions through a single extraction. Our findings show that the bioavailable fractions represent less than 20% of the ΣREEs fraction in all soil samples examine. Similarly, the oral bioaccessibility obtained by two in vitro methods (Gastric protocol and Gastric-Intestinal protocol) and by the single extraction tests represented less than 20% of the ΣREE contents. The non-carcinogenic risks and the carcinogenic risks associated to REEs oral exposure were low for children and adults. The extractions with 0.01 mol L-1 CaCl2 showed great potential as a method for measuring the REEs bioaccessible fraction.


Multiscale analysis on spatiotemporal dynamics of energy consumption CO2 emissions in China: Utilizing the integrated of DMSP-OLS and NPP-VIIRS nighttime light datasets.
CO2 emissions caused by socioeconomic development and energy consumption in China have put enormous pressure on emissions reduction for Chinese government. In response to CO2 emissions reduction in China, this study integrated the Defense Meteorological Satellite Program's Operational Linescan System (DMSP-OLS) stable nighttime light (SNL) data and Suomi National Polar-orbiting Partnership (NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) composite data, and established the integrated nighttime light datasets from 1992 to 2016. The estimated CO2 emissions model utilizing the integrated nighttime light datasets and statistical CO2 emissions at the provincial level from 1995 to 2016 were established. Finally, spatiotemporal dynamics of CO2 emissions were simulated from multiscale. The results clearly showed that: (1) The fitting results of regression relationship between DMSP-OLS SNL data and NPP-VIIRS composite data met the accuracy requirements. The CO2 emissions estimated model was valid. (2) The total amount of energy consumption CO2 emissions in China had increased from 1889.3340 Mt in 1995 to 4683.3165 Mt in 2016, with a total growth of 2.47 times. (3) The high CO2 emissions regions were clearly agglomerated in eastern coastal China from the pixel scale, the highest CO2 emissions provinces were concentrated in Hebei and Shandong, the high CO2 emissions prefecture cities were concentrated in Around Bohai Gulf area, eastern coastal China and some developed cities, and the high CO2 emissions counties were concentrated in eastern coastal China and western energy intensive counties. (4) The relatively-slow growth accounted for the highest proportion among the five growth types, and the CO2 emissions rapid growth regions were concentrated in eastern China at provincial, prefectural and county scale. The western regions accounted for the largest area proportion in five growth types at prefectural scale. We provided policy implications based on the results, which was beneficial to propose mitigation CO2 emissions reduction in China.


On the possible adaptive value of coprophagy in free-ranging chimpanzees.
Coprophagy occurred during major periods of feeding on fruits of Dialium spp. (Caesalpiniaceae) in a group of orphaned chimpanzees released in Conkouati Douli National Park, Republic of Congo. Since stress, boredom or food scarcity could not explain coprophagy according to our daily behavioral and veterinary control observations, we suggest that Dialium seeds were the item of interest in the feces. Two types of Dialium seeds were commonly found in the feces after chimpanzees swallowed the mesocarp and whole seeds together. These seeds were either whole and hard or whole/broken and soft imbibed. A mechanical and/or chemical effect of the gut passage may enable the chimpanzees to chew and ingest the seeds, thus providing nutritional intake.


Thrombocytopathy due to a defect of the platelet membrane complex.
A new type of primary thrombocytopathy is described. Three main alterations were found: (1) a defect of the aggregation reaction with ADP, epinephrine and collagen and a normal response to ristocetin and arachidonic acid; (2) a moderate deficiency of platelet procoagulant activity, and (3) a combined hypertrophy of the two membrane systems of the platelet--the open canalicular and the dense tubular. The latter defect is shown as an abnormal membrane complex situated on one of the platelet poles. This thrombocytopathy is discussed as a new variety of primary platelet disorder.


ZEB1-Mediated Transcriptional Upregulation of circWWC3 Promotes Breast Cancer Progression through Activating Ras Signaling Pathway.
Zinc finger E-box binding homeobox 1 (ZEB1) has been widely recognized as an important driver of tumor growth and metastasis. However, nothing is known about ZEB1-regulated circular (circ)RNAs in cancer. In the current study, we evaluated the function of a novel ZEB1-regulated circRNA derived from the WWC3 gene locus, circWWC3 in breast cancer progression. We found that ZEB1 upregulated circWWC3 expression but not the linear WWC3 mRNA expression. circWWC3 is highly expressed in breast cancer tissues and is associated with the poor prognosis of breast cancer patients. Silencing of circWWC3 significantly suppresses the proliferation, migration, and invasion of breast cancer cells. Mechanically, circWWC3 upregulates multiple oncogenes' expression of the Ras signaling pathway through acting as the sponge of microRNA (miR)-26b-3p and miR-660-3p. Moreover, short hairpin (sh)RNA-mediated knockdown of circWWC3 partially antagonized ZEB1-mediated breast cancer growth and metastasis in vivo. Our findings reveal that ZEB1-mediated upregulation of circWWC3 promotes breast cancer progression through activating Ras signaling pathway, which provides a potential therapeutic target and prognostic biomarker for breast cancer.


Telomerase: its clinical relevance in the diagnosis of bladder cancer.
More than 50 years ago, Papanicolaou recognized the importance of a non-invasive technique for the diagnosis and follow-up of patients with carcinoma of the urinary bladder. Cystoscopy, however, has remained the 'gold standard' since no currently available non-invasive method can compete with cystoscopy's sensitivity and specificity. The detection of the ribonucleoprotein telomerase or the telomerase subunits human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in urine samples offer new diagnostic perspectives. The present article presents a review of publications in the literature and evaluates their clinical relevance. The experimental studies reported to date are very promising and show that telomerase exactly fulfils the requirements for a good diagnostic marker for carcinoma of the urinary bladder. The diagnostic application remains in an experimental stage and telomerase is still several steps away for routine use as a clinical parameter. The remaining steps leading to its routine clinical application will be discussed.


MBL2 single nucleotide polymorphism diversity among four ethnic groups as revealed by a bead-based liquid array profiling.
In the present work we established a rapid, cost-effective and high-throughput method for genotyping using a multiplexed microsphere-based suspension array platform - Luminex xMAP which enabled us to analyze 3 SNPs in the MBL2 gene promoter and 5' UTR, and 3 coding SNPs exon 1 haplotypes, associated with different levels of MBL2 expression. Using this system MBL2 diversity in four different ethnic groups, namely, Asian (Japanese), Caucasian, Hispanic and African-American-assessed. Results showed significant variability in terms of allele, genotype, and haplotype distribution. Characteristic MBL haplotype patterns were defined for each ethnic group. A prevalence of haplotypes coding functional proteins capable of complement activation and pathogen opsonization was observed. Regardless of the significant diversity of individual haplotypes, a high, almost similar (25-28%) proportion of haplotypes associated with MBL deficiency was found in the four ethic groups. The proportion of individuals homozygous for the haplotypes resulting in complete MBL2 deficiency was also significant (2-10%). Considering the role of MBL2 in innate immunity and as a clinically relevant marker, the genotyping approach developed and the knowledge of the genetic variation in different ethnic groups will be relevant to future medical genetic studies.


Survival Prediction After Transarterial Chemoembolization for Hepatocellular Carcinoma: a Deep Multitask Survival Analysis Approach.
The accurate prediction of postoperative survival time of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is important for postoperative health care. Survival analysis is a common method used to predict the occurrence time of events of interest in the medical field. At present, the mainstream survival analysis models, such as the Cox proportional risk model, should make strict assumptions about the potential random process to solve the censored data, thus potentially limiting their application in clinical practice. In this paper, we propose a novel deep multitask survival model (DMSM) to analyze HCC survival data. Specifically, DMSM transforms the traditional survival time prediction problem of patients with HCC into a survival probability prediction problem at multiple time points and applies entropy regularization and ranking loss to optimize a multitask neural network. Compared with the traditional methods of deleting censored data and strong hypothesis, DMSM makes full use of all the information in the censored data but does not need to make any assumption. In addition, we identify the risk factors affecting the prognosis of patients with HCC and visualize the importance of ranking these factors. On the basis of the analysis of a real dataset of patients with BCLC stage B HCC, experimental results on three different validation datasets show that the DMSM achieves competitive performance with concordance index of 0.779, 0.727, and 0.780 and integrated Brier score (IBS) of 0.172, 0.138, and 0.135, respectively. Our DMSM has a comparatively small standard deviation (0.002, 0.002, and 0.003) for IBS of bootstrapping 100 times. The DMSM we proposed can be utilized as an effective survival analysis model and provide an important means for the accurate prediction of postoperative survival time of patients with BCLC stage B HCC.


Prevalence, knowledge, and lifestyle-associated risk factors of dyslipidemia among Ghanaian type-2 diabetes mellitus patients in rural and urban areas: A multicenter cross-sectional study.
Dyslipidemia in diabetes mellitus has been linked to unhealthy lifestyle and bad eating habits. However, this association has not been well studied among rural and urban Ghanaian populations. In this study, we determined the prevalence, knowledge, and lifestyle-associated risk factors of dyslipidemia among Ghanaian type-2 diabetes mellitus (T2DM) patients in rural and urban areas. This comparative multicentre-cross-sectional study recruited 228 T2DM outpatients attending the St. Michael Hospital, Pramso (rural) and Kumasi South Regional Hospital (urban), Ghana for routine check-ups. Self-structured questionnaire was used to collect sociodemographic, knowledge, and lifestyle characteristics. Fasting blood samples were taken to measure lipid profiles. Dyslipidemia was defined per the American Diabetes Association criteria. All p < 0.05 were considered statistically significant. The overall prevalence of dyslipidemia was 79/228 (34.7%). Dyslipidemia was more prevalent among urban participants 43 (18.9%) than rural participants 36 (15.8%). Twenty-seven (11.7%) had adequate knowledge about the risk factors, complications, and management of diabetes. Eating supper after 7 p.m. [adjusted odds ratio = 3.77, 95% confidence interval (1.70-8.37), p = 0.001] significantly increased one's risk of having dyslipidemia by 3.8-fold compared to eating supper earlier (before 5 p.m.). Dyslipidemia is increasing among T2DM patients in both urban and rural areas and it's independently influenced by eating supper after 7 p.m. Most participants were ignorant of the risk factors, complications, and management of diabetes. Adjusting eating habits and increasing diabetes awareness programs to sensitize the general public can mitigate the increasing prevalence of dyslipidemia in both urban and rural areas.


Levels of mannose-binding lectin (MBL) associates with sepsis-related in-hospital mortality in women.
Mannose-binding lectin (MBL) mediates the innate immune response either through direct opsonisation of microorganisms or through activation of the complement system. There are conflicting data whether MBL deficiency leads to increased susceptibility to infections or not. The aim of this study was to determine if low levels of mannose-binding lectin (MBL) predict sepsis development, sepsis severity and outcome from severe sepsis or septic shock. Patients aged 18 years or more with documented sepsis within 24 h after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Plasma levels MBL were determined in stored samples from health surveys (baseline) and from ICU admission (acute phase). The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined with 1300 ng/mL as cut-off for low levels. We identified 148 patients (61.5% women) with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 122 also had samples from the acute septic phase. Both high MBL levels in the acute phase (odds ratio [95% confidence interval]) (2.84 [1.20-6.26]), and an increase in MBL levels from baseline to the acute phase (3.76 [1.21-11.72]) were associated with increased risk for in-hospital death in women, but not in men (0.47 [0.11-2.06]). Baseline MBL levels did not predict future sepsis, sepsis severity or in-hospital mortality. An increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.


Shigella flexneri bacteraemia.
Shigellosis is usually a non-invasive enteric disease, rarely accompanied by extra-intestinal manifestations. Shigella septicaemia is therefore reported in a child aged 10 months. In the laboratory the organism was resistant to ampicillin and only moderately susceptible to chloramphenicol. The patient responded well to cotrimoxazole to which the organism isolated was susceptible in vitro. We recommend that blood as well as faeces should be cultured in exceptionally ill patients with suspected or otherwise confirmed shigella infection.


Improved method for obtaining streptomycin-dependent mutants from Pasteurella multocida and Pasteurella haemolytica, using N-methyl-N'-nitro-N-nitrosoguanidine.
N-Methyl-N'-nitro-N-nitrosoguanidine was used in a modified and improved procedure to obtain streptomycin-dependent mutants of type A Pasteurella multocida and type 1 Pasteurella haemolytica. The relative virulence of these mutants was determined by mouse inoculation with and without streptomycin.


Methods of determing biokinetics of arsenate accumulation and release in Microcystis aeruginosa regulated by common environmental factors: Practical implications for enhanced bioremediation.
Only little information is available on combined effects of abiotic environmental factors on algal arsenate (AsV ) metabolic biokinetics. Herein, we demonstrated the methods of using the Taguchi statistical method to investigate four environmental factors including AsV , nitrate (N), orthophosphate (P) and pH for their combined effects on algal growth and arsenic (As) uptake but also extracellular adsorption of Microcystis aeruginosa, as well as As release from dead algal cells. Results showed that an increase of N facilitated M. aeruginosa growth and thus was the principal factor for the algal maximum specific growth rate ( μmax ). P was vital to AsV bioconcentration factor (BCF) and As partition coefficients (LogKd ) released from deal algal cells. AsV impacted the extracellular As adsorption onto the algal cells, which thereby increased with increasing initial AsV level. The initial pH had an imperative effect on the AsV uptake (ku ) and release rate (Ke ) from the dead cells. Collectively, the condition of low P, high N and alkaline pH level was favorable to As accumulation rate of living cells and restrictive to As release rate from dead cells of M. aeruginosa. The obtained information can pave a road for extensive understanding on efficient utilization of As bioremediation of algae in practical environment. •Principal factors were identified on AsV metabolic biokinetics by Taguchi method.•High N and pH but low P fasten AsV uptake and reduce As efflux from dead cells.•AsV only as the main factor impacted As extracellular adsorption on algal cells.


Copper-catalyzed oxidative C(sp3)-H/C(sp2)-H cross-coupling en route to carbocyclic rings.
Copper-catalyzed selective coupling of C(sp3)-H bonds with C(sp2)-H bonds has been developed. An aniline module was used as a directing group to generate an aminyl radical, which selectively cleaves the secondary and tertiary C(sp3)-H bonds via a 1,5-HAT process to forge six-membered carbocyclic rings.


Influence of cold soil and snowcover on photosynthesis and leaf conductance in two Rocky Mountain conifers.
The influence of cold soil and snowcover on photosynthesis and conductance of Picea engelmannii and Pinus contorta was investigated early in the growing season in the Medicine Bow Mountains, Wyoming, USA. Trees of both species growing in cold soil (<1°C) associated with snowpack had 25-40% lower leaf photosynthesis than trees in warm soils (>10°C). In cold soils leaf conductance of both species was lower, but more so in Pinus, leading to lower intercellular CO2 concentrations and greater stomatal limitation of photosynthesis. Soil temperature had no effect on predawn and midday shoot water potentials of Pinus and Picea and lower photosynthesis and conductance did not appear to be a result of lower bulk shoot water potential. Predawn, as well as midday, water potentials of Pinus were consistently higher than Picea suggesting that Pinus may have deeper roots, although trenching experiments indicated young Picea trees have more extensive lateral root systems than similar sized Pinus trees. Young Picea trees (<2 m in height) in snowbanks were capable of utilizing warmer soil 4 m from their base. Under similar conditions Pinus in snowbanks had lower photosynthesis and conductance than controls and Pinus did not appear capable of utilizing warmer soils nearby. Under full sunlight, PPFD reflected from the snow surface was 400-1400 μmol m-2 s-1 higher than from snow-free surfaces. This reflected light resulted in a 10%-20% increase in photosynthesis of Picea. The beneficial effect of reflected light was apparent whether or not photosynthesis was reduced by low soil temperatures.


Mechanism and quantitative contribution of the pentose pathway to the glucose metabolism of Morris hepatoma 5123C.
An investigation of the mechanism and quantitative contribution of the pentose phosphate pathway in the glucose metabolism of Morris Hepatoma 5123C is reported. Morris Hepatoma 5123C has an active non-oxidative segment of pentose pathway as judged by its ability to convert ribose 5-P to hexose 6-P in a standard assay. Based on compliance with qualitative and quantitative criteria, the cells exhibit the L-type pentose pathway reaction sequence rather than the F-type pathway. This compliance included the formation of intermediates characteristic of the L-type pathway, namely arabinose 5-P, octulose mono- and bisphosphates and sedoheptulose 1,7-bisphosphate, during the dissimilation of ribose 5-P to hexose 6-P. The intermediary role of arabinose 5-P was suggested by the incorporation of its carbon into various intermediates and products of the pentose pathway. Intermediary roles for ido octulose mono- and bisphosphates were supported by their participation in the reaction catalyzed by the phosphotransferase enzyme of the L-type pentose pathway. Presence of L-type PP reactions was further affirmed by 14C-prediction labelling experiments using [5-14C]- and [2-14C]glucose as specifically labelled substrates. Using two methods of measurement, the F-type pentose cycle made a negligibly small contribution to glucose metabolism, while the measured value of the L-type pentose pathway accounted for 30% (approx.) of the total glucose metabolism of these cells, a value consistent with the high activity of the enzymes of the L-type pentose pathway in Morris Hepatoma 5123C cells and the very high activity of the non-oxidative segment of the pathway in vitro. The findings validate the proposal that the L-type pentose pathway reactions constitute the non-oxidative segment of the pathway in Morris Hepatoma 5123C cells. Reasons involving pyruvate recycling reactions show why there is low incorporation of 14C-isotope in C-1 of glucose 6-P, when [4,5,6-14C]glucose and [6-14C]glucose are L-type PP test substrates in intact cells.


Stem cell factor inhibition reduces Th2 inflammation and cellular infiltration in a mouse model of eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is a T helper (Th)2-mediated inflammatory disorder characterized endoscopically by eosinophilic infiltration leading to fibrosis of the esophagus. Stem cell factor (SCF), a multifunctional cytokine, is upregulated in several allergic diseases, including in patients with EoE. Mast cells and eosinophils express c-kit, the cell surface receptor for SCF, and have been found to play an important role in EoE. Therefore, we investigated whether blocking SCF represents a potential therapeutic approach for EoE. Esophageal inflammation was induced in mice using peanut allergen. In mice with experimental EoE, we found that SCF was upregulated in the esophageal tissue. In EoE mice injected with a polyclonal antibody specific for SCF, we observed a decrease in both mast cells and eosinophils by histological and flow cytometric analysis. Furthermore, Th2 cytokines in the esophagus were decreased in anti-SCF treated mice, as were levels of Th2 cytokines from lung-draining and esophageal lymph nodes. Serum levels of peanut-specific immunoglobulin E were reduced following treatment with anti-SCF. In Kitlf/f-Col1-Cre-ERT mice, which have SCF deleted primarily in myofibroblasts that develop in EoE, we observed similar results as the anti-SCF treated animals for inflammatory cell accumulation, cytokines, and histopathology. These results indicate that therapeutic treatments targeting SCF can reduce allergic inflammation in EoE.


Tumor necrosis factor α upregulates the bile acid efflux transporter OATP3A1 via multiple signaling pathways in cholestasis.
Cholestasis is a common condition in which the flow of bile from the liver to the intestines is inhibited. It has been shown that organic anion-transporting polypeptide 3A1 (OATP3A1) is upregulated in cholestasis to promote bile acid efflux transport. We have previously shown that the growth factor fibroblast growth factor 19 and inflammatory mediator tumor necrosis factor α (TNFα) increased OATP3A1 mRNA levels in hepatoma peritoneal lavage cell/PRF/5 cell lines. However, the mechanism underlying TNFα-stimulated OATP3A1 expression in cholestasis is unknown. To address this, we collected plasma samples from control and obstructive cholestasis patients and used ELISA to detect TNFα levels. We found that the TNFα levels of plasma and hepatic mRNA transcripts were significantly increased in obstructive cholestatic patients relative to control patients. A significant positive correlation was also observed between plasma TNFα and liver OATP3A1 mRNA transcripts in patients with obstructive cholestasis. Further mechanism analysis revealed that recombinant TNFα induced OATP3A1 expression and activated NF-κB and extracellular signal-regulated kinase (ERK) signaling pathways as well as expression of related transcription factors p65 and specificity protein 1 (SP1). Dual-luciferase reporter and chromatin immunoprecipitation assays showed that recombinant TNFα upregulated the binding activities of NF-κB p65 and SP1 to the OATP3A1 promoter in peritoneal lavage cell/PRF/5 cells. These effects were diminished following the application of NF-κB and ERK inhibitors BAY11-7082 and PD98059. We conclude that TNFα stimulates hepatic OATP3A1 expression in human obstructive cholestasis by activating NF-κB p65 and ERK-SP1 signaling. These results suggest that TNFα-activated NF-κB p65 and ERK-SP1 signaling may be a potential target to ameliorate cholestasis-associated liver injury.


The association of mediastinal mass in the formation of thrombi in pediatric patients with non-lymphoblastic lymphomas.
Children diagnosed with cancer are at a significantly higher risk of developing a thrombotic event (TE) compared with the general population. The rarity of these events makes it difficult to discern the specific risk factors; however, age, sex, presence of central venous lines, inherited thrombophilia, and mediastinal mass may play a role. The primary aim of this study is to identify prognostic characteristics of children diagnosed with non-lymphoblastic lymphomas associated with a greater risk of developing a TE early on in their disease, with an increased focus on mediastinal mass characteristics. Retrospective chart review of pediatric patients diagnosed with non-lymphoblastic lymphoma between 2004 and 2014 at St. Jude Children's Research Hospital. TE occurred in 8.5% (n = 28/330) of individuals at a median of 21 days from the diagnosis of a non-lymphoblastic lymphoma, with 60% of TEs occurring within 30 days of diagnosis. Of the variables evaluated, only presence of a peripherally inserted central catheter (odds ratio [OR]: 3.14 [95% CI: 1.24-7.98; P = 0.02]) and degree of superior vena cava (SVC) compression of > 25% increased the odds of developing a TE (OR: 2.2 [95% CI: 1.01-4.93; P = 0.048]). Pediatric patients with non-lymphoblastic lymphoma are at increased risk of developing TEs. In contrast to previous studies, the presence of a mediastinal mass alone was not associated with a higher risk of TE, but individuals with a mediastinal mass with 25% or greater degree of SVC compression were more likely to develop a TE. This finding highlights a high-risk group of children who may benefit from prophylactic anticoagulation.


Mesectodermal leiomyoma of the ciliary body: a tumor of presumed neural crest origin.
Two benign tumors of the ciliary body diagnosed as neurogenic tumors by light microscopy were shown by electron microscopy to be composed of smooth muscle cells with unusual morphologic features. The light-microscopic appearance of a background fibrillary matrix imparting a "neural" appearance was the result of the interweaving of myriad cell processes filled with thin cytoplasmic filaments possessing fusiform densities. The perikaryon of the tumor cells was relatively free of filaments and displayed mitochondria and stacks of rough-surfaced endoplasmic reticulum suggestive of Nissl substance. The basis for these remarkable "hybrid" tumor cells--combining myogenic and neurogenic characteristics--is believed to reside in the neural crest origin of the smooth muscle of the ciliary body (mesectoderm). The histogenetic implications of mesectodermal tissue and the tumors that it spawns are discussed.


Arthroscopic decompression of suprapatellar cyst: case report.
Bursae around the knee reduce friction between moving structures. When involution of suprapatellar septum fails to occur ("complete septum"), then suprapatellar bursa may stay completely separated from the knee joint cavity to form a cystic cavity. In the case of the increased volume, suprapatellar bursitis can cause painful suprapatellar swelling. The aim is to point to the possibility of arthroscopic decompression of suprapatellar cyst. In the case presented, the indication for knee arthroscopy was based on clinical examination, ultrasonography and magnetic resonance studies. The preoperative diagnosis was verified intra-operatively, and intra-articular cyst decompression was performed by arthroscopy. At the final examination 8 months postoperatively, the patient still had no pain, swelling and had full range of motion. This minimally invasive operative procedure resulted in a satisfactory anatomic and functional outcome. In this case report, we present a patient with suprapatellar cyst submitted to arthroscopic cyst decompression.


Biosynthesis of polyhydroxyalkanoate copolymers from mixtures of plant oils and 3-hydroxyvalerate precursors.
The combination of plant oils and 3-hydroxyvalerate (3HV) precursors were evaluated for the biosynthesis of polyhydroxyalkanoate (PHA) copolymers containing 3HV monomers by Cupriavidus necator H16. Among various mixtures of plant oils and 3HV-precursors, the mixture of palm kernel oil and sodium propionate was suitable for the biosynthesis of high concentration of PHA (6.8gL(-1)) containing 7mol% of 3HV. The 3HV monomer composition can be regulated in the range of 0-23mol% by changing culture parameters such as the initial pH, and the nitrogen source and its concentration. PHA copolymers with high weight-average molecular weights (Mw) ranging from 1,400,000 to 3,100,000Da were successfully produced from mixtures of plant oils and 3HV-precursors. The mixture of plant oils and sodium propionate resulted in PHA copolymers with higher M(w) compared to the mixture of plant oils and sodium valerate. DSC analysis on the PHA containing 3HV monomers showed the presence of two distinct melting temperature (Tm), which indicated that the PHA synthesized might be a blend of P(3HB) and P(3HB-co-3HV). Sodium propionate appears to be the better precursor of 3HV than sodium valerate.


'The spirit is willing, but the flesh is weak?': systemic unknown-knowns for ergonomics in India.
While the worldwide ergonomics community increases its sophistication in solving global problems, specific systemic challenges still plague Indians in urban mega-cities such as Mumbai. This paper aims to highlight the gaps using the knowns-unknowns framework, which exists in the Indian ergonomics community's capability to address such systemic challenges. Within this framework, the epistemological category of 'unknown-knowns' is explicated further using a case study of urban accidental deaths and injuries in Mumbai, India. These systemic casualties are essential to note because they are not only hidden from public awareness but can be avoided by proper ergonomics interventions. The article concludes with four main directions for the Indian ergonomics community in solving systemic problems in terms of, (a) capacity-building, (b) advocacy; (c) developing all realms of ergonomics with particular emphasis on complex systems; (d) developing India-centric pathways for ergonomics as a discipline. Practitioner's summary: This paper aims to highlight gaps in the academic Indian ergonomics community's capacity to solve public systemic problems. An India-centric way forward for awareness, engagement, and academic capacity building is suggested to develop a comprehensive national ergonomics mission.


Percutaneous treatment of iatrogenic iliocaval fistula related to endograft placement for abdominal aortic aneurysm.
The authors report a case of iatrogenic dissection occurring during endovascular treatment of an abdominal aortic aneurysm. The dissection was related to catheterization maneuvers that led to the development of a symptomatic arteriovenous fistula, which was successfully closed by coil embolization.


Retrograde Dissection and Reentry: Strategies: Common Pitfalls and Troubleshooting.
The retrograde dissection reentry (RDR) technique is often required to treat the most complex chronic total occlusions (CTOs). This involves a sequence of procedural steps with many potential pitfalls. Procedural planning, knowledge of the equipment, including task-specific wires and microcatheters, and the ability to systematically trouble shoot is necessary to achieve consistent success. With the combination of more complex anatomy and collateral crossing, RDR is associated with higher rates of procedural complications, which the CTO operator must be specifically trained to avoid and to manage.


Genotyping of mitochondrial aldehyde dehydrogenase in blood samples using allele-specific oligonucleotides: comparison with phenotyping in hair roots.
Deficiency of mitochondrial aldehyde dehydrogenase (ALDH I) is an inborn error of metabolism that is responsible for acute alcohol sensitivity (flushing response) observed only in Orientals of Mongoloid origin. Our previous studies using electrophoretic enzyme detection have shown that this deficiency is prevalent among Japanese, Chinese, and other Orientals. We report here the genotyping of ALDH I locus in blood samples of 218 South Korean individuals by means of hybridization analysis with allele-specific oligonucleotide probes and enzymatically amplified human genomic DNA. The results of genotyping are compared with the phenotype analysis in hair roots of the same individuals. Among 62 apparently deficient phenotypes, 58 heterozygote and 4 homozygote deficient genotypes were observed.


Effect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: A double-blinded, randomized controlled trial.
To investigate the effects of saffron (Crocus sativus L.) on lipid profile, glycemic and antioxidant status in overweight/obese individuals with prediabetes. In this randomized, double-blind, placebo-controlled trial, the prediabetic patients were randomly assigned to receive saffron (15 mg/d) pills or placebo for eight weeks. Serum levels of lipid profile, fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), creatinine, and diphenylpycrylhydrazyl (DPPH) radical scavenging activity were assessed biochemically at baseline and at 8 weeks after treatment. The adverse events, if any, were also recorded. Seventy-five of participants (36 in treatment and 39 in placebo groups) completed the study. Within-group comparisons revealed a significant effect of saffron supplementation on FBS (118.11 ± 3.55 vs. 109.14 ± 6.23), HbA1c (5.85 ± 0.12 vs. 5.70 ± 0.11), and DPPH (11.06 ± 3.24 vs. 13.46 ± 3.33) levels (P < 0.005 for all). In adjusting models, there was a significant reduction in FBS by -7.97 mg/dL, and HbA1c by -0.15% in saffron group compared to placebo. Moreover, saffron intake tended to increase in DPPH radical scavenging activity (2.4% vs. -0.85% in saffron and placebo groups, respectively). However, no significant changes in anthropometric measures, lipid profile, and renal markers were observed after saffron intake compared with placebo. Saffron supplementation could improve glycemic and antioxidant indices in overweight/obese individuals with prediabetes, however, no beneficial effect was observed on lipid profile and anthropometric parameters. (IRCT20120913010826N19).


Long-term physical activity outcomes of home-based lifestyle interventions among breast and prostate cancer survivors.
Few studies have investigated long-term effects of physical activity (PA) interventions. The goal of this study was to evaluate whether or not increased levels of moderate to vigorous physical activity (MVPA) were maintained by cancer survivors 1 year after receipt of two home-based interventions. The FRESH START trial randomized 543 breast and prostate cancer survivors to 1-of-2 mailed print diet and exercise interventions: sequentially-tailored vs. standardized (attention control). Each arm received eight mailings over a 1-year period, with follow-up at 1 and 2 years. This analysis focuses solely on the 400 participants who had suboptimal levels of MVPA at baseline (measured by the 7-Day Physical Activity Recall) and who completed the 2-year study. Median minutes of MVPA at baseline, 1-year and 2-year follow-up in the tailored intervention arm were as follows: 0, 90, and 60 min/week, respectively. The corresponding values in the attention control group were 0, 30, and 30 min/week. Significant improvements in MVPA from baseline to 2-year follow-up were observed in both study arms (p < 0.01). While significant between-arm differences were observed at 1-year follow-up (p < 0.01), there was only the suggestion of a trend (p = 0.08) at 2-year follow-up. This study provides evidence that mailed-print exercise interventions result in significant and sustainable improvements in MVPA among newly diagnosed cancer survivors that are observed well after the intervention is complete. While tailored interventions, as compared to standardized materials, appear to produce superior improvements in MVPA initially, these differences diminish over time.


The differential influence of PZM21, a nonrewarding μ-opioid receptor agonist with G protein bias, on behavioural despair and fear response in mice.
A growing body of evidence points out the involvement of the µ-opioid receptors in the modulation of stress-related behaviour. It has been suggested that µ-opioid receptor agonists may attenuate behavioural despair following animals' exposure to an acute, inescapable stressor. Moreover, morphine was shown to ameliorate fear memories caused by a traumatic experience. As typical µ-opioid receptor agonists entail a risk of serious side effects and addiction, novel, possibly safer and less addictive agonists of this receptor are currently under investigation. One of them, PZM21, preferentially acting via the G protein signalling pathway, was previously shown to be analgesic, but less addictive than morphine. Here, we aimed to further test this ligand in stress-related behavioural paradigms in mice. The study has shown that, unlike morphine, PZM21 does not decrease immobility in the forced swimming and tail suspension tests. On the other hand, we observed that both mice treated with PZM21 and those receiving morphine presented a slight attenuation of freezing across the consecutive fear memory retrievals in the fear conditioning test. Therefore, our study implies that at the range of tested doses, PZM21, a nonrewarding representative of G protein-biased µ-opioid receptor agonists, may interfere with fear memory consolidation while having no beneficial effects on behavioural despair in mice.


Neurodevelopment: Maintaining function during circuit reconfiguration.
Neural circuits change during development or following experience by adding neurons and rewiring connections, but mapping such processes is technically daunting. A new study traces maturation of an entire circuit in subcellular detail, revealing continuous functionality under gradual structural change.


The effect of induced hyperglucagonaemia on the Zucker fatty rat.
The effect of chronic treatment with a long-acting glucagon preparation on liver glucagon and insulin receptors, adenylate cyclase and plasma lipids has been examined in Zucker fatty rats (fa/fa) and their lean littermates (Fa/-). Liver insulin and glucagon receptors were examined using radioreceptor assay techniques. Neither fatty nor lean rats showed any change in insulin receptors after glucagon treatment. Glucagon receptors of the fatty rats showed a 33% drop in the number of the glucagon receptors after glucagon treatment, whilst there was no such change in the lean group. Plasma membranes of the treated fatty rats and their controls bound only 50% as much insulin per mg of liver membrane protein as those of the treated lean rats and their controls. Glucagon treatment raised plasma NEFA in lean rats and reduced them in fatty ones. Plasma cholesterol levels were reduced in both groups of animals as were plasma triglycerides, though to a lesser degree in fatty than in lean animals. Glucagon treatment increased basal and stimulated adenylate cyclase activity in the lean rats and even more so in the fatty ones. The data lend no support to the concept that hypertriglyceridaemia in fatty Zucker rats is a consequence of abnormal glucagon responsiveness.


The effect of different graft tensioning in anterior cruciate ligament reconstruction: a prospective randomized study.
A prospective study was performed to establish the influence on stability of tensioning the graft after anterior cruciate ligament reconstruction with a bone-patellar tendon-bone graft. There were 38 consecutive patients randomly divided into two groups; in the first group (19 patients) the graft was tensioned at 20 N, and in the second group the tension was 40 N. Evaluation included Lysholm scores, instrumented Lachman tests, IKDC level, and lateral radiographs to measure the tibia position versus the femur. One year after surgery we did not find any significant difference between the two groups. We conclude that the importance of graft tensioning has yet to be established in the clinical situation. Based on our results, graft tension of 20 N seems to be sufficient, without the risk of overconstraining the knee joint.


Occurrence of GCH1 gene mutations in a group of Indian dystonia patients.
The aim of this study is to examine the role of GCH1 among Indians affected with dopa responsive dystonia (DRD) and early onset Parkinson's disease (EOPD). The patients (n = 76 including 19 DRD and 36 EOPD) and controls (n = 138) were screened for variants in GCH1 by PCR amplification of exons, splice junctions and 1 kb upstream region followed by SSCP and DNA sequencing. Four novel variants (p.Met1Val, p.Val204_205del, IVS3+68A>G, and IVS5-6T>G) were identified in 10 patients but not in the controls. In addition to two nonsynonymous changes, identified in four DRD patients in heterozygous condition, one intronic variant (IVS5-6T>G) could be linked to pathogenesis of the disease since it has the potential of altering the splice site as assessed by in silico analysis. Patients carrying different nonsynonymous variants had remarkable variation in clinical phenotype. Consistent with earlier reports, severity of clinical phenotype and the age of onset varied among family members harboring the same mutation. No mutation was detected in the EOPD patients. Three novel mutations in GCH1 gene have been found and are shown to be associated with variable clinical phenotypes mostly within the spectrum of DRD. The mutations identified represent 15.79% (3/19) of east Indian DRD patient cohort.


Experiences of initiating and maintaining a vegan diet among young adults: A qualitative study.
A vegan diet, which excludes all animal-derived products, has been associated with some improvements in health, while also conferring environmental benefits. Understanding the psychological determinants of successfully switching to a vegan diet will help to inform the design of interventions supporting long-term dietary change. Studies to date have tended to focus on reasoned motives underlying the decision to initiate such a dietary shift. Yet, focusing on reasons for switching may overlook the importance of a broader range of psychological factors that may help or hinder attempts to maintain a vegan diet. This qualitative interview study, the timing of which coincided with UK Covid-19 lockdowns, documented experiences of 20 young adults (17 female; mean age 22y) who attempted to adopt a vegan diet in the past nine months and had or had not successfully maintained this change. Reflexive Thematic Analysis identified five themes surrounding initiation and maintenance. A theme of 'motives, expectations and cues to switching' showed that switching was motivated by ethical or health concerns, and cued by Veganuary, lockdown or health issues. 'The effortfulness of switching' captured experiences of the perceived burden imposed by adhering to the diet due to, for example, a perceived lack of accessible vegan options. The 'flexibility of dietary rules' theme showed that many found the 'no animal products' rule clear but restrictive, so allowed themselves occasional non-meat animal products. 'Social acceptability concerns' captured the importance of acceptance from vegan and non-vegan family and friends, and 'satisfaction with the switch' described the perceived benefits that sustained maintenance for many. Our findings suggest that interventions should seek to support people to overcome potentially unforeseen practical and social challenges to adhering to a vegan diet.


[Free dermal fat graft for coverage of the median nerve following failed carpal tunnel release].
We wished to evaluate the effectiveness of a free dermal fat graft for covering the median nerve in order to improve function after failure of carpal tunnel release. Eight patients with nine failures of carpal tunnel release were reviewed for this retrospective study. They all had significant perineural fibrosis. We performed a free dermal fat graft harvested from the inguinal region on the same side. The mean follow-up was 37 months (range 6 to 112). All patients had a clinical examination, a disability arm and shoulder scoring (DASH) and magnetic resonance imaging (MRI). Five patients were satisfied or very satisfied with the procedure although only two patients returned to work. Mean grip strength was 13 kg (43% of non-operated hand) and the two-point discrimination test was normal or subnormal six times on the eight wrists tested. The mean DASH score was 43 out of 100. MRI scans on eight wrists showed a fat signal in all patients and enhanced signal with gadolinium contrast in six cases. Free dermal fat graft offers a good covering for the median nerve over the carpal tunnel in cases of failure of carpal tunnel release. MRI showed viability of the graft. Clinical results show improvement but symptoms of median nerve irritation persisted. Permanent intraneural changes may explain these limited results.


Conversion of arteriovenous shunts to fistulae for maintenance haemodialysis: its applicability in a developing country.
Arteriovenous shunts in the forearm of 30 patients with end-stage renal disease were converted to arteriovenous fistulae using the same, previously cannulated blood vessels. The shunts were done because these patients needed immediate dialysis. After 2-4 weeks when the cephalic veins had dilated sufficiently shunts were converted to fistulae. In 28 patients fistulae were usable within 24-48 hours without interruption of the dialysis schedule and without loss of access site. In one patient the use was delayed for 20 days while a local skin infection was treated. In another patient the fistulae did not function.


The influence of soccer-specific fatigue on peak isokinetic torque production of the knee flexors and extensors.
Epidemiological findings of higher muscular thigh strain injury incidence during the latter stages of soccer match play have been attributed to fatigue. Soccer-specific fatigue will significantly reduce peak isokinetic torque of the knee flexors and extensors. Descriptive laboratory study. Ten male professional soccer players (mean age, 24.7 +/- 4.4 years; body mass, 77.1 +/- 8.3 kg; maximum oxygen consumption [VO(2) max], 63.0 +/- 4.8 mL/kg/min) completed an intermittent treadmill protocol replicating the activity profile of match play. Before exercise and at 15-minute intervals, each player completed 1 of 2 randomized isokinetic dynamometer protocols. The first protocol quantified peak concentric knee extensor and flexor torque, while the second quantified peak concentric and eccentric knee flexor torque at isokinetic speeds of 180, 300, and 60 deg/s (3.14, 5.25, and 1.05 rad/s) with 5 repetitions at each speed. Concentric knee extensor and flexor peak torque were maintained throughout the duration of the exercise protocol, irrespective of movement speed. However, peak eccentric knee flexor torques at the end of the game (T(300eccH105) = 127 +/- 25 N.m) and at the end of the passive half-time interval (T(300eccH60) = 133 +/- 32 N.m) were significantly reduced relative to the first 15 minutes (T(300eccH00) = 167 +/- 35 N.m, P < .01; T(300eccH15) = 161 +/- 35 N.m, P = .02). Eccentric knee flexor strength decreases as a function of time and after the half-time interval. This suggests a greater risk of injuries at these specific times, especially for explosive movements, in accord with epidemiological observations.