Confirmation that mutations in DDX59 cause an autosomal recessive form of oral-facial-digital syndrome: Further delineation of the DDX59 phenotype in two new families.
We report three probands from two unrelated consanguineous families of South Asian origin who all carry the same rare novel homozygous variant within the dead box helicase gene DDX59 in association with features of oral-facial-digital syndrome (OFDS). DDX59 variants have been reported previously in an unclassified, autosomal recessive form of OFDS; clinically associated with features including tongue lobulation, cleft palate, frontal bossing, hypertelorism and postaxial polydactyly. All three probands had lobulated tongues with tongue hamartomas, abnormal tongue tip, developmental delay and microcephaly, with just one proband demonstrating polydactlyly. The novel DDX59 variant was identified through autozygosity studies followed by sequencing of homozygous regions identified. It affects a stop codon, extending the protein product and is therefore predicted to be pathogenic. It is only the third reported DDX59 mutation associated with OFDS reported so far.


Capecitabine Regulates HSP90AB1 Expression and Induces Apoptosis via Akt/SMARCC1/AP-1/ROS Axis in T Cells.
Transplant oncology is a newly emerging discipline integrating oncology, transplant medicine, and surgery and has brought malignancy treatment into a new era via transplantation. In this context, obtaining a drug with both immunosuppressive and antitumor effects can take into account the dual needs of preventing both transplant rejection and tumor recurrence in liver transplantation patients with malignancies. Capecitabine (CAP), a classic antitumor drug, has been shown to induce reactive oxygen species (ROS) production and apoptosis in tumor cells. Meanwhile, we have demonstrated that CAP can induce ROS production and apoptosis in T cells to exert immunosuppressive effects, but its underlying molecular mechanism is still unclear. In this study, metronomic doses of CAP were administered to normal mice by gavage, and the spleen was selected for quantitative proteomic and phosphoproteomic analysis. The results showed that CAP significantly reduced the expression of HSP90AB1 and SMARCC1 in the spleen. It was subsequently confirmed that CAP also significantly reduced the expression of HSP90AB1 and SMARCC1 and increased ROS and apoptosis levels in T cells. The results of in vitro experiments showed that HSP90AB1 knockdown resulted in a significant decrease in p-Akt, SMARCC1, p-c-Fos, and p-c-Jun expression levels and a significant increase in ROS and apoptosis levels. HSP90AB1 overexpression significantly inhibited CAP-induced T cell apoptosis by increasing the p-Akt, SMARCC1, p-c-Fos, and p-c-Jun expression levels and reducing the ROS level. In conclusion, HSP90AB1 is a key target of CAP-induced T cell apoptosis via Akt/SMARCC1/AP-1/ROS axis, which provides a novel understanding of CAP-induced T cell apoptosis and lays the experimental foundation for further exploring CAP as an immunosuppressant with antitumor effects to optimize the medication regimen for transplantation patients.


Access to curriculum for students with disabilities at higher education institutions: How does the National University of Lesotho fare?
Creating access to curricula at institutions of higher education for students with disabilities requires a concerted effort from management and other key stakeholders to identify students' needs and create opportunities for success. This paper presents the findings of a study which examined students with disabilities' access to curricula at a higher education institution in Lesotho. Data for this qualitative study were collected using three methods: in-depth interviews, focus group discussions and document analysis. Eleven students with various types of impairments and 15 academic and non-academic staff members currently working in close proximity to students with disabilities participated in this study. The findings reveal inconsistencies between the institution's admission policy of non-discrimination according to disability status and its practices. These inconsistencies are discussed under the following themes: (1) access at admission level, (2) management of disability data, (3) support by the special education unit, (4) teaching strategies, (5) support by lecturers, (6) availability of assistive technology, (7) special concessions and (8) students' coping mechanisms. We recommend that a clear policy concerning the support of students with disabilities be developed with the following aims: guide decisions on how disability data should be used, define roles that different university departments must play in facilitating access to curricula for all students, influence suitable development of teaching and learning resources, stimulate research on success and completion rates of students with disabilities and mandate restructuring of programmes that are currently inaccessible to students with disabilities. Key stakeholders, including students with disabilities, disabled persons' organisations, disability rights activists, and staff should be involved in such policy design.


Gamma-Hydroxybutyrate Increases Resting-State Limbic Perfusion and Body and Emotion Awareness in Humans.
Gamma-hydroxybutyrate (GHB) is a GHB-/GABA-B receptor agonist inducing a broad spectrum of subjective effects including euphoria, disinhibition, and enhanced vitality. It is used as treatment for neuropsychiatric disorders including narcolepsy and alcohol withdrawal, but is also a drug of abuse. Non-medical users report enhancement of body and emotion awareness during intoxication. However, the neuronal underpinnings of such awareness alterations under GHB are unknown so far. The assessment of regional cerebral blood flow (rCBF) by pharmacological magnetic resonance imaging (phMRI) enables the elucidation of drug-induced functional brain alterations. Thus, we assessed the effects of GHB (35 mg/kg p.o.) in 17 healthy males on rCBF and subjective drug effects, using a placebo-controlled, double-blind, randomized, cross-over design employing arterial spin labeling phMRI. Compared to placebo, GHB increased subjective ratings for body and emotion awareness, and for dizziness (p<0.01-0.001, Bonferroni-corrected). A whole-brain analysis showed increased rCBF in the bilateral anterior cingulate cortex (ACC) and the right anterior insula under GHB (p<0.05, cluster-corrected). ACC and insula rCBF are correlated with relaxation, and body and emotion awareness (p<0.05-0.001, uncorrected). Interaction analyses revealed that GHB-induced increase of body awareness was accompanied by increased rCBF in ACC, whereas relaxation under GHB was accompanied by elevated rCBF in right anterior insula (p<0.05, uncorrected). In conclusion, enhancement of emotion and body awareness, and increased perfusion of insula and ACC bears implications both for the properties of GHB as a drug of abuse as well as for its putative personalized potential for specific therapeutic indications in affective disorders.


Sustainability and impact of the implementation of a frailty checklist for the acute medical unit: experience from a tertiary public hospital in Singapore.
Accelerated population ageing is associated with an increasing prevalence of frailty. International guidelines call for systematic assessment and timely interventions for older persons requiring acute care. Checklists have been applied successfully in healthcare settings. This study describes the implementation of a safety checklist for frailty in the acute medical unit (AMU) of a tertiary public hospital in Singapore. We explored the sustainability of processes up to 6 months after initial implementation. Additionally, we investigated process and system outcome benefits following the implementation of the checklist. This retrospective observational study used case notes review of patients admitted to the AMU of a tertiary public hospital in Singapore from February to August 2019. Process outcomes measured to include compliance with AMU frailty checklist assessments and interventions at 24 hours of hospital admission. System and patient outcomes studied to include the length of hospital stay; 30-day emergency department reattendance rate; 30-day hospital readmission rate and inpatient mortality. Propensity scores were used to create balanced cohorts for comparison between those with complete and incomplete compliance with the checklist. Logistic regression was used to adjust for known confounders. Average weekly (all-or-nothing) compliance with the frailty checklist (14.7%) was sustained for 6 months. Where assessments detected high risk, appropriate interventions were appropriately triggered (44%-97.4%). While trends to benefit systems and patient outcomes were present, these were not statistically significant. Contextual patterns are discussed. A safety checklist for frailty was feasibly implemented in the AMU. The checklist was a complex intervention. Full compliance with the checklist was challenging to achieve. Further research assessing optimal patient selection criteria and how checklists may shift team behaviour is a priority.


Stabilization of Mode-Dependent Impulsive Hybrid Systems Driven by DFA With Mixed-Mode Effects.
This paper is concerned with mode-dependent impulsive hybrid systems driven by deterministic finite automaton (DFA) with mixed-mode effects. In the hybrid systems, a complex phenomenon called mixed mode, caused in time-varying delay switching systems, is considered explicitly. Furthermore, mode-dependent impulses, which can exist not only at the instants coinciding with mode switching but also at the instants when there is no system switching, are also taken into consideration. First, we establish a rigorous mathematical equation expression of this class of hybrid systems. Then, several criteria of stabilization of this class of hybrid systems are presented based on semi-tensor product (STP) techniques, multiple Lyapunov-Krasovskii functionals, as well as the average dwell time approach. Finally, an example is simulated to illustrate the effectiveness of the obtained results.


Parameters important in fabricating enzyme electrodes using self-assembled monolayers of alkanethiols.
The fabrication of enzyme electrodes using self-assembled monolayers (SAMs) has attracted considerable interest because of the spatial control over the enzyme immobilization. A model system of glucose oxidase covalently bound to a gold electrode modified with a SAM of 3-mercaptopropionic acid was investigated with regard to the effect of fabrication variables such as the surface topography of the underlying gold electrode, the conditions during covalent attachment of the enzyme and the buffer used. The resultant monolayer enzyme electrodes have excellent sensitivity and dynamic range which can easily be adjusted by controlling the amount of enzyme immobilized. The major drawback of such electrodes is the response which is limited by the kinetics of the enzyme rather than mass transport of substrates. Approaches to bringing such enzyme electrodes into the mass transport limiting regime by exploiting direct electron transfer between the enzyme and the electrode are outlined.


Modular Nitrogen-Doped Concave Polycyclic Aromatic Hydrocarbons for High-Performance Organic Light-Emitting Diodes with Tunable Emission Mechanisms.
Although bowl-shaped N-pyrrolic polycyclic aromatic hydrocarbons (PAHs) can achieve excellent electron-donating ability, their application for optoelectronics is hampered by typically low photoluminescence quantum yields (PLQYs). To address this issue, we report the synthesis and characterization of a series of curved and fully conjugated nitrogen-doped PAHs. Through structural modifications to the electron-accepting moiety, we are able to switch the mechanism of luminescence between thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP), and to tune the overall PLQY in the range from 9 % to 86 %. As a proof of concept, we constructed solid-state organic light-emitting diode (OLED) devices, which has not been explored to date in the context of concave N-doped systems being TADF/RTP emitters. The best-performing dye, possessing a peripheral trifluoromethyl group adjacent to the phenazine acceptor, exhibits yellow to orange emission with a maximum external quantum efficiency (EQE) of 12 %, which is the highest EQE in a curved D-A embedded N-PAH to date.


Effects of infiltrating lymphocytes and estrogen receptor on gene expression and prognosis in breast cancer.
The involvement of the immune system for the course of breast cancer, as evidenced by varying degrees of lymphocyte infiltration (LI) into the tumor is still poorly understood. The aim of this study was to evaluate the prognostic value of LI in breast cancer samples using microarray-based screening for LI-associated genes. Starting from the observation that most published ER gene signatures are heavily influenced by the LI effect, we developed and applied a novel approach to dissect molecular signatures. Further, a meta-analysis encompassing 1,044 hybridizations showed that LI alone is not sufficient to highlight breast cancer patients with different prognosis. However, for ER positive patients, high LI was associated with shorter survival times, whereas for ER negative patients, high LI is significantly associated with longer survival. Annotation of LI, in addition to ER status, is important for breast cancer patient prognosis and may have implications for the future treatment of breast cancer.


Hit evaluation of an α-helical peptide: Ala-scan, truncation and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor.
RNA polymerase (RNAP) remains a relatively underexplored target with only rifampicin and fidaxomicin in clinical use. Hence, the concurrent rise in bacterial resistance rate urges the search for novel RNAP inhibitors with a novel mode of action. In this work, we investigated the impact of several systematic modifications including sidechain-to-sidechain macrocylization in the α-helical content and biological activity of a previously identified inhibitory sigma factor fragment. Ala-scan results, peptide truncation from both the N- and C-terminus and modifications inspired by other RNAP inhibitors revealed novel structure activity relationships but did not yield a superior sequence. Additionally, four insertion points for non-natural amino acids bearing side chains required for macrocylization were explored. Linear precursors showed improved stabilization of the α-helical content compared to the original sequence as demonstrated by circular dichroism (CD) spectroscopy. However, this increase in α-helicity did not translate into improved biological activity. Instead, complete abolishment of RNAP inhibitory activity occurred. We hypothesize three possible reasons for such a discrepancy and offer the basis for further optimization efforts for this peptidic RNAP inhibitor.


Detection of Bacillus cereus flagellar antigen by enzyme-linked immunosorbent assay (ELISA)
A serological typing scheme of Bacillus cereus has been developed by immunochemical analyses of flagellar antigen using an agglutination method. Enzyme-linked immunosorbent assay (ELISA) for the classification of flagellar serotype of Bacillus cereus had greater sensitivity. 10-500 times, than that of agglutination method. The specificity of flagellar antigen and antibody was determined by immunogold electron microscopy and ELISA inhibition assay. Application of ELISA is useful for the detection of the small amounts and many kinds of antigen-antibody reactions.


Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA): New Insights and Opportunities.
The polymerization-induced self-assembly (PISA) process is a useful synthetic tool for the efficient synthesis of polymeric nanoparticles of different morphologies. Recently, studies on visible light initiated PISA processes have offered a number of key research opportunities that are not readily accessible using traditional thermally initiated systems. For example, visible light mediated PISA (Photo-PISA) enables a high degree of control over the dispersion polymerization process by manipulation of the wavelength and intensity of incident light. In some cases, the final nanoparticle morphology of a single formulation can be modulated by simple manipulation of these externally controlled parameters. In addition, temporal (and in principle spatial) control over the Photo-PISA process can be achieved in most cases. Exploitation of the mild room temperature polymerizations conditions can enable the encapsulation of thermally sensitive therapeutics to occur without compromising the polymerization rate and their activities. Finally, the Photo-PISA process can enable further mechanistic insights into the morphological evolution of nanoparticle formation such as the effects of temperature on the self-assembly process. The purpose of this mini-review is therefore to examine some of these recent advances that have been made in Photo-PISA processes, particularly in light of the specific advantages that may exist in comparison with conventional thermally initiated systems.


Single pemetrexed is noninferior to platinum-based pemetrexed doublet as first-line treatment on elderly Chinese patients with advanced nonsquamous nonsmall cell lung cancer.
To evaluate the clinical efficacy and toxicity of single pemetrexed treatment compared with platinum-based pemetrexed doublet pemetrexed-based as first-line treatment for advanced nonsquamous nonsmall cell lung cancer (NS-NSCLC) in elderly Chinese patients. The study retrospectively reviewed 175 elderly Chinese patients with NS-NSCLC from June 2010 to September 2013: 90 patients received single pemetrexed treatment, 45 received pemetrexed plus oxaliplatin, and 40 received pemetrexed plus carboplatin. Clinical efficacy was assessed using disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). DCR, OS, and PFS did not significantly differ between single pemetrexed treatment (OS: 14.9 months; DCR: 62.2%; PFS: 3.3 months), pemetrexed plus oxaliplatin (OS: 16.5 months; DCR: 71.1%; PFS: 4.5 months), and pemetrexed plus carboplatin (OS: 15.5 months; DCR: 70.0%; PFS: 4.6 months) groups. Pemetrexed treatment caused significantly lower incidences of adverse events, such as hepatotoxicity and peripheral nerve injury. Performance status (PS), TNM stage, and Thymidylate synthase (TS) expression were predictive factors of DCR. Pemetrexed chemotherapy cycles, PS, and TNM stage were independent prognostic factors. Single pemetrexed was noninferior to platinum-based pemetrexed doublet for clinical efficacy and safety in elderly Chinese patients with advanced NS-NSCLC. Chemotherapy cycles, performance status, and TNM stage were independent prognostic factors.


[Plasma-derived products: therapeutic biological products].
The status of proprietary medicinal product has been conferred upon plasma derived products (PDP) by the European Community in its directive issued on the 14 of June 1989. This directive requires each Member State to comply with the current regulations applicable to medicinal products related to production, control and registration of PDP. A different evolution characterized the American regulation in which PDP have been classified as biological products, submitted to a particular regulation since 1992. These different conceptions led the authors to systematically review the specificities of PDP in comparison to classical medicinal products: plasmatic raw material, production of active ingredients and manufacturing of products in the same facility, divergent production of several products from a single starting material, infection risks and variability characterizing biological products, registration and distribution. The analysis of complementary regulation issued to adapt the pharmaceutical principles to the PDP shows that it does not provide all the expected answers to the specificities of the PDP. This shows the advantages that could be expected by giving a status of biological therapeutic product to the PDP. This could above all allow to federate qualified people and data in order to take into account more accurate and more immediate information about risks which may arise in very dispersed fields. This could also serve as a reminder of the ethical principles attached to the preparation of products coming from a human source.


Effect of glucose load and of insulin on the metabolism of glucose and of palmitate in sheep.
1. Simultaneous measurements of the entry rates of palmitate and glucose have been made in Merino sheep (wethers), starved for 24hr., by using constant infusions of [9,10-(3)H(2)]palmitate and [U-(14)C]glucose. 2. The infusion of glucose into the peripheral circulation of the sheep lowered the endogenous entry of both glucose and palmitate. Since palmitate is roughly metabolically representative of the free fatty acid fraction, there was no marked change in the calories available to the sheep. 3. The infusion of insulin into either the peripheral or portal circulation increased the uptake of glucose and decreased the uptake of palmitate by the tissues of the sheep. 4. The infusion of insulin into the peripheral circulation produced a depression in glucose entry after about 80min., whereas the infusion of insulin into the portal circulation produced an almost immediate depression in glucose entry. 5. The hypoglycaemia produced gave rise to an increase in free fatty acid production followed by an increase in glucose production. 6. No direct effect of insulin on the metabolism of free fatty acids has been demonstrated by the techniques used. The effect of insulin on the metabolism of free fatty acids is apparently mediated through its effect on glucose metabolism.


The pathological anatomy of digital enucleation for benign prostatic hyperplasia and its application to endoscopic resection.
A detailed study of the macroscopic and microscopic anatomy of the prostate enlarged by benign hyperplasia and of the effects of enucleation is presented; based on this study in the cadaver, some aspects of endoscopic resection are described. The study and its findings are described in Part I and in Part II some aspects of endoscopic resection are dealt with as 3 questions: (1) Do technical considerations allow resection of the whole adenoma without encroachment on the shell? (2) Is it desirable and feasible to attempt the resection of the glandular tissue of the shell? (3) May resection impair continence even though injury has not been caused by the cutting loop? The discussion is concerned with 3 subjects: the morphology of the prostate, the prostatic capsule and the sphincter system.


[Place of molecular imaging in the management of prostate cancer].
In the management of prostate cancer in recent years, innovative therapies have appeared requiring precise and reliable disease detection. In 2021, new generation imaging (PET/CT, multiparametric MRI, PET/MRI) have their place at all stages of the prostate cancer natural history to help target the lesion(s) and guide therapy and improve the results obtained. PSMA PET/CT is currently the leader in this type of imaging with a complete offer during the disease: both from diagnosis, to recurrence or in the oligo-metastatic and metastatic stage resistant to castration with a pivotal role in the PSMA theranostic approach. However, multiparametric MRI also has many detection advantages when the prostate is left in place, which suggests the potential major benefit of hybrid PSMA PET/MRI imaging.


Intoxication with taxus baccata: cardiac arrhythmias following yew leaves ingestion.
The use of yew leaves (Taxus Baccata) as a means of deliberate self-harm is infrequent. The potent effect of the toxin is primarily cardiac and results in rhythm alterations and ultimately ventricular fibrillation. As there is no known antidote, and classic antiarrhythmic therapy proves to be ineffective, a prompt diagnosis is of great importance as immediate supportive action is the only valuable alternative. This case describes a 43-year-old women who attempted suicide by ingesting the leaves of Taxus Baccata. We discuss the effects and the difficulty of treatment associated with yew leaf poisoning.


Hyperbilirubinaemia a predictive factor for complicated acute appendicitis: a study in a tertiary care hospital.
To study the role of hyperbilirubinaemia as a predictive factor for appendiceal perforation in acute appendicitis. The prospective, descriptive study was conducted at the Abbasi Shaheed Hospital and the Karachi Medical and Dental College, Karachi, from January 2010 to June 2012. It comprised all patients coming to the surgical outpatient department and emergency department with pain in the right iliac fossa with duration less than seven days. They were clinically assessed for signs and symptoms of acute appendicitis and relevant tests were conducted. Patients were diagnosed as a case of acute appendicitis on the basis of clinical and ultrasound findings, and were prepared for appendicectomy. Per-operative findings were recorded and specimens were sent for histopathology to confirm the diagnosis. SPSS version 10 was used to analyse the data. Of the 71 patients, 37 (52.10%) were male and 34 (47.90%) were female. The age range was 3-57 years, and most of the patients (n = 33; 46.5%) were between 11 and 20 years. Besides, 63 (89%) patients had pain in the right iliac fossa of less than four-days duration, while 8 (11%) had pain of longer duration.Total leukocyte count was found to be elevated in 33 (46.5%) patients, while total serum bilirubin was elevated in 41 (57.70%). Ultrasound of abdomen showed 9 (12.70%) patients having normal appearance of appendix and 59 (83.30%) had inflamed appendix. Four (5.60%) patients had no signs of inflammation on naked eye appearance per operatively. Histopathology of appendix showed 10 (14.10%) patients had non-inflammatory appendix. Patients with signs and symptoms of acute appendicitis and a raised total serum bilirubin level indicated a complication of acute appendicitis requiring an early intervention to prevent peritonitis and septicaemia. A raised serum bilirubin level is a good indicator of complicated acute appendicitis, and should be included in the assessment of patients with suspected complicated acute appendicitis.


[Efficacy of adalimumab for Crohn's disease in real clinical practice].
To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn's disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. The findings demonstrate the efficacy and safety of ADA used in clinical practice.


[Effects of lithium on primary cultured cerebrocortical neurons of rat].
To explore the neuroprotection and the impact on brain development of lithium, the effects of lithium salt on the growth and survival of primary cultured cerebrocortical neurons were studied. The technique of primary cultured cerebrocortical neurons of newborn rats with serum-free medium was established, and the growth and survival of neurons treated with different doses of lithium chloride (0.625, 1.250, 2.500, 5.000, 10.000 mmol/L) were observed. The length of neuronal synapse, cell viability by MTT reduction assay were also measured. The neurons were brighter, germinated rapidly, the neuronal synapse lengthened markedly, and the neurons viability was also better after treated with lithium chloride. Among the five doses, 5.000 mmol/L had the best effect [(53.80 +/- 5.84) micro m, P < 0.01]. Lithium chloride can promote the growth and survival of neurons.


Dual-3D Femtosecond Laser Nanofabrication Enables Dynamic Actuation.
Strategies that can make general materials smart are highly desired for developing artificial shape-morphing systems and devices. However, at present, it still lacks universal technologies that enable designable prototyping of deformable 3D micro-nanostructures. Inspired by natural automation systems, for instance, tendrils, leaves, and flowers deform dynamically under external stimuli by varying internal turgor, we report a dual-3D femtosecond laser processing strategy for fabricating smart and deformable 3D microactuators based on general photopolymers. By programming the size and distributions of voxels at the nanoscale, both the 3D profile and the 3D internetwork of a general photopolymer could be tailored in a controlled manner; thus, 3D microstructures encoded with precisely tailored networks could perform predictable deformations under certain stimuli. Using this dual-3D fabrication approach, energetic 3D microactuators, including a smart microflower, a responsive microvale, and an eight-finger microclaw, that permit controllable manipulation have been successfully developed.


Objective voice analysis in dysphonic patients: new data including nonlinear measurements.
This report describes a comparative study of objective voice evaluation using a multiparametric protocol including aerodynamic parameters and linear and nonlinear acoustic parameters recorded on an EVA(R) workstation and perceptual voice analysis by a jury. A total of 449 samples were retrospectively selected including 391 patients with pathological voices (308 women and 141 men) and 58 controls with normal voices (38 women and 20 men). A prospective complementary study concerning 43 female patients and 3 controls is presented. Objective measures included fundamental frequency (Fo), intensity, jitter, signal-to-noise ratio (SNR), Lyapunov coefficient (Lya), oral airflow (OAF), estimated subglottic pressure (ESGP), maximum phonatory time (MPT) and vocal range. A jury of 4 experienced listeners was instructed to classify voice samples (continuous speech) according to the G (overall dysphonia) component of the GRBAS score on a Visual Analogue Scale (VAS) secondarily transformed in a scale ranging from 0 for normal to 3 for severe dysphonia. It was shown that a nonlinear combination of only 7 parameters in women (vocal range, Lya, ESGP, MPT, OAF, SNR, and Fo) and 6 parameters in men (vocal range, Lya, OAF, ESGP, Fo, SNR) allowed classification of 81% voice samples in the same grade as the jury in women and 84% in men. In the prospective study, 80.5% were correctly classified with the same set of objective measurements. The relative importance of the different objective parameters in this type of discriminant analysis is dealt with. Special emphasis is placed on Lya.


Roles, function and relevance of LAG3 in HIV infection.
HIV causes several forms of immune dysfunction that need to be addressed in a functional cure for HIV. Immune exhaustion describes a dysfunctional phenotype caused by chronic cellular activation. Lymphocyte activation gene-3 (LAG3) is one of several negative coreceptors known as immune checkpoints that contribute to this exhaustion phenotype. Antibodies targeting immune checkpoints are now used clinically to restore immunity against cancer and hold promise in restoring immunity during HIV infection. Here, we summarize current knowledge surrounding LAG3 and discuss its relevance during HIV infection and the potential for LAG3-targeting antibodies in a functional HIV cure.


Aerosol Transmission of Infectious Disease and the Efficacy of Personal Protective Equipment (PPE): A Systematic Review.
Health care professionals and governmental agencies are in consensus regarding contact and droplet transmission of infectious diseases. However, personal protective equipment (PPE) efficacy is not considered for aerosol or airborne transmission of infectious diseases. This review discusses the inhalation of virus-laden aerosols as a viable mechanism of transmission of various respiratory infectious diseases and PPE efficacy. The Preferred Reporting Items for Systematic reviews, and Meta-Analysis (PRISMA) guidelines was used. The transmission of infectious disease is of concern for all respirable diseases discussed (SARS-CoV-1, SARS-CoV-2, MERS, influenza, and tuberculosis), and the effectiveness of facemasks is dependent on the efficiency of the filter, fit, and proper use. PPE should be the last resort in preventing the spread of infectious disease and should only be used for protection and not to control the transmission.


Expression of adhesion molecular proteins in the cochlear lateral wall of normal and PARP-1 mutant mice.
Sound can damage peripheral cochlear function through a number of mechanisms, and emerging evidence suggests that inflammation may be one of them. Using immunohistochemistry and poly (ADP-ribose) polymerase-1 (PARP-1) mutant mice, we tested whether PARP-1 contributes to loud-sound induced cochlear lateral wall damage by triggering inflammatory effects, including upregulating intercellular adhesion molecule-1 (ICAM-1), P-selectin and platelet-endothelial cell-adhesion molecule-1 (PECAM-1). In control conditions, we found that there was no detectable poly-ADP-ribose (PAR) in the marginal cells and microvessels. ICAM-1 was expressed only at low levels in the vessels of the stria vascularis and the spiral ligament. P-selectin and PECAM-1 were barely detected and only in the vessels of the spiral ligament. Following loud-sound exposure, PAR was detected in numbers of marginal cells and some vessels of the spiral ligament. Also, an elevated expression of ICAM-1 was demonstrated in some vessels of the stria vascularis and spiral ligament. Increased expression of P-selectin and PECAM-1 were mainly located in the vessels of the spiral ligament, while increased populations of non-migrated and migrated leukocytes were observed in the area of the spiral ligament. However, neither increased expression of adhesion proteins nor increased population of leukocytes, were observed in the PARP-1 knockout mouse. We thus conclude that loud-sound stress activates the expression of adhesion molecular proteins in the lateral wall and that PARP-1 modulates inflammation-linked protein expression and leukocyte migration.


A Propensity Score Matching Analysis of Transradial Versus Transfemoral Approaches in Octogenarians Undergoing Percutaneous Coronary Intervention.
Despite the widespread adoption of the transradial approach for elderly patients undergoing percutaneous coronary intervention (PCI) in clinical practice, data on octogenarians in China are still relatively limited. This study sought to compare both the safety and efficacy of transradial intervention (TRI) and transfemoral intervention (TFI) in octogenarians in China. We identified 254 octogenarians who underwent PCIs in Fuwai Hospital, Beijing, China between January 1, 2006 and April 30, 2011. TRI was used in 184 patients and TFI was used in 70 patients. Incidence rates of in- hospital and 1-year clinical outcomes were compared between the two groups. Ono-to-one propensity score matching (PSM) was performed to control for potential bias. A total of 48 pairs were matched. Baseline and procedural characteristics were balanced between the TRI and TFI groups. Patients undergoing TRI had significantly fewer access site complications (10.3% vs. 20.0%, p = 0.040), although this difference did not remain significant in propensity score-matched patients (10.4% vs. 22.9%, p = 0.100). After PSM, the patients undergoing TRI were less likely to have major post-PCI bleeding (0 vs. 12.5%, odds ratio 0.47, 95% confidence interval 0.37-0.58, p = 0.026). There were no statistical differences in the incidence rates of major adverse cardiac events (a composite of cardiac death, myocardial infarction, and target vessel revascularization) and their components both during hospitalization and at 1-year. Compared with TFI, TRI was safer and more feasible for octogenarians undergoing PCI.


Incidence of joint involvement in early rheumatoid arthritis.
The frequency of joint involvement is described in 102 patients seen within one year of onset of rheumatoid arthritis. The joints most commonly affected were metacarpophalangeal, proximal interphalangeal and wrists, followed by metatarsophalangeal and shoulders. The least commonly affected were the hips and spine. Temporomandibular and cervical spine involvement often occurred even in these early stages. Where there was unilateral involvement of corresponding joints there was a marked tendency for one side of the body to be more often affected. The arthritis was predominantly peripheral. There was a marked gradation of frequency in the small joints of the hands. The patients were followed prospectively for a mean 4.5 years and outcome assessed. An eventually more severe disease was associated with early writst and metatarsophalangeal joint involvement.


[Antigenicity of trophoblast cells and their significance for placentation and tolerance of human allogenic ova ].
Due to the elucidation of transplantation phenomena of the human allogenic egg, as yet unknown, the antigenicity of each trophoblastic cells was estimated using a cell culture technique introducing the immunofluorescence method. It was studied by means of an immunological model like the fetomaternal incompatibility in the classic AB0-blood system. The in vitro cultured placenta cells (epithelials cells of the chorionic villi, the Langhanscells, the Hofbauercells and also their's daughter cells) were investigated concerning the presence of A- and B-bloodgroup antigens, whereas the direct and indirect immunofluorescence method was introduced. It was confirmed that the chorionic villi epithelial cells are always antigen-less ones. The Langhanscells possess the A- and B-transplantation antigens within their nuclei membranes only. But in Hofbauercells the presence of the antigens could be found within the cell membrane, within the nuclei membrane and also the cytoplasma of the daughter cells. The lack of transplantation antigens in the epithelial layer of the chorionic villi enable as well the placentation and further development of the human allogenic egg.


[Study on the prevalence of tic disorders in schoolchildren aged 7-16 years old in Wenzhou].
To study the epidemiological features of tic disorders (TD) among schoolchildren in Wenzhou area. Stratified cluster sampling was carried out to investigate TD in 9742 schoolchildren aged 7 to 16 years old in Wenzhou. The average prevalence rate of TD among school-age children was 104/10 000 (166/10 000 for males, 29/10 000 for females). There was a significantly higher prevalence rate for males than that for females (chi(2) = 43.96, P < 0.001, prevalence ratio = 5.7, prevalence ratio 95% CI: 3.20 - 10.30). The prevalence rates of clinical subtypes in males was significantly higher than that of females while pupils was significantly higher than that in high school students (chi(2) = 11.33, P < 0.01, prevalence ratio = 2.2, prevalence ratio 95% CI: 1.37 - 3.43). Prevalence rate of transient tic disorders (TTD), chronic motor vocal tic disorder (CMVTD), tourette syndrome (TS) were 34/10 000, 27/10 000 and 43/10 000 respectively with the highest among 9-10 years old group. The mean onset age of TD was 8.5 +/- 2.8 years. The peak of onset was among 6-10 year olds. The rate of delayed diagnosis of the disorders was 69.3% and the median in delayed diagnosis was 1.0 year. TD is a common disease with high rate of misdiagnoses among schoolchildren in Wenzhou area. Physicians and population should be trained to identify the syndromes and to practice correct diagnosis and effective treatment as early as possible.


Water absorbed by polyaniline emeraldine tends to organize, forming nanodrops.
Interactions, in terms of both binding energies and microscopic organization, of water molecules absorbed by hydrophilic polyaniline emeraldine base have been investigated using quantum mechanical calculations, molecular dynamics simulation, FTIR spectroscopy, and (1)H NMR. From an enthalpic point of view, water molecules interact more favorably with imine nitrogen atoms than with amine ones, even though the latter are entropically favored with respect to the former because of their two binding sites. Quantum mechanical results show that interaction energies of water molecules reversibly absorbed but organized individually around a binding site range from 3.0 to 6.3 kcal/mol, which is in good agreement with activation energies of 3-5 kcal/mol previously determined by thermodynamic measurements. The irreversible absorption of water to produce C-OH groups in rings of diimine units has been examined considering a three steps process in which water molecules act as both acidic and nucleophilic reagent. Although calculations predict that the whole process is disfavored by 5-8 kcal/mol only, FTIR and (1)H NMR detected the existence of reversibly absorbed water but not of C-OH groups. Both the binding energies and the structural information provided by molecular dynamics simulations have been used to interpret the existence of two types of physisorbed water molecules: (i) those that interact individually with polymer chains and (ii) those immersed in nanodrops that are contained within the polymeric matrix. The binding energies calculated for these two types of water molecules are fully consistent with the thermodynamic activation energies previously reported.


Age-related and depot-specific changes in white adipose tissue of growth hormone receptor-null mice.
Growth hormone receptor-null (GHR(-/-)) mice are dwarf, insulin sensitive, and long-lived in spite of increased adiposity. However, their adiposity is not uniform, with select white adipose tissue (WAT) depots enlarged. To study WAT depot-specific effects on insulin sensitivity and life span, we analyzed individual WAT depots of 12- and 24-month-old GHR(-) (/-) and wild-type (WT) mice, as well as their plasma levels of selected hormones. Adipocyte sizes and plasma insulin, leptin, and adiponectin levels decreased with age in both GHR(-) (/-) and WT mice. Two-dimensional gel electrophoresis proteomes of WAT depots were similar among groups, but several proteins involved in endocytosis and/or cytoskeletal organization (Ehd2, S100A10, actin), anticoagulation (S100A10, annexin A5), and age-related conditions (alpha2-macroglobulin, apolipoprotein A-I, transthyretin) showed significant differences between genotypes. Because Ehd2 may regulate endocytosis of Glut4, we measured Glut4 levels in the WAT depots of GHR(-) (/-) and WT mice. Inguinal WAT of 12-month-old GHR(-) (/-) mice displayed lower levels of Glut4 than WT. Overall, the protein changes detected in this study offer new insights into possible mechanisms contributing to enhanced insulin sensitivity and extended life span in GHR(-) (/-) mice.


Enantioseparation of ofloxacin and its four related substances with ligand exchange-micellar electrokinetic chromatography using copper(II)-L-isoleucine complex as chiral selector.
A ligand-exchange micellar electrokinetic capillary electrophoresis system with copper(II)-L-isoleucine complexes as the chiral selector incorporated in micelles of sodium dodecyl sulfate (SDS) was developed for the enantioseparation of ofloxacin and its four related substances (impurities A, C, E, and F). The effects of important parameters affecting separation such as buffer pH, SDS concentration, chiral selector concentration, and organic additive were investigated in detail. Under optimum experimental conditions, enantioseparation of ofloxacin, impurities A, C, E, and F enantiomers was accomplished with resolutions of 4.28, 2.83, 3.40, 3.58, and 2.46, respectively. Further, simultaneous separation of impurities A, C, E, and F enantiomers was achieved using 10 mmol/L NH4 OAc as the running buffer containing 4 mmol/L copper sulfate,20 mmol/L L-isoleucine, 20 mmol/L SDS, and 5% methanol at pH 8.5. To the best of our knowledge, the simultaneous enantioseparation of four impurities of ofloxacin has not been reported previously.


Quality of life scores: an independent prognostic variable in a general population of cancer patients receiving chemotherapy. The National Cancer Institute of Canada Clinical Trials Group.
This report examines the prognostic associations between QOL scores measured by the EORTC QLQ-C30 and survival in a large heterogeneous population of cancer patients. Eight hundred and fifty-one cancer patients who were to receive chemotherapy were enrolled in two National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) antiemetic trials. All patients completed the EORTC QLQ-C30 immediately prior to their first chemotherapy. Survival data were available and obtained for 474 of 639 patients (74%). Cox's proportional hazards model was used to assess the independent impact of QOL and demographic variables on survival. Presence of metastatic disease, diagnosis of lung or ovarian cancer, ECOG performance status, global quality of life and emotional functioning were significantly associated with survival. Global QOL was predictive in all patients, in subgroups of patients with metastatic disease, with breast and lung cancer and other tumour types. In patients with low global quality of life scores, patients with low emotional functioning ratings lived longer than did patients with high emotional functioning ratings. Patients with high global QOL live significantly longer than do patients with low global QOL. The relationship between emotional functioning in patients with low global QOL and survival needs confirmation.


Gene expression profiling toward understanding of ALS pathogenesis.
Although more than 130 years have gone by since the first description in 1869 by Jean-Martin Charcot, the mechanism underlying the characteristic selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) has remained elusive. Modest advances in this research field have been achieved by the identification of copper/zinc superoxide dismutase 1 (SOD1) as one of the causative genes for rare familial ALS (FALS) and by the development and analysis of mutant SOD1 transgenic mouse models. However, in sporadic ALS (SALS) with many more patients, causative or critical genes situated upstream of the disease pathway have not yet been elucidated and no available disease models have been established. To approach genes causative or critical for ALS, gene expression profiling in tissues primarily affected by the disease has represented an attractive research strategy. We have been working on screening these genes employing and combining several new technologies such as cDNA microarray, molecular indexing, and laser capture microdissection. Many of the resultant genes are of intense interest and may provide a powerful tool for determining the molecular mechanisms of ALS. However, we have barely arrived at the starting point and are confronting an enormous number of genes whose roles remain undetermined. Challenging tasks lie ahead of us such as identifying which genes are really causative for ALS and developing a disease model of SALS with due consideration for the expression changes in those genes.


The modulation of value-driven attentional capture by exploration for reward information.
Previous studies on value-driven attentional capture (VDAC) have demonstrated that the uncertainty of reward value modulates attentional allocation via associative learning. However, it is unclear whether such attentional exploration is executed based on the amount of potential reward information available for refining value prediction or the absolute size of reward prediction error. The present study investigated the effects of reward information (information entropy) and prediction error (variance) on attentional bias while controlling for the influence of the strength of reward association. Participants were instructed to search for either a red or green target circle and respond to the line orientation within the target. Each target color was associated with reward contingencies with different levels of uncertainty. In Experiment 1, one color was paired with a single reward value (zero entropy and variance) and the other with multiple reward values (high entropy and variance). In Experiment 2, one color had a high-entropy, low-variance reward contingency and the other had the inverse. Attentional interference for distractors with high entropy was consistently greater than low or zero entropy distractors. In addition, in Experiment 3, when distractors with an identical level of variance were given, information entropy was observed to modulate the attentional bias toward distractors. Lastly, Experiment 4 revealed that distractors associated with contrasting levels of variance, while information entropy was kept identical, failed to modulate VDAC. These results indicate that value-based attention is primarily allocated to cues that provide maximal information about the reward outcomes and that information entropy is one of the key predictors mediating attentional exploration and associative learning. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


The evolution of well-aligned amorphous carbon nanotubes and porous ZnO/C core-shell nanorod arrays for photosensor applications.
Well-aligned amorphous carbon nanotube (a-CNT) and porous ZnO/C core-shell nanorod (NR) arrays were fabricated for the first time by a proposed deposition-etching-evaporation (DEE) route. The arrays were prepared by deposition of carbon on the surface of well-aligned ZnO NR arrays by thermal decomposition of acetone followed by spontaneous etching and evaporation of core-ZnO. By utilizing the decomposition of acetone as well as distinct degrees of interaction between intermediate products and ZnO, well-aligned nonporous ZnO/C core-shell NR, porous ZnO/C core-shell NR, and a-CNT arrays were separately prepared by varying the working temperature from 400 to 700 °C. Scanning electron microscopy and high-resolution transmission electron microscopy show that the thickness of carbon shells increases from 3 to 10 nm with the increase in working temperature. Raman spectra demonstrate slight sp(2) bonds of carbon, indicating small graphite regions embedded in amorphous carbon nanoshells. The E(2) peaks of ZnO reduce with the increase in substrate temperature. Photoresponse measurements of ZnO/C NR arrays shows enhancement of both photoresponsivity and response velocity, and the interference of humidity with regard to photosensing is effectively reduced by the capping of carbon nanoshells. The work not only provides an effective route to improve the photosensing of semiconductor nanomaterials for practical applications, but also sheds light on preparing various hollow carbon and porous ZnO/C core-shell nanostructures with distinct morphologies by employing the routes presented in the paper on diverse ZnO nanostructures for optoelectrochemical applications.


Intraperitoneal-Free Cancer Cells Represent a Major Prognostic Factor in Colorectal Peritoneal Carcinomatosis.
Intraperitoneal-free cancer cells are considered as an important prognostic tool in gastric and ovarian cancer. However, their significance in colorectal cancer remains more controversial. This study aimed to determine the role of intraperitoneal-free cancer cells as a prognostic tool in the outcome in colorectal peritoneal carcinomatosis treated with curative intent by complete cytoreductive surgery. This study is an analysis of a prospectively maintained database. Between 1991 and 2012, all patients treated in a single institution for colorectal peritoneal carcinomatosis by complete cytoreductive surgery with peritoneal cytology available were evaluated. Peritoneal cytology was stained in the conventional way (May Grumwald Giemsa). Among a population of 162 patients treated for colorectal peritoneal carcinomatosis by complete cytoreductive surgery, 38 presented positive intraperitoneal-free cancer cells (23.5%). Systemic chemotherapy was administered to 135 patients (85%) during the preoperative course. Median follow-up was 34.5 months. Median overall survival was 19 and 44 months for positive and negative intraperitoneal-free cancer cells (p = 0.018). In multivariate analysis, Peritoneal Carcinomatosis Index and positive intraperitoneal-free cancer cells were significant prognostic factors of overall survival (HR, 2.3 (1.18-4.52), p = 0.014; HR, 1.9 (1.08-3.38), p = 0.027). Retrospective analysis and the long period were limitations of study. Along with the Peritoneal Carcinomatosis Index, intraperitoneal-free cancer cells are a strong prognostic factor for patients treated with curative intent for colorectal peritoneal carcinomatosis by complete cytoreductive surgery. The presence of intraperitoneal-free cancer cells should lead to the consideration of different treatment strategies such as extensive intraperitoneal lavage, targeted intraperitoneal therapies, or repeated intraperitoneal chemotherapy.


Simulation-optimization model for production planning in the blood supply chain.
Production planning in the blood supply chain is a challenging task. Many complex factors such as uncertain supply and demand, blood group proportions, shelf life constraints and different collection and production methods have to be taken into account, and thus advanced methodologies are required for decision making. This paper presents an integrated simulation-optimization model to support both strategic and operational decisions in production planning. Discrete-event simulation is used to represent the flows through the supply chain, incorporating collection, production, storing and distribution. On the other hand, an integer linear optimization model running over a rolling planning horizon is used to support daily decisions, such as the required number of donors, collection methods and production planning. This approach is evaluated using real data from a blood center in Colombia. The results show that, using the proposed model, key indicators such as shortages, outdated units, donors required and cost are improved.


The estrogen‑like protective effect of Lycium barbarum polysaccharides in reducing oxidative stress on myocardial cells from ovariectomized rats.
Previous studies have demonstrated that ovariectomy may lead to a reduction in antioxidative biomarkers in the myocardium, thus suggesting that estrogens may serve a protective role in the suppression of oxidative stress. Lycium barbarum polysaccharides (LBP) are a well‑known antioxidant Chinese traditional medicine, which appear to have a similar function to estrogens with regards to the regulation of cardiac function. In the present study, 30 Sprague‑Dawley rats were randomly divided into the following groups: Sham operation group, ovariectomized (OVX) group, estradiol valerate group, high‑dose LBP (LBP‑H) group and low‑dose LBP (LBP‑L) group. All of the rats were provided tap water, estradiol valerate or LBP for 12 weeks. In addition, all rats were ovariectomized, with the exception of rats in the sham operation group, which underwent fat removal only. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH‑px), catalase (CAT) and superoxide dismutase activities were subsequently examined. The protein expression levels of cleaved caspase‑9, cleaved caspase‑3 and phosphorylated‑protein kinase B (p‑Akt) were also assessed. The results demonstrated that high‑dose LBP decreased the enhanced levels of ROS and MDA in OVX rats, whereas GSH‑px and CAT activities were increased in the LBP‑H group compared with in OVX rats. Furthermore, the expression levels of cleaved caspase‑9 and cleaved caspase‑3 were significantly upregulated in the OVX group, whereas high‑dose LBP exerted protective effects on OVX rats by decreasing the expression of apoptotic proteins. Conversely, p‑Akt expression was decreased in the OVX group and was increased in the LBP‑H group. These results indicated that LBP is essentially involved in cardiac protection by inhibiting apoptosis in response to oxidative stress. In addition, improvement of antioxidant status by LBP is associated with the Akt signaling pathway in the myocardium of OVX rats.


Evaluation of exposure to electromagnetic radiofrequency radiation in the indoor workplace accessible to the public by the use of frequency-selective exposimeters.
The aim of the study was to identify and assess electromagnetic radiofrequency radiation (EMRR) exposure in a workplace located in a publicly accessible environment, and represented by offices (where exposure is caused by various transmitters of local fixed indoor and outdoor wireless communication systems). The investigations were performed in 45 buildings (in urban and rural areas in various regions of Poland), using frequency-selective electric field strength (E-field) exposimeters sensitive to the EMRR with a frequency range of 88-2500 MHz, split into 12 sub-bands corresponding to the operating frequencies of typical EMRR sources. The variability of the E-field was analyzed for each frequency range and the total level of exposure by statistical parameters of recorded exposimetric profiles: minimum, maximum, median values and 25-75th - percentiles. The main sources of exposure to EMRR are mobile phone base transceiver stations (BTS) and radio-television transmitters (RTV). The frequency composition in a particular office depends on the building's location. The E-field recorded in buildings in urban and rural areas from the outdoor BTS did not exceed respectively: medians - 0.19 and 0.05 V/m, 75th percentiles -0.25 and 0.09 V/m. In buildings equipped with the indoor BTS antennas the E-field did not exceed: medians - 1 V/m, 75th percentiles - 1.8 V/m. Whereas in urban and rural areas, the median and 75th percentile values of the E-field recorded in buildings located near the RTV (within 1 km) did not exceed: 1.5 and 3.8 V/m or 0.4 and 0.8 V/m, for radio FM band or for TV bands, respectively. Investigations confirmed the practical applicability of the exposimetric measurements technique for evaluating parameters of worker's exposure in both frequency- and time-domain. The presented results show EMRR exposure of workers or general public in locations comparable to offices to be well below international limits.


Psychiatric hospital reform in low-income and middle-income countries Structured Individualised inTervention And Recovery (SITAR): a two-arm pragmatic randomised controlled trial study protocol.
Low-income and middle-income settings like India have large treatment gaps in mental healthcare. People with severe mental disorders face impediments to their clinical and functional recovery, and have large unmet needs. The infrastructure and standards of care are poor in colonial period psychiatric hospitals, with no clear pathways to discharge and successfully integrate recovered individuals into the community. Our aim is to study the impact of psychiatric hospital reform on individual patient outcomes in a psychiatric hospital in India. Structured Individualised inTervention And Recovery (SITAR) is a two-arm pragmatic randomised controlled trial, focusing on patients aged 18-60 years with a hospital stay of 12-120 months and a primary diagnosis of psychosis. It tests the effectiveness of structural and process reform with and without an individually tailored recovery plan on patient outcomes of disability (primary outcome WHO Disability Assessment Scale), symptom severity, social and occupational functioning and quality of life. A computer-generated permuted block randomisation schedule will allocate recruited subjects to the two study arms. We aim to recruit 100 people into each trial arm. Baseline and outcome measures will be undertaken by trained researchers independent to the case managers providing the individual intervention. A health economic analysis will determine the costing of implementing the individually tailored recovery plan. The study will provide answers to important questions around the nature and process of reforms in institutional care that promote recovery while being cognizant of protecting human rights, and dignity. Ethical approval for SITAR was obtained from a registered ethics committee in India (Institutional Ethics Committee VikasAnvesh Foundation, VAF/2018-19/012 dated 6 December 2018) and the University of Warwick's Biomedical and Scientific Research Ethics Committee (REGO-2019-2332, dated 21 March 2019), and registered on the Central Trial Registry of India (CTRI/2019/01/017267). Trial results will be published in accordance to CONSORT guidelines.


Long-term pharmacokinetics of an extract of isoflavones from red clover (Trifolium pratense).
To study the pharmacokinetics of isoflavones from red clover (Trifolium pratense) after long-term administration as a once-daily dietary supplementary. Fourteen (14) subjects who had been consuming a low-isoflavone diet for 2 weeks were given an oral dose of two isoflavone tablets (approximately 80 mg of total isoflavones) daily for 2 weeks and appeared for a study day at 9:00 AM after an overnight fast on the day that they were to receive the last dose. Plasma samples were collected for a 48-hour period after the last dose. Plasma isoflavones were assayed by high-performance liquid chromatography (HPLC). Trough plasma levels were significantly higher for daidzein and genistein after long-term dosing than levels taken prior to the commencement of the study and plasma levels of isoflavones after long-term dosing were in the range previously reported in populations that consume an isoflavone-rich diet. The plasma half-lives observed after long-term administration were, in most cases, consistent with once-daily administration. Isoflavones have pharmacokinetic characteristics that suggest that once-daily administration is adequate when they are administered long-term as dietary supplements.


Long-Range Detection of French Nuclear Tests of 1960.
With a relatively small number of strategically located ground-level air-filter stations, it has been possible to detect the presence of radioactive debris from the French nuclear test of February 1960 at a great distance from the test site, and to obtain data on the time of arrival of this debris and the extent of its northsouth spread.


The lubricating activity of human synovial fluids.
The lubricating abilities of human synovial fluids were measured using a rotating cartilage-on-glass apparatus. A total of 247 human fluids were lubrication-tested. Of these, 20 of the 180 knee fluids from patients with degenerative/traumatic joint disease lubricated less well than normal bovine synovial fluid. The remainder of the fluids from the knee and other joints were equivalent to normal bovine synovial fluid in their lubricating properties. The concentrations of hyaluronic acid, protein, and sialic acid and the relative viscosity of 117 human fluid samples were determined, but no relationships between the gross composition and the lubricating abilities were apparent.


The reliability of tuberculin skin test in the diagnosis of latent tuberculosis infection in psoriasis patients: A case-control study.
Tuberculin skin test (TST), which is used in the diagnosis of latent tuberculosis infection, may cause Koebner's phenomenon and false-positive results in psoriasis patients. The purpose of this study is to compare TST with QuantiFERON-TB Gold Plus (QFT-plus) test in psoriasis patients and to determine the effects of psoriasis on TST results. Ninety-two psoriasis patients and 30 control subjects were included in the study. QFT-plus test, TST, and prick test to distinguish the increase of induration because of the skin trauma were performed on both groups. The demographics, risk factors for latent tuberculosis infection, BCG vaccination history, Koebner's history, psoriasis severity, and treatment history of the patients were recorded. The effects of these variables on test results were investigated by comparing those with control group. The criteria of National Tuberculosis Diagnosis and Treatment Guidelines were used in the evaluation of test results, and threshold value of positivity for TST was taken as 10 mm in BCG-vaccinated patients who are planned to start biological treatment. Prick test results were negative in the control group. There was no significant relation between the results of prick test and TST induration diameters in the patient group. Although TST positivity was significantly higher in patients (62%) compared with control group (33%), QFT-plus test results were not statistically different between two groups. Agreement between two tests was determined to be low in patient group with 48% (K = 0.1), and it was determined to be moderate with 77% in control group (K = 0.4). QFT-plus test was found to be negative in 46 of 57 TST-positive patients (80.7%) in patient group. It was determined in both groups that vaccination did not have any effect on test results. When threshold value was lowered to 5 mm in patient group without considering BCG reaction, the number of TST-positive patients increased from 57 to 65. Mean TST induration diameter was 10 mm and 14 mm in cases with mild and moderate to severe clinical manifestation, respectively (P = .04). However, no effect of disease period and treatment was determined on both test results. TST positivity was higher in psoriasis patients compared with control group. It was considered due to the increased reaction of the skin to mycobacterial antigens rather than the Koebner's response. Although TST results were not affected by BCG, it was concluded that a 10-mm threshold value of positivity was a suitable approach in order to reduce the number of patients receiving unnecessary preventive treatment in patients who are considered to initiate biologic agents. Furthermore, it was also concluded that QFT-plus test may be preferred in psoriasis patients since it is applied in vitro and its specificity is higher and not affected by disease severity.


Fenretinide causes emphysema, which is prevented by sphingosine 1-phoshate.
Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 µg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive cells were measured. Hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF) and other related proteins were analyzed by Western blot analysis. Immunohistochemical analysis of HIF-1α was also performed. Ceramide, dihydroceramide, S1P, and dihydro-S1P were measured by mass spectrometer. Chronic intraperitoneal injection of fenretinide increased the alveolar airspace surface area and increased the number of caspase-3 positive cells in rat lungs. Fenretinide also suppressed HIF-1α and VEGF protein expression in rat lungs. Concomitant injection of S1P prevented the decrease in the expression of HIF-1α, VEGF, histone deacetylase 2 (HDAC2), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein expression in the lungs. S1P injection also increased phosphorylated sphingosine kinase 1. Dihydroceramide was significantly increased by fenretinide injection and S1P treatment prevented the increase in dihydroceramide levels in rat lungs. These data support the concept that increased de novo ceramide production causes alveolar septal cell apoptosis and causes emphysema via suppressing HIF-1α. Concomitant treatment with S1P normalizes the ceramide-S1P balance in the rat lungs and increases HIF-1α protein expression via activation of sphingosine kinase 1; as a consequence, S1P salvages fenretinide induced emphysema in rat lungs.


STREAM and FAST-MI - Pharmacoinvasive therapy: A continued role for fibrinolysis in the primary PCI era.
Data from the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial(6) and 5-year results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI)(7) are evaluated for further evidence on the effectiveness and safety of a pharmacoinvasive approach for patients presenting with acute ST-segment elevation myocardial infarction (STEMI).


Randomised trial of indwelling pleural catheters for refractory transudative pleural effusions.
Refractory symptomatic transudative pleural effusions are an indication for pleural drainage. There has been supportive observational evidence for the use of indwelling pleural catheters (IPCs) for transudative effusions, but no randomised trials. We aimed to investigate the effect of IPCs on breathlessness in patients with transudative pleural effusions when compared with standard care. A multicentre randomised controlled trial, in which patients with transudative pleural effusions were randomly assigned to either an IPC (intervention) or therapeutic thoracentesis (TT; standard care). The primary outcome was mean daily breathlessness score over 12 weeks from randomisation. 220 patients were screened from April 2015 to August 2019 across 13 centres, with 33 randomised to intervention (IPC) and 35 to standard care (TT). Underlying aetiology was heart failure in 46 patients, liver failure in 16 and renal failure in six. In primary outcome analysis, the mean±sd breathlessness score over the 12-week study period was 39.7±29.4 mm in the IPC group and 45.0±26.1 mm in the TT group (p=0.67). Secondary outcomes analysis demonstrated that mean±sd drainage was 17 412±17 936 mL and 2901±2416 mL in the IPC and TT groups, respectively. A greater proportion of patients had at least one adverse event in the IPC group (p=0.04). We found no significant difference in breathlessness over 12 weeks between IPCs or TT. TT is associated with fewer complications and IPCs reduced the number of invasive pleural procedures required. Patient preference and circumstances should be considered in selecting the intervention in this cohort.


The response to hypoxia of arterial chemoreceptors in fetal sheep and new-born lambs.
Carotid chemoreceptor activity was detected in each of fourteen halothane or pentobarbitone anaesthetized exteriorized fetal lambs of 90-143 days gestational age. Activity was about 5 Hz at a Pa,O2 of 25 mmHg and it increased as Pa,O2 was reduced, either by compressing the umbilical cord or by reducing the (FIO2) oxygen fraction of the gas used to ventilate the ewe. Activity increased briskly when 1-2 ml CO2-saturated saline was injected retrogradely into the lingual artery, but not when saline of pH 7.4 or fetal arterial blood was injected. In two fetuses near-term chemoreceptor activity was recorded continuously whilst the umbilical cord was ligated and ventilation with air started. Activity increased 200-500% as Pa,O2 fell, but then fell to below control as Pa,O2 rose. We suggest that these changes in activity reflect those occurring naturally at birth. No spontaneous chemoreceptor activity could be detected on the day of birth in twelve pentobarbitone anaesthetized lambs delivered vaginally or by Caesarean section at 135-146 days. Single baroreceptor activity could however be recorded in these lambs, and chemoreceptor activity could be elicited by hypercapnia. Spontaneous chemoreceptor activity was detected in six of seven lambs more than 2 days old. In eight conscious lambs the steady-state respiratory response to isocapnic hypoxia was variable on the day of birth. In six of these lambs the response was significantly greater by the third day. We conclude that the arterial chemoreceptors are active and responsive in the fetus, but quiescent in the lamb on the day of birth when Pa,O2 has risen. The hypoxic sensitivity of the chemoreceptors is reset from the fetal to the adult range over the next few days.


Estimations of electric field effects on the oxygen reduction reaction based on the density functional theory.
By varying the external electric field in density functional theory (DFT) calculations we have estimated the impact of the local electric field in the electric double layer on the oxygen reduction reaction (ORR). Potentially, including the local electric field could change adsorption energies and barriers substantially, thereby affecting the reaction mechanism predicted for ORR on different metals. To estimate the effect of local electric fields on ORR we combine the DFT results at various external electric field strengths with a previously developed model of electrochemical reactions which fully accounts for the effect of the electrode potential. We find that the local electric field only slightly affects the output of the model. Hence, the general picture obtained without inclusion of the electric field still persists. However, for accurate predictions at oxygen reduction potentials close to the volcano top local electric field effects may be of importance.


Congenital diaphragmatic hernia-influence of fetoscopic tracheal occlusion on outcomes and predictors of survival.
The morbidity of infants with congenital diaphragmatic hernia (CDH) who had undergone foetal endoscopic tracheal occlusion (FETO) to those who had not was compared and predictors of survival regardless of antenatal intervention were identified. FETO was undertaken on the basis of the lung to head ratio or the position of the liver. A retrospective review of the records of 78 CDH infants was undertaken to determine the lung-head ratio (LHR) at referral and prior to birth, maximum oxygen saturation in the labour suite and neonatal outcomes. The 43 FETO infants were born earlier (mean 34 versus 38 weeks) (p < 0.001). They had a lower mean LHR at referral (0.65 versus 1.24) (p < 0.001) but not prior to birth and did not have a higher mortality than the 35 non-FETO infants. The FETO infants required significantly longer durations of ventilation (median: 15 versus 6 days) and supplementary oxygen (28 versus 8 days) and hospital stay (29 versus 16 days). Overall, the best predictor of survival was the OI in the first 24 h. The FETO group had increased morbidity, but not mortality. The lowest oxygenation index in the first 24 h was the best predictor of survival regardless of antenatal intervention. • Randomised controlled trials have demonstrated that foetal endotracheal occlusion (FETO) in high risk infants with congenital diaphragmatic hernia is associated with a higher survival rate. • Mortality is greater in foetuses who underwent FETO and delivered prior to 35 weeks of gestation. What is New: • Infants who had undergone FETO compared to those who had not had significantly longer durations of mechanical ventilation, supplementary oxygen and hospital stay. • Regardless of antenatal intervention, the lowest oxygenation index in the first 24 h was the best predictor of survival.


Mortality, nutrition and health in Lofa County Liberia five years post-conflict.
Liberia remains in transition from a state of humanitarian emergency to development, and Lofa County was the epicentre of recent conflict. This study aimed to estimate mortality and malnutrition and evaluate access to health services, water and sanitation. The survey was conducted in April 2009 and employed a 46 cluster×20 design (n=920 households) with probability proportional to size sampling. The crude mortality rate was 24.3/1000/year (CI: 19.0 to 29.6) or 0.67/10,000/day (CI: 0.52 to 0.81). The global acute malnutrition rate was 7.9% (CI: 5.4 to 8.9), and the severe acute malnutrition rate was 4.5% (CI: 2.9 to 6.7). Access to basic health services was relatively good according to a variety of indicators; however, access to sanitation was low, with 39.5% of households reporting access to toilets or latrines. Despite high rates of displacement and infrastructure destruction, population health appears to be relatively stable 5 years post-conflict, though a continued focus on reconstruction and development is needed.


Intention to use and actual use of electronic information resources: further exploring Technology Acceptance Model (TAM).
Following up a previous study that examined public health students' intention to use e-resources for completing research paper assignments, the present study proposed two models to investigate whether or not public health students actually used the e-resources they intended to use and whether or not the determinants of intention to use predict actual use of e-resources. Focus groups and pre- and post-questionnaires were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that the determinants of intention-to-use significantly predict actual use behavior. Direct impact of perceived usefulness and indirect impact of perceived ease of use to both behavior intention and actual behavior indicated the importance of ease of use at the early stage of technology acceptance. Non-significant intention-behavior relationship prompted thoughts on the measurement of actual behavior and multidimensional characteristics of the intention construct.


Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery.
Human-induced pluripotent stem cells (hiPSCs) and CRISPR/Cas9 gene editing system represent two instruments of basic and translational research, which both allow to acquire deep insight about the molecular bases of many diseases but also to develop pharmacological research.This review is focused to draw up the latest technique of gene editing applied on hiPSCs, exploiting some of the genetic manipulation directed to the discovery of innovative therapeutic strategies. There are many expediencies provided by the use of hiPSCs, which can represent a disease model clinically relevant and predictive, with a great potential if associated to CRISPR/Cas9 technology, a gene editing tool powered by ease and precision never seen before.Here, we describe the possible applications of CRISPR/Cas9 to hiPSCs: from drug development to drug screening and from gene therapy to the induction of the immunological response to specific virus infection, such as HIV and SARS-Cov-2.


Anti-TNF-alpha antibody normalizes serum leptin in IL-2 deficient mice.
A recent study reports that the interleukin-2 deficient (IL-2(-/-)) mouse model of autoimmune and inflammatory bowel disease (IBD) with elevated pro-inflammatory cytokine production has elevated leptin concentrations during food deprivation. The objective of this study was to examine whether increased tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, contributes to the abnormally elevated leptin in IL-2(-/-) mice. Eight week old, IL-2(-/-) and wild-type control (IL-2(+/+)), male mice were fed regular laboratory mouse food for two weeks. At the end of the study, blood was collected in the fed state, IL-2(-/-) and IL-2(+/+) mice were injected with either anti-TNF-alpha monoclonal antibody or normal saline, and blood was collected in the starved state. The IL-2(-/-) mice consumed less food and lost weight. Administration of anti-TNF-alpha antibody markedly reduced serum leptin concentrations in IL-2(-/-) and control mice after food deprivation. Serum leptin in the IL-2(-/-) mice not receiving anti-TNF-alpha antibody increased significantly in the starved state. Serum concentrations of TNF-alpha were higher in IL-2(-/-) mice compared to controls in both the fed and starved state. These results suggest that elevated TNF-alpha may be one mechanism for the sustained elevated leptin observed in IL-2(-/-) mice during food deprivation.


[Rapidly evolving pulmonary bullous degeneration in HIV-infected patients. Description of 4 cases and review of the literature].
Cavitary lung lesions are common in intravenous drug-addicts (IVDA) and in AIDS patients. Four cases are reported of IVDA patients with HIV positive serology who developed an initially thick-walled lesion, which grew rapidly and evolved into bullous lesions. The negative results in microbiological investigations for Pneumocystis carinii, Nocardia spp., staphylococci; the topographic superposition on a previous tuberculous lesion; a prolonged asymptomatic period; and a particularly rapid evolution in all cases led us to consider the rapidly evolving bullous degeneration to be more than a casual finding. Previous infection with M. tuberculosis in AIDS patients might somehow influence on the later development of a rapidly growing, fatal, bullous degenerative lesion. The elucidation of the pathogenic mechanisms of these lesions was hampered by the lack of pathological studies.


[A coagulative type of pulmonary surfactant depletion--a mechanism of damage to the pulmonary surfactant system].
Plasma proteins, in particular fibrinogen and its degradation products leaking into air spaces in various forms of lung injuries, can adversely affect surfactant function. Two types of interaction of pulmonary surfactant with plasma proteins have been described: (1) a reversible type of interaction of surfactant with plasma proteins, and (2) a coagulative type of surfactant inactivation. The physiological significance of the latter mode of surfactant inactivation remains controversial. The purpose of this study was to determine the relative importance of these two modes of surfactant inactivation in an alveolar model. Surfactant-fibrinogen mixtures were prepared by adding fibrinogen at various concentrations to a standard preparation of surfactant-TA (suspended in Tris buffered saline at the final concentration of 1.25 mg/ml). To one of the mixtures were added caCl2 and thrombin, and the resulting fibrin clot was removed from the mixture by passing through polyethylene telephthalate filter. The surface activity of surfactant-TA suspension and the mixtures of surfactant-TA and fibrinogen before and after fibrin formation was examined during adsorption and dynamic compression using a pulsating bubble surfactometer. The concentrations of total phospholipid and surfactant-associated proteins (SP-B and SP-C) were also measured in these samples. Similar studies were performed with natural surfactant and dipalmitoylphosphatidylcholine (DPPC). Retarded adsorption of surfactant-TA and an increased minimum surface tension were observed in fibrinogen concentrations exceeding 2(-5) mg/ml. The inhibitory effect of fibrinogen on surfactant function reversed completely by 10-min after dynamic bubble pulsations. The magnitude of retarded adsorption and a lessening the ability to lower the minimum surface tension during dynamic bubble compression were significantly greater in the surfactant-fibrinogen mixtures after removal of the fibrin clots than in those before fibrin formation in fibrinogen concentrations exceeding 2(-3) mg/ml. More than 90% of both phospholipid and SP -B, C of surfactant-TA was incorporated into the fibrin clot in fibrinogen concentrations of > 2(-3) mg/ml. Similar results were obtained with natural surfactant or DPPC. At a fixed fibrinogen concentration of 2 mg/ml the fibrin clot removal was accompanied by a 90% loss of surfactant-TA in its concentration range of 1.25-40 mg/ml. Scanning electron microscopic examinations showed that numerous particles of surfactant-TA were seen embedded in fibrin network. The results of this study suggest that the coagulative type of pulmonary surfactant depletion may be more important than the reversible type of pulmonary surfactant inactivation by fibrinogen.


J5 prevents endotoxin shock in suckling rats.
A sublethal dose of endotoxin (lipopolysaccharide: LPS) can induce endotoxin tolerance. It is not well known whether LPS feeding causes endotoxemia and endotoxin tolerance in the newborn. Since Rc mutant Escherichia coli LPS (J5) does not have toxic or lethal effects, J5 is used to induce endotoxin tolerance in this study. This study showed that both an intraperitoneal (ip) injection and feeding of Rc mutant Escherichia coli LPS (J5) induced endotoxin tolerance in suckling rats.


Secretome Analysis of Host Cells Infected with Toxoplasma gondii after Treatment of Human Epidermal Growth Factor Receptor 2/4 Inhibitors.
Toxoplasma gondii, a ubiquitous, intracellular parasite of the phylum Apicomplexa, infects an estimated one-third of the human population as well as a broad range of warm-blooded animals. We have observed that some tyrosine kinase inhibitors suppressed the growth of T. gondii within host ARPE-10 cells. Among them, afatinib, human epithermal growth factor receptor 2 and 4 (HER2/4) inhibitor, may be used as a therapeutic agent for inhibiting parasite growth with minimal adverse effects on host. In this report, we conducted a proteomic analysis to observe changes in host proteins that were altered via infection with T. gondii and the treatment of HER2/4 inhibitors. Secreting proteins were subjected to a procedure of micor basic reverse phase liquid chromatography, nano-liquid chromatography-mass spectrometry, and ingenuity pathway analysis serially. As a result, the expression level of heterogeneous nuclear ribonucleoprotein K, semaphorin 7A, a GPI membrane anchor, serine/threonine-protein phosphatase 2A, and calpain small subunit 1 proteins were significantly changed, and which were confirmed further by western blot analysis. Changes in various proteins, including these 4 proteins, can be used as a basis for explaining the effects of T. gondii infections and HER2/4 inhibitors.


Role of the symphato-adrenal system in hemorrhagic hyperglycemia.
Arterial and venous plasma glucose concentration was determined at intervals in cats subjected to hemorrhagic hypotension at 50 mm Hg. The rapid rise of arterial plasma glucose after hemorrhage could be attributed to an increase release of glucose from the liver. This hyperglycemia could not be eliminated by bilateral adrenalectomy or by sectioning of the hepatic sympathetic nerves, although the response was somewhat depressed by the latter procedure. On the other hand the hyperglycemia was virtully abolished after adrenalectomy when combined with bilateral sectioning of the major and minor splanchnic nerves. The level of plasma glucagon during hemorrgage increased in cats with an intact sympatho-adrenal system, but was unchanged in animals with combined splanchnic sympathectomy and adrenalectomy. It is concluded that, during hemorrhage, the sumpatho-adrenal system influences the glucose output from the liver by three different reflex mechanisms: (a) release of catecholamines from the adrenal glands; (b) direct sympathetic nerve influence on the liver; and (c) release of glucagon from the pancreas.


Neutrophil-derived S100A8/A9 promotes apoptosis of intestinal epithelial cells in children with duodenal ulcers.
Duodenal ulcer significantly reduces quality of life and safety in children; however, the mechanism of the pathogenesis in children with duodenal ulcer remains unclear. S100A8/A9, which plays a critical role in the occurrence and development of inflammation, has attracted a lot of interest recently. Here, we identified that S100A8/A9 are highly expressed in the serum of children with duodenal ulcers, and this is of excellent diagnostic value. Animal experiments have proved that inhibition of S100A8/A9 can repair ulcer progression. In addition, further study has shown that S100A8/A9, mainly produced by neutrophil, can enhance the apoptosis of intestinal epithelial cells and promote the growth in children with duodenal ulcers. Thus, our research proves the value of S100A8/A9 in the diagnosis and treatment of children with duodenal ulcers.


Alu repeats and human genomic diversity.
During the past 65 million years, Alu elements have propagated to more than one million copies in primate genomes, which has resulted in the generation of a series of Alu subfamilies of different ages. Alu elements affect the genome in several ways, causing insertion mutations, recombination between elements, gene conversion and alterations in gene expression. Alu-insertion polymorphisms are a boon for the study of human population genetics and primate comparative genomics because they are neutral genetic markers of identical descent with known ancestral states.


Primary blast injury: update on diagnosis and treatment.
: Injuries from combat and terrorist explosions are increasing worldwide. As such, physicians can expect to treat more patients with complex and unique patterns of injury produced not only by fragments and blunt trauma, but also by high-pressure air expanding from the detonation center. : Tissue damage from the blast wave or primary blast injury can be an important cause of occult trauma to the ocular, aural, pulmonary, cardiovascular, musculoskeletal, and neurologic systems. Awareness of the extensive corporal effects of the blast wave is an essential prerequisite to diagnosis. : This article focuses on the incidence, risk factors, diagnosis, management, and screening for primary blast injury.


Prognostic Significance of Sarcopenia in Patients with Unresectable Advanced Esophageal Cancer.
The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04-2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.


Heat stress protection against mesenteric I/R-induced alterations in intestinal mucosa in rats.
Prior induction of heat shock protein 70 (HSP70) protects against ischemia-reperfusion (I/R) mucosal injury, but the ability of HSP70 to affect I/R-induced alterations in epithelial cell function is unknown. Rats subjected to whole body hyperthermia (41.5-42 degrees C for 6 min) increased HSP70 and heat shock factor 1 mRNA expression, reaching a maximum 2 h after heat stress and declining thereafter. HSP70 production was maximally elevated at 4 h after heat stress and remained elevated until after 12 h. Heat stress alone had no effect on mucosal function except to enhance secretion in response to ACh. Heat stress provided complete morphological protection against I/R-induced mucosal injury but did not confer a similar protection against I/R-induced decreases in mucosal resistance, sodium-linked glucose absorption, or tachykinin-mediated chloride secretion. Heat stress, however, attenuated the I/R-induced suppression of ACh response, and this effect was dependent on enteric nerves. Thus induction of heat shock protein 70 is associated with the preservation of mucosal architecture and attenuation of some specific functional alterations induced by I/R.


Direct Discrimination of Edible Oil Type, Oxidation, and Adulteration by Liquid Interfacial Surface-Enhanced Raman Spectroscopy.
The quality and safety of edible oils is a momentous but formidable challenge, especially regarding identification of oil type, oxidation, and adulteration. Most conventional analytical methods have bottlenecks in sensitivity, specificity, accessibility, or reliability. Surface-enhanced Raman spectroscopy (SERS) is promising as an unlabeled and ultrasensitive technique but limited by modification of inducers or surfactants on metal surfaces for oil analysis. Here, we develop a quantitative SERS analyzer on two-liquid interfacial plasmonic arrays for direct quality classification of edible oils by a portable Raman device. The interfacial plasmonic array is self-assembled through mixing the gold nanoparticle (GNP) sols and oil sample dissolved in chloroform without any surfactants or pretreatments. Different kinds of edible oils dissolved in chloroform directly participate in self-assembly of plasmonic arrays that finally localizes onto a three-dimensional (3D) oil/water interface. The 3D plasmonic array is self-healing, shape adaptive, and can be transferred to any glass containers as a substrate-free SERS analyzer for direct Raman measurements. It produces sensitive responses of SERS on different kinds of edible oils. By virtue of principal component analysis (PCA), this analyzer is able to quickly distinguish six edible oils, oxidized oils, and adulterated oils. Moreover, the solvent chloroform generates unique and stable SERS bands that can utilized as an inherent internal standard (IIS) to calibrate SERS fluctuation and greatly improve quantitation accuracy. Compared to conventional lab methods, this analyzer avoids complex and time-consuming preprocessing and provides significant advantages in cost, speed, and utility. Our study illuminates a facile way to determine edible oil quality and promises great potential in food quality and safety analysis.


Looking beyond the cosmetic tattoo lesion near the eyebrow: Screening the lungs.
Cosmetic tattooing has become a risk factor for several adverse reactions related to inks, procedures, and associated clinical conditions. Development of a sarcoid reaction to the inserted tattoo pigment in the skin is not common. We report a 45 year-old patient with history of dyspnea and mild cough since two years who had subsequently developed reddish, scaly lesions in her 15-year old tattoo done near her right eyebrow. Skin biopsy of the tattoo lesion revealed cutaneous sarcoidosis which led to further investigations and a diagnosis of pulmonary sarcoidosis. The present case highlights the fact that cutaneous sarcoidosis can develop in a long-standing tattoo. Also such a patient should be screened for systemic sarcoidosis disease.


Improved Software to Browse the Serial Medical Images for Learning.
The thousands of serial images used for medical pedagogy cannot be included in a printed book; they also cannot be efficiently handled by ordinary image viewer software. The purpose of this study was to provide browsing software to grasp serial medical images efficiently. The primary function of the newly programmed software was to select images using 3 types of interfaces: buttons or a horizontal scroll bar, a vertical scroll bar, and a checkbox. The secondary function was to show the names of the structures that had been outlined on the images. To confirm the functions of the software, 3 different types of image data of cadavers (sectioned and outlined images, volume models of the stomach, and photos of the dissected knees) were inputted. The browsing software was downloadable for free from the homepage (anatomy.co.kr) and available off-line. The data sets provided could be replaced by any developers for their educational achievements. We anticipate that the software will contribute to medical education by allowing users to browse a variety of images.


Tryptophan repressor of Escherichia coli shows unusual thermal stability.
Differential scanning calorimetry demonstrates that the tryptophan repressor of Escherichia coli is unusually resistant to thermal denaturation. The dimeric protein undergoes reversible dissociative unfolding at pH 7.5 centered at about 90 degrees C. The thermal stability may be due in part to the unusual structure of the protein, which is composed of two identical intertwined polypeptide chains.