Developing mathematical proficiency in the Australian context: implications for students with learning difficulties.
The teaching of mathematics in Australian schools has received considerable attention over the past decade. States and territories have designed and implemented new mathematics syllabi, and education sectors have supported teachers through sustained professional learning initiatives. Whereas the major focus of these initiatives has been on students constructing mathematical knowledge from a range of learning activities and quality instruction, the education of students with difficulties in learning mathematics has been given little direct attention. This analysis of current syllabus developments and professional learning initiatives highlights the risk of exposing students with learning difficulties to fragile program designs and classroom instruction. The research literature is also examined to propose ways in which these fragilities can be addressed.


Are controls in schizophrenia research "normal"?
The psychiatric assessment by structured interview and family history of mental disorder in normal volunteers recruited by advertisement for a study of brain structure and function in psychosis is described. Nine of 51 volunteers (17.6%) who passed a phone screen were excluded after a structured interview for major psychopathology. Of 35 completers, 10 (28.6%) had subthreshold mood or substance use but were included in the study. Only 16 subjects (45%) had a negative family history by FH-RDC. Diagnoses in family members included substance abuse (31%), mood disorder (11%), psychosis (9%), and other/undiagnosed (14%). Ventricular enlargement was evaluated by magnetic resonance imaging in two planes. Ventricular size was bimodally distributed in the males, and the group with larger ventricles was more educated and had higher scores on the 8 (Schizophrenia) scale of the MMPI (F = 5.44, p = .0099). Our results suggest that 'normal' volunteers for psychiatric research have personal or family psychopathology which motivates them to participate. As the sensitivity of biological instrumentation increases, the characteristics of the control group must be anticipated in the design and recruitment.


A case of possible atypical demyelinating event of the central nervous system following COVID-19.
After the novel coronavirus disease outbreak first began in Wuhan, China, in December 2019, the viral epidemic has quickly spread across the world, and it is now a major public health concern. Here we present a 21-year-old male with encephalomyelitis following intermittent vomiting and malaise for 4 days. He reported upper respiratory signs and symptoms 2 weeks before this presentation. Two cerebrospinal fluid (CSF) analyses were notable for mononuclear pleocytosis, elevated protein (more than 100 mg/dl), and hypoglycorrhachia. Brain Magnetic Resonance Imaging (MRI) showed bilateral posterior internal capsule lesions extending to the ventral portion of the pons and a marbled splenium hyperintensity pattern. Cervical and thoracic MRI showed longitudinally extensive transverse myelitis (LETM), none of which were enhanced with gadolinium. Both the AQP4 and MOG antibodies were negative. Spiral chest computed tomography (CT) scan confirmed to COVID-19 as did the high IgG level against coronavirus, but the oropharyngeal swabs were negative. Neurological manifestations of COVID-19 have not been adequately studied. Some COVID-19 patients, especially those suffering from a severe disease, are highly likely to have central nervous system (CNS) manifestations. Our case is a post-COVID-19 demyelinating event in the CNS.


Time-resolved enantiomer-exchange probed by using the orbital angular momentum of X-ray light.
Molecular chirality, a geometric property of utmost importance in biochemistry, is now being investigated in the time-domain. Ultrafast chiral techniques can probe the formation or disappearance of stereogenic centers in molecules. The element-sensitivity of X-rays adds the capability to probe chiral nuclear dynamics locally within the molecular system. However, the implementation of ultrafast techniques for measuring transient chirality remains a challenge because of the intrinsic weakness of chiral-sensitive signals based on circularly polarized light. We propose a novel approach for probing the enantiomeric dynamics by using the orbital angular momentum (OAM) of X-ray light, which can directly monitor the real-time chirality of molecules. Our simulations probe the oscillations in excited chiral formamide on different potential energy surfaces and demonstrate that using the X-ray OAM can increase the measured asymmetry ratio. Moreover, combining the OAM and SAM (spin angular momentum) provides stronger dichroic signals than linearly polarized light, and offers a powerful scheme for chiral discrimination.


The effect of random blood transfusions on immunoglobulin production by peripheral blood mononuclear cells from uraemic patients.
The effect of blood transfusion on humoral immunity in chronic renal failure was studied by examining immunoglobulin production in vitro, in patients awaiting renal transplantation. Pokeweed mitogen (PWM) induced IgG plaque formation was normal in non-transfused uraemic patients while both spontaneous and Staphylococcus aureus Cowan I (SAC) induced immunoglobulin production were reduced. Five to ten units of third party blood transfusion reduced PWM-driven B cell differentiation, but had no effect on SAC-induced plaque formation, while spontaneous production of immunoglobulin was either enhanced or unaffected. As it is known that the response to SAC is less affected by suppressor T cell activity than that to PWM, these differences in the inhibitory effects of blood transfusion on B cell differentiation are further evidence that transfusion may act by increasing suppressor T cell activity.


Identification, characterization, and nucleotide sequence of the F17-G gene, which determines receptor binding of Escherichia coli F17 fimbriae.
Enterotoxigenic Escherichia coli strains express fimbriae which mediate binding to intestinal mucosal cells. The F17 fimbriae mediate binding to N-acetylglucosamine-containing receptors present on calf intestinal mucosal cells. These fimbriae consist of F17-A subunit peptides. Analysis of the F17 gene cluster indicated that at least the F17-A, F17-C, F17-D, and F17-G genes are indispensable to obtain adhesive F17 fimbriae (unpublished data). Genetic evidence is presented that the F17-G protein, a minor fimbrial component, is required for the binding of the F17 fimbriae to the intestinal villi. The F17-G gene was cloned and sequenced. An open reading frame of 1,032 bp encoding a polypeptide of 344 amino acids, starting with a signal sequence of 22 residues, was localized. The F17-G mutant strain produced F17 fimbriae which were morphologically identical to the fimbriae purified from strains which contained the intact F17 gene cluster. However, this F17-G mutant could no longer adhere to calf villi. The F17-G locus was shown to act in trans: transformation of the F17-G mutant strain, still expressing the genes F17-A, F17-C, and F17-D, with a vector expressing the F17-G gene restored the binding activity of this mutant strain.


Vps4a Regulates Autophagic Flux to Prevent Hypertrophic Cardiomyopathy.
Autophagy has stabilizing functions for cardiomyocytes. Recent studies indicate that an impairment in the autophagy pathway can seriously affect morphology and function, potentially leading to heart failure. However, the role and the underlying mechanism of the endosomal sorting complex required for transport (ESCRT) family protein, in particular the AAA-ATPase vacuolar protein sorting 4a (Vps4a), in regulating myocardial autophagy remains unclear. In the present study, cardiomyocyte-specific Vps4a knockout mice were generated by crossing Vps4aflox/flox (Vps4afl/fl) with Myh6-cre transgenic mice. As a result, we observed a partially dilated left ventricular (LV) chamber, a significant increase in heart weight to body weight ratio (HW/BW), and heart weight to tibial length ratio (HW/TL), hypertrophic cardiomyopathy and early lethality starting at 3 months of age. Hematoxylin-eosin (HE), immunofluorescence assay (IFA), and Western blot (WB) revealed autophagosome accumulation in cardiomyocytes. A transcriptome-based analysis and autophagic flux tracking by AAV-RFP-GFP-LC3 showed that the autophagic flux was blocked in Vps4a knockout cardiomyocytes. In addition, we provided in vitro evidence demonstrating that Vps4a and LC3 were partially co-localized in cardiomyocytes, and the knockdown of Vps4a led to the accumulation of autophagosomes in cardiomyocytes. Similarly, the transfection of cardiomyocytes with adenovirus (Adv) mCherry-GFP-LC3 further indicated that the autophagic flux was blocked in cells with deficient levels of Vps4a. Finally, an electron microscope (EM) showed that the compromised sealing of autophagosome blocked the autophagic flux in Vps4a-depleted cardiomyocytes. These findings revealed that Vps4a contributed to the sealing of autophagosomes in cardiomyocytes. Therefore, we demonstrated that Vps4a deletion could block the autophagic flux, leading to the accumulation of degradation substances and compromised cardiac function. Overall, this study provides insights into a new theoretical basis for which autophagy may represent a therapeutic target for cardiovascular diseases.


Chemical composition and pharmacological activities of Pisum sativum.
Consumption of vegetables has been proven to be effective in the prevention of different diseases. Traditionally edible aerial part of Pisum sativum L. subsp. sativum (Fabaceae) is used to treat diabetes, heart diseases and as blood purifier. Present study was aimed to explore the traditional use of aerial parts of P. sativum as a source of antidiabetic agent. In addition, antioxidant activity and chemical composition was carried out. Total polyphenol content was spectrophotometrically determined using Folin Chiocalteu's reagent while the flavonoids by aluminum chloride colorimetric assay. Identification of compounds of the extract was made through HPLC and LCMS. Antihyperglycemic activity was assessed by oral glucose tolerance test in mice. Antioxidant activity was determined by DPPH free radical scavenging and reducing power assay. Total polyphenol and total flavonoids content were found to be 51.23 mg gallic acid equivalent and 30.88 mg quercetin equivalent per gram of dried plant extract respectively. Ellagic acid and p-coumeric acid were detected through HPLC. A total of eight compounds including naringenin, β-sitosterol were indentified through LCMS. In OGTT, extract (200 mg/kg bw) showed a 30.24% decrease (P< 0.05) in blood glucose levels at 30 min compared to the normal control. The extract showed IC50 value of 158.52 μg/mL in DPPH scavenging assay and also showed comparable reducing power. Along with other compounds ellagic acid and β-sitosterol present in the extract may be responsible for its antioxidant as well as antihyperglycemic activities. Altogether these results rationalize the use of this vegetable in traditional medicine.


[The rule of metastatic pelvic lymph node distribution in patients with early stage cervical carcinoma].
To investigate the distribution of metastatic pelvic lymph nodes in the women with early stage cervical carcinoma, and the feasibility of dividing these nodes into three stations in those patients. (99m)Tc-DX of 2 ml was injected into the cervix to a depth of 5 to 10 mm at 3, 6, 9, 12 o'clock positions preoperatively in 196 patients with early stage cervical cancer. Pelvic lymphadenectomy and radical hysterectomy were performed in all patients. Pelvic lymph nodes were detected by gamma-probe. The sentinel lymph nodes (SLN) were determined if the radioactivity reached 5 times higher than that in the ipsilateral nodes. All resected pelvic lymph nodes were examined by histopathology with HE stained serial sections. Of the 196 patients, 41 were found to have metastasis in 83 lymph nodes. The metastatic rate was 78.3% (65/83) in the parametrial and obturator lymph nodes, 20.5% (17/83)in the internal and external iliac lymph nodes, 1.2% (1/83) in the commmon iliac lymph nodes. Of the 22 patients with metastatic parametrial lymph nodes, metastatic external iliac lymph nodes were detected in 5 patients, and metastatic internal iliac lymph nodes in 3 patients. Among the 19 patients with metastatic obturator lymph nodes, metastatic external iliac lymph nodes were found in 4 patients, and metastatic internal iliac lymph nodes in 3 cases. It was shown by Chi-sqare test that the metastases in parametrial and/or obturator lymph nodes were positively correlated with lymph node metastases in other pelvic sites. Eighty-one SLN were found to have metastasis. The metastatic rate of parametrial and obturator SLN was 79.0% (64/81) versus 21.0% (17/81) of internal and external iliac SLN. No statistically significant difference in 1- and 3-yr survival was observed between the groups with and without metastasis in parametrial and obturator lymph nodes, while the 5-yr survival rate in the patients without metastatic lymph node was 93.2%, significantly higher than that of patients with lymphatic metastasis (65.1%). It is feasible for cervical cancer to divide the pelvic lymph nodes into three levels. The level I lymph nodes consist of parametrial and obturator lymph nodes. Internal and external iliac lymph nodes can be considered as level II lymph nodes, and the common iliac and inguinal lymph nodes as level III nodes. A rational treatment plan can be made according to the distribution of metastatic pelvic lymph nodes.


Interactions between sleep, other body rhythms, immune responses, and exercise.
Biological rhythms can influence both exercise tolerance and immune function. Most studies have focussed upon circadian rhythms, but some circaseptan, circatrigintan, and circannual cycles have also been described. Rhythms may have an endogenous or an exogenous basis. Endogenous rhythms originate in the cells of the suprachiasmatic nucleus. Impulses from this region pass to the pineal gland, where they regulate the production of melatonin, a compound that modulates the sleep/wakefulness cycle. Endocrine, physiological, and psychological parameters all show evidence of periodicity. Most components of the immune system, both cellular and humoral, also show large rhythmic changes. It is not yet clear how far such periodicity is secondary to changes in other body systems. Nevertheless, the magnitude of variation is such that it is vital to obtain experimental and control data at identical time points in both acute and chronic studies of exercise and immune function. Disturbance of the sleep/wakefulness cycle can constitute a form of stress, with adverse consequence for immune function.


Stressful life events and Graves' disease.
The role of stressful life events in the onset of Graves' disease (toxic diffuse goitre) is controversial. However, the numerous early clinical reports that supported such an association were not adequately controlled and specificity of the diagnosis could be questioned. Later studies have not shown a causal relation, but these studies were small, did not have proper controls, or epidemiological methods were inappropriate. To assess possible associations between life events, heredity, social support, and Graves' disease, we have done a population-based case-control study in a defined area with about 1 million inhabitants. Over 2 years, 208 (95%) of 219 eligible patients with newly-diagnosed Graves' disease and 372 (80%) of all selected matched controls answered an identical mailed questionnaire about marital status, occupation, drinking and smoking habits, physical activity, familial occurrence of thyroid disease, life events, social support, and personality. Compared with controls, patients claimed to have had more negative life events in the 12 months preceding the diagnosis, and negative life-event scores were also significantly higher (odds ratio 6.3, 95% confidence interval 2.7-14.7, for the category with the highest negative score). Individuals who had relatives with thyroid disease (especially first-degree and second-degree relatives) were more likely to have Graves' disease (3.6, 2.2-5.9). Slightly more patients than controls were divorced (1.8, 1.0-3.3) and reported a less frequent intake of alcohol (0.4, 0.2-0.8). When results were adjusted for possible confounding factors in multivariate analyses, risk estimates were almost unchanged. These findings indicate that negative life events and hereditary factors may be risk factors for Graves' disease.


Monoclonal antibodies in cancer therapy.
The need for improved specificity in cancer therapy is apparent. With the advent of monoclonal antibodies, the possibility of specifically targeted therapy is being considered. Early trials of monoclonal antibody in experimental animals and humans have indicated its ability to traffic to specific tumor sites and to localize on or around the tumor cells displaying antigens to which the antibody is directed. This evidence of specific targeting, along with preliminary evidence of therapeutic efficacy for monoclonal antibodies and immunoconjugates with drugs, toxins, and isotopes is encouraging. The current status of clinical trials with monoclonal antibodies is reviewed and an example of the experimental approach for the development of immunoconjugates in animal models is presented.


Unveiling the Potential of Marine Biopolymers: Sources, Classification, and Diverse Food Applications.
Environmental concerns regarding the usage of nonrenewable materials are driving up the demand for biodegradable marine biopolymers. Marine biopolymers are gaining increasing attention as sustainable alternatives in various industries, including the food sector. This review article aims to provide a comprehensive overview of marine biopolymers and their applications in the food industry. Marine sources are given attention as innovative resources for the production of sea-originated biopolymers, such as agar, alginate, chitin/chitosan, and carrageenan, which are safe, biodegradable, and are widely employed in a broad spectrum of industrial uses. This article begins by discussing the diverse source materials of marine biopolymers, which encompass biopolymers derived from seaweed and marine animals. It explores the unique characteristics and properties of these biopolymers, highlighting their potential for food applications. Furthermore, this review presents a classification of marine biopolymers, categorizing them based on their chemical composition and structural properties. This classification provides a framework for understanding the versatility and functionality of different marine biopolymers in food systems. This article also delves into the various food applications of marine biopolymers across different sectors, including meat, milk products, fruits, and vegetables. Thus, the motive of this review article is to offer a brief outline of (a) the source materials of marine biopolymers, which incorporates marine biopolymers derived from seaweed and marine animals, (b) a marine biopolymer classification, and (c) the various food applications in different food systems such as meat, milk products, fruits, and vegetables.


Ocular Involvement of Granulomatosis with Polyangiitis.
Granulomatosis with polyangiitis (GPA), formerly referred to as Wegener's disease, is a form of ANCA-associated vasculitis. It manifests mainly in the kidneys and the upper respiratory tract, but ocular involvement is not uncommon. In this article, four cases with ocular manifestations are presented with comprehensive photographic documentation. We describe the way to proper diagnosis, which may be long, the possible treatment, and the final outcomes. Our patients had the following ocular manifestations of GPA: retinal vasculitis, anterior necrotizing scleritis, medial orbital wall and orbital floor erosion with middle face deformation, compressive optic neuropathy due to retrobulbar inflammatory mass, and the abscess of the eyelids, inflammatory intraorbital mass causing exophthalmos and diplopia. This manuscript includes the description of severe forms of GPA, the initial signs and symptoms, relapses, and difficulties in achieving remission. The extraocular involvement is described with diagnostic modalities and laboratory findings. One of the reported cases was diagnosed by an ophthalmologist on the basis of ocular symptoms in the early stages of the disease. Our outcomes are compared with those discussed in the literature.


Puncture of shoulder, elbow, and carpal joints in goats and sheep.
The forelimbs joints and bones of 16 normal goats and sheep were studied to determine optimal injection techniques for the shoulder, elbow, and carpal joints. Based on the findings, trial injections of marker substances were made in 8 anesthetized animals. The joints were then dissected and rates of success were determined, and they were 88% of shoulder, 87% of elbow, 94% of radiocarpal, and 81% of midcarpal and carpometacarpal joints.


Bone marrow toxicity in HCV genotype 5a-infected patient after peg-IFN alpha-2a and ribavirin therapy.
The optimal therapy for HCV-related chronic hepatitis is the combination of pegylated interferon alpha (peg-IFN alpha) plus ribavirin (RBV). Unfortunately, both peg-IFN alpha and RBV are responsible for a wide range of adverse events and potentially severe toxicities, particularly hematological alterations. Indeed, RBV is generally responsible for anemia through hemolysis, while peg-IFN alpha induces more commonly leukopoenia and thrombocytopenia, presumably through bone marrow toxicity. Actually, data regarding histopathological bone marrow alterations in HCV-infected patients following IFN-alpha therapy is scanty. We report a case of a HCV-infected cirrhotic patient, who developed bone marrow alterations following one-year peg-IFN alpha plus RBV treatment, and we describe the associated histopathological features. Our case report provides new significant insight on the histopathological changes occurring in bone marrow of HCV-infected cirrhotic patients during peg-IFN alpha-2a plus RBV treatment, providing also additional information on potential bone marrow toxicity in the course of IFN-based treatments.


E-Cigarettes-a review of the evidence-harm versus harm reduction.
The World Health Organization estimates there are 1.1 billion cigarette smokers across the globe and that tobacco related deaths number 7 million per year. Electronic nicotine delivery systems (ENDS) are available to contribute options for smoking cessation and include e-cigarettes, e-hookahs, vape pens, mods, and vaping. The growing use of ENDS, or e-cigarettes, in the US and globally across populations is dramatic. Although users may think that e-cigarettes are less harmful than combustible tobacco products, the evidence shows that there are known risks and harms for users. E-cigarettes have varying amounts of toxicants, nicotine, and carcinogens and put the user at risk for lung diseases and COVID-19 similar to smokers. Currently, most governing bodies have not approved e-cigarettes as a smoking cessation tool but do state if a person has failed conventional smoking cessation treatments that e-cigarettes used alone for the short term may help those to quit combustible tobacco and nicotine. A shared decision-making approach should be used when discussing e-cigarettes as a harm reduction tool. More studies and long-term data are needed to assess potential benefits and harms. What is known is that prevention efforts and policy are needed to avoid adolescents and other vulnerable populations from initiating tobacco or e-cigarette use.


Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities.
Gliomas represent the most common malignant primary brain tumors, and a high-grade subset of these tumors including glioblastoma are particularly refractory to current standard-of-care therapies including maximal surgical resection and chemoradiation. The prognosis of patients with these tumors continues to be poor with existing treatments and understanding treatment failure is required. The dynamic interplay between the tumor and its microenvironment has been increasingly recognized as a key mechanism by which cellular adaptation, tumor heterogeneity, and treatment resistance develops. Beyond ongoing lines of investigation into the peritumoral cellular milieu and microenvironmental architecture, recent studies have identified the growing role of mechanical properties of the microenvironment. Elucidating the impact of these biophysical factors on disease heterogeneity is crucial for designing durable therapies and may offer novel approaches for intervention and disease monitoring. Specifically, pharmacologic targeting of mechanical signal transduction substrates such as specific ion channels that have been implicated in glioma progression or the development of agents that alter the mechanical properties of the microenvironment to halt disease progression have the potential to be promising treatment strategies based on early studies. Similarly, the development of technology to measure mechanical properties of the microenvironment in vitro and in vivo and simulate these properties in bioengineered models may facilitate the use of mechanical properties as diagnostic or prognostic biomarkers that can guide treatment. Here, we review current perspectives on the influence of mechanical properties in glioma with a focus on biophysical features of tumor-adjacent tissue, the role of fluid mechanics, and mechanisms of mechanical signal transduction. We highlight the implications of recent discoveries for novel diagnostics, therapeutic targets, and accurate preclinical modeling of glioma.


Embeddings of a strange attractor into R3.
The algorithm for determining a global Poincaré section is applied to a previously studied dynamical system on R2 x S1 and a one-parameter family of embeddings of the strange attractor it generates into R3. We find that the topological properties of the attractor are embedding dependent to a limited extent. These embeddings rigidly preserve mechanism, which is a simple stretch and fold. The embeddings studied show three discrete topological degrees of freedom: parity, global torsion, and braid type of the genus-one torus bounding the embedded attractor.


Establishment and Enforcement of Operational Rules at an Unsanctioned Safe Drug Consumption Site in the United States, 2014-2020.
Objectives. To examine how operational rules are established and enforced at an unsanctioned safe consumption site (SCS) operating in the United States. Methods. We conducted 44 qualitative interviews with people who use drugs, staff members, and volunteers at an unsanctioned SCS and analyzed them using an inductive thematic approach. Results. Rule-making processes were largely driven by concerns raised by service users rather than driven by external pressures, and iterated rapidly in response to changing needs. The unsanctioned nature of the site produced an environment where bottom-up rule-making was critical to generating a shared sense of ownership of the site and where enforcement was necessarily fluid. Conclusions. Removing external restrictions on operational rules for SCSs results in a flexible set of rules that are highly responsive to the social and public health needs of people who use drugs. Legislation and regulations of SCSs should aim to place as few hard limits on operating conditions as possible to maximize involvement of and responsiveness to people who use drugs. (Am J Public Health. 2022;112(S2):S166-S172. https://doi.org/10.2105/AJPH.2022.306714).


[Cryotherapy is useful and safe in the prevention of oral mucositis after high-dose melphalan (L-PAM)].
We prospectively assessed the effectiveness of cryotherapy after high-dose L-PAM to prevent oral mucositis. Cryotherapy with ice tips was commenced 15 minutes before L-PAM administration, and continued until the end of administration. Twenty-six patients were enrolled in this study. Thirteen patients with myeloma were treated with 200 mg/m2 L-PAM followed by autologous peripheral blood stem cell transplantation, and 13 patients (4 AML, 4 MDS, 2 ALL, 2 lymphoma and 1 CML) were treated with 140 mg/m2 L-PAM followed by allogeneic stem cell transplantation. Grade 1 mucositis occurred in four of 13 patients (31%) with 200 mg/m2 L-PAM, and 2 of 13 patients (16%) with 140 mg/m2 L-PAM. Only one patient had grade 2 mucositis, and no grade 3 mucositis were observed. The procedure was well tolerated in all patients. These data suggest that cryotherapy is effective to minimize L-PAM-induced oral mucositis.


Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease.
Alzheimer's disease (AD) is a neurodegenerative disease that inhibits cognitive functions and has no cure. This report reviews the current diagnostic standards for AD with an emphasis on early diagnosis using the cerebrospinal fluid (CSF) biomarkers amyloid-beta, t-tau, and p-tau and fluorodeoxyglucose positron emission tomography imaging. Abnormal levels of these CSF biomarkers and decreased cerebral uptake of glucose have recently been used in the early diagnosis of AD in experimental studies. These promising biomarkers can be measured using immunoassays performed in singleplex or multiplex formats. Although presently, there are no Food and Drug Administration-approved in vitro diagnostics (IVDs) for early detection of AD, a multiplex immunoassay measuring a panel of promising AD biomarkers in CSF may be a likely IVD candidate for the clinical AD diagnostic market. Specifically, the INNO-BIA AlzBio3 immunoassay kit, performed using bead arrays on the xMAP Luminex analyzer, allows simultaneous quantification of amyloid-beta, t-tau, and p-tau biomarkers. AD biomarkers can also be screened using enzyme-linked immunosorbent assays that are offered as laboratory-developed tests.


Membrane potential oscillations and corticothalamic connectivity in rat associational thalamic neurons in vitro.
Thalamic relay neurons were recorded from the dorsolateral and lateroposterior nuclei of the rat thalamus in a superfused explant preparation. The mean membrane potential of these cells was -67 +/- 7 mV, input resistance 114 +/- 31 M omega and spike amplitude 75 +/- 6 mV. Low-threshold slow membrane potential oscillations (1-4 Hz) were present in about 46% of the neurons. They occurred either spontaneously or following a membrane potential perturbation. In a subpopulation of cells, we also observed a high-threshold membrane oscillation when cells were depolarized above -45 mV. This oscillation consisted of bursts of low-amplitude spikes interrupted by rhythmic after-hyperpolarizations. Stimulation of the corticothalamic pathway elicited prolonged inhibitory postsynaptic potentials in associational thalamic neurons. In the presence of picrotoxin, corticothalamic input evoked prominent excitatory postsynaptic responses that showed marked short-term synaptic plasticity. Our results suggest that associational thalamic neurons maintained in vitro have a strong tendency to exhibit membrane oscillations. In addition, they receive a direct excitatory cortical input that remained functional in explant preparation.


Two polymorphs of afobazole from powder diffraction data.
Afobazole {systematic name: 2-[2-(morpholin-4-yl)ethylsulfanyl]-1H-benzimidazole} is a new anxiolytic drug and Actins, Auzins & Petkune [(2012). Eur. Patent EP10163962] described four polymorphic modifications. In the present study, the crystal structures of two monoclinic polymorphs, 5-ethoxy-2-[2-(morpholin-4-ium-4-yl)ethylsulfanyl]-1H-benzimidazol-3-ium dichloride, C15H23N3O2S(2+)·2Cl(-), (II) and (IV), have been established from laboratory powder diffraction data. The crystal packing and conformation of the dications in (II) and (IV) are different. In (II), there are channels in the [001] direction, which offer atmospheric water molecules an easy way of penetrating into the crystal structure, thus explaining the higher hygroscopicity of (II) compared with (IV).


Identification of Peptides of Small Extracellular Vesicles from Bone Marrow-Derived Macrophages.
Small extracellular vesicles (sEVs) are typically secreted by the exocytosis of multivesicular bodies (MVBs). These nanovesicles with a diameter of <200 nm are present in various body fluids. These sEVs regulate various biological processes such as gene transcription and translation, cell proliferation and survival, immunity and inflammation through their cargos, such as proteins, DNA, RNA, and metabolites. Currently, various techniques have been developed for sEVs isolation. Among them, the ultracentrifugation-based method is considered the gold standard and is widely used for sEVs isolation. The peptides are naturally biomacromolecules with less than 50 amino acids in length. These peptides participate in a variety of biological processes with biological activity, such as hormones, neurotransmitters, and cell growth factors. The peptidome is intended to systematically analyze endogenous peptides in specific biological samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Here, we introduced a protocol to isolate sEVs by differential ultracentrifugation and extracted peptidome for identification by LC-MS/MS. This method identified hundreds of sEVs-derived peptides from bone marrow-derived macrophages.


Transport and endogenous release of vitamin B12 in the dually perfused human placenta.
The kinetics for vitamin B12, cobalamin (Cbl), transfer across the human placenta, and the retention of the endogenous Cbl and its release into the maternal and fetal compartments were investigated in a dually perfused human term placenta in vitro. After 4 hours of perfusion following a single bolus injection (peak maternal perfusate 94 fmol/ml) of 57Co-Cbl into the maternal reservoir, the maternal [57Co-Cbl] rapidly decreased whereas the fetal [57Co-Cbl] was only 9% of the final maternal [57Co-Cbl]. Even though there was a limited transfer of 57Co-Cbl to the fetus, the placenta rapidly accumulated Cbl. At 4 hours, 18% of the initial 57Co-Cbl dose was in the placenta; only 3% of the initial dose was in the fetal perfusate. Also after 4 hours, [57Co-Cbl] was bound > 95% to transcobalamin (TC)I/III-like proteins in the maternal perfusate, whereas Cbl was bound to TCI/III- and TCII-like proteins with some free in the fetal perfusate. In the cytosol, > 95% of the [57Co-Cbl] was bound (80% to TCII-like and 19% to TCI/III-like proteins). When no exogenous Cbl was added, total endogenous [Cbl] in the maternal circulation increased with time during 8 hours of perfusion at a rate of 0.25 +/- 0.12 pmol/gm per hour. Only 2% of this Cbl was free, whereas 98% was bound to specific binding proteins. Neither plateau values nor equilibration with the fetal side were noted. In the fetal circulation, there was a release of Cbl at a rate of 0.015 +/- 0.003 pmol/gm per hour, which was 99.99% bound. Thus the human placenta rapidly concentrates Cbl in the perfused lobule with little distribution of Cbl to nonperfused areas. Therefore, the human placenta modulates the asymmetric transfer of vitamin B12 on the basis of release of specific Cbl-binding proteins (TCI/III- and TCII-like) into the maternal and fetal perfusates.


[Assessment of mental status at the drivers of the vehicles after using alcohol or drunk driving].
Alcohol changes the behavior and works toward making behavior carrying a risk, such as driving in the state of intoxication, work at height, using machines requiring full medical fitness, breach of security at work. The aim of the study was to present a preliminary assessment of the mental state of drivers by gender, to driving under the influence of alcohol or in a state of intoxication, who volunteered for the study to the Regional Occupational Health Centre in Kielce and psychological analysis of the type of decisions which the driver received after the testing. 526 papers were assessed psychological examination of drivers surveyed in 2004, 2007 and 2010 who received a positive psychological judgment of the scheduled date of follow-up examination or negative. In 2012, an additional random sample of 50 drivers who ran a vehicle under the influence of alcohol were assessed using the general health Questionnaire (GHQ-The General Health Questionnaires) David Goldberg. Of the 526 drivers surveyed 3774 due to mental disorders received a favorable ruling or negative term. Psychological judgments of 526 400 were issued to the timing of follow-up examination and negative 126th. The 320 drivers had alcohol dependence syndrome. That 155 was referred to the outpatient alcohol treatment centers facilities located near their place of residence. Only 3 drivers in Group 50 evaluated using a questionnaire GHQ had symptoms of depression. An important reason for inability to drive are the irregularities observed in psychological tests. In 35% are impaired motor skills, 23% personality disorder, 20% of changes in tests assessing intelligence and memory. There was no significant relationship (p = 0.5583) between gender and the concentration of GGT in the category of normal.


The ammonium sulfate inhibition of human angiogenin.
In this study, we investigate the inhibition of human angiogenin by ammonium sulfate. The inhibitory potency of ammonium sulfate for human angiogenin (IC50 = 123.5 ± 14.9 mm) is comparable to that previously reported for RNase A (119.0 ± 6.5 mm) and RNase 2 (95.7 ± 9.3 mm). However, analysis of two X-ray crystal structures of human angiogenin in complex with sulfate anions (in acidic and basic pH environments, respectively) indicates an entirely distinct mechanism of inhibition. While ammonium sulfate inhibits the ribonucleolytic activity of RNase A and RNase 2 by binding to the active site of these enzymes, sulfate anions bind only to peripheral substrate anion-binding subsites of human angiogenin, and not to the active site.


[The impact of antibiotic treatment in patients with influenza-like illness].
To study the etiology of influenza-like illness (ILI) in Beijing, and to investigate the impact of antibiotic treatment on outcomes. This was a prospective cohort study. Patients with diagnosis of influenza-like illness were prospectively enrolled for study of bacterial and viral pathogens. Demographic characteristics, underlying diseases, respiratory and extrapulmonary symptoms, laboratory tests were also collected for analysis of relationship between drug therapy and outcomes. A total of 476 cases were enrolled between Dec. 2006 and Apr. 2007, of whom 454 cases were used for analysis. Influenza virus was the most common pathogen( n = 197, 43.4%), with other pathogens rarely seen. The mean age of the patients was (33 +/- 13) years, and the ratio of male to female was 1.1:1. Twenty four patients (5.3% ) received influenza vaccine. The rate of antibiotic prescription after onset of illness was 63.4%, but none received antiviral drugs such as Oseltamivir and amantadine. Compared with influenza-negative patients, patients with influenza were older, had more underlying diseases and had greater severity of symptoms such as cough, sore throat, headache and myalgia (but with no statistical differences). The influenza syndrome (T > or = 39 degrees C plus cough, sore throat and headache or myalgia) was more common in the influenza group compared to the influenza-negative patients (P < 0.05). The ratio of antibiotic prescription was 67% in the influenza group, and the total white blood cell and platelet count, percentage of neutrophils were higher in antibiotic treatment patients compared with non-antibiotic treatment patients (P < 0.01). The cost in patients who received antibiotics was twice as much as non-antibiotic treatment patients (P < 0.05), but the defervescence time and respiratory symptom alleviation time did not differ. Cox regression analysis showed that the total white blood count and the differentials (OR value 1.049 and 1.014, respectively), but not antibiotic use were the independent risk factors for longer defervescence time. Influenza virus was the most common pathogen for adult patients with ILI in Beijing city during the winter and the spring seasons. Antibiotic treatment of adult patients with ILI did not improve illness resolution, while the cost was increased significantly.


Bilateral peripheral facial palsy secondary to lymphoma in a patient with HIV/AIDS: a case report and literature review.
Neurological complications represent one of the most important causes of morbidity and mortality in patients with HIV/AIDS. However, peripheral neuropathy comprises only 5% to 20% of the total neurological complications and facial nerve palsy, especially when it is bilateral, is a less common manifestation. Peripheral facial palsy has been considered as a possible neurological complication of the early stage of HIV infection but the number of reported cases in the literature is limited. Histological findings of nervous tissue in peripheral facial palsy at an early stage of HIV infection include a degenerative and not suppurative inflammatory process, but its etiology remains obscure. Peripheral facial palsy in the late stage of HIV infection is characterized by an advanced immunological deficit and generally it is secondary to an opportunistic infection of the CNS, such as neurotoxoplasmosis and lymphoma. However, this peripheral attack of the facial nerve is not very common at this late stage of HIV infection. Bilateral peripheral facial palsy as a complication of non-Hodgkin s lymphoma is considered an extremely rare entity. There are no published reports of bilateral peripheral facial palsy secondary to lymphomas or other neoplasms of the CNS in immunosuppressed patients. Non-Hodgkin s lymphoma (NHL) has been considered a late and relatively common manifestation of HIV infection, but an exact cause for the higher incidence of this malignant neoplasm in HIV/AIDS patients is still uncertain.


The aortic intima in organ culture. Response to culture conditions and partial endothelial denudation.
A culture technique for whole blood vessel wall that preserves an intact and regenerative endothelium has been developed. The retention of an intact endothelium allows careful observation of the tissue as it responds to culture conditions, responses that include a change of replication timing and the induction of particulate endocytosis. Complete and normal regeneration of the endothelium in explants has made possible evaluation of the differences between the regeneration of endothelial cell monolayers and regeneration of intima in vivo. From these comparisons it appears that the shorter induction time of endothelial migration and proliferation and the more rapid migration in endothelial cell monolayers are due to effects of the culture medium or plastic culture surface, while the higher than normal cell density found in the intima after wound recovery in vivo probably is due to the dynamics of the blood vessel itself. The ability to control cell-cell interactions on the cultured tissue has made possible the investigation of gap junction-mediated metabolic interactions in regenerating intima. Results indicate that the disruptive effects of intimal regeneration do not depend on or produce an obvious change in junction-mediated nucleotide transfer between endothelial cells.


Positive ion pair cooperativity exhibited for the binding of phosphate under physiological conditions.
The synthesis of a heteroditopic receptor which exhibits positive cooperativity for the binding of phosphate ion pairs under physiological conditions. Optimised complementarity between crown ether host and metal guest leads to increased binding affinity, Ka.


[Cardiac events and 5-year survival after acute coronary syndromes].
To evaluate the incidence of cardiac events and survival in patients with first acute coronary syndromes during 5-year period. Data on 732 patients admitted with first acute coronary syndrome were collected in a database. During hospitalization period 45.4% of the patients received reperfusion therapy. During follow-up period (4.49+/-2.1 years) 215 (29.4%) patients had cardiac events: 15.3%--myocardial revascularization, 8.1%--repeated myocardial infarction, 11.5%--cardiovascular deaths. The highest (5%) mortality rate was during first year, whereas during the following four years--1.5% annually. Kaplan-Meier analysis for survival free of cardiovascular death revealed that mortality rates were higher among patients who were > or =65 years old (long-rank test, p=0.02); had heart failure at admission (p=0.003), left ventricular ejection fraction <40% (p=0.04), significance diastolic dysfunction (p=0.035), III-IV degrees mitral regurgitation (p=0.00006); did not received reperfusion therapy (p=0.007). The analysis of this long-term follow-up data shows that the patients with acute coronary syndromes carry a high risk of death and need better treatment strategies to reduce risk.


Spinosad- and Deltamethrin-Induced Impact on Mating and Reproductive Output of the Maize Weevil Sitophilus zeamais.
Assessments of acute insecticide toxicity frequently focus on the lethal effects on individual arthropod pest species and populations neglecting the impacts and consequences of sublethal exposure. However, the sublethal effects of insecticides may lead to harmful, neutral, or even beneficial responses that may affect (or not) the behavior and sexual fitness of the exposed insects. Intriguingly, little is known about such effects on stored product insect pests in general and the maize weevil in particular. Thus, we assessed the sublethal effects of spinosad and deltamethrin on female mate-searching, mating behavior, progeny emergence, and grain consumption by maize weevils. Insecticide exposure did not affect the resting time, number of stops, and duration of mate-searching by female weevils, but their walking velocity was compromised. Maize weevil couples sublethally exposed to deltamethrin and spinosad exhibited altered reproductive behavior (walking, interacting, mounting, and copulating), but deltamethrin caused greater impairment. Curiously, higher grain consumption and increased progeny emergence were observed in deltamethrin-exposed insects, suggesting that this pyrethroid insecticide elicits hormesis in maize weevils that may compromise control efficacy by this compound. Although spinosad has less of an impact on weevil reproductive behavior than deltamethrin, this bioinsecticide also benefited weevil progeny emergence, but did not affect grain consumption. Therefore, our findings suggest caution using either compound, and particularly deltamethrin, for controlling the maize weevil, as they may actually favor this species population growth when in sublethal exposure requiring further assessments. The same concern may be valid for other insecticides as well, what deserves future attention.


[Tics and Tourette's syndrome in children].
The article represents a review of modern literature on tics and Tourette's syndrome in paediatric population and describes recent advances in neurogenetics, neuroanatomy and neurotransmitter heterogeneity of the disease pathogenesis. The analysis of the literature supports the plausibility of transformation of tics and Tourette's syndrome from psychiatric disorders into neurological disorders (according to ICD-11) based on recent data on neurophysiology and functional neuroanatomy. Neuroanatomy of motor behaviour is described as the most complex self-regulating neural network of thalamo-cortical loop, basal ganglia in combination with the limbic system, insular and cingulate cortex with involvement of hippocampus, subthalamic region and cerebellum. The evaluation of pharmaceutical treatment options has been carried out, including a review of successful local experience in treating tics in paediatric patients with hopantenic acid, topiramate and neuropeptides of cortexin.


Social balance on networks: Local minima and best-edge dynamics.
Structural balance theory is an established framework for studying social relationships of friendship and enmity. These relationships are modeled by a signed network whose energy potential measures the level of imbalance, while stochastic dynamics drives the network toward a state of minimum energy that captures social balance. It is known that this energy landscape has local minima that can trap socially aware dynamics, preventing it from reaching balance. Here we first study the robustness and attractor properties of these local minima. We show that a stochastic process can reach them from an abundance of initial states and that some local minima cannot be escaped by mild perturbations of the network. Motivated by these anomalies, we introduce best-edge dynamics (BED), a new plausible stochastic process. We prove that BED always reaches balance and that it does so fast in various interesting settings.


Mitral valve surgery for dilated cardiomyopathy with mitral regurgitation.
Outcomes of surgery for non-ischemic non-valvular dilated cardiomyopathy with associated mitral regurgitation were assessed in 8 consecutive patients who underwent 9 mitral valve operations between 2001 and 2004. Mitral valve replacement was performed when the coaptation depth exceeded 10 mm. Two patients initially underwent mitral valvuloplasty, and 6 underwent valve replacement. One patient had valve replacement soon after valvuloplasty. Transthoracic echocardiography was performed immediately before surgery, before discharge, and during follow-up. Transesophageal echocardiography was carried out intraoperatively to assess valvular and ventricular function. Postoperative mean functional class was significantly better than the preoperative value (2.4 +/- 0.7 vs. 3.3 +/- 0.7), and the improvement was sustained during follow-up (2.0 +/- 0.7). The ejection fraction and left ventricular end-diastolic dimension did not improve. One patient died without leaving hospital and two died during follow-up. The 2- and 4-year survival rates were 75.0% and 37.5%. Mitral valve surgery improved functional class without obvious changes in ejection fraction or left ventricular end-diastolic dimension.


Evaluating the performance of equations for estimating glomerular filtration rate.
Glomerular filtration rate (GFR) is an important indicator of kidney function, critical for detection, evaluation and management of chronic kidney disease (CKD). GFR cannot be practically measured in most clinical or research settings; therefore, estimating equations are used as a primary measure of kidney function. A considerable body of literature now evaluates the performance of GFR estimating equations. The results of these studies are often not comparable, because of variation in GFR measurement methods, endogenous filtration marker assays and tools by which the equations were evaluated. In this article, methods for the evaluation of GFR estimating equations are discussed. Topics addressed include statistical methods used in development and validation of equations; explanation of measures of performance used for evaluation, with focus on distinction between bias, precision and accuracy, and with reference to examples of published evaluations of creatinine- and cystatin C-based equations; explanation of errors in GFR estimates; and challenges and questions in reporting performance of GFR estimating equations.


Validation of Italian students' self-ratings on the SSIS SEL brief scales.
Despite increasing interest in measuring social and emotional learning (SEL), there is a lack of European-validated tools for assessing the efficacy of SEL programs. The aim of this study was to validate an Italian version of the social skills improvement system (SSIS) SEL brief scales-student form. Participants were 1,175 students (mean age: 11.02 years; SD: 2.42; range: 8-16 years; males: 46.8%) recruited at schools in Northern Italy. Initial confirmatory factor analysis encountered a series of challenges, implying non-convergence of the original five-factor measurement model (self-awareness, self-management, social awareness, relationship skills, and responsible decision-making) based on the Collaborative on Academic Social Emotional Learning (CASEL) competency framework established with students in the United States. Further exploratory and confirmatory analyses supported a four-factor model that remained partially invariant across gender groups. The Italian version of the SSIS SEL brief scales was thus shown to be an efficient measurement tool for estimating social and emotional learning in students. We discuss the implications of findings in relation to selecting valid and reliable instruments for assessing children's and adolescents' SEL competencies, while considering the culturally-situated nature of the constructs under study.


Design and synthesis of ferrocene probe molecules for detection by electrochemical methods.
A series of ferrocenyl conjugates to fatty acids have been designed and synthesized to establish the key properties required for use in biomolecular binding studies. Amperometric detection of the ferrocene conjugates was sought in the region of 0.3 V (vs Ag/AgCl) for use in protein/blood solutions. Different linkers and solubilizing moieties were incorporated to produce a conjugate with optimal electrochemical properties. In electrochemical studies, the linker directly attached to the ferrocene was found to affect significantly the E(1/2) value and the stability of the ferrocenium cation. Ester-linked ferrocene conjugates had E(1/2) ranging from +400 to +410 mV, while amide-linked compounds ranged from +350 to +370 mV and the amines +260 to +270 mV. Folding of long-chain substituents around the ferrocene, also significantly affected by the choice of linker, was inferred as a secondary effect that increased E(1/2). The stability of the ferrocenium cation decreased systematically as E(1/2) increased. Disubstituted ferrocene ester and amide conjugates, with oxidation potentials of +640 and +570 mV, respectively, showed only a barely discernible reduction wave in cyclic voltammetry at 50 mV/s. Electrochemical measurements identified two lead compounds with the common structural characteristics of an amide and carbamate linker (compounds 17 and 21) with a C(11) fatty acid chain attached. It is envisaged that such molecules can be used to mimic and study the biomolecular binding interaction between fatty acids and molecules such as human serum albumin.


Acupuncture utilization in Taiwan.
The objective of this study was to examine the prevalence of acupuncture utilization in Taiwan by people over 20 years of age. Stratified cluster sampling was used to randomly select 20 villages and neighborhoods (townships), a total of 8,280 people, from northern, central, southern and eastern Taiwan. A structured questionnaire was used to collect information during home visits. A total of 5,805 questionnaires were valid for use in the study. The complete rate of home visits was 70.1%; 73.2% of those interviewed recognized acupuncture as one of the common therapeutic methods used in traditional Chinese medicine, whereas only 12.4% had received acupuncture treatment. Typical interviewees who had received acupuncture treatment were generally ethnic from southern Fukien and aged from 30-39 years; 58.3% of the 716 interviewees had received acupuncture treatment from licensed practitioners, while the remainder were treated by non-licensed practitioners. The response rate to the questionnaire was high (70.1%). However, the percentage of people who had received acupuncture treatment was only 12.4%, while many people (73.2%) were familiar with it. Approximately 40% of those who received acupuncture treatment did so from non-licensed practitioners. This may reveal either a lack of awareness by the public or a lack of public protection of health and safety.


[Prevalence of penicillin-insensitive Streptococcus pneumoniae and its response to oral beta lactam antibiotics at a primary pediatric office].
Penicillin (PC) resistance of Streptococcus pneumoniae was tested by oxacillin disk method (Bauer-Kirby method) of the strains collected at the primary pediatric office. The rate of oxacillin resistance of S. pneumoniae was 36.4% in 1990, 41.4% in 1991, and 51.9% in 1992, respectively. The efficacy of oral antibiotics in the treatment of PC-insensitive S. pneumoniae infections was also studied retrospectively in 234 cases. Treatment failure rate was 17.7% in the amoxicillin group, 8.7% in the cefpodoxime proxetil group, while it was 42.9% in the cefixime group. These differences were statistically significant. From these data prevalence of PC-insensitive S. pneumoniae is very high in Japanese children, and amoxicillin and cefpodoxime proxetil can be used for the treatment of outpatients with PC-insensitive S. pneumoniae infections.


Deliver the promise: RNAs as a new class of molecular entities for therapy and vaccination.
The concepts of developing RNAs as new molecular entities for therapies have arisen again and again since the discoveries of antisense RNAs, direct RNA-protein interactions, functional noncoding RNAs, and RNA-directed gene editing. The feasibility was demonstrated with the development and utilization of synthetic RNA agents to selectively control target gene expression, modulate protein functions or alter the genome to manage diseases. Rather, RNAs are labile to degradation and cannot cross cell membrane barriers, making it hard to develop RNA medications. With the development of viable RNA technologies, such as chemistry and pharmaceutics, eight antisense oligonucleotides (ASOs) (fomivirsen, mipomersen, eteplirsen, nusinersen, inotersen, golodirsen, viltolarsen and casimersen), one aptamer (pegaptanib), and three small interfering RNAs (siRNAs) (patisiran, givosiran and lumasiran) have been approved by the United States Food and Drug Administration (FDA) for therapies, and two mRNA vaccines (BNT162b2 and mRNA-1273) under Emergency Use Authorization for the prevention of COVID-19. Therefore, RNAs have become a great addition to small molecules, proteins/antibodies, and cell-based modalities to improve the public health. In this article, we first summarize the general characteristics of therapeutic RNA agents, including chemistry, common delivery strategies, mechanisms of actions, and safety. By overviewing individual RNA medications and vaccines approved by the FDA and some agents under development, we illustrate the unique compositions and pharmacological actions of RNA products. A new era of RNA research and development will likely lead to commercialization of more RNA agents for medical use, expanding the range of therapeutic targets and increasing the diversity of molecular modalities.


Human antimicrobial peptides in ocular surface defense.
Sight depends on the passage of light through the transparent cornea and being focused on the fovea. Its exposed position renders it vulnerable to microbial infection. The cornea has developed a wide array of defense mechanisms against infection, of which endogenous antimicrobial peptides (AMPs) are key. AMPs are essentially small molecular weight cationic peptides with a wide range of activity against virus, bacteria, fungi and parasites. Some proteins such as RNases and S100As are also included in this group. Several AMPs act synergistically allowing low expression of multiple AMPs to act efficiently. AMPs also have a range of non-microbicidal functions and serve as signaling molecules, immunomodulators; show anti-tumour activity, and influence vascularization and wound healing. Different toll-like receptors (TLR) have been implicated in the preferential induction of specific AMPs. A range of bacteria, including mycobacteria tuberculosis, viruses including herpes virus, fungi and parasites including acanthamoeba, that cause ocular infections have been shown to induce specific AMPs via TLR activation. Non-TLR mediated induction of AMP expression can occur and several molecules such as L-isoleucine, sodium butyrate, vitamin D3, phenylbutyrate, vasoactive intestinal peptide, and etinostat have been identified in this regard. Given the rising microbe resistance to antibiotics, the slow rate of development of new antibiotics and the limited access to effective antibiotics by patients living in the developing world, an ideal solution would be to find AMPs that are effective singly or in combination with each other or other antimicrobial proteins to reduce, if possible eliminate reliance on antibiotics alone.


[Buccal mucosa urethroplasty in anterior urethral strictures].
Buccal mucosal graft can be used for succesfull repair in both pendulous and bulbar strictures. We present our experience with buccal mucosal graft repair in 8 patients with onlay patch that varies from 4 to 16 cm. in length. Three pendulous, two bulbar and three panurethral strictures were repaired. These patients were observed for 36 to 60 months. No stricture recurrences were observed. Only one patient had lower lip paresthesia for six months.


Association between childcare educators' practices and preschoolers' physical activity and dietary intake: a cross-sectional analysis.
Childcare educators may be role models for healthy eating and physical activity (PA) behaviours among young children. This study aimed to identify which childcare educators' practices are associated with preschoolers' dietary intake and PA levels. This cross-sectional analysis included 723 preschoolers from 50 randomly selected childcare centres in two Canadian provinces. All data were collected in the fall of 2013 and 2014 and analysed in the fall of 2015. PA was assessed using Actical accelerometers during childcare hours for 5 consecutive days. Children's dietary intake was measured at lunch on 2 consecutive days using weighed plate waste and digital photography. Childcare educators' nutrition practices (modelling, nutrition education, satiety recognition, verbal encouragement and not using food as rewards) and PA practices (informal and formal PA promotion) were assessed by direct observation over the course of 2 days, using the Nutrition and Physical Activity Self-Assessment for Child Care tool. Associations between educators' practices and preschoolers' PA and dietary intake were examined using multilevel linear regressions. Overall, modelling of healthy eating was positively associated with children's intake of sugar (β=0.141, 95% CI 0.03 to 0.27), while calorie (β=-0.456, 95% CI -1.46 to -0.02) and fibre intake (β=-0.066, 95% CI -0.12 to -0.01) were negatively associated with providing nutrition education. Not using food as rewards was also negatively associated with fat intake (β=-0.144, 95% CI -0.52 to -0.002). None of the educators' PA practices were associated with children's participation in PA. Modelling healthy eating, providing nutrition education and not using food as rewards are associated with children's dietary intake at lunch in childcare centres, highlighting the role that educators play in shaping preschoolers' eating behaviours. Although PA practices were not associated with children's PA levels, there is a need to reduce sedentary time in childcare centres.


ROCK1 translocates from non-caveolar to caveolar regions upon KCl stimulation in airway smooth muscle.
Airway smooth muscle (ASM) membrane depolarization through KCl opens L-type voltage dependent Ca2+ channels (Ca(v)1.2); its opening was considered the cause of KCl contraction. This substance is used to bypass intracellular second messenger pathways. It is now clear that KCl also activates RhoA/Rho kinase (ROCK) pathway. ROCK isoforms are characterized as ROCK1 and ROCK2. Because ROCK1 seems the most abundant isotype in lung, we studied its participation in KCl stimulated bovine ASM. With methyl-beta-cyclodextrin (MbetaCD) we disrupted caveolae, a membrane compartment considered as the RhoA/ROCK assembly site, and found that KCl contraction was reduced to the same extent (~26%) as Y-27632 (ROCK inhibitor) treated tissues. We confirmed that KCl induces ROCK activation and this effect was annulled by Y-27632 or MbetaCD. In isolated plasmalemma, ROCK1 was localized in non-caveolar membrane fractions in Western blots from control tissues, but it transferred to caveolae in samples from tissues stimulated with KCl. Ca(v)1.2 was found at the non-caveolar membrane fractions in control and MbetaCD treated tissues. In MbetaCD treated tissues stimulated with KCl, contraction was abolished by nifedipine; only the response to Ca(v)1.2 opening remained as the ROCK component disappeared. Our results show that, in ASM, the KCl contraction involves the translocation of ROCK1 from non-caveolar to caveolar regions and that the proper physiological response depends on this translocation.


Intracellular localization and endocytosis of brush border enzymes in the enterocyte-like cell line Caco-2.
Immunoelectron microscopy was used to localize the brush border hydrolases sucrase-isomaltase (SI) and dipeptidylpeptidase IV (DPPIV) in the human colon carcinoma cell line Caco-2. Both enzymes were detected at the microvillar membrane, in small vesicles and multivesicular bodies (MVBs), and in lysosomal bodies. In addition, DPPIV was found in the Golgi apparatus, a variety of apical vesicles and tubules, and at the basolateral membrane. To investigate whether the hydrolases present in the lysosomal bodies were endocytosed from the apical membrane, endocytic compartments were marked with the endocytic tracer cationized ferritin (CF). After internalization from the apical membrane through coated pits, CF was first recovered in apical vesicles and tubules, and larger electronlucent vesicles (early endosomes), and later accumulated in MVBs (late endosomes) and lysosomal bodies. DPPIV was localized in a subpopulation of both early and late endocytic vesicles, which contained CF after 3 and 15 min of uptake, respectively. Also, internalization of the specific antibody against DPPIV and gold labeling on cryosections showed endocytosed DPPIV in both early and late endosomes. However, unlike CF, no accumulation of DPPIV was seen in MVBs or lysosomal bodies after longer chase times. The results indicate that in Caco-2 cells the majority of brush border hydrolases present in lysosomal bodies are not endocytosed from the brush border membrane. Furthermore, the labeling patterns obtained, suggest that late endosomes may be involved in the recycling of endocytosed DPPIV to the microvilli.


Optimizing growth opportunities during the managed care revolution.
Despite reports to the contrary, managed care is pervasive and growing. By understanding employers' needs and how those needs are forcing managed care to change, hospital and physician provider organizations can create growth opportunities for themselves. To optimize their organizations' financial performance under managed care contracts, healthcare financial managers of providers should develop an overall managed care strategy for their organizations that includes customer-service initiatives and system planning and development, instead of focusing only on contract negotiation.


Multifocal primary cutaneous nodular amyloidosis.
Nodular cutaneous amyloidosis (NCA), the least common form of primary cutaneous amyloidosis, is characterized clinically by waxy, purpuric plaques and nodules and histologically by amyloid deposits in the dermis and subcutaneous tissue. We present a patient who developed multiple, non-contiguous NCA lesions over a three year period without evidence of systemic disease. We reviewed the literature and found few other cases of this unusual presentation.


Occurrence and distribution of Salmonella serovars in carcasses and foods in southern Italy: Eleven-year monitoring (2011-2021).
Salmonella is one of the most common agents of foodborne illness. The genus Salmonella includes two species (Salmonella bongori and S. enterica) and six subspecies (enterica I, salamae II, arizonae IIIa, diarizonae IIIb, houtenae IV, and indica VI), each of which contains multiple serotypes associated with animal and human infections. The aim of the study was to evaluate the presence of Salmonella spp. in carcasses of food-producing animals and foods in southern Italy and the serovar distribution among different sources. From 2011 to 2021, a total of 12,246 foods and 982 samples from animal carcasses were collected and analyzed. The overall percentage of positive samples was 5.84% (N = 773) and a significant increase in prevalence was observed by comparing the years 2011-2015 (257, 3.27%) and 2016-2021 (516, 9.61%; p < 0.05). The highest percentage of positive food samples was observed in "Meat and Meat Products" (N = 327/2,438, 13.41%) followed by "Fish and fishery products" (N = 115/1,915, 6.01%). In carcasses, the highest percentage of positive samples was reported from broilers (N = 42/81, 51.85%) followed by buffalo (N = 50/101, 49.50%) and pork (N = 140/380, 36.84%). After typing, the isolates were assigned to the species S. enterica and to the subspecies: enterica (N = 760, 98.32%), diarizonae (N = 8, 1.03%), salamae (N = 3, 0.39%) and houtenae (N = 2, 0.26%). S. Infantis was the most frequently detected (N = 177, 24.76%), followed by S. Derby (N = 77, 10.77%), monophasic S. Typhimurium (N = 63, 8.81%), S. Typhimurium (N = 54, 7.55%), and S. Rissen (N = 47, 6.57%). By comparing the sampling period 2011-2015 with that of 2016-2021, an increase in the prevalence of S. Infantis and monophasic S. Typhimurium and a decrease of S. Typhimurium were recorded (p < 0.05). Thus, present data suggest that, despite the implementation of national and European control strategies to protect against Salmonella, the prevalence of this pathogen in southern Italy is still increasing and a change of national control programs to protect against Salmonella are necessary.


Social information use and the evolution of unresponsiveness in collective systems.
Animal groups in nature often display an enhanced collective information-processing capacity. It has been speculated that natural selection will tune this response to be optimal, ensuring that the group is reactive while also being robust to noise. Here, we show that this is unlikely to be the case. By using a simple model of decision-making in a dynamic environment, we find that when individuals behave rationally and are subject to selection based on their accuracy, optimality of collective decision-making is not attained. Instead, individuals overly rely on social information and evolve to be too readily influenced by their neighbours. This is due to a classic evolutionary conflict between individual and collective interest. The result is a sub-optimal system that is poised on the cusp of total unresponsiveness. Individuals in the evolved group exhibit delayed reactions to changes in the environment, before responding with rapid, socially reinforced transitions, reminiscent of familiar human and animal social systems (markets, stampedes, fashions, etc.). Our results demonstrate that behaviour of this type may not be pathological, but instead could represent an evolutionary attractor for such collective systems.


VDJbase: an adaptive immune receptor genotype and haplotype database.
VDJbase is a publicly available database that offers easy searching of data describing the complete sets of gene sequences (genotypes and haplotypes) inferred from adaptive immune receptor repertoire sequencing datasets. VDJbase is designed to act as a resource that will allow the scientific community to explore the genetic variability of the immunoglobulin (Ig) and T cell receptor (TR) gene loci. It can also assist in the investigation of Ig- and TR-related genetic predispositions to diseases. Our database includes web-based query and online tools to assist in visualization and analysis of the genotype and haplotype data. It enables users to detect those alleles and genes that are significantly over-represented in a particular population, in terms of genotype, haplotype and gene expression. The database website can be freely accessed at https://www.vdjbase.org/, and no login is required. The data and code use creative common licenses and are freely downloadable from https://bitbucket.org/account/user/yaarilab/projects/GPHP.


Integrating health information systems: a critical appraisal.
The aim of this paper is to critically assess some of the underlying assumptions behind these initiatives and analyze the dominant expressions, forms and mechanisms of integration. This paper employs a discourse analysis to elicit the notion of integration of information systems and its consequences for electronic patient record systems. An alternative strategy is outlined, encouraging a more decentralized, multi-vocal approach acknowledging the productive role of related and duplicated information and preserving the existing variety of information systems.


Efficacy of disinfectants and detergents intended for a pig farm environment where Salmonella is present.
Disinfection is a useful component of disease control, although products and chemical groups vary in their activity against different pathogens. This study investigated the ability of fifteen disinfectants to eliminate pig-associated Salmonella. Active compounds of products included chlorocresol, glutaraldehyde/formaldehyde, glutaraldehyde/quaternary ammonium compounds (QAC), iodine, peracetic acid and potassium peroxomonosulphate. Six detergents were also tested for their ability to dislodge faecal material, and interactions with specific disinfectants. Eight serovars were screened against all products using dilution tests and a monophasic Salmonella Typhimurium strain was selected for further testing. The disinfectants were tested using models to replicate boot dip (faecal suspension) and animal housing (surface contamination) disinfection respectively at the Department for Environment, Food and Rural Affairs Approved Disinfectant General Orders (GO) concentration, half GO and twice GO. Stability over time and ability to eliminate Salmonella in biofilm was also assessed. The most effective products were then field tested. Most products at GO concentration eliminated Salmonella in the faecal suspension model. One glutaraldehyde/QAC and one glutaraldehyde/formaldehyde-based product at GO concentration eliminated Salmonella in the surface contamination model. Chlorocresol-based products were more stable in the faecal suspension model. One chlorocresol and the glutaraldehyde/formaldehyde-based product were most successful in eliminating Salmonella from biofilms. All products tested on farm reduced bacterial log counts; the glutaraldehyde/QAC based product produced the greatest reduction. The type of product and the application concentration can impact on efficacy of farm disinfection; therefore, clearer guidance is needed to ensure the appropriate programmes are used for specific environments.


Multiple signaling pathways control stimulus-secretion coupling in rat peritoneal mast cells.
Fura-2 and membrane capacitance measurements were performed to investigate intracellular Ca2+ concentration [( Ca2+]i) and secretory responses of rat peritoneal mast cells following secretagogue stimulation. Compound 48/80 and internally applied guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]) induced transient rises in [Ca2+]i and caused membrane capacitance increases as secretion occurred. The 48/80-induced Ca2+ transients and secretory responses were blocked by guanosine 5'-[beta-thio]diphosphate and neomycin, indicating that inositolphospholipid breakdown mediated by guanine nucleotide-binding regulatory protein (G protein) plays an important role in stimulus-secretion coupling. However, pertussis toxin did not block Ca2+ transients induced by 48/80 or GTP[gamma-S], whereas secretory responses were either abolished (48/80) or developed only after a considerable delay (GTP[gamma-S]). Similar effects were obtained by perfusing cells with cAMP: (i) Ca2+ transients following stimulation with 48/80 remained unaffected by cAMP, but secretory responses were abolished; (ii) GTP[gamma-S] induced normal Ca2+ transients and degranulation in the presence of cAMP. Pretreatment of mast cells with phorbol 12-myristate 13-acetate (PMA) abolished 48/80- and GTP[gamma-S]-induced Ca2+ transients (but not inositol trisphosphate-induced Ca2+ transients), whereas secretion still occurred. At the same time, the Ca2+ requirement for secretion was reduced by PMA. These results indicate that secretion in mast cells is under control of an as yet unidentified signaling pathway that involves a G protein. This pathway is distinct from inositolphospholipid turnover and may provide the triggering mechanism for secretion, whereas the inositolphospholipid pathway serves to increase [Ca2+]i and renders the secretory process more sensitive to [Ca2+]i by activating protein kinase C. Persistent activation of protein kinase C through phorbol ester imposes negative feedback control on the inositolphospholipid pathway, whereas cAMP may inhibit the unidentified signaling pathway.


Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology.
Alzheimer's disease (AD) is an aging-related neurodegenerative disease and accounts for majority of human dementia. The hyper-phosphorylated tau-mediated intracellular neurofibrillary tangle and amyloid β-mediated extracellular senile plaque are characterized as major pathological lesions of AD. Different from the dysregulated growth control and ample genetic mutations associated with human cancers, AD displays damage and death of brain neurons in the absence of genomic alterations. Although various biological processes predominately governing tumorigenesis such as inflammation, metabolic alteration, oxidative stress and insulin resistance have been associated with AD genesis, the mechanistic connection of these biological processes and signaling pathways including mTOR, MAPK, SIRT, HIF, and the FOXO pathway controlling aging and the pathological lesions of AD are not well recapitulated. Hence, we performed a thorough review by summarizing the physiological roles of these key cancer-related signaling pathways in AD pathogenesis, comprising of the crosstalk of these pathways with neurofibrillary tangle and senile plaque formation to impact AD phenotypes. Importantly, the pharmaceutical investigations of anti-aging and AD relevant medications have also been highlighted. In summary, in this review, we discuss the potential role that cancer-related signaling pathways may play in governing the pathogenesis of AD, as well as their potential as future targeted strategies to delay or prevent aging-related diseases and combating AD.


Protective effect of Specnuezhenide on islet β cell of rats with gestational diabetes mellitus.
Gestational diabetes mellitus (GDM) refers to diabetes mellitus and impaired glucose tolerance first diagnosed during pregnancy without previous history of the disease. Usually, GDM has a high risk of inducing type 2 diabetes mellitus. The incidence of GDM is increasing year by year worldwide, and it seriously affects the quality of life of patients, and increases the risk to pregnancy. Specnuezhenide (SPZ) is a characteristic active component of Ligustrum lucidum, a plant which exerts a variety of pharmacological effects. In this study, the protective effect of SPZ on β cells in gestational diabetes mellitus rats was investigated in a rat model of gestational diabetes. Based on oral glucose tolerance test, ELISA, qRT-PCR and western blotting assays, It was found that SPZ effectively improved blood sugar control and glucose tolerance in gestational diabetic rats, inhibited inflammation in islet tissue, and reduced inflammation-mediated insulin resistance.


[Spontaneous thrombosis of the splenic artery pseudoaneurysms].
The authors demonstrate relatively rare case of evolution and spontaneous thrombosis of the postpancreatitic pseudoaneurysm of the splenic artery, which developed from a pancreatic pseudocyst. The miniinvasive therapeutic approach to the pancreatic pseudoaneurysms is discussed.


European experience of regulating distance selling of medicines for Ukraine.
Some countries have already tried and tested mechanisms of regulating distance sales as form of distribution of medicines that have been used more or less effectively for a fairly long time. Herewith, so far, the approach of the competent authorities of some countries including Ukraine can be called prevailing in quantitative terms under which the official prohibition on distance sales of medicines is set. The aim of this study is a detailed examination of the nature of the prohibition of the medicines distance selling in Ukraine, namely the an analysis of advantages and disadvantages of this form of distribution of medicines and identification of appropriate ways for gradual repeal of the prohibition in terms of regulatory reform in Ukraine in the sphere of circulation of medicines due to the process of adaptation of statutory regulation in this area to the EU legislation. This study is based on Ukrainian regulation acts, Council Directives 97/7/EC, 2000/31/EC, 2001/83/EC, scientific works and opinions of progressiveminded people in this sphere. Such methods as dialectical, comparative, analytic, synthetic and comprehensive have been used in the article. Reception of the described experience of regulation in EU will allow a further review of the principles of regulation in Ukraine in the sphere of medicines with a shift in the main emphasis in the direction of ensuring adequate consumer rights in this area and preventing the risks of patients' and public health.


Intraluminal brachytherapy in the treatment of bile duct carcinomas.
Patients with carcinoma of the biliary tract have a poor prognosis because the disease is often unresectable at diagnosis. Intraluminal brachytherapy has been reported as an effective treatment for localized cholangiocarcinoma of the biliary tract. The purpose of our study was to analyse the survival of patients treated with brachytherapy and make some recommendations regarding its use. Fifteen patients underwent brachytherapy via a trans-hepatic approach at the Royal Prince Alfred Hospital from 1983 to 1993. Eleven patients had low-dose rate brachytherapy and four patients had high-dose rate treatment. There were nine males and six females. The median age was 64 years. Other treatment included bypass procedures in two patients, endoscopic stents in 14 patients and external beam irradiation in one patient. The median survival was 12.5 months and 47% of the patients survived 1 year. The only complication reported was cholangitis which was seen in one patient. There did not seem to be any difference in survival or complications between low- and high-dose rate brachytherapy. We conclude that the addition of intraluminal brachytherapy after biliary drainage prolongs survival and is a safe and effective treatment, but patients still have a high rate of local failure, and further studies will be needed to address this problem.


Metabolic bone disease in adolescents: recognition, evaluation, treatment, and prevention.
Bone is a metabolically active organ that undergoes constant remodeling. Bone is very important for maintaining homeostasis of calcium and phosphorous in the body. Disorders of bone metabolism may encompass disease processes involving underactive or overactive bone turnover. The spectrum of abnormal bone metabolism includes rickets and osteomalacia; osteopenia and osteoporosis; osteogenesis imperfecta, renal osteodystrophy; osteopetrosis and osteosclerosis; and effect of pharmacologic therapies on bone metabolism. The recognition, evaluation, treatment, and prevention of these conditions will be discussed after a brief description of normal bone metabolism.


TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion.
Toll like receptor 4 (TLR4) is an important pattern recognition receptor with the ability to drive potent innate immune responses and also to modulate adaptive immune responses needed for long term protection. Activation of TLR4 by its ligands is mediated by engagement of the adapter proteins MyD88 (myeloid differentiation factor 88) and TRIF (Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta). Previously, we showed that TRIF, but not MyD88, plays an important role in allowing TLR4 agonists to adjuvant early T cell responses. In this study, we investigated the T cell priming events that are regulated specifically by the TRIF signaling branch of TLR4. We found that TRIF deficiency prevented the TLR4 agonist lipid A from enhancing T cell proliferation and survival in an adoptive transfer model of T cell priming. TRIF deficient DC showed defective maturation as evidenced by their failure to upregulate co-stimulatory molecules in response to lipid A stimulation. Importantly, TRIF alone caused CD86 and CD40 upregulation on splenic DC, but both TRIF and MyD88 were required for CD80 upregulation. The impairment of T cell adjuvant effects and defective DC maturation in TRIF (lps/lps) mice after TLR4 stimulation was mainly due to loss of type I IFN production, indicating that type I interferons are central to TLR4's adjuvant effects. These results are useful for the continued development of TLR4 based vaccine adjuvants that avoid inflammatory risks while retaining beneficial immune response.


Mechanisms of lineage specification in Caenorhabditis elegans.
The studies of cell fate and lineage specification are fundamental to our understanding of the development of multicellular organisms. Caenorhabditis elegans has been one of the premiere systems for studying cell fate specification mechanisms at single cell resolution, due to its transparent nature, the invariant cell lineage, and fixed number of somatic cells. We discuss the general themes and regulatory mechanisms that have emerged from these studies, with a focus on somatic lineages and cell fates. We next review the key factors and pathways that regulate the specification of discrete cells and lineages during embryogenesis and postembryonic development; we focus on transcription factors and include numerous lineage diagrams that depict the expression of key factors that specify embryonic founder cells and postembryonic blast cells, and the diverse somatic cell fates they generate. We end by discussing some future perspectives in cell and lineage specification.


Declarative and procedural learning in schizophrenia: a test of the integrity of divergent memory systems.
A comparison of learning rates between schizophrenia patients and normals on measures tapping different memory systems may provide clues about relatively preserved areas of learning in schizophrenia. The present study assessed declarative (nonsense syllable list learning) and procedural (pursuit rotor tracking) learning in a group of chronic schizophrenia inpatients and a group of normal adults. Approximately equivalent baselines were obtained for the two groups on both measures. The results revealed a significant group trial interaction on the declarative memory measure, exemplified by a shallower learning slope for the patient group. For the procedural learning measure, there was no significant group block interaction; that is, both groups showed similar learning slopes. These findings suggest a relative preservation of selected procedural aspects of learning in schizophrenia.


Fostering Broad Oral Language Skills in Preschoolers from Low SES Background.
Socioeconomic disparities increase the probability that children will enter school behind their more advantaged peers. Early intervention on language skills may enhance language and literacy outcomes, reduce the gap and, eventually, promote school readiness of low-SES (Socioeconomic Status) children. This study aimed to analyze the feasibility and effectiveness of a brief narrative-based intervention (treatment vs. control group) aimed to foster broad oral language skills in preschoolers (N = 69; Mean age = 5.5, SD = 4 months) coming from low-SES families. Moreover, it was analyzed whether children's initial vocabulary mediates the intervention's responsiveness. Results have shown that children in treatment group obtained greater gains than children in control group in almost all intervention-based measures. There is also some evidence for the generalizability of the intervention to other skills not directly trained during the intervention. Moreover, it was found that children's initial vocabulary mediates the intervention's responsiveness showing that children with high vocabulary made greater gains in higher-level components of language comprehension, whereas children with low vocabulary made higher gains in vocabulary. Taken together, our findings suggest that a relatively brief, but quite intensive narrative-based intervention, may produce improvements on broad oral language skills in preschoolers from low-SES backgrounds.


Ovarian cancer and ascites: A questionnaire on current management in the United kingdom.
A questionnaire on ovarian cancer ascites management was sent to members of the British Gynaecological Cancer Society (BGCS), the National Gynaecological Oncology Nurses, and the Assoication of Palliative Medicine. Questions were asked on diuretics, hematologic investigations, paracentesis, and duration of stay. Nine hundred ninety-five questionnaires were distributed, of which 492 replies were received (49% response rate). Fifty-five percent of responders used paracentesis as first-line management of ovarian cancer ascites (15% diuretics). Seventy-five percent performed some blood tests in relation to paracentesis. Ultrasound was used by 43.6% during paracentesis (15.7% for direct visualization, 27.9% to mark an entry site). Seventy-seven percent used a Bonanno catheter. Eighty-three percent used no intravenous fluids during paracentesis, and there was a wide variation in the amount and rate of drainage of ascites (1 L maximum up to free drainage of all ascites, median 5 L; 0.5 L per hour to free drainage). Gynecologists tended to use more interventions (paracentesis, ultrasound, and intravenous fluids) than palliative care physicians or medical oncologists, while palliative care physicians used fewer interventions but admitted patients for longer periods of time. This identified several areas for future study: the value of hematologic investigations, the use of outpatient management for paracentesis, and the use of ultrasound and the rate of drainage of ascites.


Aneuploidy: the impact of chromosome imbalance on nuclear organization and overall genome expression.
The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression.


Knowledge and Attitudes of Bangkok Metropolitan Women towards HPV and Self-Sampled HPV Testing.
To evaluate knowledge of Bangkok women regarding HPV and self-sampled HPV testing, and their attitudes towards testing. Thai women who had lived in Bangkok for more than 5 years, aged 25-to-65 years old, were invited to join the study. Participating women were asked to a complete self-questionnaire (Thai language), with literate assistance as needed. The questionnaire was divided into 3 parts: (I) demographic data, (II) knowledge and (III) attitudes towards self-sampled HPV testing. Before proceeding to Part III of the questionnaire, a 15-minute educational video of self-sampled HPV testing was presented to all participants. Among 2,810 women who answered the questionnaires, 33.7% reported that they did not know about HPV. The characteristic features of these women were older age (>50 years), lower income (<600 USD/month), unemployed status, and non-attendees at cervical cancer screening. Only small numbers of women (4.6%) responded that they had heard about self-sampled HPV testing. After having information, 59.6% would not use the self-sampled HPV testing as a method of cervical cancer screening (non-acceptance). Factors significantly associated with the non-acceptance were older age, lower income, having no knowledge about HPV or self-collected HPV testing, a perception that the testing was unreliable and a concern that they might not be able to perform it correctly. Nearly half and almost all Bangkok women did not know about HPV and self-sampled HPV testing, respectively. Approximately 60% of Bangkok women refused to do the self-sampled HPV testing. Significant negative attitudes were concerns that the testing would be unreliable and a lack of confidence to perform the procedure correctly. Education about HPV and self-sampled HPV testing, ease of the procedure, or the testing models may increase rate of acceptability or positive attitudes.


Reconstruction of an integrated genome-scale co-expression network reveals key modules involved in lung adenocarcinoma.
Our goal of this study was to reconstruct a "genome-scale co-expression network" and find important modules in lung adenocarcinoma so that we could identify the genes involved in lung adenocarcinoma. We integrated gene mutation, GWAS, CGH, array-CGH and SNP array data in order to identify important genes and loci in genome-scale. Afterwards, on the basis of the identified genes a co-expression network was reconstructed from the co-expression data. The reconstructed network was named "genome-scale co-expression network". As the next step, 23 key modules were disclosed through clustering. In this study a number of genes have been identified for the first time to be implicated in lung adenocarcinoma by analyzing the modules. The genes EGFR, PIK3CA, TAF15, XIAP, VAPB, Appl1, Rab5a, ARF4, CLPTM1L, SP4, ZNF124, LPP, FOXP1, SOX18, MSX2, NFE2L2, SMARCC1, TRA2B, CBX3, PRPF6, ATP6V1C1, MYBBP1A, MACF1, GRM2, TBXA2R, PRKAR2A, PTK2, PGF and MYO10 are among the genes that belong to modules 1 and 22. All these genes, being implicated in at least one of the phenomena, namely cell survival, proliferation and metastasis, have an over-expression pattern similar to that of EGFR. In few modules, the genes such as CCNA2 (Cyclin A2), CCNB2 (Cyclin B2), CDK1, CDK5, CDC27, CDCA5, CDCA8, ASPM, BUB1, KIF15, KIF2C, NEK2, NUSAP1, PRC1, SMC4, SYCE2, TFDP1, CDC42 and ARHGEF9 are present that play a crucial role in cell cycle progression. In addition to the mentioned genes, there are some other genes (i.e. DLGAP5, BIRC5, PSMD2, Src, TTK, SENP2, PSMD2, DOK2, FUS and etc.) in the modules.


An open-source human-in-the-loop BCI research framework: method and design.
Brain-computer interfaces (BCIs) translate brain activity into digital commands for interaction with the physical world. The technology has great potential in several applied areas, ranging from medical applications to entertainment industry, and creates new conditions for basic research in cognitive neuroscience. The BCIs of today, however, offer only crude online classification of the user's current state of mind, and more sophisticated decoding of mental states depends on time-consuming offline data analysis. The present paper addresses this limitation directly by leveraging a set of improvements to the analytical pipeline to pave the way for the next generation of online BCIs. Specifically, we introduce an open-source research framework that features a modular and customizable hardware-independent design. This framework facilitates human-in-the-loop (HIL) model training and retraining, real-time stimulus control, and enables transfer learning and cloud computing for the online classification of electroencephalography (EEG) data. Stimuli for the subject and diagnostics for the researcher are shown on separate displays using web browser technologies. Messages are sent using the Lab Streaming Layer standard and websockets. Real-time signal processing and classification, as well as training of machine learning models, is facilitated by the open-source Python package Timeflux. The framework runs on Linux, MacOS, and Windows. While online analysis is the main target of the BCI-HIL framework, offline analysis of the EEG data can be performed with Python, MATLAB, and Julia through packages like MNE, EEGLAB, or FieldTrip. The paper describes and discusses desirable properties of a human-in-the-loop BCI research platform. The BCI-HIL framework is released under MIT license with examples at: bci.lu.se/bci-hil (or at: github.com/bci-hil/bci-hil).


Priapism associated with trazodone therapy: case report.
A case of priapism associated with trazodone is described. Erection subsided spontaneously after 4 hours, with subsequent potency unimpaired. No published reports of priapism with antidepressants were located, but 11 cases have been reported to the manufacturers.


Motivated and able: when is facebook used to seek friendship and social support?
When employing adaptive behaviors to a changing environment, ability and motivation work hand in hand. Our goal was to investigate how ability and motivation interact when utilizing Facebook for social support and friendship. We predicted that well-being and perceived social support would be negatively related to motivation to use Facebook for social support and friendship. We also predicted that computer-mediated communication (CMC) competence would positively related to these motives. A survey of 282 college students tested our mediational model. Results indicated that perceived social support mediated the relationship between well-being and motivations to use Facebook for social support, but only when CMC competence was high, meaning students experienced this relationship only when both motivated and able to use Facebook for the purpose of seeking social support. The results suggest that interventions to increase CMC competence through Facebook use can help students garner greater social support and improve overall well-being.