The Influence of Teacher-Student Interaction on the Effects of Online Learning: Based on a Serial Mediating Model.
During the COVID-19 pandemic, online education has become an important approach to learning in the information era and an important research topic in the field of educational technology as well as that of education in general. Teacher-student interaction in online education is an important factor affecting students' learning performance. This study employed a questionnaire survey to explore the influence of teacher-student interaction on learning effects in online education as well as the mediating role of psychological atmosphere and learning engagement. The study involved 398 college students studying at Chinese universities as the research object. Participants filled out a self-report questionnaire. The study found that (1) the level of teacher-student interaction positively affected students' learning effects (r = 0.649, p < 0.01). (2) The psychological atmosphere mediated the positive effect of the level of teacher-student interaction on learning effects with mediating effect value of 0.1248. (3) Learning engagement mediated the positive effect of teacher-student interaction on learning effects with a mediating effect value of 0.1539. (4) The psychological atmosphere and learning engagement play a chain-mediating role in the mechanism of teacher-student interaction affecting students' learning effects; that is, teacher-student interaction promotes students' learning engagement by creating a good psychological atmosphere, which, in turn, influences learning effects. The mediating effect value was 0.0403. The results indicate that teacher-student interaction not only directly affects students' learning effects but also influences students' learning effects through the mediating effect of the psychological atmosphere and learning engagement.


IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia.
The influx of neutrophils into tissues in response to inflammatory stimuli involves C-X-C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro, but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C-X-C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blocked by IL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1beta that was decreased by Il-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS- treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1beta and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.


Family members' experiences of assisted dying: A systematic literature review with thematic synthesis.
Families' experiences of assisted dying are under-investigated and families are rarely considered in clinical guidelines concerning assisted dying. To systematically review family experiences of assisted dying. A systematic literature review using thematic synthesis. MEDLINE, Embase, CINAHL, AMED (Allied and Complementary Medicine) and PsycINFO databases (January 1992 to February 2019). Studies investigating families' experiences on the practice of legalised assisted dying were included. We excluded studies prior to legalisation within the jurisdiction, secondary data analysis and opinion papers. Nineteen articles met the inclusion criteria. Publications were derived from four countries: The Netherlands, United States (Oregon, Washington and Vermont), Canada and Switzerland. Dutch studies predominately investigated family involvement in euthanasia, while Swiss and American studies only reported on assisted suicide. Eleven studies had a qualitative design, using predominately in-depth interviews; seven were retrospective surveys. Five analytical themes represented families' experiences in assisted dying: (1) context of the decision, (2) grounding the decision, (3) cognitive and emotional work, (4) experiencing the final farewell and (5) grief and bereavement. The results showed that families can be very involved in supporting patients seeking assisted dying, where open communication is maintained. Family involvement appeared to be influenced by the type of legislation in their country and the families' perception of the social acceptability of assisted dying. Our data confirm that families across all jurisdictions are involved in assisted suicide decision and enactment. Family needs are under-researched, and clinical guidelines should incorporate recommendations about how to consider family needs and how to provide them with evidence-based tailored interventions.


Diagnostic accuracy of squamous cervical lesions studied in spatula-cytobrush smears.
The cytologically positive cases found in 25,300 cervical smears of spatula samples and 6,168 smears prepared by combined spatula-Cytobrush sampling were analyzed. The diagnostic accuracy (the correlation between the cytologic and histologic diagnoses) was the same for both types of sampling. As to the histologic diagnosis, the rates of severe dysplasia, carcinoma in situ and squamous carcinoma in the spatula-Cytobrush group were more than twice as high as in the spatula group. In the spatula group, the majority of abnormal cells was of the mature type. In the spatula-Cytobrush group, the majority of smears contained a mixture of immature and mature abnormal cells. The more immature lesions, which are often located higher in the endocervical canal, seem to be better sampled by the Cytobrush. The results indicate that the Cytobrush reaches areas that a spatula cannot reach, resulting in a higher diagnostic efficiency.


Investigating pediatric HIV research ethics in the field.
Physician and nurse researchers, Institutional Review Board members, and parents of children with HIV were asked, during interviews, to describe their views on the ethical issues involved in the conduct of clinical drug research that uses as subjects children who are seropositive for HIV. Twenty-eight interviews at four clinical sites were completed. Two significant ethical topic issues were identified. The study presents and analyzes, using bioethical perspectives, (1) factors that affect access of seropositive children to care and (2) concerns that the respondents presented about the amount of risk appropriate for the afflicted children.


Mutations of the act promoter in Myxococcus xanthus.
Mutations within the -12 and -24 elements provide evidence that the act promoter is recognized by sigma-54 RNA polymerase. Deletion of the -20 base pair, which lies between the two conserved elements of sigma-54 promoters, decreased expression by 90%. In addition, mutation of a potential enhancer sequence, around -120, led to an 80% reduction in act gene expression. actB, the second gene in the act operon, encodes a sigma-54 activator protein that is proposed to be an enhancer-binding protein for the act operon. All act genes, actA to actE, are expressed together and constitute an operon, because an in-frame deletion of actB decreased expression of actA and actE to the same extent. After an initially slow phase of act operon expression, which depends on FruA, there is a rapid phase. The rapid phase is shown to be due to the activation of the operon expression by ActB, which completes a positive feedback loop. That loop appears to be nested within a larger positive loop in which ActB is activated by the C signal via ActA, and the act operon activates transcription of the csgA gene. We propose that, as cells engage in more C signaling, positive feedback raises the number of C-signal molecules per cell and drives the process of fruiting body development forward.


Fluid balance charts: do they measure up?
Many current nursing activities are performed without regular reviews of their usefulness. The recording of fluid gains and losses on a fluid balance chart is one such activity. This article explores the practice of fluid monitoring on the wards of a university teaching hospital.


[The Treatment of Cancer Cachexia].
Cancer cachexia is defined as a multifactorial syndrome that causes anorexia and an ongoing loss of skeletal muscle mass (with or without loss of fat mass). When patients got cachexia, the effectiveness and tolerance for anti-cancer therapy is reduced, leading to their poor prognosis. Although known as such disease, there had been no effective cure for cancer cachexia. Ghrelin is a peptide hormone that promotes appetite and improve cachexia. However, there is a limitation as a drug because its half-life is short and must be intravenous injected. Anamorelin is a first novel drug, an orally active, non- peptidic ghrelin mimetic and growth hormone secretagogue approved in Japan in January 2021. Like ghrelin, anamorelin also increases the appetite and lean body mass of patients with cancer cachexia. On the other hand, in clinical trials, there was no statistical significance for increasing the 6-minute walk test distance and recovering non-dominant hand grip strength. As for the functional recovery, a new program has been developed for non-pharmacotherapy with nutritional and exercise interventions. These 2 kinds of interventions will become effective anti-cachexia therapy. Research is also underway to produce anti-cachexia drugs other than anamorelin. Somes are already in their clinical trials. Anti-cachexia therapy will be a new option for treating advanced cancer.


Two-Dimensional Transthoracic Echocardiography-Based Diagnosis of Right Ventricular Aneurysm: A Neglected Issue in Patients with Coronary Artery Disease: Case Series and Literature Review.
Right ventricular (RV) aneurysm is a very rare ventricular lesion. An aneurysm is formed mainly as a complication of myocardial infarction (MI). As an RV aneurysm is a potentially life-threatening occurrence, its appropriate diagnosis is of great significance. However, right-sided heart diseases, especially RV aneurysms, have been neglected for years. Recent studies in the literature have elucidated the role of the right side of the heart in patients' prognosis and response to treatment. However, RV aneurysm has been scarcely investigated, and most of the attention has been given to the left ventricular aneurysm in patients with ischemic heart diseases (IHD). Herein, we investigated a total of 625 patients with IHD referred for two-dimensional transthoracic echocardiography (2D TTE), among whom 18 were diagnosed with RV aneurysms through precise examination of several TTE views. The characteristics of these cases, including demographics, medical history, and results of cardiac tests (which the patients underwent previously), were recorded and presented. This study emphasized the importance of performing a meticulous 2D TTE evaluation and a thorough examination of different views by an expert echocardiographer, with special attention to the presence of an RV aneurysm in a patient suffering from IHD who presented either with acute coronary syndrome, including MI, or chronic IHD. The scarcity of information, especially in terms of complications and the most appropriate diagnostic methods, calls for further studies in this regard.


Prevalence of skin diseases among students with disabilities in Mansoura, Egypt.
Children with disabilities may be particularly susceptible to skin disorders, therefore the aim of this study was to estimate the prevalence of skin disease among such children in Mansoura, Egypt. A total of 636 students with disabilities (76 blind, 446 deaf-mute and 114 mentally retarded) and 720 sex and age matched students (control) who did not have these disabilities were given a thorough dermatological examination. We found 89.5% of blind students, 99.3% of deaf students and 100% of mentally retarded students had 1 or more skin diseases (both infectious and non-infectious) in comparison to 24.2% of the control group. Strict hygienic measures, periodic skin examination and health education of persons caring for students with disabilities are recommended.


Investigating parylene-HT as a substrate for human cell patterning.
We demonstrate, for the first time, how parylene-HT on SiO2 substrates can be used as a human cell patterning platform. We demonstrate this platform with hNT astrocytes, derived from the human NTera2.D1 cell line. We show how hNT astrocytes are attracted to Parylene-HT and repelled by the SiO2 and are shown to adopt a similar morphology as that attained on standard tissue culture polystyrene. Furthermore, parylene-HT was capable of patterning the astrocytes achieving a ratio of 8:1 for cells on parylene compared to SiO2. Thus, as parylene-HT has similar physical properties to parylene-C with the addition of UV and thermal resistance, parylene-HT represents a desirable alternative substrate for human cell patterning.


How Psychedelic-Assisted Treatment Works in the Bayesian Brain.
Psychedelics are experiencing a renaissance in clinical research. In recent years, an increasing number of studies on psychedelic-assisted treatment have been conducted. So far, the results are promising, suggesting that this new (or rather, rediscovered) form of therapy has great potential. One particular reason for that appears to be the synergistic combination of the pharmacological and psychotherapeutic interventions in psychedelic-assisted treatment. But how exactly do these two interventions complement each other? This paper provides the first account of the interaction between pharmacological and psychological effects in psychedelic-assisted treatment. Building on the relaxed beliefs under psychedelics (REBUS) hypothesis of Carhart-Harris and Friston and the contextual model of Wampold, it argues that psychedelics amplify the common factors and thereby the remedial effects of psychotherapy. More precisely, psychedelics are assumed to attenuate the precision of high-level predictions, making them more revisable by bottom-up input. Psychotherapy constitutes an important source of such input. At best, it signalizes a safe and supportive environment (cf. setting) and induces remedial expectations (cf. set). During treatment, these signals should become incorporated when high-level predictions are revised: a process that is hypothesized to occur as a matter of course in psychotherapy but to get reinforced and accelerated under psychedelics. Ultimately, these revisions should lead to a relief of symptoms.


A Kazal-type inhibitor with thrombin specificity from Rhodnius prolixus.
A thrombin-specific inhibitor with an apparent molecular mass of 11 kDa has been purified from the insect Rhodnius prolixus. Amino-terminal protein sequence analysis allowed the molecular cloning of the corresponding cDNA. The open reading frame codes for a protein of about 103 amino acid residues and displays an internal sequence homology of residues 6-48 with residues 57-101 indicating a two-domain structure. Based on the amino acid sequence the two domains exhibit high homology to protease inhibitors belonging to the Kazal-type family. Model building suggests that the first domain binds to the active site with residue His10 pointing into the specificity pocket. From gel filtration and tight-binding inhibition experiments the inhibitor appears to form 1:1 complexes with thrombin. Periplasma-directed heterologous expression of the rhodniin cDNA in Escherichia coli yields the intact thrombin inhibitor. Natural and recombinant rhodniin both display inhibition constants of about 2 x 10(-13) M.


Growth studies in Jena, Germany: Changes in body size and subcutaneous fat distribution between 1975 and 1995.
This report presents results of an anthropological investigation on Jena, Germany, schoolchildren from 1995. Stature and weight, body mass index (BMI), and four skinfolds (biceps, triceps, subscapular, suprailiac) are presented for children 7-14 years of age and are compared with results of investigations on schoolchildren carried out in Jena in 1975 and 1985. Between those years, in both sexes there were no significant differences in stature, weight, and consequently in the BMI. In this timespan, a trend toward a reduction of subcutaneous fat was noted. A different development was observed in the period 1985-1995. Stature as well as body weight increased, and because the increase in weight was greater than expected from the increase in stature, there also was an increase in the BMI. A large increase in overall subcutaneous fatness was also found. In 1995, the highest amount of body fat was observed in Jena children since 1975. Changes in the distribution of subcutaneous fat tissue occurred. Between 1975 and 1985, the ratio of trunk to extremity skinfolds (T/E ratio) decreased significantly in boys and girls in all ages, but increased between 1985 and 1995. In spite of this increase, children had the largest T/E ratio in 1975. Changes in the nutritional situation and other factors in living conditions, possibly related to the unification of Germany in 1989 influencing somatic development, are considered. Am. J. Hum. Biol. 10:579-587, 1998. © 1998 Wiley-Liss, Inc.


What am I 'living' with? Growing up with HIV in Uganda and Zimbabwe.
As paediatric HIV treatment has become increasingly available across the world, the global perinatally infected cohort is ageing. However, we know surprisingly little about what it is like to grow up with HIV in resource-stretched settings. We draw on findings from a prospective, qualitative study with HIV-positive children, their carers and healthcare workers from four clinics in Uganda and Zimbabwe to examine children's experiences of living with HIV on treatment. We consider how the HIV experience is made in a symbiotic relationship between children, carers and healthcare workers and shaped by broader discourses. Despite the radical development in prognosis for children, their experience of HIV is largely constructed in relation to a language of 'sickness' through the promotion of medicalised talk and the recounting of past illness stories. This narrow narrative framework both reflects and reproduces core dimensions of the lived experience of growing up with HIV, which emphasises an absence of resilient healthiness in the face of ongoing vulnerability and risk. The challenges that children encounter in articulating alternative narratives that prioritise the relative buoyancy of their health is indicative of the broader uncertainty that exists around the future for these children at this point in the epidemic.


Iron-controlled infection with Neisseria meningitidis in mice.
An iron-controlled infection was obtained after the intraperitoneal infection of Neisseria meningitidis strain M1011 into normal mice. The infection progressed rapidly but then disappeared in concert with the disappearance of plasma transferrin iron. Parenteral iron dextran enhanced and prolonged the infection in mice at dosages above 15 mg of Fe per kg. Studies on the distribution of iron dextran within the physiological iron pools and the importance of timing with the iron dextran addition indicated that high serum iron, available early during infection, was necessary to promote infection. High levels of iron in the reticuloendothelial system did not stimulate infection. A working hypothesis to explain the roles of iron in infection was developed: N. meningitidis obtains iron for growth from the transferrin pool, and iron dextran maintains transferrin iron levels during infection.


Systematic review: Effective characteristics of nursing homes and other residential long-term care settings for people with dementia.
In response to the need for an evidence-based review of factors within long-term care settings that affect the quality of care, this review compared characteristics of nursing homes and other residential long-term care settings for people with dementia and their informal family caregivers with respect to health and psychosocial outcomes. Databases were searched for literature published between 1990 and March 2012 that met review criteria, including that at least 80% of the subject population had dementia. Fourteen articles meeting review criteria that were of at least fair quality were found: four prospective cohort studies, nine randomized controlled trials (RCTs), and one nonrandomized controlled trial. Overall, low or insufficient strength of evidence was found regarding the effect of most organizational characteristics, structures, and processes of care on health and psychosocial outcomes for people with dementia and no evidence for informal caregivers. Findings of moderate strength of evidence indicate that pleasant sensory stimulation reduces agitation for people with dementia. Also, although the strength of evidence is low, protocols for individualized care and to improve function result in better outcomes for these individuals. Finally, outcomes do not differ between nursing homes and residential care or assisted living settings for people with dementia except when medical care is indicated. Given the paucity of high-quality studies in this area, additional research is needed to develop a sufficient evidence base to support consumer selection, practice, and policy regarding the best settings and characteristics of settings for residential long-term care of people with dementia.


[Occurrence of HIV antigens in patients with acquired immunodeficiency syndrome].
A total of 74 serum samples from 37 AIDS patients were analysed for HIV antigen and results were correlated with duration of the disease, predominant symptoms, T4 lymphocyte count in peripheral blood, and antiviral therapy. The prevalence of HIV-Ag increased with duration of AIDS and T4 lymphocyte depletion. It was also higher in patients who were not treated with antiviral therapy than in treated persons. No correlation was found between HIV-Ag and clinical picture of AIDS. HIV antigenemia indicates a poor prognosis and can be regarded as an additional parameter of monitoring of AIDS patients.


[Seroprevalence of IgG anti-HAV in hospital employees below 40 years old].
Hepatitis A is an acute infectious disease transmitted by fecal-oral route. As the incidence of hepatitis A has been increased in Gwangju and Chonnam province of Korea recently, the number of hepatitis A patients in hospital employees has also increased. Thus, we investigated the seroprevalence of IgG anti-HAV in hospital employees below 40 years old. We analysed the seroprevalence of anti-HAV IgG from 1,002 Chonnam national university hospital employees (men: 190, women: 812) who were below 40 years old. The age group was divided by 5 years; 21-25 years old 199 (19.9%), 26-30 years old 426 (42.5%), 31-35 years old 215 (21.5%), 36-40 years old 162 (16.1%). Overall seropositive rate of IgG anti-HAV was 32.8% (329/1,002). The seropositive rate of men was 40.5% (77/190) and that of women was 31.0% (252/812). The seropositive rates of each age group were 1.5% (3/199) in 21-25 years old, 21.6% (92/426) in 26-30 years old, 48.4% (104/215) in 31-35 years old, and 80.2% (130/162) in 36-40 years old. The seropositivity rate of the high risk group (doctors, nurses, technicians) was 28.9% (234/809). The seropositive rate of IgG anti-HAV was the lowest in early twenties of hospital employees and below 50% in early thirties. Therefore, hepatitis A vaccination may be warranted in the hospital employees below the early thirties.


[FUNCTIONAL SOMATIC SYNDROMES AMONG ETHIOPIAN IMMIGRANTS IN ISRAEL].
The psychiatric classifications of disease (DSMIV; ICD-10) relate to a family of high incidence somatoform disorders whose use isn't uniform and cannot be measured. DSM-5 presents the term "cultural conceptualization of distress", which attempts to describe the cultural construct and its influences on mental distress and symptom presentation. Somatization among immigrants poses a diagnostic, treatment and research challenge due to cultural differences such as wrong understanding of their symptoms that may lead to misdiagnosis and to prescribing wrong and possibly harmful treatment and unnecessary hospitalization. This challenge is greater when encountering Ethiopian new immigrants due to the significant doctor-patient cultural gaps on one hand, and the community's heterogeneity, on the other. The Integrative Culture Sensitive Assessment and Treatment Model helps structure the diagnostic and treatment processes appropriately. Two culture-related functional somatic disorders are presented, alongside with their diagnosis and treatment: The "Ken-Ken" syndrome (worms in the ear) - where the patient complains worms have entered her ear and head influencing her daily functioning, and the "prolonged pregnancy" syndrome, where the menopausal woman believes she is pregnant for many years and that the fetus "has turned into bone". This article presents the somatization mechanism via two culture-related case studies of Ethiopian new immigrants to Israel suffering from emotional distress via culturally different symptomatology. It further presents an integrated cultural oriented treatment approach as a way to reduce overuse of primary and secondary medical services.


Adult orbital xanthogranuloma with associated adult-onset asthma.
: The authors report a case of adult orbital xanthogranuloma with associated adult-onset asthma in a 44-year-old man. Adult orbital xanthogranuloma was diagnosed on the basis of the clinical findings of bilateral, indurated, yellow eyelid lesions in a patient presenting with adult-onset asthma. Incisional biopsy of the eyelid lesions demonstrated a diffuse histiocytic infiltrate of the orbit and Touton giant cells without evidence of necrobiosis. Systemic evaluation failed to show evidence of bone lesions or paraproteinemia. When patients present with atypical indurated yellow eyelid lesions, a biopsy should be considered. If Touton giant cells are present, a systemic evaluation should be undertaken to rule out both Erdheim-Chester disease and necrobiotic xanthogranuloma. If no systemic findings are present, other than the possibility of adult-onset asthma, the rare entity of adult orbital xanthogranuloma should be considered.


[C-reactive protein inhibits the expression of hypoxia-inducible factor-1alpha in human umbilical vein endothelial cells in hypoxic condition].
To investigate the effect of C-reactive protein (CRP) on expression of hypoxia-inducible factor-1alpha (HIF-1alpha). Using CoCl(2) (100 micromol/L) to simulate hypoxic condition for culturing human umbilical vein endothelial cells (HUVECs), we examined the effects of CRP on expression of HIF-1alpha. The proteins were extracted from the cells after a 24-hour exposure of the cells to CRP of varied concentrations in the presence of CoCl(2), and Western blotting was performed for quantification of HIF-1alpha expression, the results were analyzed statistically with SPSS software. CRP at the concentration of 5 microg/ml decreased the expression of HIF-1alpha (P<0.001), producing the maximum inhibitory effect at the concentration of 100 microg/ml, an effect exhibiting dose-dependence. CRP inhibits the expression of HIF-1alpha in HUVECs subjected to hypoxic condition, which serves as an important evidence for the inhibitory effect of CRP on angiogenesis in hypoxic condition.


[Genetic alterations of transcription cofactors in solid tumors].
Many hormones exert their effects through specific nuclear receptors which belong to a superfamily of ligand-activated transcription factors. These receptors control target gene expression through the recruitment of different cofactors acting as transcription activation or repression mediators, generally as parts of multiprotein complexes. The importance and the role in physiopathology of these different cofactors only begin to be defined. Different types of alterations affecting genes coding nuclear receptor transcription cofactors have indeed been described in cancer. The most important examples are gene amplification that leads to overexpression and gene mutations or translocations introducing qualitative modifications. This paper aims at bringing together the corresponding literature and focuses on gene alterations observed in solid tumors.


[Prevalence of various urination disorders in residents of the Republic of Dagestan].
to evaluate the prevalence of various urination disorders in residents of the Republic of Dagestan, and, thus, to improve their diagnosis and treatment. 584 residents (264 men and 320 women) from different regions of the Republic of Dagestan took part in an anonymous questionnaire survey: 165 residents of Makhachkala, including 92 men and 73 women; 86 residents of Derbent and villages of Southern Dagestan, including 30 men and 56 women; 73 residents of Khasavyurt and Kizilyurt, including 34 men and 39 women; 53 residents of Buynaksk, including 19 men and 34 women; 42 residents of Izberbash, including 19 men and 23 women; 58 residents of the Kaspiysk, 29 men and 29 women; 42 residents of Kayakent, 4 men and 38 women; 65 residents of other regions of the Republic of Dagestan (Karabudakhkent, Gumbet, Gunibsk, Shamil, Khunzakh, Botlikh, Kazbek, Levashin, Tlyaratin, and Tsumadin regions), 37 men and 28 women. According to the survey of the residents of the Republic of Dagestan, a significant prevalence of various urinary disorders (63.5%) was found among both men (61.7%) and women (65.0%). Unfortunately, not all patients seek medical advice with complaints of dysuria (55.5%). The fact that 18.8% of patients do not know that they can get help, and 24.1% believe that they do not have a good doctor in their region can be considered as the most an unfavorable moment in terms of the reasons for the refusal of visiting a doctor.. All this findings suggest the need for educational programs both for physicians and the population (educative activities).


[Autoimmune hepatitis and anti-Ro antibodies. Is there a link?].
Antinuclear antibodies (ANA) are considered to be markers of autoimmune disease. Several specific reactivities of ANA are known, among them the Ro (SS-a) complex. Although the presence of anti-Ro antibodies is widely known in systemic connective tissue diseases such as lupus erythematous or Sjögren's syndrome, few studies have attempted to link this finding with autoimmune hepatitis (AIH). We present a case of acute AIH in a 55-year-old woman who tested positive for anti-Ro 60 kD antibodies. The Ro (SS-A) antigen is a complex ribonucleoprotein whose structure is still the subject of debate. Two fractions, of 50 and 60 kD, have been identified. A review of the literature revealed frequencies of 21-34% for anti-Ro 52 kD and of 9-13-6% for anti-Ro 60 kD in AIH. Although no relationship has been demonstrated between this complex and the etiopathogenic mechanisms or clinical patterns of AIH, we propose that multicenter investigations with large series should be performed before the possible involvement of anti-Ro antibodies in these diseases is definitively ruled out.


JCL roundtable: High-density lipoprotein function and reverse cholesterol transport.
High-density lipoproteins (HDL) have been known since the 1960s to be associated with protection from atherosclerotic cardiovascular disease. However, the mechanisms of this protection are unclear. The extent to which HDL per se vs other correlated metabolic factors may mitigate atherosclerosis has been seriously questioned. In fact, new epidemiologic studies have found that in some clinical settings, very high HDL cholesterol levels correlate with increased atherosclerotic risk. Most importantly, over the past 2 decades, randomized clinical trials targeting HDL have failed to reproduce the usual epidemiologic inverse relation of HDL cholesterol to atherosclerotic events. In this roundtable discussion, we bring together 3 expert investigators working in the HDL field to elucidate questions of HDL function. One area of agreement is that reverse cholesterol transport remains a primary hypothesis for an anti-atherogenic role of HDL. Bioassays that measure cholesterol efflux capacity of HDL (or of apolipoprotein [apo] B-depleted plasma) have emerged as potentially accurate surrogates for reverse cholesterol transport. ApoA-I is the major functional apoprotein of HDL, but apoE- and apoC-III-containing subpopulations of HDL may have significant roles. Anti- and pro-inflammatory functions of various HDL particles, as well as the role of oxidative and other modifications, are gaining attention.


A Bayesian approach for population pharmacokinetic modelling of sirolimus.
To explore a Bayesian approach for the pharmacokinetic analysis of sirolimus concentration data arising from therapeutic drug monitoring (poorly informative concentration-time point design), and to explore possible covariate relationships for sirolimus pharmacokinetics. Sirolimus concentration-time data were available as part of routine clinical care from 25 kidney transplant recipients. Most samples were taken at or near the trough time point at steady state. The data were analyzed using a fully conditional Bayesian approach with PKBUGS (v 1.1)/WinBUGS (v 1.3). Features of the data included noncompliance and missing concentration measurements below the limit of sensitivity of the assay. Informative priors were used. A two-compartment model with proportional residual error provided the best fit to the data (consisting of 315 sirolimus concentration-time points). The typical value for the apparent clearance (CL/F ) was 12.5 l h(-1) at the median age of 44 years. Apparent CL was found to be inversely related to age with a posterior probability of a clinically significant effect of 0.734. A population pharmacokinetic model was developed for sirolimus using a novel approach. Bayesian modelling with informative priors allowed interpretation of a significant covariate relationship, even using poorly informative data.


Shaking hands with a computer: an examination of two methods of organizational newcomer orientation.
The current study investigated the effects of using a computer-based orientation program on organizational socialization and attitudinal outcomes. In a quasi-experimental field study, 261 newcomers either participated in a group, social-based orientation session or an individual, computer-based orientation session. Consistent with hypotheses, results indicated that participation in the computer-based orientation session led to lower levels of socialization in the more socially rich content areas, whereas the more information-based content areas were not affected. Levels of socialization mediated the effects of computer-based orientation on the more distal attitudinal outcomes of affective organizational commitment and job satisfaction. Computer-based orientation participation also negatively affected supervisor ratings of socialization. The results demonstrate the importance of newcomer orientations and socialization outcomes during organizational entry and that training method can be an important moderator of orientation practices.


Initial Specimen Diversion Device Utilization Mitigates Blood Culture Contamination Across Regional Community Hospital and Acute Care Facility.
A West Virginia regional community hospital incorporated an initial specimen diversion device (ISDD) into conventional blood culture protocol with the objective to bring the hospital-wide blood culture contamination (BCC) rate from a 3.06% preintervention rate to a target performance level below 1%. Emergency department staff, laboratory phlebotomists, and nursing staff on acute-critical care floors were trained on ISDD (Steripath Gen2, Magnolia Medical Technologies, Inc., Seattle, WA) operating procedure and utilized the device for blood culture sample collection with adult patients from September 2020 through April 2021. Of 5642 blood culture sets collected hospital-wide, 4631 were collected with the ISDD, whereas the remaining sets were collected via the conventional method. The ISDD BCC rate of 0.78% differed from the conventional method BCC rate of 4.06% observed during the intervention period (chi-squared test P < 0.00001). The ISDD group attained a sub-1% BCC rate to satisfy the intervention objective.


Structure, magnetism and photomagnetism of mixed-ligand tris(pyrazolyl)methane iron(ii) spin crossover compounds.
A range of bis-facial tridentate chelate complexes of type [Fe((R-pz)(3)CH)((3,5-Me(2)pz)(3)CH)](BF(4))(2) has been characterised that contain two different tris-pyrazolylmethane ligands, with variations in R being H (complex crystallised as polymorphs and ) and 4-Me (), as well as R = H with a CH(2)OH arm off the methane carbon (). A tris(pyridyl)methane analogue is also described (). The tris(3,5-dimethylpyrazolyl)methane co-ligand (3,5-Me(2)pz), and the BF(4)(-) counterion, are constant throughout. The spin-crossover properties of these Fe(ii) d(6) compounds have been probed in detail by variable temperature magnetic, Mössbauer spectral and crystallographic methods. The effects of distortions from octahedral symmetry around the Fe(ii) centres, of crystal solvate molecules (1.5 MeCN in and 2 MeCN in ) and of supramolecular/crystal packing, are discussed. In the case of , subtle twisting of pyrazole rings occurs, as a function of temperature, that has a greater effect upon the relative positions of the Fe(ii) chelate molecules in polymorph than in polymorph ; this is thought to drive the cooperativity differences observed in the magnetism of the polymorphs. Comparisons are also made between to and their homoleptic, parent [Fe(L)(2)] (2+) materials. The complexes were screened for the LIESST (light induced excited spin state trapping) effect by measurements of diffuse absorption spectra on the surface of powder samples, at different temperatures. One example, , showed a 2-step thermal spin crossover transition and it was probed in detail for its photomagnetic features. The T(LIESST) and T(1/2) values for did not obey an empirical relationship, T(LIESST) = 150 - 0.3T(1/2) followed by many Fe(ii)(N-donor)(6) crossover compounds of the bis-tridentate (meridional) type, and possible reasons for this are discussed.


Effect of pyridostigmine on the hydrocortisone-mediated decrease of circulating growth hormone levels in acromegaly.
The aims of our study were to investigate the effect of the acetylcholinesterase inhibitor pyridostigmine (PD) administration on growth hormone (GH) secretion in acromegaly and to investigate the effects of PD on GH levels following an i.v. infusion of hydrocortisone in acromegaly. We studied five adult patients with active acromegaly, three men and two women with a mean age of 60 +/- 5 years (range 47-71 years) and a mean BMI of 27 +/- 0.7 kg/m2 (range 24-28 kg/m2). All the patients underwent: 1) placebo, 2 tablets po or 2) PD, 120 mg po, at time -60 plus a bolus i.v. injection of 100 mg hydrocortisone succinate in 2 ml saline at time 0 followed by an i.v. infusion of 250 mg hydrocortisone succinate in 250 ml saline from 0 to 120 min, or 3) PD, po or 4) placebo, po at time -60 plus a bolus i.v. injection of 2 ml saline followed by an i.v. infusion of 250 ml saline from 0 to 120 min. Serum GH values did not significantly change after PD administration compared to those during placebo treatment and with respect to baseline levels. In all of the acromegalic patients during hydrocortisone succinate infusion, GH values clearly decreased with respect to basal levels in varying degrees, with a nadir between 90 and 180 minutes after the beginning of hydrocortisone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


The use of permanganate as a sequencing reagent for identification of 5-methylcytosine residues in DNA.
The use of permanganate as a reagent for DNA sequencing by chemical degradation has been studied with respect to its specificity for 5-methylcytosine residues. At weakly acidic pH and room temperature, 0.2 mM potassium permanganate reacts preferentially with thymine, 5-methylcytosine, and to a lesser extent with purine residues, while cytosine remains essentially intact. Permanganate oxidation is, therefore, a suitable DNA sequencing reaction for positive discrimination between 5-methylcytosine and unmethylated cytosine.


Biosurfactant yields and nutrient consumption of Pseudomonas fluorescens 378 studied in a microcomputer controlled multifermentation system.
Production of biosurfactant AP-6 and consumption of carbon (succinic acid) and nitrogen (ammonium ions) by Pseudomonas fluorescens 378 were studied under different growth conditions. The study was performed in a microcomputer controlled multibatch fermentation system which enabled simultaneous running of 10 fermentors. The fermentors were mantled glass vessels, temperature controlled by circulated water, and mixing was arranged by magnetic stirrers. They were connected to the computer system (pH measurement and control) via signal conditioning cards. The microcomputer had a 128 kbytes RAM, two 800-kbyte floppy disc drives, a graphic terminal, and expansion cards. Biosurfactant production was independent of the carbon-to-nitrogen ratio and the phosphorus content in the medium. Omitting the Fe(III) supplement to the medium increased the product yield by 120%. Changes in oxygen transfer rate and pH in the iron deficient cultures did not have any effect on the product yield. Iron deficiency increased the cell consumption of carbon source. Consumption of carbon source in relation to nitrogen uptake (carbon/nitrogen quotient) increased with increasing quotient in the growth medium. The uptake of carbon and nitrogen changed in the intervals of 1.2-1.5 g/g biomass and 0.09-0.16 g/g biomass, respectively. The consumption of carbon increased from 1.5 g/g biomass to 2.0 g/g biomass when the medium concentration of phosphorus was decreased from 0.18 to 0.027 g/L.


MiR-129-5p/TRIP13 affects malignant phenotypes of colorectal cancer cells.
Aberrant miR-129-5p expression is a key modulator of cancer development. But how the miRNA affects colorectal cancer (CRC) remains unclear. This study was designed to illustrate the underlying mechanism of miR-129-5p in CRC. MiR-129-5p expression at cellular level was assayed by qRT-PCR. Its role in CRC cell phenotypes was studied by cell function experiments. The binding relationship between miR-129-5p and TRIP13 was analyzed and verified by target changed to bioinformatics prediction and dual-luciferase detection. Furthermore, the functional mechanism based on miR-129-5p and TRIP13 in CRC was studied through rescue experiments. CRC cell lines presented prominently lower miR-129-5p levels than the normal colon epithelial cell line. The forced miR-129-5p level suppressed CRC cell growth. TRIP13 was proved to be a target of miR-129-5p in CRC cells, and miR-129-5p overexpression reduced TRIP13 expression. TRIP13 knockdown resulted in cell cycle arrest. Additionally, TRIP13 overexpression restored the impacts of miR-129-5p overexpression on cell malignant phenotypes and cell cycle. MiR-129-5p down-regulated TRIP13 expression, thereby restraining the malignant progression of CRC cells. The findings may offer a new target for molecular therapy of CRC.


Tenoxicam-associated hepatic injury: a case report and review.
A 51-year-old woman developed jaundice while taking tenoxicam. A full evaluation, including ultrasound, computed tomography, endoscopic cholangiography and liver biopsy, confirmed the diagnosis of mixed hepatic injury. The patient's jaundice and all other liver function abnormalities normalized 1 month after she discontinued taking tenoxicam. This is the first case report of mixed hepatic injury, confirmed with biopsy, associated with tenoxicam. Tenoxicam should be considered as a potential cause of hepatic injury when other more common aetiologies have been excluded.


Innovating Maternal and Child Health: Incentive Prizes to Improve Early Childhood Development.
Protecting and advancing maternal and child health is a critical goal to both society and to the economy, given that their health is a predictor of the next generation's health. Yet despite this recognition, many of the communities aiming to improve maternal and child health still problem-solve in silos: age silos, disease silos, organizational silos, disciplinary silos, data silos, and communication silos, often created or exacerbated by the disconnected approaches to research, funding, and reporting. These silos limit discovery and spread of new solutions to important maternal and child health problems. In this paper, we will discuss federal incentive prizes as a tool to break down silos and to engineer cognitive diversity and transdisciplinary collaboration. In 2018, the United States Health Resources and Services Administration, Maternal and Child Health Bureau (HRSA MCHB) launched the "Maternal and Child Health Bureau Grand Challenges," a suite of four prize competitions totaling $1.5 million addressing critical issues in maternal and child health. These included federal challenges designed to (1) prevent childhood obesity in low-income communities, (2) improve the remote monitoring of pregnancy, (3) improve care coordination and planning for children with special health care needs, and (4) prevent opioid misuse among pregnant women and new mothers. The ability to incentivize innovation to address critical public health issues cannot rest in the private sector alone. Complementing other investments, the Challenge mechanism's power to catalyze the rapid development of innovative solutions can improve how we address barriers to achieve optimal maternal and child health for the families that we serve.


Burning charcoal: an indigenous method of committing suicide in Hong Kong.
Carbon monoxide (CO) poisoning by burning charcoal has become one of the most common ways of committing suicide in Hong Kong since late 1998. The evolution of the phenomenon was explored in the current study. Information about completed suicides between January 1996 and December 1999 was obtained from the Hong Kong death registry and hospital authority, and information about ambient temperature and humidity was obtained from the Hong Kong Observatory. News on completed suicides by burning charcoal was collected by computer search using the data bank of 6 major Hong Kong newspapers. The data were analyzed. CO poisoning by burning charcoal rose from 0% of all Hong Kong suicides in 1996 and 1997 to 1.7% in 1998 and 10.1% in 1999. The monthly incidence rate bore a reciprocal relationship with the ambient temperature. Suicidal pacts were overrepresented, and past history of mental illness was uncommon. Both demographic and clinical features of suicides by burning charcoal resembled those of suicides by domestic gas poisoning. The overall suicide rate remained unchanged in the above period. Suicide by burning charcoal is a new variant of domestic gas poisoning. A host of biopsychosocial and ethnological factors are responsible for the birth and indigenization of the method.


Fasting as possible complementary approach for polycystic ovary syndrome: Hope or hype?
Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women.


Clinical applicability of deep learning-based respiratory signal prediction models for four-dimensional radiation therapy.
For accurate respiration gated radiation therapy, compensation for the beam latency of the beam control system is necessary. Therefore, we evaluate deep learning models for predicting patient respiration signals and investigate their clinical feasibility. Herein, long short-term memory (LSTM), bidirectional LSTM (Bi-LSTM), and the Transformer are evaluated. Among the 540 respiration signals, 60 signals are used as test data. Each of the remaining 480 signals was spilt into training and validation data in a 7:3 ratio. A total of 1000 ms of the signal sequence (Ts) is entered to the models, and the signal at 500 ms afterward (Pt) is predicted (standard training condition). The accuracy measures are: (1) root mean square error (RMSE) and Pearson correlation coefficient (CC), (2) accuracy dependency on Ts and Pt, (3) respiratory pattern dependency, and (4) error for 30% and 70% of the respiration gating for a 5 mm tumor motion for latencies of 300, 500, and 700 ms. Under standard conditions, the Transformer model exhibits the highest accuracy with an RMSE and CC of 0.1554 and 0.9768, respectively. An increase in Ts improves accuracy, whereas an increase in Pt decreases accuracy. An evaluation of the regularity of the respiratory signals reveals that the lowest predictive accuracy is achieved with irregular amplitude patterns. For 30% and 70% of the phases, the average error of the three models is <1.4 mm for a latency of 500 ms and >2.0 mm for a latency of 700 ms. The prediction accuracy of the Transformer is superior to LSTM and Bi-LSTM. Thus, the three models have clinically applicable accuracies for a latency <500 ms for 10 mm of regular tumor motion. The clinical acceptability of the deep learning models depends on the inherent latency and the strategy for reducing the irregularity of respiration.


Detection of West Nile virus antigen in mosquitoes and avian tissues by a monoclonal antibody-based capture enzyme immunoassay.
An antigen capture immunoassay to detect West Nile (WN) virus antigen in infected mosquitoes and avian tissues has been developed. With this assay purified WN virus was detected at a concentration of 32 pg/0.1 ml, and antigen in infected suckling mouse brain and laboratory-infected mosquito pools could be detected when the WN virus titer was 10(2.1) to 10(3.7) PFU/0.1 ml. In a blindly coded set of field-collected mosquito pools (n = 100), this assay detected WN virus antigen in 12 of 18 (66.7%) TaqMan-positive pools, whereas traditional reverse transcriptase PCR detected 10 of 18 (55.5%) positive pools. A sample set of 73 organ homogenates from naturally infected American crows was also examined by WN virus antigen capture immunoassay and TaqMan for the presence of WN virus. The antigen capture assay detected antigen in 30 of 34 (88.2%) TaqMan-positive tissues. Based upon a TaqMan-generated standard curve of infectious WN virus, the limit of detection in the antigen capture assay for avian tissue homogenates was approximately 10(3) PFU/0.1 ml. The recommended WN virus antigen capture protocol, which includes a capture assay followed by a confirmatory inhibition assay used to retest presumptive positive samples, could distinguish between the closely related WN and St. Louis encephalitis viruses in virus-infected mosquito pools and avian tissues. Therefore, this immunoassay demonstrates adequate sensitivity and specificity for surveillance of WN virus activity in mosquito vectors and avian hosts, and, in addition, it is easy to perform and relatively inexpensive compared with the TaqMan assay.


Family theory and the scientific method.
The evolution of family interactional research reveals a transformation from the theoretical concerns of a novel cybernetic paradigm to methodological problems of a prior mechanistic one. This change can be understood, within a cybernetic perspective, as an example of the characteristic functioning of adaptive systems attempting to maintain themselves unchanged under changed circumstances. A turn to a focus on method results in theoretical self-correction and the implicit retention of a mechanistic paradigm. This eliminates those most novel aspects of family interactional research that suggested the beginning of a cybernetic paradigm. A mechanistic methodology for family interaction research can be understood as an analogue to ritual in social systems. A primary attribute of ritual, sanctity, self-reflexively defines certain basic premises as unquestionable. By this, it regulates the beliefs of those who act it out, and eliminates the most radial novelty that confronts these beliefs. The evolution of family interactional research and its changing relationship to its methodology is an example of this process, the introduction and rejection of novelty by self-regulating systems. In this case, a challenge to the basic premises of a mechanistic paradigm is subverted, using its method as the arbitrator of validity in family interactional research.


Gender differences in small intestinal endothelial function: inhibitory role of androgens.
Although gender differences exist in cardiovascular endothelial function, it remains unclear whether such differences are also seen in small intestinal endothelial function. To determine this, untreated male, age-matched proestrus female, castrated male, and 17beta-estradiol (E2)-treated noncastrated male rats were studied. Dose response curves to ACh and nitroglycerin (NTG) were determined by measuring changes in perfusion pressure by using an isolated small intestinal perfusion model. Endothelium-derived nitric oxide (NO) production/release was indirectly determined by the ability of intact endothelium to suppress serotonin (10(-5) M)-induced perfusion pressure changes. Intestinal tissue levels of NO were also measured. Moreover, plasma levels of androgen and E2 were determined and correlated with ACh (10(-8) M)-induced perfusion pressure reductions. ACh-induced intestinal perfusion pressure reductions in proestrus females, castrated males, and E2-treated noncastrated males were significantly higher than in untreated males. NTG-induced perfusion pressure reductions were not significantly different among groups. Perfusion pressures after administration of serotonin (10(-5) M) and intestinal tissue levels of NO in proestrus females, castrated males, and E2-treated noncastrated males were also significantly higher than in untreated males. Plasma androgen levels in proestrus females, castrated males, and in E2-treated noncastrated males were significantly lower compared with untreated males. There was a positive correlation between plasma androgen and ACh-reduced perfusion pressure; however, E2 levels did not show a similar relationship. Thus androgens appear to play an inhibitory role in small intestinal endothelial function. These properties in male vessels can be modulated by decreasing the level of circulating androgens or by E2 treatment.


Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on mitochondrial function and lipid metabolism.
Obesity-related increase in body fat mass is a risk factor for many diseases, including type 2 diabetes. Controlling adiposity by targeted modulation of adipocyte enzymes could offer an attractive alternative to current dietary approaches. Brown adipose tissue, which is present in rodents but not in adult humans, expresses the mitochondrial uncoupling protein 1 (UCP1) that promotes cellular energy dissipation as heat. Here, we report on the direct metabolic effects of forced UCP1 expression in white adipocytes derived from a murine (3T3-L1) preadipocyte cell line. After stable integration, the ucp1 gene product was continuously expressed during differentiation and reduced the total lipid accumulation by approximately 30% without affecting other adipocyte markers, such as cytosolic glycerol-3-phosphate dehydrogenase activity and leptin production. The expression of UCP1 also decreased glycerol output and increased glucose uptake, lactate output, and the sensitivity of cellular ATP content to nutrient removal. However, oxygen consumption and beta-oxidation were minimally affected. Together, our results suggest that the reduction in intracellular lipid by constitutive expression of UCP1 reflects a downregulation of fat synthesis rather than an upregulation of fatty acid oxidation.


Helicobacter muricola sp. nov., a novel Helicobacter species isolated from the ceca and feces of Korean wild mouse (Mus musculus molossinus).
A slowly growing microaerophilic Helicobacter strain was isolated from the ceca and fecal pellets of Korean wild mice (Mus musculus molossinus). This bacterial strain possessed a pair of nonsheathed bipolar flagella, was positive for urease, catalase and oxidase, and reduced nitrate to nitrite. It proved susceptible to nalidixic acid and resistant to cephalodine, and did not hydrolyze hippurate. On the basis of phenotypic characteristics and 16S rRNA gene sequence analysis, the isolate represents a new species of the genus Helicobacter, for which the name Helicobacter muricola sp. nov. is proposed; the type strain of the new species is w-06T.


Optimising medical elastomer performance.
The ability of DSC to detect and quantify the degree of cure is a major tool for optimising the property and processing of elastomer components. The rapid and information-rich OIT measurements can be applied in numerous ways to monitor and develop antioxidant packages. In addition, through some less applied tests, subtle differences between ionising radiation sources for sterilisation can be quantified and put to use in an advantageous way, for example, with reduction in surface tack and maintenance of mechanical strength in a surgical glove.


Development and in vitro assessment of alginate bilayer films containing the olive compound hydroxytyrosol as an alternative for topical chemotherapy.
Topical chemotherapy is the application of cancer drugs directly onto the skin, which has become a standard treatment for basal cell carcinoma. Due to the promising results in the treatment of skin cancer, topical chemotherapy has recently been applied to breast cancer patients because some breast cancer tissues are only superficial. Hydroxytyrosol, a phenolic compound from olives that is present in high amounts in Hidrox(®) olive extract, has been shown to have a protective effect on normal cells and selective antitumor activities on cancerous cells. The aims of the present study were to develop an alginate bilayer film containing Hidrox(®) and to investigate its potential use as a topical chemotherapeutic agent. Alginate films were characterized for swelling and for physical, thermal, rheological, and mechanical properties. Drug content uniformity and in vitro drug release tests were also investigated. The alginate bilayer films containing Hidrox(®), HB2, showed controlled release of hydroxytyrosol at a flux of 0.094±0.009 mg/cm(2)/h. The results of the cytotoxic assay showed that the HB2 films were dose-dependent and could significantly reduce the growth of breast cancer cells (MCF-7) at 150 μg/mL for a cell viability of 29.34±4.64%. In conclusion, an alginate bilayer film containing Hidrox(®) can be a potential alternative for topical chemotherapeutic agent for skin and breast cancer treatment.


Unusually large numbers needed to treat for radical prostatectomy in prostate cancer patients with PSA velocity ≤2 ng/ml/year.
The numbers needed to treat (NNT) and the corresponding confidence intervals for patients with prostate cancer and defined annual PSA increases (PSA velocity, PSAV) have not been described previously. The objective of this study is to assess NNT, numbers needed to treat to harm and corresponding confidence intervals for radical prostatectomy (RP) in patients with prostate cancer defined as a PSAV ≤2 ng/ml/year. NNT following RP were estimated in risk groups defined by PSAV using mortality statistics and hazard ratios obtained in a noncontrolled trial. As no suited control group and no appropriate randomized trials were available for doing this calculation and as such trials are unlikely to become available in the near future we have calculated our NNTs as published previously by using relative risk reduction from an earlier randomized trial (RCT) comparing RP with watchful waiting (WW) [Can J Urol 2006;13(suppl 1):48-55]. For preoperative PSAV >2 ng/ml/year, NNT for RP were estimated at 25, whereas for preoperative PSAV ≤2 ng/ml/year, the estimate was 618. The lower 95% confidence limits (NNTBl) were 9 and 126, respectively (treatment with benefit). The implications emerging from these findings are discussed by comparison with published NNT values from other RCTs. The lower 95% confidence limit for preoperative PSAV ≤2 ng/ml/year was found to be large in comparison. The NNT estimate obtained here for PSAV >2 ng/ml/year and its lower 95% confidence interval is comparable to values in other studies on prostate cancer for therapies considered to be effective, while the estimated NNT for patients with PSAV ≤2 ng/ml/year is large in comparison. We conclude that the benefits of RP for localized prostate cancer with preoperative PSAV ≤2 ng/ml/year may be considered small. There are several limitations to our findings, the most important of which lies in the fact that while PSAV remains significantly associated with outcomes, the predictive value of PSA measurements is low. While PSAV >2 ng/ml/year clearly indicates a need for surgery, a PSAV ≤2 ng/ml/year should imply further decision making.


Posterior pharyngeal wall carcinoma presenting as sudden onset bilateral upper limb radiculopathy.
This report describes the case of an elderly gentleman who presented with sudden onset bilateral upper limb radiculopathy and neck stiffness. On neck radiography, erosion of the fourth cervical vertebral body was seen. Further evaluation revealed the cause to be a moderately differentiated squamous cell carcinoma of the posterior pharyngeal wall. In spite of prompt initiation of radiation therapy with concurrent steroids, the patient died of progressive disease within 3 weeks of initial presentation.


phi X174 genome-capsid interactions influence the biophysical properties of the virion: evidence for a scaffolding-like function for the genome during the final stages of morphogenesis.
During the final stages of phi X174 morphogenesis, there is an 8.5-A radial collapse of coat proteins around the packaged genome, which is tethered to the capsid's inner surface by the DNA-binding protein. Two approaches were taken to determine whether protein-DNA interactions affect the properties of the mature virion and thus the final stages of morphogenesis. In the first approach, genome-capsid associations were altered with mutant DNA-binding proteins. The resulting particles differed from the wild-type virion in density, native gel migration, and host cell recognition. Differences in native gel migration were especially pronounced. However, no differences in protein stoichiometries were detected. An extragenic second-site suppressor of the mutant DNA-binding protein restores all assayed properties to near wild-type values. In the second approach, phi X174 was packaged with foreign, single-stranded, covalently closed, circular DNA molecules identical in length to the phi X174 genome. The resulting particles exhibited native gel migration rates that significantly differed from the wild type. The results of these experiments suggest that the structure of the genome and/or its association with the capsid's inner surface may perform a scaffolding-like function during the procapsid-to- virion transition.


Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus.
Levels of pituitary growth hormone (GH), a metabolic homeostatic factor with strong lipolytic activity, are decreased in obese individuals. GH declines prior to the onset of weight gain in response to excess caloric intake and hyperinsulinemia; however, the mechanism by which GH is reduced is not clear. We used transgenic mice expressing the human GH (hGH) gene, GH1, to assess the effect of high caloric intake on expression as well as the local chromosome structure of the intact GH1 locus. Animals exposed to 3 days of high caloric intake exhibited hyperinsulinemia without hyperglycemia and a decrease in both hGH synthesis and secretion, but no difference in endogenous production of murine GH. Efficient GH1 expression requires a long-range intrachromosomal interaction between remote enhancer sequences and the proximal promoter region through "looping" of intervening chromatin. High caloric intake disrupted this interaction and decreased both histone H3/H4 hyperacetylation and RNA polymerase II occupancy at the GH1 promoter. Incorporation of physical activity muted the effects of excess caloric intake on insulin levels, GH1 promoter hyperacetylation, chromosomal architecture, and expression. These results indicate that energy homeostasis alters postnatal hGH synthesis through dynamic changes in the 3-dimensional chromatin structure of the GH1 locus, including structures required for cell type specificity during development.


Taking smart steps toward clinical integration.
Health systems should take five key steps in the early phases of establishing a clinically integrated network (CIN): Establish the operating model and implementation timeline. Identify who to include. Define what's in it for the physicians. Agree on the tenets that will make the CIN stick. Understand when to say no.


Symptom burden, palliative care need and predictors of physical and psychological discomfort in two UK hospitals.
The requirement to meet the palliative needs of acute hospital populations has grown in recent years. With increasing numbers of frail older people needing hospital care as a result of both malignant and non-malignant conditions, emphasis is being placed upon understanding the physical, psychological and social burdens experienced by patients. This study explores the extent of burden in two large UK hospitals, focusing upon those patients who meet palliative care criteria. Furthermore, the paper explores the use of palliative services and identifies the most significant clinical diagnostic and demographic factors which determine physical and psychological burden. Two hospital surveys were undertaken to identify burden using the Sheffield Profile for Assessment and Referral to Care (SPARC). The Gold Standards Framework (GSF) is used to identify those patients meeting palliative care criteria. Participants were identified as being in-patients during a two-week data collection phase for each site. Data was gathered using face-to-face interviews or self-completion by patients or a proxy. Descriptive analyses highlight prevalence and use of palliative care provision. Binary logistic regression assesses clinical diagnostic predictor variables of physical and psychological burden. The sample consisted of 514 patients and elevated physical, psychological and social burden is identified amongst those meeting palliative care criteria (n = 185). Tiredness (34.6%), pain (31.1%), weakness (28.8%) and psychological discomfort (low mood 19.9%; anxiety 16.1%) are noted as being prevalent. A small number of these participants accessed Specialist Palliative Care (8.2%). Dementia was identified as a predictor of physical (OR 3.94; p < .05) and psychological burden (OR 2.88; p < .05), being female was a predictor of psychological burden (OR 2.00; p < .05). The paper highlights elevated levels of burden experienced by patients with palliative care requirements. Moreover, the paper also indicates that a large proportion of such patients are not in receipt of palliative approaches to their care. Furthermore, the paper identifies that those with non-malignant illnesses, especially dementia, may experience high levels of physical and psychological burden.


Ecology, feeding and natural infection by Leishmania spp. of phlebotomine sand flies in an area of high incidence of American tegumentary leishmaniasis in the municipality of Rio Branco, Acre, Brazil.
Phlebotomine sand flies (Diptera: Psychodidae) are insects of medical importance due to their involvement in the zoonotic transmission of Leishmania spp. to vertebrates. The aim of this work was to study the ecology of the sand fly fauna of two types of environments, a rural environment (the Transacreana Road) and an urban park (Horto Florestal Park), both located in the municipality of Rio Branco in the state of Acre, Brazil. Additionally, this study intended to investigate Leishmania infection and blood meal sources of these sand flies using molecular techniques. The sand fly fauna was studied in different environments (i.e. forest and peridomestic environments in a rural area, and an urban forest) using Shannon traps and HP light traps to collect sand fly specimens over 13 consecutive months (December 2014 to January 2016). For investigating natural infection by Leishmania and the source of sand fly blood meals, DNA samples were extracted from female sand flies and subjected to polymerase chain reaction targeting ITS1 and cytb genes. DNA sequencing was subsequently used to identify species of Leishmania and the source of blood meals. A total of 2515 individual sand flies of 43 species were collected and identified, Trichophoromyia auraensis (839; 33.35%), Trichophoromyia spp. (537; 21.35%) and Evandromyia saulensis (187; 7.43%) were more abundant in the rural area (S = 41 species) than in the urban forest. No significant differences were found in species richness between forest and peridomestic environments in the rural area (H = 0.04; P > 0.05), but a larger number of species was found in the forest. Leishmania DNA was sequenced in 13 samples, confirming the presence of L. (V.) braziliensis in Th. auraensis (n = 1), Ev. saulensis (n = 2), Ev. walkeri (n = 1), Ps. llanosmartinsi (n = 1), Pi. nevesi (n = 2), Ps. davisi (n = 1), Ps. ayrozai (n = 1), Pa. aragaoi (n = 1), Ny. antunesi (n = 1) and Ev. infraspinosa (n = 1). Only Ps. ayrozai possessed a sequence similar to that of L. (V.) guyanensis (99%). Through microscopic analysis, five specimens of Ev. saulensis were found to possess flagellate forms in the hindgut, with an infection rate of 2.4%. Samples from 33 fed females were submitted to cytb gene amplification, for which sequencing determined that all were similar to the sequence deposited on GenBank for Gallus gallus (domestic chicken). The high abundance of Trichophoromyia auraensis and Ev. saulensis, and the detection of L. (V.) braziliensis DNA, suggests that both species may be vectors of American tegumentary leishmaniasis. Psychodopygus ayrozai was found to be infected by L. (V) braziliesnsis and L. (V.) guyanensis, and although collected in low abundance, it may be a potential vector in the region. The sand fly fauna was found to be rich and diverse with predominance of the genus Psychodopygus. Identification of food sources of fed females showed that 100% amplified a gene region compatible with the domestic chicken, which although considered refractory in the disease transmission cycle, may have an influence on the population dynamics of sand flies.


Effects of smoking abstinence, smoking cues and nicotine replacement in smokers with schizophrenia and controls.
The mechanisms underlying the low smoking cessation rates among smokers with schizophrenia (SS) are unknown. In this laboratory study, we compared the responses of 21 SS and 21 non-psychiatric controls (CS) to manipulations of 5-hour smoking abstinence, transdermal nicotine replacement (0 mg, 21 mg and 42 mg), and in vivo smoking cues. Results indicate that SS were more sensitive than CS to the effects of acute abstinence on carbon monoxide (CO) boost, but not more sensitive to the effects of abstinence on urge levels or withdrawal symptoms. SS and CS did not differ in urge response to in vivo smoking cues, but SS were less consistent in their reactions. These findings suggest that heightened sensitivity to the effects of abstinence on smoke intake may partially account for the low cessation rates experienced by SS, but other potential mechanisms should be explored using behavioral laboratory models.


NanoPack: visualizing and processing long-read sequencing data.
Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences. The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License. The source code can be found at https://github.com/wdecoster/nanopack, together with links to separate scripts and their documentation. The scripts are compatible with Linux, Mac OS and the MS Windows 10 subsystem for Linux and are available as a graphical user interface, a web service at http://nanoplot.bioinf.be and command line tools. Supplementary data are available at Bioinformatics online.


Lung cancer and family-centered patient concerns.
The risk factors, diagnosis, management, and outcomes for lung cancer (LC) are a family experience. Genetic and environmental factors interact to predispose certain groups to LC, including family member, and the family or caregiving unit experiences the disease course as an interdependent group. This qualitative study examined the concerns and preferences of LC patients about incorporating family in addressing their lung cancer experiences and cancer risks. This project aims to identify concerns and preferences for addressing family history documentation, risk assessment, prevention, and follow-up issues for LC patients and their family. We held focus groups (FG) to discuss the format and timing of addressing these preferences and concerns. The qualitative data was analyzed using a grounded theory approach. 7 FG totaling 17 participants were conducted. The mean age was 64. All patients had advanced lung cancer. Participants included five males; nine African-Americans; three current, 11 former and three never smokers. Five participants had parents or grandparents with LC. Two had siblings with LC. Six themes were identified: (1) Varied journeys to LC diagnosis. (2) Mixed patient perceptions of cancer causation. (3) Limited documentation and utilization of family history. (4) Diverse attitudes toward smoking cessation. (5) A range of discussions about cancer risk, prevention, and screening. (6) Implications for implementation of family-centered cancer care and health promotion. The diagnosis of LC, its management, and outcomes occur in the family context. The diagnosis represents a potential teachable moment with opportunity to reduce the risk of LC development or improve early detection in a population at higher risk of developing lung cancer. Lung cancer patients are interested in discussing risk factors, prevention, and diagnosis of lung cancer for their relatives.


Effect of metyrapone on cortisol binding capacity in plasma.
Metyrapone was added in vivo to six different samples of normal plasma (0.1 mg/ml plasma) and administered orally (30 mg/kg) to 5 adrenalectomized patients. An increased ratio free, non protein-bound cortisol: total cortisol in plasma was demonstrated after metyrapone in all six in vitro studies and in 4 of the 5 adrenalectomized patients. These findings may explain the accelerating effect of metyrapone on cortisol metabolism.


Emerging Treatment Strategies in Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer death in well-developed countries. Therapeutic advances in PDAC to date have been modest. Recent progress to understand the molecular landscape of the disease has opened new treatment opportunities for a small subset of patients, frequently those with KRAS wild-type disease. Novel treatment strategies in PDAC include, among others, the use of nanotechnology and metabolic reprogramming. In addition, new strategies are being investigated, which are designed to overcome the resistance to checkpoint inhibitors, targeting DNA repair pathways including mismatch repair, increasing antigen presentation through the use of vaccines, targeting various signaling pathways, and reprogramming the tumor microenvironment. Here, we review the landscape of PDAC treatment strategies and some of these new agents.


[A case of primary malignant retroperitoneal mesothelioma needed to differentiate adrenal tumor].
Malignant mesothelioma is a neoplasm which tends to develop along serosal surfaces, such as the pleura and peritoneum. We report a rare case of malignant retroperitoneal mesothelioma in a 27-year-old woman. The patient was admitted with a chief compliant of intermittent high fever once a month, and left retroperitoneal tumor was detected by dynamic abdominal computed tomography. Since an adrenal tumor was suspected, laparoscopic tumor extirpation was performed. Immunohistochemically tumor cells were positive for calretinin and thrombomodulin, but negative for carcinoembryonic antigen (CEA) and Ber-Ep4. Based on these findings, primary malignant retroperitoneal mesothelioma was diagnosed.


Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart.
Unexplained bleeding episodes are associated with ventricular assist devices (VAD) and can occur in part due to acquired von Willebrand syndrome (AVWS). AVWS is characterised by loss of high molecular weight (HMW) multimers of von Willebrand factor (VWF) and decreased ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. Loss of multimers can occur as VWF is subjected to increased shear stress, which occurs in presence of VADs. We studied 12 patients who required mechanical support of their native heart for terminal cardiac insufficiency. Nine patients underwent placement of a VAD, while three underwent placement of a total artificial heart (TAH), which is connected directly to heart and large cardiac vessels without cannulas. Within one day of VAD implantation, four of five patients evaluated demonstrated loss of HMW multimers and impaired VWF function. AVWS was present within two weeks of implantation in eight of nine patients, and in all seven tested patients after >/=3 months. Patients with different VAD types developed varying severities of AVWS. After VAD explantation, HMW multimers were detectable and VWF function normalised in all patients. AVWS was not observed in the TAH patients studied. Our findings demonstrate that patients with an implanted VAD experience a rapid onset of AVWS that is quickly and completely reversed after device explantation. In addition, TAH patients do not develop AVWS. These results suggest that shear stress associated with exposure of blood to VAD cannulas and tubes may contribute to the development of AVWS.


Sex-specific alterations in whole body energetics and voluntary activity in heterozygous R163C malignant hyperthermia-susceptible mice.
Malignant hyperthermia (MH) is characterized by induction of skeletal muscle hyperthermia in response to a dysregulated increase in myoplasmic calcium. Although altered energetics play a central role in MH, MH-susceptible humans and mouse models are often described as having no phenotype until exposure to a triggering agent. The purpose of this study was to determine the influence of the R163C ryanodine receptor 1 mutation, a common MH mutation in humans, on energy expenditure, and voluntary wheel running in mice. Energy expenditure was measured by indirect respiration calorimetry in wild-type (WT) and heterozygous R163C (HET) mice over a range of ambient temperatures. Energy expenditure adjusted for body weight or lean mass was increased (P < .05) in male, but not female, HET mice housed at 22°C or when housed at 28°C with a running wheel. In female mice, voluntary wheel running was decreased (P < .05) in the HET vs WT animals when analyzed across ambient temperatures. The thermoneutral zone was also widened in both male and female HET mice. The results of the study show that the R163C mutations alters energetics even at temperatures that do not typically induce MH.


An analytical observational study on chronic kidney disease of unknown etiology at a rural tertiary care hospital in West Bengal.
Chronic kidney disease of unknown etiology (CKDu) has been a growing concern in the Indian population causing significant morbidity and mortality in these recent years. Thus, it is vital to understand the probable risk factors associated with its manifestation. This study aims to assess the distribution of various etiologies among CKD patients, investigate all the probable risk factors associated with CKDu, and estimate the health-related quality of life (QoL) among all CKDu patients in the study area. It was an analytical, observational, cross-sectional study where one objective had a case-control study design. It was conducted at Bankura Sammilani Medical College in Bankura district, West Bengal, during July 2022-August 2022. A total of 198 patients have been studied through detailed interviews using a predesigned, pretested, semi-structured schedule. Potential risk factors and their strength of association were analyzed with the help of multivariate logistic regression. It was found that the prevalence of CKDu was almost 71% in the study population, mostly affecting agricultural workers (67.17%), daily laborers (46.46%), and construction workers. Perceived heat stress, excessive daily dietary intake of salt, and drinking contaminated water are the factors that had shown the strongest association with the occurrence of CKDu in this population. The deterioration in QoL in CKDu pretty much mirrors that of CKD. CKDu is definitely an occupational disease, mostly affecting the wage workers and farmers spending long hours in unhealthy work environments. Environmental exposure to heavy metals must be checked and dietary modification must be done through counseling to regulate salt intake. CKDu, as a rising public health concern certainly needs special attention and immediate planning as it has a different etiopathology than CKD and the affected population, disease progression, and risk factors are markedly distinctive as well.


Renal-Limited Thrombotic Microangiopathy due to Bevacizumab Therapy for Metastatic Colorectal Cancer: A Case Report.
An 88-year-old Japanese man received bevacizumab for colorectal cancer with liver and peritoneal metastasis, during which nephrotic range proteinuria occurred (7.66 g/day). Renal biopsy showed endothelial damage with subendothelial swelling and a double contour of the glomerular basement membrane, which indicated a diagnosis of thrombotic microangiopathy (TMA). After bevacizumab was stopped, proteinuria decreased to 1 g/day. During the clinical course, this patient had no extrarenal manifestations. This case suggests that renal injury induced by bevacizumab is characterized by nephrotic range proteinuria and histological TMA, and is a renal-limited condition that differs from systemic TMA related to thrombotic thrombocytopenic purpura.


Waiting for liver transplantation in Canada: waitlist history 2000--2004 and sensitivity analysis for the future.
This study comprises a historical review of liver transplants performed in Canada during 2000--2004, and sensitivity analyses to assess the impact of possible changes in the operation of the waitlists. In the first part, overall statistics are reported, and the notable impact that blood type plays in affecting waiting time is discussed. Waiting times and numbers of transplants are also reported by gender, age, and geographic region (waitlist), and statistical analyses of the patient placement and cadaveric donations processes are performed. These analyses establish that the service times of an appropriate queuing model are closely approximated by an exponential distribution. Consequently, the resulting distribution for the waiting time from placement until transplant is well described by a different exponential distribution. The GI/M/1 queuing model is then used to perform a number of sensitivity analyses. The sensitivity analyses attempt to quantify the impact of no change in policy via a lottery system, and likely increases in cadaveric and/or living donor sources that would be needed to bring stability to the system. The results can be used by relevant authorities, together with information on success rates for publicity campaigns and living donor matching campaigns, to assess where further efforts should be made to reduce waiting times.


A geometric approach to problems in birational geometry.
A classical set of birational invariants of a variety are its spaces of pluricanonical forms and some of their canonically defined subspaces. Each of these vector spaces admits a typical metric structure which is also birationally invariant. These vector spaces so metrized will be referred to as the pseudonormed spaces of the original varieties. A fundamental question is the following: Given two mildly singular projective varieties with some of the first variety's pseudonormed spaces being isometric to the corresponding ones of the second variety's, can one construct a birational map between them that induces these isometries? In this work, a positive answer to this question is given for varieties of general type. This can be thought of as a theorem of Torelli type for birational equivalence.


Breast-feeding and population growth.
Abandonment of breast-feeding in parts of the world where contraception is not in common use may mean both higher birthrates and, especially among the poor, higher infant death rates. In this article estimates of the magnitude of these effects are made.


Drugs and personality: extraversion-introversion.
Eysenck theorizes that stimulants induce introversion and that depressants induce extraversion; common sense suggests opposite expectations. Scores on the extraversion scale of the Eysenck Personality Inventory yielded statistically significant differences among carefully matched series of heavy, chronic users of cocaine, amphetamine, opiates, barbiturate/sedative-hypnotics, and a comparable series of nonusers. Cocaine users and opiates users were found to be more introverted; amphetamine users, barbiturates users, and nonusers were more extraverted . These findings did not fully support either set of hypotheses. These data also implied that, if drugs influence extraversion, they do so only by suppressing it. Data from two other measures of extraversion were consistent with this hypothesis.


Synergistic role of staphylococcal proteases in the induction of influenza virus pathogenicity.
Several strains of Staphylococcus aureus have been found to secrete proteases that activate infectivity of influenza virus by proteolytic cleavage of the hemagglutinin. The enzymes of the bacterial strains Wood 46 and M 86/86 have been characterized in some detail and were found to be serine proteases. In their substrate specificities and inhibitor sensitivities they proved to be similar to, but not identical with trypsin and plasmin. The hemagglutinin of an individual virus strain could be cleaved by the proteases of some but not all staphylococcal strains, and a given enzyme could cleave only some but not all hemagglutinins analyzed. When mice were coinfected intranasally with the appropriate strains of influenza virus and S. aureus, the hemagglutinin was readily activated allowing multiple cycles of virus replication in the lung. Under these conditions, the animals came down with a fatal disease exhibiting extended lesions in the lung tissue. In contrast, after infection with virus or bacteria alone, there were no significant pathological changes. When the staphylococcal strain did not contain a protease that was able to activate the hemagglutinin of the coinfecting virus strain, the animals did not exhibit disease. These observations demonstrate that coinfecting bacteria can play an essential role in the development of influenza pneumonia by providing a protease suitable for cleavage activation of the hemagglutinin.


Benzothiazoles - scaffold of interest for CNS targeted drugs.
Benzothiazole compounds represent heterocyclic systems comprising a benzene ring fused with a thiazole ring containing nitrogen and sulphur in its structure. Besides the presence of a benzothiazole core in naturally occurring molecules, synthesized compounds containing a benzothiazole moiety in their structure proved to be a significant class of potential therapeutics, as they exhibit biological effects such as antitumor, antibacterial, antitubercular, antiviral, anthelmintic, antidiabetic and many others. Apart from the aforementioned peripheral or microbial active sites, benzothiazole analogues are also biologically active compounds in the central nervous system, where some approved drugs containing a benzothiazole moiety have already been identified and are used in the treatment of various neurological disorders. New benzothiazole molecules are currently under development and are being evaluated for several uses including diagnostics and as therapeutic drug candidates for the treatment of epilepsy and neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and amyotrophic lateral sclerosis amongst others.


CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation.
To investigate the effects of CD151 on the activity of endothelial NO synthase (eNOS), and ECV304 migration, proliferation and tube formation. pAAV-CD151 and pAAV-anti-CD151 were constructed and used to transiently transfect ECV304 mediated with Lipofectamine 2000. After transfection, the expression of CD151 was measured by Western blotting. Cell migration assay was performed using Boyden transwell; proliferation assay was evaluated using the 3- [4,5-dimethylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method, and tube formation test was examined on matrigel. eNOS activity was assayed by L- [3H]citrulline production from L-[3H]arginine. The involvement of eNOS was explored using an eNOS inhibitor (L-NAME) and the effects in the process were observed. CD151 promotes cell migration, proliferation and tube formation. In addition, CD151 increases eNOS activity. Moreover, cell migration, proliferation and tube formation induced by CD151 are inhibited when L-NAME is used, which indicates that there is an involvement of eNOS in CD151-induced cell migration, cell proliferation and tube formation. CD151 promotes ECV304 migration, proliferation and tube formation. The mechanism is that CD151 increases eNOS activity. This result also suggests that eNOS is involved in the angiogenic effects of CD151.


Pityriasis lichenoides chronica presenting with bilateral palmoplantar involvement.
Pityriasis lichenoides is an uncommon, acquired, idiopathic, self-limiting skin disease that poses a challenge to patients and clinicians to diagnose and treat. Several variants exist including pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis lichenoides chronica (PLC), and febrile ulcer-onecrotic Mucha-Habermann disease. Precise classification can be difficult due to an overlap of clinical and histologic features. In this case report we describe a patient with a rare presentation of PLC exhibiting bilateral palmoplantar involvement and mimicking psoriasis. We review the literature and discuss the clinical course, pathogenesis, and current treatment modalities of PLC.


Nelfinavir augments proteasome inhibition by bortezomib in myeloma cells and overcomes bortezomib and carfilzomib resistance.
HIV protease inhibitors (HIV-PI) are oral drugs for HIV treatment. HIV-PI have antitumor activity via induction of ER-stress, inhibition of phospho-AKT (p-AKT) and the proteasome, suggesting antimyeloma activity. We characterize the effects of all approved HIV-PI on myeloma cells. HIV-PI were compared regarding cytotoxicity, proteasome activity, ER-stress induction and AKT phosphorylation using myeloma cells in vitro. Nelfinavir is the HIV-PI with highest cytotoxic activity against primary myeloma cells and with an IC50 near therapeutic drug blood levels (8-14 μM), irrespective of bortezomib sensitivity. Only nelfinavir inhibited intracellular proteasome activity in situ at drug concentrations <40 μM. Ritonavir, saquinavir and lopinavir inhibited p-AKT comparable to nelfinavir, and showed similar synergistic cytotoxicity with bortezomib against bortezomib-sensitive cells. Nelfinavir had superior synergistic activity with bortezomib/carfilzomib in particular against bortezomib/carfilzomib-resistant myeloma cells. It inhibited not only the proteasomal β1/β5 active sites, similar to bortezomib/carfilzomib, but in addition the β2 proteasome activity not targeted by bortezomib/carfilzomib. Additional inhibition of β2 proteasome activity is known to sensitize cells for bortezomib and carfilzomib. Nelfinavir has unique proteasome inhibiting activity in particular on the bortezomib/carfilzomib-insensitive tryptic (β2) proteasome activity in intact myeloma cells, and is active against bortezomib/carfilzomib-resistant myeloma cells in vitro.


Contemporary Role of Echocardiography for Clinical Decision Making in Patients During and After Cancer Therapy.
Early recognition of cancer therapy-related cardiac dysfunction (CTRCD) provides an opportunity to mitigate cardiac injury and risk of developing late cardiac events. Echocardiography serves as the cornerstone in the detection and surveillance of CTRCD in patients during and after cancer therapy. Guidelines from professional societies and regulatory agencies have been published on approaches to surveillance, diagnosis, and treatment of CTRCD, although adoption as standard of care remains limited given the lack of evidence on the prognostic value of asymptomatic left ventricular (LV) dysfunction in the oncology population. The frequency of cardiac monitoring and the appropriateness of the Food and Drug Administration (FDA)-recommended cardiac monitoring schedule in all patients receiving trastuzumab for breast cancer has been challenged. Interruption versus continuation of oncological therapy in the setting of asymptomatic LV dysfunction remains a clinical conundrum given the uncertain balance of the risk of cardiac dysfunction and benefit of oncology efficacy. Despite their limitations, echocardiographic measures of LV function continue to play a pivotal role in clinical decision making, with global longitudinal strain emerging as a promising tool in informing and facilitating the selection of cancer treatment and optimizing cardiovascular outcomes. This review highlights the key recommendations of the existing guidelines and discusses recent developments in cardio-oncology imaging practices with the aim of providing practical guidance on the role and use of echocardiography in challenging clinical cases in cardio-oncology.


Malignant disease as a risk factor for surgical site infection.
Postoperative infections are a great constituent of surgical complications. The most common one is surgical site infection (SSI), as well as vaginal and/or urinary tract infections, infections affecting distant organs and systems and systemic circulation leading to sepsis and septic shock. Our aim was to emphasize the effect of malignant disease on postoperative infection and to establish malignant disease as a risk factor for SSI, per se. We designed a retrospective study in which 538 women who underwent surgery in the Gynecology and Obstetrics Clinical Center of Serbia during a six-month period in 2009 were analyzed. We collected relevant data regarding SSI incidence (CDC definitions), malignant disease (primary site, type and stage) and other potential risk factors for SSI. We used descriptive statistics, chi-square and Student's t test for comparison of variables with statistical significance atp < 0.05. We also used univariate, multivariate logistic regression and ROC analysis. Surgical site infection was present in 40 patients (7.5%). Univariate analysis revealed that the following factors were significantly related to SSI: age, malignant disease, stage of malignant disease, surgery longer than 120 min, postmenopause, diabetes mellitus, positive preoperative vaginal culture, ASA score and intraoperative blood loss. Multivariate analysis showed that the most important risk factors that contribute to SSI with RR of 4 and 5 are, respectively, FIGO II and FIGO III/IV stage of malignant disease (FIGO II p < 0.05 RR = 4.097; FIGO III/IV < 0.01 RR = 5.061). In our study malignant disease erupted as the most important risk factor for SSI. This brings us to question the pathophysiological mechanisms and systemic effects associated with malignant disease. There are few studies discussing the issue of malignancy as an isolated risk factor that 4-5 fold increases the risk of SSIs. It is of utmost interest to define protocols of antimicrobial prophylaxis for gynecological malignancy surgery as are suggested for some other malignancies.