Drug allergy evaluation for betalactam hypersensitivity: Cross-reactivity with cephalosporines, carbapenems and negative predictive value.
There are no studies on cross-reactivity of betalactams among patients allergic to penicillin, or on the negative predictive value (NPV) of penicillin allergy evaluation from Arabian Gulf countries. We aimed to assess the role and NPV of drug provocation test (DPT) for betalactam hypersensitivity reactions in patients referred for allergy evaluation in Kuwait. Skin test (ST) was performed for all patients with a history of betalactam hypersensitivity, other than anaphylaxis. Patients with a negative ST were challenged with a DPT containing phenoxymethyl penicillin or the culprit drug. Patients with anaphylaxis or who tested positive to betalactams were then challenged with a DPT containing cefuroxime, meropenem or ceftriaxone. Patients who tested negative were contacted by phone to evaluate subsequent betalactam intake. A total of 214 patients were tested for betalactam hypersensitivity. We had 91(42.5%) positive cases. Among positives, there were 78 (85.7%) patients with an initial reaction to penicillin and 13 (14.3%) who reacted to cephalosporin. DPT with alternative betalactam was performed in fifty who tested positive for betalactam hypersensitivity and 45 (90%) tolerated alternative antibiotics. Phone calls to 113 (59.8%) patients with negative betalactam testing showed that among 40(35.4%) patients who were successfully contacted; 17 (15%) took betalactams and 23 (20%) did not. Among the 17 patients who took betalactams, our calculated NPV for penicillin testing range from 88.2 to 100%, as the 2 patients who reported a reaction refused confirmatory retesting. Carbapenems and cephalosporines can be safely given to penicillin allergic patients by means of skin testing and if negative, proceeding with a graded challenge. Our calculated NPV for penicillin testing is similar to other studies.


Heme oxygenase 1: a novel oncogene in multiple gynecological cancers.
Heme oxygenase 1 (HO-1), also known as heat shock protein 32 (HSP32), is a stress-inducible enzyme. In the past, it was believed to participate in maintaining cell homeostasis, reducing oxidative stress damage and exerting anti-apoptotic effects. When exposed to noxious stimulation, the expression of HO-1 in the body will increase, antagonizing these oxidative stresses and protecting our bodies. Recently, many studies showed that HO-1 was also highly-expressed in multiple gynecological cancers (such as ovarian cancer, cervical cancer and endometrial cancer), suggesting that it should be closely related to cell proliferation, metastasis, immune regulation and angiogenesis as an oncogene. This review summarizes the different effects of HO-1 under normal and diseased conditions with a brief discussion of its implications on the diagnosis and treatment of gynecological cancers, aiming to provide a new clue for prevention and treatment of diseases.


Ascorbic acid and the oxidative processes in pea root cell wall isolates: characterization by fluorescence and EPR spectroscopy.
A comparative fluorescence and oxygen radical-sensitive spin trap EPR spectroscopic study of isolated cell walls (with proteins or deproteinated), in the presence and absence of ascorbate and H(2)O(2) is presented. Fluorescence spectra indicate the presence of at least two fluorophores, one degraded and the other synthesized after reduction or oxidation, indicating phenol di/polymerization. DEPMPO spin trap measurements show that isolated cell walls are capable of oxygen-dependent hydroxyl radical generation in the absence of NADH or other reductants, ascorbate addition, or deproteination of the cell wall abolishing the signal due to hydroxyl radicals.


[Anorectal malignant melanoma. Report of three cases].
The authors report three cases of primary anorectal malignant melanoma in order to discuss the various diagnostic problems, therapeutic modalities and to remind of the prognostic factors of this rare and unknown affliction. The diagnosis is unfortunately realized in the advanced stage. Mrs B.O, 55 years old, presented rectal hemorrhages and false meeds since a year, the clinical examination showed rectal tumor that bleeds with touch. The mass has been biopsed during the rectoscopy and the diagnosis of the malignant melamoma has been confirmed. Abdominoperitoneal amputation had been realized. Mr F.K, 35 years old, hospitalized because of constipation and rectal hemorrhages that evolve since 7 months with loss of weight and alteration of the general state. The rectal touch emphasizes a budy rectal polypoid tumor about 6 cm that the biopsies confirmed the diagnosis of invasive malignant. A Hartman's operation has been realized. A resection of the tumoral bud has been realized 3 months later, the patient died 4 months after that. Mrs F.K, 50 years old, presented since 50 days relapsing rectorrhages. The rectal touch showed a rectal tumor far about 6 cm from the amal margin, the biopsy during the rectoscopy confirmed the diagnosis of the pigmented and little invasive malignant melanoma. The abdominal exhography showed hepatic metastases and a resection by endo-mal way in order to reduce the tumor has been realized. The inclusion of the primary anorectal malignant melanoma in the diagnosis of the afflictins of the anorectal region would permit an improvement of this affliction prognosis, this is still unfortunate when the diagnosis is late. Its treatment is still surgical, the role of the other therapies still needs to be defined.


Reduction of nerve growth factor receptor immunoreactivity in ischaemic gerbil hippocampal CA1 neurons after treatment with L-threo-3,4-dihydroxyphenylserine (DOPS).
Nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells can be increased after the treatment with L-threo-3,4-dihydroxyphenylserine (DOPS). Since the increase of NGF is not blocked by the treatment with decarboxylase inhibitor, DOPS may have direct effect to increase the NGF content. NGF and its receptor (NGFR) are suggested to play an important role in the neuronal survival and regeneration under pathologic conditions. In this study, we studied a possible protective effect of DOPS against the hippocampal CA1 cell death after transient forebrain ischaemia in gerbils in relation to the change of NGFR immunoreactivity. We found that treatment with DOPS (300 mg kg-1) in combination with a decarboxylase inhibitor (benserazide, 10 mg kg-1) protected ischaemic hippocampal CA1 cell against delayed neuronal death (neuronal density = 125 +/- 24 mm-1) as compared to the treatment with vehicle (49 +/- 11 mm-1) (p < 0.01). The immunoreactivity for NGFR was scarcely present in the sham-control CA1 area but was induced from 1 h and markedly expressed at 7 days after recirculation in the vehicle group. However, it was slightly and transiently induced from 8 h to 2 days in the DOPS plus benserazide treated group. These data suggest that the protective role of DOPS on the ischaemic hippocampal CA1 cells may act through the NGF and its receptor system.


The Elkins Hypnotizability Scale: Assessment of Reliability and Validity.
Measuring hypnotizability is an integral part of hypnosis research and is also relevant for predicting effectiveness of hypnosis-based therapies. The Elkins Hypnotizability Scale (EHS) was designed to meet the needs of modern hypnosis research and clinical practice. Reliability, validity, and normative data were explored by subjecting 230 participants to the EHS and Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C). The EHS demonstrated adequate internal consistency (α = .78), its items showed good discriminating ability, and scores of the two scales were highly correlated (ρ = .86). Results indicate that the EHS is a reliable and valid tool to assess hypnotizability. Further research is needed to establish its role as a surrogate for the SHSS:C.


Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.
Choroidal neovascularization (CNV) is a major cause of visual impairment in patients suffering from wet age-related macular degeneration (AMD), particularly when refractory to intraocular anti-VEGF injections. Here we report that treatment with the oral mineralocorticoid receptor (MR) antagonist spironolactone reduces signs of CNV in patients refractory to anti-VEGF treatment. In animal models of wet AMD, pharmacological inhibition of the MR pathway or endothelial-specific deletion of MR inhibits CNV through VEGF-independent mechanisms, in part through upregulation of the extracellular matrix protein decorin. Intravitreal injections of spironolactone-loaded microspheres and systemic delivery lead to similar reductions in CNV. Together, our work suggests MR inhibition as a novel therapeutic option for wet AMD patients unresponsive to anti-VEGF drugs.


Taste masking technologies in oral pharmaceuticals: recent developments and approaches.
Taste is one of the most important parameters governing patient compliance. Undesirable taste is one of several important formulation problems that are encountered with certain drugs. Oral administration of bitter drugs with an acceptable degree of palatability is a key issue for health care providers, especially for pediatric patients. Several oral pharmaceuticals, numerous food and beverage products, and bulking agents have unpleasant, bitter-tasting components. So, any pharmaceutical formulation with a pleasing taste would definitely be preferred over a competitor's product and would translate into better compliance and therapeutic value for the patient and more business and profits for the company. The desire of improved palatability in these products has prompted the development of numerous formulations with improved performance and acceptability. This article reviews the earlier applications and methodologies of taste masking and discusses the most recent developments and approaches of bitterness reduction and inhibition for oral pharmaceuticals.


The role of recurrence plots in characterizing the output-unemployment relationship: an analysis.
We analyse the output-unemployment relationship using an approach based on cross-recurrence plots and quantitative recurrence analysis. We use post-war period quarterly U.S. data. The results obtained show the emergence of a complex and interesting relationship.


Predicting photon cascade emission in Pr3+ doped fluorides.
We present a theoretical approach, based on a density functional theoretic parametrization of a model Hamiltonian, that allows for the determination of the complete electronic 4fn and 4fn-15d valence manifolds of a lanthanide ion impurity in different host lattices in an easy, fast and reliable way. The model accounts for the electrostatic interactions, ligand field splitting due to the surroundings of the impurity and spin-orbit coupling effects, which means that the parametrization is transferable to different ligand environments. The model is applied to several Pr3+ doped fluorides, which are of great interest for designing warm white lighting devices. We show that the model correctly predicts which of them presents photon-cascade emission as experimentally observed. We also determine the absorption (emission) spectra from the dipolar transition probabilities from the lowest 4f2 (4f5d) state to the states of the 4f5d (4f2) manifold of the Pr3+ impurity, in agreement with the available experimental data. The present approach can be applied to other impurity-doped systems where the accurate determination of the valence impurity states is crucial for characterizing the relevant properties of the system.


Recombination and horizontal transfer of nodulation and ACC deaminase (acdS) genes within Alpha- and Betaproteobacteria nodulating legumes of the Cape Fynbos biome.
The goal of this work is to study the evolution and the degree of horizontal gene transfer (HGT) within rhizobial genera of both Alphaproteobacteria (Mesorhizobium, Rhizobium) and Betaproteobacteria (Burkholderia), originating from South African Fynbos legumes. By using a phylogenetic approach and comparing multiple chromosomal and symbiosis genes, we revealed conclusive evidence of high degrees of horizontal transfer of nodulation genes among closely related species of both groups of rhizobia, but also among species with distant genetic backgrounds (Rhizobium and Mesorhizobium), underscoring the importance of lateral transfer of symbiosis traits as an important evolutionary force among rhizobia of the Cape Fynbos biome. The extensive exchange of symbiosis genes in the Fynbos is in contrast with a lack of significant events of HGT among Burkholderia symbionts from the South American Cerrado and Caatinga biome. Furthermore, homologous recombination among selected housekeeping genes had a substantial impact on sequence evolution within Burkholderia and Mesorhizobium. Finally, phylogenetic analyses of the non-symbiosis acdS gene in Mesorhizobium, a gene often located on symbiosis islands, revealed distinct relationships compared to the chromosomal and symbiosis genes, suggesting a different evolutionary history and independent events of gene transfer. The observed events of HGT and incongruence between different genes necessitate caution in interpreting topologies from individual data types.


Induction of sister chromatid exchanges by the peroxisome proliferators 2,4-D, MCPA, and clofibrate in vivo and in vitro.
Phenoxy acid herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) have been found to induce proliferation of peroxisomes in the liver cells of rodents in the same manner as the hypolipidemic drug clofibrate. Both phenoxy acid herbicides and clofibrate (ethyl-alpha-p- chlorophenoxyisobutyrate ) are suspected carcinogens. The present study reports the effect of these agents on the induction of sister chromatid exchange (SCE) in the blood lymphocytes of exposed rats (100 mg/kg with 2,4-D and MCPA, 200 mg/kg with clofibrate for 2 weeks in one intragastric dose/day), in the bone marrow cells of exposed Chinese hamsters (100 mg/kg, treatments as above), and in Chinese hamster ovary (CHO) cells in vitro (10(-5), 10(-4), and 10(-3) M, for 1 h). In the experiments in vitro, the effects of purified 2,4-D and MCPA phenoxy acids were studied, in addition to those of the commercial herbicide formulations and clofibrate. No increase of SCE frequency was observed in the blood lymphocytes of the exposed rats in comparison with the controls. In the bone marrow cells of the exposed Chinese hamsters, a slight increase of SCE was found in the group treated with MCPA but not in the groups treated with 2,4-D or clofibrate. A slight increase in the number of SCEs was characteristic of all the treated CHO cell cultures, both with and without a rat liver microsomal activation system (S9 mix). No clear dose-related effects, however, could be discerned with any of the compounds, and no differences in the SCE induction were observed between the commercial herbicide products and the purified phenoxy acetic acids. The present results support the data which indicate that 2,4-D, MCPA, and clofibrate do not act as direct DNA-damaging agents.


Recovery patterns of spores of putrefactive anaerobe 3679 in various subculture media after heat treatment.
A comparative study was made of the heat resistance of spores of putrefactive anaerobe 3679 grown in two different sporulation media and of the recovery pattern of these spores in several subculturing media after treatment with moist and dry heat. The heat resistance of the spores was characterized in the form of D and z values. The D values were determined by the modified Schmidt method. The z values were established by the graphic method. The results revealed significant differences in D and z values, depending on the type of heat and sporulation and subculture media. Spores grown in beef heart infusion showed higher heat resistance than those grown in Trypticase. Among the seven subculture media used, the largest number of spores was recovered in beef infusion. The magnitude of the D values at 121.1 C obtained with spores heated in moist heat decreased, depending on the subculture medium used, in the following order: beef infusion, pea infusion, yeast extract, liver infusion, Eugonbroth, Trypticase, synthetic medium. With spores subjected to dry heat, D values at 148.9 C decreased with the subculture medium in the following order: beef infusion, yeast extract, pea infusion and liver infusion, Trypticase, Eugonbroth, synthetic medium. The z values obtained with spores subjected to dry heat were approximately double those obtained with moist heat. Their relative magnitude varied slightly, depending on the type of subculture medium used. However, the relative magnitudes of the D values and z values with reference to the subculture media used were different with moist heat from those obtained with dry heat. Two theories are discussed as possible explanations for the logarithmic order of death of bacterial spores. The results obtained in these experiments, together with the findings of other workers, are most compatible with the theory that heat treatment of spores results in an increased rate of random injury to the genetic material of the spores.


A retrospective pilot study: management of patients with heart failure.
An epidemic disease - a major cause of chronic disability - congestive heart failure adversely affects the health of millions. Congestive heart failure is the most frequent cause of cardiovascular hospital admissions and shares a significant responsibility for the high cost of healthcare. Despite medical and technological advances, studies show that the treatment of heart failure is suboptimal. Physician knowledge and awareness of appropriate treatment may contribute to patient compliance and improve delivery of healthcare. The purpose of this article is to examine how patients with heart failure in a heart failure clinic are managed. Recommendations are proposed and the role of nurses and clinicians in heart failure management is discussed.


Current status of Helicobacter pylori association with haematological and cardiovascular diseases: A mini review.
Helicobacter pylori infection is considered the most commonly prevalent gastrointestinal pathogen where it manages to survive despite the hostile environment of human stomach, leading to various gastric diseases including gastric cancer. Due to the chronic inflammatory state induced by H. pylori and its interaction with host immune system have diverted researchers to investigate its correlation with systemic diseases outside of the gastrointestinal tract. This literature review was done to explore the association of H. pylori infection with haematological and cardiovascular diseases. We used medical subject heading (MeSH) terms "Helicobacter pylori" with "inflammation," "haematological diseases," "coronary heart diseases" or "vascular diseases" to search PubMed database. All relevant studies identified from 2005 to 2015 were included. As many of the studies are small-scale or showed weak association, further studies are needed to address the role of H. pylori in pathogenesis of haematological and cardiovascular diseases.


Umbilical cord care. A study of bacitracin ointment vs. triple dye.
Umbilical cord colonization rates were examined over a 4-year period following topical application of bacitracin (1978-1980) or triple dye (1980-1982). A total of 2402 cords were cultured: 1229 following bacitracin cord care and 1173 after triple dye application. Cords treated with bacitracin had significantly higher colonization rates when compared to triple dye prophylaxis. Bacterial colonization with Staphylococcus epidermidis and group B beta-hemolytic streptococcus was found only after bacitracin prophylaxis. Our data support the use of triple dye for routine cord care and suggest that bacitracin application may increase the rate of group B streptococcal colonization.


Prevalence and prognostic value of atrial fibrillation in patients with cardiac sarcoidosis.
The prognostic value of the presence of atrial fibrillation (AF) in patients at the time of cardiac sarcoidosis (CS) diagnosis is unknown. This study aimed to investigate the association between AF at the time of CS diagnosis and patient prognosis. This study is a post-hoc analysis of Illustration of the Management and Prognosis of Japanese Patients with CS, a multicentre, retrospective observational study that evaluated the clinical characteristics and prognosis of patients with CS. The primary endpoint was the combined endpoint of all-cause death and hospitalization due to heart failure. After excluding patients with missing data about AF status, 445 patients (62 ± 11 years, 36% males) diagnosed with CS according to the Japanese current diagnostic guideline were analysed. Compared to patients without AF, patients with AF (n = 46, 10%) had higher levels of brain natriuretic peptide and a higher prevalence of heart failure hospitalizations. During a median follow-up period of 3.2 years (interquartile range, 1.7-5.8 years), 80 primary endpoints were observed. Kaplan-Meier curve analysis indicated that concomitant AF at the time of diagnosis was significantly associated with a high incidence of primary endpoints (log-rank P = 0.002). This association was retained after adjusting for known risk factors including log-transformed brain natriuretic peptide levels and left ventricular ejection fractions [hazard ratio, 1.96 (95% confidence interval, 1.05-3.65); P = 0.035]. The presence of AF at the time of CS diagnosis is associated with higher incidence of all-cause death and heart failure hospitalization.


"OBE" Concept for New Training Mode of Electronic Information Science and Technology Professionals under Big Data Analysis.
As an educational concept based on learning output, OBE (Outcome-Based Education) is student-centered and emphasizes students' personal progress and learning achievement. Based on BD (big data) analysis, this paper proposes a new talent training mode for the electronic information science and technology specialty. This model employs BD analysis technology to examine the correlation index between social demand and talent cultivation, based on the employment situation of students in the country in previous years. The teaching reform was carried out under the OBE concept, and a new training scheme was formed. Training objectives, graduation requirements, curriculum system, and continuous improvement mechanism were all determined. This paper proposes an algorithm for determining the degree of similarity between the knowledge required by the organization and the knowledge held by its employees. The person with the highest similarity is identified as the training candidate by the algorithm, and the training candidate is then trained according to the knowledge that the organization requires. Talent training in the field of electronic information science and technology has yielded positive results.


Binge Viewing, Sleep, and the Role of Pre-Sleep Arousal.
To investigate the prevalence of binge viewing, its association with sleep and examine arousal as an underlying mechanism of this association. Four hundred twenty-three adults (aged 18-25 years old, 61.9% female) completed an online survey assessing regular television viewing, binge viewing, sleep quality (Pittsburgh Sleep Quality Index), fatigue (Fatigue Assessment Scale), insomnia (Bergen Insomnia Scale), and pre-sleep arousal (Pre-Sleep Arousal Scale). Regression analyses were conducted. Mediation analysis was performed using PROCESS Macro. There were 80.6% who identified themselves as a binge viewer. Among those who binge viewed (n = 341), 20.2% had binge viewed at least a few times a week during the past month. Among poor sleepers (Pittsburgh Sleep Quality Index > 5), 32.6% had a poor sleep quality associated with being a binge viewer. Higher binge viewing frequency was associated with a poorer sleep quality, increased fatigue and more symptoms of insomnia, whereas regular television viewing was not. Cognitive pre-sleep arousal fully mediated these relationships. New viewing styles such as binge viewing are increasingly prevalent and may pose a threat to sleep. Increased cognitive arousal functions as the mechanism explaining these effects. Measures of media exposure should take into account the user's level of engagement with media. Interventions aimed at (1) alerting viewers about excessive viewing duration and (2) reducing arousal before sleep may be useful ways to tackle sleep problems in binge viewers.


Impact of self-perceived bothersomeness on health-related quality of life in women with overactive bladder symptoms.
The objective of this study was to examine the impact of self-perceived bothersomeness of overactive bladder (OAB) symptoms on the health-related quality of life (QOL). A total of 92 women with a mean age of 53.3 (range 23-79) years suffering from OAB were included in the study. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and King's Health Questionnaire (KHQ) were used to assess the QOL. The patients were divided into two groups according to the bothersomeness degree of OAB: 'low' and 'moderate' to 'high'. The SF-36 and the KHQ scores of the patients were significantly different from those of the controls (p <0.05), except for three domains of the SF-36. No difference in the results of the frequency-volume charts was observed between the two patient groups. The scores of the SF-36 and the KHQ domains did not correlate with the data of the frequency-volume charts. Significant differences were found between the two patient groups for most domains of the SF-36 (p <0.05). Significant differences were also detected in most domains of the KHQ (p <0.05). Objective data are not a sensitive tool for measuring the QOL in women with OAB symptoms. Our findings suggest that patient-perceived bothersomeness significantly influences QOL and that strategies for assessing bothersomeness should be developed to evaluate the QOL in these patients.


Cysteine synthase from rape leaves.
Cysteine synthase [O-Acetyl-L-serine acetate-lyase (adding hydrogen-sulfide) EC 18.104.22.168] has been highly purified from the extract of rape, Brassica chinensis var. Komatsuna. The purified preparation appeared to be homogeneous on Sephadex G-100 gel filtration and dodecylsulfate-polyacrylamide gel electrophoresis, showing a molecular weight of about 62,000. The latter method also suggested that this enzyme was composed of two identical subunits. The enzyme contained 2 moles of pyridoxal phosphate per mole of enzyme.


Changes in Marijuana Use Over the Transition Into Marriage.
Reductions in substance use tend to coincide with marriage, as both may occur during emerging adulthood. During the transition to marriage, it is possible that one's spouse may be the influence that causes the reduction in substance use. Data on participants (N = 471 couples) for this report are taken from a longitudinal study of early marriage. The objective of the current analysis is to determine if having a spouse who uses marijuana is associated with a greater likelihood of one's own use. Additionally, we are interested in spousal influence and cessation. The findings support spousal influence. Husbands are more likely to start using marijuana if their wives use marijuana, but the reverse is not true. Husbands also are more likely to stop using if their spouses do not use. During the transition into marriage, the drug use of one spouse does affect the other. However, this influence appears to be unidirectional, with wives influencing their husbands more often.


Modelling inorganic solids and their interfaces: a combined approach of atomistic and electronic structure simulation techniques.
We are seeking to combine the reliability of the structures and energies obtained from quantum mechanical methods with the insights given by larger scale simulations, which are better able to search configurational space. We will discuss our recent work using quantum mechanical methods, based on DFT, which have been applied to the study of a number of solids. Al2O3, CeO2, MnO2 and CaCO3, and compare these with results using atomistic simulation where the forces between atoms are modelled using interatomic potentials. The results show that such quantum methods can be used successfully to screen the different potential models and where necessary, provide sufficient data to allow us to re-consider the potential models. In addition, we show examples where the quantum based methods can give further insights into the reactivity, particularly of surfaces. However, it still remains computationally expensive to search all possible configurations and by using the atomistic simulations to search through different configurations we can identify new structures which can be verified with the quantum based simulations.


[Mechanisms and detection of G-induced loss of consciousness].
High sustained +Gz acceleration induced loss of consciousness (G-LOC) is the main factor that causes flying accident. This paper reviewed the mechanisms and its physiological detection. During slow onset rate (SOR) acceleration, cerebral ischemia/hypoxia are the mechanisms of G-LOC, during rapid onset rate (ROR) acceleration, G-LOC might be related to mechanical intracranial hypertension, but the direct experimental data were lacking. Arterial blood pressure of eye level and cerebral oxygen saturation are important among the physiological indices of G-LOC detection.


The home care work environment's relationships with work engagement and burnout: A cross-sectional multi-centre study in Switzerland.
This study aimed to investigate the levels of burnout and work engagement among home care workers in Switzerland and to test their association with job demands and job resources. We conducted a multi-centre, cross-sectional survey in the German-speaking part of Switzerland with a convenience sample of seven home care agencies. Data were collected between September 2017 and January 2018. We assessed burnout with the Maslach Burnout Inventory (MBI) and work engagement with the Utrecht Work Engagement Scale (UWES) as well as job demands (overtime, work-family conflicts, experienced aggression and work stressors) and job resources (predictability, staffing, teamwork, leadership, collaboration, social support, sense of community, feedback). To investigate the levels of burnout and work engagement, we applied descriptive statistics. Based on Bakker and colleagues' Job Demands-Resources model, we used a path analysis to test the associations of job demands and job resources with burnout and work engagement. We analysed data from 448 home care workers (response rate 61.8%, mean age 44 years (SD 13.2), 96% female). The frequency of burnout in our sample was low, while that of work engagement was high. Job demands correlated positively with emotional exhaustion (β = .54, p < .001) and negatively with work engagement (β = -.25, p < .001). Job resources correlated negatively with emotional exhaustion (β = -.28, p < .001) and positively with work engagement (β = .41, p < .001). Work-family conflicts and work stressors correlated strongest with emotional exhaustion, whereas social support and feedback were found to correlate strongest with work engagement. Improvements to the home care work environment might enhance work engagement and reduce burnout. Corrective interventions could focus on reducing specific aspects of job demands, such as work-family conflicts and work stressors, as well as on increasing aspects of job resources, especially social support and feedback.


Eligibility and exclusion of hemochromatosis patients as voluntary blood donors.
Hereditary hemochromatosis patients are excluded in many countries as voluntary blood donors. In 1991, changes in the Canadian Red Cross policy allowed healthy hemochromatosis patients to become voluntary donors. The medical histories of 208 hemochromatosis patients were evaluated for eligibility for blood donation from a large prospective database of hemochromatosis patients. A survey that determined the success or exclusion of 81 patients for blood donation and the reasons for their exclusion based on Canadian Red Cross donor exclusion criteria was analyzed. Of 208 hemochromatosis patients, 140 (67%) were eligible for blood donation. Criteria for exclusion were other illnesses excluded by Canadian Red Cross criteria and the use of contraindicated medications. Fifty-one per cent of patients had attempted to donate blood, with only 7% being successful. A large number of potential blood donors are excluded from blood donation inappropriately despite changes in eligibility criteria to the contrary. Further public and health education is needed to increase awareness and, thus, increase blood donation by potential donors.


Antiretroviral Treatment Interruptions Among Black and Latina Transgender Women Living with HIV: Characterizing Co-occurring, Multilevel Factors Using the Gender Affirmation Framework.
Black and Latina transgender women (BLTW) are disproportionately impacted by HIV but remain underrepresented in HIV and health services research. Between March 2016 and May 2017, BLTW (N = 201) were recruited in Baltimore, Maryland and Washington, DC through convenience sampling for a survey assessing multilevel determinants of HIV risk and treatment outcomes. Interviews concluded with a rapid oral HIV test. Bivariate and multivariable logistic regression modeling was performed to identify gender affirmation-related correlates of self-reported HIV treatment interruptions (HIVTIs) among BLTW living with HIV who had initiated antiretroviral therapy (ART) (n = 96). Among them, 57.3% (n = 55) reported at least one HIVTI. Unmet surgical needs (aOR = 1.6), past-year marijuana use (aOR = 14.6), and no current hormone use (aOR = 24.9) were significantly (p < 0.05) associated with HIVTIs in multivariable analysis. Unmet need for gender affirmation may inhibit ART adherence, highlighting opportunities to mitigate care interruptions in alignment with community needs and goals.


A strategy for rapid and efficient sequencing of Lys-C peptides by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry post-source decay.
A modification procedure for Lys-C peptides is described which simplifies the correct assignment of the amino acid sequence. Release of the C-terminal lysine from Lys-C peptides by carboxypeptidase B and subsequent N-terminal acetylation of the resulting peptides leads to predictable shifts of the C- and N-terminal fragment ions in Matrix-assisted laser desorption/ionisation time-of-flight post-source decay mass spectra and facilitates the correct assignment of mostly complete amino acid sequences for oligopeptides. The derived sequences of peptides from unknown proteins were used to search in databases for homologous protein sequences. Our method was applied to an unknown protein isolated from eggs of Drosophila melanogaster, resulting in the identification of a peptidyl prolyl cis-trans-isomerase.


Clinical usefulness of terbutaline in the management of placenta praevia.
Terbutaline was given to five patients with complete placenta praevia in order to prevent massive bleeding while at the same time prolonging the pregnancy. The longest period gained on therapy was 48 days and the shortest was 6 days. Doses of terbutaline used in these periods were 0.71-4.47 mg/dl. No serious complications were observed.


On the "true-false" memory syndrome: the problem of clinical evidence.
A patient in twice-a-week psychoanalytic psychotherapy began to recover childhood memories of chronic sexual abuse, including oral, anal and genital penetration. These memories sometimes included bizarre content that created skepticism regarding their authenticity. However, this dubious quality was in marked contrast to the internal consistency, continuity, and emotional authenticity of the psychotherapeutic process. Criteria for attempting to distinguish between fantasy and reality are noted. Despite their tenuous nature, these criteria are important because, most frequently, they will be the only data available within the clinical situation.


Point of care diaphragm ultrasound in mechanically ventilated children: A predictive tool to detect extubation failure.
Children should be weaned from the ventilator once their clinical condition improves. Extubation failure is associated with poorer clinical outcomes in children. Predictive indicators of successful extubation are needed. This study aims to evaluate the predictive value of ultrasonographic diaphragm imaging could help predict weaning success. In this prospective, observational study conducted between March and December 2021, children between 1 month and 10 years of age who were mechanically ventilated for more than 48 h were included. Diaphragm ultrasound (DUS) examinations were performed at the end of 2-h extubation readiness test (ERT). The end-inspiratory thickness (DTi), end-expiratory thickness (DTe), diaphragmatic thickening fraction (DTF), diaphragmatic excursion (DE), inspiratory slope (IS), and expiratory slope (ES) were evaluated. Twenty-four (60%) patients were successfully extubated, while 16 (40%) required invasive or noninvasive mechanical ventilation support which were classified as failed extubation group. Three of the sixteen patients in the failed extubation group required reintubation. DTF was significantly greater in the successful weaning group (55.05 ± 23.75% vs. 30.9 ± 10.38%) (p < 0.001). DE was significantly greater in the successful weaning group (14 ± 4.4 mm vs. 11.05 ± 3.25 mm) (p < 0.001). DTF and DE were found to have a sensitivity and specificity of 91.67%, 87.50%, 83.33%, and 81.25%, respectively. Diaphragm ultrasound is a feasible and promising tool to guide physicians during weaning from invasive mechanical ventilation. Among all DUS measurements, the DE and DTF indexes showed better performance in extubation failure than other diaphragmatic parameters.


Regulation of human trophoblast cell syncytialization by transcription factors STAT5B and NR4A3.
In human trophoblast cells, cyclic AMP or its inducer forskolin (FSK) activates two downstream signaling molecules, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), both of which induce syncytialization, cell fusion, and the production of human chorionic gonadotropin (hCG) and progesterone. However, a transcription factor other than GCM1 and molecular mechanisms associated with these events have not been well characterized. To identify novel transcription factors involved in syncytialization of cAMP-stimulated human choriocarcinoma BeWo cells, the microarray analysis was performed with RNAs extracted from PKA- or EPAC-selective cAMP analog-stimulated BeWo cells, from which two up-regulated transcription factors, STAT5 and NR4A3, were found. The knockdown of STAT5B decreased FSK-induced cell fusion and the expression of syncytialization markers, CGB, syncytin1, syncytin2, GCM1, and OVOL1, but NR4A3 knockdown increased FSK-induced cell fusion and the expression of CGB and syncytin2. These findings indicated that cAMP-PKA up-regulated STAT5B, followed by increase in syncytin2 expression through GCM1 and OVOL1, resulting in cell fusion and hCG production, while cAMP-PKA-up-regulated NR4A3 could decrease syncytin2 expression, and suggested that both positive and negative effects of STAT5B and NR4A3, respectively, are required to control the degree of syncytialization in human trophoblast cells.


Macrophage migration inhibitory factor is involved in antineutrophil cytoplasmic antibody-mediated activation of C5a-primed neutrophils.
C5a is important for antineutrophil cytoplasmic antibody (ANCA)-mediated activation of neutrophils. The present study aimed to assess the role of macrophage migration inhibitory factor (MIF) in ANCA-mediated activation of C5a-primed neutrophils. The effects of MIF on ANCA-mediated neutrophil respiratory burst and degranulation were determined. In addition, the effect of a MIF antagonist on the activation of C5a-primed neutrophils was assessed. MIF treatment resulted in increased membrane proteinase-3 (mPR3) expression on neutrophils and enhanced myeloperoxidase (MPO) amounts in neutrophil culture supernatants. The concentration of MIF was significantly higher in the neutrophils supernatant primed with C5a (negative control: 14.2 ± 1.16 ng/ml; C5a: 45.8 ± 2.8 ng/ml, P < 0.001 vs. negative control; C5a + IgG: 44.8 ± 1.93 ng/ml, P < 0.001 vs. negative control; C5a + MPO-ANCA: 73.0 ± 5.5 ng/ml, P < 0.001 vs. C5a; and C5a + PR3-ANCA: 69.4 ± 5.35 ng/ml, P < 0.001 vs. C5a). MIF primed neutrophils to undergo respiratory burst and degranulation in response to ANCA. Indeed, mean fluorescence intensity (a measure of respiratory burst) was significantly higher in MIF-primed neutrophils activated with MPO-ANCA-positive IgG or PR3-ANCA-positive IgG compared with non-primed neutrophils. Meanwhile, a MIF antagonist reduced oxygen radical production in C5a-primed neutrophils treated with patient-derived ANCA-positive IgG. MIF can prime neutrophils to undergo ANCA-mediated respiratory burst and degranulation. Blocking MIF resulted in reduced ANCA-mediated activation of C5a-primed neutrophils. These findings indicated that the interaction between MIF and C5a may contribute to ANCA-mediated neutrophil activation.


Copper(II)-Catalyzed Nitroaldol (Henry) Reactions: Recent Developments.
Self-assembled copper(II) complexes are described as effective catalysts for nitroaldol (Henry) reactions on water. The protocol involves a heterogeneous process and the catalysts can be recovered and recycled without loss of activity. Further, C2-symmetric N,N'-substituted chiral copper(II) salan complexes are found to be more effective catalysts than chiral copper(II) salen complexes for reactions in homogeneous catalysis, with high enantioselectivities. The reactions involve bifunctional catalysis, bearing the properties of a Brønsted base, as well as a Lewis acid, to effect the reaction in the absence of external additives.


Regenerative release of calcium from functionally discrete subcellular stores by inositol trisphosphate.
Fluorescence imaging was used to determine the spatial and temporal patterns of subcellular calcium (Ca2+) liberation induced in Xenopus oocytes by photorelease of inositol 1,4,5-trisphosphate (InsP3) from a caged precursor. Increasing levels of InsP3 evoked Ca2+ release that began in a graded manner but, at varying threshold levels of InsP3, localized sites then showed transient and asynchronous 'puffs' of Ca2+ release. With higher levels of InsP3, Ca2+ from adjacent sites formed a focus for initiation of a propagating Ca2+ wave. The results show that InsP3-sensitive Ca2+ stores are arranged as distinct and functionally independent units, and that Ca2+ is released in both graded and regenerative fashions.


NHS failing its black and minority workforce.
The findings are in and are far from surprising. The first report of the NHS Workforce Race Equality Standard (WRES) was published on June 2 and contains a highly predictable litany of woe: black and minority ethnic (BME) staff are more likely than white staff to be bullied or abused, wherever they work.


Reasons and Risk Factors for Delayed Discharge After Total Knee Arthroplasty Using an Opioid-Sparing Discharge Protocol.
In this study, we aimed to assess the length of hospital stay after total knee arthroplasty in a European healthcare setting. We also aimed to investigate risk factors and reasons for delayed discharge when using an opioid-sparing fast-track protocol. From our institutional database, we retrospectively identified all primary elective unilateral total knee arthroplasties performed during January to December 2015. Both patient-related and surgery-related variables were collected from our databases. Risk factors were analyzed using multivariable logistic regression analysis. The median length of stay (LOS) was 3 days. Independent risk factors for delayed discharge were higher age, higher American Society of Anesthesiologists score, general anesthesia, surgery performed toward the end of the week, longer duration of surgery, longer stay in the post-anesthesia care unit, and shorter preoperative walking distance. The main reasons for delayed discharge were delayed functional recovery and pain. This study identified several independent risk factors for an LOS longer than 3 days. These risk factors add to the current knowledge on which patients have an increased risk of prolonged LOS, and which patients should be targeted when striving to further reduce the LOS.


Wilckodontics--an alternative adult orthodontic treatment method: rational and application.
Adult orthodontics poses a challenge for practitioners as it involves unique biomechanical considerations due to biologic age related changes and lack of skeletal growth potential. Dental risks in adult orthodontics include, amongst others, root resorption and periodontal complications. As modern life calls for quick and efficient orthodontic treatments, a novel orthodontic modality was developed utilizing adjunctive periodontal surgery that includes bone corticotomy combined with bone augmentation. This multidisciplinary team approach: Periodontally Accelerated Osteogenic Orthodontics (PAOO) or Wilckodontics seems to be promising not only for reducing orthodontic treatment duration, but also for biological aspects during and after orthodontic treatment. PAOO enhances bone remodeling and augmentation, accelerates tooth movement and significantly reduces the duration of treatment. The presented cases manifest the biologic benefit of profound enlargement in the envelope of motion reducing the need for extraction and eliminating the need for aggressive intervention of surgically-assisted rapid maxillary expansion. PAOO serves as a reasonable and safe option for the growing demand of shortened treatment duration of adult teeth movement in three dimensions. Further research is recommended for an in depth evaluation of the long-term stability claimed to be advantageous in this modality.


Patient satisfaction with home-birth care in The Netherlands.
One of the necessary elements in an obstetric system of home confinements is well-organized postnatal home care. In The Netherlands home care assistants assist midwives during home delivery, they care for the new mother as well as the newborn baby, instruct the family on infant health care and carry out household duties. The growing demand for postnatal home care is difficult to meet; this has resulted in a short supply of the most popular day care programme and a level of provision which does not result in adequate services. This study acknowledges the patient perspective of maternity home care in order to contribute to its organization. The majority (79%) of service centres were willing to participate. A total of 1812 (81%) women who recently gave birth to a child responded to a postal questionnaire addressing the quality of care according to five dimensions: availability, continuity, interpersonal relationships, outcome and assistant's expertise. Almost one-third of the new mothers rated the availability as inadequate while the assistant's expertise was rated positively. Postnatal maternity home care is personalized, small-scale, and recognizes childbirth as a life event. Furthermore, it is relatively inexpensive and contributes to the satisfaction of recipients.


Brugada syndrome clinical update.
Brugada syndrome (BrS) was initially described in southeast Asians with a structurally normal heart presenting with polymorphic ventricular tachycardia and fibrillation. This condition is marked by J-point elevation ≥ 2 mm with coved-type ST segment elevation followed by negative T wave inversions in at least one precordial lead (V1 or V2) when other etiologies have been excluded. These changes on electrocardiogram (EKG) can either be spontaneous or manifest after sodium channel blockade. The worldwide prevalence of BrS is about 0.4%; however, it is higher in the Asian population at 0.9%. This article will review the current hypotheses regarding the pathophysiology, spectrum of clinical presentation, strategies for prevention of sudden cardiac death and the treatment for recurrent arrhythmias in BrS.


A descriptive study of the extent to which self-perceived needs of parents are met in paediatric units in Iceland.
The purpose of this study was to identify the extent to which parents of 2-12-year-old hospitalized children perceive their needs to be met in paediatric units, what variables influence parents' perception, and whether parents need help from the hospital to meet their needs. Parents perceived that most of their needs were met fully or to some extent. The need to be able to stay with the child 24 h a day was perceived as fully met by all parents. Needs perceived as important but poorly met were as follows: written information about the child's health status, information about financial assistance and follow-up after discharge. Independent variables identified as being related to the extent to which individual needs were met were as follows: parents' age (p < or = 0.05), distance between home and hospital (p < or = 0.05), parents' education (p < or = 0.05), length of hospital stay (p < or = 0.01) and severity of child's illness (p < or = 0.01). Most parents perceived that they needed help from the hospital to meet their needs. These findings call for identification of effective interventions to meet parents' needs.


Role of artificial nutrition in patients undergoing surgery for esophageal cancer.
Malnourished cancer patients undergoing major surgical treatments are at a high risk of morbidity and mortality. As compared to patients affected by other tumors, the highest rate of malnutrition (78.9%) was found in those with esophageal cancer due to postoperative complications. The impact of perioperative nutritional support on outcome in esophageal cancer patients undergoing surgery is analyzed. Strategies that can be used to preserve or restore the nutritional condition in patients throughout treatment are illustrated. Oral supplementation, and enteral or parenteral nutrition are among several methods of support. Enteral option is to be preferred because the intestinal integrity is preserved, the risk of complications is reduced and costs are lower. Prevention or correction of nutrient depletion in severely malnourished esophageal cancer patients remarkably reduces or eliminates malnutrition-related morbidity and mortality. Therefore to identify and treat malnutrition is of the utmost importance.


Importance of nondopaminergic features in evaluating disease severity of Parkinson disease.
The aim of this study was to explore the role of predominantly nondopaminergic (PND) features in evaluating disease severity and progression of Parkinson disease (PD). Principal component analysis was used on the baseline data of 396 patients to explore consistency of interrelations between important PND domains (cognitive impairment, depressive symptoms, excessive daytime sleepiness, psychotic symptoms, autonomic dysfunction, and postural instability and gait difficulty) across different ranges of disease duration. Hereafter, we evaluated the reliability and validity of a composite score of all PND domains and examined reproducibility of the findings in a large independent cohort. Principal component analysis revealed a consistent 1-factor solution across groups with different disease durations. Cronbach α of the total group was 0.75 for the PND composite score, and corrected item-total correlations were all above the criterion value of 0.3. Validity of the PND composite score was confirmed by significant positive correlations with Hoehn and Yahr stage, severity of motor symptoms, disease duration, and age. Findings were replicated in the independent cohort. Our findings show the robustness of a composite score of PND domains as a measure of disease severity across the disease course of PD. Composite measures of PND domains, which largely are insensitive to dopaminergic medication, may provide a more complete and accurate evaluation of disease severity and progression in PD.


BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition.
Although targeting oncogenic mutations in the BRAF serine/threonine kinase with small molecule inhibitors can lead to significant clinical responses in melanoma, it fails to eradicate tumors in nearly all patients. Successful therapy will be aided by identification of intrinsic mechanisms that protect tumor cells from death. Here, we used a bioinformatics approach to identify drug-able, "driver" oncogenes restricted to tumor versus normal tissues. Applying this method to 88 short-term melanoma cell cultures, we show that the antiapoptotic BCL2 family member BCL2A1 is recurrently amplified in ∼30% of melanomas and is necessary for melanoma growth. BCL2A1 overexpression also promotes melanomagenesis of BRAF-immortalized melanocytes. We find that high-level expression of BCL2A1 is restricted to melanoma due to direct transcriptional control by the melanoma oncogene MITF. Although BRAF inhibitors lead to cell cycle arrest and modest apoptosis, we find that apoptosis is significantly enhanced by suppression of BCL2A1 in melanomas with BCL2A1 or MITF amplification. Moreover, we find that BCL2A1 expression is associated with poorer clinical responses to BRAF pathway inhibitors in melanoma patients. Cotreatment of melanomas with BRAF inhibitors and obatoclax, an inhibitor of BCL2A1 and other BCL2 family members, overcomes intrinsic resistance to BRAF inhibitors in BCL2A1-amplified cells in vitro and in vivo. These studies identify MITF-BCL2A1 as a lineage-specific oncogenic pathway in melanoma and underscore its role for improved response to BRAF-directed therapy.


Measuring Radiation Toxicity Using Circulating Cell-Free DNA in Prostate Cancer Patients.
After radiation therapy (RT), circulating plasma cell-free DNA (cfDNA) released in response to RT damage to tissue can be measured within hours. We examined for a correlation between cfDNA measured during the first week of therapy and early and late gastrointestinal (GI) and genitourinary (GU) toxicity. Patients were eligible for enrollment if they planned to receive proton or photon RT for nonmetastatic prostate cancer in the setting of an intact prostate or after prostatectomy. Blood was collected before treatment and on sequential treatment days for the first full week of therapy. Toxicity assessments were performed at baseline, weekly during RT, and 6 months and 12 months after RT. Data were analyzed to examine correlations among patient-reported GI and GU toxicities. Fifty-four patients were evaluable for this study. Four (7%) and 3 (6%) patients experienced acute and late grade 2 GI toxicity, respectively. Twenty-two (41%) and 18 (35%) patients experienced acute and late grade 2 GU toxicity, respectively. No patients developed grade 3 or higher toxicity. Grade 2 acute GI toxicity, but not grade 2 acute GU toxicity, was significantly correlated with pre-RT cfDNA levels and on all days 1, 2, 3, 4, and 5 of RT (P < .005). Grade 2 late GI toxicity, but not GU toxicity, was significantly correlated with pre-RT cfDNA levels (P = .021). Based on this preliminary study, cfDNA levels can potentially predict the subset of patients destined to develop GI toxicity during prostate cancer treatment. Given that the toxicity profiles of the various fractionations and modalities are highly similar, the data support the expectation that cfDNA could provide a biological estimate to complement the dose-volume histogram. A test of this hypothesis is under evaluation in a National Cancer Institute-funded multi-institutional study.


Sometimes a cigar [magazine] is more than just a cigar [magazine]: pro-smoking arguments in Cigar Aficionado, 1992-2000.
Since its first issue in 1992, few periodicals have enjoyed the rapid growth and international popularity of Cigar Aficionado. Although the magazine professes to simply celebrate "the good life and the joys of cigar smoking," we argue that it serves a more insidious function; specifically, the periodical supplies readers with 7 persuasive strategies aimed at rebuking dominant anti-smoking health assertions: (a) the cigars-are-not-cigarettes argument, (b) the life-is-dangerous argument, (c) the health-benefits argument, (d) the moderation argument, (e) the old-smokers argument, (f) the bad-science argument, and (g) the good-science argument. These pro-smoking arguments ultimately serve to relieve the cognitive dissonance associated with the consumption of a potentially deadly product and to maintain a loyal readership, free from guilt or anxiety.


The total volar forearm musculocutaneous free flap for reconstruction of extended forequarter amputations.
Forequarter amputation is performed for resection of large, invasive tumors of the shoulder girdle region. A substantial defect can usually be closed with local or regional flaps; however, a subset of the forequarter amputation group has emerged at this institution with more complex issues. These patients have extensively more invasive posterior tumors, some with chest wall/rib invasion. Local/regional flaps in these situations are inadequate, and free tissue transfer is the only viable option. The forequarter specimen can sometimes be used as a donor site, thereby eliminating the usual donor site morbidity. Variations of the total forearm free flap have been sparsely described in the literature--the majority being case reports of either pure fasciocutaneous or "filet of forearm" flaps. We report a series of 4 patients treated over a 5 year period at this institution using the previously undescribed total volar forearm musculocutaneous free flap based on the brachial artery and its venae comitantes. This flap includes the entire musculature of the volar forearm with fasciocutaneous extensions on either side of the musculocutaneous unit. All potentially ischemic dorsal musculature is discarded, leaving a flap that has central bulk and a relatively large dimension. The entire flap remains extremely well vascularized, and a substantial surface area of as much as 45 x 25 cm can be attained. A pedicle as long as 20 cm can be dissected as far proximally in the arm as is oncologically safe. A single artery and vein are anastomosed to either the intrathoracic or neck vessels. All four flaps survived completely with uncomplicated wound healing. The total volar forearm musculocutaneous flap is extremely well vascularized and highly reliable. The flap as described provides the ideal combination of large surface area, muscle bulk, and long vascular pedicle. It can be dissected rapidly to minimize ischemic time and could therefore be applicable to traumatic forequarter amputations. It has become the flap of choice for reconstruction of extended oncological forequarter amputation defects.


Infectious agents in arthritis and autoimmunity.
Abstract The distinctions between infection, chronic arthritis, and autoimmune diseases have steadily blurred over the past decades. The proposed pathomechanisms underlying these interesting associations include putative pathways from infection to innate and adaptive immunity, molecular mimicry, and certain microbial and host factors. This article further reviews the spectrum of microbial agents implicated in some rheumatic diseases and cites the potential clinical application of this expanding field of knowledge in the prevention and treatment of chronic inflammatory and autoimmune diseases.


Methods and matrices: approaches to identifying miRNAs for nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is a solid tumor of the head and neck. Multimodal therapy is highly effective when NPC is detected early. However, due to the location of the tumor and the absence of clinical signs, early detection is difficult, making a biomarker for the early detection of NPC a priority. The dysregulation of small non-coding RNAs (miRNAs) during carcinogenesis is the focus of much current biomarker research. Herein, we examine several miRNA discovery methods using two sample matrices to identify circulating miRNAs (c-miRNAs) associated with NPC. We tested two miRNA discovery workflows on two sample sources for miRNAs associated with NPC. In the first workflow, we assumed that NPC tumor tissue would be enriched for miRNAs, so we compared miRNA expression in FFPE from NPC cases and controls using microarray and RNA-Seq technologies. Candidate miRNAs from both technologies were verified by qPCR in FFPE and sera from an independent NPC sample set. In a second workflow, we directly interrogated NPC case and control sera by RNA-Seq for c-miRNAs associated with NPC, with candidate c-miRNAs verified by qPCR in the sera from the same independent NPC sample set. Both microarray and RNA-Seq narrowed the miRNA signature to 1-5% of the known mature human miRNAs. Moreover, these two methods produced similar results when applied to the same sample type (FFPE), with RNA-Seq additionally indicating "unknown" miRNAs associated with NPC. However, we found different miRNA profiles in NPC sera compared to FFPE using RNA-Seq, with the few overlapping miRNAs found to be significantly up-regulated in FFPE significantly down-regulated in sera (and vice versa). Despite the different miRNA profiles found in FFPE and sera, both profiles strongly associated with NPC, providing two potential sources for biomarker signatures for NPC. We determined that the direct interrogation of sera by RNA-Seq was the most informative method for identifying a c-miRNA signature associated with NPC. We also showed that there are different miRNA expression profiles associated with NPC for tumor tissue and sera. These results reflect on the methods and meaning of miRNA biomarkers for NPC in tissue and peripheral blood.


[Strategic planning models at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán].
The Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (Spanish acronym INCMNSZ) is a third tier healthcare facility operated by the Mexican Ministry of Health, ando ver the years various strategic planning models have been used in its development. This paper present a brief overview of some of those strategic planning models and their application and concludes with a discussion of the lessons learned and challenges than remain.


Solid fuel use is associated with anemia in children.
Over 3 billion people use solid fuels as a means of energy and heating source, and ~ 50% of households burn them in inefficient, poorly ventilated stoves. In 2010, ~ 43% of the 640 million preschool children in 220 countries suffered from a certain degree of anemia, with iron deficiency as the main cause in developed countries whereas its causes remained multifactorial in the undeveloped group. In this study, we explore the relations of country-wide variables that might affect the people's health status (from socioeconomic status to more specific variables such as water access). We found independent relationship between solid fuel use and anemia in children under five years old (p < 0.0001), taking into account the prevalence of anemia in pregnant woman and the access to improved water sources. Countries in which the population uses solid fuel the most have over three times higher anemia rates in children than countries with the lowest prevalence of solid fuels use. There is still a complex relationship between solid fuels use and anemia, as reflected in its worldwide significance (p < 0.05) controlled for measles immunization, tobacco consumption, anemia in pregnant mothers, girl's primary education, life expectancy and improved water access but not (p > 0.05) when weighing for sanitation access or income per capita.


A case study on rheumatoid arthritis.
At a time when many managed care organizations increasingly shift costs to patients through tiered formularies and widening copay differentials, biologic agents represent a significant clinical and financial challenge unlikely to be managed optimally with tiered formularies and greater patient cost sharing. The information discussed in this article is intended for healthcare professionals involved with rheumatoid arthritis therapy, including but not limited to physicians in both the inpatient and outpatient setting, and for other managed care professionals, including medical directors, pharmacy directors, long-term care decision makers, nurses, pharmacists, and case managers.


Breast Cancer and Proteomics: The inaugural Mammary Gland Proteome Initiative (MGPI) workshop 12-13 July 2007, Cambridge, UK.
Breast cancer proteomics has progressed to a level where further development requires the coordination and cooperation of research strategies and resources. The Mammary Gland Proteome Initiative (MGPI) aims to provide a platform to promote such a coordination of comprehensive studies of mammary glands in health and disease. An inaugural MGPI workshop, Breast Cancer and Proteomics, was held in Cambridge, UK in July 2007. The workshop outlined the development of the MGPI, with emphasis on four specific programs: (i) breast cancer, (ii) standardisation, deposition and processing of data, (iii) technology and (iv) logistics.


The 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2) states of the SO(2) (+) ion studied using multiconfiguration second-order perturbation theory.
The 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2) electronic states of the SO(2) (+) ion have been studied using multiconfiguration second-order perturbation theory (CASPT2) and two contracted atomic natural orbital basis sets, S[6s4p3d1f]/O[5s3p2d1f] (ANO-L) and S[4s3p2d]/O[3s2p1d] (ANO-S), and the three states were considered to correspond to the observed X, B, and A states, respectively, in the previous experimental and theoretical studies. Based on the CASPT2/ANO-L adiabatic excitation energy calculations, the X, A, and B states of SO(2) (+) are assigned to 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2), respectively, and our assignments of the A and B states are contrary to the previous assignments (A to (2)A(2) and B to (2)B(2)). The CASPT2/ANO-L energetic calculations also indicate that the 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2) states are, respectively, the ground, first excited, and second excited states at the ground-state (1 (2)A(1)) geometry of the ion and at the geometry of the ground-state SO(2) molecule. Based on the CASPT2/ANO-L results for the geometries, we realize that the experimental geometries (determined by assuming the bond lengths to be the same as the neutral ground state of SO(2)) were not accurate. The CASPT2/ANO-S calculations for the potential energy curves as functions of the OSO angle confirm that the 1 (2)B(2) and 1 (2)A(2) states are the results of the Renner-Teller effect in the degenerate (2)Pi(g) state at the linear geometry, and it is clearly shown that the 1 (2)B(2) curve, as the lower component of the Renner splitting, lies below the 1 (2)A(2) curve. The UB3LYP/cc-pVTZ adiabatic excitation energy calculations support the assignments (A to (2)B(2) and B to (2)A(2)) based on the CASPT2/ANO-L calculations.


Megakaryocytic cell lines.
Megakaryocytic cell lines, established from the blood of patients with leukaemia, provide us with a unique opportunity to study the proliferation, differentiation and maturation of megakaryocytes. Eighteen human and three animal cell lines that express some megakaryocytic features have been described in the literature. Many of these cell lines have primitive multiphenotypic properties of erythroid, myeloid and megakaryocytic cells, while some show more restricted megakaryocyte-specific markers. The most consistent cell marker of megakaryocytic cell lines is the presence of platelet membrane glycoprotein (GPIIb-IIIa) in human cell lines and that of acetylcholinesterase in mouse or rat cell lines. The expressions of GPIb, von Willebrand factor and platelet peroxidase are variable among different cell lines, perhaps reflecting different stages of differentiation or a neoplastic nature of immortal cell lines. Treatment of many of these cell lines with phorbol esters leads to enhanced expression of the megakaryocytic programme.


The influence of cyclophosphamide on antibody formation in the mouse.
A single injection of cyclophosphamide (CY) (300 mg/kg) 8 h prior to immunization results in a complete suppression of the antibody formation in mice. The effect of CY on the number and activity of the surviving cells in the lymphoid organs was studied. For all organs tested there was a decrease in cell numbers to 10% or less till day 3, followed by an increase in cell numbers in bone marrow, spleen and lymph nodes. The increase in cell numbers in the thymus was delayed till after day 11. The bone marrow reached normal levels on day 7. The spleen surpassed the normal levels on day 11, reaching cell numbers which were 50% over the normal ones. For the thymus cells this was found only on day 21. The numbers of lymph node cells remained low and reached normal levels or higher only when the mice were stimulated after CY treatment. This effect of stimulation was further seen in the spleen cell numbers, where after stimulation with antigen in Freund's complete adjuvant (FCA) or only FCA cell numbers of 200% of normal values were obtained. The suppression of antibody formation by CY could be restored by cells from spleen, lymph nodes, Peyer's patches or thymus and bone marrow, indicating a defect in both B and T cells caused by CY treatment. The target cell of CY treatment was studied by reconstitution of anergic mice with spleen or lymph node cells of CY treated mice with or without addition of normal bone marrow and thymus cells. This revealed that although the B cells is the main target cell of CY action, the impact on the T cell population is also considerable. When however CY treatment is followed by antigenic stimulation, there is a steep increase in the activity of the lymph node cells when bone marrow cells are added. This phenomenon resembles the education of thymus cells in the spleen of lethally irradiated mice in the presence of antigen.


Unilateral temporal haemianopia in a patient with non-small cell lung cancer: intraocular metastasis despite chemotherapy.
A 70-year-old lady with non-small-cell lung cancer receiving chemotherapy presented with gradually worsening visual disturbance for 2 weeks. She had no history of seizures or weakness. Physical examination revealed an isolated left sided temporal haemianopia. A brain MRI performed on admission showed a new left intraocular lesion highly suspicious for metastasis. CT scan showed cancer disease progression despite chemotherapy. She was managed palliatively.


Genetic control of resistance to murine malaria.
Strain variation in the level of resistance to malaria was investigated in inbred mice after infection with Plasmodium chabaudi. Following intraperitoneal infection with the typing dose of parasitized erythrocytes, mice of 11 inbred strains could be separated using survival time as the criterium into resistant and susceptible groups. Genetic analysis of F1 hybrid and backcross progeny derived from one of the most resistant (B10.A) and from the most susceptible (A/J) strains as parents suggested that host resistance in this strain combination was genetically controlled by a dominant, non-H-2-linked, autosomal gene or closely linked genes. Analysis of the mechanisms of resistance to P chabaudi showed (1) phenotypic expression of the resistance gene was apparent within 6 days of infection as a significant difference between resistant and susceptible mice in the level of parasitemia; (2) the level of host NK cell activity was not related to the level of host resistance to malaria; (3) compared with susceptible A/J mice, resistant B10.A hosts had an augmented erythropoietic response during the course of malaria as well as during phenylhydrazine-induced anemia and (4) treatment with BCG or P acnes resulted in an equal degree of protection, measured by parasitemia and survival, in both resistant and susceptible mice.


Systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder: a case report and review of literature.
Systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder (EBV + LPD) has predominantly been observed among pediatric patients as a life-threatening condition. The present study presents a rare case of EBV + LPD in an adult with good outcome. This patient's history is more than 2 years and her condition was stable. She received 6 cycles of chemotherapy cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP). The evaluation was complete remission. The low levels of EBV-DNA in the peripheral blood may have potential benefit factor for the sensitivity to the chemotherapy and good outcome.


The effect of community-managed palliative care program on quality of life in the elderly in rural Tamil Nadu, India.
HelpAge India has been facilitating community-managed palliative care program in the villages of Tamil Nadu, India. To evaluate the effect of perceived quality of life in the elderly in the project villages in rural Tamil Nadu. It was a community-based evaluation study. Considering the mean difference of 0.6, design effect-2, precision-5%, power 80%, and 10% non-response, a sample size of 450 elderly persons (more than 60 years) was adequate. Sample was selected by two-stage cluster sampling. Tamil version of "WHO-Quality of Life-brief questionnaire" was used. Trained interviewers made house-to-house visits and obtained information by personally interviewing the subjects. The mean score for perceived physical quality of life in the project area was (10.47 ± 1.80 SD) high than the mean score (10.17 ± 1.82 SD) in the control area (P = 0.013) and the mean score for psychological support (10.13 ± 2.25 SD) in project area was high than the mean score (9.8 ± 2.29 SD) in control area (P = 0.043). There was no effect on domain of social relationship and environment. In the project villages, the perceived physical quality of life and psychological support among elderly persons was significantly better than the control villages.


Enteral nutrition in sepsis patients.
Sepsis, with its associated complications, is a leading cause of death in intensive care units. It is a major public health problem world-wide. The altered metabolism, severe condition and specific organ failure in sepsis patients get entangled in a vicious circle. Their treatment should invariably include nutritional support. The present survey summarizes the sepsis-induced metabolic changes so that they can be adequately compensated by nutritional support using specialized enteral formulas. We argue the necessity of introducing new efficient formulas as part of the so called immunonutrition. The basic requirements these formulas should meet are: 1. to provide sufficient amount of protein and energy substrate that can preserve the muscle function; 2. to be a source of substances that stimulate and protect enterocytes with restriction of bacterial translocation; 3. to help keep the liver function normal; 4. by including various substances with immunomodulating features to prevent and compensate the disturbances in the immune response.


The use of the ISIS optical scanner in the management of the braced adolescent idiopathic scoliosis patient.
Thirty-four adolescent female patients with right thoracic idiopathic scoliosis were followed for a mean of 8.6 months to document progression of scoliosis curvature during bracewear. Prediction of change by deviation of the lateral asymmetry index on ISIS examination were compared with measured change on standard upright roentgenograms. A one-to-one correlation was found in 50% of the patients; five patients were predicted to have stayed the same or decreased by ISIS and showed increase on x-ray measurement. Eight patients were predicted to have stayed the same or decreased by x-ray measurement and showed increase by ISIS. Although a weak positive correlation exists between change by x-ray examination and change by ISIS examination in a braced population, the clinical usefulness of the ISIS method in following a braced population has not been proven.


Effective and selective cell retention and recovery from whole blood by electroactive thin films.
Hematogenous metastatic spread causes most cancer patient deaths. Because circulating tumor cells (CTCs) are highly relevant to early metastatic spread, the capture or detection of these cells provides a diagnostic tool for patients with metastatic conditions. Herein, we demonstrate a programmable electroactive multilayered material platform with a smart electrically induced "switch" that captures CTCs from biological plasma with high efficiency and releases the captured cells flexibly. The released cells are still viable and proliferative, which facilitates the detection of trace levels of CTCs by amplification. Furthermore, the inherent rough characteristics of the nanoparticle-composed interface can promote capture efficiency and cell purification by integration with a simple microfluidic device. This elegant, inexpensive, and versatile platform for cell sorting and enrichment makes subsequent molecular and cell biological analysis achievable. The strategy has broad implications for favoring fundamental cancer biology research, for the diagnosis and monitoring of cancer individually, and for advanced intervention based on blood purification.


[Psychological Characteristics of Patients With Stress-induced Arterial Hypertension: a Violation of the Regulation of Emotions as a Central Link of Pathogenesis].
The study of emotional and personality characteristics of patients with hypertension in the workplace (HW) and comparative assessment of the effectiveness of antihypertensive therapy in these patients. The study included 170 patients c hypertensive disease stage II, 1-2-th degree, aged 32-52 years, including 85 patients with and 85 patients without WAH, and 82 healthy subjects matched for age and sex. To carry out simulation of the situation of emotional intensity (level of claims assessment process - UE) and a modified version of the test Rosenzweig. Patients with WAH were randomized into 2 groups: patients of group 1 received bisoprolol, 2nd group -eprosartan. If target blood pressure (BP) in 2 weeks, all patients were added indapamide retard. At baseline and after 16 weeks of treatment was carried out daily monitoring of blood pressure and the working day. When modeling a situation of emotional intensity in patients with WAP become, compared with patients without a healthy and WAH, revealed (1) marked increase in systolic blood pressure - 16.1, 4.1 and 3.0 mmHg, respectively (p <0,001 ), (2) the dominance of motivation "avoid failure" (UP underestimated in 34.1% of cases, unformed UP - in 21.2% of cases, healthy - 14.6% and 3.7% of cases, cootvetstvenno, p<0,001 in patients without WAH - 20% and 11.8%, respectively, p<0,05). Patients with WAP become different from normal was significantly (p<0.05) the number of the selected blshim emotionally meaningful situations (9.7 and 7.8, respectively) and emotional descriptors (11 and 7, respectively). Patients with WAH differ significantly (p<0,05) more frequent than in healthy, the use of ineffective strategies of emotion regulation in an emotionally meaningful situations: the suppression of the expression of emotions (38.3 and 20.3%, respectively), rumination and disasterization (19 and 11.8%, respectively) and more rare - high performance: sequential actualization of new meanings (25.7 and 31.7%, respectively) and the strategy of interactive subject-subject transformations (12.6 and 25.2%, respectively). After 16 weeks of treatment showed a significant (p<0,001) reduction of blood pressure in the 1st and 2nd groups. The number of patients achieving target blood pressure, at 2, 4 and 6 weeks, respectively, was as follows: 14 in the bisoprolol group and 93 (100%), in the eprosartan group - 0, 52 (100%). Both groups showed significant (p <0,001) reduction in mean daytime and nighttime blood pressure in the weekdays and weekends. In the group of bisoprolol showed a significant (p <0,01) higher average daily decrease in systolic blood pressure in the working day, compared with eprosartan group (26.2 and 19.3 mm Hg, respectively). Patients with WAP become emotionally meaningful situations frequently resorted to repression of emotions, choose the inefficient strategies of emotion regulation, they noted the expressed reaction of BP in response to the emotional burden. Antihypertensive therapy based on bisoprolol, is highly effective and has advantages over circuit-based therapy with eprosartan.


[Factors influencing platelet aggregation in patients with acute coronary syndrome].
To study factors influencing platelet aggregation in patients with acute coronary syndrome (ACS). The investigation enrolled 147 patients with ACS. Their blood was sampled on days 1, 3-5, and 8-12 days after the onset of ACS. All the patients received acetylsalicylic acid (ASA) 300 mg on day 1, then 100 mg/day and clopidogrel 300-600 mg on day 1, then 75-150 mg/day. Platelet aggregation was analyzed in 65 patients on day 1 after ASA intake, but prior to clopidogrel therapy. The aggregation was induced by 5 and 20 pmol of ADP. With the use of clopidogrel 75 mg/day on day 3-5, platelet aggregation was reduced by 2.1 and 1.7 times for 5 and 20 μmol of ADP, respectively, as compared to day 1 (ASA without clopidogrel) and remained unchanged on days 8-12. Increasing the dose of clopidogrel up to 150 mg/day potentiated its antiaggregatory effect. On day 1 (ASA without clopidogrel), there was a direct correlation between platelet aggregation levels and mean platelet volume (MPV) (correlation coefficients (r), 0.526 (p < 0.001) and 0.368 (p = 0.015) for 5 and 20 μmol of ADP, and between platelet aggregation levels and glycoprotein (GP) IIb-IIIa (r = 0.387; p = 0.002 and r = 0.411 (p < 0.001) for 5 and 20 μmol of ADP. No similar correlations were found on days 3-5 and 8-12 of administration of ASA and clopidogrel. The genetic polymorphism of GP lIb-Illa (GP Ila Leu33Pro) was not noted to affect platelet aggregation. Examining the effects of genetic variations in cytochrome P450 isoform CYP2C19 (a clopidogrel metabolizer) revealed the enhanced aggregation stimulated with 20 μmol of ADP in the carriers of slowly clopidogrel-metabolizing haplotype of CYP2C19 (differences were found on days 3-5 as compared to rapidly and routinely metabolizing haplotypes). In the patients with ACS, platelet aggregation is influenced by MPV, GP IIb-IIIa levels, and CYP2C19 polymorphism and is not by GP IIb-IIIa polymorphism.


Influenza vaccination in patients with haematologic malignancies: analysis of practices in 200 patients in a single center.
Despite recent studies demonstrating immunogenicity and tolerance of influenza vaccine in patients with haematologic malignancies, practices are still heterogeneous. The aim of this study was to analyse practices and factors influencing vaccination in a single centre, in the light of recent literature data. Two hundred patients with haematologic malignancies were included and filled out a standardized questionnaire about influenza vaccination. They were observed prospectively during the epidemic season. Our study revealed a poor uptake of influenza vaccination (vaccinal rate: 25.5%), in particular in patients younger than 65 y and those with no comorbidities. The main reasons for not being vaccinated were: the vaccination was not suggested to patients (53.7%), vaccination was contraindicated by doctors (24.2%), the patient refused it (21.5%). The main reasons for physicians for contraindicating the vaccine were: haematologic malignancy could be worsened by vaccination (33.3%), vaccination could generate illness or asthenia (27.8%), vaccination would not be efficient (16.7%), unknown (22.2%). We believe that a better knowledge by physicians of tolerance and efficiency of the vaccine could enhance the vaccination coverage.


[The impact of the coronavirus pandemic on the mental health of critical care workers].
The coronavirus pandemic has focused attention on the importance of critical care and highlighted the shortage of critical care specialists. Due to increasing workloads and high mortality rates, healthcare professionals were exposed to higher levels of physical and psychological stress during the pandemic than before. Our study investigated the effects of the coronavirus outbreak on the emotional, mental and moral stress of intensive care professionals. Our workgroup performed paper-based surveys among caregivers in the Department of Anaesthesiology and Intensive Therapy at Semmelweis University. The first survey was conducted at the start of the pandemic in 2020, the second survey was conducted after the third wave in 2021. We applied validated questionnaires (Professional Quality of Life, Demoralization Scale, Perceived Stress Scale, Impact of Event Scale, and Posttraumatic Growth Inventory), collected demographic data and information on lifestyle, recreation, dietary habits, and accepting psychological support. The number and demographic characteristics of the participants in the two studies are different, reflecting the changes in the workforce during the pandemic. Our results revealed no differences between the working and socio-demographic groups before the outbreak, however, one year later, nurses scored significantly higher on all negative psychological scales compared to other groups. Only a minority of the respondents had sought psychological support (9.5-12.7%), although more than a third of respondents reported the need for psychological support. Employees in new work positions showed significantly increased posttraumatic growth (2.91 ± 0.82 vs. 2.20 ± 1.06, p = 0.016). These findings demonstrate that nurses are the most strained workgroup during an uncertain and stressful period. The available mental support alone is not enough to help caregivers. Further steps are needed to improve the mental health of critical care workers. Orv Hetil. 2023; 164(42): 1646-1655.


Neuroanatomical and cognitive mediators of age-related differences in episodic memory.
Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging.


High-Dose Deferoxamine Treatment Disrupts Intracellular Iron Homeostasis, Reduces Growth, and Induces Apoptosis in Metastatic and Nonmetastatic Breast Cancer Cell Lines.
Mounting evidence suggest that iron overload enhances cancer growth and metastasis; hence, iron chelation is being increasingly used as part of the treatment regimen in patients with cancer. Now whether iron chelation depletes intracellular iron and/or disrupts intracellular iron homeostasis is yet to be fully addressed. MCF-7 and MDA-MB-231 breast cancer cells treated with increasing concentrations of the iron chelator deferoxamine were assessed for intracellular iron status, the expression of key proteins involved in iron metabolism, cell viability, growth potential, and apoptosis at different time points following treatment. Treatment with deferoxamine at 1, 5, or 10 μM for 24 or 48 hours, while not leading to significant changes in intracellular labile iron content, upregulated the expression of hepcidin, ferroportin, and transferrin receptors 1 and 2. In contrast, deferoxamine at 30, 100, or 300 μM for 24 hours induced a significant decrease in intracellular labile iron, which was associated with increased expression of hepcidin, ferritin, and transferrin receptors 1 and 2. At 48 hours, there was an increase in intracellular labile iron, which was associated with a significant reduction in hepcidin and ferritin expression and a significant increase in ferroportin expression. Although low-dose deferoxamine treatment resulted in a low to moderate decrease in MCF-7 cell growth, high-dose treatment resulted in a significant and precipitous decrease in cell viability and growth, which was associated with increased expression of phosphorylated Histone 2A family member X and near absence of survivin. High-dose deferoxamine treatment also resulted in a very pronounced reduction in wound healing and growth in MDA-MB-231 cells. These findings suggest that high-dose deferoxamine treatment disrupts intracellular iron homeostasis, reduces cell viability and growth, and enhances apoptosis in breast cancer cells. This is further evidence to the potential utility of iron chelation as an adjunctive therapy in iron-overloaded cancers.


Aggregated myocilin induces russell bodies and causes apoptosis: implications for the pathogenesis of myocilin-caused primary open-angle glaucoma.
Primary open-angle glaucoma with elevated intraocular pressure is a leading cause of blindness worldwide. Mutations of myocilin are known to play a critical role in the manifestation of the disease. Misfolded mutant myocilin forms secretion-incompetent intracellular aggregates. The block of myocilin secretion was proposed to alter the extracellular matrix environment of the trabecular meshwork, with subsequent impediment of aqueous humor outflow leading to elevated intraocular pressure. However, the molecular pathogenesis of myocilin-caused glaucoma is poorly defined. In this study, we show that heteromeric complexes composed of wild-type and mutant myocilin were retained in the rough endoplasmic reticulum, aggregating to form inclusion bodies typical of Russell bodies. The presence of myocilin aggregates induced the unfolded protein response proteins BiP and phosphorylated endoplasmic reticulum-localized eukaryotic initiation factor-2alpha kinase (PERK) with the subsequent activation of caspases 12 and 3 and expression of C/EBP homologous protein (CHOP)/GADD153, leading to apoptosis. Our findings identify endoplasmic reticulum stress-induced apoptosis as a pathway to explain the reduction of trabecular meshwork cells in patients with myocilin-caused glaucoma. As a consequence, the phagocytotic capacity of the remaining trabecular meshwork cell population would be insufficient for effective cleaning of aqueous humor, constituting a major pathogenetic factor for the development of increased intraocular pressure in primary open-angle glaucoma.


The Role of Alcohol Expectancies in Sexual Risk Behaviors Among Adolescents and Young Adults in the Democratic Republic of the Congo.
Considering the increased risk of HIV among alcohol users, we explored the role of individual alcohol expectancies in risk behaviors among youth in the Democratic Republic of the Congo. We surveyed 1,396 adolescents (ages 15-19) and young adults (ages 20-24) on alcohol and sexual behaviors in May, 2010. We assessed expectancies of alcohol use (1) leading to sex or positive sexual experiences; (2) diminishing one's ability to resist unwanted sex; and (3) diminishing one's ability to use or negotiate use of condoms. Adjusted logistic regression models assessed the association between alcohol use and alcohol expectancies with unprotected sex and multiple sex partners (MSP). Participants reporting alcohol use (36.8%) were more likely to have engaged in unprotected sex and MSP than nondrinkers (adjusted odds ratio [AOR]: 2.87, 95% confidence interval [CI]: 2.29-3.60; AOR: 3.73 95% CI: 2.94-4.72, respectively). Among alcohol users, after adjusting for drinking quantity, moderate expectancies of alcohol leading to positive sexual experiences were significantly associated with MSP among adolescent boys (AOR: 4.20, 95% CI: 1.49-11.86) and girls (AOR: 3.97, 95% CI: 1.36-11.60), whereas high expectancies were significant among young adult men (AOR: 2.70, 95% CI: 1.19-6.10). Among adolescent girls who used alcohol, adjusted odds of unprotected sex were elevated among those with expectancies of diminished ability to refuse unwanted sex (AOR: 5.13, 95% CI: 1.41-16.64) or to negotiate condom use (AOR: 16.22; 2.08-126.8). HIV prevention efforts for youth should acknowledge the role of alcohol expectancies in sexual risk behaviors and tailor programs to address different roles of expectancies in males and females.


Decreased uterine perfusion--a cause of infertility.
There have been several causes of infertility attributed to gamete quality, congenital anatomical abnormalities and surgical complications. Published research into the reasons for failure of implantation of embryos has been confined to histochemical and histological studies of the endometrium. This paper presents preliminary data from an ongoing study to test the hypothesis that poor uterine perfusion is a cause of failure of implantation of embryos. It would follow that poor uterine perfusion is a cause of infertility. One-hundred-and-fifty-three patients who had been unsuccessful in conceiving despite three previous in-vitro fertilization attempts have been studied. Doppler ultrasound studies of the ascending branch of the uterine artery, during spontaneous ovarian cycles, revealed a poor mid-secretory uterine response in 48% of patients studied. Patients with poor mid-secretory uterine response were treated with orally administered hormone therapy to improve the mid-secretory uterine response prior to subsequent embryo replacement. The results of subsequent in-vitro fertilization therapy in patients with good uterine response and in women with improved uterine response after hormone therapy are presented. The numbers of patients in each group are insufficient for statistical analyses, but the trends observed support the hypothesis that poor uterine blood flow is a cause of infertility. Further evaluation is warranted.


Secondary liposarcoma of the ovary.
This report is the first description of a secondary ovarian liposarcoma. The primary growth was in the mediastinum. The growth rate of the ovarian tumor was very rapid, but the patient died of cardiopulmonary causes. The mode of spread is discussed, and it probably occurred by transcelomic migration and surface implantation.


Comparability and validity of cancer registry data in the northwest of Russia.
Despite the elaborate history of statistical reporting in the USSR, Russia established modern population-based cancer registries (PBCR) only in the 1990s. The quality of PBCRs data has not been thoroughly analyzed. This study aims at assessing the comparability and validity of cancer statistics in regions of the Northwestern Federal District (NWFD) of Russia. Data from ten Russian regional PBCRs covering ∼13 million (∼5 million in St. Petersburg) were processed in line with IARC/IACR and ENCR recommendations. We extracted and analyzed all registered cases but focused on cases diagnosed between 2008 and 2017. For comparability and validity assessment, we applied established qualitative and quantitative methods. Data collection in NWFD is in line with international standards. Distributions of diagnosis dates revealed higher variation in several regions, but overall, distributions are relatively uniform. The proportion of multiple primaries between 2008 and 2017 ranged from 6.7% in Vologda Oblast to 12.4% in Saint-Petersburg. We observed substantial regional heterogeneity for most indicators of validity. In 2013-2017, proportions of morphologically verified cases ranged between 61.7 and 89%. Death certificates only (DCO) cases proportion was in the range of 1-14% for all regions, except for Saint-Petersburg (up to 23%). The proportion of cases with a primary site unknown was between 1 and 3%. Certain cancer types (e.g., pancreas, liver, hematological malignancies, and CNS tumors) and cancers in older age groups showed lower validity. While the overall level of comparability and validity of PBCRs data of four out of ten regions of NWFD of Russia meets the international standards, differences between the regions are substantial. The local instructions for cancer registration need to be updated and implemented. The data validity assessment also reflects pitfalls in the quality of diagnosis of certain cancer types and patient groups.


Vertebrate reservoirs and secondary epidemiological cycles of vector-borne diseases.
Vector-borne diseases of importance to human and domestic animal health are listed and the increasing emergence of syndromes, new epidemiological cycles and distributions are highlighted. These diseases involve a multitude of vectors and hosts, frequently for the same pathogen, and involve natural enzootic cycles, wild reservoirs and secondary epidemiological cycles, sometimes affecting humans and domestic animals. On occasions the main reservoir is in the domestic environment. Drivers for secondary cycles are mainly related to human impacts and activities and therefore, for purposes of prevention and control, the focus needs to be on the socioecology of the diseases. Technical and therapeutical solutions exist, and for control there needs to be a clear understanding of the main vertebrate hosts or reservoirs and the main vectors. The targets of interventions are usually the vector and/or secondary epidemiological cycles and, in the case of humans and domestic animals, the spillover or incidental hosts are treated. More attention needs to be given to the importance of the political economy in relation to vector-borne diseases, as many key drivers arise from globalisation, climate change and changes in structural ecologies. Attention to reducing the risk of emergence of new infection cycles through better management of the human-animal-environment interface is urgently needed.