2-aminoanthracene as an analytical tool with the acetylation reaction catalyzed by arylamine N-acetyltransferase.
The polynuclear aromatic amine, 2-aminoanthracene, was found to be acetylated with high efficiency in the presence of acetyl-CoA by pigeon liver arylamine N-acetyltransferase (EC 220.127.116.11). As a consequence of acetylation the fluorescence properties of the compound dramatically change and the reaction time course can be easily followed fluorometrically at the emission wavelength of 425 nm upon excitation at 360 nm. When 2-aminoanthracene is employed with pigeon arylamine N-acetyltransferase, as the ultimate acceptor of the acetyl group in coupled fluorometric assays, it is possible to measure enzymatic activities, such as pyruvate dehydrogenase or carnitine acetyltransferase, in continuous assays rapidly and with high sensitivity or to determine with as much sensitivity important metabolites such as acetylcarnitine or acetyl-CoA.


[Thyroid cancer in an endemic goiter region].
On the basis of an analysis of 1062 operations on the thyroid gland the authors make a conclusion that incidence of cancer of the thyroid gland in the focus of the moderate goiter endemia is 9,6%. Three stages of the development of cancer of the thyroid gland are established: a) precancer, b) latent stage of cancer (histological findings), c) stage of manifest cancer. Complex methods of treatment were used such as radical operation followed by the obligatory radiation therapy (in patients having no contraindications) and permanent treatment by thyroidine in combination with chemotherapy (on indications). Remote results followed in 92 patients during 9 years were quite satisfactory. Recurrences were found in 2 patients.


Driving Forces for Covalent Assembly of Porphyrins by Selective C-H Bond Activation and Intermolecular Coupling on a Copper Surface.
Recent synthesis of covalent organic assemblies at surfaces has opened the promise of producing robust nanostructures for functional interfaces. To uncover how this new chemistry works at surfaces and understand the underlying mechanisms that control bond-breaking and bond-making processes at specific positions of the participating molecules, we study here the coupling reaction of tetra(mesityl)porphyrin molecules, which creates covalently connected networks on the Cu(110) surface by utilizing the 4-methyl groups as unique connection points. Using scanning tunneling microscopy (STM), state-of-the-art density functional theory (DFT), and Nudged Elastic Band (NEB) calculations, we show that the unique directionality of the covalent bonding is found to stem from a chain of highly selective C-H activation and dehydrogenation processes, followed by specific intermolecular C-C coupling reactions that are facilitated by the surface, by steric constraints, and by anisotropic molecular diffusion. These insights provide the first steps toward developing synthetic rules for complex two-dimensional covalent organic chemistry that can be enacted directly at a surface to deliver specific macromolecular structures designed for specific functions.


Pathogen burden, cytomegalovirus infection and inflammatory markers in the risk of premature coronary artery disease in individuals of Indian origin.
Coronary artery disease (CAD) occurs at an earlier age in South Asians compared with other ethnic groups. Infection and inflammation show a positive association with the disease. To investigate the association of infection and inflammatory markers with premature CAD in the Indian Atherosclerosis Research Study population. Antibody titres for Chlamydia pneumoniae, cytomegalovirus (CMV), Helicobacter pylori, herpes simplex virus and levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen and secretory phospholipase A2, were measured in 866 individuals (433 CAD patients and matched controls). All individuals were followed-up for recurrent cardiac events for four years. ANOVA was used to study the association of infection and inflammation with CAD. The present study found that the odds of CAD occurrence was 2.42 (95% CI 1.26 to 4.64; P<0.008), with all four infections and increased in the presence of hsCRP (OR 4.67 [95% CI 1.43 to 15.25]); P=0.011). Only anti-CMV antibody levels were a significant risk factor for CAD occurrence (OR 2.23 [95% CI 1.20 to 4.15]; P=0.011) and recurrent cardiac events (OR 1.94 [95% CI 0.85 to 4.45]; P=0.015). Mean values of the inflammatory biomarkers IL-6 (P=0.035), fibrinogen (P=0.014), hsCRP (P=0.010) and secretory phospholipase A2 (P=0.002) increased with CMV antibody levels. Incorporating hsCRP and IL-6 in the risk prediction models significantly increased the OR to 2.56 (95% CI 1.16 to 5.63; P=0.019) with a c statistic of 0.826. Pathogen burden, especially CMV infection in combination with inflammatory markers, is a significant predictor of CAD risk in the young Indian population.


Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer.
We present the functional characterization of a pseudogene associated recurrent gene fusion in prostate cancer. The fusion gene KLK4-KLKP1 is formed by the fusion of the protein coding gene KLK4 with the noncoding pseudogene KLKP1. Screening of a cohort of 659 patients (380 Caucasian American; 250 African American, and 29 patients from other races) revealed that the KLK4-KLKP1 is expressed in about 32% of prostate cancer patients. Correlative analysis with other ETS gene fusions and SPINK1 revealed a concomitant expression pattern of KLK4-KLKP1 with ERG and a mutually exclusive expression pattern with SPINK1, ETV1, ETV4, and ETV5. Development of an antibody specific to KLK4-KLKP1 fusion protein confirmed the expression of the full-length KLK4-KLKP1 protein in prostate tissues. The in vitro and in vivo functional assays to study the oncogenic properties of KLK4-KLKP1 confirmed its role in cell proliferation, cell invasion, intravasation, and tumor formation. Presence of strong ERG and AR binding sites located at the fusion junction in KLK4-KLKP1 suggests that the fusion gene is regulated by ERG and AR. Correlative analysis of clinical data showed an association of KLK4-KLKP1 with lower preoperative PSA values and in young men (<50 years) with prostate cancer. Screening of patient urine samples showed that KLK4-KLKP1 can be detected noninvasively in urine. Taken together, we present KLK4-KLKP1 as a class of pseudogene associated fusion transcript in cancer with potential applications as a biomarker for routine screening of prostate cancer.


Analysis of antibody responses to protective antigen-based anthrax vaccines through use of competitive assays.
The licensed anthrax vaccine and many of the new anthrax vaccines being developed are based on protective antigen (PA), a nontoxic component of anthrax toxin. For this reason, an understanding of the immune response to PA vaccination is important. In this study, we examined the antibody response elicited by PA-based vaccines and identified the domains of PA that contribute to that response in humans as well as nonhuman primates (NHPs) and rabbits, animal species that will be used to generate efficacy data to support approval of new anthrax vaccines. To this end, we developed a competitive enzyme-linked immunosorbent assay (ELISA), using purified recombinant forms of intact PA and its individual domains. We found that PA-based vaccines elicited IgG antibodies to each of the four PA domains in all three species. We also developed a competitive toxin neutralization assay, which showed that rabbits, NHPs, and humans all have functional antibody populations that bind to domains 1, 3, and 4. While the domain specificities of the antibody responses elicited by PA-based vaccines were similar in humans, NHPs, and rabbits, competitive assays suggested that humans may have a more significant secondary population of IgG antibodies that bind to partially unfolded or incorrectly folded PA. These findings provide information that will be useful when linking animal protection data to humans via an antibody bridge to establish efficacy of new anthrax vaccines.


Recovery of sensorimotor gating without G protein adaptation after repeated D2-like dopamine receptor agonist treatment in rats.
Sensorimotor gating, a neural process severely disrupted in patients with schizophrenia, can be measured by assessing prepulse inhibition (PPI) of acoustic startle responses. PPI is disrupted in experimental animals by stimulation of D(2)-like dopamine receptors in the nucleus accumbens (NAc). We examined the effect of repeated treatment with a selective dopamine D(2)-like receptor agonist, quinpirole, and characterized the molecular substrates of the resulting PPI adaptation. Animals were treated once daily for 10 or 28 consecutive days with quinpirole (0.0, 0.05, 0.1, or 0.3 mg/kg, s.c.), and the effect on PPI was assessed throughout the treatment period. PPI was reduced after acute quinpirole administration, but gradually increased with repeated treatment. Quinpirole-induced PPI disruption was attenuated after 10 days of treatment at lower doses, but complete recovery was not apparent until the treatment period was extended to 28 days. Since chronic drug exposure can alter the dopamine system, we sought to characterize the effects of repeated quinpirole treatment on G proteins coupled to D(2)-like receptors in the NAc. Guanosine 5'-O-(3-[(35)S]thiotriphosphate) ([(35)S]GTPgammaS) binding and Western blot analysis revealed that repeated quinpirole treatment had no effect on NAc D(2)-like receptor G protein function or G protein levels. These data indicate that repeated activation of D(2)-like receptors by quinpirole produces tolerance in the absence of receptor or G protein changes, suggesting that the locus of dopaminergic adaptation might be at the intracellular level.


Synthesis, characterization, and computational study of complexes containing Pt···H hydrogen bonding interactions.
Complexes [Pt(C6F5)(bzq)L] (bzq = 7,8-benzoquinolinate; L = 8-hydroxyquinoline, hqH (1); 2-methyl-8-hydroxyquinoline, hqH' (2)) have been prepared by replacing the labile acetone ligand in the starting material [Pt(C6F5)(bzq)(Me2CO)]. The (1)H NMR spectra of 1 and 2 show that the signals attributable to the hydroxyl proton of the hqH or hqH' ligands are displaced downfield 2.64 ppm for 1 and 2.74 ppm for 2 with respect to the respective free ligands. Moreover, in both complexes the signals present platinum satellites with J(Pt,H) coupling constant of 67.0 Hz for 1 and 80.6 Hz for 2. All these features are indicative of the existence of Pt···H-O hydrogen bonds in solution for these complexes. The structures of complexes 1 and 2 have been established by an X-ray diffraction study and allow us to confirm the existence of these interactions in the solid state too. Thus, in both cases the hydroxyl hydrogen atom is pointing toward the metal center, and the measured geometric parameters involving this hydrogen are Pt-H = 2.09(4) Å, O-H = 0.94(4) Å, Pt-H-O 162(4)°, for 1, and Pt-H = 2.10(4) Å, O-H = 0.91(4) Å, Pt-H-O 162(4)°, for 2, all of which are fully compatible with a hydrogen bond system. Complexes 1 and 2 and the analogues [Pt(C6F5)3(hqH)](-) (A) and [Pt(C6F5)3(hqH')](-) (B), prepared some time ago in our laboratory and also showing Pt···H-O hydrogen bonds, have been the object of theoretical calculations to obtain better insight into the Pt···H interactions. Their density functional theory (DFT) calculated structures show excellent agreement with the X-ray determined ones (1, 2, and B). Topological analyses of the electron density function (ρ(r)) have been performed on the four complexes according to Bader's Atoms In Molecules theory. These analyses reveal a bond path that relates the platinum atom and the hydroxyl hydrogen atom, as well as the corresponding bond critical points. The values of the Laplacian ∇(2)ρ(r) and local energy density H(r) indicate that these are closed shell, electrostatic interactions, but with partial covalence. The deprotonation of the OH fragment in 1 and 2 with BuLi leads to the formation of the unexpected trinuclear complexes (NBu4)[Li{Pt(C6F5)(bzq)(L)}2] (L = hq (3), hq' (4)). The X-ray structures of these have shown a change in the coordination of the deprotonated hq and hq', which are now bonded to the Pt atoms through their O atoms, and which are bridging the Pt and Li metal atoms.


Palladium catalyzed oxidative coupling of α-enolic dithioesters: a new entry to 3,4,5-trisubstituted 1,2-dithioles via a double activation strategy.
An operationally simple, facile, and convenient one-pot straightforward method for the construction of 3,4,5-trisubstituted 1,2-dithioles has been explored and developed via palladium catalyzed self-coupling of α-enolic dithioesters for the first time. Pd(0) efficiently catalyzes the activation and cleavage of S-H and C-S bonds to achieve cascade coupling, which results in the concomitant formation of new S-S and C-C bonds. Optimization data, substrate scope, and mechanistic insights are discussed.


Analysis of candidate genes through a proteomics-based approach in primary cell lines from malignant melanomas and their metastases.
Proteomics provides a powerful approach for screening alterations in protein expression and post-translational modification associated with particular human diseases. In this study, the analysis of protein expression was focused on malignant melanoma in order to determine the candidate genes involved in tumour progression. The proteomes of cultured melanocytes and of cell lines from primary and metastatic lesions of one malignant melanoma patient were profiled using two-dimensional electrophoresis (2-DE) and mass spectrometry. Differentially expressed proteins were confirmed by 2-DE and mass spectrometry on an additional four malignant melanoma cell lines. Total RNA from the first subset of cell lines was used for quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of the candidate genes identified after proteomics analysis. A very high similarity was observed in the 2-DE maps of two malignant melanoma cell lines derived from primary and secondary lesions of the same patient. Mass spectrometry identified 37 proteins which were found to be more abundant in tumour cells in comparison with control melanocytes (as confirmed on additional cell lines), with a relatively high prevalence of stress proteins. Eight candidate genes (PRDX2, HSP27, HSP60, HSPA8, HSP9B, STIP1, PDI and P4HB) were further characterized by evaluating their messenger RNA expression levels through real-time RT-PCR analysis. Overexpression of HSP27, HSP60 and HSPA8 and downregulation of PRDX2 were observed in cells from metastatic malignant melanoma in comparison with those from primary melanoma. Although further investigations with larger numbers of paired normal and tumour samples are needed, our findings strongly suggest that the dysregulation of stress pathways may be involved in melanoma progression.


Prognostic value of noninvasive risk stratification in younger and older patients referred for evaluation of suspected coronary artery disease.
The purpose of this investigation is to explore the relationship of patient gender and age on coronary artery disease diagnostic evaluation and to assess the impact of noninvasive testing results on coronary revascularization rates and cardiac event-free survival. Retrospective observational cohort. From a series of 5322 consecutively tested patients from a Midwestern university tertiary medical center, a hospital cohort of 1345 patients with clinically suspected coronary artery disease was enrolled from 1988 through 1989. Cardiac risk factor and symptom profiles were worse in women, whereas rates of positive test results were similar in both sexes. Multivariable-adjusted risk for follow-up diagnostic testing was 1.8 and 1.9 times greater, respectively, for men < or = and > 65 years of age than for women (P < .01). Younger women were 4.9 times (P = .001) more likely to experience a cardiac event than younger men, with no differences between younger and older women (relative risk = 1.1; P > .20). Overall cardiac event rates were 2.3, 7.4, 16.7, and 20.2% for young men, young women, older women, and older men, respectively. Initial screening was delayed 2 to 7 times longer for older and younger women compared with men (P < .001); the greatest delays were observed for younger women. Diagnostic follow-up and subsequent cost of total care from initial evaluation through 2 years of follow-up were higher for men than for women (P < .0001), with older women having the lowest rate of subsequent diagnostic and interventional follow-up. In the highest risk patients, subsequent utilization rates were 40 and 20% higher for younger and older men than for similarly aged women. In particular, diabetics were less likely to undergo follow-up diagnostic testing and revascularization (67% younger women). Age appears to significantly and differently influence decisions regarding noninvasive and invasive medical service utilization in men and women and may partially account for variable outcomes in this and previous gender-based comparisons.


Future disability projections could be improved by connecting to the theory of a dynamic equilibrium.
Projections of future trends in the burden of disability could be guided by models linking disability to life expectancy, such as the dynamic equilibrium theory. This article tests the key assumption of this theory that severe disability is associated with proximity to death, whereas mild disability is not. Using data from the GLOBE study (Gezondheid en Levensomstandigheden Bevolking Eindhoven en omstreken), the association of three levels of self-reported disabilities in activities of daily living with age and proximity to death was studied using logistic regression models. Regression estimates were used to estimate the number of life years with disability for life spans of 75 and 85 years. Odds ratios of 0.976 (not significant) for mild disability, 1.137 for moderate disability, and 1.231 for severe disability showed a stronger effect of proximity to death for more severe levels of disability. A 10-year increase of life span was estimated to result in a substantial expansion of mild disability (4.6 years) compared with a small expansion of moderate (0.7 years) and severe (0.9 years) disability. These findings support the theory of a dynamic equilibrium. Projections of the future burden of disability could be substantially improved by connecting to this theory and incorporating information on proximity to death.


The hybrid histidine kinase Hk1 is part of a two-component system that is essential for survival of Borrelia burgdorferi in feeding Ixodes scapularis ticks.
Two-component systems (TCS) are principal mechanisms by which bacteria adapt to their surroundings. Borrelia burgdorferi encodes only two TCS. One is comprised of a histidine kinase, Hk2, and the response regulator Rrp2. While the contribution of Hk2 remains unclear, Rrp2 is part of a regulatory pathway involving the spirochete's alternate sigma factors, RpoN and RpoS. Genes within the Rrp2/RpoN/RpoS regulon function to promote tick transmission and early infection. The other TCS consists of a hybrid histidine kinase, Hk1, and the response regulator Rrp1. Hk1 is composed of two periplasmic sensor domains (D1 and D2), followed by conserved cytoplasmic histidine kinase core, REC, and Hpt domains. In addition to its REC domain, Rrp1 contains a GGDEF motif characteristic of diguanylate cyclases. To investigate the role of Hk1 during the enzootic cycle, we inactivated this gene in two virulent backgrounds. Extensive characterization of the resulting mutants revealed a dramatic phenotype whereby Hk1-deficient spirochetes are virulent in mice and able to migrate out of the bite site during feeding but are killed within the midgut following acquisition. We hypothesize that the phosphorelay between Hk1 and Rrp1 is initiated by the binding of feeding-specific ligand(s) to Hk1 sensor domain D1 and/or D2. Once activated, Rrp1 directs the synthesis of cyclic dimeric GMP (c-di-GMP), which, in turn, modulates the expression and/or activity of gene products required for survival within feeding ticks. In contrast to the Rrp2/RpoN/RpoS pathway, which is active only within feeding nymphs, the Hk1/Rrp1 TCS is essential for survival during both larval and nymphal blood meals.


Pharmaceutical Approaches on Antimicrobial Resistance: Prospects and Challenges.
The rapid increase in pathogenic microorganisms with antimicrobial resistant profiles has become a significant public health problem globally. The management of this issue using conventional antimicrobial preparations frequently results in an increase in pathogen resistance and a shortage of effective antimicrobials for future use against the same pathogens. In this review, we discuss the emergence of AMR and argue for the importance of addressing this issue by discovering novel synthetic or naturally occurring antibacterial compounds and providing insights into the application of various drug delivery approaches, delivered through numerous routes, in comparison with conventional delivery systems. In addition, we discuss the effectiveness of these delivery systems in different types of infectious diseases associated with antimicrobial resistance. Finally, future considerations in the development of highly effective antimicrobial delivery systems to combat antimicrobial resistance are presented.


Calcium improves apoplastic-cytosolic ion homeostasis in salt-stressed Vicia faba leaves.
Salinity disturbs both apoplastic and cytosolic Ca2+ and pH ([Ca2+]apo, [Ca2+]cyt, pHapo and pHcyt) homeostasis, and decreases plant growth. Seedlings of Vicia faba L. cv. Fuego were cultivated in hydroponics for 7 days under control, salinity (S), extra Ca (Ca) or salinity with extra Ca (S+Ca) conditions. The [Ca2+]apo, and pHapo in the leaves were then recorded in parallel by a pseudoratiometric method, described here for the first time. Lower [Ca2+]apo and higher pHapo were obtained under salinity, whereas extra Ca supply increased the [Ca2+]apo and acidified the pHapo. Moreover, the ratiometric imaging recorded that [Ca2+]cyt and pHcyt were highest in S+Ca plants and lowest in control plants. After all pretreatments, direct addition of NaC6H11O7 to leaves induced a decrease in [Ca2+]apo in control and S+Ca plants, but not in S and Ca plants, and only slightly affected pHapo. Addition of NaCl increased [Ca2+]cyt in protoplasts from all plants but only transiently in protoplasts from S+Ca plants. Addition of NaCl decreased pHcyt in protoplasts from Ca-pretreated plants. We conclude that Ca supply improves both apoplastic and cytosolic ion homeostasis. In addition, NaC6H11O7 probably causes transport of Ca from the apoplast into the cytosol, thereby leading to a higher resting [Ca2+]cyt.


Independent association between type 2 diabetes mellitus and hypertension over a period of 10 years in a large inpatient population.
Diabetes mellitus (DM) and hypertension (HTN) are common risk factors for heart disease in the population. The goal of this study was to evaluate independent association between type 2 DM and HTN using a very large database. We used ICD-9 codes for type 2 DM (250.00, 250.02) and HTN (401.0, 401.1, 401.9) from the Nationwide Inpatient Sample (NIS) database. We randomly selected the years in the database between 1992 and 2002. We used uni- and multi-variate analysis to evaluate any association between type 2 DM and HTN adjusting for co-morbid conditions. The 1992 database contained a total of 6,195,744 patients. Type 2 DM was associated with 37.5% of patients with HTN vs. 11.4% of the control group (odds ratio (OR): 4.63, Confidence interval (CI) 4.61-4.693, p < 0.001). The 2002 database contained a total of 7,853,982 patients. Type 2 DM was associated with 57.2% of patients with HTN vs. 22.9% of the control group (OR: 4.49, CI 4.47-4.52, p < 0.001). Using multivariate analysis adjusting for age, gender, hyperlipidemia, obesity, smoking, and chronic renal failure, type 2 DM remained independently associated with HTN in both years (for the year 1992: OR: 2.49, CI: 2.47-2.51, p < 0.001 and for the year 2002 OR: 2.19, CI: 2.18-2.20, p < 0.001). The same association was persistently found using samples for each year between 1992 and 2002. The presence of type 2 DM is strongly associated with HTN. This association is independent of co-morbid conditions and was persistent with similar odds ratio over a period of 10 years.


Clinico-pathological analysis of jaw tumours and tumour-like conditions at the Kenyatta national hospital.
This paper presents an analysis of 568 jaw tumours and tumour-like conditions seen at the Kenyatta National Hospital over a period of fifteen years. For descriptive purposes, the term tumour is used here in its wider context to cover both neoplastic and dysplastic jaw lesions which present primarily as jaw swellings. The study reveals a pattern consistent with other African series and suggests a more aggressive progression and younger age at onset than elsewhere.


Alberta's Rural Physician Action Plan: an integrated approach to education, recruitment and retention.
This paper describes the development and characteristics of a comprehensive, integrated and sustained program for the education, recruitment and retention of physicians for rural practice in Alberta--the Rural Physician Action Plan. The participation of key stakeholders (including government, the provincial medical association, the licensing authority, faculties of medicine, practising rural physicians and regional health authorities) and a sustained program budget have been key organizational issues for success. Critical to the effectiveness of this program has been the focus on professional and lifestyle issues targeting 3 distinct groups: physicians in training, physicians in practice, and rural communities and health authorities. Substantial program funding since 1991-92 of up to $3 million per year has increased rural-based activities significantly. For example, 87% of medical students and 91% of residents in family medicine in Alberta now experience 4 weeks or more of rural practice. The authors believe that the historic issues and recent trends militating against recruitment and retention of rural physicians will continue unchecked without comprehensive and sustained approaches such as Alberta's Rural Physician Action Plan.


Exploring National Trends and Organizational Predictors of Violence and Mistreatment From Patients and Visitors.
Rising incidents of violence and mistreatment of healthcare workers by patients and visitors have been reported. U.S. healthcare workers are five times more likely to experience nonfatal workplace violence (WPV) than workers in any other profession. However, less is known about the national trends in the incidence of violence and mistreatment in healthcare. The specific organizational and individual-level factors that relate to stress arising from these occurrences specifically by patients and family members are also not fully understood. The goals of this study were to examine national trends of violence toward healthcare workers, understand which populations are most vulnerable to stress from violence and mistreatment, and explore organizational factors that are related to these occurrences. Data were collected from three sources: (1) The Bureau of Labor Statistics Intentional Injury by Another Person data for the period 2011-2020, (2) data from a large national workers' compensation claim services provider for the period 2018-2022, and (3) results from a survey distributed at a large medical center in June and July 2022. Data were represented graphically and analyzed using multivariate regression and dominance analysis to identify specific predictors of WPV and mistreatment among healthcare workers. Of the total surveyed sample, 23.7% of participants reported mistreatment from patients or visitors as a major stressor and 14.6% reported WPV from patients or visitors as a major stressor. Stress from mistreatment and WPV was most frequently reported by nurses, employees aged 18 to 24 years other than nurses, those who identified as White, and those who identified as female or a gender minority. The emergency room (ER) showed the highest percentages of stress from mistreatment (61.8%) and violence (55.9%) from patients or visitors. The top predictors of stress from WPV and mistreatment by patients or visitors among healthcare workers ranked high to low were working in the ER, working as a nurse, a lack of necessary supplies or equipment, patient or visitor attitudes or beliefs about COVID-19, and working in a hospital-based unit. In addition to protecting employees as a moral imperative, preventing WPV is critical for organizational performance. Employee productivity is estimated to decrease up to 50% in the 6 to 18 weeks following an incident of violence, while turnover can increase 30% to 40%. An effective WPV prevention plan and a proactive approach to supporting the physical and mental health conditions that may result from WPV can mitigate the potential costs and exposures from these incidents. Organizations must also set clear expectations of behavior with patients and visitors by refusing to tolerate violence and mistreatment of caregivers. The impact of WPV can remain present and active for up to 8 years following an incident. Policy-level interventions are also needed. Currently, there are no federal protections for healthcare workers related to violence, though some states have made it a felony to abuse healthcare workers.


Systemic lupus erythematosus in Staphylococcus aureus hyperimmunoglobulinaemia E syndrome.
The prevalence of autoimmune diseases, including systemic lupus erythematosus, is increased in failure of certain host defence mechanisms. Systemic lupus erythematosus, however, has not been recorded as a late complication of the Staphylococcus aureus hyperimmunoglobulinaemia E (hyper-IgE) syndrome. Such a case was investigated in a man suffering from a classic example of the syndrome. Antinuclear antibodies were analysed on a molecular basis. The emergence of immunological and clinical features of systemic lupus erythematosus in patients with defective host defence mechanisms against staphylococcal infections is unlikely to be fortuitous and may help elucidate the pathogenesis of systemic lupus erythematosus. The observations will also aid the long term management of patients with S aureus hyper-IgE syndrome.


Analysis of arc emission spectra of stainless steel electric arc furnace slag affected by fluctuating arc voltage.
Control of chromium oxidation in the electric arc furnace (EAF) is a significant problem in stainless steel production due to variations of the chemical compositions in the EAF charge. One potential method to control chromium oxidation is to analyze the emission spectrum of the electric arc in order to find indicators of rising chromium content in slag. The purpose of this study was to determine if slag composition can be gained by utilizing electric arc emission spectra in the laboratory environment, despite electric arc voltage fluctuations and varying slag composition. The purpose of inducing voltage fluctuation was to simulate changes in the industrial EAF process. The slag samples were obtained from Outokumpu Stainless Oy Tornio Works, and three different arc currents were used. The correlation analysis showed that the emission spectra offer numerous peak ratios with high correlations to the X-ray fluorescence-measured slag CrO(x)/FeO(x) and MnO/SiO2 ratios. These ratios are useful in determining if the reduction agents have been depleted in the EAF. The results suggest that analysis of laboratory-scale electric arc emission spectra is suitable for indicating the high CrO(x) or MnO content of the slag despite the arc fluctuations. Reliable analysis of other slag components was not successful.


Joint reconstruction of multi-channel, spectral CT data via constrained total nuclear variation minimization.
We explore the use of the recently proposed 'total nuclear variation' (TVN) as a regularizer for reconstructing multi-channel, spectral CT images. This convex penalty is a natural extension of the total variation (TV) to vector-valued images and has the advantage of encouraging common edge locations and a shared gradient direction among image channels. We show how it can be incorporated into a general, data-constrained reconstruction framework and derive update equations based on the first-order, primal-dual algorithm of Chambolle and Pock. Early simulation studies based on the numerical XCAT phantom indicate that the inter-channel coupling introduced by the TVN leads to better preservation of image features at high levels of regularization, compared to independent, channel-by-channel TV reconstructions.


There is a Danish Christmas tune indicating that Santa can cause traffic hazards. The question is, however, whether there are other dangers associated with closer contacts to reindeers during Christmas. A literature search reveals a need for cautiousness, should one be tempted to try to get a glimpse of - or even to pad - Rudolph on the back on Christmas Eve.


The effects of isotretinoin on the ovarian reserve of females with acne.
There are some side effects of isotretinoin in many organs. However, a study investigating the effects of isotretinoin on the human ovarian reserve has not been reported previously. The study was conducted to investigate possible effects of isotretinoin on ovarian reserve. Serum anti-Müllerian hormone (AMH) levels were measured at the beginning and at the end of isotretinoin treatment in 22 patients with acne and in 22 women without. The mean AMH level before treatment was 5.77 ng/mL in the study group and 3.79 ng/mL in the control group (p = 0.008). Following treatment, the mean AMH level was 4.69 ng/mL in the study group. This mean AMH level after treatment was statistically lower than the AMH level before treatment (p = 0.012). There was no significant difference between the mean AMH level at the end of treatment and that of the control group (p = 0.20). The high level of pre-treatment AMH levels could be an evidence of hyperandrogenism in women with acne, even if they are not identified as having polycystic ovary syndrome (PCOS) or hyperandrogenism. Decrease in AMH levels following exposure to isotretinoin may suggest that it has a detrimental effect on the ovaries.


"Switchable water": aqueous solutions of switchable ionic strength.
"Salting out" is a standard method for separating water-soluble organic compounds from water. In this method, adding a large amount of salt to the aqueous solution forces the organic compound out of the aqueous phase. However, the method can not be considered sustainable because it creates highly salty water. A greener alternative would be a method that allows reversible salting out. Herein, we describe aqueous solutions of switchable ionic strength. Aqueous solutions of a diamine in water have essentially zero ionic strength but are converted by CO(2) into solutions of high ionic strength. The change is reversible. Application to the reversible salting out of THF from water is described.


Comparative measurement of gas temperature in a graphite atomizer by a two-line method of iron and nickel spectral lines in graphite furnace atomic absorption spectrometry.
The gas temperature of atomospheric gas in a graphite atomizer was measured during an atomization stage in graphite furnace atomic absorption spectrometry (GF-AAS), by using a two-line method under the assumption of Boltzmann distribution. Iron and nickel were chosen as the probe elements to compare the gas temperatures obtained with different pairs of spectral lines. The atomic absorptions of two iron atomic lines and those of two nickel atomic lines were simultaneously monitored to obtain their absorbances for the temperature determination. Their gas temperatures were lower than the wall temperature which was monitored by the conventional temperature control for GF-AAS. Furthermore, the temporal variations at the atomizing stage were different between the iron lines and the nickel lines: the maximum peak of the nickel gas temperature appeared to be more delayed and broadly than that of the iron gas temperature. This result could be attributed to the fact that nickel species began to be atomized a little behind iron species, probably because it was more difficult to reduce nickel oxide with graphite carbon than an iron oxide when these oxide species would be formed at the charring stage. A graphite furnace varies the temperature during the atomizing-duration time and also the distribution becomes inhomogeneous at different portions; therefore, the gas temperature would provide overall information along the optical path of incident radiation, when the probe elements diffuse in the furnace. The two-line method enables variations not only in the gas temperature but in the atomizing of probe elements to be directly determined, due to the ability of remote sensing and rapid response.


Potential impact of methyl isobutyl ketone (MIBK) on phenols degradation in an UASB reactor and its degradation properties.
Methyl isobutyl ketone (MIBK) as a solvent is extensively used for the phenols extraction from the wastewater, so it is unavoidable to expose in the effluent due to the solubility and leakage problem. The present study evaluated the impact of MIBK on phenols degradation in an UASB reactor and analyzed its degradation properties. The results indicated that the continuous dosing (0.1gL-1) and impact (10gL-1) of MIBK had limited effect on phenols removal (1-2% reduction) in the UASB reactor, but the specific methanogenic activity (SMA) values of sludge decreased by 45-75% after MIBK exposure. Anaerobic degradation rate of MIBK fitted well to a pseudo-first-order kinetic equation with respect to the initial concentration of 35mgL-1 (k=0.0115h-1, R2=0.9664). Furthermore, the relative methane generation rate constants of MIBK were 0.00816, 0.00613, 0.00273, and 0.00207d-1 at the initial concentrations of 0.1, 0.5, 5, and 10gL-1, respectively. MIBK showed higher inhibitory effect on the methanogenesis than on phenols degradation. This study pointed out that the industrial installations should consider the influence of solvent on anaerobic treatment of phenolic wastewater.


Fate and Behavior of Gunshot Residue-A Review.
A review of the literature concerning the fate and behavior of gunshot residue (GSR) is presented. A number of concomitant parameters including firearm and ammunition type, plume and GSR material characteristics, travel distances, chemical composition and GSR morphology are critically discussed in relation to their effects on the distribution and deposition, transfer and persistence processes of GSR. The underlying mechanisms associated with such processes are also considered. Knowledge of these processes on GSR materials could provide valuable information concerning scene preservation and subsequent forensic sampling. The number of GSR particles deposited can vary significantly with each firearm discharge, highlighting the potential to produce distinctive data in each individual case. With the continual development and compositional changes of new ammunition types, further evaluation of the effect these processes may have on GSR evidence and their possible influence on the interpretation of the analytical results should be given due consideration.


FOG: Fragment Optimized Growth algorithm for the de novo generation of molecules occupying druglike chemical space.
An essential feature of all practical de novo molecule generating programs is the ability to focus the potential combinatorial explosion of grown molecules on a desired chemical space. It is a daunting task to balance the generation of new molecules with limitations on growth that produce desired features such as stability in water, synthetic accessibility, or drug-likeness. We have developed an algorithm, Fragment Optimized Growth (FOG), which statistically biases the growth of molecules with desired features. At the heart of the algorithm is a Markov Chain which adds fragments to the nascent molecule in a biased manner, depending on the frequency of specific fragment-fragment connections in the database of chemicals it was trained on. We show that in addition to generating synthetically feasible molecules, it can be trained to grow new molecules that resemble desired classes of molecules such as drugs, natural products, and diversity-oriented synthetic products. In order to classify our grown molecules, we developed the Topology Classifier (TopClass) algorithm that is capable of classifying compounds, for example as drugs or nondrugs. The classification accuracies obtained with TopClass compare favorably with the literature. Furthermore, in contrast to "black-box" approaches such as Neural Networks, TopClass brings to light characteristics of drugs that distinguish them from nondrugs.


Patient-caregiver dyads in pancreatic cancer: identification of patient and caregiver factors associated with caregiver well-being.
We aimed to examine the psychosocial well-being in the pancreas cancer patient-caregiver dyad, and determine patient and caregiver characteristics that predict caregiver distress. This was a cross-sectional, observational study. Demographics and caregiving characteristics were gathered from patients and caregivers. Caregivers completed validated instruments investigating anxiety, depression, perceived stress and caregiver burden. Over a period of eleven months, 128 patient-caregiver dyads were enrolled. Patient and caregiver distress scores were not associated with patient clinical disease burden. Patient distress was a significant predictor of concurrent caregiver distress, anxiety, depression, and perceived burden. Younger caregivers were also associated with higher caregiver anxiety and perceived burden. Additionally, number of caregiving activities and caregiver overall health status were predictors of concurrent caregiver depression and perceived stress. Certain pancreatic cancer patient and caregiver variables may negatively impact the well-being of caregivers. Future efforts should focus on development and implementation of comprehensive caregiver support programs for those at risk for psychosocial distress.


Clinical Evaluation of Implant-Supported Removable Partial Dentures With a Stress-Breaking Attachment.
The stress-breaking ball (SBB) attachment can distribute the occlusal force equally between the alveolar ridge and the implants. The purpose of this study was to evaluate the implant-supported distal extension removable partial dentures (RPDs) with SBB attachment in 10 patients who were partially edentulous. This randomized crossover study was designed to compare the function of RPDs with and without healing abutments and SBB attachments to support the posterior aspects of the RPDs. Mandibular jaw movements during mastication and the occlusal force and contact area were measured with a commercially available tracking device and pressure-sensitive sheets. Using a visual analog scale, 4 criteria-chewing, retention, stability, and comfort-were evaluated. All of the data obtained were analyzed using a 1-way analysis of variance (α = 0.05). There were no significant differences in either the mean time or the coefficient of variation among the SBB attachments and healing abutments of implant-supported removable partial dentures (ISRPDs) and conventional removable partial dentures (CRPDs). SBB attachments and healing abutments of ISRPDs had greater forces and contact areas than those of CRPDs with significant differences. For all criteria, patients preferred SBB attachments to healing abutments and CRPDs. The implant-supported distal extension RPDs with SBB attachment improved denture stability and patients' satisfaction.


Early biochemical consequences of denervation in fast and slow skeletal muscles and their relationship to neural control over muscle differentiation.
1. One week after denervation several biochemical characteristics of the fast extensor digitorum longus and slow soleus muscles from adult rats were investigated and compared with the characteristics of the corresponding unoperated contralateral muscles. 2. After these short periods of denervation-induced atrophy, the isolated myosins showed unchanged ATPase (adenosine triphosphatase) activities, but there was the expected difference between fast and slow muscle. 3. The specific activities of several soluble enzymes and their characteristic patterns were found to be only slightly modified in both the extensor and soleus muscles after denervation, as were most of the activities measured in the isolated mitochondria. 4. The most significant modifications were in the isolated sarcoplasmic reticulum, and appeared to be specific to either slow or fast muscle. 5. Denervation of slow muscle led to a marked increase of Ca(2+)-transport rates, and of the specific activity of the Mg(2+)-activated K(+)-modulated Ca(2+)-stimulated ATPase, together with changes in the polyacrylamide-electrophoretic profiles of the microsomal membrane protein. Transformation of these several properties of slow muscle sarcoplasmic reticulum to those of fast muscle sarcoplasmic reticulum was further substantiated by electron-microscopic analysis after negative staining. Control experiments with tenotomized soleus muscle gave negative results. 6. The isolated sarcoplasmic reticulum from fast muscle showed a slight diminution of ATPase-linked Ca(2+)-transport activity and a selective increase of rotenone-insensitive NADH-cytochrome c reductase activity, in addition to a greater emphasis on slow-type electrophoretic components of the structural membrane protein. 7. The significance of these results in relation to specific differentiating influences from motor nerves is discussed.


Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7.
Nigella sativa or black seed extract has been reported to show various medicinal benefits. Thymoquinone which is an active compound of its seed has been reported to contain anti-cancer properties. The study addressed the anti-cancer efficiency of long-term in vitro treatment with thymoquinone towards human breast cancer cell lines MCF-7. Cell proliferation was determined with CellTiter 96 Aqueous. Non-Radioactive Cell Proliferation Assay Kit. It was followed with trypan blue exclusion test to determine the percentage of viable cells. The study incorporated cell cycle assay to distinguish cell distribution at various cell cycle phases using Cycletest Plus DNA Reagent Kit. The apoptosis detection kit was used to determine the percentage of apoptotic and necrotic cells using flow cytometry. The 50% inhibitory concentration (IC50) value determined using the proliferation assay was 25 μM thymoquinone. Late apoptotic cell percentage increased rapidly when treatment duration was increased to 24 h with 25 and 100 μM thymoquinone. Further analysis using cell cycle assay showed thymoquinone inhibition of breast cancer cell proliferation at minimal dose 25 μM and led to S phase arrest significantly at 72 h treatment (P = 0.009). It was also noted elevation sub-G1 peak following treatment with 25 μM thymoquinone for 12 h. Increase in thymoquinone to 50 μM caused G2 phase arrest at each time-point studied. In general thymoquinone showed sustained inhibition of breast cancer cell proliferation with long-term treatment. Specificity of phase arrest was determined by thymoquinone dose.


Cutaneous Light Chain Deposition Disease: A Report of 2 Cases and Review of the Literature.
Light chain deposition disease (LCDD) is a rare systemic disorder with deposition of mostly monoclonal amorphous nonamyloid light chains in multiple organs. Renal involvement with rapidly progressing renal failure presents the dominant manifestation of LCDD. Approximately 20%-30% of patients show symptomatic cardiac or liver involvement. Cutaneous manifestations are extremely rare with only a few published cases. We report 2 additional cases of cutaneous LCDD without detectable systemic disease.


Use of hematopoietic colony-stimulating factors: comparison of the 1994 and 1997 American Society of Clinical Oncology surveys regarding ASCO clinical practice guidelines. Health Services Research Committee of the American Society of Clinical Oncology.
The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess whether more appropriate patterns of colony-stimulating factor (CSF) use occurred after the publication of ASCO evidence-based practice guidelines in 1994 and 1996 for patients with solid tumors or lymphoma. In 1994 and 1997, questionnaires describing clinical scenarios were mailed to ASCO members who practiced medical oncology. Physicians were asked the extent to which they preferred to use a CSF for primary prophylaxis, secondary prophylaxis, or treatment of neutropenic complications. Multiple regression analyses were used to determine predictors of overall propensity to use CSFs and, when using a CSF, propensity to support longer schedules of CSF use. Decreased use of CSFs was shown in the following situations: (1) treatment for febrile neutropenia without localizing signs (39% in 1994 v 29% in 1997) or with a right lower lobe infiltrate (54% v 46%); (2) primary prophylaxis with paclitaxel for ovarian cancer (20% v 11%) or cyclophosphamide, doxorubicin, and vincristine chemotherapy for small-cell lung cancer (8.4% v 4.6%); and (3) secondary prophylaxis after afebrile neutropenia following chemotherapy for germ cell tumors (44.5% v 36.0%). One third fewer physicians supported the extended use of CSFs until an absolute neutrophil count >/= 10,000/mm(3) or a WBC count >/= 10,000/mm(3) was reached, both counts serving as criteria for stopping CSF therapy. However, we observed high rates of CSF use despite ASCO guideline recommendations against use in the following clinical situations: (1) primary prophylaxis in patients at low risk of febrile neutropenia (6% v 16%); (2) secondary prophylaxis late in the course of curative and palliative therapy (80% v 53%); and (3) treatment of afebrile and uncomplicated febrile neutropenia (30% v 60%). In 1994 and 1997, fee-for-service physicians were more likely than other physicians to prefer use of CSF support while maintaining treatment dose and schedule instead of using dose-reduction strategies, and, when using a CSF, they were more likely to support longer CSF treatment schedules (P <.05 for both scenarios). Decreased use and more appropriate use of CSFs in accordance with ASCO guideline recommendations occurred from 1994 to 1997, but there remain many opportunities to reduce CSF use with no clinical harm. Many oncologists continue to support the use of CSFs in scenarios and with scheduling criteria that the guidelines and evidence do not support. ASCO's evidence-based guidelines should be linked with formal continuous quality improvement initiatives to substantially improve the quality of supportive oncology care.


Oxidation of ryanodine receptor (RyR) and calmodulin enhance Ca release and pathologically alter, RyR structure and calmodulin affinity.
Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in heart failure (HF) and arrhythmias. Altered RyR2 domain-domain interaction (domain unzipping) and calmodulin (CaM) binding affinity are allosterically coupled indices of RyR2 conformation. In HF RyR2 exhibits reduced CaM binding, increased domain unzipping and greater SR Ca leak, and dantrolene can reverse these changes. However, effects of oxidative stress on RyR2 conformation and leak in myocytes are poorly understood. We used fluorescent CaM, FKBP12.6, and domain-peptide biosensor (F-DPc10) to measure, directly in cardiac myocytes, (1) RyR2 activation by hydrogen peroxide (H2O2)-induced oxidation, (2) RyR2 conformation change caused by oxidation, (3) CaM-RyR2 and FK506-binding protein (FKBP12.6)-RyR2 interaction upon oxidation, and (4) whether dantrolene affects 1-3. H2O2 was used to mimic oxidative stress. H2O2 significantly increased the frequency of Ca(2+) sparks and spontaneous Ca(2+) waves, and dantrolene almost completely blocked these effects. H2O2 pretreatment significantly reduced CaM-RyR2 binding, but had no effect on FKBP12.6-RyR2 binding. Dantrolene restored CaM-RyR2 binding but had no effect on intracellular and RyR2 oxidation levels. H2O2 also accelerated F-DPc10-RyR2 association while dantrolene slowed it. Thus, H2O2 causes conformational changes (sensed by CaM and DPc10 binding) associated with Ca leak, and dantrolene reverses these RyR2 effects. In conclusion, in cardiomyocytes, H2O2 treatment markedly reduces the CaM-RyR2 affinity, has no effect on FKBP12.6-RyR2 affinity, and causes domain unzipping. Dantrolene can correct domain unzipping, restore CaM-RyR2 affinity, and quiet pathological RyR2 channel gating. F-DPc10 and CaM are useful biosensors of a pathophysiological RyR2 state.


Late gastrointestinal hemorrhage after gastric bypass.
Hemorrhage from the excluded gastric segment or duodenum after gastric bypass is an uncommon late complication and poses both diagnostic and therapeutic difficulties. We describe 4 cases of late gastrointestinal (GI) hemorrhage after gastric bypass. 4 patients who underwent previous Roux-en-Y gastric bypass (RYGBP) presented for management of severe GI hemorrhage. Their history, diagnostic work-up, management, and surgical pathology are reviewed. In all 4 patients, preoperative diagnostic evaluation including nuclear scintigraphy, endoscopy, and angiography failed to localize the source of bleeding. Intraoperative endoscopy of the gastric remnant and subtotal gastrectomy were performed in all 4 patients. The mean time interval between RYGBP operation and gastrectomy was 15.5 years (range 13-17 years). In 3 of 4 patients, the source of bleeding was documented on pathologic examination of the resected gastric remnant and duodenum. At a mean follow-up of 15 months, none of the patients developed recurrent GI hemorrhage. GI hemorrhage after RYGBP can be a diagnostic and therapeutic dilemma. Intraoperative endoscopy of the excluded stomach and subtotal gastrectomy should be considered when the source of bleeding is not identified by conventional diagnostic techniques.


Effects of Methanol Extract of Wedelia chinensis Osbeck (Asteraceae) Leaves against Pathogenic Bacteria with Emphasise on Bacillus cereus.
The antibacterial activity of the methanol extract of Wedelia chinensis leave was studied and tested against three pathogenic Gram positive bacteria (Bacillus cereus, B. subtilis and Stapylococcus aureus) and three pathogenic Gram negative bacteria (Escherichia coli, Proteus rettgeri and Pseudomonas aeruginosa) by the disk diffusion assay and broth dilution methods. The extract exhibited favourable antibacterial activity against the bacterial cells but was more potent against Gram positive bacteria with the minimum inhibition concentration of 3.12 to 6.25 mg/ml compared to the Gram negative bacteria which had minimum inhibition concentration values of 25 mg/ml. The time-kill study suggested that the extract possessed bactericidal properties at higher concentrations and eradicated the growth of bacterial cells. The major abnormalities occurred to the bacterial cells after exposed to the extract were complete alterations in their morphology and collapsed of the cells beyond repair. The methanol extract of W. chinensis may be an effective antibacterial agent to treat bacterial infections.


SSZ-26 and SSZ-33: Two Molecular Sieves with Intersecting 10- and 12-Ring Pores.
The framework structures of two closely related molecular sieves, SSZ-26 and SSZ-33, are described. These materials possess a previously missing but desired structural feature in a group of industrially significant zeolites. They contain a three-dimensional pore system that provides access to the crystal interior through both 10- and 12-rings. This property is a consequence of the organic structure-directing agents used in the synthesis of these materials. These materials are examples of the purposeful design of a micropore architecture. Both SSZ-26 and SSZ-33 contain the 4=4-1 building unit that had been previously found only in natural zeolites.


Brain Complexity and Psychiatric Disorders.
Objective: In recent years, researchers and neuroscientists have begun to use a variety of nonlinear techniques for analyzing neurophysiologic signals derived from fMRI, MEG, and EEG in order to describe the complex dynamical aspects of neural mechanisms. In this work, we first attempted to describe different algorithms to estimate neural complexity in a simple manner understandable for psychiatrists, psychologists, and neuroscientists. Then, we reviewed the findings of the brain complexity analysis in psychiatric disorders and their clinical implications. Method : A non-systematic comprehensive literature search was conducted for original studies on the complexity analysis of neurophysiological signals such as electroencephalogram, magnetoencephalogram, and blood-oxygen-level-dependent obtained from functional magnetic resonance imaging or functional near infrared spectroscopy. The search encompassed online scientific databases such as PubMed and Google Scholar. Results: Complexity measures mainly include entropy-based methods, the correlation dimension, fractal dimension, Lempel-Ziv complexity, and the Lyapunov exponent. There are important differences in the physical notions between these measures. Our literature review shows that dementia, autism, and adult ADHD exhibit less complexity in their neurophysiologic signals than healthy controls. However, children with ADHD, drug-naïve young schizophrenic patients with positive symptoms, and patients with mood disorders (i.e., depression and bipolar disorder) exhibit higher complexity in their neurophysiologic signals compared to healthy controls. In addition, contradictory findings still exist in some psychiatric disorders such as schizophrenia regarding brain complexity, which can be due to technical issues, large heterogeneity in psychiatric disorders, and interference of typical factors. Conclusion: In summary, complexity analysis may present a new dimension to understanding psychiatric disorders. While complexity analysis is still far from having practical applications in routine clinical settings, complexity science can play an important role in comprehending the system dynamics of psychiatric disorders.


The effects of cadmium on photosynthesis of Phaseolus vulgaris - a fluorescence analysis.
Bean plants (Phaseolus vulgaris L. cv. Scarlett), germinated in darkness for I week, were transferred to light (200 μmol m-2 s-1 ) and cultivated for I week in a complete nutrient solution. After this period, cadmium ions in the form of CdSO4 were added at the concentrations of 0.10.20 and 50 μM. The effects of this metal on the properties of photosystem II photochemistry were studied by means of modulated fluorescence analysis. Steady state photochemical quenching. non-photochemical quenching and terminal fluorescence were determined in control and cadmiumtreated plants. We postulate that, during short term exposure of plants to cadmium in the early stages of growth, the Calvin cycle reactions are more likely than photosystem II to be the primary target of the toxic influence of cadmium. The reduced demand for ATP and NADPH upon Calvin cycle inhibition causes a down-regulation of photosystem II photochemistry and of the yield of linear electron transport.


Do Clinicians Understand Quality Metric Data? An Evaluation in a Twitter-Derived Sample.
Despite significant efforts and cost, quality metrics do not consistently influence practice. While research has focused on improving data through statistical risk-adjustment, whether clinicians understand these data is unknown. Therefore, we assessed clinician comprehension of central line-associated blood stream infection (CLABSI) quality metric data. Cross-sectional survey with an 11-item test of CLABSI data comprehension. Each question assessed 1 of 3 concepts concerning CLABSI understanding: basic numeracy, risk-adjustment numeracy, and risk-adjustment interpretation. Hypothetical data were used and presented in a validated format. Clinicians were recruited from 6 nations via Twitter to take an online survey. Clinician eligibility was confirmed by assessing responses to a question regarding CLABSI. The primary outcome was percent correct of attempted questions pertaining to the presented CLABSI data. Ninety-seven clinicians answered at least 1 item, providing 939 responses; 72 answered all 11 items. The mean percentage of correct answers was 61% (95% confidence interval [CI], 57%-65%). Overall, doctor performance was better than performance by nurses and other respondents (68% [95% CI, 63%-73%] vs. 57% [95% CI, 52%-62%], P = 0.003). In basic numeracy, mean percent correct was 82% (95% CI, 77%-87%). For risk-adjustment numeracy, the mean percent correct was 70% (95% CI, 64%-76%). Risk-adjustment interpretation had the lowest average percent correct, 43% (95% CI, 37%-49%). All pairwise differences between concepts were statistically significant at P <0.05. CLABSI quality metric comprehension appears low and varies substantially among clinicians. These findings may contribute to the limited impact of quality metric reporting programs, and further research is needed. Journal of Hospital Medicine 2017;12:18-22.


Mild and moderate pre-dialysis chronic kidney disease is associated with increased coronary artery calcium.
It is increasingly evident that patients with chronic kidney disease (CKD) are more likely to die from heart disease than kidney failure. This study evaluated whether pre- dialysis CKD is an independent risk factor for coronary artery calcium (CAC). A total of 544 consecutive patients who underwent CAC scoring were analyzed. Eleven patients requiring hemodialysis were excluded. Patients were divided into three groups: normal glomerular filtration rate (GFR) (GFR > 90 mL/min/1.73 m²), mild CKD (90 ≥ GFR > 60 mL/min/1.73 m²), and moderate CKD (60 ≥ GFR > 30 mL/min/1.73 m²). Continuous and categorical variables were compared using analysis of variance and the χ² statistic. A multiple logistic regression model was used for detecting the association between total CAC score and GFR. An unadjusted model was used, followed by a second model adjusted for covariates known to be related to CAC. Another multivariable binary logistic model predicting the presence of CAC (>10) was performed and odds of incidence of CAC (>10) were calculated among the three GFR subgroups. After adjustment for covariates, patients with mild CKD had mean CAC scores 175 points higher than those with the referent normal GFR (P = 0.048), while those with moderate CKD had mean CAC scores 693 points higher than the referent (P < 0.001). After adjustment for covariates, patients with mild CKD were found to be 2.2 times more likely (95% confidence interval 1.3-3.7, P = 0.004) and patients with moderate CKD were 6.4 times more likely (95% confidence interval 2.9-14.3, P < 0.001) to have incident CAC compared with the group with normal GFR. Mild and moderate pre-dialysis CKD are independent risk factors for increased mean and incident CAC.


Defining the relationship between rotator cuff injury and proximal humerus fractures.
The purpose of our study was to correlate radiographic characteristics with rotator cuff tendon injury on magnetic resonance imaging after fractures of the proximal humerus. We prospectively obtained magnetic resonance imaging on 30 patients with proximal humerus fractures after classifying each fracture radiographically using Neer and AO systems and determining the displacement of the greater tuberosity. Twelve patients (40.0%) had either complete ruptures or avulsions of at least one of the rotator cuff muscles. No abnormality was identified in the rotator cuff musculature in nine patients (29%). Severity of injury to the rotator cuff tendons increased substantially with respect to increasing AO and Neer classes and 5 mm or greater displacement of the greater tuberosity fragment. Additional study is needed to determine the exact role of rotator cuff tendon injury in the ultimate function attained by patients with proximal humerus fractures.


Down's syndrome screening is unethical: views of today's research ethics committees.
Screening for Down's syndrome forms part of routine obstetric practice. Ethical considerations relating to genetic screening form a major part of the workload of research ethics committees. This study investigated the attitudes of research ethics committee members to several conditions varying in clinical severity and prognosis, including Down's syndrome. The members of 40 randomly chosen research ethics committees were surveyed. A simple questionnaire comprising 19 clinical scenarios based around four "clinical" conditions was designed to review conditions that were potentially embarrassing, affecting life span but not mental ability, premature death, and intellectual impairment with a risk of neonatal cardiac defects (Down's syndrome). Screening tests with different degrees of effectiveness were described and the diagnostic test descriptions ranged from having no risk to an unaffected fetus to causing spontaneous abortion of two normal fetuses for each affected fetus identified. Replies were graded on a scale of 1 to 5. Seventy seven replies were received from 28 different research ethics committees. Screening was supported for treatment of a life threatening condition (95% in favour) but screening for conditions of a slight increase in premature death (14% in favour) or cosmetic features (10% in favour) were considered unethical. Views were ambiguous (49% in favour) about conditions involving significant shortening of lifespan. Down's syndrome screening was considered more ethical when described as a serious condition (56% in favour) than when the clinical features were described (44% in favour). Once increased rates of spontaneous abortion on confirmatory testing were added, 79% (21% in favour) and 86% (14% in favour) stated that screening was unethical (for "serious" and "clinical features" descriptions, respectively). Down's syndrome screening raises ethical concerns about genetic testing in general that need to be dealt with before the introduction of any prenatal screening test.


Phosphoproteome analysis of human liver tissue by long-gradient nanoflow LC coupled with multiple stage MS analysis.
Reversible protein phosphorylation plays a critical role in liver development and function. Comprehensively cataloging the phosphoproteins and their phosphorylation sites in human liver tissue will facilitate the understanding of physiological and pathological mechanisms of liver. Owing to lacking of efficient approach to fractionate phosphopeptides, nanoflow-RPLC with long-gradient elution was applied to reduce the complexity of the phosphopeptides in this study. Two approaches were performed to further improve the coverage of phosphoproteome analysis of human liver tissue. In one approach, ten-replicated long-gradient LC-MS/MS runs were performed to analyze the enriched phosphopeptides, which resulted in the localization of 1080 phosphorylation sites from 495 proteins. In another approach, proteins from liver tissue were first fractionated by SDS-PAGE and then long-gradient LC-MS/MS analysis was performed to analyze the phosphopeptides derived from each fraction, which resulted in the localization of 1786 phosphorylation sites from 911 proteins. The two approaches showed the complementation in phosphoproteome analysis of human liver tissue. Combining the results of the two approaches, identification of 2225 nonredundant phosphorylation sites from 1023 proteins was obtained. The confidence of phosphopeptide identifications was strictly controlled with false discovery rate (FDR) < or = 1% by a MS(2)/MS(3) target-decoy database search approach. Among the localized 2225 phosphorylated sites, as many as 70.07% (1559 phosphorylated sites) were also reported by others, which confirmed the high confidence of the sites determined in this study. Considering the data acquired from low accuracy mass spectrometer and processed by a conservative MS(2)/MS(3) target-decoy approach, the number of localized phosphorylation sites obtained for human liver tissue in this study is quite impressive.


Effects of a transdiagnostic unguided Internet intervention ('velibra') for anxiety disorders in primary care: results of a randomized controlled trial.
Internet-based cognitive-behavioural treatment (ICBT) for anxiety disorders has shown some promise, but no study has yet examined unguided ICBT in primary care. This randomized controlled trial (RCT) investigated whether a transdiagnostic, unguided ICBT programme for anxiety disorders is effective in primary care settings, after a face-to-face consultation with a physician (MD). We hypothesized that care as usual (CAU) plus unguided ICBT would be superior to CAU in reducing anxiety and related symptoms among patients with social anxiety disorder (SAD), panic disorder with or without agoraphobia (PDA) and/or generalized anxiety disorder (GAD). Adults (n = 139) with at least one of these anxiety disorders, as reported by their MD and confirmed by a structured diagnostic interview, were randomized. Unguided ICBT was provided by a novel transdiagnostic ICBT programme ('velibra'). Primary outcomes were generic measures, such as anxiety and depression symptom severity, and diagnostic status at post-treatment (9 weeks). Secondary outcomes included anxiety disorder-specific measures, quality of life, treatment adherence, satisfaction, and general psychiatric symptomatology at follow-up (6 months after randomization). CAU plus unguided ICBT was more effective than CAU at post-treatment, with small to medium between-group effect sizes on primary (Cohen's d = 0.41-0.47) and secondary (Cohen's d = 0.16-0.61) outcomes. Treatment gains were maintained at follow-up. In the treatment group, 28.2% of those with a SAD diagnosis, 38.3% with a PDA diagnosis, and 44.8% with a GAD diagnosis at pretreatment no longer fulfilled diagnostic criteria at post-treatment. The unguided ICBT intervention examined is effective for anxiety disorders when delivered in primary care.


Bisulfite oligonucleotide-capture sequencing for targeted base- and strand-specific absolute 5-methylcytosine quantitation.
Epigenetic regulation through DNA methylation (5mC) plays an important role in development, aging, and a variety of diseases. Genome-wide studies of base- and strand-specific 5mC are limited by the extensive sequencing required. Targeting bisulfite sequencing to specific genomic regions through sequence capture with complimentary oligonucleotide probes retains the advantages of bisulfite sequencing while focusing sequencing reads on regions of interest, enables analysis of more samples by decreasing the amount of sequence required per sample, and provides base- and strand-specific absolute quantitation of CG and non-CG methylation levels. As an example, an oligonucleotide capture set to interrogate 5mC levels in all rat RefSeq gene promoter regions (18,814) and CG islands, shores, and shelves (18,411) was generated. Validation using whole-genome methylation standards and biological samples demonstrates enrichment of the targeted regions and accurate base-specific quantitation of CG and non-CG methylation for both forward and reverse genomic strands. A total of 170 Mb of the rat genome is covered including 6.6 million CGs and over 67 million non-CG sites, while reducing the amount of sequencing required by ~85 % as compared to existing whole-genome sequencing methods. This oligonucleotide capture targeting approach and quantitative validation workflow can also be applied to any genome of interest.


Climbing up the pay-for-performance learning curve: where are the early adopters now?
The diffusion of performance-based payment incentives is arguably the most striking change in the U.S. health care system since the managed care era. Because there is little knowledge about best practices, sponsors of payment-incentive programs must learn by doing. We examine the experiences of twenty-seven early adopters and profile the evolution of their pay-for-performance (P4P) strategies as well as perceptions of key lessons learned. Our findings suggest that leading-edge sponsors of P4P have expanded the reach of their efforts, particularly with regard to specialists, and increasingly are focused on outcome and cost-efficiency measures, rather than clinical process measures alone.


[The defect in cytochrome c553 in non-photosynthetic mutant cells of Chlamydomonas reinhardii].
The light electron transport in non-photosynthetic mutants of Chlamydomonas reinhardii A-36 and A-68 with a decreased content of cytochrome c553 was studied. The light-induced changes of absorption at 520, 559, 563 nm were shown to occur in the films of intact cells and in cell fragments. However, no maximum of the "light minus dark" difference absorption spectra of mutants belonging to cytochrome c553 was revealed. The electron transport from water to NADP+ or ferricyanide in the mutants was completely blocked; however, it was partly restored by an addition of exogenous cytochrome c553 to the cell fragments. A conclusion on the genetic damage of cytochrome c553 in mutants A-36 and A-68 was made. The localization of the cytochrome in the electron transport chain between the photosystems was demonstrated.


[Pharmacokinetics of n-(5-oxynicotinoyl)-L-glutamic acid calcium salt upon bolus administration in rats and rabbits: interspecies extrapolation].
The pharmacokinetics of N-(5-oxynicotinoyl)-L-glutamate (ONG) was studied in rats (doses, 20, 100 and 500 mg/kg) and rabbits (50 mg/kg) after bolus administration of calcium salt of N-(5-oxynicotinoyl)-L-glutamic acid (Ampasse preparation). The ONG concentration in the blood serum was determined by HPLC assay with fluorimetric detection. The lower limit of accurate detection for ONG was 100 ng/ml. The ONG pharmacokinetics in rats was linear at relatively small doses (20-100 mg/kg) but nonlinear at a large dose (500 mg/kg). The ONG concentration decay had a two-phase character in both rats and rabbits, so that the pharmacokinetic profiles were fitted to a biexponential equation of the two-compartment model. Systemic pharmacokinetic parameters determined in rats and rabbits, respectively, were as follows: total clearance, 18 and 15 ml/(min kg); steady state distribution volume, 330 and 880 ml/kg; mean retention time, 0.3 and 1.0 h; half-life, 0.73 and 2.3 h. Using the allometric approach to the interspecies extrapolation of the pharmacokinetic data, the half-life of ONG in humans is predicted to be 4 h.


Synthesis, antimicrobial, anticancer evaluation and QSAR studies of thiazolidin-4-ones clubbed with quinazolinone.
A series of 3-(5-(arylidene)-2-(aryl)-4-oxothiazolidin-3-yl)-2-phenylquinazolin-4(3H)-one derivatives (1-18) was synthesized in appreciable yield and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial and anticancer potentials. Antimicrobial properties of the title compounds were investigated against Gram positive and Gram negative bacterial as well fungal strains. 3-(5-(3- Methoxybenzylidene)-2-(4-(dimethylamino)phenyl)-4-oxothiazolidin-3-yl)-2-phenyl quinazolin-4(3H)-one (16, pMICam = 1.71 µM/ml) was found to be the most active antimicrobial agent. The anticancer evaluation of synthesized compounds against human colon (HCT116) cancer cell line indicated that 3-(5-(4-bromobenzylidene)-2-(3-chlorophenyl)-4- oxothiazolidin-3-yl)-2-phenylquinazolin-4(3H)-one (7, IC50 = 5.27 µM) was the most active anticancer agent and was more potent than standard drug, 5-fluorouracil (IC50 = 6.00 µM). QSAR models developed for antimicrobial activity of synthesized compounds indicated that antimicrobial activity of synthesized 4-thiazolidinone derivatives was governed by the topological parameters, valence first and second order molecular connectivity indices ((1)Χ(v) and (2)Χ(v)) and the electronic parameters, total energy (Te) and cosmic energy (Cos E).


Characterization of Bacteroides fragilis hemolysins and regulation and synergistic interactions of HlyA and HlyB.
This study describes the presence of 10 hemolysin orthologs in the genome of the opportunistic human anaerobic pathogen Bacteroides fragilis, which is currently classified as a nonhemolytic bacterium. The hemolysins were designated HlyA through HlyI plus HlyIII. All cloned hemolysin genes were able to confer hemolytic activity to a nonhemolytic Escherichia coli strain on blood agar plates. Interestingly, HlyH was found to be present in the genome of the B. fragilis NCTC9343 strain but absent in strains 638R, YCH46, and Bacteroides thetaiotaomicron VPI-5482. The hemolysins HlyA, HlyB, and HlyIII were selected for further characterization. HlyA, HlyB, and HlyIII were cytolytic to erythrocytes on liquid hemolytic assay. When hlyA and hlyB were expressed together in a nonhemolytic E. coli strain, the strain showed enhanced hemolytic activity on blood agar plates. Further analysis revealed that HlyA and HlyB have synergistic hemolytic activity as detected by the liquid hemolytic assay. In addition, the two-component hemolysins HlyA and HlyB form a protein-protein complex in vivo as determined by bacterial two-hybrid system assay. The hlyB and hlyA genes are organized in an operon that is coordinately regulated by iron and oxygen. Northern blot hybridization analysis revealed that hlyBA were expressed as a bicistronic mRNA induced approximately 2.5-fold under low-iron conditions and repressed in iron-rich medium. The normal iron-regulated expression of hlyBA mRNA was lost in the furA mutant strain. In contrast, the hlyA gene was also expressed as a single mRNA in iron-rich medium, but its expression was reduced approximately threefold under low-iron conditions in a Fur-independent manner. This suggests that hlyA alone is regulated by an unidentified iron-dependent regulator. Moreover, the expression levels of hlyBA and hlyA were reduced about threefold following oxygen exposure and treatment with hydrogen peroxide. Taken together, these results suggest that iron and oxidative stress have an effect on the control of hlyBA and hlyA transcriptional levels. A hlyBA mutant was constructed, and its hemolytic activity was greatly diminished compared to those of the hlyIII mutant and parent strains. In addition, the hlyBA mutant had a significant modification in colony morphology and growth deficiency compared to the parent strain. The implications of these findings for the pathophysiology of B. fragilis in extraintestinal infections and competition in ecological systems for this organism are discussed.


Adrenergic stimulation of substrate utilization by cardiac myocytes isolated from rainbow trout.
A method is described for the isolation of calcium-tolerant myocytes from adult rainbow trout. Isolated myocytes remain viable for at least 4 h in suspension as indicated by (1) maintenance of ATP, phosphocreatine (PCr) and glycogen levels; (2) maintenance of the integrity of cell membranes, shown by low rates of leakage of lactate dehydrogenase (LDH) to the medium and exclusion of Trypan Blue; (3) the ability to metabolize substrates; and (4) sensitivity to adrenergic agonists. CO2 production from both glucose and lactate was sensitive to adrenergic stimulation, with the following order of potency: isoproterenol greater than noradrenaline much greater than adrenaline greater than phenylephrine, which indicates the presence of beta 1-adrenoceptors. Myocytes isolated from trout acclimated to 20 degrees C in the summer were more sensitive to beta-adrenergic stimulation than myocytes isolated from trout acclimated to 9 degrees C in either summer or winter. In the absence of exogenous fuel, there was a net reduction in myocyte glycogen content and glycogenolysis was further stimulated by 10(-7) mmol l-1 noradrenaline. However, in the presence of exogenous fuel (either 5 mmol l-1 lactate or 5 mmol l-1 glucose), glycogen was 'spared' and noradrenaline-stimulated glycogenolysis was apparently inhibited.


Transanal advancement flap repair of transsphincteric fistulas.
The purpose of this study was to evaluate the healing rate of transsphincteric perianal fistulas after transanal advancement flap repair and to examine the impact of this procedure on fecal continence. Between January 1992 and January 1997, 44 consecutive patients with a transsphincteric perianal fistula passing through the middle or upper third of the external anal sphincter underwent transanal advancement flap repair. There were 34 male patients, and the median age was 44 (range, 19-72) years. Twenty-four patients (55 percent) had previously undergone one or more prior attempts at repair. With the patient in prone jackknife position, the internal opening of the fistula was exposed using a Parks retractor. The crypt-bearing tissue around the internal opening and the overlying anoderm was excised. A layer of mucosa, submucosa, and internal sphincter fibers was mobilized 4 to 6 cm proximally. The base of the flap was approximately twice the width of its apex. The flap was advanced and sutured to the anoderm below the level of the internal opening. The median follow-up was 12 months. Fecal continence was evaluated in 43 patients by means of a questionnaire. Transanal advancement flap repair was successful in 33 patients (75 percent). Success was inversely correlated with the number of prior attempts. In patients with no or only one previous attempt at repair the healing rate was 87 percent. In patients with two or more previous repairs the healing rate dropped to 50 percent. In 15 patients (35 percent) continence deteriorated after transanal advancement flap repair. Twenty-six patients (59 percent) had a completely normal continence preoperatively. Ten of these patients (38 percent) encountered soiling and incontinence for gas after the procedure, whereas three subjects (12 percent) complained of accidental bowel movements. Eighteen patients (41 percent) had continence disturbances at the time of admission to our hospital. In two of these patients (11 percent), incontinence deteriorated. The results of transanal advancement flap repair in patients with no or only one previous attempt at repair are good. In patients who have undergone two or more previous attempts at repair the outcome is less favorable. Remarkably, the number of previous attempts did not adversely affect continence status.


Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection.
This study compared the incidence of HIV-1 variants harboring mutations conferring resistance to thymidine analogues, ie, thymidine analogue mutations (TAMs), nonnucleoside reverse transcriptase (RT) inhibitors (NNMs), lamivudine (3TC) (ie, M184V), and protease inhibitors (PIs) acquired in primary HIV infection (PHI) (n = 59) to their observed prevalence in a corresponding potential transmitter (PT) population of persons harboring resistant infections (n = 380). Both of these populations in the context of this cohort analysis possessed similar demographics. Whereas the frequencies of observed TAMs, NNMs, M184V, and protease-associated mutations (PRAMs) were similar in the PT groups, the prevalence of M184V and major PI mutations were significantly lower in the PHI group (PHI/PT ratios of 0.14 and 0.39, respectively). There was a decreased prevalence in the PHI population of resistant viruses co-expressing NNMs or TAMs with M184V compared with viruses that harbored NNMs or TAMs in the absence of M184V (P < 0.0001). It was also observed that individuals in the PT subgroups who harbored RT mutations or PRAMs with M184V had lower levels of plasma viremia than individuals who lacked M184V (P < 0.05). These findings suggest that both decreased viremia and viral fitness in the case of M184V-containing HIV-1 variants may impact on viral transmissibility.


Morphometric Study of Subpubic Angle in Human Fetuses.
The symphysis pubis is formed at the confluence of the pubic bones. Each pubic bone consists of a body and two rami; the superior ramus is joined with the ilium and the inferior ramus with the ischium. The two bones meet in the midline at the pubic symphysis. The two inferior rami at the lower border of pubic symphysis subtend the subpubic angle. In females the subpubic angle is more than 90° and in males it is less than 90°. Most of the previous studies on the subpubic angle have been in children or adults, therefore data on fetuses did merit. The aims of the present study were to measure the subpubic angle in developing human fetuses of different gestational age, whether it is sex dependent and to compare the results with that in the adults. A cross-sectional study conducted in the Department of Anatomy JN Medical College, AMU Aligarh, over a period of two years. A total of 41 fetuses immersion fixed in 10% formalin were obtained from the museum department of anatomy. For the purpose of study fetuses were divided into five groups according to gestational age. Group I comprises fetuses of 14-18weeks, group II 19-22weeks, group III 23-26weeks, group IV 27-30weeks, groupV >30weeks of gestation. Pubic symphyses were dissected, cleaned and subjected to radiological examination in the anteroposterior plane. With the help of radiographs subpubic angle was measured. Readings obtained were analysed statistically. Subpubic angle ranged between 58°-64° throughout intrauterine life. Maximum angle (63°- 64°) was observed in group I and V and in the rest of the groups it was less than 60°, with highly significant (p-value<0.001) increase in the last group. Statistically significant sexual dimorphism was observed in group I and II fetuses (p-value <0.001). Subpubic angle was more in females during the first half and in the terminal part of gestation. Subpubic angle remained acute throughout the intrauterine life, with significant widening in fetuses more than 30 weeks of gestation. Marked sexual dimorphism was noticed only in fetuses of 14-18 weeks and 19-22 weeks of gestation fetuses, although the values were invariably less than 90° (acute) in both the sexes but in females towards the higher side as in adults. Assessment of symphysis and subpubic arch during antenatal ultrasonography of pregnant women can be done to diagnose congenital widening of the symphysis or absence of symphysis altogether.


Clinical update on COVID-19 in pregnancy: A review article.
The data pertaining to the COVID-19 pandemic has been rapidly evolving since the first confirmed case in December 2019. This review article presents a comprehensive analysis of the current data in relation to COVID-19 and its effect on pregnant women, including symptoms, disease severity and the risk of vertical transmission. We also review the recommended management of pregnant women with suspected or confirmed COVID-19 and the various pharmacological agents that are being investigated and may have a role in the treatment of this disease. At present, it does not appear that pregnant women are at increased risk of severe infection than the general population, although there are vulnerable groups within both the pregnant and nonpregnant populations, and clinicians should be cognizant of these high-risk groups and manage them accordingly. Approximately 85% of women will experience mild disease, 10% more severe disease and 5% critical disease. The most common reported symptoms are fever, cough, shortness of breath and diarrhea. Neither vaginal delivery nor cesarean section confers additional risks, and there is minimal risk of vertical transmission to the neonate from either mode of delivery. We acknowledge that the true effect of the virus on both maternal and fetal morbidity and mortality will only be evident over time. We also discuss the impact of social isolation can have on the mental health and well-being of both patients and colleagues, and as clinicians, we must be mindful of this and offer support as necessary.


Anterior versus posterior approach total hip arthroplasty: patient-reported and functional outcomes in the early postoperative period.
Direct anterior approach total hip arthroplasty (DA THA) has been reported to improve early outcomes compared to posterior approach THA up to 6 weeks postoperatively. Limited weekly outcomes data are available prior to 6 weeks. We evaluate outcomes including when patients first drive a car, leave home, and discontinue their assist device. Patients undergoing THA for primary osteoarthritis were prospectively enrolled. Outcomes data were collected preoperatively and postoperatively at weekly intervals for 6 weeks. 111 patients (55 DA and 56 posterior approach) were enrolled. There was no significant difference (p > 0.05) in pre-surgical Patient-Reported Outcomes Measurement Information System (PROMIS) scores or modified Harris Hip Score (mHHS).Postoperatively, the DA THA group had decreased length of stay (p = 0.0002) and increased distance walked on postoperative day 1 and 2 (p = 0.011, p = 0.0004). The DA group had lower pain scores (p < 0.05) and required less day 1 and total narcotics (p = 0.029, p = 0.01). The DA cohort had improved PROMIS Physical Function scores and mHHS up to 5 weeks postoperatively. DA patients discontinued their assistive device 8 days earlier (p = 0.01), left home 3 days earlier (p = 0.001), and drove a car 5 days earlier (p = 0.01). Patients undergoing DA THA discontinued their assistive device, left their home, and drove a car sooner than posterior approach patients. We found improvement in physical function with DA, and it persisted up to 5 weeks postoperatively. Furthermore, DA patients had significantly shorter length of stay, improved mobilisation, decreased narcotic requirements and improved inpatient pain scores compared to posterior approach THA. Future randomised controlled study should be performed to minimise the biases inherent in this study methodology and confirm the results.


How Do Older Adults in a Sub-Saharan African Community Perceive and Cope With Their Disability? An Interpretive Phenomenological Analysis.
Objective: The study explored the perceptions and coping strategies employed by older adults in a Sub-Saharan African community in relation to their disabilities. Methods: The research utilized an Interpretive Phenomenological Analysis methodology and conducted semi-structured interviews with a purposive sample of households. The study recruited a total of 36 older adults aged 65 years and above, aiming to capture a diverse range of insights and perspectives within the Sub-Saharan African community. Results: Three interrelated themes pertaining to the perception of disability emerged: the impact of old age, disabilities caused by diseases, and disabilities attributed to external factors such as witchcraft. In coping with disability, two interrelated themes emerged: pragmatic coping strategies and unpragmatic coping strategies. Conclusion: This study offers valuable insights into the nuanced perception of disability and coping mechanisms utilized by older adults within the Sub-Saharan African community. By exploring their lived experiences, the findings contribute to a better understanding of the challenges they face. These insights have important implications for policy development and public health initiatives.


A serologic survey for Brucella canis in dogs on a military base.
A survey for Brucella canis antibodies in dogs was conducted at an Air Force Base in Missippi in 1976. The rapid slide agglutination test was used as a screening test prior to determination of titers by the standard tube agglutination test. Of 6 sera reacting positively by the slide technique, only 1 was confirmed positive by the tube agglutination technique. The seropositive rate among stray dogs apprehended on the base was 7.6%, whereas the seropositive rate among pet dogs was 0%.


Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease.
Glycosylation represents an important modification that regulates biological processes in tissues relevant for disease pathogenesis in systemic sclerosis (SSc), including the endothelium and extracellular matrix. Whether patients with SSc develop antibodies to carbohydrates is not known. To determine the prevalence and clinical phenotype associated with serum IgG antibodies recognising distinct glycans in patients with SSc. Pooled serum samples from patients with SSc and controls were screened for the presence of specific anticarbohydrate antibodies using a novel array containing over 300 glycans. Antibody titres to 4-sulfated N-acetyl-lactosamine (4S-LacNAc, (4OSO3)Galβ1-4GlcNAc) were determined in 181 individual serum samples from patients with SSc by ELISA and associated with disease phenotype. 4S-LacNAc was identified as a target in pooled SSc serum. Anti-4S-LAcNAc antibodies were detected in 27/181 patients with SSc (14.9%) compared with 1/40 healthy controls (2.5%). Sulfation at position C4 of galactose (4S-LacNAc) was found to be critical for immunogenicity. Anti-4S-LacNAc antibody-positive patients with SSc had a higher prevalence of pulmonary hypertension by echocardiography than anti-4S-LacNAc-negative patients (15/27 (55.7%) vs 49/154 (31.8%), p=0.02) with an OR of 2.6 (95% CI 1.1 to 6.3). Anti-4S-LacNAc-positive patients accounted for 23.4% of all patients with pulmonary hypertension. Serum from patients with SSc contains IgG antibodies targeting distinct sulfated carbohydrates. The presence of anti-4S-LacNAc antibodies is associated with a high prevalence of pulmonary hypertension. These results suggest that specific post-translational carbohydrate modifications may act as important immunogens in SSc and may contribute to disease pathogenesis.


Effects of nebivolol on biomarkers in elderly patients with heart failure.
Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure. In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT-BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour necrosis factor-alpha (TNF-α), serum uric acid (SUA), symmetrical dimethyl arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA) at baseline (before study drug), at 6 months and 12 months in a prespecified substudy. One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample. There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo (P=0.08) and sFas showed a numerical increase in patients on placebo (P=0.08). Mean baseline LVEF was 35% in both groups and at 12 months was 43% on nebivolol group and 34% on placebo group (P=0.01). There were trends but no clear changes associated with nebivolol in neurohormones, cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure. Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure.


[Gastrectomy preserving pylorus and pyloric vagus].
Gastrectomy preserving pylorus and pyloric vagus was done in 32 cases to preventing complications caused by conventional gastric resection. This operation, similar to Billroth I (B-I) and Billroth II (B-II) in reducing acidity, was effective in preventing reflux and dumping syndrome. But the results of this operation were better than those of B-I and B-II according to postoperative gastric emptying test, fat and protein digestion, gastric biopsy, body weight, and patients' general conditions.


Resveratrol protects neuronal-like cells expressing mutant Huntingtin from dopamine toxicity by rescuing ATG4-mediated autophagosome formation.
Parkinsonian-like motor deficits in Huntington's Disease (HD) patients are associated with abnormal dopamine neurotransmission in the striatum. Dopamine metabolism leads to the formation of oxidized dopamine quinones that exacerbates mitochondrial dysfunction with production of reactive oxygen species (ROS) that eventually lead to neuronal cell death. We have previously shown that dopamine-induced oxidative stress triggers apoptotic cell death in dopaminergic neuroblastoma SH-SY5Y cells hyper-expressing the mutant polyQ Huntingtin (polyQ-Htt) protein. Dopamine toxicity was paralleled by impaired autophagy clearance of the polyQ-Htt aggregates. In this study, we found that Dopamine affects the stability and function of ATG4, a redox-sensitive cysteine-protein involved in the processing of LC3, a key step in the formation of autophagosomes. Resveratrol, a dietary polyphenol with anti-oxidant and pro-autophagic properties, has shown neuroprotective potential in HD. Yet the molecular mechanism through which Resveratrol can protect HD cells against DA is not known. Here, we show that Resveratrol prevents the generation of ROS, restores the level of ATG4, allows the lipidation of LC3, facilitates the degradation of polyQ-Htt aggregates and protects the cells from Dopamine toxicity. The present findings provide a mechanistic explanation of the neuroprotective activity of Resveratrol and support its inclusion in a therapeutic regimen to slow down HD progression.