Housing and Health: Here We Go Again.
Housing is one of the major determinants of human health and the current COVID-19 pandemic has highlighted its relevance. The authors summarize the main issues, including dimensional standards, indoor air quality, safety, accessibility, neighborhoods, and area characteristics. The authors propose an operating scheme in order to implement actions to improve residential wellbeing on a local, national, and international level.


Theory of Linear and Nonlinear Surface-Enhanced Vibrational Spectroscopies.
The vibrational spectroscopy of molecules adsorbed on metal nanoparticles can be enhanced by many orders of magnitude so that the detection and identification of single molecules are possible. The enhancement of most linear and nonlinear vibrational spectroscopies has been demonstrated. In this review, we discuss theoretical approaches to understanding linear and nonlinear surface-enhanced vibrational spectroscopies. A unified description of enhancement mechanisms classified as either electromagnetic or chemical in nature is presented. Emphasis is placed on understanding the spectral changes necessary for interpretation of linear and nonlinear surface-enhanced vibrational spectroscopies.


Prevalence of MTD among Patients with Functional Dysphagia.
To assess the prevalence of laryngeal muscle tension patterns among patients with functional dysphagia. Retrospective study. The study took place at a university medical center. The medical charts and laryngeal video recordings were reviewed for all patients who presented with dysphagia and who were referred for barium swallow between 2012 and 2017. A total of 170 cases were identified. Only those with normal findings on barium swallow and the absence of vocal fold pathology (exudative lesions, masses or tumors, paresis, and paralysis), referred to as functional dysphagia, were included in this study. Information retrieved included swallowing and phonatory symptoms in addition to patterns of laryngeal muscle tension. The mean ± SD age of the total group was 41.90 ± 15.10 years with a male:female ratio of 4:1. Seventy-five percent had evidence of at least 1 type of laryngeal muscle tension pattern. The most common pattern was type III, characterized by supraglottic anteroposterior compression (13 of 20), followed by type II, characterized by medial compression of the false vocal folds (5 of 20); only 1 patient had muscle tension pattern type IV, characterized as sphincter-like closure of supraglottic structures. The most common laryngopharyngeal symptom was throat discomfort when swallowing (35%), followed by throat clearing and choking/coughing when eating and drinking (25%). The high prevalence of laryngeal muscle tension pattern among patients with functional dysphagia supports the notion that laryngeal tension may be one of the underlying causes of dysphagia.


Mechanism of reaction of melatonin with human myeloperoxidase.
Recently, it was suggested that melatonin (N-acetyl-5-methoxytryptamine) is oxidized by activated neutrophils in a reaction most probably involving myeloperoxidase (Biochem. Biophys. Res. Commun. (2000) 279, 657-662). Myeloperoxidase (MPO) is the most abundant protein of neutrophils and is involved in killing invading pathogens. To clarify if melatonin is a substrate of MPO, we investigated the oxidation of melatonin by its redox intermediates compounds I and II using transient-state spectral and kinetic measurements at 25 degrees C. Spectral and kinetic analysis revealed that both compound I and compound II oxidize melatonin via one-electron processes. The second-order rate constant measured for compound I reduction at pH 7 and pH 5 are (6.1 +/- 0.2) x 10(6) M(-1) s(-1) and (1.0 +/- 0.08) x 10(7) M(-1) s(-1), respectively. The rates for the one-electron reduction of compound II back to the ferric enzyme are (9.6 +/- 0.3) x 10(2) M(-1) s(-1) (pH 7) and (2.2 +/- 0.1) x 10(3) M(-1) s(-1) (pH 5). Thus, melatonin is a much better electron donor for compound I than for compound II. Steady-state experiments showed that the rate of oxidation of melatonin is dependent on the H(2)O(2) concentration, is not affected by superoxide dismutase, and is quickly terminated by sodium cyanide. Melatonin can markedly inhibit the chlorinating activity of MPO at both pH 7 and pH 5. The implication of these findings in the activated neutrophil is discussed.


Identification of multipotent progenitors in the embryonic mouse kidney by a novel colony-forming assay.
Renal stem or progenitor cells with a multilineage differentiation potential remain to be isolated, and the differentiation mechanism of these cell types in kidney development or regeneration processes is unknown. In an attempt to resolve this issue, we set up an in vitro culture system using NIH3T3 cells stably expressing Wnt4 (3T3Wnt4) as a feeder layer, in which a single renal progenitor in the metanephric mesenchyme forms colonies consisting of several types of epithelial cells that exist in glomeruli and renal tubules. We found that only cells strongly expressing Sall1 (Sall1-GFP(high) cells), a zinc-finger nuclear factor essential for kidney development, form colonies, and that they reconstitute a three-dimensional kidney structure in an organ culture setting. We also found that Rac- and JNK-dependent planar cell polarity (PCP) pathways downstream of Wnt4 positively regulate the colony size, and that the JNK pathway is also involved in mesenchymal-to-epithelial transformation of colony-forming progenitors. Thus our colony-forming assay, which identifies multipotent progenitors in the embryonic mouse kidney, can be used for examining mechanisms of renal progenitor differentiation.


Cotranscription of the electron transport protein genes nifJ and nifF in Enterobacter agglomerans 333.
A nucleotide sequence showing extensive homology to the nifF gene, which codes for a flavodoxin involved in nitrogen fixation in Klebsiella pneumoniae, was localized on the plasmid pEA3 of Enterobacter agglomerans and determined. The analysis of transcriptional fusions, as well as transcript protection assays, indicated a novel nif gene organization, that is, the cotranscription of nifJ and nifF.


Factors affecting the potentiometric response of all-solid-state solvent polymeric membrane calcium-selective electrode for low-level measurements.
An all-solid-state calcium-selective electrode was constructed with poly(pyrrole) solid-contact doped with calcium complexing ligand Tiron. The potentiometric response of this sensor can have a linear range down to 10(-)(9) M with a slope close to Nernstian and detection limit equal to 10(-)(9.6). The effects of pH and the activity of the interfering ion in the conditioning solution on the potentiometric behavior of the constructed sensors were examined. Potential stability, reproducibility, and impedance studies were performed. The selectivity of the constructed electrode is better than that of the conventional calcium-selective electrode with internal filling solution of 10(-)(2) M CaCl(2) and comparable to that of the best liquid-contact electrodes.


Prevalence of Interictal Epileptiform Discharges in Children Less Than One Year of Age Referred for Polysomnography.
This study aimed to identify the prevalence of interictal epileptiform discharges (IEDs) in patients less than one year of age referred for polysomnogram (PSG), to quantify the number of IEDs and characterize sleep stage(s) during which IEDs occur, and to relate the reason for PSG referral and IED frequency. This was a retrospective cohort study of children less than 12 months of age referred for PSG studies. Fifty study participants had sufficient EEG data, and 49 were included in the study analysis. We identified an IED prevalence rate of 28% over the 2-year study period. The mean number (Standard Deviation; SD) of IEDs per hour of total sleep time was 0.4 (1.2). IEDs occurred most frequently in non-rapid eye movement (NREM) stages 2 and 3 of sleep. The most common reason for PSG referral in this patient cohort was for obstructive sleep apnea (OSA) (42/50). We concluded that patients less than 12 months of age referred for PSG may have abnormal brain activity. The relationship of that activity to PSG findings is unclear. This study offers a systematic process of identifying IEDs that should prompt referral to a neurologist for further evaluation.


Impact of perimenopausal symptomatology on quality of life in Mongolian women.
This cross-sectional study focussed on perimenopausal Mongolian women and aimed to determine the quality of life (QOL) and risk factors in this population. We collected data on 392 women using a predesigned questionnaire and classified the participants according to menopausal status. We used The Menopause Rating Scale (MRS) and the World Health Organisation Quality of Life (WHOQOL)-BREF. Blood pressure (p = .003) and body mass index (p = .02) were significantly high, whereas sexual activity was significantly decreased in postmenopausal women (p = .001). In perimenopausal women, somatovegetative (p = .003) and psychological (p = .025) symptoms were significantly severe, and menopausal symptom severity was significantly higher (p = .017). Menopausal symptoms (p = .02) and monthly sexual activity (p = .005) significantly influenced overall QOL. Sexuality had a significantly negative effect on psychological health (p = .03). Age, occupation, menopausal stage and somatovegetative symptoms have significant effects on health-related QOL (p< .05). Our findings showed that menopausal symptoms and sexual activity significantly affect QOL in middle-aged Mongolian women.Impact StatementWhat is already known on this subject? Women experience physiological changes at the onset of menopause. However, as their oestrogen levels decline, many women also experience physical, psychological and somatovegetative symptoms. Postmenopausal health has been the main issue affecting middle-aged women, until recently. Here, we showed that menopausal transition is a turning point for middle-aged women and suggest that more attention should be paid to the health of perimenopausal women in Mongolia.What do the results of this study add? The study results showed that perimenopausal women had a higher prevalence of health-related problems than postmenopausal women, including weight gain, cardiovascular symptoms and vasomotor symptoms. The prevalence of genitourinary health problems increased with age.What are the implications of these findings for clinical practice and/or further research? General practitioners and gynaecologists in Mongolia should acquire a better understanding of the physiological changes that occur during menopause and pay greater attention to genitourinary issues as they affect general, health-related quality of life.


Na:K pump abundance and function in MDCK cells: effect of low ambient potassium.
Side-specific expression and activity of Na:K pump was studied in Madin-Darby canine kidney (MDCK) cells, a tissue culture model of distal renal tubular epithelium, exposed to low ambient potassium. Confluent monolayers grown on teflon filters in dual chambers were treated with a low K+ medium from 45 min to 72 h. After both acute (45 min) and longer-term (24-72 h) exposure to low K+ (0.7 mM), cation cycling rate of existing pump units increased substantially, while there was no significant change in total cell Na-K-ATPase activity or in basolateral surface pump density. Although a small quantity of Na:K pumps (less than 10%) was consistently present apically, it also did not increase after exposure to low K+, or when the monolayers were provided K+ only from the apical side. In MDCK monolayers low K+ enhances the rate of K+ uptake by the existing pump units but does not increase the total number of pumps or their deployment on either cell surface.


Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?
Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of 'omics' technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment.


Behind Closed Doors: Individual and Joint Pornography Use Among Romantic Couples.
Most previous research on the associations between pornography use and relational well-being has utilized individual data sets that have limited scholars' ability to truly understand the dyadic nature of pornography use within romantic couples. Using a dyadic data set of 240 committed heterosexual couples from the United States, we explored actor and partner associations between pornography use, sexual dynamics, and relational well-being. We also explored how couple pornography use and partner knowledge of pornography use were associated with well-being. Results suggested that female pornography use was associated with higher female sexual desire but no other dependent variables. Male pornography use was associated with a wide array of negative well-being indicators, including less male and female relationship satisfaction, lower female sexual desire, and lower male positive communication. Couple pornography use was associated with higher reported sexual satisfaction for both partners but no other well-being indicators. Partner knowledge of use had little direct association with well-being, but some evidence suggested that unknown individual use may be associated with less sexual satisfaction but more relationship satisfaction. Results suggest that different configurations of use among heterosexual couples are associated with varying relational well-being indicators.


Physical and mental correlates of hearing impairment in the elderly in Japan.
Seven hundred and forty seven elderly people aged from 65 to 98 (209 male and 538 female) admitted to the Geriatric Health Service Facility were evaluated with pure-tone audiometry, Office of Population Censuses and Surveys (OPCS) personal care severity score, OPCS hearing severity score, Mini-mental State Examination (MMSE) and Self-rating Depression Scale (SDS). A single correlation study indicated that the hearing level significantly correlated with age, OPCS hearing severity score, MMSE total score and SDS total score. A multiple regression analysis showed that age, OPCS hearing severity score, and MMSE total score were significantly associated with the hearing level. We demonstrated here that the objective auditory function strongly correlated with the cognitive function measured by MMSE total score, suggesting that a regular audiological check-up and the early detection of the hearing impairment could contribute to the maintenance of the quality of life in the elderly.


Efficacy and safety of adding fenofibrate 160 mg in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy.
Patients with mixed hyperlipidemia and at high risk of coronary heart disease may not achieve recommended low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol goals on statin monotherapy. This study was designed to evaluate the efficacy and safety of a fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy in high-risk patients not at their LDL cholesterol goal on pravastatin 40 mg. In this 12-week, multicenter, randomized, double-blind, double-dummy, parallel-group study, after a run-in on pravastatin 40 mg, 248 patients were randomly assigned to fenofibrate/pravastatin combination therapy or to pravastatin monotherapy. Combination therapy produced significantly greater complementary decreases in non-HDL cholesterol (primary end point) than pravastatin monotherapy (-14.1% vs -6.1%, p = 0.002). Significantly greater improvements were also observed in LDL cholesterol (-11.7% vs -5.9%, p = 0.019), HDL cholesterol (+6.5% vs +2.3%, p = 0.009), triglycerides (-22.6% vs -2.0%, p = 0.006), and apolipoprotein B (-12.6% vs -3.8%, p <0.0001). Significantly more patients receiving the fenofibrate/pravastatin combination therapy than pravastatin alone achieved the LDL cholesterol (<100 mg/dl) and non-HDL cholesterol (<130 mg/dl) goals (p <0.01). Combination therapy was generally well tolerated with incidences of clinical and laboratory adverse experiences similar between the 2 groups. In conclusion, the fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy significantly improved the global atherogenic lipid profile in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy.


Topical antimicrobial therapy in the prevention of early childhood caries.
Early childhood caries (ECC) is microbiologically characterized by heavy infection of mutans streptococci (ms) on dental surfaces. Accordingly, it is reasonable to speculate that suppression of dental ms levels would decrease risk for ECC. On this basis, randomized double blind, placebo controlled pilot study was performed to test this concept. The study population consisted of 31 subjects (age: 12 to 19 mos; sex: 18F/13M) who were clients of a Women, Infants, and Children (WIC) clinic in Puerto Rico. Inclusion criteria included: (1) unremarkable medical history; (2) presence of 4 maxillary primary incisors (PMI) with no visible defects; (3) clinically caries free; (4) use of a nursing bottle at naptime and/or bedtime which contained a cariogenic substrate; (5) two consecutive ms positive cultures (utilizing Mitis-Salivarius-Bacitracin (MSB) agar) from pooled PMI plaque. The subjects were randomized into 2 groups. The 15 subjects in the experimental group and the 16 subjects in the control group were evaluated every 2 months during the study period. At each evaluation, the subjects had 10% povidone iodine (experimental group) or placebo (control group) applied to their dentition. The placebo was commercial instant tea (without lemon or sweetener) and deionized water. Treatment failure was defined as the appearance of a white spot lesion(s) on any of the PMI during the study period. The mean duration of observation to treatment failure was 155 days; the mean duration of observation for treatment success was 217 days. Five of the 16 control subjects and 0 of the 15 experimental subjects experienced treatment failure (Fisher's exact test: P = 0.04). The Kaplan-Meier estimate for incidence of treatment failure in the placebo group was 48% over 357 days (P = 0.02). These observations suggest that topical antimicrobial therapy reduces risk for the development of ECC in high-risk children.


[Occupation-specific illnesses in musicians].
Performance-related disorders in musicians are most often caused by multiple risk factors. They are based on the chronic complex, rapid and forceful work that requires highest precision, as well as on poor ergonomic conditions and psychological strain. Predominantly, the musculo-skeletal system of the upper extremity and the spine is affected by acute or chronic pain syndromes and neurological disorders. Stage fright and psychological tension frequently generate somatoform disorders and may contribute to the chronification of physical disabilities in musicians. Depending on the individual characteristics, the actual professional activity and the specific instrument, the performance-related risk factors and disorders differ widely. Early and regular prevention clearly contributes to a reduction of medical problems in musicians.


Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum.
Corynebacterium glutamicum is a biotin auxotrophic bacterium in which glutamate production is induced under biotin-limited conditions. During glutamate production, anaplerotic reactions catalyzed by phosphoenolpyruvate carboxylase (PEPC) and a biotin-containing enzyme pyruvate carboxylase (PC) are believed to play an important role in supplying oxaloacetate in the tricarboxylic acid cycle. To understand the distinct roles of PEPC and PC on glutamate production by C. glutamicum, we observed glutamate production induced under biotin-limited conditions in the disruptants of the genes encoding PEPC (ppc) and PC (pyc), respectively. The pyc disruptant retained the ability to produce high amounts of glutamate, and lactate was simultaneously produced probably due to the increased intracellular pyruvate levels. On the other hand, the ppc knockout mutant could not produce glutamate. Additionally, glutamate production in the pyc disruptant was enhanced by overexpression of ppc rather than disruption of the lactate dehydrogenase gene (ldh), which is involved in lactate production. Metabolic flux analysis based on the 13C-labeling experiment and measurement of 13C-enrichment in glutamate using nuclear magnetic resonance spectroscopy revealed that the flux for anaplerotic reactions in the pyc disruptant was lower than that in the wild type, concomitantly increasing the flux for lactate formation. Moreover, overexpression of ppc increased this flux in both the pyc disruptant and the wild type. Our results suggest that the PEPC-catalyzed anaplerotic reaction is necessary for glutamate production induced under biotin-limited conditions, because PC is not active during glutamate production, and overexpression of ppc effectively enhances glutamate production under biotin-limited conditions.


Initial increase in blood CD4(+) lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues.
Previous studies proposed a dynamic, steady-state relationship between HIV-mediated cell killing and T-cell proliferation, whereby highly active antiretroviral therapy (HAART) blocks viral replication and tips the balance toward CD4(+) cell repopulation. In this report, we have analyzed blood and lymph node tissues obtained concurrently from HIV-infected patients before and after initiation of HAART. Activated T cells were significantly more frequent in lymph node tissue compared with blood at both time points. Ten weeks after HAART, the absolute number of lymphocytes per excised lymph node decreased, whereas the number of lymphocytes in the blood tended to increase. The relative proportions of lymphoid subsets were not significantly changed in tissue or blood by HAART. The expression levels of mRNA for several proinflammatory cytokines (IFN-gamma, IL-1beta, IL-6, and macrophage inflammatory protein-1alpha) were lower after HAART. After therapy, the expression of VCAM-1 and ICAM-1 -- adhesion molecules known to mediate lymphocyte sequestration in lymphoid tissue -- was also dramatically reduced. These data provide evidence suggesting that initial increases in blood CD4(+) cell counts on HAART are due to redistribution and that this redistribution is mediated by resolution of the immune activation that had sequestered T cells within lymphoid tissues.


Research agendas.
WHILE EACH ARTICLE IN THIS ISSUE OF JERHRE raises important questions that call for empirical research, one article-the editorial-subsumes all issues raised by the rest of the articles herein. It is a call to make full use of the allowed freedom to design an improved system of ethical problem solving and ethical oversight in human research. Being an ethical researcher is often cast in terms of compliance with ethics committee rules. In some contexts those rules, inflexibly applied, may cause unnecessary delay, damage and hindrance to important research projects. Stated otherwise, they may impose unethical requirements on research. Yet it is the very inaction or compliance of researchers and research administrators that causes us to fail to help create systems of research oversight that work-that foster valid and ethical research and advance human society.


Complications after early surgery for congenital cataracts.
To study the type and frequency of complications requiring additional surgery in infants operated on for congenital cataract before 12 months of age. The medical records of 57 infants who underwent surgery for unilateral and bilateral congenital cataracts during a five-year-period were reviewed retrospectively. The follow-up period ranged from 9 to 70 months with a mean of 37 months. Cataract extraction was performed on 83 eyes. Thirty-eight operations for after-cataracts were performed on 32 out of 83 eyes. Fourteen vitrectomies were made on 11 eyes because of pupillary block glaucoma. Glaucoma requiring trabeculectomy developed in eight eyes 2 to 14 months after cataract extraction. This type of glaucoma occurred almost exclusively in eyes operated on during the first two months of life. Complications requiring additional surgery are very common in infants operated on for congenital cataracts during the first year of life. Glaucoma requiring trabeculectomy developed particularly in infants who had their cataract extraction very early. Glaucoma development was not more common in infants operated on for after-cataract.


Comparison of Clinical, Functional, and Radiological Outcomes of Total Knee Arthroplasty Using Conventional and Patient-Specific Instrumentation.
Recently, patient-specific instrumentation (PSI) systems have been developed in order to increase the accuracy of component positioning during total knee arthroplasty (TKA); however, the findings of previous studies are controversial in this regard. In the current randomized clinical study, the outcomes of computer tomography (CT)-based PS (patient specific)-guided TKA were compared to the results of conventional instrumentation (CVI) TKA. The guides were designed on the basis of distal femoral and proximal tibial pin orientation of the conventional related guides. The present study was carried out on 24 TKA candidates randomly assigned to two PSI (n=12) and CVI (n=12) groups. The patients were postoperatively followed for 2 years. Then, the hip-knee-ankle angle (HKAA), femoral component flexion, and orientation of components in the coronal plane were measured. In addition, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Knee Society Score (KSS) questionnaire were completed for all the patients. The rate of the outliers of the HKAA was higher in the CVI group (41.7% and 8.3%; P=0.077); nevertheless, the difference was not significant in this regard. The rate of the outliers of other radiographic measurements and operational time were similar in both groups. Furthermore, there was no significant difference between the two groups in terms of the WOMAC and KSS. The CT-based PS-guided TKA may result in the improved postoperative mechanical alignment of the limb and should be considered in complicated TKAs. However, future studies should investigate whether the results of PSI TKA support the considerably higher costs of this technique.


Effects of variety and storage duration on the nutrient digestibility and the digestible and metabolisable energy content of maize fed to growing pigs.
The objective of this research was to determine the effects of variety and storage duration on the nutrient digestibility and the digestible (DE) and metabolisable (ME) energy content in maize when fed to growing pigs. Four maize varieties (LS1, LS2, LS3 and LS4) were hand-harvested from the same growing area in China in early October of 2012. The samples were sun dried to about 14% moisture content and then stored in the warehouse of the Fengning Pig Experiment Base at China Agricultural University for 0, 3 or 10 months. Twenty-four barrows of about 33 kg body weight were used and allotted to a completely randomised block design with four diets and six replicate pigs per diet. Pigs were individually housed in metabolic crates. The four experimental diets were formulated by mixing 96.8% of each variety of maize with 3.2% vitamins and minerals. A 5-day collection period followed a 7-day diet acclimation period. The results indicated that the DE and ME contents of maize and the apparent total tract digestibility (ATTD) of organic matter (OM), dry matter, gross energy (GE), neutral detergent fibre, acid detergent fibre (ADF), crude protein (CP) and ether extract (EE) were significantly (p < 0.05) influenced by maize variety and storage duration. With an extension of storage duration from 0 to 10 months, the DE and ME of maize and the ATTD of OM, GE, ADF, CP and EE changed in a quadratic manner (p < 0.05), and 3 months of storage exceeded 0 months of storage by 1.84%, 1.43%, 0.31%, 0.32%, 15.37%, 2.11% and 5.02%, respectively. The DE, ME of maize and the ATTD of OM, GE, ADF, CP and EE decreased by 3.67%, 6.00%, 0.97%, 1.40%, 30.54%, 3.92% and 20.93%, respectively, at 10 months of storage compared to 3 months of storage. No interaction was observed between maize variety and storage duration in DE and ME contents in maize. In conclusion, under the conditions of this study, most of the nutrient digestibility and the DE and ME contents of maize increased from 0 to 3 months and decreased from 3 to 10 months.


Gel-Based Luminescent Conductive Materials and Their Applications in Biosensors and Bioelectronics.
The gel is an ideal platform for fabricating materials for bio-related applications due to its good biocompatibility, adjustable mechanical strength, and flexible and diversified functionalization. In recent decades, gel-based luminescent conductive materials that possess additional luminescence and conductivity simultaneously advanced applications in biosensors and bioelectronics. Herein, a comprehensive overview of gel-based luminescent conductive materials is summarized in this review. Gel-based luminescent conductive materials are firstly outlined, highlighting their fabrication methods, network structures, and functions. Then, their applications in biosensors and bioelectronics fields are illustrated. Finally, challenges and future perspectives of this emerging field are discussed with the hope of inspire additional ideas.


Effects of a reduced-visit prenatal care clinical practice guideline.
A prenatal care guideline that decreased scheduled visits to 9 was introduced at a military community hospital in 2000. We hypothesized patients would have fewer clinic visits with no difference in maternal and neonatal outcomes under the new schedule. We designed a retrospective cohort study involving patients who delivered after 20 weeks gestation during 1999 (1647) and 2000 (1710). We measured the number of antenatal visits to clinic and labor and delivery (L&D) per patient. We assessed maternal and neonatal outcomes. Power was adequate to detect a 25-g change in birth weight. Descriptive, chi(2), and t test statistics were used. The number of prenatal visits decreased from 10.9 +/- 2.8 to 9.2 +/- 2.6 (P < .001) per patient. Outpatient visits to L&D increased by 31 per month, P = .01. Post-term deliveries decreased from 10.4 to 8.1%, P = .01. Maternal and neonatal outcomes did not decline. Patient satisfaction did not change. Application of the prenatal care guideline was associated with a reduction in prenatal visits but a small increase in L&D visits that did not persist after the initial year. No adverse perinatal or patient satisfaction outcomes were noted. This guideline is efficient in delivering prenatal care with no changes in perinatal outcomes or patient satisfaction.


Regulating Histone Deacetylase Signaling Pathways of Myeloid-Derived Suppressor Cells Enhanced T Cell-Based Immunotherapy.
Immunotherapy has emerged as a promising approach to combat immunosuppressive tumor microenvironment (TME) for improved cancer treatment. FDA approval for the clinical use of programmed death receptor 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors revolutionized T cell-based immunotherapy. Although only a few cancer patients respond to this treatment due to several factors including the accumulation of immunosuppressive cells in the TME. Several immunosuppressive cells within the TME such as regulatory T cells, myeloid cells, and cancer-associated fibroblast inhibit the activation and function of T cells to promote tumor progression. The roles of epigenetic modifiers such as histone deacetylase (HDAC) in cancer have long been investigated but little is known about their impact on immune cells. Recent studies showed inhibiting HDAC expression on myeloid-derived suppressor cells (MDSCs) promoted their differentiation to less suppressive cells and reduced their immunosuppressive effect in the TME. HDAC inhibitors upregulated PD-1 or PD-L1 expression level on tumor or immune cells sensitizing tumor-bearing mice to anti-PD-1/PD-L1 antibodies. Herein we discuss how inhibiting HDAC expression on MDSCs could circumvent drawbacks to immune checkpoint inhibitors and improve cancer immunotherapy. Furthermore, we highlighted current challenges and future perspectives of HDAC inhibitors in regulating MDSCs function for effective cancer immunotherapy.


[Risk factors for short-term outcome of patients with HBV-related acute-on-chronic liver failure].
To investigate the risk factors for the short-term outcome of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and to establish a risk model for predicting the short-term outcome of these patients. A total of 338 patients with HBV-related ACLF who were admitted to 30 Lod hospital of PLA hospital from January 2010 to January 2014 were enrolled, and a prospective clinical follow-up was performed for them. Multivariate logistic regression was used to determine the risk factors for short-term (12 weeks) outcome, the predictive model with logistic regression equation was established, and the predictive value of this model was evaluated. The multivariate logistic regression analysis showed that age, a family history of hepatitis B, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), white blood cell (WBC), platelet (PLT), international normalized ratio (INR), total bilirubin (TBil), total bile acid (TBA), creatinine, Na, HBV DNA, and HBeAg were the independent risk factors for the short-term outcome of these patients. Logistic(p) = -4.466 + 1.192 age + 1.631 family history of hepatitis B + 1.091 HE + 1.631 HRS + 1.208 WBC -1.487 PLT + 1.092 INR + 1.446 TBil + 1.608 TBA -1.101 CHE + 1.279 CRE -1.713 Na + 1.032 HBV DNA + 0.833 HBeAg. The area under the receiver operating characteristic curve of the model for the prediction of short-term outcome was 0.930, the cut-off value was 3.16, the sensitivity was 0.860, and the specificity was 0.871. With the increasing scores of the equation, the mortality of patients tended to increase gradually. Age, a family history of hepatitis B, HE, HRS, WBC, PLT, INR, TBil, TBA, CHE, CRE, Na, HBV DNA, and HBeAg are the independent risk factors for the short-term outcome of patients with HBV-related ACLF. The model for predicting short-term outcome established on the basis of independent risk factors has a better clinical value in guiding clinical therapy.


Constructing universal multiplex PCR systems for comparative genotyping.
Analysis of length polymorphisms at STR loci in the human genome has become a standard approach for comparative genotyping in many areas including disease research and diagnostics, parentage assessment, investigations of human diversity, and forensic science. The simultaneous analysis of multiple STR loci through multiplex PCR and multicolor fluorescence detection offers sample conservation, high throughput, and automated genetic analysis. Careful design and optimization of tetranucleotide STR multiplexes has led to reliable, standardized systems that powerfully differentiate and distinguish individual human DNA profiles. The development of these multiplex systems involved a rigorous experimental strategy that included careful selection of PCR primer sequences (for yield, specificity, and multiplex compatability), along with optimization of PCR component concentrations, thermal cycling parameters, and fluorescence detection conditions. This developmental approach rendered well-characterized DNA typing systems that are high performing (sensitive, specific, and balanced), optimized to universal parameters (same reaction conditions), resilient to fluctuations in reaction conditions, and simple to implement and use routinely.


Nurse's Knowledge of Neuropathic Pain.
The aim of our study was to determine the levels of information and awareness of the nurses who work on neuropathic pain in the departments of physical medicine and rehabilitation, neurology and neurosurgery. A total of 60 nurses (20 per each department) who work in the physical medicine and rehabilitation, neurology and neurosurgery departments of Beyhekim State Hospital of Konya in Turkey took part in the study. The level of information and awareness of the nurses on neuropathic pain were assessed via a questionnaire prepared by specialists in the light of recent literature. The questionnaire was composed of 30 questions including the definition, symptoms, treatment and management of neuropathic pain. None of 60 nurses participating in the study were given any previous in-service training on neuropathic pain. According to the assessments, 80% of nurses (48) were found not to have sufficient knowledge about definition of neuropathic pain; 83.3% (50) about diseases causing neuropathic pain; 83.3% (50) about symptoms of neuropathic pain; and 90% (54) about management of neuropathic pain. The findings obtained from the nurses of these three departments showed no statistically significant relation. Our findings indicated that the knowledge of participants' about neuropathic pain who work in these three departments seriously lack of information. Informing nurses about neuropathic pain during in-service training will be an important step towards improving the quality of services provided.


Perceptual functions in prosopagnosia.
Some patients with prosopagnosia may have an apperceptive basis to their recognition defect. Perceptual abnormalities have been reported in single cases or small series, but the causal link of such deficits to prosopagnosia is unclear. Our goal was to identify candidate perceptual processes that might contribute to prosopagnosia, by subjecting several prosopagnosic patients to a battery of functions that may be necessary for accurate facial perception. We tested seven prosopagnosic patients. Three had unilateral right occipitotemporal lesions, two had bilateral posterior occipitotemporal lesions, and one had right anterior-to-occipital temporal damage along with a small left temporal lesion. These lesions all included the fusiform face area, in contrast to one patient with bilateral anterior temporal lesions. Most patients had impaired performance on face-matching tests and difficulty with subcategory judgments for non-face objects. The most consistent deficits in patients with lesions involving the fusiform face area were impaired perception of spatial relations in dot patterns and reduced contrast sensitivity in the 4 to 8 cycles deg(-1) range. Patients with bilateral lesions were impaired in saturation discrimination. Luminance discrimination was normal in all but two patients, and spatial resolution was uniformly spared. Curvature and line-orientation discrimination were impaired in only one patient, who also had the most difficulty with more basic-level object recognition. We conclude that deficits in luminance, spatial resolution, curvature, line orientation, and contrast at low spatial frequencies are unlikely to contribute to apperceptive prosopagnosia. More relevant may be contrast sensitivity at higher spatial frequencies and the analysis of object spatial structure. Deficits in these functions may impair perception of subtle variations in object shape, and may be one mechanism by which the recognition defect in prosopagnosia can extend to other classes of object subcategorization.


Effect of early mobilisation after skin grafting to lower limbs.
We undertook a prospective, randomised study of 50 consecutive patients admitted for split-thickness skin grafting to the lower extremities below the inguinal ligament. All types of wounds and skin defects were included. Postoperatively, 25 patients were randomised to early mobilisation and 25 were confined to bed for four days postoperatively. Otherwise the two groups were treated in exactly the same way. Fourteen days postoperatively the healing of the grafts was assessed by two nurses who did not know whether the patients had been mobilised early or late. The overall primary healing rate of the grafts in patients who had been mobilised early was 20/25 (80%), which did not differ from that among patients who were mobilised late (22/25) (88%). We therefore recommend early mobilisation for both economic and humanitarian reasons.


Thermostability of membrane systems in organic solvents.
Two multisubunit enzymes of the inner mitochondrial membrane, cytochrome oxidase and the H+-ATPase may be transferred into highly apolar solvents as protein-lipid complexes. At 70 degrees C and an initial water concentration of 13 microliters per ml organic solvent (toluene), the half-life of the ATPase was approx. 11 h, whereas that of cytochrome oxidase was about 100 s. Thermostability of cytochrome oxidase could be increased more than 100-times by decreasing the water concentration to 3 microliters per ml toluene. At this latter concentration of water the half-life of the ATPase at 90, 80 and 70 degrees C was 5, 48 and 96 h, respectively.


Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.
Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.


Semicylindrical acoustic transducer from a dielectric elastomer film with compliant electrodes.
A semicylindrical acoustic transducer was constructed using a dielectric elastomer film with compliant electrodes that is an electroactive polymer composed of a polyurethane elastomer base and polyethylene dioxythiophene/polystyrene sulfonate electrodes. The use of this dielectric elastomer is advantageous because polyurethane is a common material that keeps its shape without any rigid frame. Because the dielectric elastomer films are essentially incompressible, electric-field-induced thickness changes are usually translated into much larger changes of the film area and side length. Here it is proposed that this change in side length can be utilized for sound generation when the film is bent into a semicylindrical shape. Accordingly, a semicylindrical acoustic transducer was fabricated using a film of thickness of 300 μm and its acoustic characteristics were investigated. The transducer can be operated at low applied voltages by reducing the film thickness, as long as the film is thick enough to generate sufficient force to overcome sound radiation impedance. The second harmonic distortion of the transducer was also investigated as a function of the ratio of the direct current bias voltage to the alternating current audio signal amplitude.


Discovery of Novel Allosteric HCV NS5B Inhibitors. 2. Lactam-Containing Thiophene Carboxylates.
Lomibuvir (1) is a non-nucleoside, allosteric inhibitor of the hepatitis C virus NS5B polymerase with demonstrated clinical efficacy. Further development efforts within this class of inhibitor focused on improving the antiviral activity and physicochemical and pharmacokinetic properties. Recently, we reported the development of this series, leading to compound 2, a molecule with comparable potency and an improved physicochemical profile relative to 1. Further exploration of the amino amide-derived side chain led to a series of lactam derivatives, inspired by the X-ray crystal structure of related thiophene carboxylate inhibitors. This series, exemplified by 12f, provided 3-5-fold improvement in potency against HCV replication, as measured by replicon assays. The synthesis, structure-activity relationships, in vitro ADME characterization, and in vivo evaluation of this novel series are discussed.


Polymeric Materials for Conversion of Electromagnetic Waves from the Sun to Electric Power.
Solar photoelectric energy converted into electricity requires large surface areas with incident light and flexible materials to capture these light emissions. Currently, sunlight rays are converted to electrical energy using silicon polymeric material with efficiency up to 22%. The majority of the energy is lost during conversion due to an energy gap between sunlight photons and polymer energy transformation. This energy conversion also depends on the morphology of present polymeric materials. Therefore, it is very important to construct mechanisms of highest energy occupied molecular orbitals (HOMO)s and the lowest energy unoccupied molecular orbitals (LUMO)s to increase the efficiency of conversion. The organic and inorganic solar cells used as dyes can absorb more photons from sunlight and the energy gap will be less for better conversion of energy to electricity than the conventional solar cells. This paper provides an up-to-date review on the performance, characterization, and reliability of different composite polymeric materials for energy conversion. Specific attention has been given to organic solar cells because of their several advantages over others, such as their low-energy payback time, conversion efficiency and greenhouse emissions. Finally, this paper provides the recent progress on the application of both organic and inorganic solar cells for electric power generations together with several challenges that are currently faced.


Posterior embryotoxon may not be a forme fruste of Axenfeld-Rieger's Syndrome.
Axenfeld-Rieger Syndrome is a disorder of morphogenesis which is autosomal dominantly inherited. One of the main ocular features associated with Axenfeld-Rieger is posterior embryotoxon, which is a prominent anteriorly displaced Schwalbe's line. This can be found in up to 15% of normal eyes, without any clinical significance or may represent a forme fruste of an anterior segment dysgenesis. Many large case series studies of Axenfeld-Rieger had used the presence of posterior embryotoxon with iris strands extending from the peripheral iris to Schwalbe's line, as inclusion criterion for this condition. We report a case of Axenfeld-Rieger syndrome without posterior embryotoxon and the abnormalities of the angle, but with other features to support the diagnosis of Axenfeld-Rieger Syndrome.


Predicting a target exercise heart rate that reflects the anaerobic threshold in nonbeta-blocked hemodialysis patients: The Karvonen and heart rate reserve formulas.
The aim of this study was to evaluate constants of the Karvonen (k) and heart rate reserve (HRR) (α) formulas that correspond to the anaerobic threshold (AT) to conveniently estimate the intensity of exercise therapy in nonbeta-blocked patients undergoing hemodialysis. Twenty-three patients undergoing hemodialysis performed cardiopulmonary exercise testing (CPX) and their HR at AT was measured. The predictor coefficients for a target HR corresponding to AT were calculated for each patient based on CPX. Interclass correlation coefficients (ICC) and Bland-Altman analysis were used to evaluate the reliability of the formulas. Mean values of coefficient k of the Karvonen formula and α of the HRR formula were 0.24 ± 0.11 and 17.4 ± 8, respectively. The target HR calculated with k = 0.24 and α = 17 had significant ICC between HR at AT (0.74 and 0.77, respectively; P < 0.05). Using the Karvonen and HRR formulas to determine a target HR corresponding to AT is a simple and easy method that can be used to develop exercise programs for hemodialysis patients.


Combined oral contraceptives do not influence post-exercise hypotension in women.
The aim of the present study was to examine the pattern of cardiovascular recovery from exercise in 15 women (age, 20.3 +/- 1.4 years; body mass, 61.5 +/- 4.3 kg) across two phases of oral contraceptive (OC) use: 21 days of consumption and 7 days of withdrawal. Cardiovascular recovery was measured in the supine position for 60 min following 30 min of exercise at 60% maximal rate of oxygen consumption (VO2,max). Central and peripheral haemodynamics were assessed during consumption and withdrawal of the OC pill using occlusion plethysmography, Doppler flowmetry and echocardiography. Significant hypotension occurred following exercise (P < 0.05), returning to baseline values after 60 min. The peak hypotension occurred 5 min into recovery. Cardiac output and heart rate were elevated for 60 min following exercise (P < 0.05), whilst stroke volume remained at baseline values. Heart rate was greater throughout recovery during consumption compared to withdrawal (P < 0.05); however, although there was a trend for greater responses during consumption, phase of OC use did not affect the other central cardiovascular variables (P > 0.05). Post-exercise blood flow parameters were not significantly affected by exercise or OC phase; however, calf blood flow was greater, and resistance to flow lower during consumption (P > 0.05). The pattern of post-exercise fluctuations in cardiovascular parameters may differ from those seen in men, whilst oestrogen variation may influence research findings.


[Prolonged abdominal discomfort, ascites and pleural fluid].
A 67-year-old man had been examined for 1.5 years for hypersedimentation, abdominal discomfort and pleural effusion, but the cause had remained unclear. With progressive weight loss the patient was admitted to the ward for examinations, whereupon the diagnosis of a rare disease began to unravel.


Vinyl chloride-specific mutations in humans and animals.
Vinyl chloride is a potent hepatocarcinogen which reacts with DNA to generate etheno bases. In order to determine whether mutational patterns in target genes in vivo are characteristic of vinyl chloride and could be explained by the mutagenic properties of the etheno bases, human and rat liver tumours associated with exposure to vinyl chloride were analysed for point mutations in the ras and p53 genes. In this paper, we review these data and report our latest results on animal tumours. Two alterations were found which could be attributed to a direct effect of vinyl chloride: a GC-->AT transition which leads to a GGC-->GAC mutation at codon 13 of the Ki-ras gene in human liver angiosarcomas, and lesions at AT base pairs, mostly AT-->TA transversions, which lead to mutations in the p53 gene in human and rat angiosarcomas and to a CAA-->CTA mutation at codon 61 of the Ha-ras gene in rat hepatocellular carcinomas.


Transvenous laser lead extraction in patients with congenital complete heart block.
Data on lead management in patients with congenital complete heart block (CCHB) with cardiac implantable electronic devices are lacking. The purpose of this study was to describe the natural history and outcomes in patients with CCHB with cardiac implantable electronic devices undergoing transvenous lead extraction (TLE). Data on all attempted TLE procedures in patients with CCHB at 2 institutions between 2011 and 2021 were collected from a retrospective registry. Overall, 16 patients (mean age at transvenous device implant 13.8 ± 4.7 years) were included. Before TLE, patients underwent an average of 2.25 ± 1.3 generator changes, 3 (19%) underwent cardiac resynchronization therapy upgrade, and 7 (44%) underwent a lead revision with subsequently abandoned leads. Mean patient age at TLE was 34.4 ± 9.4 years with a mean duration of lead implant of 19.2 ± 6.9 years. Lead malfunction (n = 11 [69%]) and infection (n = 5 [31%]) were the most common indications for TLE. A total of 38 leads were removed, with complete procedural success achieved in 14 of 16 (87.5%). Two (12.5%) major complications occurred, including right ventricular laceration and superior vena cava tear requiring sternotomies. All patients survived at 1-year follow-up. Patients with CCHB represent a unique cohort highlighted by several generator changes, lead revisions, and abandoned leads at a young age, along with a long duration of lead dwelling time and a high prevalence of lead malfunction requiring TLE. There may be a high risk of major complications during TLE, suggesting TLE should be performed only in experienced centers. Larger studies are needed to confirm these findings.


Clinical features of lupus myositis versus idiopathic myositis: a review of 30 cases.
Myositis is a rare but well-recognized complication of systemic lupus erythematosus (SLE). It is reputed to be milder than primary myositis in terms of morbidity and treatment response. This study compares clinical and laboratory features of idiopathic inflammatory myositis in patients with and without evidence of SLE overlap. We performed a case note review of 30 patients with probable or definite polymyositis/dermatomyositis of whom 11 also had definite or probable SLE. Lupus patients were slightly younger at diagnosis than those with primary disease, and more likely to be female. At presentation, quadriceps strength (expressed as a percentage of expected) was significantly reduced in both the lupus (48.9%; 95% CI 29.0-70.4%) and primary (52.0%; 95% CI 43.6-59.4%) myositis groups, and serum creatine phosphokinase (expressed as a multiple of the upper limit of normal) was significantly elevated (11.2; 95% CI 5.3-29.1 vs 10.7; 95% CI 6.1-17.6). During a mean (S.D.) follow-up period of 7.4 (4.1) yr, both groups tended to follow either a relapsing and remitting, or a chronic persistent course, and when last seen quadriceps muscle strength remained significantly depressed. One of the lupus patients and two of the primary myositis patients died due to direct complications of the disease, and one further death was attributable to a complication of therapy. Our results suggest that lupus myositis is often as severe as primary disease and should be treated with equal vigour.


Area-selective atomic layer deposition of Ru on electron-beam-written Pt(C) patterns versus SiO2 substratum.
Area selectivity is an emerging sub-topic in the field of atomic layer deposition (ALD), which employs opposite nucleation phenomena to distinct heterogeneous starting materials on a surface. In this paper, we intend to grow Ru exclusively on locally pre-defined Pt patterns, while keeping a SiO2 substratum free from any deposition. In a first step, we study in detail the Ru ALD nucleation on SiO2 and clarify the impact of the set-point temperature. An initial incubation period with actually no growth was revealed before a formation of minor, isolated RuO x islands; clearly no continuous Ru layer formed on SiO2. A lower temperature was beneficial in facilitating a longer incubation and consequently a wider window for (inherent) selectivity. In a second step, we write C-rich Pt micro-patterns on SiO2 by focused electron-beam-induced deposition (FEBID), varying the number of FEBID scans at two electron beam acceleration voltages. Subsequently, the localized Pt(C) deposits are pre-cleaned in O2 and overgrown by Ru ALD. Already sub-nanometer-thin Pt(C) patterns, which were supposedly purified into some form of Pt(O x ), acted as very effective activation for the locally restricted, thus area-selective ALD growth of a pure, continuous Ru covering, whereas the SiO2 substratum sufficiently inhibited towards no growth. FEBID at lower electron energy reduced unwanted stray deposition and achieved well-resolved pattern features. We access the nucleation phenomena by utilizing a hybrid metrology approach, which uniquely combines in-situ real-time spectroscopic ellipsometry, in-vacuo x-ray photoelectron spectroscopy, ex-situ high-resolution scanning electron microscopy, and mapping energy-dispersive x-ray spectroscopy.


Are effects of the symmetric and asymmetric tonic neck reflexes still visible in healthy adults?
When a cat's head is rotated in a transverse plane to one side, the legs on that side of the body extend, while on the other side, they flex (asymmetric tonic neck reflexes ATNR). On the contrary, when the head is rotated in a sagittal plane both legs flex when the head flexes, and extend when the head extends (symmetric tonic neck reflexes STNR). These reflexes have also been found in newborn babies and are thought to be a motor primitive, which is suppressed later in life. Still, using a test in which children sit on hand and knees, the ATNR and STNR can be found in children up to 9 years of age. This may suggest that these reflexes may still be involved in motor control in these children. Whether this is also the case in full-grown adults has thus far only been studied using coarse methods. Thus, for the current study, we set out to measure in detail whether the ATNR/STNR can still be evoked in healthy adult subjects. We measured 10 subjects who were asked to sit on their hands and knees while (1) their head was rotated left and right by an experimenter, (2) their head was flexed and extended by an experimenter. Kinematics was registered using a Vicon system. Elbow and head angles were detrended, and a regression analysis was performed, to investigate the effects of head angle on elbow angle. Results clearly showed the existence of the ATNR and STNR in adult subjects. A next step will be to assess the effects of the ATNR and STNR during everyday motor control tasks, such as making head rotations while driving a bike.


An Update on Maternal Use of Antiepileptic Medications in Pregnancy and Neurodevelopment Outcomes.
Antiepileptic drugs (AEDs) are prescribed commonly to women of childbearing age. In utero exposure to some AEDs can have significant cognitive and behavioral consequences for the unborn child. Recently, prospective studies of women taking AEDs during pregnancy have added significantly to our understanding of cognitive and behavioral teratogenic risks posed by fetal AED exposure. Valproate is clearly associated with impaired cognitive development as well as an increased risk of disorders such as autism and autism spectrum disorder. Exposure to carbamazepine, lamotrigine, levetiracetam, or phenytoin monotherapy is associated with more favorable cognitive and behavioral outcomes than valproate, but more data are required to clarify if these AEDs have more subtle effects on cognition and behavior. There are insufficient data on the developmental effects of other AEDs in humans. Further, the underlying mechanisms of cognitive teratogenesis are poorly understood, including the genetic factors that affect susceptibility to AEDs.


Dietitian preceptor knowledge, skills, attitudes, and training: key informant perceptions.
Through consultation with Canadian dietitian informants, we aimed to identify the desired knowledge, skills, and attitudes (KSA) for preceptors, training opportunities, and the barriers that prevent preceptor training. In this qualitative study, an open-ended survey was sent electronically to 100 key informants across Canada. Informants had experience as preceptors or with dietitian preceptors. Informants were asked to reflect upon the desired KSA, training needs, and barriers to training for dietitian preceptors. Categories of responses under each of these headings were developed on the basis of informants' responses. Forty-nine key informants completed the survey, for a 49% response rate. Of the respondents, 41% (20/49) were in clinical practice and 35% (17/49) worked in community/public health areas. The knowledge and skills domains consisted of themes related to teaching and learning, including assessing, planning, and evaluating. Attitudes expressed included considering learners as colleagues and the training of learners as a professional responsibility. Perceived barriers to training preceptors included workload demands and a lack of recognition from peers and employers for this work. Dietitian preceptor training opportunities ranged from no training to formal programs. These findings are integral to the basic understanding of the desired KSA and training needs of Canadian dietitian preceptors.


Hypovolemia-induced reversible severe mitral regurgitation due to left ventricular outflow tract obstruction.
We describe a hypertensive patient who developed profound cardiogenic shock after treatment with nitrates and diuretics. Echocardiography revealed a marked left ventricular outflow tract obstruction with severe mitral regurgitation that were reversible after aggressive fluid therapy.


Combined analysis of inorganic elements and sugars for the identification of red pepper powder containing undeclared ingredients.
This study sought to identify adulterated red pepper powder (RPP) containing undeclared ingredients, such as salts, glucose, Monascus red pigments, and other plant ingredients (e.g., wheat flour, garlic powder, onion powder) using element and sugar analysis methods. Analytical data were obtained for 66 samples of authentic RPP and 12 samples of adulterated RPP. The variables selected to identify the authenticity of RPP include Na, Cl, K, maltohexaose, and maltoheptaose, which partly or totally originate from RPP, salts, or Monascus red pigments. All the 12 samples of commercial seasoned RPP used as models of adulterated RPP and all the 20 blind samples containing ≥10% (w/w) of commercial seasoned RPP were correctly identified by applying the range of the five variables found for the authentic RPP samples. Our findings suggest that combined analyses of the above five constituents could be used to identify adulterated RPP containing undeclared ingredients. PRACTICAL APPLICATION: Adulteration of high-priced spice products, including red pepper powder (RPP), has increasingly become a public concern worldwide as it endangers consumer health and represents economic fraud. This study provides analytical methods that can accurately determine the authenticity of RPP. They would become effective means for protecting producers and suppliers against unfair competition and consumers against health threats.


Innovations in child protective services inservice training: commitment to excellence.
The overwhelming obstacles to effective CPS intervention created by increasing reports of abuse and neglect, funding shortfalls, and the lack of qualified workers have prompted national efforts to reform the public child welfare system in the United States. Organizations such as the American Public Welfare Association, the Children's Defense Fund, the Child Welfare League of America, and the National Association of Social Workers are currently working closely with other national organizations to develop legislative proposals that will enable child welfare agencies to be more responsive to the needs of children and families. A critical component of this reform is the need to recruit, train, and retain qualified and competent CPS workers. The four training programs described in this article are examples of innovative programs seeking to enhance service delivery by enhancing the knowledge and skills of their staff members. Although the four programs were developed in very different political and social climates and within diverse organizational structures, they all provide useful lessons in how to develop efficient and effective training for workers delivering protective services for children. Any national, state, or local efforts to design and develop new CPS training programs should take into account the significant strides made by these agencies.


Accumulation of 8-hydroxydeoxyguanosine, L-arginine and Glucose Metabolites by Liver Tumor Cells Are the Important Characteristic Features of Metabolic Syndrome and Non-Alcoholic Steatohepatitis-Associated Hepatocarcinogenesis.
To uncover mechanisms and explore novel biomarkers of obesity, type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH)-associated hepatocarcinogenesis, cellular and molecular alterations in the liver, and hepatocellular carcinomas (HCCs) were investigated in NASH model 60-week-old Tsumura, Suzuki, Obese Diabetic (TSOD) mice and NASH HCC patients. Markedly elevated lipid deposition, inflammation, fibrosis, and peroxisome proliferation in the liver, preneoplastic lesions, and HCCs of TSOD mice were accompanied by accumulation of polysaccharides in the cellular cytoplasm and nuclei and increase of oxidative DNA damage marker, 8-hydroxydeoxyguanosine (8-OHdG) formation in the liver and altered foci. Metabolomics of TSOD mice HCCs demonstrated significant elevation of the concentration of amino acid L-arginine, phosphocreatine, S-adenosylmethionine/S-adenosylhomocysteine ratio, adenylate, and guanylate energy charges in coordination with tremendous rise of glucose metabolites, mostly fructose 1,6-diphosphate. L-arginine accumulation in HCCs was associated with significant under-expression of arginase 1 (ARG1), suppression of the urea cycle, methionine and putrescine degradation pathways, activation of Ser and Thr kinase Akt AKT, phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinase 1/2 (ERK1/2) kinases, β-catenin, mammalian target of rapamycin (mTOR), and cell proliferation. Furthermore, clinicopathological analysis in 20 metabolic syndrome/NASH and 80 HCV-positive HCC patients demonstrated significant correlation of negative ARG1 expression with poor tumor differentiation, higher pathological stage, and significant decrease of survival in metabolic syndrome/NASH-associated HCC patients, thus indicating that ARG1 could become a potential marker for NASH HCC. From these results, formation of oxidative stress and 8-OHdG in the DNA and elevation of glucose metabolites and L-arginine due to ARG1 suppression in mice liver cells are the important characteristics of T2DM/NASH-associated hepatocarcinogenesis, which may take part in activating oxidative stress resistance, synthesis of phosphocreatine, cell signaling, methylation, and proliferation.


Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.
Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.


Root and Nodule Enzymes of Ammonia Assimilation in Two Plant-Conditioned Symbiotically Ineffective Genotypes of Alfalfa (Medicago sativa L.).
Biochemical and physiological parameters associated with nitrogen metabolism were measured in nodules and roots of glasshouse-grown clones of two symbiotically ineffective alfalfa (Medicago sativa L.) genotypes supplied with either NO(3) (-) or NH(4) (+). Significant differences were observed between genotypes for nodule soluble protein concentrations and glutamine synthetase (GS) and glutamate synthase (GOGAT) specific activities, both in untreated controls and in response to applied N. Nodule soluble protein of both genotypes declined in response to applied N, while nodule GS, GOGAT, and glutamate dehydrogenase (GDH) specific activities either decreased or remained relatively constant. In contrast, no genotype differences were observed in roots for soluble protein concentrations and GS, GOGAT, and GDH specific activities, either in untreated controls or in response to applied N. Root soluble protein levels and GS and GOGAT specific activities of N-treated plants increased 2- to 4-fold within 4 days and then decreased between days 13 and 24. Root GDH specific activity of NH(4) (+)-treated plants increased steadily throughout the experiment and was 50 times greater than root GS or GOGAT specific activities by day 24.Enzymological data indicate that nodules of these ineffective alfalfa genotypes are uniquely differentiated plant organs. Decreasing or constant plant GS and GOGAT specific activities in ineffective nodules in response to applied N suggest that factors in addition to N supply are involved in the induction of high levels of plant ammonia-assimilating enzymes in nodules. Genotype differences observed for nodule enzyme specific activities support the concept that ineffectiveness may be expressed in different ways within the nodule. Senescence was evident in ineffective nodules of N-treated plants of both genotypes, indicating that nodule senescence induced by applied N may not be closely linked to symbiotic effectiveness in alfalfa. Data for ammonia-assimilating enzymes in roots suggest the GS/GOGAT pathway operates only at low levels of soil N and that GDH functions to detoxify high levels of soil NH(4) (+).


Release of excess amyloid beta protein from a mutant amyloid beta protein precursor.
The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimer's disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta.


Evaluation of a simple, rapid and field-adapted diagnostic assay for enterotoxigenic E. coli and Shigella.
Understanding the global burden of enterotoxigenic E. coli (ETEC) and Shigella diarrhea as well as estimating the cost effectiveness of vaccines to control these two significant pathogens have been hindered by the lack of a diagnostic test that is rapid, simple, sensitive, and can be applied to the endemic countries. We previously developed a simple and rapid assay, Rapid Loop mediated isothermal amplification based Diagnostic Test (RLDT) for the detection of ETEC and Shigella spp. (Shigella). In this study, the RLDT assay was evaluated in comparison with quantitative PCR (qPCR), culture and conventional PCR for the detection of ETEC and Shigella. This validation was performed using previously collected stool samples from endemic countries, from the travelers to the endemic countries, as well as samples from a controlled human infection model study of ETEC. The performance of RLDT from dried stool spots was also validated. RLDT resulted in excellent sensitivity and specificity compared to qPCR (99% and 99.2% respectively) ranging from 92.3 to 100% for the individual toxin genes of ETEC and 100% for Shigella. Culture was less sensitive compared to RLDT. No significant differences were noted in the performance of RLDT using samples from various sources or stool samples from moderate to severe diarrhea or asymptomatic infections. RLDT performed equally well in detection of ETEC and Shigella from the dried stool samples on filter papers. This study established that RLDT is sufficiently sensitive and specific to be used as a simple and rapid diagnostic assay to detect ETEC and Shigella in endemic countries to determine disease burden of these pathogens in the national and subnational levels. This information will be important to guide public health and policy makers to prioritize resources for accelerating the development and introduction of effective preventative and/or treatment interventions against these enteric infections.


Spectinomycin.
Spectinomycin is a broad-spectrum aminocyclitol antibiotic that is highly effective in the treatment of uncomplicated gonorrhea. It is the drug of choice for the treatment of gonorrhea that fails to respond to other therapy and is a good alternative drug in the treatment of penicillin-allergic patients. Spectinomycin should be considered the drug of choice in the treatment of gonorrhea in areas where penicillinase-producing strains of Neisseria gonorrhoeae are prevalent. Spectinomycin is not predictably effective in the treatment of oral pharyngeal gonorrhea but may be used in penicillin-allergic patients with disseminated gonorrhea. While spectinomycin has some activity against other human pathogens, it is unlikely that this agent will be found useful in infections other than those due to Neisseria gonorrhoeae.


A multi-stage virtual screening of FDA-approved drugs reveals potential inhibitors of SARS-CoV-2 main protease.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Repurposing of approved pharmaceutical drugs for COVID-19 treatment represents an attractive approach to quickly identify promising drug candidates. SARS-CoV-2 main protease (Mpro) is responsible for the maturation of viral functional proteins making it a key antiviral target. Based on the recently revealed crystal structures of SARS-CoV-2 Mpro, we herein describe a multi-stage virtual screening protocol including pharmacophore screening, molecular docking and protein-ligand interaction fingerprints (PLIF) post-docking filtration for efficient enrichment of potent SARS-CoV-2 Mpro inhibitors. Potential hits, along with a cocrystallized control were further studied via molecular dynamics. A 150-ns production trajectory was followed by RMSD, free energy calculation, and H-bond analysis for each compound. The applied virtual screening protocol led to identification of five FDA-approved drugs with promising binding modes to key subsites of the substrate-binding pocket of SARS-CoV-2 Mpro. The identified compounds belong to different pharmaceutical classes, including several protease inhibitors, antineoplastic agents and a natural flavonoid. The drug candidates discovered in this study present a potential extension of the recently reported SARS-CoV-2 Mpro inhibitors that have been identified using other virtual screening protocols and may be repurposed for COVID-19 treatment.


Risk Acceptance and Desire for Shared Decision Making in Pediatric Computed Tomography Scans: A Survey of 350.
The dual goals of this study were to assess the level of radiation risk parents are comfortable with and also whether they expect a shared decision making conversation. A convenience sample of adult patients in the emergency department was surveyed. Participants were educated regarding the associated radiation risk with computed tomography (CT) scans. They were then surveyed about their willingness to accept the risk of radiation exposure to their children given varying degrees of pretest probability of a clinically significant finding. Additionally, participants were surveyed regarding whether a physician should provide shared decision making. A total of 350 surveys were collected. For low, moderate, and high pretest probability of a positive finding on CT, the proportion of participants who would want a CT for their child was 37% (95% confidence interval [95% CI], 32-43%), 70% (95% CI, 65-75%), and 89% (95% CI, 85-92%), respectively. If the likelihood of a positive CT scan was very low (<5%), 24% (95% CI, 20-29%) were willing to have the study performed on their child. Participants would not want a CT for their child regardless of the probability of finding significant pathology in 9% of those surveyed (28/315). Participants wanted a physician to counsel them before ordering a potentially dangerous test in 93% of the surveys. In a test with an estimated 1:1000 risk of cancer, 91% of participants felt that a doctor should always discuss the risk before ordering the study. Parents are less willing to accept the risk of radiation from CT scan on their child as the likelihood of positive findings decrease. Parents overwhelmingly want an informed discussion before getting a potentially dangerous test.


Genomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals novel recurrent driver mutations.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with variable prognosis. It represents 15% of diagnosed pediatric ALL cases and has a threefold higher incidence among males. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Using an integrative approach combining genomic and transcriptomic data, we molecularly characterized 30 pediatric T-ALLs and identified common recurrent T-ALL targets such as FBXW7, JAK1, JAK3, PHF6, KDM6A and NOTCH1 as well as novel candidate T-ALL driver mutations including the p.R35L missense mutation in splicesome factor U2AF1 found in 3 patients and loss of function mutations in the X-linked tumor suppressor genes MED12 (frameshit mutation p.V167fs, splice site mutation g.chrX:70339329T>C, missense mutation p.R1989H) and USP9X (nonsense mutation p.Q117*). In vitro functional studies further supported the putative role of these novel T-ALL genes in driving transformation. U2AF1 p.R35L was shown to induce aberrant splicing of downstream target genes, and shRNA knockdown of MED12 and USP9X was shown to confer resistance to apoptosis following T-ALL relevant chemotherapy drug treatment in Jurkat leukemia cells. Interestingly, nearly 60% of novel candidate driver events were identified among immature T-ALL cases, highlighting the underlying genomic complexity of pediatric T-ALL, and the need for larger integrative studies to decipher the mechanisms that contribute to its various subtypes and provide opportunities to refine patient stratification and treatment.


Interactor-mediated nuclear translocation and retention of protein phosphatase-1.
Protein Ser/Thr phosphatase-1 (PP1) is a ubiquitous eukaryotic enzyme that controls numerous cellular processes by the dephosphorylation of key regulatory proteins. PP1 is expressed in various cellular compartments but is most abundant in the nucleus. We have examined the determinants for the nuclear localization of enhanced green fluorescent protein-tagged PP1 in COS1 cells. Our studies show that PP1gamma(1) does not contain a functional nuclear localization signal and that its nuclear accumulation does not require Sds22, which has previously been implicated in the nuclear accumulation of PP1 in yeast (Peggie, M. W., MacKelvie, S. H., Bloecher, A., Knatko, E. V., Tatchell, K., and Stark, M. J. R. (2002) J. Cell Sci. 115, 195-206). However, the nuclear targeting of PP1 isoforms was alleviated by the mutation of their binding sites for proteins that interact via an RVXF motif. Moreover, one of the mutants with a cytoplasmic accumulation and decreased affinity for RVXF motifs (PP1gamma(1)-F257A) could be re-targeted to the nucleus by the overexpression of nuclear interactors (NIPP1 (nuclear inhibitor of PP1) and PNUTS (PP1 nuclear targeting subunit)) with a functional RVXF motif. Also, the addition of a synthetic RVXF-containing peptide to permeabilized cells resulted in the loss of nuclear enhanced green fluorescent protein-PP1gamma(1). Finally, NIPP1(-/-) mouse embryos showed a nuclear hyperphosphorylation on threonine, consistent with a role for NIPP1 in the nuclear targeting and/or retention of PP1. Our data suggest that both the nuclear translocation and the nuclear retention of PP1 depend on its binding to interactors with an RVXF motif.


Empowering Nurses to Provide Humanized Care in Canadian Hospital Care Units: A Qualitative Study.
Previous studies have reported a conflict between nurses' motivation to provide humanized care and practical requirements impeding them from doing so. This exploratory descriptive qualitative study aimed to explore nurses' perspectives on humanized care, the challenges they face, and, most importantly, their recommendations to overcome these barriers. Semistructured individual interviews were conducted with 17 auxiliary and registered nurses working in various health care units in a Canadian hospital. Participants demonstrated a good understanding of what humanized care covers and entails. They also described it as the very core of their profession and main source of job satisfaction. However, nurses reported that they are confronted with organizational barriers, mainly a lack of staff, the burden of administrative tasks, unsuitable physical environments or equipment, and little managerial support. Nurses stressed the need for a cultural change in managerial practices in order to be able to improve their provision of humanized care. Based on the findings, 4 structuring recommendations were identified: adopting an institutional policy promoting the implementation of humanized care, incorporating humanized care in nurses' tasks and procedures, improving participatory management, and ensuring adequate staffing.


[Evaluation of polymerase chain reaction method for monitoring of fungal infection in compromised hosts].
Diagnosis of fungal infections in compromised hosts has been difficult because of insufficient sensitivity and specificity of conventional methods such as culturing and serum testing. Therefore, antifungal agents are usually started in febrile patients who are resistant to antibiotics even if these monitoring tests were negative. In this study, therefore, in order to increase the reliability of these monitoring, polymerase chain reaction (PCR) methods for detection of blood fungus were also performed in compromised hosts including 14 patients with hematological malignancies and one with solid tumor who were undergoing chemotherapies. From these patients, total of 56 peripheral blood samples was collected periodically, irrespective of the presence of infectious signs. At each time point of venopuncture, status of the patient was allocated to one of the followings: A, receiving an intravenous antifungal therapy because of sustaining fever which had not responded to prior antibiotic therapies and also positive for culturing and/or serum beta-D-glucan tests; B, receiving an additional intravenous antifungal therapy but negative for culturing and serum-tests; C, febrile but not yet receiving any intravenous fungal therapy; D, afebrile status. During the study, 10 blood samples from 3 patients were allocated in group A, and one sample of them was positive while remaining 9 were all negative for PCR. Six samples from 4 patients were in group B, and one was PCR positive while remaining 5 were negative. Fifteen samples from 7 patients were in group C, and 3 were positive and 12 were negative for PCR. Twenty-five samples were in group D, and 5 were positive and 20 were negative for PCR. Thus, the results from fungal PCR in these patients were in some case showed discrepancies from those expected from the clinical course and/or conventional monitoring tests. Further evaluation of fungal PCR may gain insight into the more precise diagnosis of fungal infection in these patients.


Expression and distribution of NOS1 and NOS3 in the myocardium of angiotensin II-infused rats.
Studies have indicated a complex functional interaction between angiotensin (Ang) II and NO in the heart. The purpose of the present study was to examine the protein expression and tissue distribution of NO synthases 1 (NOS1) and 3 (NOS3) in the myocardium of rats that underwent continuous infusion of Ang II at 2 different rates (10 and 40 ng. kg(-1). min(-1)) for 6 days. Mean arterial pressure increased by approximately 15 mm Hg in rats infused with Ang II at 40 ng. kg(-1). min(-1), but it remained close to the values observed in saline-infused rats ( approximately 110 mm Hg) when Ang II was infused at 10 ng. kg(-1). min(-1). The protein expression of a 160-kDa NOS1 and a 135-kDa NOS3 were found to increase ( approximately 200%) in the myocardium of rats infused with both subpressor and pressor doses of Ang II. Immunohistochemistry studies showed that NOS1 and NOS3 are differentially expressed in myocardial cells. NOS1 was detected in cardiac myocytes and in smooth muscle cells of small and large coronary arteries, whereas NOS3 was detected in the endothelium and in perivascular and interstitial tissues, but NOS3 was not detected in cardiac or smooth muscle cells. Ang II infusion enhanced the tissue immunoreactivity of both isoforms in their specific locations but did not change the distribution throughout the myocardium. Myocardium staining with anti-angiotensin type 1 (AT(1)) receptor antibody indicated that AT(1) receptor is expressed in cardiac myocytes, coronary smooth muscle cells, and interstitial and perivascular tissues. Ang II infusion did not change the protein expression and distribution of AT(1) receptor in the myocardium. These results indicate that long-term increases in the circulating levels of Ang II modulate the protein expression of NOS1 and NOS3 and, consequently, the function of the local myocardial NO system.


Efficacy of combined inspiratory intercostal and expiratory muscle pacing to maintain artificial ventilation.
Many patients with ventilator-dependent quadriplegia have coincident phrenic nerve injury and therefore cannot be offered phrenic nerve pacing. The purpose of this study was to assess the utility of combined inspiratory intercostal and expiratory muscle pacing to provide complete ventilatory support. Studies were performed in 15 anesthetized dogs. An electrode was positioned on the epidural surface of the upper thoracic spinal cord to activate the inspiratory intercostal muscles; a separate electrode was positioned on the epidural surface of the lower thoracic spinal cord to activate the expiratory muscles. In an attempt to replicate the effects of inspiratory intercostal pacing alone in humans, stimulus parameters during upper thoracic spinal cord stimulation were adjusted to provide suboptimal levels of ventilation (end-tidal PCO2 of 55 to 60 mm Hg). Expiratory muscle activation was triggered electrically by the inspiratory signal with a 4.2-s delay resulting in alternate inspiratory and expiratory muscle pacing at a combined rate of 14 breaths/min. Combined pacing was maintained for an arbitrary period of 3 h. Initial intercostal muscle pacing alone resulted in an end-tidal PCO2 of 57.1 +/- 1.1 mm Hg. After the addition of expiratory muscle pacing, end-tidal PCO2 fell to 36.3 +/- 1.2 mm Hg. Tidal volume during both inspiratory and expiratory muscle pacing and end-tidal PCO2 remained stable throughout the study period. Our results suggest that combined alternate inspiratory and expiratory muscle pacing may be a viable alternative method of artificial ventilation in ventilator-dependent quadriplegic patients.


Comparison of 2,2'-bipyridine and 2,2'-bipyridyl-N,N'-dioxide as ligands in zinc complexes.
The complexation abilities of 2,2'-bipyridine (bipy) and 2,2'-bipyridyl-N,N'-dioxide (bipydiox) toward zinc(II) and the influence of these ligands on the properties and reactivities of the investigated complexes are compared by means of mass spectrometry, IR multiphoton dissociation spectroscopy, and theoretical calculations. The binding energy of bipydiox to zinc is slightly smaller than that of bipy, namely, by 0.1 eV in the mixed complex [(bipy)(bipydiox)ZnCl](+). Accordingly, the differences in the properties and reactivities of the complexes of zinc(II)/bipydiox and zinc(II)/bipy are only minor. The mechanism of decarboxylation of [(L)Zn(CH(3)COO)](+) (L = bipy or bipydiox) is investigated in detail. The substantial difference between the ligands stems only from the possibility of oxygen transfer from bipydiox, which is here, however, observed only as a high-energy channel in the fragmentation of complexes [(bipydiox)Zn(CH(3)COO)](+).


Motivational interviewing: an effective brief intervention for alcohol and drug abuse patients.
Inadequate motivation is a crucial factor for the substance abuser's inability to change harmful behavior. Although not widely implemented in advanced nursing practice, the motivational interviewing strategies have great utility in interactions with substance abuse patients in primary care settings. This article provides implementation strategies for an effective independent nursing intervention that can be utilized to manage drug and alcohol abuse behaviors.


Colloquium paper: a phylogenetic perspective on the distribution of plant diversity.
Phylogenetic studies are revealing that major ecological niches are more conserved through evolutionary history than expected, implying that adaptations to major climate changes have not readily been accomplished in all lineages. Phylogenetic niche conservatism has important consequences for the assembly of both local communities and the regional species pools from which these are drawn. If corridors for movement are available, newly emerging environments will tend to be filled by species that filter in from areas in which the relevant adaptations have already evolved, as opposed to being filled by in situ evolution of these adaptations. Examples include intercontinental disjunctions of tropical plants, the spread of plant lineages around the Northern Hemisphere after the evolution of cold tolerance, and the radiation of northern alpine plants into the Andes. These observations highlight the role of phylogenetic knowledge and historical biogeography in explanations of global biodiversity patterns. They also have implications for the future of biodiversity.


Histochemical changes and apoptosis in degenerating taste buds of the rat circumvallate papilla.
The present study was designed to examine the histochemical changes and occurrence of apoptosis in taste buds of rat circumvallate papillae following bilateral transection of the glossopharyngeal nerve. Following transection of the glossopharyngeal nerve, the number of taste buds was not altered until post-operative day 3 (PO3), but decreased significantly thereafter. The number of cells within a taste bud, however, decreased significantly from PO2. In normal, uninjured animals, approximately 15.4%, 9.0%, and 7.7% of taste bud cells were labeled with antibodies for phospholipase C beta2 subunit (PLCbeta2), a marker for type II cells, neural cell adhesion molecule (NCAM), a marker for type III cells, and Jacalin, a marker for type IV cells, respectively. Following gustatory nerve injury, the ratio of cells expressing markers of type III and type IV decreased gradually from PO2, and Jacalin-labeled taste bud cells disappeared on PO3. Under normal conditions, immunoreactivity for single-strand DNA (ssDNA), a marker of apoptosis, was detected in the nuclei of PLC beta2-immunoreactive cells and cells showing no labeling for PLCbeta2, NCAM, or Jacalin. On PO1, the number of taste bud cells showing ssDNA immunoreactivity increased to double that of normal uninjured animals; these ssDNA-immunoreactive cells were also labeled with NCAM and Jacalin as well as PLCbeta2. The present results suggest that denervation of the gustatory nerve causes apoptosis in all types of taste bud cells, resulting in the rapid degeneration of taste buds.


Bicarbonate reduces serum prolactin increase induced by exercise to exhaustion.
The aim of the study was to examine the effect of acid-base status on serum prolactin (PRL) concentration postexercise. Seven male recreational athletes participated in two experimental trials separated by 1 wk. In the respective trial, subjects received either a placebo infusion (normal isotonic saline) or an alkali infusion (isotonic sodium bicarbonate) before and during exercise. Venous and capillary blood samples were drawn at rest, immediately after a 10-min warm-up period, and after a maximal ramp test on a cycle ergometer, as well as at 3, 6, 10, and 15 min postexercise. Power output, HR, capillary blood lactate concentration, carbon dioxide pressure (PCO2), and partial oxygen pressure (PO2) did not differ between trials at any point in time. Capillary PO2 did not change from resting values, but a significant increase (P < 0.05) was found from the end of warm-up to 3 min of the recovery period. Exercise induced a significant (P < 0.01) decrease in capillary blood bicarbonate concentration (HCO3-), pH, base excess (BE), and PCO2 at exhaustion and during the recovery period. Significantly higher HCO3-, pH, and BE were found during bicarbonate infusion and postexercise in comparison with the placebo trial. Serum PRL concentration was significantly increased 3 min postexercise until the end of the placebo trial, whereas after bicarbonate infusion, serum PRL concentration did not change from values at rest. Significant (P < 0.01) differences between trials in serum PRL concentration were found 10 and 15 min postexercise. The present study suggests that acidosis is a stimulus for exercise-induced PRL secretion.


IAEA survey of dental cone beam computed tomography practice and related patient exposure in nine Central and Eastern European countries.
Cone beam CT (CBCT) in dentistry and maxillofacial surgery is a widely used imaging method for the assessment of various maxillofacial and dental pathological conditions. The objective of this study was to summarize the results of a multinational retrospective-prospective study that focused on patient exposure in this modality. The study included 27 CBCT units and 325 adult and paediatric patients, in total. Data on patients, clinical indications, technical parameters of exposure, patient dose indicator, or, alternatively, dose to phantom were collected. The dose indicator used was air kerma-area product, PKA. In most scanners operators are offered with a variety of options regarding technical parameters, especially the field of view size. The median and the third quartile value of PKA for adult patients in 14 different facilities were 820 mGy cm² and 1000 mGy cm² (interquartile range = 1058 mGy cm²), and 653 mGy cm² and 740 mGy cm² (interquartile range = 1179 mGy cm²) for children, as reported by four different institutions. Phantom dose data were reported from 15 institutions, and median PKA ranged from 125 mGy cm² to 1951 mGy cm². Median PKA values varied by more than a 10-fold between institutions, mainly due to differences in imaging protocol used, in particular field of view and tube current-exposure time product. The results emphasize the need for a cautious approach to using dental CBCT. Imaging only when the clinical indications are clear, accompanied with the appropriate radiographic techniques and the optimum imaging protocol, will help reduce radiation dose to patients.


Gpr17 in AgRP Neurons Regulates Feeding and Sensitivity to Insulin and Leptin.
Hypothalamic neurons expressing agouti-related peptide (AgRP) regulate eating and glucose metabolism. Ablation of FOXO1 in AgRP neurons of mice results in reduced food intake, leanness, improved glucose homeostasis, and increased sensitivity to insulin and leptin. We tentatively identified G-protein-coupled receptor Gpr17 as an effector of FOXO1 orexigenic signals in AgRP neurons. In this study, we generated and characterized AgRP neuron-specific Gpr17 knockout mice (Agrp-Gpr17(-/-)) to test the hypothesis that Gpr17 regulates appetite, energy expenditure, and metabolism. Agrp-Gpr17(-/-) mice show reduced food intake, increased relative energy expenditure, and increased satiety, resulting in leanness and reduced body fat. They also show increased central nervous system sensitivity to insulin and leptin and reduced plasma glucose excursions following the administration of glucose or pyruvate. In summary, AgRP neuron-specific Gpr17 knockouts phenocopy FOXO1 knockouts in the same cell type, thus supporting our original hypothesis and providing further impetus to develop Gpr17 antagonists for the treatment of obesity.


Can psychiatric terminology be translated into legal regulation? The anorexia nervosa example.
To explore the tension between the definition of mental illness in clinical psychiatry and its embodiment in legislation applied by tribunals reviewing decisions to treat. Severe anorexia nervosa is used as a case exemplar of the tension between the appropriate narrative to express the clinical imperative to treat and the law's focus on finer technical language which secures individual civil rights and liberties. Australian and international experience is reviewed. The paper finds that the clinical and the legal narratives about how to 'define' mental illness do differ at the formal level of expression where they necessarily intersect in the setting of tribunal review of involuntary treatment decisions. However, in practice mental health admissions and tribunal reviews generally endorse the clinical applications of that more capacious and fluid terminology of clinical psychiatry. While tribunal reviews of clinical decisions may occasionally require clinicians to participate in an unfamiliar legal dialogue about narrowly construed definitions of mental illness, tribunals apply more complex tests which are sensitive to clinical practice and good therapeutic objectives.