Supplementation with multiple micronutrients for breastfeeding women for improving outcomes for the mother and baby.
Globally, more than two billion people are estimated to be deficient in key vitamins and minerals, particularly iodine, iron and zinc. The majority of these people live in low-income settings and are typically deficient in more than one micronutrient. However, micronutrient deficiency among breastfeeding mothers and their infants also remains an issue in high-income settings, specifically among women who avoid meat and/or milk, women who may lack sufficient supplies of vitamin B12 and vitamin D, and/or women who are iron-deficient. Young children, pregnant and lactating women are particularly vulnerable to micronutrient deficiencies. They not only have a relatively greater need for vitamins and minerals because of their physiological state, but are also more susceptible to the harmful consequences of deficiencies. Multiple-micronutrient supplementation might be an option to solve these problems. The objective of this review was to evaluate the effects of multiple-micronutrient supplementation in breastfeeding mothers on maternal and infant outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and reference lists of retrieved studies. Randomised controlled trials of multiple-micronutrient supplementation of three or more micronutrients versus placebo, no supplementation or supplementation with two or fewer micronutrients, irrespective of dosage of micronutrients, in breastfeeding mothers. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We found no studies that compared multiple-micronutrient supplementation (with three or more micronutrients) versus supplementation with two or fewer micronutrients.Two small studies (involving a total of 52 women) were included. One study compared multiple micronutrients with placebo and the other study compared multiple micronutrients with a group who received no supplementation. The studies were carried out in Brazil (36 adolescent mothers) and the USA (16 women) and included women with a low socioeconomic status. A lack of information in the study reports meant that risk of bias could not be adequately assessed (unclear risk of bias for many domains). There were no quantitative data for any of this review's outcomes so meta-analysis was not possible.Neither of the studies reported on the primary outcomes of interest in this review: maternal morbidity (febrile illness, respiratory tract infection, diarrhoea), adverse effects of micronutrients within three days of receiving the supplement, infant mortality (defined as a child dying before completing the first year of age).One study reported qualitatively on maternal anaemia (a secondary outcome of this review) - the study found that multiple-micronutrient supplementation was effective for recuperating from anaemia but there were no data for inclusion in our analyses. Maternal satisfaction was not reported in the included studies. Similarly, none of this review's infant secondary outcomes were reported in the included studies: clinical micronutrient deficiency; morbidity episodes (febrile illness, respiratory tract infection, diarrhoea, other), adverse effects of micronutrients within three days of receiving the supplement. We found no evidence to quantitatively assess the effectiveness of multiple-micronutrient supplementation in improving health outcomes in mother and baby. The results of this review are limited by the small numbers of studies available, small sample sizes and the studies not reporting on the outcomes of interest in this review. There is no evidence to evaluate potential adverse effects of multiple-micronutrient supplements, particularly excess dosages.There is a need for high-quality studies to assess the effectiveness and safety of multiple-micronutrient supplementation for breastfeeding women for improving outcomes for the mother and her baby. Further research should focus on whether multiple-micronutrient supplementation during lactation compared with none, a placebo or supplementation with fewer than two micronutrients is beneficial to maternal and infant health outcomes. Future studies should collect data on outcomes beyond micronutrient concentrations, for example: maternal and infant morbidity, adverse effects, maternal satisfaction, the risks of excess supplementation, and potential adverse interactions between the micronutrients and the other outcomes. This would help to bridge the gap between research on intermediary outcomes and health outcomes in order to develop sound policy in this field. Future studies could more precisely assess a variety of multiple-micronutrient combinations and different dosages and look at how these affect maternal and infant health outcomes. Larger studies with longer follow-up would improve the quality of studies and provide stronger evidence. In most of the included studies, bias could not be adequately assessed due to lack of information, therefore attention should be given to adequate methods of randomisation and allocation concealment, adequate methods of blinding of the participants, providers and the outcome assessors to improve the methodological quality of studies in this field.


Comparison of metabolic control among diabetic subjects at two clinics.
A cross-sectional study was conducted to investigate whether glucose control in 20 non-insulin-dependent diabetic subjects seen at a remote rural clinic was comparable to control achieved in 66 diabetic subjects seen at the regional hospital clinic. Sampling was done to assure that study subjects were representative of all care-seeking, diagnosed diabetics in a well-defined Navajo community. The two groups of patients were comparable in terms of age, sex, and duration of diabetes from time of diagnosis. Compliance with care, hospitalization rates, and complication rates were similar in each group. Results showed no significant differences in glycemic control between the rural clinic (mean fasting plasma glucose = 177, mean random plasma glucose = 227) and the regional hospital clinic (mean fasting plasma glucose = 187, mean random plasma glucose = 249). The percentages of diabetics under "acceptable" control by American Diabetes Association guidelines was 40 percent at the rural clinic and 29 percent at the hospital clinic (P greater than .05). The authors conclude that adequacy of glycemic control in diabetics is not compromised by providing care at a remote rural clinic.


Genome-Wide Epistatic Interaction Networks Affecting Feed Efficiency in Duroc and Landrace Pigs.
Interactions among genomic loci have often been overlooked in genome-wide association studies, revealing the combinatorial effects of variants on phenotype or disease manifestation. Unexplained genetic variance, interactions among causal genes of small effects, and biological pathways could be identified using a network biology approach. The main objective of this study was to determine the genome-wide epistatic variants affecting feed efficiency traits [feed conversion ratio (FCR) and residual feed intake (RFI)] based on weighted interaction SNP hub (WISH-R) method. Herein, we detected highly interconnected epistatic SNP modules, pathways, and potential biomarkers for the FCR and RFI in Duroc and Landrace purebreds considering the whole population, and separately for low and high feed efficient groups. Highly interacting SNP modules in Duroc (1,247 SNPs) and Landrace (1,215 SNPs) across the population and for low feed efficient (Duroc-80 SNPs, Landrace-146 SNPs) and high feed efficient group (Duroc-198 SNPs, Landrace-232 SNPs) for FCR and RFI were identified. Gene and pathway analyses identified ABL1, MAP3K4, MAP3K5, SEMA6A, KITLG, and KAT2B from chromosomes 1, 2, 5, and 13 underlying ErbB, Ras, Rap1, thyroid hormone, axon guidance pathways in Duroc. GABBR2, GNA12, and PRKCG genes from chromosomes 1, 3, and 6 pointed towards thyroid hormone, cGMP-PKG and cAMP pathways in Landrace. From Duroc low feed efficient group, the TPK1 gene was found involved with thiamine metabolism, whereas PARD6G, DLG2, CRB1 were involved with the hippo signaling pathway in high feed efficient group. PLOD1 and SETD7 genes were involved with lysine degradation in low feed efficient group in Landrace, while high feed efficient group pointed to genes underpinning valine, leucine, isoleucine degradation, and fatty acid elongation. Some SNPs and genes identified are known for their association with feed efficiency, others are novel and potentially provide new avenues for further research. Further validation of epistatic SNPs and genes identified here in a larger cohort would help to establish a framework for modelling epistatic variance in future methods of genomic prediction, increasing the accuracy of estimated genetic merit for FE and helping the pig breeding industry.


Using health-related quality of life assessments to evaluate care support within Medicaid.
CareOregon, an Oregon-based not-for-profit Medicaid health plan, successfully piloted a "CareSupport" model that identifies high-risk members and clinically stratifies them for intervention. Internal analyses indicate that CareSupport lowers utilization and cost; CareOregon, however, has lacked patient-reported outcome data on the health-related quality of life (HRQL) of CareSupport participants. Between September 2005 and November 2006, we conducted a pilot study in which the Health Utilities Index Mark 3 (HUI3), a generic preference-based measure of health status and HRQL, was integrated into CareOregon's existing screening algorithm for possible admission into CareSupport. We obtained baseline data on 616 CareSupport candidates and 4-month HUI3 follow-up data on 143 candidates (104 CareSupport 39 non-CareSupport). On a 0.00 (dead)-to-1.00 (perfect health) scale, the mean overall baseline HUI3 score for CareSupport patients was 0.18 (0.20 for non-CareSupport patients), comparable to baseline means reported elsewhere for much older patients immediately after suffering serious acute medical events, such as stroke or hip fracture. A 0.05 mean 4-month improvement in overall HRQL among CareSupport enrollees relative to non-CareSupport enrollees was clinically important but not statistically significant. A 0.10 improvement in HUI3 emotion was both statistically significant and clinically important. Study results provide good preliminary evidence of the value of patient-reported outcomes in clarifying individual illness burden and assessing intervention effectiveness.


Effect of 3-methylcholanthrene administration on expression of cytochrome P-450 isoforms induced by phenobarbital in rat hepatocytes.
The effects of an inducer on expression of cytochrome P-450 (P-450) isoforms induced antecedently by another inducer are unknown. Thus, we examined the amount of phenobarbital (PB)-inducible P-450 isoforms (P-450 2B1/2B2) in hepatocytes from rats injected first with PB and then with 3-methylcholanthrene (MC) (PB+MC-treated animals) by quantitative immunohistochemistry. In addition, expression of P-450 2B2 mRNA was examined by in situ hybridization. In PB-treated animals, P-450 2B1/2B2 content increased in perivenular and midzonal hepatocytes. In PB+MC-treated animals, however, the PB-induced increase in 2B1/2B2 content was suppressed in perivenular hepatocytes but promoted in midzonal hepatocytes. The hybridization signal for P-450 2B2 mRNA appeared almost exclusively in perivenular hepatocytes after 24 hr of PB injection and disappeared after 48 hr of injection. In PB+MC-treated animals, however, strong hybridization signal was observed in midzonal and perivenular hepatocytes after 48 hr of PB injection. The promotion of the increase in P-450 2B1/2B2 content in midzonal hepatocytes in PB+MC-treated animals probably corresponds to the strong hybridization signal, whereas there appeared to be a divergence between the intensity of the signal and the content in perivenular hepatocytes. The results indicate that MC administration drastically influences the pattern of expression of P-450 isoforms induced by PB in perivenular and midzonal hepatocytes.


Rebamipide suppresses mite-induced asthmatic responses in NC/Nga mice.
Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma.


The impact of rate and rhythm control strategies on quality of life for patients with atrial fibrillation: a protocol for a systematic review.
Atrial fibrillation (AF) is the most common heart arrhythmia globally and it adversely affects the quality of life (QoL). Available rate and rhythm control strategies equally reduce mortality but may impact QoL differently. A number of systematic reviews have focused on the impact of specific strategies on QoL, though a 2006 review synthesized the evidence on the effect of all strategies on QoL, allowing for a clinically important comparison between the types of strategies. Many trials have been published since the review undertook the search in 2005; therefore, an update is needed. This systematic review aims to provide an update to the 2006 review on the impact of all rate and rhythm control strategies on QoL in people with AF. The following four databases and three clinical trial registries will be searched for primary studies: CENTRAL, MEDLINE, Embase, CINAHL, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and ClinicalTrialsRegister.eu. No language restriction will be applied. The search will be limited to 2004 or later publication year to allow overlap with the search conducted by the 2006 review authors. Any randomized control trial that reports the QoL of adult (≥ 18 years) AF patients following an eligible rate or rhythm control intervention will be eligible for inclusion. Eligible interventions (and comparators) include pacing, atrioventricular node junction and bundle of HIS ablation, pharmacological therapy, radio frequency catheter ablation, cryoablation, pulmonary vein isolation, maze operation, pace maker implantation, and defibrillator implantation. Two reviewers will independently screen for eligible studies, extract the data using a piloted tool, and assess bias by QoL outcome using the RoB 2 tool. The suitability of conducting a meta-analysis will be assessed by the clinical and methodology similarities of included studies. If it is feasible, standardized mean differences will be pooled using a random-effects model and assessed appropriately. The findings from this review will allow for meaningful comparisons between various rate and rhythm control strategies regarding their impact on QoL. This review will be useful for a wide range of stakeholders and will be crucial for optimizing the overall wellbeing of AF patients. PROSPERO CRD42021290542.


Nonmydriatic fundus photography in screening for treatable diabetic retinopathy.
Diabetic retinopathy is a complication of both insulin-dependent (type I) and non-insulin-dependent (type II) diabetes. The American Diabetes Association and others recommend screening for retinopathy, beginning 5 years after onset of symptoms for patients with type I diabetes and at the time of diagnosis for patients with type II diabetes. Ideally, diabetic patients are evaluated at recommended intervals by an ophthalmologist. Realistically, however, this is often not feasible, for reasons both of cost and availability. There is evidence that many diabetic patients are being referred too late for intervention, perhaps in part due to lax screening and detection, often the responsibility of internists and other primary care physicians. Data supports the need for a cheap, widely available, easy-to-use, effective screening tool for detecting treatable diabetic retinopathy. To this end, several studies have evaluated nonmydriatic fundus photography, and compared it with more-established methods of detecting diabetic retinal disease. The real question to be considered is whether nonmydriatic fundus photography will help to detect early treatable retinopathy better than the average physician using ophthalmoscopy. Several studies support its usefulness in this regard, and are discussed in this review. Questions remain, however, and further study is warranted in evaluating its potential role.


Lifestyle during pregnancy: neurodevelopmental effects at 5 years of age. The design and implementation of a prospective follow-up study.
It has been suggested that even mild exposure to alcohol, caffeine, smoking, and poor diet may have adverse long-term neurodevelopmental effects. In addition, there is evidence that timing of high exposures (e.g. binge drinking) can have particularly negative effects. This paper describes the design and implementation of The Lifestyle During Pregnancy Study addressing major methodological challenges for studies in this field. The study examines the effects of lifestyle during pregnancy on offspring neurodevelopment. In 2003, we initiated a prospective follow-up of 1750 mother-child pairs, sampled on the basis of maternal alcohol drinking patterns from The Danish National Birth Cohort (DNBC), a study of 101,042 pregnancies enrolled 1997-2003. Data collection in the DNBC involved four prenatal and postnatal maternal interviews, providing detailed information on maternal alcohol drinking patterns before and during pregnancy, caffeine intake, smoking, diet, and other lifestyle, medical, and sociodemographic factors. At the age of 5 years, the children and their mothers participated in a comprehensive assessment of neurobehavioural development focusing on global cognition, specific cognitive functions, and behaviour. Two new tests assessing attention and speed of information processing among children were developed, and data on important potential confounders such as maternal intelligence quotient, vision, and hearing abilities were collected. Efforts were made to standardise procedures and obtain high inter-rater reliability. We expect that the study will illuminate the significance or lack of significance of maternal lifestyle during pregnancy and contribute to better understanding the effects of alcohol drinking during pregnancy at low to moderate consumption levels.


Malaria and Japan's colonial frontier: Manchuria, 1900s-1940s.
This article examines the malaria problem among Chinese migrant laborers in Manchuria, particularly laborers on the South Manchuria Railway's mining sites, the Fushun Mines, during the first half of the twentieth century. Almost all of the malaria cases in Manchuria were caused by the parasite Plasmodium vivax, which rarely causes death but leads to debilitation and makes sufferers susceptible to other illnesses. Malaria epidemics in Manchuria during this period were the result of Japan's economic and military exploitation. The expansion of malaria mosquito habitats caused by large-scale constructions and development of mines and massive immigration for these industries led to these epidemics. Most of the malaria victims were Chinese laborers who worked for Japanese businesses and no less than two-thirds of these patients were reportedly from Fushun, where the Fushun Mines were located. The living and working conditions of the laborers made them vulnerable to various diseases, including malaria. As Japanese employers concentrated on the human-centered approach to malaria control general sanitary reforms were often ignored. After the promulgation of the Five-Year Industrial Development Plan of Manchukuo and the outbreak of the Second-Sino Japanese War, Japanese authorities' attitude to malaria among Chinese laborers changed dramatically. A steady supply of labor was essential to enable the production of more coal for the war-efforts as the Fushun Mines were designated a key industry for Japan's national defense. To achieve this manpower efficiency was crucial but malaria epidemics decreased the productivity of labor. As the coal shortage was considered a great obstacle for Japanese and Manchukuo industries, as well as for the conduct of the war, the malaria problem among Chinese laborers could no longer be ignored.


Host Immunity Alters Community Ecology and Stability of the Microbiome in a Caenorhabditis elegans Model.
A growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation-and the consequences for the ecology of these communities-remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affect the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here, we show that these phenomena can be quantitatively analyzed in the tractable nematode host Caenorhabditis elegans Mutants in innate immunity, in particular the DAF-2/insulin growth factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild-type nematodes. We analyzed the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and concluded that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We tested this hypothesis by introducing a minor perturbation into the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of interspecies interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology.IMPORTANCE Here, we used a Caenorhabditis elegans microbiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of the host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.


Cardiomyocyte proliferation in cardiac development and regeneration: a guide to methodologies and interpretations.
The newt and the zebrafish have the ability to regenerate many of their tissues and organs including the heart. Thus, a major goal in experimental medicine is to elucidate the molecular mechanisms underlying the regenerative capacity of these species. A wide variety of experiments have demonstrated that naturally occurring heart regeneration relies on cardiomyocyte proliferation. Thus, major efforts have been invested to induce proliferation of mammalian cardiomyocytes in order to improve cardiac function after injury or to protect the heart from further functional deterioration. In this review, we describe and analyze methods currently used to evaluate cardiomyocyte proliferation. In addition, we summarize the literature on naturally occurring heart regeneration. Our analysis highlights that newt and zebrafish heart regeneration relies on factors that are also utilized in cardiomyocyte proliferation during mammalian fetal development. Most of these factors have, however, failed to induce adult mammalian cardiomyocyte proliferation. Finally, our analysis of mammalian neonatal heart regeneration indicates experiments that could resolve conflicting results in the literature, such as binucleation assays and clonal analysis. Collectively, cardiac regeneration based on cardiomyocyte proliferation is a promising approach for improving adult human cardiac function after injury, but it is important to elucidate the mechanisms arresting mammalian cardiomyocyte proliferation after birth and to utilize better assays to determine formation of new muscle mass.


Ascorbic acid in the prevention and treatment of cancer.
This review is aimed at the systematic mapping of ascorbic acid in the prevention and/or treatment of cancer in clinical and non-clinical studies from 2011 to 2015, in order to understand dose-response variations as well as its mechanisms of action as an antioxidant and antitumor agent. Seventy-eight articles were retrieved from the PubMed/Bireme database, of which only 30 included ascorbic acid in the prevention and/or treatment of cancer. However, there are controversies regarding doses and a lack of clinical studies featuring its mechanism of action more clearly. Other studies are needed to understand dose-response variations, as well as its targeting mechanisms of action, both as an antioxidant and antitumor agent, to assist treatment and prevention of cancer, aiming at better quality of life for both patients and the general population.


Sequential antibiotic therapy in the laboratory and in the patient.
Laboratory experiments suggest that rapid cycling of antibiotics during the course of treatment could successfully counter resistance evolution. Drugs involving collateral sensitivity could be particularly suitable for such therapies. However, the environmental conditions in vivo differ from those in vitro. One key difference is that drugs can be switched abruptly in the laboratory, while in the patient, pharmacokinetic processes lead to changing antibiotic concentrations including periods of dose overlaps from consecutive administrations. During such overlap phases, drug-drug interactions may affect the evolutionary dynamics. To address the gap between the laboratory and potential clinical applications, we set up two models for comparison-a 'laboratory model' and a pharmacokinetic-pharmacodynamic 'patient model'. The analysis shows that in the laboratory, the most rapid cycling suppresses the bacterial population always at least as well as other regimens. For patient treatment, however, a little slower cycling can sometimes be preferable if the pharmacodynamic curve is steep or if drugs interact antagonistically. When resistance is absent prior to treatment, collateral sensitivity brings no substantial benefit unless the cell division rate is low and drug cycling slow. By contrast, drug-drug interactions strongly influence the treatment efficiency of rapid regimens, demonstrating their importance for the optimal choice of drug pairs.


Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.
Coronary artery disease is an important complication of hypertension. Therefore, the effects of antihypertensive therapy on the endothelial nitric oxide (NO)/L-arginine pathway and vascular smooth muscle were studied in left anterior descending coronary arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Angiotensin II (AT1) receptor antagonists CGP 48369 and valsartan, angiotensin-converting enzyme inhibitor benazepril HCl, and calcium antagonist nifedipine were used as antihypertensive agents. Rings were examined in myograph systems for isometric tension recording. In untreated WKY and SHR rings, acetylcholine (10(-9) to 10(-5) mol/L) but not bradykinin, substance P (both 10(-6) mol/L), or thrombin (1 U/mL) induced comparable endothelium-dependent relaxations. These relaxations were markedly decreased by NG-monomethyl-L-arginine (10(-4) mol/L) and fully prevented by N omega-nitro-L-arginine methyl ester (10(-4) mol/L) or methylene blue (10(-5) mol/L). In vitro treatment of WKY and SHR rings with benazeprilat, CGP 48369, or valsartan (3 x 10(-7) mol/L) did not affect responses to acetylcholine. In SHR, chronic therapy for 8 weeks with benazepril HCl, CGP 48369, valsartan, or nifedipine (each 10 mg.kg-1.d-1 PO) similarly reduced blood pressure and increased endothelium-dependent relaxations to acetylcholine (log shift at IC50, ie, half-maximal inhibition of a preceding contraction, 10-, 8-, 13-, and 13-fold, P < .05 versus control), whereas relaxations to the NO donor 3-morpholino sydnonimine (SIN-1, 10(-9) to 10(-5) mol/L) remained unaffected. In WKY, chronic therapy with nifedipine (10 mg.kg-1.d-1 PO) affected neither blood pressure nor relaxations to acetylcholine or SIN-1. In rat coronary arteries, NO is synthesized via the endothelial L-arginine pathway and released after stimulation with acetylcholine. In SHR, chronic antihypertensive therapy with either angiotensin receptor antagonists, an angiotensin-converting enzyme inhibitor, or a calcium antagonist specifically increased the normal endothelium-dependent relaxations to acetylcholine, probably because of their blood pressure-lowering effects, whereas the responsiveness of vascular smooth muscle to NO remained unaffected.


Recent advances in histamine research: closing remarks.
In an attempt to highlight some of the more interesting problems of current histamine research several issues have been considered, including the difficulty of finding selective drugs, particularly agonists, the problems of receptor and organ selectivity, and the mystery of the biological function of histamine receptors in smooth muscle. These problems were raised in one form or another by speakers at this symposium and it is clear that despite the many exciting advances reported in the earlier communication many mysteries remain.


Hypercoagulability as a cause of sudden neurosensory hearing loss.
Fourteen patients with a documented sudden neurosensory hearing loss and four patients with other diseases causing neurosensory hearing loss were studied. The standardized coagulation workup included hematocrit, activated partial thromboplastin generation time, thrombin generation, prothrombin time, phase platelet count, platelet adhesivity, protamine sulfate, serum antithrombin III activity, fibrinogen, and Factor VIII values. Ony those patients having documented evidence of a neurosensory hearing loss occurring within hours or days were included in this study. Eight of the 14 paitents with a documented sudden neurosensory hearing loss satisfied our laboratory criteria for a diagnosis of in vitro hypercoagulability. Three of these patients had abnormal thrombin generation values, 4 had abnormal serum antithrombin III values, and 1 had an elevated platelet count. Four other patients with other diseases causing neurosensory hearing loss did not show evidence of in vitro hypercoagulability. It would appear from this data that coagulation abnormalities play a role in the pathogenesis of sudden neurosensory hearing loss.


Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study.
Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC. Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts. The study enrolled a total of 1589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group [mean age, 64.0 (9.9) years; 766 (48.2%) were females and 823 (51.8%) were males]. All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 months, P =0.002) and CSS (33.0 vs. 27.0 months, P =0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival ( P =0.003, HR=0.782; 95% CI, 0.667-0.917 for OS; P =0.004, HR=0.784; 95% CI, 0.663-0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates. Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.


Physiological and morphological adaptations of the fruit tree Ziziphus rotundifolia in response to progressive drought stress.
The physiological basis of drought resistance in Ziziphus rotundifolia Lamk., which is an important, multipurpose fruit tree of the northwest Indian arid zone, was investigated in a greenhouse experiment. Three irrigation regimes were imposed over a 34-day period: an irrigation treatment, a gradual drought stress treatment (50% of water supplied in the irrigation treatment) and a rapid drought stress treatment (no irrigation). Changes in gas exchange, water relations, carbon isotope composition and solute concentrations of leaves, stems and roots were determined. The differential rate of stress development in the two drought treatments did not result in markedly different physiological responses, but merely affected the time at which they were expressed. The initial response to decreasing soil water content was reduced stomatal conductance, effectively maintaining predawn leaf water potential (Psi(leaf)), controlling water loss and increasing intrinsic water-use efficiency, while optimizing carbon gain during drought. Carbon isotope composition (delta13C) of leaf tissue sap provided a more sensitive indicator of changes in short-term water-use efficiency than delta13C of bulk leaf tissue. As drought developed, osmotic potential at full turgor decreased and total solute concentrations increased in leaves, indicating osmotic adjustment. Decreases in leaf starch concentrations and concomitant increases in hexose sugars and sucrose suggested a shift in carbon partitioning in favor of soluble carbohydrates. In severely drought-stressed leaves, high leaf nitrate reductase activities were paralleled by increases in proline concentration, suggesting an osmoprotective role for proline. As water deficit increased, carbon was remobilized from leaves and preferentially redistributed to stems and roots, and leaves were shed, resulting in reduced whole-plant transpiration and enforced dormancy. Thus, Z. rotundifolia showed a range of responses to different drought intensities indicating a high degree of plasticity in response to water deficits.


Back-End, CMOS-Compatible Ferroelectric Field-Effect Transistor for Synaptic Weights.
Neuromorphic computing architectures enable the dense colocation of memory and processing elements within a single circuit. This colocation removes the communication bottleneck of transferring data between separate memory and computing units as in standard von Neuman architectures for data-critical applications including machine learning. The essential building blocks of neuromorphic systems are nonvolatile synaptic elements such as memristors. Key memristor properties include a suitable nonvolatile resistance range, continuous linear resistance modulation, and symmetric switching. In this work, we demonstrate voltage-controlled, symmetric and analog potentiation and depression of a ferroelectric Hf0.57Zr0.43O2 (HZO) field-effect transistor (FeFET) with good linearity. Our FeFET operates with low writing energy (fJ) and fast programming time (40 ns). Retention measurements have been performed over 4 bit depth with low noise (1%) in the tungsten oxide (WOx) readout channel. By adjusting the channel thickness from 15 to 8 nm, the on/off ratio of the FeFET can be engineered from 1 to 200% with an on-resistance ideally >100 kΩ, depending on the channel geometry. The device concept is using earth-abundant materials and is compatible with a back end of line (BEOL) integration into complementary metal-oxide-semiconductor (CMOS) processes. It has therefore a great potential for the fabrication of high-density, large-scale integrated arrays of artificial analog synapses.


Cervical Myelopathy Caused by Invaginated Laminae of the Axis into the Spinal Canal in a Pediatric Patient.
Cervical myelopathy caused by invaginated laminae of the axis is an extremely rare entity. Advanced imaging techniques are useful to define this rare pathology and site of the spinal canal compression. Surgical removal of the floating laminae is commonly an adequate treatment method. Fusion procedures should be added in the presence of instability. There are few cases of invaginated anomalous laminae of the axis in the literature. In this report, to the best of our knowledge having reviewed the literature, the youngest and first female patient is presented.


New algorithms to represent complex pseudoknotted RNA structures in dot-bracket notation.
Understanding the formation, architecture and roles of pseudoknots in RNA structures are one of the most difficult challenges in RNA computational biology and structural bioinformatics. Methods predicting pseudoknots typically perform this with poor accuracy, often despite experimental data incorporation. Existing bioinformatic approaches differ in terms of pseudoknots' recognition and revealing their nature. A few ways of pseudoknot classification exist, most common ones refer to a genus or order. Following the latter one, we propose new algorithms that identify pseudoknots in RNA structure provided in BPSEQ format, determine their order and encode in dot-bracket-letter notation. The proposed encoding aims to illustrate the hierarchy of RNA folding. New algorithms are based on dynamic programming and hybrid (combining exhaustive search and random walk) approaches. They evolved from elementary algorithm implemented within the workflow of RNA FRABASE 1.0, our database of RNA structure fragments. They use different scoring functions to rank dissimilar dot-bracket representations of RNA structure. Computational experiments show an advantage of new methods over the others, especially for large RNA structures. Presented algorithms have been implemented as new functionality of RNApdbee webserver and are ready to use at http://rnapdbee.cs.put.poznan.pl. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Affiliations with medical care providers.
Two analytical techniques are applied to a household survey of Rhode Island residents to develop the concept of an affiliation with medical care provider. A modification of a deviant case analysis is used to examine those people who are extreme in terms of the numbers of affiliations that they have with medical care providers. Overall, 4.1% of the sample have no affiliations and 7.3% have four or more affiliations. One of the most important variables in distinguishing those people with an unusual number of affiliations is a subjective variable of health status--whether they worry about their health. Nonparticipants rarely worry about their health and are generally in good health, while those with a high number of affiliations worry a great deal, regardless of their actual health status. A multiple regression analysis reveals that the variables of number of health conditions, sex, insurance, worry about health, income, disability days, and family structure are significantly related to mean number of affiliations with an R2 of 19.5%. Discussion includes the study's implications both for greater understanding of how and why people seek care and for application in the further development of a social psychological model of health behavior.


How Mixed-Effects Modeling Can Advance Our Understanding of Learning and Memory and Improve Clinical and Educational Practice.
Purpose A key goal of researchers, clinicians, and educators within the fields of speech, language, and hearing sciences is to support the learning and memory of others. To do so, they consider factors relevant to the individual, the material to be learned, and the training strategy that can maximize learning and retention. Statistical methods typically used within these fields are inadequate for identifying the complex relationships between these factors and are ill equipped to account for variability across individuals when identifying these relationships. Specifically, traditional statistical methods are often inadequate for answering questions about special populations because samples drawn from these populations are usually small, highly variable, and skewed in distribution. Mixed-effects modeling provides advantages over traditional statistical techniques to answer complex questions while taking into account these common characteristics of special populations. Method and Results Through 2 examples, I illustrate advantages of mixed-effects modeling in answering questions about learning and memory and in supporting better translation of research to practice. I also demonstrate key similarities and differences between analysis of variance, regression analyses, and mixed-effects modeling. Finally, I explain 3 additional advantages of using mixed-effects modeling to understand the processes of learning and memory: the means to account for missing data, assess the contribution of variations in delay intervals, and model nonlinear relationships between factors. Conclusions Through mixed-effects modeling, researchers can disseminate accurate information about learning and memory to clinicians and educators. In turn, through enhanced statistical literacy, clinicians and educators can apply research findings to practice with confidence. Overall, mixed-effects modeling is a powerful tool to improve the outcomes of the individuals that researchers and practitioners serve within the fields of speech, language, and hearing sciences.


Identification of differentially expressed genes and pathways for intramuscular fat deposition in pectoralis major tissues of fast-and slow-growing chickens.
Intramuscular fat (IMF) is one of the important factors influencing meat quality, however, for chickens, the molecular regulatory mechanisms underlying this trait have not yet been determined. In this study, a systematic identification of candidate genes and new pathways related to IMF deposition in chicken breast tissue has been made using gene expression profiles of two distinct breeds: Beijing-you (BJY), a slow-growing Chinese breed possessing high meat quality and Arbor Acres (AA), a commercial fast-growing broiler line. Agilent cDNA microarray analyses were conducted to determine gene expression profiles of breast muscle sampled at different developmental stages of BJY and AA chickens. Relative to d 1 when there is no detectable IMF, breast muscle at d 21, d 42, d 90 and d 120 (only for BJY) contained 1310 differentially expressed genes (DEGs) in BJY and 1080 DEGs in AA. Of these, 34-70 DEGs related to lipid metabolism or muscle development processes were examined further in each breed based on Gene Ontology (GO) analysis. The expression of several DEGs was correlated, positively or negatively, with the changing patterns of lipid content or breast weight across the ages sampled, indicating that those genes may play key roles in these developmental processes. In addition, based on KEGG pathway analysis of DEGs in both BJY and AA chickens, it was found that in addition to pathways affecting lipid metabolism (pathways for MAPK & PPAR signaling), cell junction-related pathways (tight junction, ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton), which play a prominent role in maintaining the integrity of tissues, could contribute to the IMF deposition. The results of this study identified potential candidate genes associated with chicken IMF deposition and imply that IMF deposition in chicken breast muscle is regulated and mediated not only by genes and pathways related to lipid metabolism and muscle development, but also by others involved in cell junctions. These findings establish the groundwork and provide new clues for deciphering the molecular mechanisms underlying IMF deposition in poultry. Further studies at the translational and posttranslational level are now required to validate the genes and pathways identified here.


ST segment change and T wave amplitude ratio in lead aVR associated with coronary artery disease severity in patients with non-ST elevation myocardial infarction: A retrospective study.
Non-ST elevation myocardial infarction (NSTEMI) severity is difficult only with electrocardiogram (ECG). In most cases, NSTEMI patients are followed with cardiac enzymes without early invasive intervention if no severe chest pain exists in the emergency department (ED) or coronary intensive care unit (CICU).Our aim was to evaluate association between CAD severity and ST segment change in lead aVR (STaVR)/T wave amplitude in lead aVR (TAaVR) ratio in patients with NSTEMI.We included 306 patients with NSTEMI in the ED between 2015 and 2016. STaVR and TAaVR values were measured from 12-derivation ECG underwent on admission to the ED. The absolute values of STaVR and TAaVR were calculated and the following were obtained; ratio 1:|STaVR|/|TAaVR|, ratio 2:|TAaVR|/|STaVR|, and ratio 3: by dividing the variable with larger absolute value to other variable with smaller absolute value (|larger value|/|smaller value|). The SYNTAX score (SS) was calculated from coronary angiography in all patients.In analysis of the bivariate correlation between SS and ratios; significantly positive, strongly with ratio 3 (r = 0.692, P < .001), and only ratio 3 was determined to be an independent predictor for SS in linear regression analysis (OR: 0.642, 95% CI: 0.432-0.853, P = .001).Severity of CAD may be estimated by evaluating STaVR and TAaVR ratio in patients with NSTEMI.


Cascade of Solitonic Excitations in a Superfluid Fermi gas: From Planar Solitons to Vortex Rings and Lines.
We follow the time evolution of a superfluid Fermi gas of resonantly interacting ^{6}Li atoms after a phase imprint. Via tomographic imaging, we observe the formation of a planar dark soliton, its subsequent snaking, and its decay into a vortex ring, which, in turn, breaks to finally leave behind a single solitonic vortex. In intermediate stages, we find evidence for an exotic structure resembling the Φ soliton, a combination of a vortex ring and a vortex line. Direct imaging of the nodal surface reveals its undulation dynamics and its decay via the puncture of the initial soliton plane. The observed evolution of the nodal surface represents dynamics beyond superfluid hydrodynamics, calling for a microscopic description of unitary fermionic superfluids out of equilibrium.


Treatment of experimental pneumonia due to penicillin-resistant Streptococcus pneumoniae in immunocompetent rats.
A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in immunocompetent rats and could be used to explore the pathophysiology and to evaluate optimal therapy of this infection in the immunocompetent host.


Two new species of the Fusarium solani species complex isolated from compost and hibiscus (Hibiscus sp.).
Two new species in the Fusarium solani species complex (FSSC) are described and introduced. The new taxa are represented by German isolates CBS 142481 and CBS 142480 collected from commercial yard waste compost and vascular tissue of a wilting branch of hibiscus, respectively. The phylogenetic relationships of the collected strains to one another and within the FSSC were evaluated based on DNA sequences of 6 gene loci. Due to the limited sequence data available for reference strains in GenBank, however, a multi-gene phylogenetic analysis included partial sequences for the internal transcribed spacer region and intervening 5.8S nrRNA gene (ITS), translation elongation factor 1-alpha (tef1) and the RNA polymerase II second largest subunit (rpb2). Morphological and molecular phylogenetic data independently showed that these strains are distinct populations of the FSSC, nested within Clade 3. Thus, we introduce Fusarium stercicola and Fusarium witzenhausenense as novel species in the complex. In addition, 19 plant species of 7 legume genera were evaluated for their potential to host the newly described taxa. Eighteen plant species were successfully colonized, with 6 and 9 of these being symptomatic hosts for F. stercicola and F. witzenhausenense, respectively. As plants of the family Fabaceae are very distant to the originally sourced material from which the new taxa were recovered, our results suggest that F. stercicola and F. witzenhausenense are not host-specific and are ecologically fit to sustain stable populations in variety of habitats.


Cardiovascular effects of antimuscarinic agents and beta3-adrenergic receptor agonist for the treatment of overactive bladder.
Overactive bladder (OAB) syndrome is common in the general population, particularly in elderly patients. Antimuscarinic drugs (AMs) are considered the mainstay pharmaceutical treatment of OAB whereas β3-adrenoceptor agonists, such as mirabegron, represent a good alternative. Owing to the important role of muscarinic and β3 receptors in cardiovascular (CV) tissue and to the fact that OAB patients often have CV comorbidities, the safety-profile of these drugs constitute an important challenge. The aim of this review is to evaluate the CV effects of AMs and mirabegron in OAB. A systematic literature search from inception until December 2017 was performed on PubMed and Medline. AMs are generally considered to have good CV safety profile but, however, they may cause undesirable adverse events, such as dry mouth, constipation. CV AEs are rare but noteworthy, the most common CV consequences related to the use of these drugs are constituted by an increase in HR and QT interval. Mirabegron has similar efficacy and tolerability to AMs but causes less adverse events, with either modest hypertension and modest increase in HR (<5 bpm) being the most commonly reported.


Pain: A Statistical Account.
Perception is seen as a process that utilises partial and noisy information to construct a coherent understanding of the world. Here we argue that the experience of pain is no different; it is based on incomplete, multimodal information, which is used to estimate potential bodily threat. We outline a Bayesian inference model, incorporating the key components of cue combination, causal inference, and temporal integration, which highlights the statistical problems in everyday perception. It is from this platform that we are able to review the pain literature, providing evidence from experimental, acute, and persistent phenomena to demonstrate the advantages of adopting a statistical account in pain. Our probabilistic conceptualisation suggests a principles-based view of pain, explaining a broad range of experimental and clinical findings and making testable predictions.


Reductions in crop yields across China from elevated ozone.
Exposure of crops to high concentrations of ozone can cause substantial reductions in yield that pose a serious threat to global food security. Here we provide comprehensive estimates of yield losses for key crops across China between 2014 and 2017 attributed to ozone using a number of new approaches. We use an air quality model at 5 km resolution and crop-specific dose-response functions developed for both concentration- and flux-based metrics. We bias correct modelled ozone concentrations and metrics using observations from more than 1000 locations. We find that on a 4-year average basis, production losses of key crops are 34-91 million metric tonnes (Mt/yr), dependent on the approach used, with highest losses in Henan province. At a national level, loss of winter wheat production derived using a China-specific dose-response function increased by 82% from 2014 to 2017, with large interannual variations in the North China Plain and in eastern China. Winter wheat losses estimated using flux-based functions, which require robust simulation of stomatal conductance and underlying vegetation physiology, are significantly lower, at 30 Mt/yr. We show that the definition of the growing season may have a greater impact on estimated losses than small biases in ozone surface concentrations. Although uncertainties remain, our findings demonstrate that increasing ozone concentrations have substantial adverse impacts on crop yields and threaten food security in China. It is important to control ozone concentrations to mitigate these negative impacts.


A preliminary study for the development of a scale to assess perceptions about physicians.
This study aimed to develop a scale that can be used to assess the perceptions of the community about physicians and their medical practice. A Likert-type scale was developed and applied to 220 subjects twice within a 7-10 day interval. Internal consistency reliability and test-retest reliability were used as indicators of the reliability of the scale. Chronbach's alpha values obtained from two reliability tests were 0.82 and 0.83, respectively, and correlation coefficient between the two tests was 0.61. The mean value of items indicated that perceptions about physicians were between "negative" and "neutral". The reliability of this scale was found to be at acceptable levels and therefore it can be used to assess the perceptions of people from different social classes about physicians.


Hepatic Cancers Overview: Surgical and Chemotherapeutic Options, How Do Y-90 Microspheres Fit in?
Hepatocellular cancer (HCC) is most common primary liver malignancy in adults. Treatment for HCC is a multispecialty undertaking, with surgical, locoregional, and systemic options available. Choice of treatment depends upon patient and disease factors. Surgical therapy, including resection and transplantation, is the primary curative treatment and is best suited to patients with early disease. More advanced disease may be amenable to locoregional therapies to "bridge" to transplantation, downstage disease, or as destination therapy for unresectable cases. These include percutaneous ablation, transarterial therapy, external radiation, and radioembolization with yttrium-90 conjugated beads. Patients with more advanced disease may benefit most from systemic chemotherapeutic or small molecule inhibitor options available, many of which have only been recently FDA approved. Immunotherapy is the newest component of HCC treatment. The Y-90 consultant should be familiar with all modalities of HCC treatment and the interplay between them.


Usefulness of the Beagle Model in the Evaluation of Paracetamol and Ibuprofen Exposure after Oral Administration to Pediatric Populations: An Exploratory Study.
The present study aimed to explore the usefulness of beagle dogs in combination with physiologically based pharmacokinetic (PBPK) modeling in the evaluation of drug exposure after oral administration to pediatric populations at an early stage of pharmaceutical product development. An exploratory, single-dose, crossover bioavailability study in six beagles was performed. A paracetamol suspension and an ibuprofen suspension were coadministered in the fasted-state conditions, under reference-meal fed-state conditions, and under infant-formula fed-state conditions. PBPK models developed with GastroPlus v9.7 were used to inform the extrapolation of beagle data to human infants and children. Beagle-based simulation outcomes were compared with published human-adult-based simulations. For paracetamol, fasted-state conditions and reference-meal fed-state conditions in beagles appeared to provide adequate information for the applied scaling approach. Fasted-state and/or reference-meal fed-state conditions in beagles appeared suitable to simulate the performance of ibuprofen suspension in pediatric populations. Contrary to human-adult-based translations, extrapolations based on beagle data collected under infant-formula fed-state conditions appeared less useful for informing simulations of plasma levels in pediatric populations. Beagle data collected under fasted and/or reference-meal fed-state conditions appeared to be useful in the investigation of pediatric product performance of the two investigated highly permeable and highly soluble drugs in the upper small intestine. The suitability of the beagle as a preclinical model to understand pediatric drug product performance under different dosing conditions deserves further evaluation with a broader spectrum of drugs and drug products and comparisons with pediatric in vivo data.


Predicting Risk for Opioid Misuse in Chronic Pain with a Single-Item Measure of Catastrophic Thinking.
Chronic pain patients are frequently treated with opioid medications in primary care, where brief measures of risk for opioid misuse have great utility. Catastrophic thinking is a clinically relevant and potentially modifiable factor associated with several chronic pain outcomes, including risk for opioid misuse. This study examined the utility of a single-item measure of pain-related catastrophizing in predicting risk of opioid misuse. 119 chronic pain patients completed the Coping Strategies Questionnaire catastrophizing item, Pain Catastrophizing Scale (PCS), and Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Area under the receiver operator curve (AUC) and linear regression were used to examine predictive utility of the catastrophizing item. The catastrophizing item demonstrated a fair ability to discriminate those with high risk for opioid misuse on the SOAPP-R (AUC = 0.74), whereas the PCS demonstrated good discrimination (AUC = 0.85). The single item alone accounted for 30% of variance in SOAPP-R scores. A single question assessing pain catastrophizing has utility for predicting risk for opioid misuse. In addition, it provides the primary care provider with information on a potentially modifiable risk factor that can be addressed within the context of a brief clinical visit.


Flexible assertive community treatment teams can change complex and fragmented service systems: experiences of service providers.
Implementing innovative health service models in existing service systems is complicated and context dependent. Flexible assertive community treatment (FACT) is a multidisciplinary service model aimed at providing integrated care for people with severe mental illness. The model was developed in the Netherlands and is now used in several countries, such as Norway. The Norwegian service system is complex and fragmented, with challenges in collaboration. Limited research has been performed on FACT teams and other new integrative health service models as part of such systems. However, such knowledge is important for future adjustments of innovation processes and service systems. Our aim was to explore how FACT teams are integrated into the existing formal public service system, how they function and affect the system, and describe some influencing factors to this. We sought to address how service providers in the existing service system experience the functioning of FACT teams in the system. Five focus group interviews were undertaken 3 years after the FACT teams were implemented. Forty service providers representing different services from both levels of administration (primary and specialist healthcare) from different Norwegian regions participated in this study. Team leaders of the FACT teams also participated. Service providers were recruited through purposeful sampling. Interviews were analysed using thematic text analysis. The analysis revealed five main themes regarding FACT teams: (1) They form a bridge between different services; (2) They collaborate with other services; (3) They undertake responsibility and reassure other services; (4) They do not close all gaps in service systems; and (5) They are part of a service system that hampers their functioning. The FACT teams in this study contributed to positive changes in the existing service system. They largely contributed to less complex and fragmented systems by forming a bridge and undertaking responsibility in the system and by collaborating with and reassuring other services; this has reduced some gaps in the system. The way FACT teams function and needs of the existing system appear to have contributed positively to these findings. However, complexity and fragmentation of the system partly hamper functioning of the FACT teams.


Rabbit hindlimb glucose uptake assessed with positron-emitting fluorodeoxyglucose.
The feasibility of estimating skeletal muscle glucose uptake in vivo was examined by using the glucose analogue 2-[18F]deoxy-2-fluoro-D-glucose (2-[18F]FDG) in the rabbit hindlimb. A pair of collimated coincidence gamma photon detectors was used to monitor the accumulation of tracer in the tissue after 2-[18F]FDG injection. Time-activity curves were generated on a second-by-second basis under control conditions, during increased contractile activity, or hyperinsulinemia. The arterial input of 2-[18F]FDG, plasma glucose, lactate, free fatty acids, and insulin were determined. A graphical (Patlak plot) procedure was used to determine the fractional rate of tracer phosphorylation and therefore trapping in the muscle. From the graphical analysis, the estimated rate of glucose phosphorylation (R) in the unperturbed state was calculated to be 0.037 mumol.min-1.ml-1 of tissue. During perturbation by electrical stimulation, an increase in the rate of tracer phosphorylation (K) was observed. No change in the rate of tracer phosphorylation was observed during hyperinsulinemia. The results support the use of 2-[18F]FDG and the graphical procedure for the noninvasive assessment of glucose uptake by skeletal muscle in vivo. The method described is sensitive to changes in the rate of tracer uptake with respect to time and physiological interventions.


Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis.
Epidemiological, biochemical, animal model and clinical trial data described in this overview strongly suggest that polyunsaturated fatty acids, particularly n-6 fatty acids, have a role in the pathogenesis and treatment of multiple sclerosis (MS). Data presented provides further evidence for a disturbance in n-6 fatty acid metabolism in MS. Disturbance of n-6 fatty acid metabolism and dysregulation of cytokines are shown to be linked and a "proof of concept clinical trial" further supports such a hypothesis. In a randomised double-blind, placebo controlled trial of a high dose and low dose selected GLA (18:3n-6)-rich oil and placebo control, the high dose had a marked clinical effect in relapsing-remitting MS, significantly decreasing the relapse rate and the progression of disease. Laboratory findings paralleled clinical changes in the placebo group in that production of mononuclear cell pro-inflammatory cytokines (TNF-alpha, IL-1beta) was increased and anti-inflammatory TGF-beta markedly decreased with loss of membrane n-6 fatty acids linoleic (18:2n-6) and arachidonic acids (20:4n-6). In contrast there were no such changes in the high dose group. The improvement in disability (Expanded Disability Status Scale) in the high dose suggests there maybe a beneficial effect on neuronal lipids and neural function in MS. Thus disturbed n-6 fatty acid metabolism in MS gives rise to loss of membrane long chain n-6 fatty acids and loss of the anti-inflammatory regulatory cytokine TGF-beta, particularly during the relapse phase, as well as loss of these important neural fatty acids for CNS structure and function and consequent long term neurological deficit in MS.


Barriers, Attitudes, and Influences Towards Dietary Intake Amongst Elite Rugby Union Players.
Background: Dietary intakes can impact an athletes health and performance. Although evidence exists about what an athlete should eat, an athlete's nutritional intake is influenced by many factors. The limited research available suggests the main barriers preventing optimal nutritional intakes reported by athletes are lack of time, food accessibility, poor cooking skills, costs, taste, and time spent in "off-season." Although these factors have been shown to influence dietary intake they remain relatively unexplored in Rugby Union. This study aimed to describe the nutritional influences on dietary intake amongst Rugby Union player's. Methods: This was a qualitative study utilising in person individual interviews with all participants. Participants were Rugby Union players (n = 30) for either a Super Rugby franchise or one of their development squads in New Zealand. Participant's undertook recorded face to face interviews, which were later transcribed. A thematic approach was used to code the transcripts by the primary coder and the themes were subsequently evaluated by the research team. Results: Childhood upbringing, organisational skills, time and food security also emerged as barriers. Body composition and sport nutrition knowledge emerged as both barriers and enablers to nutritional intake. Influence on performance was an enabler to optimal dietary intake. Fully professional rugby players have access to dietitians, whereas development and semi-professional rugby players only have limited if any access, and they were more likely to seek nutritional information via social media. Conclusion: This study suggests a need for greater nutrition education at developmental levels with an emphasis on affordable food choices, meal planning and skills for interpreting online nutrition information.


Causal inference between rheumatoid arthritis and prostate cancer.
It is unclear if the association between rheumatoid arthritis (RA) and a higher risk of prostate cancer (Pca) reflects a causal relationship. We conducted a meta-analysis and used the Mendelian randomization method (MR) to evaluate the association between RA and Pca risk. A meta-analysis and subgroup analysis of the incidence of Pca in patients with RA was conducted. To determine whether genetically elevated RA levels were causally linked to Pca, two MR samples were employed. To eliminate gender-related bias, we conducted a stratified analysis of the GWAS data for RA by gender, specifically including 140,254 males. Additional MR analysis was also performed to determine potential confounding factors influencing the association between genetically susceptible RA and Pca. In total, 409,950 participants were enrolled in 20 trials to investigate the Pca risk in patients with RA. The meta-analysis suggested that RA was unrelated to the Pca risk (SIR = 1.072, 95% CI, 0.883-1.261). However, a subgroup analysis showed that low smoking rates might increase the Pca risk in patients with RA by 24%. The MR analysis showed that increased genetic susceptibility to RA was related to a high Pca risk (OR = 36.20, 95%CI = 1.24-1053.12, P = 0.037). The causality estimation of MR-Egger, Weighted mode, Simple mode, and Weighted median method were similar in direction and magnitude. Although our meta-analysis found no correlation between RA and Pca risk, MR analyses supported a causal relationship between genetic susceptibility to RA and increased prostate risk. Early attention to Pca risk in patients with RA may be important for improving prognosis and mortality in such patients. Further research is needed to determine the etiology of RA attributed to Pca and its underlying mechanisms.


Efficacy and safety of topical selamectin to eradicate pinworm (Syphacia spp.) infections in rats (Rattus norvegicus) and mice (Mus musculus).
We evaluated the efficacy and safety of topical selamectin, a novel avermectin, in eliminating naturally acquired Syphacia muris infections in rats and S. obvelata infections in mice. S. muris-positive rats were assigned randomly to 4 groups: selamectin (0.6 mg/kg), selamectin (6.0 mg/kg), fenbendazole-medicated (150 ppm) chow, and untreated. S. obvelata-positive mice were allocated into 4 groups similar to those for rats. Animals not exposed to pinworm-contaminated bedding were designated as negative controls. Treatment success was assessed weekly by anal tape impressions and by necropsy examinations at the end of week 9. Evaluations of intestinal contents at necropsy revealed that, although safe, topical selamectin was 100% ineffective in eliminating Syphacia spp. infections in rats and mice. Treatment with fenbendazole-medicated chow resulted in negative anal tape impressions beginning at week 2 in rats and week 1 in mice. Negative anal tape impressions in fenbendazole-treated animals were confirmed by negative intestinal content evaluations. Of the 2 treatments evaluated, fenbendazole-medicated chow remains an effective and practical method to eliminate pinworm infections in mice and rats.


Change in smoking, diet, and walking for exercise in Blacks.
Positive changes in one health behavior may be accompanied by other constructive health behavior changes. Thus, the authors investigated the association of smoking reduction and cessation to changes in fruit and vegetable (FV) intake and engaging in walking for exercise. This study included 539 Black light smokers (≤10 cigarettes per day ≥25 days/month) enrolled in a 2 × 2 factorial study (placebo vs. nicotine gum, health education vs. motivational interviewing). Reducing cigarette consumption (p = .02) and quitting smoking (p < .01), as well as receiving the nicotine gum (p = .04), was associated with increased FV intake, after controlling for baseline FV intake. Compared with those who did not reduce their smoking, both reducers (p < .001) and quitters (p < .001) were more likely to walk for exercise at follow-up, after controlling for baseline walking status (p = .01). Thus, addressing one health risk behavior may prompt other positive health behaviors, which may argue for developing interventions targeting multiple health risk behaviors.


Establishment and characterization of a chimeric infectious cDNA clone of classical swine fever virus.
Classical swine fever virus (CSFV) causes a highly contagious disease among swine that has an important economic impact worldwide. There are two important CSFV strains in China, Shimen and hog cholera lapinized virus (HCLV). Shimen strain is highly virulent while HCLV, also referred to as C-strain, is a live attenuated vaccine strain considered to be one of the most effective and safest live vaccines. In this study, a chimeric infectious cDNA clone of CSFV named pT7SM-c was engineered by replacing the E(rns) genomic region of an infectious clone of CSFV Shimen strain, pT7SM, with the same region obtained from HCLV. RNA transcripts of pT7SM-c containing an engineered EcoRI site that served as a genetic marker were directly infectious in PK15 cells. The rescued virus vT7SM-c showed similar growth kinetics and cytopathic effect with the parental virus vT7SM in the cells. The chimeric infectious cDNA clone can be used as a practical tool for further studying of the virulence, protein function and pathogenesis of CSFV through genetic manipulation.


[Risk/protective factors and prevention programs for drug dependence in Peru].
Risk/ protective factors (RPF) are main elements for the analysis, understanding and formulation of answers for the prevention of drug dependences. The objective of this article is to present a literature review about the RPF and their implications in the design of preventive programs. It will focus on individual (genetic aspects, early experiences and psicosocial skills), family (parental control and monitoring, permissiveness, parenting styles), peer (group pressure and social norms) and communitarian (disorganization) RPF. On the other hand, the need of incorporating a multifactor conceptual framework for the preventive approach to drug dependences, articulating the intervention spaces (school, family and community), assuming and evolving perspective allowing the implementations of sustained actions is evidenced. On top, the implications for future research and public policy formulation are discussed.


Nursing home-acquired bloodstream infection.
This article reviews published studies of nursing home-acquired BSI in North America to determine whether there have been changes in the epidemiology of this infection in the past 20 years and to define indications for blood cultures in the nursing home setting. A Medline search was conducted for the period from 1980 to August 2003. Seven studies of nursing home-acquired BSI were identified. The incidence of nursing home-acquired BSI was low (0.3 episode per 1,000 resident care-days). Sources of BSI changed little during the past two decades, with urinary tract infection representing approximately 50% of the episodes. The bacteriology also did not change substantially during the past 20 years; gram-negative bacilli were isolated in approximately 50% of the episodes and Escherichia coli was the most commonly isolated organism. In the most recent study, covering the period 1997-2000, resistance to fluoroquinolones and broad-spectrum penicillins and cephalosporins was uncommon among gram-negative blood isolates; MRSA was the most common resistant organism causing nursing home-acquired BSI. Case-fatality rates changed little during the past 20 years; urinary tract infection was associated with the lowest mortality and pneumonia had the highest case-fatality rate. There has been little change in the epidemiology of nursing home-acquired BSI in the past 20 years. Given the low incidence of BSI and the low overall yield of positive results of blood cultures (probably < or = 6%), there is currently no support for the routine use of blood cultures in the nursing home setting.


[The development and testing of reagents kit for detection and qualitative evaluation of DNA of methicillin sensitive and methicillin resistant Staphylococcus aureus and also methicillin resistant coagulase negative Staphylococcus spp. applying technique of polymerase chain reaction in "real time" mode].
The reagents kit is developed to identify and quantitatively detect DNA of methicillin sensitive and methicillin resistant Staphylococcus aureus, methicillin resistant coagulase negative Staphylococcus spp. in biological material using technique of polymerase chain reaction with hybridizational fluorescent detection and having higher analytical and diagnostic characteristics. The application of the given reagents kit makes it possible to optimize the epidemiologic monitoring of propagation of methicillin resistant strains of Staphylococcus spp. Significantly decreasing duration and laboriousness of study.


SBS symptoms in relation to dampness and ventilation in inspected single-family houses in Sweden.
To investigate the relationships between symptoms compatible with the sick building syndrome (SBS) in adults and building dampness and ventilation in single-family houses. Within the Swedish BETSI study, a national sample of single-family houses were inspected by professional building experts, and adults living in the houses answered a questionnaire on SBS. Relationships between building factors and SBS were analysed using logistic regression. Of the respondents, 23% reported having had weekly SBS symptoms during the last three months. A large proportion of houses exhibited building or construction problems. In total, 40% of houses had dampness problems in the foundation, and this was related to a higher prevalence of both mucous and dermal symptoms, and any SBS symptoms. Furthermore, high air humidity was related to more symptoms, with the relationship with absolute humidity being stronger than that with relative humidity or moisture load. Symptoms were also more prevalent in houses with a high U value, reflecting a poor thermal insulation. Compared to natural ventilation, living in a house with mechanical supply and exhaust ventilation was related to a lower prevalence of general symptoms and any SBS symptoms, but there were only weak associations between measured air exchange rate and symptoms. A large proportion of single-family houses have dampness problems in the foundation, and pollutants may enter the living space of the house and affect the health of the occupants. Furthermore, absolute air humidity should be measured more often in indoor air studies.


Sulfated tyrosines of thyroglobulin are involved in thyroid hormone synthesis.
Thyroid hormone synthesis is under the control of thyrotropin (TSH), which also regulates the sulfation of tyrosines in thyroglobulin (Tg). We hypothesized that sulfated tyrosine (Tyr[S]) might be involved in the hormonogenic process, since the consensus sequence required for tyrosine sulfation to occur was observed at the hormonogenic sites. Porcine thyrocytes, cultured with TSH but without iodide in the presence of [(35)S]sulfate, secreted Tg which was subjected to in vitro hormonosynthesis with increasing concentrations of iodide. A 63% consumption of Tyr[S] (1 residue) was observed at 40 atoms of iodine incorporated into Tg, corresponding to a 40% hormonosynthesis efficiency. In addition, hyposulfated Tg secreted by cells incubated with sodium chlorate was subjected to in vitro hormonosynthesis. With 0.5 Tyr[S] residue (31% of the initial content), the efficiency of the hormonosynthesis was 29%. In comparison, when hormonosynthesis was performed by cells, with only 0.25 Tyr[S] residue (16% of the initial content), the hormonosynthesis efficiency fell to 18%. These results show that there exists a close correlation between the sulfated tyrosine content of Tg and the production of thyroid hormones.


Effects of smoking cessation on β-cell function, insulin sensitivity, body weight, and appetite.
To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, β-cell function, and appetite. Twenty-seven long-term smokers (n=27; nine females/18 males, 28±1 years, 22.9±0.6 kg/m(2)) attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; n=14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and β-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured. AFTER 3 MONTHS' SMOKING ABSTINENCE, BODY WEIGHT, AND FAT MASS WERE INCREASED (+4 AND +22% RESPECTIVELY, P0.05) AND FASTING INSULIN SENSITIVITY DETERIORATED (QUICKI: post, 0.37±0.02 vs baseline, 0.41±0.2; P<0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after >3 months' smoking abstinence (P<0.01). Carbohydrate ingestion increased after stopping smoking (P<0.05). NPY fasting levels were increased after >3 months (P<0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged. Smoking cessation is associated with transient metabolic changes including increased β-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.


Day-night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics.
The cerebrospinal fluid (CSF) provides mechanical protection for the brain and serves as a brain dispersion route for nutrients, hormones, and metabolic waste. The CSF secretion rate is elevated in the dark phase in both humans and rats, which could support the CSF flow along the paravascular spaces that may be implicated in waste clearance. The similar diurnal CSF dynamics pattern observed in the day-active human and the nocturnal rat suggests a circadian regulation of this physiological variable, rather than sleep itself. To obtain a catalog of potential molecular drivers that could provide the day-night-associated modulation of the CSF secretion rate, we determined the diurnal fluctuation in the rat choroid plexus transcriptomic profile with RNA-seq and in the CSF metabolomics with ultraperformance liquid chromatography combined with mass spectrometry. We detected significant fluctuation of 19 CSF metabolites and differential expression of 2,778 choroid plexus genes between the light and the dark phase, the latter of which encompassed circadian rhythm-related genes and several choroid plexus transport mechanisms. The fluctuating components were organized with joint pathway analysis, of which several pathways demonstrated diurnal regulation. Our results illustrate substantial transcriptional and metabolic light-dark phase-mediated changes taking place in the rat choroid plexus and its encircling CSF. The combined data provide directions toward future identification of the molecular pathways governing the fluctuation of this physiological process and could potentially be harnessed to modulate the CSF dynamics in pathology.


Ocular and periocular tumors in 855 Asian Indian geriatric patients.
The objective of this study was to describe the eye tumors in Asian Indian geriatric population (age >60 years) presenting to a multitier ophthalmology hospital network in India. This was a retrospective study of 855 Asian Indian geriatric patients. During the 3-year study period, 855 geriatric patients were diagnosed with eye tumors. The mean age at presentation with an ocular or periocular tumor was 68 years (median, 67 years; range, 60-91 years). There were 458 (54%) benign tumors and 397 (46%) malignant tumors. The distribution of benign versus malignant tumors in different age groups was 324 (71%) versus 259 (65%) in 60-70 years, 116 (25%) versus 99 (25%) in 71-80 years, and 18 (4%) versus 39 (10%) in >80 years' age groups. The three most common benign tumors included eyelid cyst (n = 99, 22%), eyelid nevus (n = 50, 11%), and pseudotumor or nonspecific orbital inflammatory disease (n = 38, 8%). The three most common malignant tumors included ocular surface squamous neoplasia (OSSN) (n = 208, 52%), periocular sebaceous gland carcinoma (n = 68, 17%), and periocular basal cell carcinoma (n = 25, 6%). Overall, OSSN was the most common tumor in all age groups (22% of all tumors in 60-70 years, 27% in 71-80 years, and 39% in >80 years' age groups). Overall, there is an increasing trend of malignant tumors with increasing age. OSSN is the most common tumor in the geriatric population encountered in a referral-based comprehensive ocular oncology practice in India.


Innate Immune Molecule NLRC5 Protects Mice From Helicobacter-induced Formation of Gastric Lymphoid Tissue.
Helicobacter pylori induces strong inflammatory responses that are directed at clearing the infection, but if not controlled, these responses can be harmful to the host. We investigated the immune-regulatory effects of the innate immune molecule, nucleotide-binding oligomerization domain-like receptors (NLR) family CARD domain-containing 5 (NLRC5), in patients and mice with Helicobacter infection. We obtained gastric biopsies from 30 patients in Australia. We performed studies with mice that lack NLRC5 in the myeloid linage (Nlrc5møKO) and mice without Nlrc5 gene disruption (controls). Some mice were gavaged with H pylori SS1 or Helicobacter felis; 3 months later, stomachs, spleens, and sera were collected, along with macrophages derived from bone marrow. Human and mouse gastric tissues and mouse macrophages were analyzed by histology, immunohistochemistry, immunoblots, and quantitative polymerase chain reaction. THP-1 cells (human macrophages, controls) and NLRC5-/- THP-1 cells (generated by CRISPR-Cas9 gene editing) were incubated with Helicobacter and gene expression and production of cytokines were analyzed. Levels of NLRC5 messenger RNA were significantly increased in gastric tissues from patients with H pylori infection, compared with patients without infection (P < .01), and correlated with gastritis severity (P < .05). H pylori bacteria induced significantly higher levels of chemokine and cytokine production by NLRC5-/- THP-1 macrophages than by control THP-1 cells (P < .05). After 3 months of infection with H felis, Nlrc5mø-KO mice developed gastric hyperplasia (P < .0001), splenomegaly (P < .0001), and increased serum antibody titers (P < .01), whereas control mice did not. Nlrc5mø-KO mice with chronic H felis infection had increased numbers of gastric B-cell follicles expressing CD19 (P < .0001); these follicles had features of mucosa-associated lymphoid tissue lymphoma. We identified B-cell-activating factor as a protein that promoted B-cell hyperproliferation in Nlrc5mø-KO mice. NLRC5 is a negative regulator of gastric inflammation and mucosal lymphoid formation in response to Helicobacter infection. Aberrant NLRC5 signaling in macrophages can promote B-cell lymphomagenesis during chronic Helicobacter infection.


[Familial adenomatous polyposis syndrome (FAP): pathogenesis and molecular mechanisms].
The impact that modern molecular biology has had on elucidating the genetic basis of neoplasia is best illustrated by the paradigm of sporadic and hereditary colon cancer. The clinical and hereditary picture of the familial adenomatous polyposis syndrome (FAP) implied the existence of a single gene that regulates the formation of adenomatous polyps, the precursor for most colorectal cancers. The identification of an interstitial deletion on chromosome 5q in a patient with Gardner's variant of FAP combined with classic linkage analysis facilitated the positional cloning of the adenomatous polyposis coli (APC) gene in 1991. FAP is caused by germline mutations in the APC gene. Somatic mutations in the APC gene are an early event in colorectal tumorigenesis, and can be detected in the majority of colorectal tumors. APC consists of 8,535 bp spanning 21 exons (16 translated exons) and encodes a 2,861 amino acid protein that is expressed in specific epithelial and mesenchymal cells of several fetal and adult human tissues. The APC protein is a large multidomain protein with a molecular mass of 300 kD. The best-known function of the APC protein is the Wnt-1 signaling pathway. Binding Wnt to its receptor, frizzled), leads to the inactivation of the glycogen synthase kinase 3 beta in a cytoplasmic complex with APC, beta-catenin, axin and components of the ubiquitin ligation machinery. This leads to a decrease in beta-catenin phosphorylation and inhibits its proteasomal degradation. As a consequence, increased beta-catenin is available to bind transcription factors leading to the activation of proliferative genes. In addition, APC has recently emerged as a multifunctional protein that can affect a variety of fundamental cellular processes, in particular cytoskeletal regulation and chromosomal stability. Improved understanding of both the genetics and biology of APC may, in time, culminate in preventive or therapeutic strategies specifically targeted at reducing the burden of colorectal cancer.


Occipitocervical fusion in elderly patients.
Occipitocervical disease (OCD) in elderly patients will become increasingly common as the population ages. Our experience with occipitocervical fusions (OCF) in this population suggests mixed outcomes. Twenty consecutive patients over 65 years old underwent OCF between 1995 and 2005. A retrospective review of demographic, presentation, surgical and outcome data was performed. Twenty patients averaging 75.3 years of age (range 65 to 91) were identified. All patients had evidence of myelopathy; however, the primary surgical indications were progressive spinal cord dysfunction (15), brainstem compression (3), and pain (2). Surgical approach was isolated posterior (9), or anterior transoral odontoidectomy followed by posterior stabilization (11). Overall, surgery improved function modestly; average modified Japanese Orthopedic Association functional score (improved 0.9 grades), average Ranawat Myelopathy Score (improved 0.4 grades), and average Nurick Myelopathy Grade (improved 0.6 grades). However, patients with poor preoperative functional assessment (Ranawat grade ≥ III) had greater neurologic improvement than those with good preoperative function, measured by Nurick grade improvement (1 vs. -0.28; P = .03) and Ranawat grade improvement (0.7 vs. -0.2; P = .03). Additionally, the posterior approach demonstrated significant improvement in Japanese Orthopedic Association functional assessment over patients with anterior/posterior approaches (2.2 vs. -0.3; P = .03), with fewer complications (posterior: 1 minor; anterior/posterior: 1 death, 2 major, 8 minor). Perioperative mortality occurred in 5%, and major morbidity in 10% of patients. Preventing or stabilizing neurologic deficit in patients with OCD may require OCF, despite the patient's age. In the elderly population, our data favor using the posterior approach when possible, and demonstrate greater neurologic improvement in patients with poor preoperative function.


Diseases of phenylalanine metabolism.
Continuing investigation of the system that hydroxylates phenylalanine to tyrosine has led to new insights into diseases associated with the malfunction of this system. Good evidence has confirmed that phenylketonuria (PKU) is not caused by a simple lack of phenylalanine hydroxylase. Dihydropteridine reductase deficiency as well as defects in biopterin metabolism may also cause the clinical features of phenylketonuria. Furthermore, these diseases do not respond to the standard treatment for phenylketonuria.


[The evolution of the structures of amino acid families].
Natural amino acids possessing common antiamino acids are divided into groups and families according to the genetic code algorithm a-n-n-a (amino acid-codon-anticodon-antiamino acid). In an attempt to study structural evolution of amino acid families, artificial genetic code models were constructed. It is suggested that after inclusion of asparaginase and glutamine into the coding system, one of the two natural amino acid families is split into two parts ("half-families").


[Structural changes in the chromatin during the cell differentiation of the erythroid series].
Data about the changes in the molecular organization of the cell nucleus on different levels of its structure during erythroid cell differentiation are presented. Changes are observed in DNA methylation and secondary structure. Protein composition of the chromatin and the length of the nucleosomal repeat change. Data about the peculiarities of the chromatin structure of erythroid-specific genes and their association to the nuclear skeleton are presented as well.


IgG-kappa immunoglobulin deposits involving the predescemetic region in a patient with multiple myeloma.
To report the clinico-pathologic features of corneal deposits in a patient with multiple myeloma with surgical intervention and follow-up. Interventional case report. We reviewed the patient's chart and the relevant literature on immunoglobulin corneal deposits and its prognosis. A 52-year-old man with a history of multiple myeloma underwent penetrating keratoplasty sequentially for decreased vision in both eyes secondary to abnormal corneal deposits. Pathologic examination of the keratectomy specimens, including immunohistochemistry and transmission electron microscopy, revealed IgG-kappa immunoglobulin deposits in the predescemetic region in both corneas. After keratoplasty, he regained excellent vision in both eyes, which was maintained at the end of 18 months of follow-up in both eyes despite early signs of recurrence in the right eye. His systemic condition was well controlled during the period of follow-up. Corneal deposits in multiple myeloma are well described in the literature, but there are few reports regarding the prognosis and visual function after penetrating keratoplasty. Our report shows that when the systemic condition is well controlled, penetrating keratoplasty has an excellent prognosis in these patients.


Studies in subjects with long-term nonprogressive human immunodeficiency virus infection.
In a small percentage of persons infected with human immunodeficiency virus type 1 (HIV-1), there is no progression of disease and CD4+ T-cell counts remain stable for many years. Studies of the histopathological, virologic, and immunologic characteristics of these persons may provide insight into the pathogenic mechanisms that lead to HIV disease and the protective mechanisms that prevent progression to overt disease. We studied 15 subjects with long-term nonprogressive HIV infection and 18 subjects with progressive HIV disease. Nonprogressive infection was defined as seven or more years of documented HIV infection, with more than 600 CD4+ T cells per cubic millimeter, no antiretroviral therapy, and no HIV-related disease. Lymph nodes from the subjects with nonprogressive infection had significantly fewer of the hyperplastic features, and none of the involuted features, characteristic of nodes from subjects with progressive disease. Plasma levels of HIV-1 RNA and the viral burden in peripheral-blood mononuclear cells were both significantly lower in the subjects with nonprogressive infection than in those with progressive disease (P = 0.003 and P = 0.015, respectively). HIV could not be isolated from the plasma of the former, who also had significantly higher titers of neutralizing antibodies than the latter. There was viral replication, however, in the subjects with nonprogressive infection, and virus was consistently cultured from mononuclear cells from the lymph nodes. In the lymph nodes virus "trapping" varied with the degree of formation of germinal centers, and few cells expressing virus were found by in situ hybridization. HIV-specific cytotoxic activity was detected in all seven subjects with nonprogressive infection who were tested. In persons who remain free of disease for many years despite HIV infection the viral load is low, but viral replication persists. Lymph-node architecture and immune function appear to remain intact.


Choices are inevitable: A qualitative exploration of the lifecosts of systemic lupus erythematosus.
Individuals with systemic lupus erythematosus experience considerable economic challenges. The aim of this research is to qualitatively investigate experiences of the lifecosts (direct and indirect economic costs and beyond) to those with systemic lupus erythematosus in Canada. Using a biopsychosocial conceptual framework and integrated knowledge translation approach, qualitative semi-structured interviews were conducted with 3 physicians, 5 representatives from systemic lupus erythematosus advocacy groups, and 29 adult systemic lupus erythematosus patients. Themes emerged deductively and inductively, and the theme code set was used to code all transcripts. Three dominant themes emerged: (1) impacts of systemic lupus erythematosus on quality of life, relationships, and health; (2) costs linked to healthcare; and (3) impacts of living with systemic lupus erythematosus on employment/economic standing. Whereas previous work has focused almost exclusively on the direct, individual costs of systemic lupus erythematosus, the biopsychosocial approach taken here emphasizes not only the individual and intermediate factors (such as the workplace and family), but also the system-level factors (i.e. system-level policies) that influence quality of life, healthcare, and employment/economic experiences of those with systemic lupus erythematosus. Results indicate a need to target interventions beyond the individual and their immediate context, and recognize that lifecosts are shaped significantly by systems-level action.