Self-management behaviors in older adults with asthma: associations with health literacy.
To examine self-management behaviors, including medication adherence and inhaler technique, in older adults with asthma and their association with health literacy. Observational cohort study. Primary care and pulmonary specialty practices in two tertiary academic medical centers and three federally qualified health centers in New York, New York, and Chicago, Illinois. Adults with moderate or severe persistent asthma aged 60 and older (N = 433). Outcomes were adherence to asthma controller medications, metered dose inhaler (MDI) and dry powder inhaler (DPI) techniques, having a usual asthma physician, and avoidance of four common triggers. Health literacy was assessed using the Short Test of Functional Health Literacy in Adults. The mean age was 67, and 36% of participants had marginal or low health literacy. Adherence was low (38%) overall and worse in individuals with low health literacy (22%) than in those with adequate literacy (47%, P < .001) and after adjusting for demographic factors and health status (odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.31-0.73). Similarly, inhaler technique was poor; only 38% and 54% had good MDI and DPI technique, respectively. Technique was worse in those with low health literacy (MDI technique: OR = 0.57, 95% CI = 0.38-0.85; DPI technique: OR = 0.42, 95% CI = 0.25-0.71). Asthma self-monitoring and avoidance of triggers occurred infrequently but were less consistently associated with low health literacy. Adherence to medications and inhaler technique are poor in older adults with asthma and worse in those with low health literacy. Clinicians should routinely assess controller medication adherence and inhaler technique and use low-literacy communication strategies to support self-management in older adults with asthma.


Neonatal resuscitation.
Ten million or more newborns worldwide each year need some type of resuscitation assistance. More than 1 million babies die annually from complications of birth asphyxia. Over the past 3 decades, neonatal resuscitation has evolved from disparate, word-of-mouth teaching methods to organized programs. The most widely-used curriculum is the Neonatal Resuscitation Program, which is supported by the American Academy of Pediatrics and the American Heart Association. To date more than 1.5 million individuals have been trained in the Neonatal Resuscitation Program. Resuscitation efforts are geared toward avoiding or mitigating the adverse sequelae of asphyxia neonatorum. Certain characteristics distinguish the preterm infant, including propensity to become hypothermic and higher potential for adverse neurologic and pulmonary complications from resuscitation efforts. In this era of evidence-based medicine the most recent Neonatal Resuscitation Program guidelines were developed to provide recommendations based on the best currently-available science. A number of major proposals received considerable scrutiny during the evaluation process. Many areas of neonatal resuscitation still need to be studied.


Aβ inhibition of ionic conductance in mouse basal forebrain neurons is dependent upon the cellular prion protein PrPC.
Current therapies for Alzheimer's disease (AD) address a loss of cholinergic neurons, while accumulation of neurotoxic amyloid β (Aβ) peptide assemblies is thought central to molecular pathogenesis. Overlaps may exist between prionopathies and AD wherein Aβ oligomers bind to the cellular prion protein PrP(C) and inhibit synaptic plasticity in the hippocampus (Laurén et al., 2009). Here we applied oligomeric Aβ to neurons with different PrP (Prnp) gene dosage. Whole-cell recordings were obtained from dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. In wild-type (wt) mice, Aβ₁₋₄₂ evoked a concentration-dependent reduction of whole-cell outward currents in a voltage range between -30 and +30 mV; reduction occurred through a combined modulation of a suite of potassium conductances including the delayed rectifier (I(K)), the transient outward (I(A)), and the iberiotoxin-sensitive (calcium-activated potassium, I(C)) currents. Inhibition was not seen with Aβ₄₂₋₁ peptide, while Aβ₁₋₄₂-induced responses were reduced by application of anti-PrP antibody, attenuated in cells from Prnp⁰/⁺ hemizygotes, and absent in Prnp⁰/⁰ homozygotes. Similarly, amyloidogenic amylin peptide depressed DBB whole-cell currents in DBB cells from wt mice, but not Prnp⁰/⁰ homozygotes. While prior studies give broad support for a neuroprotective function for PrP(C), our data define a latent pro-pathogenic role in the presence of amyloid assemblies.


A complex of chaperones and disulfide isomerases occludes the cytosolic face of the translocation protein Sec61p and affects translocation of the prion protein.
Secretion of newly synthesized proteins across the mammalian rough endoplasmic reticulum (translocation) is supported by the membrane proteins Sec61p and TRAM, but may also include accessory factors, depending on the particular translocation substrate. Studies designed to investigate the binding of anti-peptide antibodies to the carboxyl terminus of the alpha-subunit of Sec61 (Sec61palpha) lead us to the isolation of a complex of proteins that occlude the cytosolic face of Sec61palpha in microsomes that have been prepared by standard protocols used to study translocation in vitro [Walter, P., and Blobel, G. (1983) Methods Enzymol. 96, 84-93]. This complex was shown by nanospray tandem mass spectrometry to be composed of protein disulfide isomerase (PDI), calcium binding protein 1 (CABP1/P5), 72 kDa endoplasmic reticulum protein (ERp72), and BiP (heat shock protein A5/HSPA5), and has been named TR-PDI for "translocon-resident protein disulfide isomerase complex". This constitutes a novel location for these proteins, which are known to be major constituents of the lumen of the rough endoplasmic reticulum. We have not established the function of TR-PDI at this location, but did observe that the absence of this complex results in a relative loss of correct topology of prion protein insertion across RER membranes, indicating the possibility of a functional role in vivo.


Safety and efficacy of retropubic or transobturator midurethral slings in a randomized cohort of Turkish women.
The aim of this study was to evaluate the safety and efficacy of retropubic (RP) or transobturator (TO) midurethral slings (MUS) in a prospective randomized cohort of Turkish women. A total of 54 women with urodynamic stress urinary incontinence (SUI) were randomized to undergo either RP or TO MUS between August 2006 and February 2013 in a tertiary referral center by a single surgeon. All patients had history, physical examination, urodynamic evaluation and quality of life assessments. The validated Turkish versions of the SEAPI, ICIQ-SF and OAB-V8 questionnaires were used. The Advantage® RP and the Obtryx® TO MUS Systems were used for all RP and TO procedures. Twenty-seven patients were randomized to each group. The median follow-up was 48.5 ± 21.8 months. The median hospital stay was 24.0 ± 4.8 h and median operative time was 35.0 ± 19.9 min. The overall objective and subjective cure rates were 92.6 and 79.6%, respectively. The quality of life of all patients significantly increased after the operation compared to their preoperative status. Patients with a poorer subjective cure rate were those with mixed urinary incontinence, whose preoperative SEAPI and OAB-V8 scores were significantly higher. MUS surgery is highly effective and could safely be performed in a cohort of Turkish women with SUI in subspecialty centers by experienced surgeons. There is no significant difference between RP or TO applications in terms of safety and efficacy. Further studies with long-term follow-up data are required.


Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates.
Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25-82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m2). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.


How Do Spinal Surgeons Perceive The Impact of Factors Used in Post-Surgical Complication Risk Scores?
When deciding about surgical treatment options, an important aspect of the decision-making process is the potential risk of complications. A risk assessment performed by a spinal surgeon is based on their knowledge of the best available evidence and on their own clinical experience. The objective of this work is to demonstrate the differences in the way spine surgeons perceive the importance of attributes used to calculate risk of post-operative and quantify the differences by building individual formal models of risk perceptions. We employ a preference-learning method - ROR-UTADIS - to build surgeon-specific additive value functions for risk of complications. Comparing these functions enables the identification and discussion of differences among personal perceptions of risk factors. Our results show there exist differences in surgeons' perceived factors including primary diagnosis, type of surgery, patient's age, body mass index, or presence of comorbidities.


Defective gap junctional intercellular communication in lung cancer: loss of an important mediator of tissue homeostasis and phenotypic regulation.
Gap junctions provide direct pathways for the exchange of molecules and ions between neighboring cells, a process known as gap junctional intercellular communication (GJIC). This GJIC is important for homeostasis and regulation of mitosis, differentiation, and apoptosis. Gap junctions are present in lung airway and alveolar epithelial cells and, in addition to the above roles, might coordinate ciliary beating and surfactant secretion. GJIC is decreased in human and mouse lung carcinoma cells because of reduced expression of the gap junction protein, connexin43 (Cx43), and defects in signal transduction pathways that mediate Cx43 function. This reduced GJIC is important in the behavior of lung carcinoma cells because forced expression of Cx43 in lung carcinoma cells inhibits their growth and tumorigenicity. In this report, we summarize our studies on the role of GJIC in lung neoplasia.


Measles-associated pneumonia and hepatitis during the measles outbreak of 2018.
Background Between 2017 and 2018, Greece experienced a measles outbreak, affecting >3000 patients, most of which were unvaccinated. Measles-associated pneumonia (MAP) is the most common serious compilation of the disease, but very few recent reports regarding its presentation are available. Materials and Methods Between January and May 2018, 11 adult patients presented to our department with acute measles virus infection, hypoxia and findings on chest X-ray. Clinical, laboratory and radiological data were collected and assessed. Nine out of eleven patients had hypoxic respiratory failure. Other complications included hepatitis, cholestasis and myositis, which were observed in the majority of patients. All patients received supplementary oxygen administration, whereas five patients required continuous positive airway pressure ventilation. Scoring of the radiological examinations performed was most notable for the presence of reticular opacities and consolidations. Statistical analysis demonstrated a significant association between PaO2/FiO2 values and the presence of reticular opacities, with PaO2/FiO2 decreasing as the mean value of the reticular opacities score increased (P = .02). Conclusion To our knowledge, this is the first report demonstrating an association between PaO2/FiO2 values and the presence of reticular opacities in patients with MAP. MAP should be suspected in any patient presenting with acute onset hypoxaemia and a reticular pattern on radiological examination, especially in outbreak settings. What is known Measles infections are on the rise in Europe, with epidemics affecting several European countries, resulting from suboptimal immunisation. The most common serious complication of measles is pneumonia, which is more common in adult patients and can cause significant morbidity. It is the most common cause of death due to measles. What is new In this report, we present 11 adults with measles-associated pneumonia, who presented with the combination of acute measles virus infection, hypoxia and findings on chest X-ray. To our knowledge, this is the first report demonstrating an association between the severity of hypoxaemia and the presence of reticular opacities on chest imaging studies.


LncRNA MIR200CHG inhibits EMT in gastric cancer by stabilizing miR-200c from target-directed miRNA degradation.
Gastric cancer (GC) is a heterogeneous disease, threatening millions of lives worldwide, yet the functional roles of long non-coding RNAs (lncRNAs) in different GC subtypes remain poorly characterized. Microsatellite stable (MSS)/epithelial-mesenchymal transition (EMT) GC is the most aggressive subtype associated with a poor prognosis. Here, we apply integrated network analysis to uncover lncRNA heterogeneity between GC subtypes, and identify MIR200CHG as a master regulator mediating EMT specifically in MSS/EMT GC. The expression of MIR200CHG is silenced in MSS/EMT GC by promoter hypermethylation, associated with poor prognosis. MIR200CHG reverses the mesenchymal identity of GC cells in vitro and inhibits metastasis in vivo. Mechanistically, MIR200CHG not only facilitates the biogenesis of its intronic miRNAs miR-200c and miR-141, but also protects miR-200c from target-directed miRNA degradation (TDMD) through direct binding to miR-200c. Our studies reveal a landscape of a subtype-specific lncRNA regulatory network, providing clinically relevant biological insights towards MSS/EMT GC.


Chinese childbearing decision-making in mainland China in the post-one-child-policy era.
In 2016, China enacted its two-child policy, further lifted to a three-child policy in 2021, in response to low birth rates and imbalanced sex ratios resulting from the almost 40-year one-child policy. Despite this, China's birthrate is at a historic low as fewer parents are having children. Now more than ever, inductive explorations are needed to understand what motivates Chinese parents to have first and second children in the post-one-child policy era, particularly explorations that situate individual decision-making within the larger social context. Individual and relational choices occur in larger sociopolitical contexts. Understanding these "personal" actions involves considering how micro and macro processes inform each other. In this study, we elicited qualitative responses from Chinese mothers (N = 117) with two children in early childhood (firstborn ≤8 years old) from Liao Ning province. Most mothers were well educated, employed, and married to children's fathers. Using inductive thematic analysis procedures, we coded qualitative responses about the factors that motivated mothers to have first and second children. Our data revealed that (a) mothers expressed different reasons for having firstborns compared to secondborns, and (b) decision-making occurred against a backdrop of interacting micro-level and macro-level influences (e.g., cultural norms, national policy changes). In particular, mothers described the decision to have secondborns as more deliberative than with firstborns, considering long-term benefits siblinghood and shared demands of elderly caregiving. If efforts to stimulate the national birthrate are likely to succeed, policymakers should consider micro-level as well as macro-level factors that shape mothers' childbearing decision-making.


Effect of postharvest storage time on quality characteristics of explosion puffing dried whole shiitake mushroom (Lentinula edodes) crisps.
Non-fried shiitake mushroom (Lentinula edodes) crisps fabricated by explosion puffing drying (EPD) are receiving worldwide attention because of their crispness, convenience, nutrition and health functions. The quality of mushroom crisps varies with storage time of fresh L. edodes. Therefore, the effect of postharvest storage time (ranging from 0 to 14 days) of fresh L. edodes on quality characteristics of EPD- processed mushroom crisps was evaluated. The weight loss and total color difference of fresh L. edodes were increased to 2.95% and 24.66, but moisture content, firmness and lightness were reduced by 6.14%, 40.70% and 43.57%, respectively, after 14 days storage. The puffing degree of mushroom crisps was initially increased to its highest value (55.95%) on the 4th day storage and thereafter decreased. The highest rehydration ratio (2.36) and crispness (63.67), and lowest hardness (102.95 N) of mushroom crisps were fabricated with L. edodes on the 4th day of storage. Free water was predominant in fresh L. edodes, which was decreased for fresh L. edodes, whereas it increased initially to the maximum value and decreased thereafter for osmotic dehydrated and heat pump pre-dried L. edodes with increasing storage time. Principal component analysis and hierarchical cluster analysis confirmed that fresh L. edodes stored at different times had a remarkable effect on quality characteristics of mushroom crisps. Fresh L. edodes stored at 4 ± 1 °C for 4 days is recommended for fabrication of mushroom crisps with superior quality. This study provides a theoretical basis for selection of a suitable storage time for fresh L. edodes before EPD of crisps. © 2023 Society of Chemical Industry.


Tocotrienols have potent antifibrogenic effects in human intestinal fibroblasts.
Excessive fibroblast expansion and extracellular matrix (ECM) deposition are key events for the development of bowel stenosis in Crohn's disease (CD) patients. Tocotrienols are vitamin E compounds with proven in vitro antifibrogenic effects on rat pancreatic fibroblasts. We aimed at investigating the effects of tocotrienols on human intestinal fibroblast (HIF) proliferation, apoptosis, autophagy, and synthesis of ECM. HIF isolated from CD, ulcerative colitis (UC), and normal intestine were treated with tocotrienol-rich fraction (TRF) from palm oil. HIF proliferation was quantified by (3) H-thymidine incorporation, apoptosis was studied by DNA fragmentation, propidium iodide staining, caspase activation, and poly(ADP-ribose) polymerase cleavage, autophagy was analyzed by quantification of LC3 protein and identification of autophagic vesicles by immunofluorescence and production of ECM components was measured by Western blot. TRF significantly reduced HIF proliferation and prevented basic fibroblast growth factor-induced proliferation in CD and UC, but not control HIF. TRF enhanced HIF death by promoting apoptosis and autophagy. HIF apoptosis, but not autophagy, was prevented by the pan-caspase inhibitor zVAD-fmk, whereas both types of cell death were prevented when the mitochondrial permeability transition pore was blocked by cyclosporin A, demonstrating a key role of the mitochondria in these processes. TRF diminished procollagen type I and laminin γ-1 production by HIF. Tocotrienols exert multiple effects on HIF, reducing cell proliferation, enhancing programmed cell death through apoptosis and autophagy, and decreasing ECM production. Considering their in vitro antifibrogenic properties, tocotrienols could be useful to treat or prevent bowel fibrosis in CD patients.


Cognitive and somatic symptoms of depression are associated with medical comorbidity in patients after acute myocardial infarction.
Depression is common in patients with acute myocardial infarction (AMI) and is associated with adverse health outcomes. However, the extent to which clinical depression is related to comorbid medical conditions is unknown. This study examined the degree of association between clinical depression and medical comorbidity in patients hospitalized with AMI. Two thousand four hundred and eighty-one depressed or socially isolated patients with AMI were enrolled, as part of the National Heart, Lung, and Blood Institute-sponsored Enhancing Recovery in Coronary Heart Disease clinical trial. A structured interview was used to diagnose major and minor depression and dysthymia; severity of depression was measured by the Hamilton Rating Scale for Depression and the Beck Depression Inventory. Level of social support was measured by the ENRICHD Social Support Instrument. A modified version of the Charlson Comorbidity Index was used to measure the cumulative burden of medical comorbidity. The adjusted odds ratios (ORs) for having major depression increased linearly with medical comorbidity (ORs 1.6, 2.2, 2.7 for each increasing medical comorbidity category). This relationship remained after adjusting for coronary heart disease severity (ORs 1.4, 1.7, 1.9, P <.001). The relationship between severity of depression and medical comorbidity was also maintained after excluding somatic symptoms of depression (F = 21.5, P <.0001). Patients with AMI and clinical depression have significantly greater levels of medical comorbidity than nondepressed, socially isolated patients. Further research is needed to determine whether comorbid medical illness contributes to the more frequent rehospitalizations and increased risk of mortality associated with depression.


Collagen cross-linking: a new treatment paradigm in corneal disease - a review.
The last 2 years has seen a marked increase in the prominence of corneal collagen cross-linking as a treatment strategy for progressive keratoconus. This interest has arisen from a body of laboratory evidence documenting the biomechanical and cellular changes induced by cross-linking. The findings of this research provide a plausible rationale for its use in keratoconus to retard the progression of this common disease. The rapidly growing number of clinical reports suggests, not only a consistent stabilizing effect of cross-linking, but that a variable improvement in corneal shape and visual function may also occur in some patients. However, the marked variation in the clinical course of keratoconus, together with the challenges of accurately evaluating refractive error, visual acuity and even corneal shape in this condition, demands further evidence from randomized controlled clinical trials. The aim of this review is to summarize the theoretical basis and risks of corneal collagen cross-linking, along with the available evidence for its use in keratoconus and other corneal disease states.


Impact of MRI on a knee arthroscopy waiting list.
As part of a waiting list initiative, magnetic resonance imaging (MRI) scans were arranged for 69 patients waiting for knee arthroscopy. All patients had a clinical diagnosis of a meniscal tear. With 11 non-attenders, 58 scans were performed. Of the patients scanned, 35 had demonstrable meniscal tears, and five patients had other pathology on their scans. All patients were reviewed clinically after their scans, and 24 patients were removed from the waiting list. After a further 9 months, only one of the 24 patients removed had been re-listed for therapeutic arthroscopy. This initiative proved a cost-effective method of reducing waiting times for knee arthroscopy.


Trifunctional metal-organic platform for environmental remediation: structural features with peripheral hydroxyl groups facilitate adsorption, degradation and reduction processes.
A Cd(ii)-based metal-organic framework (MOF) {[Cd(PA)(4,4'-bpy)2](H2O)}n (where, PA = pamoic acid, and bpy = bipyridine) has been demonstrated to have trifunctional properties, namely as (i) an efficient and selective adsorbent for dyes, (ii) a visible-light-active photocatalyst for the degradation of dyes and (iii) a photocatalyst for Cr(vi) reduction. Hence, this material has a very good potential for application in environmental remediation. In particular, the MOF exhibits excellent selectivity toward cationic methylene blue (MB) dye adsorption and its separation over neutral (neutral red) and anionic (methyl orange) dyes. In addition, the catalyst has also been explored for the photocatalytic degradation of less adsorbed dyes, such as methyl orange (MO) and rhodamine B (RhB). Subsequently, the potential of the presented MOF for the photocatalytic reduction of Cr(vi) under visible light irradiation has also been investigated and the catalyst was found to reduce 95% of Cr(vi) within 3 h. Moreover, simultaneous one-pot photocatalytic reduction of Cr(vi) and dye degradation has been demonstrated with high efficiency using the same catalyst. The mechanism of adsorption could be correlated to the presence of peripheral hydroxyl groups in the MOF and the photocatalytic activity observed under visible light could be attributed to the optical properties of Cd-MOF. In principle, this work could broaden the utilization of single metal organic platform for multifunctional applications toward environmental remediation.


Population typing of the causal agent of cassava bacterial blight in the Eastern Plains of Colombia using two types of molecular markers.
Molecular typing of pathogen populations is an important tool for the development of effective strategies for disease control. Diverse molecular markers have been used to characterize populations of Xanthomonas axonopodis pv. manihotis (Xam), the main bacterial pathogen of cassava. Recently, diversity and population dynamics of Xam in the Colombian Caribbean coast were estimated using AFLPs, where populations were found to be dynamic, diverse and with haplotypes unstable across time. Aiming to examine the current state of pathogen populations located in the Colombian Eastern Plains, we also used AFLP markers and we evaluated the usefulness of Variable Number Tandem Repeats (VNTRs) as new molecular markers for the study of Xam populations. The population analyses showed that AFLP and VNTR provide a detailed and congruent description of Xam populations from the Colombian Eastern Plains. These two typing strategies clearly separated strains from the Colombian Eastern Plains into distinct populations probably because of geographical distance. Although the majority of analyses were congruent between typing markers, fewer VNTRs were needed to detect a higher number of genetic populations of the pathogen as well as a higher genetic flow among sampled locations than those detected by AFLPs. This study shows the advantages of VNTRs over AFLPs in the surveillance of pathogen populations and suggests the implementation of VNTRs in studies that involve large numbers of Xam isolates in order to obtain a more detailed overview of the pathogen to improve the strategies for disease control.


Testicular relapse of AML during chronic graft-versus-host disease induced by donor leukocyte infusion.
Treatment options for acute leukemia relapsing after allogeneic BMT include conventional chemotherapy or a second transplant; however, results are rather discouraging, the first option being associated with poor survival and the second with a high mortality rate. More recently, donor leukocyte infusion (DLI) from the original donor has been used for relapsed patients in an attempt to induce a graft-versus-leukemia (GVL) effect. This procedure is partially devoid of the toxicity inherent to a second BMT. At our Institution, a 36-year-old patient with biphenotypic AML in second complete remission after relapse following allogeneic BMT was treated with peripheral blood stem cell (PBSC)-enriched donor leukocytes, obtained after in vivo priming with rhG-CSF. The patient experienced extensive cGVHD but developed a testicular relapse while in full hematologic remission. After irradiation of the sanctuary site he remains free of disease, still with chronic GVHD, 21 months after bone marrow relapse. This case suggests that immunologically privileged sites are inaccessible to GVHD/GVL effect. This should be considered when planning salvage transplants procedures in patients at risk for extramedullary involvement.


[Recommendations for performing interventions during the COVID-19 pandemic].
Coronavirus infection (SARS-CoV-2), is a pandemic disease declared by the World Health Organization (WHO). This disease reports a high risk of contagion, especially by the transmission of aerosols in health care workers. In this scenario, aerosol exposure is increased in various procedures related to the airway, lungs, and pleural space. For this reason, it is important to have recommendations that reduce the risk of exposure and infection with COVID-19. In this document, a team of international specialists in interventional pulmonology elaborated a series of recommendations, based on the available evidence to define the risk stratification, diagnostic methods and technical considerations on procedures such as bronchoscopy, tracheostomy, and pleural procedures among others. As well as the precautions to reduce the risk of contagion when carrying out pulmonary interventions.


Differences in adverse childhood experiences (ACEs) and quality of physical and mental health between transgender and cisgender sexual minorities.
Adverse childhood experiences (ACEs) have been shown to increase risk for negative health outcomes. Recent work has shown that lesbian, gay, and bisexual (LGB) individuals, on average, have higher ACEs scores compared to heterosexual individuals. However, past ACEs research involving LGB people did not assess the influence of experiencing childhood neglect and risk for poor health among this population. Further, this previous work has been limited to LGB people, excluding transgender and gender nonconforming experiences. The purpose of this project was to assess the relationship between ACEs, gender-identity, and physical and mental health status. As part of a larger community-based participatory research study, we surveyed 477 sexual and gender minority individuals about mental and physical health, ACEs, and sociodemographic characteristics. Transgender participants reported emotional abuse, physical neglect, and emotional neglect more frequently compared to cisgender LGB people. Two logistic regression models were run to assess the influence of ACE on quality of physical and mental health. The model adjusted for ACE scores showed that ACEs explained 17.6% of the variance in mental health. Our findings show that neglect is a common experience among LGB/TGN and needs to be assessed along with other ACE domains. Further, there may exist unique adverse experiences among this population during childhood resulting from social stigma. Future research should identify and quantify these experiences as well as assess the role of adversity during adulthood on mental health.


Use of laminar flow patterning for miniaturised biochemical assays.
Laminar flow in microfluidic chambers was used to construct low (one dimensional) density arrays suitable for miniaturized biochemical assays. By varying the ratio of flows of two guiding streams flanking a sample stream, precise focusing and positioning of the latter was achieved, and reactive species carried in the sample stream were deposited on functionalized chip surfaces as discrete 50 microm wide lanes. Using different model systems we have confirmed the method's suitability for qualitative screening and quantification tasks in receptor-ligand assays, recording biotin-streptavidin interactions, DNA-hybridization and DNA-triplex formation. The system is simple, fast, reproducible, flexible, and has small sample requirements.


Efficacy of SMS Text Message Interventions for Smoking Cessation: A Meta-Analysis.
Mobile technology provides new opportunities for health promotion communication. The purpose of this study was to conduct a current and extensive meta-analytic review of SMS (short message service) text message-based interventions for individual smoking cessation. Academic Search Complete, PsycINFO, PubMed, and Scopus were reviewed for articles meeting selection criteria: 1) randomized controlled trials, 2) measured smoking cessation, and 3) intervention primarily delivered through SMS text messaging. Three and 6month follow-up of 7-day point prevalence or continuous abstinence was considered from studies meeting criteria. All analyses were conducted with intention-to-treat. Both fixed and random effects models were used to calculate the global outcome measure and confidence intervals. Thirteen studies were identified that met inclusion criteria. The studies were found to be homogeneous [Q12=12.47, p=0.14]. Odds ratios based on the random effects models suggested that interventions generally increased quit rates compared to controls, 1.36 [95% CI=1.23, 1.51]. Intervention efficacy was higher in studies with a 3month follow-up compared to 6month follow-up. Text plus programs (e.g., text messaging plus Web or in-person intervention modalities) performed only slightly better than text only programs. Pooled results also indicate message frequency schedule can affect quit rates, in which fixed schedules performed better than decreasing or variable schedules. The use of quit status assessment messages was not related to intervention efficacy. Smoking quit rates for the text messaging intervention group were 36% higher compared to the control group quit rates. Results suggest that SMS text messaging may be a promising way to improve smoking cessation outcomes. This is significant given the relatively wide reach and low cost of text message interventions. Identifying the components that make interventions efficacious will help to increase the effectiveness of such interventions.


[Morphological changes in pinealocytes during the hibernation bout in the Mongolian ground squirrel, Citellus dauricus].
Adult Mongolian ground squirrels (Citellus dauricus) were kept at 5 degrees C in winter and divided into four experimental groups according to the bout length. The first group was not hibernating until decapitation. The bout length of the second group was between 4-10 days, the third group 11-17 days and the fourth group longer than 20 days. All pineals were sampled at the end of January. Morphometric analytical procedures were used to study the ultrastructure of the distal part of the pineal gland. The statistical results demonstrated that 1) the euthermic animals have larger cross areas of pinealocyte, longer and narrower Golgi apparatus and more number of saccules of each Golgi apparatus (P less than 0.01). But they also have smaller volume density of vaculoes, less lipid droplets and associated vesicles around Golgi apparatus (P less than 0.01). 2) the hibernating animals with variety of bout length had no significant differences in the number of mitochondria, lipid droplets, lysosomes, the size of Golgi apparatus and the cross areas of nucleus and cytoplasm (P greater than 0.05). However, the number and the cross areas of vacuoles were significantly increased with the bout length (P less than 0.01). This might suggest that the bout length was not related to the metabolic activity of pinealocytes in Citellus dauricus and vacuoles might play some important roles in maintenance of individual bout of hibernation in this species.


Pomegranate wine has greater protection capacity than red wine on low-density lipoprotein oxidation.
Although there is a large body of evidence on the main role of red wine in protection of low-density lipoprotein (LDL) against oxidation, there are few data on the role of pomegranate juice, which has high phenolic content. We conducted this study considering the possible importance of pomegranate wine as an antioxidant and in order to make a comparison between red and pomegranate wines. The phenol levels of pomegranate and red wines (4,850 mg/L gallic acid equivalents and 815 mg/L gallic acid equivalents, respectively) were in accordance with their total antioxidant activity (39.5% and 33.7%, respectively). Both wines decreased LDL-diene levels following a 30-minute incubation period compared with controls (145 +/- 3.2 micromol/mg of LDL protein). However, pure pomegranate wine demonstrated a greater antioxidant effect (P < .01) on diene level (110 +/- 4.6 micromol/mg of LDL protein) than pure red wine (124 +/- 3.2 micromol/mg of LDL protein). In conclusion, we suggest that pomegranate wine has potential protective effects toward LDL oxidation, and it may be a dietary choice for people who prefer fruit wines.


Structural and functional aspects of stomata : I. Developmental studies in Polypodium vulgare.
Differential cell wall thickening in developing guard cells of Polypodium vulgare L. has been studied with particular reference to guard cell protoplast deformation and the eventual formation of the stomatal pore. Concomitant studies on the development of guard cell chloroplasts and their starch inclusions during ontogeny of the stomatal complex have provided data which have been incorporated into a model to account for the formation of the pore. Guard cell starch inclusions reach a maximum density per unit volume at the same time as the guard cell walls achieve maximum differential thickening. These events coincide with the development of the pore. It is suggested that, whilst pore formation is initiated enzymatically, the mechanical forces required to bring about the separation of the two guard cells are of an osmotic nature derived from starch hydrolysis. The development of the mesophyll in relation to the epidermis is examined in respect of the formation of substomatal chambers.


Parathyroid hormone-related protein (PTHrP) in cartilaginous and bony fish tissues.
Tissues from a range of fish were examined for the presence of parathyroid hormone-related protein (PTHrP) to investigate PTHrP protein distribution and PTHrP gene expression in jawless fish, cartilaginous fish, and bony fish. Immunoreactive PTHrP was localized using antisera to N-terminal and mid-molecule regions of human PTHrP and PTHrP gene expression examined using a digoxigenin labeled riboprobe to a conserved region of the mammalian PTHrP gene. In all of the fish studied, PTHrP protein and messenger RNA (mRNA) were localized to the skin, kidney, and skeletal muscle, following the pattern seen in higher vertebrates. Additional sites of localization for both protein and mRNA included gill, nerve cord, and pituitary, as well as developing dermal denticles and rectal gland in the elasmobranch species. The sites of PTHrP distribution indicate that PTHrP may have roles in ionoregulation as well as growth and differentiation in fish, as has been suggested in higher vertebrates. The results imply that the distribution of PTHrP is widespread in fish and that there is homology between the PTHrP molecules found in humans and fish. The conservation of localization and possible similarity of the PTHrP molecules between tetrapods and fish suggests that PTHrP has a number of fundamental roles in vertebrates. J. Exp. Zool. 284:541-548, 1999.


The food additive vanillic acid controls transgene expression in mammalian cells and mice.
Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.


Identification of North Sea molluscs with DNA barcoding.
Sequence-based specimen identification, known as DNA barcoding, is a common method complementing traditional morphology-based taxonomic assignments. The fundamental resource in DNA barcoding is the availability of a taxonomically reliable sequence database to use as a reference for sequence comparisons. Here, we provide a reference library including 579 sequences of the mitochondrial cytochrome c oxidase subunit I for 113 North Sea mollusc species. We tested the efficacy of this library by simulating a sequence-based specimen identification scenario using Best Match, Best Close Match (BCM) and All Species Barcode (ASB) criteria with three different threshold values. Each identification result was compared with our prior morphology-based taxonomic assignments. Our simulation resulted in 87.7% congruent identifications (93.8% when excluding singletons). The highest number of congruent identifications was obtained with BCM and ASB and a 0.05 threshold. We also compared identifications with genetic clustering (Barcode Index Numbers, BINs) computed by the Barcode of Life Datasystem (BOLD). About 68% of our morphological identifications were congruent with BINs created by BOLD. Forty-nine sequences were clustered in 16 discordant BINs, and these were divided in two classes: sequences from different species clustered in a single BIN and conspecific sequences divided in more BINs. Whereas former incongruences were probably caused by BOLD entries in need of a taxonomic update, the latter incongruences regarded taxa requiring further investigations. These include species with amphi-Atlantic distribution, whose genetic structure should be evaluated over their entire range to produce a reliable sequence-based identification system.


Detection of protein C activation in humans.
We have developed a radioimmunoassay (RIA) for the dodecapeptide that is liberated from protein C when this zymogen is activated by thrombin bound to thrombomodulin present on the vascular endothelium. The protein C activation peptide (PCP) was synthesized using the solid-phase method of Merrifield. Antisera were raised in rabbits to the synthetic analogue coupled to bovine serum albumin with glutaraldehyde. The antibody population obtained was used together with a 125I-labeled tyrosinated ligand and various concentrations of unlabeled PCP to construct a double antibody RIA capable of measuring as little as 10 pM of this component. We have established that the synthetic dodecapeptide has the same immunoreactivity as the native peptide and that the reactivity of protein C is less than 1/2,000 that of PCP on a molar basis. The extremely low levels of peptide in normal individuals as well as the nonspecific contributions of plasma constituents to the immunoreactive signal, necessitated the development of a procedure by which the PCP could be reproducibly extracted from plasma and concentrated approximately 20-fold. This methodology permitted us to demonstrate that the plasma PCP levels in 17 normal donors averaged 6.47 pM, and that elevations up to 180 pM were observed in individuals with evidence of disseminated intravascular coagulation. The validity of these measurements of protein C activation is supported by the fact that, in both of these situations, the RIA signal migrates on reverse-phase high pressure liquid chromatography in a manner identical to that of the native dodecapeptide. We have also noted that the mean PCP concentration in seven patients fully anticoagulated with warfarin averaged 2.61 pM. Our studies also show that PCP is cleared from the plasma of primates with a t1/2 of approximately 5 min. Given that the t1/2 of activated protein C is estimated to be 10-15 min, the latter enzyme appears to exert its effects on the activated cofactors of the coagulation system at concentrations considerably less than 1.0 nM.


A New Noninvasive Frameless Registration System for Stereotactic Cranial Biopsy: A Technical Note.
Although frame-based stereotactic biopsy is still considered the gold standard for brain biopsies, frameless robot-assisted stereotactic systems are now able to provide an equal level of safety and accuracy. However, both systems suffer from a lack of efficiency of the operative workflow. To describe the technique of a new frameless and noninvasive registration tool Neurolocate (Renishaw). This tool, combined with an intraoperative cone-beam computed tomography imaging system like O-ARM (Medtronic), might facilitate the achievement and workflow of robot-assisted stereotactic intracranial biopsies. Neurolocate is a 3-dimensional fiducial tool fixed directly on the Neuromate (Renishaw) robot arm. It consists of 5 radio-opaque spherical fiducials, whose geometry is constant. This tool made it possible to carry out the coregistration then the biopsy in the same operating time, following a five-step procedure described here. We retrospectively extracted selected preliminary results from our initial experience. Over 1 year, 23 consecutive adult patients were biopsied with Neurolocate in our center. The mean overall operative time, from patient's installation to skin closure, was 97 minutes ± 27 (SD). The entire procedure took place in a single location unit (operating room), which facilitated workflow and surgical planning. No invasive gesture was performed outside of the operating time. Neurolocate is a new frameless and noninvasive registration tool that could improve workflow and flexibility for operating room management and surgical planning. It may also increase the comfort of patients undergoing robot-assisted intracranial stereotactic biopsies. The accuracy and safety profile should be addressed in specific studies.


Multiview deconvolution approximation multiphoton microscopy of tissues and zebrafish larvae.
Imaging in three dimensions is necessary for thick tissues and small organisms. This is possible with tomographic optical microscopy techniques such as confocal, multiphoton and light sheet microscopy. All these techniques suffer from anisotropic resolution and limited penetration depth. In the past, Multiview microscopy-imaging the sample from different angles followed by 3D image reconstruction-was developed to address this issue for light sheet microscopy based on fluorescence signal. In this study we applied this methodology to accomplish Multiview imaging with multiphoton microscopy based on fluorescence and additionally second harmonic signal from myosin and collagen. It was shown that isotropic resolution was achieved, the entirety of the sample was visualized, and interference artifacts were suppressed allowing clear visualization of collagen fibrils and myofibrils. This method can be applied to any scanning microscopy technique without microscope modifications. It can be used for imaging tissue and whole mount small organisms such as heart tissue, and zebrafish larva in 3D, label-free or stained, with at least threefold axial resolution improvement which can be significant for the accurate quantification of small 3D structures.


In vivo regulation of beta-adrenergic receptors on mononuclear leukocytes and heart. Assessment of receptor compartmentation after agonist infusion and acute aortic constriction in guinea pigs.
In animals injected with a bolus of isoproterenol, beta-adrenergic receptors in both mononuclear leukocytes (MNL) and heart were sequestered away from the cell surface, and the time course (0-120 min) and dose-response patterns were similar in the two tissues. In guinea pigs given a constant infusion of isoproterenol, 0.15 mg/(kg.h), down-regulation of total receptor number occurred more quickly and to a greater extent in the MNL than in the heart. We also compared receptor sequestration after aortic constriction-induced acute heart failure. Negligible sequestration (9%) of beta-adrenergic receptors occurred in the MNL of animals treated in this manner, whereas the number of receptors in the sarcolemmal fraction decreased 61%. This selective sequestration of cardiac receptors may result from the action of high concentrations of norepinephrine (which is selective for beta 1 over beta 2 receptors) present at sympathetic nerve-cardiac cell synapses. We conclude that although receptor redistribution occurs similarly in MNL and heart in response to a circulating nonselective agonist, beta-adrenergic receptor redistribution may occur selectively in the heart in response to such stimuli as aortic constriction-induced acute heart failure that activate the sympathetic nervous system.


Does hut climate matter for piglet survival in organic production?
Piglet mortality in outdoor production systems varies across the year, and a reason for this variation could be fluctuations in hut climate, as ambient temperature might influence piglet survival, both directly and indirectly. Therefore, the aim of the current study was to investigate the impact of farrowing hut climate and year variation on stillbirth and liveborn mortality. A large-scale observational study was conducted at five commercial organic pig-producing herds in Denmark from June 2015 to August 2016. Both year variation (F 3,635=4.40, P=0.004) and farrowing hut temperature (F 2,511=6.46, P=0.002) affected the rate of stillbirths. The risk of stillborn piglets was lowest in winter and during this season larger changes in hut temperature between day 1 prepartum and the day of farrowing increased the risk of stillbirths (F 1,99=6.39, P=0.013). In addition, during the warm part of the year stillbirth rate increased at temperatures ⩾27°C. Year variation also affected liveborn mortality (F 3,561=3.86, P=0.009) with a lower rate of liveborn deaths in spring. However, the hut climate did not influence liveborn deaths. Consequently, other factors than hut climate may explain the influence of year variation on liveborn mortality. These could be light differences causing seasonality in reproduction and lactation.


From yeast to human: exploring the comparative biology of methionine restriction in extending eukaryotic life span.
Methionine restriction is a widely reported intervention for increasing life span in several model organisms. Low circulating levels of methionine are evident in the long-lived naked mole-rat, suggesting that it naturally presents with a life-extending phenotype akin to that observed in methionine-restricted animals. Similarly, long-lived dwarf mice also appear to have altered methionine metabolism. The mechanisms underlying methionine-restriction effects on life-span extension, however, remain unknown, as do their potential connections with caloric restriction, another well-established intervention for prolonging life span. Paradoxically, methionine is enriched in proteins expressed in mitochondria and may itself serve an important role in the detoxification of reactive oxygen species and may thereby contribute to delayed aging. Collectively, we highlight the evidence that modulation of the methionine metabolic network can extend life span-from yeast to humans-and explore the evidence that sulfur amino acids and the concomitant transsulfuration pathway play a privileged role in this regard. However, systematic studies in single organisms (particularly those that exhibit extreme longevity) are still required to distinguish the fundamental principles concerning the role of methionine and other amino acids in regulating life span.


Interictal epileptiform discharges in persons without a history of seizures: what do they mean?
Interictal epileptiform discharge (IED) is rarely observed in healthy volunteers without a history of seizures, but higher rates of occurrence are reported in children than in adults. Higher rates are also observed among neurologic inpatients and outpatients without a seizure history, but the risk of subsequent unprovoked seizures or epilepsy is low in healthy volunteers and patients. An exception is the patients with autism spectrum disorders, attention deficit/hyperactivity disorder, or cerebral palsy, who are predisposed to epilepsy development. However, it is currently unclear whether epilepsy risk is higher for patients with incidentally detected IED than for the patients without IED. Hospitalized patients with IED but no prior seizures often have underlying acute or progressive brain disorders. Although they have increased risk of acute seizures, the risk for subsequent unprovoked seizures or epilepsy is unknown and requires assessment on an individual basis. For patients who have psychogenic spells but no seizure history, the rate of IED detection is low, similar to that of healthy volunteers. The association between IED and transitory cognitive impairment has not been established in nonepileptic persons. Evidence thus far does not suggest that routine EEG screening of pilot candidates reduces risk of flight-related accidents.


Explaining Matching Michigan: an ethnographic study of a patient safety program.
Quality and safety improvement initiatives in healthcare often display two disconcerting effects. The first is a failure to outperform the secular trend. The second is the decline effect, where an initially promising intervention appears not to deliver equally successful results when attempts are made to replicate it in new settings. Matching Michigan, a patient safety program aimed at decreasing central line infections in over 200 intensive care units (ICUs) in England, may be an example of both. We aimed to explain why these apparent effects may have occurred. We conducted interviews with 98 staff and non-participant observation on 19 ICUs; 17 of these units were participating in Matching Michigan. We undertook further telephone interviews with 29 staff who attended program training events and we analyzed relevant documents. One Matching Michigan unit transformed its practices and culture in response to the program; five boosted existing efforts, and 11 made little change. Matching Michigan's impact may have been limited by features of program design and execution; it was not an exact replica of the original project. Outer and inner contexts strongly modified the program's effects. The outer context included previous efforts to tackle central line infections superimposed on national infection control policies that were perceived by some as top-down and punitive. This undermined engagement in the program and made it difficult to persuade participants that the program was necessary. Individual ICUs' histories and local context were also highly consequential: their past experience of quality improvement, the extent to which they were able to develop high quality data collection and feedback systems, and the success of local leaders in developing consensus and coalition all influenced the program's impact on local practices. Improved implementation of procedural good practice may occur through many different routes, of which program participation is only one. The 'phenotype' of compliance may therefore arise through different 'genotypes.' When designing and delivering interventions to improve quality and safety, risks of decline effects and difficulties in demonstrating added value over the secular trend might be averted by improved understanding of program mechanisms and contexts of implementation.


Genes for carbon metabolism and the ToxA virulence factor in Pseudomonas aeruginosa are regulated through molecular interactions of PtxR and PtxS.
Homologs of the transcriptional regulator PtxS are omnipresent in Pseudomonas, whereas PtxR homologues are exclusively found in human pathogenic Pseudomonas species. In all Pseudomonas sp., PtxS with 2-ketogluconate is the regulator of the gluconate degradation pathway and controls expression from its own promoter and also from the P(gad) and P(kgu) for the catabolic operons. There is evidence that PtxS and PtxR play a central role in the regulation of exotoxin A expression, a relevant primary virulence factor of Pseudomonas aeruginosa. We show using DNaseI-footprint analysis that in P. aeruginosa PtxR binds to the -35 region of the P(toxA) promoter in front of the exotoxin A gene, whereas PtxS does not bind to this promoter. Bioinformatic and DNaseI-footprint analysis identified a PtxR binding site in the P(kgu) and P(gad) promoters that overlaps the -35 region, while the PtxS operator site is located 50 bp downstream from the PtxR site. In vitro, PtxS recognises PtxR with nanomolar affinity, but this interaction does not occur in the presence of 2-ketogluconate, the specific effector of PtxS. DNAaseI footprint assays of P(kgu) and P(gad) promoters with PtxS and PtxR showed a strong region of hyper-reactivity between both regulator binding sites, indicative of DNA distortion when both proteins are bound; however in the presence of 2-ketogluconate no protection was observed. We conclude that PtxS modulates PtxR activity in response to 2-ketogluconate by complex formation in solution in the case of the P(toxA) promoter, or via the formation of a DNA loop as in the regulation of gluconate catabolic genes. Data suggest two different mechanisms of control exerted by the same regulator.


Comparison of myocardial contrast echocardiography with NC100100 and (99m)Tc sestamibi SPECT for detection of resting myocardial perfusion abnormalities in patients with previous myocardial infarction.
To determine whether myocardial contrast echocardiography (MCE) following intravenous injection of perfluorocarbon microbubbles permits identification of resting myocardial perfusion abnormalities in patients who have had a previous myocardial infarction. 22 patients (mean (SD) age 66 (11) years) underwent MCE after intravenous injection of NC100100, a novel perfluorocarbon containing contrast agent, and resting (99m)Tc sestamibi single photon emission computed tomography (SPECT). With both methods, myocardial perfusion was graded semiquantitatively as 1 = normal, 0.5 = mild defect, and 0 = severe defect. Among the 203 normally contracting segments, 151 (74%) were normally perfused by SPECT and 145 (71%) by MCE. With SPECT, abnormal tracer uptake was mainly found among normally contracting segments from the inferior wall. By contrast, with MCE poor myocardial opacification was noted essentially among the normally contracting segments from the anterior and lateral walls. Of the 142 dysfunctional segments, 87 (61%) showed perfusion defects by SPECT, and 94 (66%) by MCE. With both methods, perfusion abnormalities were seen more frequently among akinetic than hypokinetic segments. MCE correctly identified 81/139 segments that exhibited a perfusion defect by SPECT (58%), and 135/206 segments that were normally perfused by SPECT (66%). Exclusion of segments with attenuation artefacts (defined as abnormal myocardial opacification or sestamibi uptake but normal contraction) by either MCE or SPECT improved both the sensitivity (76%) and the specificity (83%) of the detection of SPECT perfusion defects by MCE. The data suggest that MCE allows identification of myocardial perfusion abnormalities in patients who have had a previous myocardial infarction, provided that regional wall motion is simultaneously taken into account.


Studies on the mechanism of transduction by bacteriophage phi gamma. II. Formation of transducing elements.
The formation of the transducing elements (TE) of bacteriophage phi gamma, analyzed in lysogens of the thermo-inducible derivative phi gamma hyI, has been found to parallel the formation of plaque-forming particles with a frequency of 2 X 10(-2) TE/PFU, but is mor sensitive to temperature and ti UV. Deletion of one of the prophage termini (attR) prevents normal excision and formation of plaque-forming particles, but does not affect the formation of transducing elements, which arise at a rate of nearly 10(-1) TE per induced bacterium. Transducing elements, would be formed by in situ encapsulation of a hybrid segment from a specidic point in the induced prophage, possibly the presumed packaging initiation site of the normal phage genome, before excision of the latter has occurred. Analysis of the mechanism of transduction to partly heterologous lysogens has revealed the participation of a co-infecting genome arranged in a linear fashion and has given evidence for a permutation in the sequence of transducing and nontransducing genomes. The data re consistent with a mechanism of encapsidation distinct from the Ter system even for hybrids inheriting part of the phi 80 genome, but endowed with the property to form transducing elements like those of phi gamma. Upon infection, transducing elements are formed after one cycle of lytic development with the same characteristics as those resulting from induction, but with a frequency 50 to 100 times lower. This process is dependent on the efficiency of Int promoted recombination. Superinfection experiments performed under conditions preventing Int promoted recombination reveal that any superinfecting phi gamma can promote the formation of transducing particles, depending on the presence within the host prophage of a site from which transducing genome packaging initiates.


Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions.
Tuberculosis is characterized by periods in which the disease may be quiescent or even clinically inapparent, but in which tubercle bacilli persist and retain the potential to reactivate the disease. The present study was carried out in pursuit of an in vitro model which might contribute to the understanding of the physiology of nonreplicating persisters, with oxygen limitation used as the means of inducing this state. When actively growing aerated cultures of Mycobacterium tuberculosis were suddenly placed under anaerobic conditions the bacilli died rapidly, with a half-life of 10 h. When the bacilli were grown in liquid medium without agitation, they adapted to the microaerophilic conditions encountered in the sediment; the adapted bacilli in the sediment did not replicate there but were tolerant of anaerobiosis, exhibiting a half-life of 116 h. Among the early events associated with the adaptation were the synthesis of an antigen designated URB, the function of which is not known, and a fourfold increase in isocitrate lyase activity. The bacilli later exhibited a 10-fold increase in synthesis of a glycine dehydrogenase that catalyzes the reductive amination of glyoxylate, concomitantly oxidizing NADH to NAD. Specific activities of other enzymes studied were either not affected or moderately diminished in the sedimented bacilli. It is proposed that the glyoxylate synthesis in this model serves mainly to provide a substrate for the regeneration of NAD that may be required for the orderly completion of the final cycle of bacillary replication before oxygen limitation stops growth completely. This orderly shutdown is essential to continued survival of M. tuberculosis in a quiescent form.


Lassa fever. Effective therapy with ribavirin.
In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.


Prevalence of anti-thyroid antibodies in patients with primary thyroid disorders.
To determine prevalence of thyroid antimicrosomal and antithyroglobulin antibodies among patients with primary thyroid disorders. Descriptive cross-sectional study. Kenyatta National Hospital, July 2003 to August 2004. Antimicrosomal antibodies (anti-TPOAbs) were detected in 51.4% of all the patients while 36.1% tested positive for the antithyroglobulin antibodies (anti- TgAbs). Among the hyperthyroid patients, anti-TPOAbs and anti-TgAbs were in 50.8% and 33% respectively while 53.3% and 46.7% of the hypothyroid patients tested positive for anti-TPOAbs and anti-TgAbs respectively. Most of the patients who showed positivity for anti-TgAbs (88.5%) also tested positive for anti-TPOAbs. More than half of the patients with primary thyroid disorders show presence of autoimmune thyroid markers, with anti TPO antibodies being more prevalent.


Lymphatic vascularization in primary breast cancer: HER2 overexpressing tumors contain more lymphatics than steroid receptor positive, triple-positive and triple negative breast carcinomas.
The aim of this study was to examine the relationship between the immunohistochemical subtypes of invasive breast cancer and lymphatic vascularization. One hundred and seventy nine cases of randomly selected invasive breast cancer patients, surgically treated between 2004 and 2007, were retrospectively studied. These were classified into steroid receptor positive (steroid receptor positive/ HER2 negative), triple positive (steroid receptor and HER2 positive), triple negative (steroid receptor and HER2 negative) and HER2 overexpressing (steroid receptor negative /HER2 positive) carcinomas. Appropriate immunostaining and in-situ hybridization techniques were applied and results were statistically analyzed. The median intra-tumor lymphatic vascular density and the median intra-tumor relative lymphatic vascular area were found to differ significantly among the studied groups of breast cancer (KW =49.8611; p < 0.0001 and KW =21.5122; p=0.0001 respectively). There was no significant difference in the incidence rate of axillary node involvement among the studied groups of breast cancer (χ < sup > 2 < /sup > =1.66; Df=3; p=0.6460). The present study indicates that HER2 overexpressing breast carcinomas have a consistent increase of intra-tumor lymphatic vessel counts as compared to all other subtypes. It is suggested that the newly formed vessels are probably not the only essential factor for lymphogenic spread of HER2 overexpressing breast carcinomas as they are not related to an increased incidence of lymph node metastases compared to the other studied subgroups.


The Escherichia coli MFS-type transporter genes yhjE, ydiM, and yfcJ are required to produce an active bo3 quinol oxidase.
Heme-copper oxygen reductases are membrane-bound oligomeric complexes that are integral to prokaryotic and eukaryotic aerobic respiratory chains. Biogenesis of these enzymes is complex and requires coordinated assembly of the subunits and their cofactors. Some of the components are involved in the acquisition and integration of different heme and copper (Cu) cofactors into these terminal oxygen reductases. As such, MFS-type transporters of the CalT family (e.g., CcoA) are required for Cu import and heme-CuB center biogenesis of the cbb3-type cytochrome c oxidases (cbb3-Cox). However, functionally homologous Cu transporters for similar heme-Cu containing bo3-type quinol oxidases (bo3-Qox) are unknown. Despite the occurrence of multiple MFS-type transporters, orthologs of CcoA are absent in bacteria like Escherichia coli that contain bo3-Qox. In this work, we identified a subset of uncharacterized MFS transporters, based on the presence of putative metal-binding residues, as likely candidates for the missing Cu transporter. Using a genetic approach, we tested whether these transporters are involved in the biogenesis of E. coli bo3-Qox. When respiratory growth is dependent on bo3-Qox, because of deletion of the bd-type Qox enzymes, three candidate genes, yhjE, ydiM, and yfcJ, were found to be critical for E. coli growth. Radioactive metal uptake assays showed that ΔydiM has a slower 64Cu uptake, whereas ΔyhjE accumulates reduced 55Fe in the cell, while no similar uptake defect is associated with ΔycfJ. Phylogenomic analyses suggest plausible roles for the YhjE, YdiM, and YfcJ transporters, and overall findings illustrate the diverse roles that the MFS-type transporters play in cellular metal homeostasis and production of active heme-Cu oxygen reductases.


The history of multiple personality in the United States: I: The beginnings.
The origins of the history of multiple personality in the United States may be found in the lectures and writings of Benjamin Rush. Although the case of Mary Reynolds in 1811 has been thought to be the first known case of multiple personality. Rush described three earlier cases of dissociation and attempted to explain these strange phenomena.


Cerebral microbleeds: Prevalence and relationship to amyloid burden.
To describe the prevalence of cerebral microbleeds (CMBs) and determine the association between CMBs and β-amyloid burden on PET. From the population-based Mayo Clinic Study of Aging, 1,215 participants (53% male) underwent 3-tesla MRI scans with T2* gradient recalled echo sequences from October 2011 to February 2017. A total of 1,123 participants (92%) underwent 11C-Pittsburgh compound B (PiB)-PET scans. The prevalence of CMBs was derived by adjusting for nonparticipation and standardizing to the Olmsted County, MN, population. The relationship between β-amyloid burden and CMB presence and location was tested using logistic regression models. Ordinal logistic models tested the relationship between CMB frequency and β-amyloid burden. Two hundred seventy-four participants (22.6%) had at least one CMB. CMB frequency increased with age by decade (11% aged 60-69 years, 22% 70-79 years, and 39% 80 years and older). After adjusting for age, sex, and hypertension, PiB standardized uptake value ratio (SUVR) was associated with increased odds of a CMB. The association between PiB SUVR and CMBs was location-specific; PiB SUVR was associated with lobar CMBs but not deep CMBs. Age, hypertension, and PiB SUVR were associated with increasing CMB count. CMB density was greatest in parietal and occipital regions; β-amyloid burden correlated with concentration of CMBs in all lobar regions. Among participants with multiple CMBs, greater PiB uptake occurred in the pre- and postcentral gyri superiorly, the superior parietal lobe and precuneus, the angular gyrus, inferior temporal gyrus, and temporal poles. The prevalence of CMBs increases with age. In this population-based sample, β-amyloid load was associated with lobar but not with deep CMBs.


[Use of photography as a method of information collection: a qualitative study with adolescents with cancer].
This article aims at discussing the use of photography as a method of information collection in connection with a qualitative research in a dissertation featuring the phenomenological approach with the objective of understanding the world as experienced by adolescents with cancer. The context was the Oncologic Pediatrics Admittance Unit of Hospital de Clinicas de Porto Alegre, Rio Grande do Sul, Brazil. The subjects who provided information were nine adolescents hospitalized with cancer, of age between 11 and 18 years old. In order to carry out the information collection, photography in connection with semistructured interview and the hermeneutics as interpretation method of the information were applied. Eleven themes arose evidencing the richness of the existential content that permeates the experience of the adolescent with cancer. The study revealed that the care of the adolescent with cancer requires understanding his/her experienced world, perceiving the imperceptible, listening and perceiving what he/she says without saying it, being present whenever needed and including him/her among the issues that involves his/her existence.


Osteoporosis. Definition and clinical presentation.
Osteoporosis is a skeletal condition characterized by decreased density (mass/volume) of normally mineralized bone. The reduced bone density leads to decreased mechanical strength, thus making the skeleton more likely to fracture. Postmenopausal osteoporosis (Type I) and age-related osteoporosis (Type II) are the most common primary forms of bone loss seen in clinical practice. Secondary causes of osteoporosis include hypercortisolism, hyperthyroidism, hyperparathyroidism, alcohol abuse, and immobilization. In the development of osteoporosis, there is often a long latent period before the appearance of the main clinical manifestation, pathologic fractures. The earliest symptom of osteoporosis is often an episode of acute back pain caused by a pathologic vertebral compression fracture, or an episode of groin or thigh pain caused by a pathologic hip fracture. In the diagnostic process, the extent and severity of bone loss are evaluated and secondary forms of bone loss are excluded. A careful diagnostic work-up that includes clinical history, physical examination, laboratory evaluation, bone densitometry, and radiographic imaging will allow the clinician to determine the cause of osteoporosis and to institute medical interventions that will stabilize and even reverse this frequently preventable condition.


Engaging with clinical commissioning: the attitudes of general practitioners in East Lancashire.
Clinical commissioning is the centrepiece of government health reforms. Engagement with the reforms is important if they are to bring about improvements in the quality of healthcare. This is important in any healthcare system, not just the UK National Health Service (NHS). This study draws on data from a specially commissioned survey, exploring the extent to which general practitioners (GPs) in East Lancashire are engaged with clinical commissioning. Aim The aim of this study was to assess levels of engagement with clinical commissioning using a Clinical Commissioning Engagement Scale (CCES). A six-point Likert scale CCES was distributed to all GPs within the boundary of East Lancashire Clinical Commissioning Group (CCG). The GPs are distributed across five localities that vary in terms of geography, demography and previous commissioning experience. The CCES aimed to capture comparative levels of engagement across twelve items, three for each of four dimensions of engagement: (1) personal attitude, (2) perceived capacity, (3) perceived capability and (4) opportunity. Eighty-five returns were received, representing a response rate of 35.3%. A full analysis of the data was conducted using SPSS v. 19. The results demonstrate concern for capacity and capability across the localities, where mean scores are universally well below the midpoint of the scale. However, attitude and opportunity were relatively positive indicators with mean scores above midpoint for all localities. The findings highlight the potential challenges for CCGs in engaging GPs and in particular responding to perceived problems of capability and capacity. Further research is required to shed light on whether East Lancashire is typical of other CCGs.


Eliminating bias drift error in lock-in frequency for a resonant fiber optic gyro.
The accuracy of the resonant frequency servo loop is a major concern for high-performance operation of a resonant fiber optic gyro. This is usually resolved by adopting the central frequency of the laser source to track the resonance of the optical fiber ring resonator in one direction. However, the drift of the resonant frequency arising from resonator temperature fluctuation must be eliminated to maintain this accuracy. The traditional proportional integral (PI) frequency servo loop cannot address this issue very well. For instance, a bias error as large as tens or even hundreds of degrees/hour has been observed at the demodulated output of a resonant frequency servo loop. In this paper, we propose a method to eliminate this bias error by adding a double integral term in the traditional PI-based resonant frequency servo loop. We demonstrate that the double integral term can precisely track the linear resonant frequency drift, evidenced by our experimentally achieved close-to-zero bias error of -0.0009 deg/h at the demodulated output of the resonant frequency servo loop.


Metabolic Reprograming of Microglia in the Regulation of the Innate Inflammatory Response.
Microglia sustain normal brain functions continuously monitoring cerebral parenchyma to detect neuronal activities and alteration of homeostatic processes. The metabolic pathways involved in microglia activity adapt at and contribute to cell phenotypes. While the mitochondrial oxidative phosphorylation is highly efficient in ATP production, glycolysis enables microglia with a faster rate of ATP production, with the generation of intermediates for cell growth and cytokine production. In macrophages, pro-inflammatory stimuli induce a metabolic switch from oxidative phosphorylation to glycolysis, a phenomenon similar to the Warburg effect well characterized in tumor cells. Modification of metabolic functions allows macrophages to properly respond to a changing environment and many evidence suggest that, similarly to macrophages, microglial cells are capable of a plastic use of energy substrates. Neuroinflammation is a common condition in many neurodegenerative diseases and the metabolic reprograming of microglia has been reported in neurodegeneration. Here we review the existing data on microglia metabolism and the connections with neuroinflammatory diseases, highlighting how metabolic changes contribute to module the homeostatic functions of microglia.


Tufted hairgrass (Deschampsia caespitosa) exhibits a lower photosynthetic plasticity than Antarctic hairgrass (D. antarctica).
The aim of our work was to assess photosynthetic plasticity of two hairgrass species with different ecological origins (a temperate zone species, Deschampsia caespitosa (L.) Beauv. and an Antarctic species, D. antarctica) and to consider how the anticipated climate change may affect vitality of these plants. Measurements of chlorophyll fluorescence showed that the photosystem II (PSII) quantum efficiency of D. caespitosa decreased during 4 d of incubation at 4 degrees C but it remained stable in D. antarctica. The fluorescence half-rise times were almost always lower in D. caespitosa than in D. antarctica, irrespective of the incubation temperature. These results indicate that the photosynthetic apparatus of D. caespitosa has poorer performance in these conditions. D. caespitosa reached the maximum photosynthesis rate at a higher temperature than D. antarctica although the values obtained at 8 degrees C were similar in both species. The photosynthetic water-use efficiency (photosynthesis-to-transpiration ratio, P/E) emerges as an important factor demonstrating presence of mechanisms which facilitate functioning of a plant in non-optimal conditions. Comparison of the P/E values, which were higher in D. antarctica than in D. caespitosa at low and medium temperatures, confirms a high degree of adjustability of the photosynthetic apparatus in D. antarctica and unveils the lack of such a feature in D. caespitosa.


[Role of parenteral cephalosporins for outpatients treatment of infections].
OPAT (Outpatient Parenteral Antibiotic Therapy) arose in the early 1980s in the USA and later in many other countries from the primary consideration that outpatient treatment is more cost-effective than hospitalisation. Currently, several thousand patients undergo OPAT programmes all over the world and several different bacterial infections are included in the list of treatable diseases, especially those requiring long-term parenteral treatment such as osteomyelitis and soft tissue infections. All injectable antibiotics are suitable for OPAT according to their microbiological spectrum, although clearly some pharmacological properties make one antibiotic more preferable than another. Beta-lactams represent more than half of the antibiotic world market and two-thirds of them are cephalosporins. Such a widespread use of cephalosporins is certainly due to their wide antibacterial spectrum and good tolerability. Among third-generation cephalosporins, covering the majority of micro-organisms responsible for community-acquired infections, ceftriaxone is the only one with an 8-hour half-life, thereby permitting a single daily dose, which represents a great advantage when undertaking an OPAT programme. Analysis of antibiotic consumption used for OPAT therapies, based on data collected from the International OPAT Registry project, with the participation of many countries (USA, Canada, Britain, Argentina, etc.) including Italy, shows that ceftriaxone is the most widely used antibiotic for home therapy, clearly due to the above-mentioned properties.


In Planta Arsenic Thiolation in Rice and Arabidopsis thaliana.
Inorganic and methylated thioarsenates have recently been reported to form in paddy soil pore waters and accumulate in rice grains. Among them, dimethylmonothioarsenate (DMMTA) is particularly relevant because of its high cytotoxicity and potential misidentification as nonregulated dimethylarsenate (DMA). Studying DMMTA uptake and flag leaf, grain, and husk accumulation in rice plants during grain filling, substantial dethiolation to DMA was observed with only 8.0 ± 0.1, 9.1 ± 0.6, and 1.4 ± 0.2% DMMTA remaining, respectively. More surprisingly, similar shares of DMMTA were observed in control experiments with DMA, indicating in planta DMA thiolation. Exposure of different rice seedling varieties to not only DMA but also to arsenite and monomethylarsenate (MMA) revealed in planta thiolation as a common process in rice. Up to 35 ± 7% DMA thiolation was further observed in the shoots and roots of the model plant Arabidopsis thaliana. Parameters determining the ratio and kinetics of thiolation versus dethiolation are unknown, yet, but less DMA thiolation in glutathione-deficient mutants compared to wild-type plants suggested glutathione concentration as one potential parameter. Our results demonstrate that pore water is not the only source for thioarsenates in rice grains and that especially the currently nonregulated DMA needs to be monitored as a potential precursor of DMMTA formation inside rice plants.


A drosophila model for EGFR-Ras and PI3K-dependent human glioma.
Gliomas, the most common malignant tumors of the nervous system, frequently harbor mutations that activate the epidermal growth factor receptor (EGFR) and phosphatidylinositol-3 kinase (PI3K) signaling pathways. To investigate the genetic basis of this disease, we developed a glioma model in Drosophila. We found that constitutive coactivation of EGFR-Ras and PI3K pathways in Drosophila glia and glial precursors gives rise to neoplastic, invasive glial cells that create transplantable tumor-like growths, mimicking human glioma. Our model represents a robust organotypic and cell-type-specific Drosophila cancer model in which malignant cells are created by mutations in signature genes and pathways thought to be driving forces in a homologous human cancer. Genetic analyses demonstrated that EGFR and PI3K initiate malignant neoplastic transformation via a combinatorial genetic network composed primarily of other pathways commonly mutated or activated in human glioma, including the Tor, Myc, G1 Cyclins-Cdks, and Rb-E2F pathways. This network acts synergistically to coordinately stimulate cell cycle entry and progression, protein translation, and inappropriate cellular growth and migration. In particular, we found that the fly orthologs of CyclinE, Cdc25, and Myc are key rate-limiting genes required for glial neoplasia. Moreover, orthologs of Sin1, Rictor, and Cdk4 are genes required only for abnormal neoplastic glial proliferation but not for glial development. These and other genes within this network may represent important therapeutic targets in human glioma.


'Do not Do' Recommendations in Hemophilia.
It is important to discard those practices that do not add value. As a result, several initiatives have emerged. All of them try to improve patient safety and the use of health resources. To present a compendium of "do not do recommendations" in the context of hemophilia. A review of the literature and current clinical guidelines has been made, based on the best evidence available to date. The following 13 recommendations stand out: 1) Do not delay the administration of factor after trauma; 2) do not use fresh frozen plasma or cryoprecipitate; 3) do not use desmopressin in case of hematuria; 4) do not change the product in the first 50 prophylaxis exposures; 5) do not interrupt immunotolerance; 6) do not administer aspirin or NSAIDs; 7) do not administer intramuscular injections; 8) do not do routine radiographs of the joint in case of acute hemarthrosis; 9) Do not apply closed casts for fractures; 10) do not discourage the performance of physical activities; 11) do not deny surgery to a patient with an inhibitor; 12) do not perform instrumental deliveries in fetuses with hemophilia; 13) do not use factor IX (FIX) in patients with hemophilia B with inhibitor and a history of anaphylaxis after administration of FIX. The information mentioned previously can be useful in the management of hemophilia, from different levels of care. As far as we know, this is the first initiative of this type regarding hemophilia.


Platelet function in inflammatory diseases: insights from clinical studies.
In addition to their pivotal role in hemostasis, platelets are an integral part of inflammation. Growing evidence suggests that platelets are a key component of innate and adaptive immune responses. Better understanding of the mechanisms linking platelet function to chronic inflammatory tissue damage may reveal novel targets of therapeutic intervention in immune-mediated and/or inflammatory disorders. The functional interplay between platelets and inflammation is closely implicated in the pathophysiology of a variety of human diseases. This review discusses the relationship between platelets and inflammatory and immune responses across a wide range of conditions in internal medicine.


Parathyroid adenoma apoplexy mimicking a thyroid bleeding cyst: a seemingly innocent condition that can be life-threatening.
Primary hyperparathyroidism most commonly presents with hypercalcaemia. Rarely, parathyroid apoplexy or haemorrhage mimicking a thyroid bleeding cyst is the first presentation of a parathyroid adenoma. A woman presented with a sudden-onset painful 'goitre'. Ultrasound showed a cystic nodule located posterior to rather than in the right thyroid lobe, suggesting parathyroid adenoma bleeding. Biochemistry showed mild primary hyperparathyroidism. 99mTc-pertechnetate/sestamibi showed no uptake in the nodule, which was interpreted as a cold thyroid nodule. 18F-fluorocholine PET/CT showed uptake in the nodule, suggestive of a parathyroid adenoma. Persistent mild primary hyperparathyroidism complicated by nephrolithiasis and osteopenia favoured parathyroidectomy over a wait-and-see approach. The patient was referred for parathyroidectomy along with right thyroid lobectomy. Pathology showed an adenoma, with an eccentrically located cystic structure filled with red blood cells surrounded by a thickened fibrous capsule. In conclusion, cervical pain/haemorrhage with hypercalcaemia points to the diagnosis of parathyroid apoplexy, mimicking a thyroid bleeding cyst. Workup with ultrasound and, if available, 18F-choline PET/CT allows for timely surgery, minimizing the risk of recurrent and severe bleeding. A bleeding cyst may be located posterior to rather than in the thyroid, suggesting a parathyroid haemorrhage. Neck pain and/or haemorrhage along with primary hyperparathyroidism point to parathyroid apoplexy. A two-step presentation has been described, with a first phase of local symptoms to be followed by visible and possibly life-threatening compressing bleeding. Therefore, an expedited workup is needed, allowing for timely surgery.


The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis.
Diabetes is one of the most common comorbidities, and it is associated with poorer outcomes in patients with coronavirus disease 2019 (COVID-19). Preliminary findings showed that mortality was reduced in those who consume metformin compared to those who did not, and given its low cost and widespread availability; metformin is an attractive and potential agent to mitigate excessive risk in diabetic populations. Several medical databases (Pubmed, EuropePMC, EBSCOhost, Proquest, Cochrane library) and two health-science preprint servers (preprint.org and Medrxiv) were systematically searched for relevant literature. Nine studies with 10,233 subjects were included in the qualitative and quantitative synthesis. Meta-analysis showed that metformin is associated with lower mortality in pooled non-adjusted model (OR 0.45 [0.25, 0.81], p = 0.008; I2: 63.9%, p = 0.026) and pooled adjusted model (OR 0.64 [0.43, 0.97], p = 0.035; I2: 52.1%, p = 0.064). The analysis showed that metformin consumption was associated with lower mortality. Randomized controlled trials are needed to confirm this finding.


Stiff mutant genes of phycomyces affect turgor pressure and wall mechanical properties to regulate elongation growth rate.
Regulation of cell growth is paramount to all living organisms. In plants, algae and fungi, regulation of expansive growth of cells is required for development and morphogenesis. Also, many sensory responses of stage IVb sporangiophores of Phycomyces blakesleeanus are produced by regulating elongation growth rate (growth responses) and differential elongation growth rate (tropic responses). "Stiff" mutant sporangiophores exhibit diminished tropic responses and are found to be defective in at least five genes; madD, E, F, G, and J. Prior experimental research suggests that the defective genes affect growth regulation, but this was not verified. All the growth of the single-celled stalk of the stage IVb sporangiophore occurs in a short region termed the "growth zone." Prior experimental and theoretical research indicates that elongation growth rate of the stage IVb sporangiophore can be regulated by controlling the cell wall mechanical properties within the growth zone and the magnitude of the turgor pressure. A quantitative biophysical model for elongation growth rate is required to elucidate the relationship between wall mechanical properties and turgor pressure during growth regulation. In this study, it is hypothesized that the mechanical properties of the wall within the growth zone of stiff mutant sporangiophores are different compared to wild type (WT). A biophysical equation for elongation growth rate is derived for fungal and plant cells with a growth zone. Two strains of stiff mutants are studied, C149 madD120 (-) and C216 geo- (-). Experimental results demonstrate that turgor pressure is larger but irreversible wall deformation rates within the growth zone and growth zone length are smaller for stiff mutant sporangiophores compared to WT. These findings can explain the diminished tropic responses of the stiff mutant sporangiophores. It is speculated that the defective genes affect the amount of wall-building material delivered to the inner cell wall.


Sequential analysis of multiple analytes using a surface plasmon resonance (SPR) biosensor.
A sequential analysis method for the analysis of two analytes was developed using a surface plasmon resonance (SPR) biosensor. A sample with both analytes was introduced into the single sensing region and then each analyte was analyzed sequentially. Two detection models were devised for the samples with the following composition: (1) one target analyte resulting in a sensor response without any label and the other analyte with only additional label, (2) both target analytes requiring additional labels for detection. A standard curve for each model was prepared and applied for sequential analysis of anti-bovine serum albumin (anti-BSA) antibodies and horseradish peroxidase (HRP). The errors of the sequential analysis of Models 1 and 2 were found to be less than 6%, and this method was therefore acceptable for application. No cross-reaction arising from non-specific binding among the participating antigens and antibodies was shown to occur in Models 1 and 2. For optimization of the analyte binding capacity of immunoaffinity (IA), the concentration ratio of the molecular recognition element at the immobilization step was adjusted. Subsequently, from the measurement of the maximum sensor response (R(max)), optimization of the analyte binding capacity could be made. Using Model 2, the feasibility of sequential analysis was demonstrated by detecting levels of human chorionic gonadotropin (hCG) and human albumin (hA) in healthy human urine, since both proteins are known to be related to abortion and preterm delivery during early pregnancy.


Transcriptome analysis reveals potential mechanisms underlying differential heart development in fast- and slow-growing broilers under heat stress.
Modern fast-growing broilers are susceptible to heart failure under heat stress because their relatively small hearts cannot meet increased need of blood pumping. To improve the cardiac tolerance to heat stress in modern broilers through breeding, we need to find the important genes and pathways that contribute to imbalanced cardiac development and frequent occurrence of heat-related heart dysfunction. Two broiler lines - Ross 708 and Illinois - were included in this study as a fast-growing model and a slow-growing model respectively. Each broiler line was separated to two groups at 21 days posthatch. One group was subjected to heat stress treatment in the range of 35-37 °C for 8 h per day, and the other was kept in thermoneutral condition. Body and heart weights were measured at 42 days posthatch, and gene expression in left ventricles were compared between treatments and broiler lines through RNA-seq analysis. Body weight and normalized heart weight were significantly reduced by heat stress only in Ross broilers. RNA-seq results of 44 genes were validated using Biomark assay. A total of 325 differentially expressed (DE) genes were detected between heat stress and thermoneutral in Ross 708 birds, but only 3 in Illinois broilers. Ingenuity pathway analysis (IPA) predicted dramatic changes in multiple cellular activities especially downregulation of cell cycle. Comparison between two lines showed that cell cycle activity is higher in Ross than Illinois in thermoneutral condition but is decreased under heat stress. Among the significant pathways (P < 0.01) listed for different comparisons, "Mitotic Roles of Polo-like Kinases" is always ranked first. The increased susceptibility of modern broilers to cardiac dysfunction under heat stress compared to slow-growing broilers could be due to diminished heart capacity related to reduction in relative heart size. The smaller relative heart size in Ross heat stress group than in Ross thermoneutral group is suggested by the transcriptome analysis to be caused by decreased cell cycle activity and increased apoptosis. The DE genes in RNA-seq analysis and significant pathways in IPA provides potential targets for breeding of heat-tolerant broilers with optimized heart function.