Modulation of telomere protection by the PI3K/AKT pathway.
Telomeres and the insulin/PI3K pathway are considered hallmarks of aging and cancer. Here, we describe a role for PI3K/AKT in the regulation of TRF1, an essential component of the shelterin complex. PI3K and AKT chemical inhibitors reduce TRF1 telomeric foci and lead to increased telomeric DNA damage and fragility. We identify the PI3Kα isoform as responsible for this TRF1 inhibition. TRF1 is phosphorylated at different residues by AKT and these modifications regulate TRF1 protein stability and TRF1 binding to telomeric DNA in vitro and are important for in vivo TRF1 telomere location and cell viability. Patient-derived breast cancer PDX mouse models that effectively respond to a PI3Kα specific inhibitor, BYL719, show decreased TRF1 levels and increased DNA damage. These findings functionally connect two of the major pathways for cancer and aging, telomeres and the PI3K pathway, and pinpoint PI3K and AKT as novel targets for chemical modulation of telomere protection.


Lyme disease--United States, 1999.
Lyme disease (LD) is caused by the tickborne spirochete Borrelia burgdorferi sensu lato and is the most common vectorborne disease in the United States. Surveillance for LD was initiated by CDC in 1982, and the Council of State and Territorial Epidemiologists designated it a nationally notifiable disease in January 1991. This report summarizes the number of LD cases reported to CDC during 1999. Although the number of cases decreased from 1998, the number of cases in 1999 was higher than the number reported during the early 1990s. LD can be prevented by avoiding tick-infested habitats, by using personal protective measures, by vaccination, by checking for and removing ticks attached to the body and clothes, and by reducing tick populations.


Improvement of thrombocytopenia following bone marrow transplantation by pegylated recombinant human megakaryocyte growth and development factor in mice.
We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is capable of improving thrombocytopenia and promoting thrombopoietic reconstitution following lethal irradiation and bone marrow transplantation (BMT) in mice. Immediately after receiving 10 Gy whole body irradiation (day 0), male C3H/HeN mice were inoculated with 10(6) bone marrow cells obtained from syngeneic mice. Circulating platelet counts decreased to below 4% of the normal counts with a nadir on day 10, and then returned to the normal level on day 28 in the control mice undergoing BMT. Subcutaneous consecutive treatment with PEG-rHuMGDF at doses from 10 to 300 micrograms/kg/day from day 1 for 13 days significantly improved the platelet nadir and promoted platelet recovery. The white blood cell counts and hemoglobin concentration following BMT were not influenced by the PEG-rHuMGDF. PEG-rHuMGDF-injection starting from day 5 did not improve the platelet nadir following BMT. Furthermore, administration with PEG-rHuMGDF on alternate days at 55.7 micrograms/kg/day for 7 days or at an interval of 3 days at 78 micrograms/kg/day for 4 days (twice a week for 2 weeks) had a significant efficacy, but these administration regimens had less efficacy than consecutive administration at 30 micrograms/kg/day for 13 days. The numbers of megakaryocytes and megakaryocyte progenitor cells decreased to 5 and 0.2% of normal level, respectively, in the control mice. Consecutive administration of PEG-rHuMGDF enhanced the recovery of the mean number of these cells compared to those in vehicle-treated mice, although such effects were not statistically significant except for the number of megakaryocyte progenitors on day 12. These results suggest that consecutive treatment with PEG-rHuMGDF beginning from the day after BMT may be effective in improving thrombocytopenia following BMT.


Mood disturbance in community cancer support groups. The role of emotional suppression and fighting spirit.
In this cross-sectional study, we tested whether the coping styles of emotional suppression and fighting spirit were associated with mood disturbance in cancer patients participating in professionally led community-based support groups even when demographic, medical, and group support variables were taken into account. A heterogeneous sample of 121 cancer patients (71% female, 29% male) completed the Courtauld Emotional Control Scale (CECS), the Mini-Mental Adjustment to Cancer Scale (Mini-MAC), a measure of perceived group support, and the Profile of Mood States (POMS). Consistent with hypotheses, lower emotional suppression and greater adoption of a fighting spirit, in addition to older age and higher income, were associated with lower mood disturbance. Gender, time since diagnosis, presence of metastatic disease, time in the support group, perceived group support, cognitive avoidance, and fatalism were unrelated to mood disturbance. Expression of negative affect and an attitude of realistic optimism may enhance adjustment and reduce distress for cancer patients in support groups.


Identification and characterization of cellular heterogeneity within the developing renal interstitium.
Kidney formation requires the coordinated growth of multiple cell types including the collecting ducts, nephrons, vasculature and interstitium. There is a long-held belief that interactions between progenitors of the collecting ducts and nephrons are primarily responsible for kidney development. However, over the last several years, it has become increasingly clear that multiple aspects of kidney development require signaling from the interstitium. How the interstitium orchestrates these various roles is poorly understood. Here, we show that during development the interstitium is a highly heterogeneous patterned population of cells that occupies distinct positions correlated to the adjacent parenchyma. Our analysis indicates that the heterogeneity is not a mere reflection of different stages in a linear developmental trajectory but instead represents several novel differentiated cell states. Further, we find that β-catenin has a cell autonomous role in the development of a medullary subset of the interstitium and that this non-autonomously affects the development of the adjacent epithelia. These findings suggest the intriguing possibility that the different interstitial subtypes may create microenvironments that play unique roles in development of the adjacent epithelia and endothelia.


Tubular morphology preservation and doping engineering of Sn/P-codoped hematite for photoelectrochemical water oxidation.
Tubular hematite with high-concentration, uniform doping is regarded as a promising material for photoelectrochemical water oxidation. However, the high-temperature annealing commonly used for activating doped hematite inevitably causes deformation of the tubular structure and an increase in the trap states. In the present work, Sn-doped tubular hematite on fluorine-doped tin oxide (FTO) is successfully obtained at 750 °C from a Sn-coated FeOOH tube precursor. Sn/P codoping, which is rarely considered for hematite, is also achieved via a gas phase reaction in phosphide atmosphere. The tubular morphology allows the dopant to diffuse from both the inner and outer surfaces, thus decreasing the doping profile in the radial direction. The even distribution of Sn and P synergetically increases the carrier density of hematite by one order of magnitude, which shortens the width of the depletion layer to ca. 2.3 nm (compared with 19.3 nm for the pristine sample) and leads to prolonged carrier lifetime and efficient charge separation. In addition, this codoping protocol does not introduce additional surface trap states, as evidenced by the increased charge injection efficiency and surface kinetic analysis using intensity modulated photocurrent spectroscopy (IMPS). As a result, the morphology- and doping-engineered hematite exhibits photocurrents of 0.9 mA cm-2 at 1.23 V and 3.8 mA cm-2 at 2.0 V vs. RHE under AM 1.5 G illumination (100 mW cm-2) in 1.0 M NaOH, representing 4.5-fold and 4.8-fold enhancements, respectively, compared with the photocurrents of undoped hematite. The present method is shown to be effective for preparing multi-element-doped hematite nanotubes and may find broad application in the development of other nanotubular photoelectrodes with or without doping for efficient and robust water oxidation.


Oncogenes and tumor suppressor genes: therapeutic implications.
Genetic instability is a hallmark of cancer. Alterations in DNA through mutations, deletions, and translocations affect genes that are fundamental to normal cell growth differentiation and programmed cell death. Here, we discuss these alterations as they relate to oncogenes and tumor suppressor genes. In addition, we describe the implications the changes in oncogenes and tumor suppressor genes have on designing new therapeutic strategies for the treatment of cancer.


Early Detection of Alzheimer's Disease Using Non-invasive Near-Infrared Spectroscopy.
Mild cognitive impairment (MCI) is a cognitive disorder characterized by memory impairment, wherein patients have an increased likelihood of developing Alzheimer's disease (AD). The classification of MCI and different AD stages is therefore fundamental for understanding and treating the disease. This study aimed to comprehensively investigate the hemodynamic response patterns among various subject groups. Functional near-infrared spectroscopy (fNIRS) was employed to measure signals from the frontal and bilateral parietal cortices of healthy controls (n = 8), patients with MCI (n = 9), mild (n = 6), and moderate/severe AD (n = 7) during a digit verbal span task (DVST). The concentration changes of oxygenated hemoglobin (HbO) in various subject groups were thoroughly explored and tested. Result revealed that abnormal patterns of hemodynamic response were observed across all subject groups. Greater and steeper reductions in HbO concentration were consistently observed across all regions of interest (ROIs) as disease severity developed from MCI to moderate/severe AD. Furthermore, all the fNIRS-derived indexes were found to be significantly and positively correlated to the clinical scores in all ROIs (R ≥ 0.4, P < 0.05). These findings demonstrate the feasibility of utilizing fNIRS for the early detection of AD, suggesting that fNIRS-based approaches hold great promise for exploring the mechanisms underlying the progression of AD.


ONIOM investigations of the heme degradation mechanism by MhuD: the critical function of heme ruffling.
The oxygen-dependent heme utilization degrading enzyme in Mycobacterium tuberculosis (MhuD) uniquely integrates monooxygenase and dioxygenase functions in a single active site. It cannot convert heme to biliverdin as canonical heme oxygenases but generates mycobilin without releasing carbon monoxide. Herein, by employing ONIOM calculations, we investigated the heme degradation mechanism of MhuD. Our calculations revealed that MhuD firstly follows a canonical monooxygenation mechanism to hydroxylate heme on the δ-meso carbon guided by the asparagine residue Asn7, which experiences a 21.2 kcal mol-1 energy barrier in the O-O cleavage rate-limiting step during the conversion process from ferric heme-hydroperoxy species to mycobilin. In the second degradation step, the ruffled conformation of oxoheme (oxoheme is the ferrous π radical complex formed by hydroxyheme experiencing deprotonation in the hydroxyl group and intramolecular electron transfer) imposed by the hydrophobic environment of the enzyme not only inhibits the continuing conversion of oxoheme to biliverdin but also endows the meso-carbons with radical characteristics, which turns the second degradation step to a dioxygenation reaction with 20.4 kcal mol-1 energy barrier. We further analysed the electronic structure change along the reaction process. Our calculation discovered that the ruffled structure of oxoheme is critical to the regiospecificity and even atom location selectivity, as well as the reaction mechanism of the degradation process.


Is it worthwhile to conduct a randomized controlled trial of glaucoma screening in the United Kingdom?
To assess the value of conducting a glaucoma screening randomized controlled trial in the UK. Decision model based economic evaluation and value of information analysis. Model derived from a previous health technology assessment. Model updated in terms of structure and parameter estimates with data from surveys, interviews with members of the public and health care providers and routine sources. On average, across a range of ages of initiating screening (40-60 years), glaucoma prevalence (1-5%), screening uptake (30-100%), and the performance of current case finding, screening was not cost-effective at a £30,000 threshold per quality adjusted life year (QALY) from the perspective of the National Health Service (NHS). The societal value of removing all uncertainty around glaucoma screening is £107 million at a threshold of £20,000 per QALY. For informing policy decisions on glaucoma screening, reducing uncertainty surrounding the NHS and personal social care cost of sight impairment (£74 million) was of most value, followed by reducing uncertainty in test performance (£14 million) and uptake of either screening or current eye care (£8 million each). A glaucoma screening trial in the UK is unlikely to be the best use of research resources. Further research to quantify the costs of sight impairment falling on the NHS and personal social services is a priority. Further development of glaucoma tests and research into strategies to promote the uptake of screening or current eye care such as through the use of a behavioural intervention would be worthwhile.


Reconstruction of the anophthalmic socket: lower eyelid malposition and canthal tendon laxity.
There are a number of etiologies underlying the development of socket deformity with associated lower eyelid malposition, lateral canthal tendon laxity, and/or contraction of the inferior fornix. In addition to cosmetic considerations, each of these anatomic problems can interfere with comfortable wear and retention of a prosthesis. This chapter gives an overview of these problems and details our preferred surgical approaches to repair of these anatomic deformities. Specifically discussed are techniques for: mucous membrane and ear cartilage grafting to repair lower lid inner lamellar tissue shortage, reconstruction of the inferior fornix/cul-de-sac, direct lower eyelid lateral canthal resuspension, and resuspension using a periosteal flap or autogenous fascia lata from the iliotibial tract.


Dietary iron-deficient anemia induces a variety of metabolic changes and even apoptosis in rat liver: a DNA microarray study.
Anemia can be induced by dietary iron deficiency, as well as by hemorrhagia. It may also be associated with changes in lipid metabolism. However, no global analysis detailing the consequences of iron deficiency in the liver has yet been conducted. Since the liver is a metabolically important organ and also a major iron-storing organ, we performed a comprehensive transcriptome analysis to determine the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet, approximately 3 ppm iron, ad libitum for 16 days. These rats were compared with similar rats pair-fed a control diet with a normal iron level, 48 ppm iron. The 16-day iron-deficient diet apparently induced anemia. On day 17, the rats were killed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 upregulated and 500 downregulated probe sets that characterized the iron-deficient diet group. In the upregulated probe sets, genes involved in cholesterol, amino acid, and glucose metabolism were significantly enriched, while genes related to lipid metabolism were significantly enriched in the downregulated probe sets. We also found that genes for caspases 3 and 12, which mediate endoplasmic reticulum (ER)-specific apoptosis, were upregulated in the iron-deficient group. Combined, these results suggest that iron deficiency exerts various influences, not only on nutrient metabolism but also on apoptosis, as a consequence of ER stress in the liver.


Prognostic impact of the ELN2017 risk classification in patients with AML receiving allogeneic transplantation.
In 2017, an updated European LeukemiaNet (ELN) risk classification was published allocating patients with acute myeloid leukemia (AML) to 3 risk groups on the basis of certain cytogenetic and molecular aberrations. To date, studies of the prognostic significance of the ELN2017 risk classification in the context of an allogeneic hematopoietic stem cell transplantation (HSCT) are lacking. We performed risk stratification according to the ELN2017 classification in 234 patients with AML who underwent allogeneic HSCT as a consolidation therapy. In our cohort, the risk of 39.7% of the patients was classified as favorable, that of 12.8% as intermediate, and that of 47.4% as adverse. In the context of allogeneic HSCT, the assignment to the 3 ELN2017 risk groups retained its prognostic significance, with patients with favorable risk having the best prognosis and those with adverse risk having the worst one. Subgroup analyses showed that patients with a monosomal karyotype or TP53 mutation had considerably increased relapse rates, even in the adverse-risk group. When we analyzed the impact of digital droplet PCR-based measurable residual disease (MRD) before allogeneic HSCT, MRD+ patients had impaired prognoses, with cumulative incidence of relapse and overall survival comparable to those of patients classified as having an ELN2017 adverse genetic risk. This study is the first to demonstrate that the ELN2017 classification distinguishes the 3 risk groups with significantly distinct prognoses, even after allogeneic HSCT, and emphasizes the dismal prognosis of patients with AML with TP53 mutations, monosomal karyotype, or MRD positivity after allogeneic HSCT.


Effects of genetic obesity on renal structure and function in the Zucker rat.
Although hyperphagia and obesity in the Zucker rat strain have been reported to be associated with spontaneous focal glomerulosclerosis (FGS), little is known about the age of onset and the natural history of hypertension, albuminuria, renal function, and glomerular injury in this model. We systematically investigated renal structure and function in obese male Zucker rats. Lean male littermates were used as controls. Obese rats developed glomerular mesangial matrix expansion and albuminuria by 14 weeks of age. These changes occurred despite normal inulin clearance (2.2 +/- 0.6 ml/min obese vs. 2.0 +/- 0.4 ml/min lean, P greater than 0.1) and filtration fraction (0.32 +/- 0.08 obese vs. 0.34 +/- 0.06 lean, P greater than 0.1), suggesting that increased glomerular filtration and renal plasma flow were not a prerequisite for the development of FGS. By 28 weeks of age, FGS was evident in seven of eight obese rats, and at 68 weeks of age all obese rats had marked FGS. Mean systolic blood pressure was elevated by 11 to 25 mm Hg in obese rats at all ages. Although the pathogenesis of glomerular injury is unknown, our data demonstrate that microalbuminuria, mild hypertension, and mesangial matrix expansion precede the development of progressive FGS in obese Zucker rats.


Modeling Multi-Agent Self-Organization through the Lens of Higher Order Attractor Dynamics.
Social interaction occurs across many time scales and varying numbers of agents; from one-on-one to large-scale coordination in organizations, crowds, cities, and colonies. These contexts, are characterized by emergent self-organization that implies higher order coordinated patterns occurring over time that are not due to the actions of any particular agents, but rather due to the collective ordering that occurs from the interactions of the agents. Extant research to understand these social coordination dynamics (SCD) has primarily examined dyadic contexts performing rhythmic tasks. To advance this area of study, we elaborate on attractor dynamics, our ability to depict them visually, and quantitatively model them. Primarily, we combine difference/differential equation modeling with mixture modeling as a way to infer the underlying topological features of the data, which can be described in terms of attractor dynamic patterns. The advantage of this approach is that we are able to quantify the self-organized dynamics that agents exhibit, link these dynamics back to activity from individual agents, and relate it to other variables central to understanding the coordinative functionality of a system's behavior. We present four examples that differ in the number of variables used to depict the attractor dynamics (1, 2, and 6) and range from simulated to non-simulated data sources. We demonstrate that this is a flexible method that advances scientific study of SCD in a variety of multi-agent systems.


Microbiology and potential applications of aerobic methane oxidation coupled to denitrification (AME-D) process: A review.
Aerobic methane oxidation coupled to denitrification (AME-D) is an important link between the global methane and nitrogen cycles. This mini-review updates discoveries regarding aerobic methanotrophs and denitrifiers, as a prelude to spotlight the microbial mechanism and the potential applications of AME-D. Until recently, AME-D was thought to be accomplished by a microbial consortium where denitrifying bacteria utilize carbon intermediates, which are excreted by aerobic methanotrophs, as energy and carbon sources. Potential carbon intermediates include methanol, citrate and acetate. This mini-review presents microbial thermodynamic estimations and postulates that methanol is the ideal electron donor for denitrification, and may serve as a trophic link between methanotrophic bacteria and denitrifiers. More excitingly, new discoveries have revealed that AME-D is not only confined to the conventional synergism between methanotrophic bacteria and denitrifiers. Specifically, an obligate aerobic methanotrophic bacterium, Methylomonas denitrificans FJG1, has been demonstrated to couple partial denitrification with methane oxidation, under hypoxia conditions, releasing nitrous oxide as a terminal product. This finding not only substantially advances the understanding of AME-D mechanism, but also implies an important but unknown role of aerobic methanotrophs in global climate change through their influence on both the methane and nitrogen cycles in ecosystems. Hence, further investigation on AME-D microbiology and mechanism is essential to better understand global climate issues and to develop niche biotechnological solutions. This mini-review also presents traditional microbial techniques, such as pure cultivation and stable isotope probing, and powerful microbial techniques, such as (meta-) genomics and (meta-) transcriptomics, for deciphering linked methane oxidation and denitrification. Although AME-D has immense potential for nitrogen removal from wastewater, drinking water and groundwater, bottlenecks and potential issues are also discussed.


Ancestral origins and invasion pathways in a globally invasive bird correlate with climate and influences from bird trade.
Invasive species present a major threat to global biodiversity. Understanding genetic patterns and evolutionary processes that reinforce successful establishment is paramount for elucidating mechanisms underlying biological invasions. Among birds, the ring-necked parakeet (Psittacula krameri) is one of the most successful invasive species, established in over 35 countries. However, little is known about the evolutionary genetic origins of this species and what population genetic signatures tell us about patterns of invasion. We reveal the ancestral origins of populations across the invasive range and explore the potential influence of climate and propagule pressure from the pet trade on observed genetic patterns. Ring-necked parakeet samples representing the ancestral native range (n = 96) were collected from museum specimens, and modern samples from the invasive range (n = 855) were gathered from across Europe, Mauritius and Seychelles, and sequenced for two mitochondrial DNA markers comprising 868 bp of cytochrome b and control region, and genotyped at 10 microsatellite loci. Invasive populations comprise birds that originate predominantly from Pakistan and northern areas of India. Haplotypes associated with more northerly distribution limits in the ancestral native range were more prevalent in invasive populations in Europe, and the predominance of Asian haplotypes in Europe is consistent with the higher number of Asian birds transported by the pet trade outside the native range. Successful establishment of invasive species is likely to be underpinned by a combination of environmental and anthropogenic influences.


The Psychophysiological Investigations of Myocardial Ischemia (PIMI) study: objective, methods, and variability of measures.
This study evaluated physiological, neuroendocrine, and psychological status and functioning of patients with coronary artery disease in order to clarify their role in the expression of symptoms during myocardial ischemia (MI), and to establish repeatability of responses to mental stress. Design and methods of the study are presented. One hundred ninety-six coronary artery disease patients were examined during physical and mental stress tests in four hospitals. Eligibility criteria included narrowing of at least 50% in the diameter of at least one major coronary artery or verified history of myocardial infarction, and evidence of ischemia on an exercise treadmill test. Psychological, biochemical, and autonomic function data were obtained before, during, and after exposure to mental and exercise stressors during 2 or 3 half-days of testing. Ventricular function was assessed by radionuclide ventriculography, and daily ischemia by ambulatory electrocardiography. Sixty patients returned for a short-term mental stress repeatability study. Twenty-nine individuals presumed to be free of coronary disease were also examined to establish reference values for cardiac responses to mental stress. Study participants were 41 to 80 years of age; 83 (42%) had a history of MI, 6 (3%) of congestive heart failure, and 163 (83%) of chest pain; 170 (87%) were men; and 90 (46%) had ischemia accompanied by angina during exercise treadmill testing. Ischemia during ambulatory monitoring was found in 35 of 90 (39%) patients with and 48 of 106 (45%) patients without angina during exercise-provoked ischemia. Intraobserver variability of ejection fraction changes during bicycle exercise and two mental stress tests (Speech and Stroop) was good (kappa = 1.0, .90, and .76, respectively; percent agreement = 100, 97.5, and 93.8%, respectively). Variability of assessed wall motion abnormalities during bicycle exercise was better (kappa, agreement = 85%) than during Speech or Stroop kappa and .57, percent agreement = 70% and 82.5%, respectively). Study design, quality control data, and baseline characteristics of patients enrolled for a clinical study of symptomatic and asymptomatic myocardial ischemia are described. Lower repeatability of reading wall motion abnormalities during mental stress than during exercise may be due to smaller effects on wall motion and lack of an indicator for peak mental stress.


Insulin therapy could prevent salt-induced high blood pressure in diabetes mellitus.
The effectiveness of insulin replacement therapy in the prevention of salt-induced hypertension in diabetes mellitus was examined using Alloxan diabetic rats. Early daily (eight units/day) treatment with insulin prevented the development of high blood pressure after six weeks of high-salt feeding. The mean arterial pressure (MAP) for the early insulin-treated and salt-fed group (DET-SF) was 123.37 +/- 6.37 mmHg which was close to the value for normal (control) rats 128.17 +/- 4.84 mmHg, but significantly (p < 0.001) less than that of the untreated diabetic salt-fed group (DSF) which was 164.58 +/- 8.33 mmHg. The nondiabetic salt-fed (NDSF) group had MAP of 150.27 +/- 4.24 mmHg. Late commencement of insulin therapy did not significantly affect the sensitivity of the diabetic rats to high-salt diet. The results suggest that early commencement of insulin therapy could prevent the development of high blood pressure in diabetic rats.


Quaternary Selenides EuLnCuSe3: Synthesis, Structures, Properties and In Silico Studies.
In this work, we report on the synthesis, in-depth crystal structure studies as well as optical and magnetic properties of newly synthesized heterometallic quaternary selenides of the Eu+2Ln+3Cu+1Se3 composition. Crystal structures of the obtained compounds were refined by the derivative difference minimization (DDM) method from the powder X-ray diffraction data. The structures are found to belong to orthorhombic space groups Pnma (structure type Ba2MnS3 for EuLaCuSe3 and structure type Eu2CuS3 for EuLnCuSe3, where Ln = Sm, Gd, Tb, Dy, Ho and Y) and Cmcm (structure type KZrCuS3 for EuLnCuSe3, where Ln = Tm, Yb and Lu). Space groups Pnma and Cmcm were delimited based on the tolerance factor t', and vibrational spectroscopy additionally confirmed the formation of three structural types. With a decrease in the ionic radius of Ln3+ in the reported structures, the distortion of the (LnCuSe3) layers decreases, and a gradual formation of the more symmetric structure occurs in the sequence Ba2MnS3 → Eu2CuS3 → KZrCuS3. According to magnetic studies, compounds EuLnCuSe3 (Ln = Tb, Dy, Ho and Tm) each exhibit ferrimagnetic properties with transition temperatures ranging from 4.7 to 6.3 K. A negative magnetization effect is observed for compound EuHoCuSe3 at temperatures below 4.8 K. The magnetic properties of the discussed selenides and isostructural sulfides were compared. The direct optical band gaps for EuLnCuSe3, subtracted from the corresponding diffuse reflectance spectra, were found to be 1.87-2.09 eV. Deviation between experimental and calculated band gaps is ascribed to lower d states of Eu2+ in the crystal field of EuLnCuSe3, while anomalous narrowing of the band gap of EuYbCuSe3 is explained by the low-lying charge-transfer state. Ab initio calculations of the crystal structures, elastic properties and phonon spectra of the reported compounds were performed.


[Validation of diagnostic scales of family functioning for use in primary health care services].
Care provided to patients in primary health services should include both a physical and a psychological assessment. In many cases treatment success depends on understanding individuals and their interactions, especially within the family; it is important for health professionals to be trained in this area. We investigated the validity of three well-known diagnostic scales of family functioning from the United States of America (FACES III, Beavers-Timberlawn, and GARF) for use in our setting in Porto Alegre, Brazil. The three scales were used with 31 families and compared to the results from clinical evaluations (semistructured family interviews), which were considered the gold standard. FACES III was also used with a sample of 102 families in the community. The Beavers-Timberlawn and GARF scales were strongly and positively correlated with the clinical evaluations. In contrast, our results suggest that FACES III is not a useful screening tool in primary care to detect the risk of psychiatric disorders. The Beavers-Timberlawn and GARF instruments showed great usefulness for formulating and classifying diagnoses of family functioning.


Implantable pacing lead technology.
Lead technology is reviewed, beginning with the first known permanent implant and continuing through today's state-of-the-art implant. Nondislodging transvenous leads and epimyocardial leads (sutureless, screw-in leads) are described. Conductors, insulation, and electrodes are discussed. The emphasis today appears to be on improving carbon, screw-in, porous, platinized and steroid eluting electrodes, while future developments may include very thin bipolar leads, higher pacing impedance electrodes, and easier to implant and explant devices.


Future applications of lasers in surgery and medicine: a review.
The experimental use of lasers in surgery and medicine began only shortly after the development of the first working laser system. However, the development of practical, effective, and safe surgical lasers has been lengthy with many obstacles and delays. Today the laser is used for a wide variety of surgical operations. The fundamental limits and potential for future applications of lasers in surgery and medicine are discussed.


Granulocyte colony-stimulating factor does not promote neurogenesis after experimental intracerebral haemorrhage.
Hematopoietic growth factors have been suggested to induce neuroprotective and regenerative effects in various animal models of cerebral injury. However, the pathways involved remain widely unexplored. This study aimed to investigate effects of local and systemic administration of granulocyte colony-stimulating factor on brain damage, functional recovery, and cerebral neurogenesis in an intracerebral haemorrhage whole blood injection model in rats. Eight-week-old male Wistar rats (n = 100) underwent induction of striatal intracerebral haemorrhage by autologous whole blood injection or sham procedure and were randomly assigned to either (a) systemic treatment with granulocyte colony-stimulating factor (60 μg/kg) for five-days; (b) single intracerebral injection of granulocyte colony-stimulating factor (60 μg/kg) into the cavity; or (c) application of vehicle for five-days. Bromodeoxyuridine-labelling and immunohistochemistry were used to analyze proliferation and survival of newly born cells in the sub-ventricular zone and the hippocampal dentate gyrus. Moreover, functional deficits and lesion volume were assessed until day 42 after intracerebral haemorrhage. Differences in lesion size or hemispheric atrophy between granulocyte colony-stimulating factor-treated and control groups did not reach statistical significance. Neither systemic, nor local granulocyte colony-stimulating factor administration induced neurogenesis within the dentate gyrus or the sub-ventricular zone. The survival of newborn cells in these regions was prevented by intracerebral granulocyte colony-stimulating factor application. A subtle benefit in functional recovery at day 14 after intracerebral haemorrhage induction was observed after granulocyte colony-stimulating factor treatment. There was a lack of neuroprotective or neuroregenerative effects of granulocyte colony-stimulating factor in the present rodent model of intracerebral haemorrhage. Conflicting results from functional outcome assessment require further research.


Enteric neurons synthesize netrins and are essential for the development of the vagal sensory innervation of the fetal gut.
During fetal life, vagal sensory fibers establish a reproducible distribution in the gut that includes an association with myenteric ganglia. Previous work has shown that netrin is expressed in the bowel wall and, by acting on its receptor, deleted in colorectal cancer (DCC), mediates the guidance of vagal sensory axons to the developing gut. Because the highest concentration of netrins in fetal bowel is in the endoderm, we tested the hypothesis that the ingrowth of vagal afferents to the gut would be independent of the presence of enteric neurons, although enteric neurons might influence the internal distribution of these fibers. Surprisingly, experiments indicated that the vagal sensory innervation is intrinsic neuron-dependent. To examine the vagal innervation in the absence of enteric ganglia, fetal Ret -/- mice were labeled by applying DiI bilaterally to nodose ganglia. In Ret -/- mice, DiI-labeled vagal sensory axons descended in paraesophageal trunks as far as the proximal stomach, which contains neurons, but did not enter the aganglionic bowel. To determine whether neurons produce netrins, enteric neural-crest-derived cells (ENCDCs) were immunoselected from E15 rat gut. Transcripts encoding netrin-1 and -3 were not detected in the ENCDCs, but appeared after they had given rise to neurons. When these neurons were cocultured with cells expressing c-Myc-tagged netrin-1, the neurons displayed netrin-1, but not c-Myc, immunoreactivity. Enteric neurons thus synthesize netrins. The extent to which neuronal netrin accounts for the dependence of the vagal sensory innervation on intrinsic neurons, remains to be determined.


Extinction can be estimated from moderately sized molecular phylogenies.
Hundreds of studies have been dedicated to estimating speciation and extinction from phylogenies of extant species. Although it has long been known that estimates of extinction rates using trees of extant organisms are often uncertain, an influential paper by Rabosky (2010) suggested that when birth rates vary continuously across the tree, estimates of the extinction fraction (i.e., extinction rate/speciation rate) will appear strongly bimodal, with a peak suggesting no extinction and a peak implying speciation and extinction rates are approaching equality. On the basis of these results, and the realistic nature of this form of rate variation, it is now generally assumed by many practitioners that extinction cannot be understood from molecular phylogenies alone. Here, we reevaluated and extended the analyses of Rabosky (2010) and come to the opposite conclusion-namely, that it is possible to estimate extinction from molecular phylogenies, even with model violations due to heritable variation in diversification rate. Note that while it may be tempting to interpret our study as advocating the application of simple birth-death models, our goal here is to show how a particular model violation does not necessitate the abandonment of an entire field: use prudent caution, but do not abandon all hope.


[Results of hetero-osteosynthesis in treatment of injuries of the crural bones].
The early and late results of secure heteroosteosynthesis in patients with fresh open and closed fractures and pseudarthrosis of crural bones are discussed. The most favourable results were gained in treatment of closed injuries of crural bones-80.25% of good and excellent issues. Observations for up to 6 years period over patients have demonstrated persistant functional issues with restoration of the anatomical form of the injured extremity and complete rehabilitation of the capacity for work in patients operated upon.


Breaking bad news: use of cancer survivors in role-playing exercises.
To teach medical students how to deliver a diagnosis of cancer using role-play with a cancer survivor volunteer. Medical students participated in a curricular module on "breaking bad news." Its novel aspect was the inclusion of role-playing exercises during which the student communicated the initial diagnosis of cancer to a cancer survivor volunteer. The clinical scenario was based on the volunteer's own history of cancer. The exercise required the student to become knowledgeable about the volunteer's cancer and its mode of presentation, deliver the diagnosis using previously demonstrated methods, and then receive verbal feedback from the volunteer. A panel discussion with the cancer survivor volunteers concluded the module. The efficacy of this curricular module was assessed by the students' performance during the role-playing exercise, gain in confidence in communicating bad news, and overall rating of the learning experience. The interaction of the students with the cancer survivors was the strength of this curriculum, providing the students with an important perspective on physician-patient relationships and coping with cancer. The students demonstrated a high level of adherence to preferred communication techniques, gained significant confidence with the task of "breaking bad news," and were very satisfied with the module. Participation in these role-playing exercises by the cancer survivor volunteers was viewed as emotionally demanding but also rewarding. Recruitment and retention of the volunteers were not obstacles to this activity. Role-playing with cancer survivor volunteers can be an effective method of teaching medical students how to communicate bad news.


Efficient CRISPR/Cas9 Genome Editing of Phytoene desaturase in Cassava.
CRISPR/Cas9 has become a powerful genome-editing tool for introducing genetic changes into crop species. In order to develop capacity for CRISPR/Cas9 technology in the tropical staple cassava (Manihot esculenta), the Phytoene desaturase (MePDS) gene was targeted in two cultivars using constructs carrying gRNAs targeting two sequences within MePDS exon 13. After Agrobacterium-mediated delivery of CRISPR/Cas9 reagents into cassava cells, both constructs induced visible albino phenotypes within cotyledon-stage somatic embryos regenerating on selection medium and the plants regenerated therefrom. A total of 58 (cv. 60444) and 25 (cv. TME 204) plant lines were recovered, of which 38 plant lines (19 from each cultivar) were analyzed for mutagenesis. The frequency of plant lines showing albino phenotype was high, ranging from 90 to 100% in cv. TME 204. Observed albino phenotypes were comprised of full albinos devoid of green tissue and chimeras containing a mixture of white and green tissues. Sequence analysis revealed that 38/38 (100%) of the plant lines examined carried mutations at the targeted MePDS site, with insertions, deletions, and substitutions recorded. One putatively mono-allelic homozygous line (1/19) was found from cv. 60444, while 1 (1/19) and 4 (4/19) putatively bi-allelic homozygous lines were found in 60444 and TME204, respectively. The remaining plant lines, comprised mostly of the chimeras, were found to be putatively heterozygous. We observed minor (1 bp) nucleotide substitutions and or deletions upstream of the 5' and or downstream of the 3' targeted MePDS region. The data reported demonstrates that CRISPR/Cas9-mediated genome editing of cassava is highly efficient and relatively simple, generating multi-allelic mutations in both cultivars studied. Modification of MePDS described here generates visually detectable mutated events in a relatively short time frame of 6-8 weeks, and does not require sequencing to confirm editing at the target. It therefore provides a valuable platform to facilitate rapid assessment and optimization of CRISPR/Cas9 and other genome-editing technologies in cassava.


Brain orexin promotes obesity resistance.
Resistance to obesity is becoming an exception rather than the norm, and understanding mechanisms that lead some to remain lean in spite of an obesigenic environment is critical if we are to find new ways to reverse this trend. Levels of energy intake and physical activity both contribute to body weight management, but it is challenging for most to adopt major long-term changes in either factor. Physical activity outside of formal exercise, also referred to as activity of daily living, and in stricter form, spontaneous physical activity (SPA), may be an attractive modifiable variable for obesity prevention. In this review, we discuss individual variability in SPA and NEAT (nonexercise thermogenesis, or the energy expended by SPA) and its relationship to obesity resistance. The hypothalamic neuropeptide orexin (hypocretin) may play a key role in regulating SPA and NEAT. We discuss how elevated orexin signaling capacity, in the context of a brain network modulating SPA, may play a major role in defining individual variability in SPA and NEAT. Greater activation of this SPA network leads to a lower propensity for fat mass gain and therefore may be an attractive target for obesity prevention and therapy.


[Effect of cultivation conditions on fatty acid content of Clavibacter michiganensis subsp. michiganensis lipids].
The fatty acid content of C. michiganensis subsp. michiganensis cellular lipids in different culture conditions was investigated. It was established, that it lies in a narrow range C14-C18 and belongs to isoanteiso type. The species character is constant, independent of temperature, duration of cultivation and medium content dominance of saturated branched-chain fatty acids, among which the anteiso-acids dominate, generally a-C15. A response to the temperature modification of bacteria cultivation, medium and age of culture is expressed by relations between separate fatty acids. Thus the modifications of fatty acid content, connected with age of culture and temperature of cultivation, depend on a strain. The cultivation of bacteria on a rich medium in comparison with poor one enlarges the content of nonbranched-chain and anteiso-acids in lipids.


Sacral nerve stimulation during pregnancy: case report and review of the literature.
The use of sacral nerve stimulation during pregnancy is not recommended because of the unknown effects on the offspring. There is a paucity of literature on the subject. A 25-year-old woman who had a sacral nerve stimulator for severe interstitial cystitis/bladder pain syndrome had 2 successful pregnancies. Against medical advice, she kept the stimulator activated for symptom control during the pregnancies. The first child was later diagnosed with chronic motor tic disorder, and the second had a pilonidal sinus at birth. Whether this outcome is related to the neurostimulator is unknown. The efficacy of sacral nerve stimulation decreased after each pregnancy. The safety of sacral nerve stimulation in pregnancy has not been well established. Until further research is done, we recommend that women of reproductive age with a sacral nerve stimulator be advised about contraception and that the device should be deactivated before or as soon as pregnancy is confirmed.


Attenuation in invasive blood pressure measurement systems.
Poor fidelity invasive arterial blood pressure (IABP) traces are a frequent practical problem. It is common practice to describe any such trace as being 'damped'; the resonance behaviour of IABP measurement systems having been extensively described in the literature. However, as poor quality arterial blood pressure signals are seen even with optimal pressure transduction circuits, this cannot be the sole mechanism. In this commentary the classical lumped-parameter Windkessel model is extended by postulating an additional impedance proximal to the site of IABP measurement. This impedance represents any mechanical obstruction to laminar flow. Equations are presented relating measured and actual arterial blood pressures in terms of the model impedances. The reactive properties of such a partial obstruction may lead to an IABP trace that is superficially similar in appearance to the case of an over-damped measurement system. However, this phenomenon should be termed 'attenuation' rather than 'damping' and is probably more common. The distinction is of practical importance as the behaviour of the measured systolic and diastolic pressures is different -- both are systematically underestimated and the mean arterial pressure is thus not preserved. Furthermore, this error varies inversely with the peripheral vascular resistance of the tissues distal to the measurement point, therefore apparently magnifying the effect of vasodilatation on blood pressure or derived quantities.


[Radioimmunological analysis of gonadotropic and steroid hormones in breast cancer].
A study of the blood levels of gonadotropic and steroid hormones in 321 breast cancer patients has shown that the basal levels of gonadotropin concentration in them exceed the control values (p less than 0.05); those of the follicle-stimulating hormone--in 54.1% of patients at reproductive age and in menopause less than 5 years and in 33.8% of patients in menopause over 5 years; those of luteotropin--in 50 and 93.5% of patients, respectively. Low basal levels of estradiol and progesterone were found more than 70% of breast cancer patients. A significant decrease in the level of the above hormones (p less than 0.05) was noted after polychemotherapy. An increase in the levels of corticotropin (in 54.5-65.2% of patients) and cortisol (in 81.6-84.3% of patients) was noted with progression of breast cancer. Data on the above hormones can be used as a diagnostic and prognostic test.


A meta-analysis of the treatment of panic disorder with or without agoraphobia: a comparison of psychopharmacological, cognitive-behavioral, and combination treatments.
To compare short-term efficacy of benzodiazepines, antidepressants, psychological panic management, exposure in vivo, and combination treatments in panic disorder with or without agoraphobia (PA), a meta-analysis was conducted. Included were 106 studies, pertaining to 222 treatment conditions, 5,011 patients at pretest and 4,016 at posttest. Pre/post effect sizes Cohen's d were calculated within the treatment conditions for four clinical variables: panic, agoraphobia, depression, and general anxiety. Seven large treatment conditions were used in the main analyses: high-potency benzodiazepines, antidepressants, psychological panic management, exposure in vivo, pill-placebo combined with exposure, antidepressants combined with exposure, and psychological panic management combined with exposure in vivo. First, these treatments were compared with a control condition, consisting of pill-placebo, attention placebo, and waiting list. Next, a comparison was made between the treatments. Antidepressants, psychological panic management, high-potency benzodiazepines, and antidepressants combined with exposure in vivo were superior to the control condition for panic attacks. Exposure in vivo alone was not effective for panic attacks. With regard to agoraphobic avoidance, all seven treatments were superior to the control condition. When comparing the various treatment conditions, no differences concerning panic attacks were found. For agoraphobic avoidance, the combination of antidepressants with exposure in vivo was superior to the other conditions. The combination of antidepressants with exposure in vivo is the most potent short-term treatment of PA.


Chemical studies in host-virus interactions; the mutual reactivation of T2r virus inactivated by ultraviolet light and the synthesis of desoxyribose nucleic acid.
A method has been described for following purine and pyrimidine synthesis in intact cells by measuring the ultraviolet absorption of a bacterial suspension. It has been shown that in cells infected with active virus, the rate of increase of ultraviolet absorption at 2600 A corresponded to that of DNA, although preceding DNA synthesis slightly. The amount of separation of the curves in time was determined by the multiplicity of infection. Under conditions of mutual reactivation of ultraviolet-irradiated virus, DNA synthesis was inhibited but not the increase in ultraviolet absorption. Thus a continuing purine and pyrimidine synthesis was indicated by the increase in this function. When an intact virus particle could be found within these bacteria, however, DNA synthesis began at the rate characteristic of normal infections. Certain peculiarities of lysis in this system were noted. The significance of these observations for various genetic theories has been discussed. It would appear that Luria's hypothesis of independent gene pool synthesis has probably been disproven. It has also been shown that the lesion produced by irradiation of a virus particle with ultraviolet light probably occurs in the DNA of the particle. The validity of these conclusions will depend on a knowledge of the relation of virus protein synthesis to DNA synthesis in this system.


Does subsidizing the cost of care impact on dental attendance patterns among older adults?
To assess whether eligibility for an age-related universal (pioneer generation [PG]) subsidy incentivises dental attendance by older Singaporeans. Data were collected between 2018 and 2021 from in-person interviews of Singaporean adults aged 60-90 years using a questionnaire and a clinical examination. The questionnaire included details of age, gender, ethnicity, education, residential status, socio-economic status, marital status, eligibility for subsidy (community health assistance/CHAS, PG or both) and frequency of dental attendance. The clinical examination recorded number of teeth (categorized as edentulous, 1-9 teeth;10-19 teeth; ≥20 teeth). To estimate the effect of the PG subsidy on dental attendance pattern, a regression discontinuity (RD) analysis was applied using age as the assignment variable. A total of 1172 participants aged 60-90 years (64.2% female) were recruited, with 498 (43%) being eligible for the PG subsidy. For those eligible for PG subsidy, there was a higher proportion of regular attenders than irregular attenders (53.6% vs. 46.4%). In age adjusted RD analysis, those eligible for the PG subsidy were 1.6 (95% CI: 1.0, 2.7) times more likely to report regular attendance than their PG non-eligible counterparts. The association remained strong (OR 2.1; 95% CI: 1.1-3.7) even after further controlling for demographics, socioeconomic factors, number of teeth and eligibility for the CHAS subsidy. Being eligible for the PG subsidy substantially increased the odds of regular dental attendance.


Dioncophyllines C2, D2, and F and Related Naphthylisoquinoline Alkaloids from the Congolese Liana Ancistrocladus ileboensis with Potent Activities against Plasmodium falciparum and against Multiple Myeloma and Leukemia Cell Lines.
Dioncophylline F (1), the first 5,8'-coupled dioncophyllaceous alkaloid (i.e., lacking an oxygen function at C-6 and possessing an R-configuration at C-3), was isolated from the recently described Congolese liana Ancistrocladus ileboensis. Two further, likewise Dioncophyllaceae-type, alkaloids, the dioncophyllines C2 (2) and D2 (3), were identified, along with the Ancistrocladaceae-type compound ancistrocladisine B (4), which is oxygenated at C-6 and S-configured at C-3. The structures of the new compounds were determined by spectroscopic, chemical, and chiroptical methods. The stereostructure of 1 was further confirmed by total synthesis. As a consequence of the lack of a methyl group ortho to their biaryl axes, both dioncophylline F (1) and the 7,8'-coupled dioncophylline D2 (3) occur as pairs of configurationally semistable and, thus, slowly interconverting atropo-diastereomers, whereas dioncophylline C2 (2), with its 5,1'-linkage, is configurationally stable at the axis. Eight further known naphthylisoquinolines were isolated from A. ileboensis, among them dioncophylline A (P-10), its 4'-O-demethyl analogue P-11, and 5'-O-methyldioncophylline D (7), which were found to display strong cytotoxic activities against multiple myeloma INA-6 cells (P-10 even stronger than the standard drug melphalan) and against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Moreover, the dioncophyllines 1, 3, and 7 showed high-and specific-activities against the malaria parasite Plasmodium falciparum.


Crossover from itinerant-electron to localized-electron behavior in Sr(1-x)Ca(x)CrO3 perovskite solid solution.
Polycrystalline samples of the perovskite family Sr(1-x)Ca(x)CrO(3) have been prepared at high pressure and temperature in steps of 1/6 over the range 0 ≤ x ≤ 1. Rietveld analysis shows a series of structural phase transitions from cubic to tetragonal to orthorhombic with increasing x. The cubic samples have no long-range magnetic order; the other samples become antiferromagnetically ordered below a T(N) that increases with x. At ambient pressure, the electric transport properties of the cubic and tetragonal phases are semiconducting with a small (meV range) activation energy that increases with x; the orthorhombic phase exhibits variable-range hopping rather than the small-polaron behavior typically found for mixed-valent, localized-electron configurations. Above a pressure P=P(C), a smooth insulator-metal transition is found at a T(IM) that decreases with increasing P for a fixed x; P(C) increases with x. These phenomena are rationalized qualitatively with a π(∗)-band model having a width W(π) that approaches crossover from itinerant-electron to localized-electron behavior as W(π) decreases with increasing x. The smaller size of the Ca(2+) ion induces the structural changes and the greater acidity of the Ca(2+) ion is primarily responsible for narrowing W(π) as x increases.


Purification of two components of mouse L cell interferon: electrophoretic demonstration of interferon proteins.
Mouse L cell interferon induced by Newcastle disease virus was purified by the procedure described previously (Yamamoto et al. 1974) followed by gel filtration. The two fractions obtained containing interferon species S (36000 daltons) and F (24000 daltons), respectively, were analysed electrophoretically at pH 4-3, or in the presence of sodium dodecyl sulphate (SDS) at pH 7-2. In both fractions, interferon activity was invariably associated with distinct protein bands. In the F-containing fraction there were essentially no other proteins, and in the S-containing fraction, impurity proteins were well separated from the interferon activity. The apparent mol. wt. determined by SDS-gel electrophoresis showed little or no dependence on gel concentration, suggesting that the interferons had low carbohydrate contents, and did not change after reduction with thiol reagents in SDS and urea.


CE: critical care recovery center: an innovative collaborative care model for ICU survivors.
Five million Americans require admission to ICUs annually owing to life-threatening illnesses. Recent medical advances have resulted in higher survival rates for critically ill patients, who often have significant cognitive, physical, and psychological sequelae, known as postintensive care syndrome (PICS). This growing population threatens to overwhelm the current U.S. health care system, which lacks established clinical models for managing their care. Novel innovative models are urgently needed. To this end, the pulmonary/critical care and geriatrics divisions at the Indiana University School of Medicine joined forces to develop and implement a collaborative care model, the Critical Care Recovery Center (CCRC). Its mission is to maximize the cognitive, physical, and psychological recovery of ICU survivors. Developed around the principles of implementation and complexity science, the CCRC opened in 2011 as a clinical center with a secondary research focus. Care is provided through a pre-CCRC patient and caregiver needs assessment, an initial diagnostic workup visit, and a follow-up visit that includes a family conference. With its sole focus on the prevention and treatment of PICS, the CCRC represents an innovative prototype aimed at modifying post-critical illness morbidities and improving the ICU survivor's quality of life.


[Idiopathic retroperitoneal fibrosis causing obstructive uropathy: a case report].
Idiopathic retroperitoneal fibrosis leading to obstructive uropathy is a rare disease in our country, so a typical case deserves presentation. The patient is a 56-year-old female to have a clinical manifestation of obstructive uropathy. Retrograde pyelogram permitted 5 Fr. ureteral catheter to pass the stenotic segment. At the mean-time, there was hydronephrosis, medial deviation and gradual thinning and pointing of the middle segment of the ureter (classic triad). Computed tomography revealed that retroperitoneal soft tissue plaque enveloped aorta, inferior vena cava, and bilateral ureters. The patient received ureterolysis with ureter intraperitonealization and lateralization. The plaque was pathologically proved fibrosis. Renal function became normal postoperatively.


Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus.
Biological rhythms in mammals are driven by a central circadian clock located in the suprachiasmatic nucleus (SCN). At the molecular level the biological clock is based on the rhythmic expression of clock genes. Two basic helix-loop-helix (bHLH)/PAS-containing transcription factors, CLOCK and BMAL1 (MOP3), provide the basic drive to the system by activating transcription of negative regulators through E box enhancer elements. A critical feature of circadian timing is the ability of the clockwork to be entrained to the environmental light/dark cycle. The light-resetting mechanism of the mammalian circadian clock is poorly understood. Light-induced phase shifts are correlated with the induction of the clock genes mPer1 and mPer2 and a subsequent increase in mPER1 protein levels. It has previously been suggested that rapid degradation of BMAL1 protein in the rat SCN is part of the resetting mechanism of the central pacemaker. Our study shows that BMAL1 and CLOCK proteins are continuously expressed at high levels in the mouse SCN, supporting the hypothesis that rhythmic negative feedback plays the major role in rhythm generation in the mammalian pacemaker. Using both immunocytochemistry and immunoblot analysis, our studies demonstrate that BMAL1 protein in the mouse SCN is not affected by a phase-resetting light pulse. These results indicate that rapid degradation of BMAL1 protein is not a consistent feature of resetting mechanisms in rodents.


Morbidity and mortality of pancreatic tumors undergoing surgical treatment.
Pancreatic cancer has a high mortality rate due to late diagnosis and aggressive behavior. The prognosis is poor, with 5-year survival occurring in less than 5% of cases. To analyze demographic characteristics, comorbidities, type of procedure and early postoperative complications of patients with pancreatic cancer submitted to surgical treatment. Cross-sectional study with analysis of 28 medical records of patients with malignant tumors of the pancreas in a 62 month. Data collection was performed from the medical records of the hospital. Of the total, 53,6% were male and the mean age was 60.25 years. According to the procedure, 53,6% was submitted to duodenopancreactectomy the remainder to biliodigestive derivation or distal pancreatectomy. The ductal adenocarcinoma occurred in 82,1% and 92,9% of tumors were located in the pancreatic head. Early postoperative complications occurred in 64,3% of cases and the most prevalent was intra-abdominal abscess (32,1%). Among duodenopancreactectomies 77,8% had early postoperative complications. Its necessary to encourage early detection of tumors of the pancreas to raise the number operations with curative intent. Refinements in surgical techniques and surgical teams can diminish postoperative complications and, so, operative morbimortality can also decrease over time.


A Nutritional Approach to Optimizing Pump Therapy in Type 1 Diabetes Mellitus.
Achieving optimal glucose control in individuals with type 1 diabetes (T1DM) continues to pose a significant challenge. While continuous insulin infusion systems have shown promise as an alternative to conventional insulin therapy, there remains a crucial need for greater awareness regarding the necessary adaptations for various special circumstances. Nutritional choices play an essential role in the efficacy of diabetes management and overall health status for patients with T1DM. Factors such as effective carbohydrate counting, assessment of the macronutrient composition of meals, and comprehending the concept of the glycemic index of foods are paramount in making informed pre-meal adjustments when utilizing insulin pumps. Furthermore, the ability to handle such situations as physical exercise, illness, pregnancy, and lactation by making appropriate adjustments in nutrition and pump settings should be cultivated within the patient-practitioner relationship. This review aims to provide healthcare practitioners with practical guidance on optimizing care for individuals living with T1DM. It includes recommendations on carbohydrate counting, managing mixed meals and the glycemic index, addressing exercise-related challenges, coping with illness, and managing nutritional needs during pregnancy and lactation. Additionally, considerations relating to closed-loop systems with regard to nutrition are addressed. By implementing these strategies, healthcare providers can better equip themselves to support individuals with T1DM in achieving improved diabetes management and enhanced quality of life.


Polymeric drugs based on random copolymers with antimitotic activity.
Polymeric drugs based on random copolymers with antimitotic activity were obtained by free radical copolymerization of oleyl 2-acetamido-2-deoxy-α-d-glucopyranoside methacrylate (OAGMA) and 2-ethyl-(2-pyrrolidone) methacrylate (EPM) at low and high conversion and analyzed in terms of microstructure, physicochemical, and biological properties. Reactivity ratios of monomers were found to be r(OAGMA) = 1.34 and r(EPM) = 0.98, indicating the obtaining of statistical copolymers with random sequence distribution of the comonomeric units in the macromolecular chains. The glass transition temperature of the copolymers presents a negative deviation from the predicted values according to the Fox equation, suggesting a higher flexibility of the alternating diad. Copolymeric systems with OAGMA contents between 10-50 mol % presented thermosensitive behavior in a heating process showing cloud point temperatures (CPT) in the range 45-28 °C with increasing OAGMA content and hysteresis in one heating-and-cooling cycle. In vitro glycolipid release studies revealed the stability of the ester group in culture medium. The polymeric drugs with 30 and 50 mol % OAGMA presented antimitotic activity on a human glioblastoma line, but they were less toxic on normal human fibroblast cultures.


Watchful waiting vs immediate transurethral resection for symptomatic prostatism. The importance of patients' preferences.
The rate of resection for benign prostatic hypertrophy shows considerable variability among small geographic areas. To help inform the decision to recommend prostatectomy to men with prostatism without signs of chronic retention, we performed a decision analysis to compare the expected outcomes with immediate transurethral resection and watchful waiting. Data used in the model originated from the medical literature, Medicare claims data, and patient interview studies. In our base-case analysis for 70-year-old men, immediate surgery resulted in the loss of 1.01 months of life expectancy, but when adjustments were made for quality of life, immediate surgery was favored with a net utility benefit of 2.94 quality-adjusted life-months. However, the analysis was particularly sensitive to the degree of disutility attributed to the index symptoms of prostatism. We conclude that patient preferences should be the dominant factor in the decision whether to recommend prostatectomy.


Comparison of the transcriptomes of ginger (Zingiber officinale Rosc.) and mango ginger (Curcuma amada Roxb.) in response to the bacterial wilt infection.
Bacterial wilt in ginger (Zingiber officinale Rosc.) caused by Ralstonia solanacearum is one of the most important production constraints in tropical, sub-tropical and warm temperature regions of the world. Lack of resistant genotype adds constraints to the crop management. However, mango ginger (Curcuma amada Roxb.), which is resistant to R. solanacearum, is a potential donor, if the exact mechanism of resistance is understood. To identify genes involved in resistance to R. solanacearum, we have sequenced the transcriptome from wilt-sensitive ginger and wilt-resistant mango ginger using Illumina sequencing technology. A total of 26387032 and 22268804 paired-end reads were obtained after quality filtering for C. amada and Z. officinale, respectively. A total of 36359 and 32312 assembled transcript sequences were obtained from both the species. The functions of the unigenes cover a diverse set of molecular functions and biological processes, among which we identified a large number of genes associated with resistance to stresses and response to biotic stimuli. Large scale expression profiling showed that many of the disease resistance related genes were expressed more in C. amada. Comparative analysis also identified genes belonging to different pathways of plant defense against biotic stresses that are differentially expressed in either ginger or mango ginger. The identification of many defense related genes differentially expressed provides many insights to the resistance mechanism to R. solanacearum and for studying potential pathways involved in responses to pathogen. Also, several candidate genes that may underline the difference in resistance to R. solanacearum between ginger and mango ginger were identified. Finally, we have developed a web resource, ginger transcriptome database, which provides public access to the data. Our study is among the first to demonstrate the use of Illumina short read sequencing for de novo transcriptome assembly and comparison in non-model species of Zingiberaceae.


A transnational lens into international student experiences of the COVID-19 pandemic.
We analyse the experiences of international students living in Canada during the COVID-19 pandemic through the lens of transnationalism that understands mobility as broadly uninterrupted, continuing and taken-for-granted, and international student migration (ISM) literature. With the onset of the COVID-19 pandemic, people had to contend with sudden border closures and stringent restrictions on all forms of travel. International students are regarded as the archetypal trans-migrants with frequent mobility and often multiple attachments to place. We interrogate these assumptions of mobility by drawing on interview data from 13 international students in Ontario from April to June of 2020. We found that international students experienced the pandemic transnationally and faced increased challenges, which heightened their reliance on support from transnational families, and generated anxieties about their future career and mobilities. We bring transnational theories into conversation with ISM literature to better understand international students' lived experiences in Canada during a pandemic.


Impact of microenvironmental nitrogen dioxide concentrations on personal exposures in Australia.
Indoor and outdoor NO2 concentrations were measured and compared with simultaneously measured personal exposures of 57 office workers in Brisbane, Australia. House characteristics and activity patterns were used to determine the impacts of these factors on personal exposure. Indoor NO2 levels and the presence of a gas range in the home were significantly associated with personal exposure. The time-weighted average of personal exposure was estimated using NO2 measurements in indoor home, indoor workplace, and outdoor home levels. The estimated personal exposures were closely correlated, but they significantly underestimated the measured personal exposures. Multiple regression analysis using other nonmeasured microenvironments indicated the importance of transportation in personal exposure models. The contribution of transportation to the error of prediction of personal exposure was confirmed in the regression analysis using the multinational study database.


KL Divergence-based transfer learning for cross-subject eye movement recognition with EOG signals.
Human-machine interfaces (HMIs) based on Electro-oculogram (EOG) signals have been widely explored. However, due to the individual variability, it is still challenging for an EOG-based eye movement recognition model to achieve favorable results among cross-subjects. The classical transfer learning methods such as CORrelation Alignment (CORAL), Transfer Component Analysis (TCA), and Joint Distribution Adaptation (JDA) are mainly based on feature transformation and distribution alignment, which do not consider similarities/dissimilarities between target subject and source subjects. In this paper, the Kullback-Leibler (KL) divergence of the log-Power Spectral Density (log-PSD) features of horizontal EOG (HEOG) between the target subject and each source subject is calculated for adaptively selecting partial subjects that suppose to have similar distribution with target subject for further training. It not only consider the similarity but also reduce computational consumption. The results show that the proposed approach is superior to the baseline and classical transfer learning methods, and significantly improves the performance of target subjects who have poor performance with the primary classifiers. The best improvement of Support Vector Machines (SVM) classifier has improved by 13.1% for subject 31 compared with baseline result. The preliminary results of this study demonstrate the effectiveness of the proposed transfer framework and provide a promising tool for implementing cross-subject eye movement recognition models in real-life scenarios.


Confined placental mosaicism and the association with pregnancy outcome and fetal growth: a review of the literature.
Chromosomal mosaicism can be detected in different stages of early life: in cleavage stage embryos, in blastocysts and biopsied cells from blastocysts during preimplantation genetic testing for aneuploidies (PGT-A) and later during prenatal testing, as well as after birth in cord blood. Mosaicism at all different stages can be associated with adverse pregnancy outcomes. There is an onward discussion about whether blastocysts diagnosed as chromosomally mosaic by PGT-A should be considered safe for transfer. An accurate diagnosis of mosaicism remains technically challenging and the fate of abnormal cells within an embryo remains largely unknown. However, if aneuploid cells persist in the extraembryonic tissues, they can give rise to confined placental mosaicism (CPM). Non-invasive prenatal testing (NIPT) uses cell-free (cf) DNA released from the placenta in maternal blood, facilitating the detection of CPM. In literature, conflicting evidence is found about whether CPM is associated with fetal growth restriction (FGR) and/or other pregnancy outcomes. This makes counselling for patients by clinicians challenging and more knowledge is needed for clinical decision and policy making. The objective of this review is to evaluate the association between CPM and prenatal growth and adverse pregnancy outcomes. All relevant literature has been reviewed in order to achieve an overview on merged results exploring the relation between CPM and FGR and other adverse pregnancy outcomes. The following Medical Subject Headings (MESH) terms and all their synonyms were used: placental, trophoblast, cytotrophoblast, mosaicism, trisomy, fetal growth, birth weight, small for gestational age and fetal development. A search in Embase, PubMed, Medline Ovid, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases was conducted. Relevant articles published until 16 July 2020 were critically analyzed and discussed. There were 823 articles found and screened based on their title/abstract. From these, 213 articles were selected and full text versions were obtained for a second selection, after which 70 publications were included and 328 cases (fetuses) were analyzed. For CPM in eight different chromosomes (of the total 14 analyzed), there was sufficient evidence that birth weight was often below the 5th percentile of fetal growth standards. FGR was reported in 71.7% of CPM cases and preterm birth (<37 weeks of delivery) was reported in 31.0% of cases. A high rate of structural fetal anomalies, 24.2%, in cases with CPM was also identified. High levels of mosaicism in CVS and presence of uniparental disomy (UPD) were significantly associated with adverse pregnancy outcomes. Based on the literature, the advice to clinicians is to monitor fetal growth intensively from first trimester onwards in case of CPM, especially when chromosome 2, 3, 7, 13, 15, 16 and 22 are involved. In addition to this, it is advised to examine the fetuses thoroughly for structural fetal anomalies and raise awareness of a higher chance of (possibly extreme) premature birth. Despite prematurity in nearly a fifth of cases, the long-term follow-up of CPM life borns seems to be positive. More understanding of the biological mechanisms behind CPM will help in prioritizing embryos for transfer after the detection of mosaicism in embryos through PGT-A.


Turning Toward Monitoring of Gaze Stability Exercises: The Utility of Wearable Sensors.
Few tools are currently available to quantify gaze stability retraining exercises. This project examined the utility of a head-worn inertial measurement unit (IMU) to quantify head movement frequency, velocity, and amplitude during gaze stability exercises. Twenty-eight individuals with multiple sclerosis and complaints of dizziness or a history of falls were randomly assigned to either a strength and aerobic exercise (SAE) or gaze and postural stability (GPS) group. During a 6-week intervention, participants wore a head-mounted IMU 3 times (early, middle, and late). For aim 1, the frequency, mean peak velocity, and mean peak amplitude of head turns during equivalent duration components of group-specific exercises were compared using general linear models. For aim 2, the progression of treatment in the GPS group was examined using general linear regression models for each outcome. Aim 1 revealed the GPS group demonstrated significantly greater velocity and amplitude head turns during treatment than the SAE group. The frequency of head turns did not significantly differ between the 2 groups. The aim 2 analyses demonstrated that the yaw and pitch frequency of head turns significantly increased during gaze stability exercises over the 6-week intervention. Velocity and amplitude of head turns during yaw and pitch gaze stability exercises did not significantly change. A head-worn IMU during rehabilitation distinguished between groups. Furthermore, within the GPS group, the IMU quantified the progression of the frequency of head movements during gaze stability exercises over time.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A320).


Perception and Reality of Cognitive Function: Information Processing Speed, Perceived Memory Function, and Perceived Task Difficulty in Older Adults.
This study examines the relationships between two measures of information processing speed associated with executive function (Trail Making Test and a computer-based visual search test), the perceived difficulty of the tasks, and perceived memory function (measured by the Memory Functioning Questionnaire) in older adults (aged 50+ y) with normal general health, cognition (Montreal Cognitive Assessment score of 26+), and mood. The participants were recruited from the community rather than through clinical services, and none had ever sought or received help from a health professional for a memory complaint or mental health problem. For both the trail making and the visual search tests, mean information processing speed was not correlated significantly with perceived memory function. Some individuals did, however, reveal substantially slower information processing speeds (outliers) that may have clinical significance and indicate those who may benefit most from further assessment and follow up. For the trail making, but not the visual search task, higher levels of subjective memory dysfunction were associated with a greater perception of task difficulty. The relationship between actual information processing speed and perceived task difficulty also varied with respect to the task used. These findings highlight the importance of taking into account the type of task and metacognition factors when examining the integrity of information processing speed in older adults, particularly as this measure is now specifically cited as a key cognitive subdomain within the diagnostic framework for neurocognitive disorders.


Offering telephone counseling to smokers using pharmacotherapy.
Whereas telephone-based counseling has been found to be effective in supporting smokers interested in quitting smoking, it is not known whether proactive efforts to reach smokers receiving cessation medications will enhance their likelihood of successful quitting. We had an opportunity to test, in a health plan setting, an offer of telephone-based counseling with smokers identified from health plan records as recently filling a prescription for nicotine replacement therapy or bupropion. After we removed 31 members determined to be ineligible, 1,329 were randomly allocated to receive an invitation either to telephone-based counseling (n = 663) or to a control group (n = 666). On average, 7 days (range = 3-15 days) elapsed from the day of the prescription fill until the Center for Health Promotion began calling to invite members to participate in telephone counseling. The Center for Health Promotion was able to reach 49% of those in the intervention group (323/663). Of these members, 118 (37%) declined any participation. Therefore, in response to the proactive contact, 63% (205/323) of those reached and 31% (205/663) of those eligible participated in some smoking cessation counseling. At the 3-month follow-up, we observed an increased quit rate (33.1% vs. 27.4%) among health plan members randomized to telephone-based smoking cessation counseling. The results varied by gender and amount smoked. In addition, the variables associated with quitting in a multivariate logistic regression model included older age and using more than 30 days of medication.


Adipose tissue expandability: the metabolic problems of obesity may arise from the inability to become more obese.
The prevalence of obesity is increasing and with it the prevalence of associated metabolic complications. Precisely how obesity results in metabolic disturbances remains unclear. In the face of persistent positive caloric balance, it has been postulated that the capacity of adipose tissue to safely store fat may be vital. This paper explores some of the evidence suggesting that the risk of developing metabolic disturbances is not related to how much fat an individual has, but how well their fat can expand to accommodate the caloric excess. If this is true, the metabolic consequences of obesity may arise from the inability to become more obese.


Mammoth hair: stability of alpha-keratin structure and constituent proteins.
Hair from a woolly mammoth (Mammuthus primigenius, age about 32,000 years) retains the ordered structure characteristic of alpha-keratins, but the proteins of this hair differ in composition from and are smaller than similar proteins isolated from other keratins, for example, elephant hair. It is suggested that these changes have been caused by limited proteolysis.


Implementation of a self-help mobile mental health app in COVID-19 frontline health care workers: A quality improvement project.
Frontline health care workers (FHCWs) have endured a range of adverse mental health outcomes during the COVID-19 pandemic. Despite the widespread availability and ease-of-use of self-help mobile mental health apps, little is known about the feasibility of implementing such tools among COVID-19 FHCWs in real-world nursing settings. This quality improvement project evaluated the feasibility of implementing the COVID Coach app among COVID-19 FHCWs in a skilled nursing facility. Participants endorsed high average ratings of the acceptability, appropriateness, feasibility, knowledge, perceived usefulness of the app. Implications for the broader dissemination of mobile self-help apps are discussed.


The role of PTSD symptom severity and relationship functioning in male and female veterans' mental health service use.
[Correction Notice: An Erratum for this article was reported online in Psychological Trauma: Theory, Research, Practice, and Policy on Nov 07 2022 (see record 2023-15574-001). In the original article, the second affiliation of Dawne Vogt was changed from "MGH Institute of Health Professionals, Boston, Massachusetts, United States" to "Department of Psychiatry, Boston University School of Medicine." In addition, the following sentence was deleted from the author note: "The study was funded by the National Center for PTSD." All versions of this article have been corrected.] Objective: Previous research has shown that difficulties in intimate relationships promote mental health treatment seeking for male veterans, but findings for female veterans have been mixed. The current study sought to further evaluate whether intimate relationship functioning is a motivator for mental health treatment seeking for male and female veterans and examine the impact of different types of trauma exposure on this association. Using data from a longitudinal study, we examined whether intimate relationship functioning mediated the association between posttraumatic stress disorder (PTSD) symptom severity and mental health service use (0 = no mental health services, 1 = any mental health services) in male and female veterans (N = 1,200). We used multiple groups path analysis to examine whether intimate relationship functioning mediated the association between PTSD symptom severity and mental health service use for male and female veterans. For male veterans, greater PTSD symptom severity was related to poorer intimate relationship functioning, which in turn explained increased likelihood of mental health service use (R² = .18). This mediation effect was not significant for female veterans. Our findings suggest that targeting intimate relationship functioning in treatment for male veterans may be beneficial because difficulties in these relationships appear to be a motivating factor for treatment seeking. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Maternal high-fat diet impacts endothelial function in nonhuman primate offspring.
The link between maternal under-nutrition and cardiovascular disease (CVD) in the offspring later in life is well recognized, but the impact of maternal over-nutrition on the offspring's cardiovascular function and subsequent risk for CVD later in life remains unclear. Here, we investigated the impact of maternal exposure to a high-fat/calorie diet (HFD) during pregnancy and early postnatal period on endothelial function of the offspring in a nonhuman primate model. Offspring, naturally born to either a control (CTR) diet (14% fat calories) or a HFD (36% fat calories) consumption dam, were breast-fed until weaning at about 8 months of age. After weaning, the offspring were either maintained on the same diet (CTR/CTR, HFD/HFD), or underwent a diet switch (CTR/HFD, HFD/CTR). Blood samples and arterial tissues were collected at necropsy when the animals were about 13 months of age. HFD/HFD juveniles displayed an increased plasma insulin level and glucose-stimulated insulin secretion in comparison with CTR/CTR. In abdominal aorta, but not the renal artery, acetylcholine-induced vasorelaxation was decreased remarkably for HFD/HFD juveniles compared with CTR/CTR. HFD/HFD animals also showed a thicker intima wall and an abnormal vascular-morphology, concurrent with elevated expression levels of several markers related to vascular inflammation and fibrinolytic function. Diet-switching animals (HFD/CTR and CTR/HFD) displayed modest damage on the abdominal vessel. Our data indicate that maternal HFD exposure impairs offspring's endothelial function. Both early programming events and postweaning diet contribute to the abnormalities that could be reversed partially by diet intervention.


Bonding, antibonding and tunable optical forces in asymmetric membranes.
We demonstrate that tunable attractive (bonding) and repulsive (anti-bonding) forces can arise in highly asymmetric structures coupled to external radiation, a consequence of the bonding/anti-bonding level repulsion of guided-wave resonances that was first predicted in symmetric systems. Our focus is a geometry consisting of a photonic-crystal (holey) membrane suspended above an unpatterned layered substrate, supporting planar waveguide modes that can couple via the periodic modulation of the holey membrane. Asymmetric geometries have a clear advantage in ease of fabrication and experimental characterization compared to symmetric double-membrane structures. We show that the asymmetry can also lead to unusual behavior in the force magnitudes of a bonding/antibonding pair as the membrane separation changes, including nonmonotonic dependences on the separation. We propose a computational method that obtains the entire force spectrum via a single time-domain simulation, by Fourier-transforming the response to a short pulse and thereby obtaining the frequency-dependent stress tensor. We point out that by operating with two, instead of a single frequency, these evanescent forces can be exploited to tune the spring constant of the membrane without changing its equilibrium separation.


The Effects of Different Extraction Methods on Antioxidant Properties, Chemical Composition, and Thermal Behavior of Black Seed (Nigella sativa L.) Oil.
The Nigella sativa L. popularly referred to as black seeds are widely used as a form of traditional nutrition and medicine. N. sativa seeds were used for the extraction of their oil by way of supercritical fluid extraction (SFE) and cold press (CP) to determine the physicochemical properties, antioxidant activity, and thermal behavior. The GC-MS results showed the primary constituents in the Nigella sativa oil (NSO) were Caryophyllene (17.47%) followed by thymoquinone (TQ) (11.80%), 1,4-Cyclohexadiene (7.17%), longifolene (3.5%), and carvacrol (1.82%). The concentration of TQ was found to be 6.63 mg/mL for oil extracted using SFE and 1.56 mg/mL for oil extracted by CP method. The antioxidant activity measured by DPPH and the IC50 was 1.58 mg/mL and 2.30 mg/mL for SFE oil and cold pressed oil, respectively. The ferric reducing/antioxidant power (FRAP) activity for SFE oil and CP oil was 538.67 mmol/100 mL and 329.00 mmol/100 mL, respectively. The total phenolic content (TPC) of SFE oil was 160.51 mg/100 mL and 94.40 mg/100 mL for CP oil presented as gallic acid equivalents (GAE). This research showed that a high level of natural antioxidants could be derived from NSO extracted by SFE.


A single session of hyperbaric oxygen therapy demonstrates acute and long-lasting neuroplasticity effects in humans: a replicated, randomized controlled clinical trial.
Animal studies have demonstrated anti-inflammatory, and anti-nociceptive properties of hyperbaric oxygen therapy (HBOT). However, physiological data are scarce in humans. In a recent experimental study, the authors used the burn injury (BI) model observing a decrease in secondary hyperalgesia areas (SHA) in the HBOT-group compared to a control-group. Surprisingly, a long-lasting neuroplasticity effect mitigating the BI-induced SHA-response was seen in the HBOT-preconditioned group. The objective of the present study, therefore, was to confirm our previous findings using an examiner-blinded, block-randomized, controlled, crossover study design. Nineteen healthy subjects attended two BI-sessions with an inter-session interval of ≥28 days. The BIs were induced on the lower legs by a contact thermode (12.5 cm2, 47C°, 420 s). The subjects were block-randomized to receive HBOT (2.4 ATA, 100% O2, 90 min) or ambient conditions ([AC]; 1 ATA, 21% O2), dividing cohorts equally into two sequence allocations: HBOT-AC or AC-HBOT. All sensory assessments performed during baseline, BI, and post-intervention phases were at homologous time points irrespective of sequence allocation. The primary outcome was SHA, comparing interventions and sequence allocations. Data are mean (95% CI). During HBOT-sessions a mitigating effect on SHA was demonstrated compared to AC-sessions, ie, 18.8 (10.5-27.0) cm2 vs 32.0 (20.1-43.9) cm2 (P=0.021), respectively. In subjects allocated to the sequence AC-HBOT a significantly larger mean difference in SHA in the AC-session vs the HBOT-session was seen 25.0 (5.4-44.7) cm2 (P=0.019). In subjects allocated to the reverse sequence, HBOT-AC, no difference in SHA between sessions was observed (P=0.55), confirming a preconditioning, long-lasting (≥28 days) effect of HBOT. Our data demonstrate that a single HBOT-session compared to control is associated with both acute and long-lasting mitigating effects on BI-induced SHA, confirming central anti-inflammatory, neuroplasticity effects of hyperbaric oxygen therapy.


The connexin 40 A96S mutation causes renin-dependent hypertension.
Deletion of the gap-junction-forming protein connexin40 leads to renin-dependent hypertension in mice, but whether observed human variants in connexin40, such as A96S, promote hypertension is unknown. Here, we generated mice with the A96S variant in the mouse connexin40 gene. Although mice homozygous for the A96S mutations had normal expression patterns of connexin40 in the kidney, they were hypertensive, had sixfold higher plasma renin concentrations, and had 40% higher levels of renin mRNA than controls. Renin-expressing cells were aberrantly located outside the media layer of afferent arterioles, and increased renal perfusion pressure did not inhibit renin secretion from kidneys isolated from homozygous A96S mice. Treatment with a low-salt diet in combination with an ACE inhibitor increased renin mRNA levels, plasma renin concentrations, and the number of aberrantly localized renin-producing cells. Taken together, these findings suggest that the A96S mutation in connexin40 leads to renin-dependent hypertension in mice. Modulation of renin secretion by BP critically depends on functional connexin40; with the A96S mutation, the aberrant extravascular localization of renin-secreting cells in the kidney likely impairs the pressure-mediated inhibition of renin secretion.


Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation-inducing electrical stimulation patterns.
The neurotrophin (NT) brain-derived neurotrophic factor (BDNF) plays an essential role in the formation of long-term potentiation (LTP). Here, we address whether this modulation by BDNF requires its continuous presence, or whether a local increase in BDNF is necessary during a specific time period of LTP initiation. Using electrical field stimulation of primary cultures of hippocampal neurons, we demonstrate that short high-frequency bursts of stimuli that induce LTP evoke also an instantaneous secretion of BDNF. In contrast, stimuli at low frequencies, inducing long-term depression, do not enhance BDNF secretion, suggesting that BDNF is specifically present, and thus required, at the time of LTP induction. The field-stimulation-mediated BDNF secretion depends on the formation of action potentials and is induced by IP(3)-mediated Ca(2+) release from intracellular stores. Experiments, aimed at determining the sites of NT secretion that use NT6, showed similar patterns of surface labeling by field stimulation to those shown previously by high potassium.


Nocturic frequency is related to severity of obstructive sleep apnea, improves with continuous positive airways treatment.
The purpose of this study was to determine the relationship between nocturia and obstructive sleep apnea (OSA), and the effect of continuous positive airways pressure (CPAP) therapy on nocturic frequency. This was a retrospective review of sleep studies including patients with and without evidence of OSA, before and during CPAP treatment (where relevant). Chi-squared tests compared nocturia prevalence according to sleep diagnosis, logistic regression determined predictors of nocturia, and regression analyses determined predictors of nocturic frequency. In 196 eligible studies, predictors of nocturia included increasing age and diabetes mellitus; nocturia was equally likely to occur in patients with and without OSA. In patients with OSA and nocturia, nocturic frequency was related to age, diabetes, and severity of OSA (P < .001). Patients with OSA and nocturia who were treated with CPAP demonstrated a significant decrease in nocturic frequency (P < .001). OSA severity predicts nocturic frequency. The role of testing in the triage of patients with nocturia remains to be determined.


Radiographic operations and safety in the Nigerian petroleum industry.
This work reports on a radiation safety study of the use of radioactive sources and radiation-producing machines for radiographic purposes in the Nigerian Petroleum Industry. It is a part of a wider study on the level of safety in the use of radiation in the country-a study that covered the manufacturing and petroleum industries. The survey assessment is based on minimum requirements for radiological safety, on a scale of 0-100, to protect personnel, the public, and the environment from artificial radiation sources. The survey result shows that the level of safety in the use of radiation-emitting machines for radiographic purposes is scored at 52, while it is 66 in the use of radioisotopes. Consequently, the level of safety in radiographic practices in the Nigerian Petroleum Industry is about 60% of the ideal.


Incidence of an aminoglycoside 6'-N-acetyltransferase, ACC(6')-1b, in amikacin-resistant clinical isolates of gram-negative bacilli, as determined by DNA-DNA hybridisation and immunoblotting.
Seventy amikacin-resistant clinical isolates of gram-negative bacteria belonging to nine genera were examined by immunoblotting and by DNA-DNA hybridisation for the presence of ACC(6')1b enzyme, previously called AAC(6')-4, or its encoding gene aacA1b. The organisms mostly had resistance profiles compatible with AAC(6') production and were from South and North America, the Far East and Europe. Polyclonal (rabbit) anti-AAC(6')-1b antisera and an intragenic aacA1b (aacA4) probe derived from the multiresistance plasmid pAZ007 were used. The aacA1b gene was found to be widespread. Positive hybridisation, and immunologically cross-reactive proteins, were observed in 44% of the isolates examined. They were present most frequently (greater than or equal to 70%) in isolates of Klebsiella, Escherichia and Enterobacter spp., but less often (less than or equal to 25%) in Serratia, Citrobacter, Acinetobacter and Pseudomonas spp. The strains that reacted with the probe produced enzymes that varied in their apparent mol. wts between c. 24,000 and 26,000. The existence of multiple electrophoretic forms of amikacin-acetylating enzymes of the ACC(6')-1b type may be useful in epidemiological surveys of AAC(6')-mediated amikacin resistance.