Advances in chronic rhinosinusitis in 2020 and 2021.
Major progress has been achieved in the understanding and clinical practice of chronic rhinosinusitis, with or without nasal polyps. These advances resulted in a better understanding of the pathophysiology, the distribution into subgroups, and consequently in a better management perspective using classical approaches and biologics. Pathomechanisms, endotypes and biomarkers, and finally innovative therapeutic approaches are themes especially for the more severe forms of chronic rhinosinusitis, those with uncontrolled severe nasal polyps. Biologicals against key type 2 cytokines are gaining ground in the long-term treatment approaches of often recurrent nasal polyps, and should be integrated in care pathways making use of classical and innovative treatment pathways. These areas of interest show a fast development and will profoundly change our disease management within a decade.


Social position and frailty.
This study sought to determine (1) if measures of social position are associated with frailty; (2) if any observed association between social position and frailty is a threshold or gradient effect; and (3) if any observed association is independent of possible confounders. Data were drawn from a sample of 1,751 community-dwelling adults, aged 65 and older, living in the Canadian province of Manitoba in 1991. Education, self-reported income adequacy, and self-reported income satisfaction were used as measures of social position. Frailty was graded based on functional loss, cognition, and urinary incontinence. Multivariate regression analyses revealed, after adjusting for possible confounding factors, that all measures of social position were strongly associated with frailty in a gradient, rather than a threshold, manner. We conclude that social gradients for frailty are present in older adults, although a causal mechanism is not yet clear.


A monoclonal antibody recognizing HLA-DR2 on malignant and activated cells.
A monoclonal antibody, designated NDS15.38, which recognizes a polymorphic determinant of HLA-DR, was produced from a fusion in which mice were immunized with the human B lymphoblastoid cell line GIR2 (HLA type A1, B8, 27, Cw2, DR2,7). NDS15.38 functions efficiently as an affinity column and purifies a two-chain complex of molecular weight 33 000 and 30 000 under reducing conditions. The monoclonal antibody reacts with HLA-DR2-positive B lymphoblastoid cell lines and B lymphocytes from patients with chronic lymphatic leukemia in an indirect radioactive binding assay. However, NDS15.38 does not appear to react with peripheral blood B lymphocytes from normal individuals. Using a peroxidase staining technique, NDS15.38 was shown to react with phytohemagglutin (PHA)-stimulated lymphocytes and with apparently activated B cells in the germinal centers of lymph nodes from individuals who were tissue typed as HLA-DR2. Thus it appears that NDS15.38 recognizes a polymorphic determinant of HLA-DR on malignant and stimulated cells, but not on resting cells.


Intergenerational transmission of anxiety in Chinese migrant families: The mediating role of parents' perceptions of coparenting.
There is evidence that anxiety transmits across generations. However, little is known about the intergenerational transmission of anxiety in Chinese migrant families and the potential mediators of the intergenerational transmission. Therefore, this study investigated the intergenerational transmission of anxiety from both fathers and mothers to children in Chinese migrant families and the mediating role of both mothers' and fathers' perceptions of coparenting. Participants were 477 elementary school-age children and both their parents in Chinese migrant families. Mothers and fathers self-reported their anxiety and perceptions of coparenting. Children's anxiety was measured based on maternal report and paternal report. Structural equation modelling was used to evaluate the mediating role of both mothers' and fathers' perceptions of coparenting in the intergenerational transmission of anxiety. Anxiety was transmitted across generations from both fathers and mothers to migrant children, and fathers' (but not mothers') perceptions of coparenting mediated the intergenerational transmission of anxiety from both fathers and mothers to migrant children. Causal conclusions cannot be drawn based on cross-sectional research design. Coparenting seemed to play an important role in the intergenerational transmission of anxiety. Interventions preventing the intergenerational transmission of anxiety should designate relevant effort enhancing fathers' perceptions of coparenting by changing fathers' negative perceptions and evaluations of the coparenting relationship and increasing mothers' high-quality coparenting behavior.


Transforaminal Endoscopic Foraminoplasty and Discectomy for the Treatment of a Thoracic Disc Herniation.
Transforaminal endoscopic spine surgery has emerged internationally as a minimally invasive technique that can be performed in an awake patient in the outpatient setting. Advances in high-definition endoscopic camera technologies as well as the availability of specialty graspers, reamers, drills, and other instruments that can be used down a working channel endoscope have made a myriad of spine diseases accessible to the minimally invasive spine surgeon. The major challenge inherent in the surgical treatment of thoracic disc disease is that the disc herniation is often ventral to the spinal cord. The transforaminal approach and the angled endoscopic camera are an ideal combination for creating a technical advantage to accessing thoracic disc disease.


Synergistic effect of TNF-alpha and either IL-4 or IL-13 on VCAM-1 expression by cultured human corneal fibroblasts.
To examine the role of corneal fibroblasts in the pathogenesis of vernal keratoconjunctivitis, we investigated the effects of tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-13 on the expression of vascular cell adhesion molecule (VCAM)-1 by cultured human corneal fibroblasts. Cultured human corneal fibroblasts were incubated with various combinations and concentrations of TNF-alpha, IL-4, and IL-13. The cell surface expression of VCAM-1 was subsequently evaluated by whole-cell enzyme-linked immunosorbent assay and immunocytochemistry, and the abundance of VCAM-1 mRNA in cell lysates was determined by quantitative reverse transcription and polymerase chain reaction analysis. Corneal fibroblasts incubated in the absence of cytokines exhibited minimal expression of VCAM-1. Whereas incubation of the cells with TNF-alpha, IL-4, or IL-13 alone, or with the combination of IL-4 and IL-13, induced only a small increase in VCAM-1 expression, exposure of the cells to TNF-alpha in combination with either IL-4 or IL-13 resulted in a marked synergistic increase in expression of this adhesion molecule that was both time and dose dependent. The abundance of VCAM-1 mRNA in corneal fibroblasts was also increased in a synergistic manner by incubation of the cells with TNF-alpha together with either IL-4 or IL-13. Stimulation of human corneal fibroblasts with the combination of TNF-alpha and either IL-4 or IL-13 resulted in synergistic increases in both the abundance of VCAM-1 mRNA and the cell surface expression of VCAM-1 protein. This cytokine-induced increase in VCAM-1 expression by corneal fibroblasts may contribute to eosinophil infiltration in corneal lesions associated with vernal keratoconjunctivitis.


PTEN inhibitor improves vascular remodeling and cardiac function after myocardial infarction through PI3k/Akt/VEGF signaling pathway.
Myocardial infarction (MI) is the leading cause of death from cardiovascular disease (CVD). Currently, the efficacy for MI treatment remains unsatisfactory. Therefore, it is urgent to develop a novel therapeutic strategy. Left anterior descending arteries (LAD) of mice were ligated to induce MI. Another set of mice were intravenously injected with PTEN inhibitor BPV (1 mg/kg) 1 h after LAD ligation and continued to receive BPV injection daily for the following 6 days. Mice were performed echocardiography 14 days after surgery. Mice in MI group displayed an increased expression of PTEN with impaired cardiac function, enhanced cardiomyocyte apoptosis and decreased angiogenesis. BPV treatment significantly improved cardiac function, with reduced cardiomyocyte apoptosis, promoted angiogenesis, and activated PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway. PTEN inhibitor BPV could effectively prevent myocardial infarction in mice, highlighting its potential as a candidate therapeutic drug.


Characterization of TPN729 metabolites in humans using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.
TPN729 has been reported as a novel phosphodiesterase type 5 (PDE5) inhibitor to treat erectile dysfunction, and is currently being tested in clinical trials. In addition to the potent inhibition against PDE5, TPN729 is regarded as a better alternative to provide fewer side effects and better patient compliance. Given the potential therapeutic benefits of TPN729, it is of great importance to elucidate its metabolic characteristics in drug development. This study is the first to investigate the metabolic fate of TPN729 in humans. A rapid and reliable analytical method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was established to investigate the metabolic profiles of TPN729 in human plasma, urine, and feces after its oral administration. As a result, a total of 22 metabolites were identified, of which seven were confirmed in comparison with the reference substances. The incubations of the metabolite references in human hepatocytes and aldehyde trapping experiment were further conducted to investigate its metabolic pathways. The results of the present study indicated the extensive metabolism of TPN729 in humans, including oxidative deamination, oxidative ring opening, N-dealkylation, N-oxidation, hydroxylation, dehydrogenation, lactam formation, and glucuronidation. M3 resulting from N-dealkylation was the major circulating substance detected in human plasma. The principal metabolites detected in human feces were products of oxidative deamination and oxidative ring opening. The parent drug was identified as the major component in urine. Taken together, this study provided valuable information on the metabolic fate of TPN729 in humans, and applicable analytical strategies for rapid metabolic elucidation in complex matrix samples through the useful and reliable UPLC/Q-TOF MS technique.


Hageman factor and disseminated intravascular coagulation (DIC) in newborns and rabbits.
There was no significant difference in the levels of factor XII between sick newborns and normal age-matched controls, although the levels of both groups were lower than normal older children. Detailed coagulation studies on 44 sick infants revealed 11 to have disseminated intravascular coagulation (DIC). In those with DIC, the mean Hageman factor was 20% and in those without DIC, 25% (P greater than 0.05). Rabbits given a constant infusion of lysozyme (which inhibits factor XII) showed laboratory evidence of endotoxin-induced DIC. The data suggest that neither reduced factor XII levels nor Hageman factor inhibition provided protection from DIC. The data further suggest that other coagulation pathways might be involved in order to elicit the DIC.


A new genus and species of Micropterous Blissidae (Hemiptera: Heteroptera: Lygaeoidea) from Ecuador.
The new genus Barrerablissus and the new species B. strigosus are described from Napo Province, Ecuador. A key to the known genera of the Western Hemisphere Blissidae with apterous or micropterous condition is included. Dorsal and ventral view and digital photographs of head, pronotum, scutellum, metathoracic scent gland auricle and male genital capsule are added.


Challenges and Gaps in Understanding Substance Use Problems in Transitional Age Youth.
Transitional age youth (TAY), developing from adolescence to adulthood, exhibit the highest level of alcohol and other drug use of any other age group. Risk factors mirror those for the development of problems and disorders in adolescents. Early screening of both college students and noncollege high-risk TAY in the community is critical to early and effective intervention. Brief interventions using motivational techniques are effective for many TAY, particularly for those in early stages of problem use on college campuses. Professionals in contact with TAY should be aware of evidence-based interventions and providers for substance use disorders in the community.


The Earth as a planet.
A comparison of the Earth with the Moon and other planets can help considerably in the solving of geophysical problems. Professor Cook deals with some of these problems in this article, which is a summary of the inaugural lecture he gave as professor of geophysics at Edinburgh on January 15.


Cortical and cancellous bone: age-related changes in morphologic features, fluid spaces, and calcium homeostasis in dogs.
The changes in cortical and cancellous bone that occur with aging were studied by measuring morphologic and physiologic variables for both types of bone in dogs. The percentage area of cortical and cancellous bone, rate of bone formation, vascular volume, bone water, and volume of distribution of calcium tracer all showed statistically significant changes at the time of bone maturity. Canine cortical bone cell volume progressively decreased with advancing age, and cancellous bone cell volume significantly decreased between adult and old dogs. The volume of distribution technique can be used to determine the relative contributions of cortical and cancellous bone to the total body exchangeable calcium ion pool.


Leadership self-efficacy and nurses' aspiration to leadership: An evolutionary concept analysis.
The complex nature of leadership in nursing and healthcare requires a vast skill set. Leadership self-efficacy (LSE) has emerged as an important concept to support leadership development in the nursing literature. An analysis of LSE can clarify and inform strategies for leadership development among nurses. To clarify the concept of LSE and understand how it relates to nurses' motivation and aspiration for formal leadership roles. A concept analysis using Rodgers' evolutionary method identified attributes, antecedents, and consequences of LSE. Twenty-three articles published between 1993 and 2022 were analyzed following a Boolean search of four databases - Academic Search Complete, CINAHL, MEDLINE, and Scopus. LSE is an important element of nurses' aspiration to leadership. Leadership training, individual traits, and organizational support affect levels of LSE. When LSE is increased, job performance and nurses' motivation to take on formal leadership increase. The concept analysis further expands knowledge about factors that affect LSE. It provides data on how LSE can be harnessed to support leadership development and career aspiration for nurses. Developing and nurturing LSE among nurses may be key in promoting leadership career aspirations. Nurse leaders in practice, research, and academia can use this knowledge as a guide in leadership program development.


Leumorphin, a novel opioid peptide, promotes lordosis in female rats.
The actions of leumorphin, a recently characterized endogenous opioid peptide, oppose of most opioid peptides in facilitating lordosis reflex, a major component of female sexual behavior in the rat. Maximal lordosis appeared promptly after infusion of 1 nmol leumorphin into the ventromedial hypothalamus of ovariectomized estrogen-primed rats. This facilitation lasted for as long as 5 h, unless interrupted by midbrain infusion of an antiserum to prolactin. The result is a discovery of a novel substance of remarkable strength in facilitating lordosis, an effect presumably mediated by midbrain release of prolactin.


Assessment of talipes equinovarus treated by Ponseti technique: three-year preliminary report.
The Ponseti method has become increasingly popular in the treatment of congenital talipes equinovarus (CTEV). Current methods of assessment focus on clinical, functional and radiological outcomes which are subjective and often difficult to repeat. However, integration of biomechanical evaluation can provide objective and quantifiable analysis. This study aims to evaluate the treatment outcome of CTEV patients on the basis of long-term clinical, functional and biomechanical assessment. Following treatment, five children with CTEV were reviewed annually for the period 2008-2010. Clinical and functional outcomes were graded using parental questionnaires and clinical examination. Biomechanical parameters were evaluated using digital foot pressure studies. The study group recorded good clinical and functional outcomes. However, biomechanical studies have been able to identify subtle abnormalities that would be unapparent otherwise on clinical examination. It is recommended that biomechanical assessment be integrated into the overall evaluation of the outcome of CTEV after treatment.


Opicapone Protects Against Hyperhomocysteinemia-Induced Increase in Blood-Brain Barrier Permeability.
Hyperhomocysteinemia (HHcy)-related brain vascular disorders and brain endothelial dysfunction are important characteristics of the pathogeneses of subarachnoid hemorrhage and stroke. Upregulated homocysteine (Hcy) can impair the integrity of the blood-brain barrier (BBB). Opicapone has been recently licensed for the management of Parkinson's disease (PD); however, it is unknown whether it possesses a protective effect in brain vessels against HHcy. To investigate the beneficial effects of Opicapone on BBB permeability against HHcy, we carried out both in vivo and in vitro experiments. Mice were allocated into four groups: the Control, Opicapone, HHcy, and HHcy + Opicapone. Interestingly, we found that the administration of Opicapone attenuated the increased BBB permeability in Hcy-treated mice, as determined by sodium fluorescein staining. The immunofluorescence staining showed that Opicapone prevented homocysteine-induced reduction of claudin-2 in the mice cortices. The in situ zymography assay revealed that Opicapone suppressed homocysteine-increased matrix metalloproteinases (MMPs) activity in the cortices. In bEnd.3 brain endothelial cells, Opicapone treatment ameliorated homocysteine-induced lactate dehydrogenase (LDH) release and expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Furthermore, Opicapone alleviated homocysteine-induced decrease in claudin-2 level in bEnd.3 cells. In summary, our results show that Opicapone protects against HHcy-induced BBB permeability by reducing the expression and gelatinase activity of MMPs, and increasing the expression of claudin-2.


Diagnosis of Peripheral Artery Disease Using Backflow Abnormalities in Proximal Recordings of Accelerometer Contact Microphone (ACM).
The development of an accurate, non-invasive method for the diagnosis of peripheral artery disease (PAD) from accelerometer contact microphone (ACM) recordings of the cardiac system. Mel frequency cepstral coefficients (MFCCs) are initially extracted from ACM recordings. The extracted MFCCs are then used to fine-tune a pre-trained ResNet50 network whose middle layers provide streams of high-level-of-abstraction coefficients (HLACs) which could provide information on blood pressure backflow caused by arterial obstructions in PAD patients. A vision transformer is finally integrated with the feature extraction layer to detect PAD, and stratify the severity level. This architecture is coined multi-stream-powered vision transformer (MSPViT). The performance of MSPViT is evaluated on 74 PAD and 21 healthy subjects. Sensitivity, specificity, F1 score, and area under the curve (AUC) of 99.45%, 98.21%, 99.37%, and 0.99, respectively, are reported for the binary classification which ensures accurate detection of PAD. Furthermore, MSPViT suggests average sensitivity, specificity, F1 score, and AUC of 96.66%, 97.34%, 96.29%, and 0.96, respectively, for the classification of subjects into healthy, mild-PAD, and severe-PAD classes. The silhouette score is calculated to assess the separability of clusters formed for classes in the penultimate layer of MSPViT. An average silhouette score of 0.66 and 0.81 demonstrate excellent cluster separability in PAD detection and severity classification, respectively. The achieved performance suggests that the proximal ACM-driven framework can replace state-of-the-art techniques for PAD detection. This study presents a fundamental step towards prompt and accurate diagnosis of PAD and stratification of its severity level.


Autoimmune pancreatitis mimicking pancreatic cancer.
Autoimmune pancreatitis is a particular type of pancreatitis of presumed autoimmune etiology, it is an entity distinct from all others forms of chronic pancreatitis, characterized by clinical, histopathological, radiographic, serologic and therapeutic features. This benign disease resembles pancreatic carcinoma both clinically and radiographically. A 27-year-old man presented with obstructive jaundice and evocative image of pancreatic tumor. A pancreaticoduodenectomy (Whipple operation) was performed and pathological examination of the specimen diagnosed AIP. Patient responded well to a course of corticosteroids with resolution of clinical and biological disorders. Accurate and timely diagnosis of autoimmune pancreatitis is particularly important because steroid therapy is effective and pancreatic resection is not necessary.


Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial.
We conducted this study to examine the effect of taking versus holding BP medications before hemodialysis on intradialytic hypotension (IDH). In this cluster randomized trial, each dialysis unit was randomly designated as TAKE or HOLD units. Participants within a TAKE unit were instructed to take all BP medications as prescribed, whereas participants within a HOLD unit were instructed to hold medications dosed more than once daily before hemodialysis. The intervention lasted for 4 weeks. We hypothesized that TAKE would be noninferior to HOLD on the primary outcome of asymptomatic IDH, defined as ≥30% of sessions with nadir systolic BP <90 mm Hg and on the following secondary outcomes: uncontrolled hypertension (predialysis systolic BP >160 mm Hg), failure to achieve dry weight, and shortened dialysis sessions. We randomized 10 dialysis units in a 1:1 ratio to TAKE or HOLD, which included 65 participants in TAKE and 66 participants in HOLD. We did not show that TAKE was noninferior to HOLD for the primary IDH outcome (mean unadjusted difference of 8%; 95% CI, -3% to 19%). TAKE was superior to HOLD for the outcome of uncontrolled hypertension (mean unadjusted difference of -15%, 95% CI, -28% to -1%). TAKE was noninferior to HOLD for the outcomes of failure to achieve dry weight and shortened dialysis sessions. In this cluster randomized trial that randomized patients to either taking or holding BP medications before hemodialysis, a strategy of taking BP medications dosed more than once daily was not noninferior to holding BP medications for the primary outcome of IDH, but did reduce the occurrence of uncontrolled hypertension. Whether any potential benefit of holding BP medications on reducing IDH is offset by any potential harm related to higher predialysis BP remains to be seen.


The long-term effect of generic price competition on the Hungarian statin market.
Generic competition is a vital health policy tool used in regulating the pharmaceutical market. Drug group HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase) inhibitors, widely known as "statins," was the first drug group in Hungary in which generic prescriptions became mandatory. Our aim is to analyze the changes in the retail and wholesale margins through the generic competition regarding "statins". Data was derived from the nationwide pharmaceutical database of the Hungarian National Health Insurance Fund Administration, the only health care financing agency in Hungary. We observed the turnover data regarding the HMG-CoA-reductase inhibitor "statins" from 2010 through 2019. As the drugs under review have a fixed price point in Hungary, we effectively calculated the margins. In 2010, the consumer expenditure of statins was 30.7 billion HUF ($148 million), which decreased by 59%, to 12.5 billion HUF ($42.9 million) in 2019. In 2010, the annual health insurance reimbursement of statins was 23.7 billion HUF ($114 million), which underwent a 63% decrease to 8.6 billion HUF ($29.7 million) in 2019. In 2010, the DOT turnover was 287 million days, and it increased to above 346 million days for 2019, which reflects a 20% increase over the past nine years. The monthly retail margins decreased from 334 million HUF ($1.6 million), (January, 2010) to 176 million HUF ($0.61 million), (December, 2019). The monthly wholesale margins decreased from 96.3 million HUF ($0.46 million), (January, 2010) to 41.4 million HUF ($0.14 million), (December, 2019). The most significant downturn in margins was due to the introduction of the first two blind bids. The combined DOT turnover in reference to the examined 43 products consistently increased. The decline in retail and wholesale margin and in health insurance expenditures was largely due to a reduction in the consumer price of generic medicines. DOT turnover of statins also increased significantly.


Success and failure for children born with facial clefts in Africa: a 15-year follow-up.
This study reviews the 15 year program of our Department of Pediatric Surgery for the treatment and follow-up of children born with a cleft in Benin and Togo. We analyzed files of children born in Africa with a cleft. They were referred to us through a nongovernmental organization (NGO) between 1993 and 2008 and assessed in Africa by local pediatricians before and after surgery. Operations were performed by our team. Two hundred files were reviewed: 60 cases of unilateral cleft lip, seven of bilateral cleft lip, 44 of unilateral cleft lip palate (UCLP), 29 of bilateral cleft lip palate (BCLP), 53 of cleft palate (CP), three of bilateral oro-ocular cleft, one of unilateral and two of median clefts (Binder), and one of commissural cleft. Sixty-nine (35 %) of these cases were not operated in Africa: 25 (12.5 %) had not shown up, 28 (15 %) were considered unfit for surgery (Down's syndrome, HIV-positive, malnutrition, cardiac malformation), and 16 (7.5 %) were transferred to Switzerland. Palatal fistula occurred in 20 % of UCLP, 30 % of BCLP, and 16 % of CP. Evaluation of speech after palate surgery gave less than 50 % of socially acceptable speech. Our partnership with a NGO and a local team makes it possible to treat and subsequently follow children born with a cleft in West Africa. Surgery is performed under good conditions. If aesthetic results are a success, functional results after palate surgery need further improvement to promote integration in school and social life.


[Active transport of organic acids in the proximal tubules of the surviving rat kidney normally and under various influences. II. The effect of exogenous cyclic 3',5'-AMP and of substances that alter its intracellular concentration].
Exogenous cyclic 3',5'-AMP (cAMP) and substances known to increase the intracellular concentration of this nucleotide (isoproterenol, theophylline, noradrenaline, lactate) were shown to inhibit the transport of fluorescein (a weak organic acid) into the rat renal proximal tubules at 20 degrees C. Carbacholine decreasing intracellular cAMP concentration stimulated the transport. Propranolol, a beta-adrenergic blockator, diminished significantly the inhibitory effect of noradrenaline on the transport. Lactate and carbacholine when added simultaneously, neutralize their action. The inhibitory action of intracellular cAMP on the transport is supposed to be a result of the diminition of a pool of endogenous weak organic acids which may take part in the exchange of diffusion with the marker anion across basal plasma membrane.


Spectroscopic properties of the nitric oxide derivative of ferrous man, horse, and ruminant hemoglobins: a comparative study.
The spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous man, horse, buffalo, deer, mouflon, musk ox, ox, and reindeer hemoglobin (HbNO) have been investigated in the absence of any allosteric effector at pH 6.5 (in 0.1 M 2-[N-morpholino]ethanesulphonic acid/NaOH chloride-free buffer system), as well as at 100 K and/or 20 degrees C. Man and horse HbNO show spectroscopic properties that are generally taken as typical of the high affinity state of ferrous tetrameric Hb's; on the other hand, the spectroscopic properties of ruminant (i.e., buffalo, deer, mouflon, musk ox, ox, and reindeer) HbNO are characteristic of the low affinity conformation. These results are in keeping with the functional properties of the mammalian Hb's considered and have been related to the peculiar low oxygen affinity of ruminant Hb's.


New advances in microarrays: finding the genes causally involved in disease.
Much progress has been made in the technologies available to assess global alterations in mRNA levels in clinical research samples. Although such transcript profiling can provide a powerful research tool, the broad range of options can be bewildering for the inexperienced investigator, and more often than not the limitations and pitfalls of this approach are not fully appreciated. It is important to recognize that the major goal of transcript profiling experiments can be to identify novel therapeutic targets or delineate complex patterns of gene expression that provide a potentially pathognomonic phenotype. Microarrays are therefore potentially powerful tools to address the need for high-throughput analysis techniques, but a careful postanalysis follow-up and validation of microarray experiments will be needed soon (1). A projected decrease in cost and complexity may facilitate increased availability of this technology in the physician's office, and future applications may then allow tailoring of clinical diagnosis and targeted therapeutic strategies.


Lead-free Single-molecule Switching Material with Electric, Optical, Thermal Triple Controllable Multifunction Based on Perovskite-like Crystal and Flexible Thin Film.
With the flourishing development of star molecule (CH3NH3)PbI3, organic-inorganic perovskites with multifunction and flexibility have become a worldwide focus. However, the controllable photoelectric switchable material (especially electric, optical, thermal multifunctional switches) still face great challenges, and most of them are ceramic and toxic lead-based series. Herein a lead-free perovskite-like crystal and flexible thin film, ImMC (ImMC = (HIm)6∙[MnCl4∙MnCl6]) (1), with many advantages over inorganic ceramics and lead-based perovskites, performs ideal optical and dielectric duple switching properties simultaneously. The order-disordered HIm (Im = imidazole) cations of α-type occupy two lattice sites corresponding to "Switch-ON/0" and "Switch-OFF/1" states, respectively. Interestingly, the optical and dielectric "ON/OFF or 0/1" switches can be integrated into one single-molecule single/duple channel module with high signal-noise ratio, in which the "ON/OFF" response can be precisely controlled by temperature or/and light wavelength signal to realize automatically multiple switching. In brief, the lead-free multifunctional switch opens up a brand new route and shows the mark of its real genius as a highly desirable material for its advanced applications in highly integrated circuit and ultrahigh-encrypted storage in flexible photoelectric devices.


The evolution of microtubule associated proteins - a reference proteomic perspective.
Microtubule associated proteins (MAPs), defined as proteins that bind microtubules but are not molecular motors or severing enzymes, play a key role in regulating microtubule stability in neurons. Existing studies of the evolutionary relationships between these proteins are limited to genomic data from a small number of species. We therefore used a large collection of publicly available reference-quality eukaryotic proteomes to carry out a phylogenetic analysis of microtubule associated proteins in both vertebrates and invertebrates. Complete or near-complete reference quality proteomes were obtained from Uniprot. Microtubule associated proteins were identified using InterProtScan, aligned using MUSCLE and then phylogenetic trees constructed using the WAG algorithm. We identified 889 proteins with tubulin binding domains, of which 663 were in eukaryotes, including 168 vertebrates and 64 invertebrates. The vertebrate proteins separated into three families, resembling human MAP 2, MAP4 and MAPT, respectively, while invertebrate MAPs clustered separately. We found significant variation in number of microtubule associated proteins and number of microtubule binding domains between taxa, with fish and mollusks having an unexpectedly high number of MAPs and binding domains, respectively. Our findings represent a novel analysis of the evolution of microtubule associated proteins based on publicly available proteomics data sets. We were able to confirm the phylogeny of MAPs identified based on more limited genomic analyses, and in addition, derived several novel insights on the structure and function of MAPs.


The environmental sculpting hypothesis of juvenile and adult hippocampal neurogenesis.
We propose that a major contribution of juvenile and adult hippocampal neurogenesis is to allow behavioral experience to sculpt dentate gyrus connectivity such that sensory attributes that are relevant to the animal's environment are more strongly represented. This "specialized" dentate is then able to store a larger number of discriminable memory representations. Our hypothesis builds on accumulating evidence that neurogenesis declines to low levels prior to adulthood in many species. Rather than being necessary for ongoing hippocampal function, as several current theories posit, we argue that neurogenesis has primarily a prospective function, in that it allows experience to shape hippocampal circuits and optimize them for future learning in the particular environment in which the animal lives. Using an anatomically-based simulation of the hippocampus (BACON), we demonstrate that environmental sculpting of this kind would reduce overlap among hippocampal memory representations and provide representation cells with more information about an animal's current situation; consequently, it would allow more memories to be stored and accurately recalled without significant interference. We describe several new, testable predictions generated by the sculpting hypothesis and evaluate the hypothesis with respect to existing evidence. We argue that the sculpting hypothesis provides a strong rationale for why juvenile and adult neurogenesis occurs specifically in the dentate gyrus and why it declines significantly prior to adulthood.


Hormonal activation of mammary gland peroxidase.
Ultrastructural cytochemistry was used to detect an endogenous peroxidase in the rat mammary gland. The enzyme was identified only during the latter half of pregnancy and during lactation, indicating its possible dependence upon hormones. To test this hypothesis, specific hormones associated with the development and differentiation of the mammary gland were used both in vivo and in vitro in an effort to induce, or unmask, the activity of the enzyme. Estrogen injected into nonpregnant rats induced some peroxidase activity in the mammary glands of a few animals. Two hormone combinations tested in organ cultures of mouse mammary gland were able to activate the enzyme: (1) dexamethasone + insulin and (2) dexamethasone + insulin + prolactin.


Ear reconstruction research using animal models: The effect of fat grafting on costal cartilage stents.
For congenital microtia patients with a depressed mastoid area, it is unclear whether autologous fat grafting to fill the depressed area of the cheek will affect the survival of the subsequent grafted costal cartilage stent. An animal model was used for in vivo research to provide guidance for clinical applications. Autologous costal cartilage was implanted in nude mice. Fat samples were collected at different time points and histological examination performed to analyze the activity of chondrocytes and the deposition of the chondrocyte matrix. This nude mouse fat transplantation model study showed that there were statistical differences in chondrocyte viability between the fat filling group and the control group, but there was no statistical difference in the effect on collagen content. Transplanting fat reduces the viability of chondrocytes, but has little effect on collagen matrix deposition.


Kaposiform hemangioendothelioma of the choledochus.
Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular neoplasm that mainly occurs during childhood. Although KHE may involve various organs, involvement of the choledochus has not been reported. We report a case of KHE in a 5-month-old male infant. The patient was admitted with icterus and acholic stool. Contrast computed tomography revealed a vascular tumor in the hepatic portal region causing biliary obstruction. Excision of the extrahepatic duct and hepatoportoenterostomy were performed successfully, and he has been well during 3 years of postoperative follow-up.


Partner notification techniques.
This article aimed to cover the range of techniques used in partner notification for sexually transmitted infections, including HIV. Many of the current methods were developed over the past 50 years, and very little operational research has since been undertaken to refine them. More work is needed to evaluate inexpensive strategies to improve patient referral, to determine the psychological and behavioral impact of partner notification and methods of incorporating social networks in partner notification programs.


Morphological analysis of the foramen magnum of dogs from the Iron Age.
The investigations were carried out on 37 skulls from the Van-Yoncatepe early Iron Age necropolis (in eastern Anatolia) (first group) and 11 skulls from the scythians castle from Bileskoje Iron Age (second group). The major distance between both occipital condyles and both bases of the jugular processes, the major width of the foramen magnum, height of the foramen magnum, height of the skull, height of the occipital triangle and the length of the dorsal notch were measured. A dorsal notch was present in seven dogs (six male and one female) from Van-Yoncatepe. The average length of the dorsal notch was 2.5 mm. The investigation states that the dorsal notch occurred in dogs from the Iron Age. This anatomical formation had no association with their death.


The wandering spleen.
The article presents two cases of wandering spleen in the pediatric age group. Both patients were admitted for abdominal pain. In one, the onset was sudden and, on physical examination, a mass was felt in the left hypochondrium. In the other, it was the second episode and a firm mid-abdominal mass was found. The wandering spleen is a specific clinical syndrome which should be taken into account when an abdominal tumor is found. Ultrasonography and isotopic scan are very useful diagnostic tools The wandering spleen is caused by the absence of the splenorenal ligament which allows increased mobility of the splenic hilum. Both children underwent a splenectomy and made an uneventful recovery.


The immune response to bacterial dextrans. I. Genetic control of responsiveness.
The in vivo antibody response to the thymus-independent (TI) antigen dextran B512 (Dex) was studied in various mouse strains. We found no non-responder strains but rather that the magnitude of Dex-specific plaque-forming cell and serum antibody responses varied markedly among individual mice, even if these were of the same age and litter and kept in the same environment. This was the case both for mouse strains previously described genetically as high (IgCHb,j) and for those described as low (IgCHa) responders to Dex [14]. In 'low'-responder BALB/c mice, the responsiveness to Dex increased with age, such that a large fraction of these mice responded as well as 'high'-responder C57BL/6 mice. Analysis of aged back-cross populations derived from IgCHb and IgCHa parental strains further substantiated these findings. Thus, all backcross mice, irrespective of IgCH haplotype, responded on the average equally well to Dex. According to our studies, therefore, the assignation of high or low responsiveness to IgCH locus-linked genes cannot be done unequivocally.


Development and validation of a novel assay to identify radiosensitizers that target nucleophosmin 1.
A series of indole analogs that are synthesized using the scaffold of a potent radiosensitizer, YTR107, were tested for their ability to alter the solubility of phosphorylated nucleophosmin 1 (pNPM1). NPM1 is critical for DNA double strand break (DSB) repair. In response to formation of DNA DSBs, phosphorylated T199 NPM1 binds to ubiquitinated chromatin, in a RNF8/RNF168-dependent manner, forming irradiation-induced foci (IRIF) that promote repair of DNA DSBs. A Western blot assay was developed using lead molecule, YTR107, for the purpose of screening newly synthesized molecules that target pNPM1 in irradiated cells. A colony formation assay was used to demonstrate the radiosensitization properties of the compounds. Compounds that enhanced the extractability of pNPM1 upon radiation treatment possessed radiosensitization properties.


Isoelectric focusing of basic proteases in immobilized pH gradients.
By exploiting a new, alkaline immobilized pH gradient spanning the pH 10-11 interval, it has been possible to focus and to detect, by in situ zymogramming with cellulose acetate foils impregnated with fluorogenic substrates, 2 alkaline proteases, namely elastase and trypsin. Elastase gave a sharp array of 3 bands, with the following pIs (at 10 degrees C): 10.60 (major component), 10.53 (intermediate species) and 10.45 (minor isoform). Trypsin was resolved into 2, about equally abundant, species having pIs of 10.70 and 10.53. However, the latter enzyme gave smears in between these 2 forms and also anodic to the lower pI species. As hydrophobic interaction with the Immobiline matrix was excluded, it is suggested that these smears represent product of auto-digestion due to the very alkaline pH during the focusing process.


Ischaemic preconditioning improves microvascular perfusion and oxygenation following reperfusion injury of the intestine.
Ischaemia-reperfusion (IR) injury of the intestine occurs commonly during abdominal surgery. Ischaemic preconditioning (IPC) provides a way of protecting the organ from damage inflicted by IR. This study was designed to evaluate the beneficial effect of IPC, focusing on the intestinal microcirculation and oxygenation in intestinal IR injury. Rats were allocated to three groups. Animals in the IR and IPC groups underwent 30 min of intestinal ischaemia followed by 2 h of reperfusion. In the IPC group this was preceded by 10 min of ischaemia and 10 min of reperfusion. Animals in the third group underwent laparotomy but no vascular occlusion. Intestinal microvascular perfusion, oxygenation and portal venous blood flow (PVF) were monitored continuously. At the end of the reperfusion period, blood samples were obtained for measurement of lactate dehydrogenase (LDH) and biopsies of ileum for histological evaluation. : IPC improved intestinal microvascular perfusion and tissue oxygenation significantly at the end of the reperfusion period (P < 0.001). PVF improved significantly in the IPC compared with the IR group (P = 0.005). The serum LDH concentration was significantly lower in the IPC than the IR group (mean(s.e.m.) 667.1(86.8) versus 1973.8(306.5) U/l; P < 0.001) Histological examination showed that ileal mucosa was significantly less injured in the IPC group. This study demonstrated that IPC improves intestinal microvascular perfusion and oxygenation.


Thickness-Induced Metal-Insulator Transition in Sb-doped SnO2 Ultrathin Films: The Role of Quantum Confinement.
A thickness induced metal-insulator transition (MIT) was firstly observed in Sb-doped SnO2 (SnO2:Sb) epitaxial ultrathin films deposited on sapphire substrates by pulsed laser deposition. Both electrical and spectroscopic studies provide clear evidence of a critical thickness for the metallic conductivity in SnO2:Sb thin films and the oxidation state transition of the impurity element Sb. With the shrinkage of film thickness, the broadening of the energy band gap as well as the enhancement of the impurity activation energy was studied and attributed to the quantum confinement effect. Based on the scenario of impurity level pinning and band gap broadening in quantum confined nanostructures, we proposed a generalized energy diagram to understand the thickness induced MIT in the SnO2:Sb system.


Heat labile enterotoxin of E. coli: a potential adjuvant for transcutaneous cancer immunotherapy.
Escherichia coli heat labile enterotoxin (LT) has been shown to penetrate intact skin and to activate adaptive immunity. A nontoxic mutant, nLT, and its B subunit (LTB), have been evaluated separately for their potential use as a tool for transcutaneous delivery of antigens for cancer immunotherapy. We have shown that FITC-labeled nLT is taken up by human dendritic cells (hDC) in vitro and in mouse skin, and induces maturation and activation of hDC in vitro. hDC matured with nLT enhanced nonspecific melanoma antigen uptake and presentation to autologous CD8+ T cells. In mouse in vivo studies, nLT or LTB were applied on the skin either mixed with recombinant gp100 or genetically fused with a multiepitope polypeptide (MEP). Fused LTB-MEP induced antibody production that was dependent on LTB cell binding. We conclude that LT derivatives may be useful for the transcutaneous delivery of tumor antigens for cancer immunotherapy.


Aspects concerning posterior urethral valves.
Twenty-six boys were evaluated and treated for posterior urethral valves. At the time the valves were diagnosed unilateral or bilateral vesicoureteral reflux was present in 58% of the ureters and 69% of the children, while dilatation of the upper urinary tract was present in 88% and 92%, respectively. There was a variety of symptoms and signs, but the most prominent in neonates and infants were vesical urine retention, palpable kidneys and failure to thrive, whereas in the older children voiding dysfunction, incontinence and urinary infection were the most common. Twenty-four out of 26 boys were managed by primary valve ablation and in 62.5% of them this type of treatment was adequate in resolving or sufficiently improving clinical manifestations and roentgenologic findings, requiring no further management. Urinary diversion in the form of vesicostomy and cutaneous ureterostomy was preserved for those patients who did not improve with valve ablation alone. The current aspects concerning posterior urethral valves are also discussed.


Using factor analysis to evaluate checklist items.
Relatively little research has been published examining the use of factor analytic techniques to improve the psychometric qualities of performance assessments. The purpose of the current investigation is to illustrate the potential use of structural equation modeling (SEM) with scores from a standardized patient examination. Checklist items for a single case were examined to compare two models within a SEM framework: a single, underlying "data gathering" construct and a two-factor model consisting of medical history interviewing and physical examination maneuvers. The chi2 statistics obtained were statistically significant for both the single factor (chi2=1645.8, p<.001) and the two-factor model, (chi2=1373.1; p<.001), indicating marginal model-data fit. A difference statistic was calculated (chi2=320.9; p<.001), suggesting that the two-factor model has better fit. The parameters estimated by each model could be used to evaluate checklist item performance. The results of this investigation illustrate the utility of this method in the analysis of checklist item data.


Carbon and N conservation during composting: A review.
Composting, as a conventional solid waste treatment method, plays an essential role in carbon and nitrogen conservation, thereby reducing the loss of nutrients and energy. However, some carbon- and nitrogen-containing gases are inevitably released during the process of composting due to the different operating conditions, resulting in carbon and nitrogen losses. To overcome this obstacle, many researchers have been trying to optimize the adjustment parameters and add some amendments (i.e., pHysical amendments, chemical amendments and microbial amendments) to reduce the losses and enhance carbon and nitrogen conservation. However, investigation regarding mechanisms for the conservation of carbon and nitrogen are limited. Therefore, this review summarizes the studies on physical amendments, chemical amendments and microbial amendments and proposes underlying mechanisms for the enhancement of carbon and nitrogen conservation: adsorption or conversion, and also evaluates their contribution to the mitigation of the greenhouse effect, providing a theoretical basis for subsequent composting-related researchers to better improve carbon and nitrogen conservation measures. This paper also suggests that: assessing the contribution of composting as a process to global greenhouse gas mitigation requires a complete life cycle evaluation of composting. The current lack of compost clinker impact on carbon and nitrogen sequestration capacity of the application site needs to be explored by more research workers.


Single-cell deep phenotyping of cytokine release unmasks stimulation-specific biological signatures and distinct secretion dynamics.
Cytokines are important mediators of the immune system, and their secretion level needs to be carefully regulated, as an unbalanced activity may lead to cytokine release syndromes. Dysregulation can be induced by various factors, including immunotherapies. Therefore, the need for risk assessment during drug development has led to the introduction of cytokine release assays (CRAs). However, the current CRAs offer little insight into the heterogeneous cellular dynamics. To overcome this limitation, we developed an advanced single-cell microfluidic-based cytokine secretion platform to quantify cytokine secretion on the single-cell level dynamically. Our approach identified different dynamics, quantities, and phenotypically distinct subpopulations for each measured cytokine upon stimulation. Most interestingly, early measurements after only 1 h of stimulation revealed distinct stimulation-dependent secretion dynamics and cytokine signatures. With increased sensitivity and dynamic resolution, our platform provided insights into the secretion behavior of individual immune cells, adding crucial additional information about biological stimulation pathways to traditional CRAs.


Localization and sequence analysis of poly(A) sites generating multiple dihydrofolate reductase mRNAs.
The murine dihydrofolate reductase (DHFR) gene gives rise to multiple polyadenylated mRNAs displaying heterogeneity in the length of the 3' untranslated region. These species are present in the cytoplasm at levels that vary over 2 orders of magnitude, suggesting that certain poly(A) sites are preferred over others. Previous observations have shown that three out of the four major sites of polyadenylation do not display consensus hexanucleotide (AATAAA, ATTAAA) signals. We have further analyzed the sequences involved in directing multiple polyadenylation events on the DHFR gene by focusing our attention on the 4.1- and 5.6-kilobase mRNAs, the lowest abundance DHFR species observed on RNA blot analysis. Identification and sequence analysis of the poly(A) addition sites corresponding to these species revealed appropriately positioned consensus hexanucleotide signals; additional nearby poly(A) sites were also detected which apparently do not use consensus hexanucleotides to direct poly(A) addition to DHFR mRNAs of relatively lower abundance. We have also identified polyadenylation sites downstream of the 4.1- and 5.6-kilobase sites which display consensus hexanucleotide signals and correspond to messenger species too rare for detection by routine RNA blot analysis. Our data bring to 11 the number of known functional poly(A) addition sites associated with the DHFR gene.


IgE-binding and histamine-release capabilities of the main carbohydrate component isolated from the major allergen of olive tree pollen, Ole e 1.
Pollen from olive trees (Olea europaea ) is a cause of pollinosis and an aggravating of asthma in Mediterranean regions. Recently, Ole e 1, the major allergen from olive tree pollen, has been isolated and its amino acid sequence has been elucidated. It is a glycoprotein whose carbohydrate moiety is involved in an IgE-binding epitope responsible for cross-reactivity among plant glycoproteins. However, the allergenicity of the free carbohydrate side chains remains to be clarified. The purpose of this study was to isolate the main carbohydrate component of Ole e 1 allergen and analyze its IgE-binding and histamine-release capabilities. Deglycosylation treatment of Ole e 1 with PNGase F and gel exclusion chromatography were used to isolate the main sugar component of the allergen. Sera of patients who are allergic to olive pollen and sera sensitive to Ole e 1 have been used in dot blotting assays of IgE binding to the isolated carbohydrate. Heparinized whole blood obtained from patients sensitive to Ole e 1 were stimulated by the free carbohydrate; the resulting histamine release was measured. The main sugar component of Ole e 1 has been isolated. Free carbohydrate was able to bind IgE from sera of patients allergic to olive pollen; the sera of 65% of these patients contained anticarbohydrate reacting IgE, and 100% of those patients were sensitive to Ole e 1. The free carbohydrate promoted in vitro histamine release from basophils of sensitized patients. The carbohydrate moieties of allergenic glycoproteins can constitute significant determinants on the binding to IgE of the sera from patients who are hypersensitive and can be responsible for inducing histamine release from blood cells.


Abdominal Bloating in the United States: Results of a Survey of 88,795 Americans Examining Prevalence and Healthcare Seeking.
Although abdominal bloating is a common symptom, comparatively little is known about its prevalence in the community. This study aimed to examine the prevalence of bloating and assess related health care seeking using survey data from a nationally representative sample of nearly 89,000 Americans. Participants completed the National Gastrointestinal (GI) Survey II to measure the presence and severity of GI symptoms including bloating. We assessed the prevalence of bloating in the past 7 days, as well as severity and health care seeking for bloating. Multivariable regression was performed to identify associations between the outcomes and covariates. Of 88,795 survey completers, 12,324 (13.9%) reported bloating in the past 7 days. Women and those with comorbidities (eg, irritable bowel syndrome, chronic constipation, ulcerative colitis) and concomitant GI symptoms (eg, abdominal pain, excess gas) had higher odds for bloating (all P < .001). These factors were also associated with more severe bloating (all P < .001). Among those who reported recent bloating, 58.5% never sought care for bloating-29% of whom were self-managing symptoms or were uncomfortable discussing symptoms with their providers. Bloating is common in the community because nearly 1 in 7 Americans have experienced this symptom in the past week. Women and those with certain comorbidities and concomitant GI symptoms are more likely to experience bloating and have more severe symptoms. Nearly one third of sufferers who have not sought care are managing symptoms on their own or are uncomfortable discussing it with their providers, emphasizing that efforts should be made to proactively inquire about bloating.


Divided method of intercostal nerve block reduces ropivacaine dose by half in thoracoscopic pulmonary resection while maintaining the postoperative pain score and 4-h mobilization: a retrospective study.
This study investigated whether the divided method of multi-level intercostal nerve block (ML-ICB) could reduce the ropivacaine dose required during thoracoscopic pulmonary resection, while maintaining the resting postoperative pain scores. This retrospective, single-cohort study enrolled 241 patients who underwent thoracoscopic pulmonary resection for malignant tumors between October 2020 and March 2022 at a cancer hospital in Japan. ML-ICB was performed by surgeons under direct vision. The differences in intraoperative anesthetic use and postoperative pain-related variables at the beginning and end of surgery between group A (single-shot ML-ICB; 0.75% ropivacaine, 20 mL at the end of the surgery) and group B (divided ML-ICB, performed at the beginning and end of surgery; 0.25% ropivacaine, 30 mL total) were assessed. The numerical rating scale (NRS) was used to evaluate pain 1 h and 24 h postoperatively. Intraoperative remifentanil use was significantly lower in group B (14.4 ± 6.4 μg/kg/h) than in group A (16.7 ± 8.4 μg/kg/h) (P = 0.02). The proportion of patients with NRS scores of 0 to 3 at 24 h was significantly higher in group B (85.4%, 106/124) than in group A (73.5%, 86/117) (P = 0.02). The proportion of patients not requiring postoperative intravenous rescue drugs was significantly higher in group B (78.2%, 97/124) than in group A (61.5%, 72/117) (P < 0.01). The divided method of ML-ICB could reduce the intraoperative remifentanil dose, decrease the postoperative pain score at 24 h, and curtail postoperative intravenous rescue drug use, despite using half the total ropivacaine dose intraoperatively.


Rate of forgetting in mild Alzheimer's-type dementia.
Patients with mild dementia of the Alzheimer's type (DAT) and matched controls were examined for rate of forgetting line drawings of common objects. DAT patients demonstrated rapid forgetting in the first 10 min after learning to criterion. This finding is discussed with respect to memory consolidation and neuropathologic changes in dementia of the Alzheimer's type.


Time-qualified reference intervals - chronodesms.
Methods are presented for qualifying clinical reference intervals, for individuals as well as peer groups, according to circadian and other rhythms, using chronobiologically-defined single samples or time series.


Further studies on gene polymorphism in the mainbody and geographically isolated populations of Drosophila pseudoobscura.
We have examined polymorphism at 22 additional loci in the populations from the mainbody of Drosophila pseudoobscura and an isolated population from Bogotá, Columbia, which also shows partial reproductive isolation from mainbody populations. These studies extend our previous observations of reduced gene polymorphism and apparent lack of unique allele in the Bogotá population.


An overview and categorization of dynamic arm supports for people with decreased arm function.
Assistive devices that augment arm function were already introduced during the polio era. Devices are still being developed, but a review has not been performed thus far. To create an overview and categorize assistive devices facilitating arm function in activities of daily living for people with decreased arm function. Literature review. A systematic review in three scientific literature databases. Conference proceedings, assistive technology databases, and references were searched and experts consulted. This resulted in a database of dynamic arm supports. Product information was added, and the devices were categorized. A total of 104 dynamic arm supports were found. These could be categorized as nonactuated devices (N = 39), passively actuated devices (N = 24), actively actuated devices (N = 34), or devices using the functional electrical stimulation principle (N = 7). Functionality analysis resulted in second-level categorization: tremor suppression, facilitation of anti-gravity movement, and assistance of specific joint motion. All devices could be ordered in a categorization of low complexity. Many have been developed; most have disappeared and have been succeeded by similar devices. Limitations of the devices found mainly concern interfacing and the range of motion facilitated. Future devices could make use of whatever residual strength is available in the users' arm for control. The provided overview of devices in this article and the classification developed is relevant for practitioners seeking assistive solutions for their clients as it makes the range of developed solutions both accessible and comprehensible.


Substantia nigra influences on the reticulospinal neurons: an electrophysiological and ionophoretic study in cats and rats.
The influences exerted by the substantia nigra on reticulospinal neurons and the nature of the synaptic transmitter subserving these projections have been studied in adult cats and rats. Nigral stimulation evokes discharge changes in a significant number of reticulospinal cells (32.4% in cats and 39.1% in rats) on both ipsi- and contralateral sides. The responses were short-latency inhibitions (69.5% in cats and 76.5% in rats), short-latency excitations (22.2% in cats and 23.6% in rats) and in the remaining few cases long-latency excitations. Short-latency excitations, quite similar to the nigra-induced ones, were the predominant response pattern (95.2% in cats and 96.9% in rats) elicited on reticulospinal cells following stimulation of cerebral peduncle. The stimulation of substantia nigra in rats submitted to chronic ablation of sensorimotor cortex elicited only inhibitory responses while stimulation of nigral area in rats with intranigral injection of kainic acid was still capable of evoking short-latency excitations but not short-latency inhibitions. Therefore, the former can be ascribed to activation of corticoreticular fibers running in the cerebral peduncle whereas the latter can be considered as depending on activation of nigral efferents. The nigra-influenced cells were both 'fast' and 'slow' reticulospinal neurons and resulted mainly located in most rostral regions of reticular formation. Ionophoretic application of GABA suppressed the spontaneous firing of reticulospinal cells while no effect was observed following application of dopamine. The nigra-induced inhibitions were abolished by GABA-antagonist bicuculline and not by dopamine-antagonist fluphenazine.(ABSTRACT TRUNCATED AT 250 WORDS)


Global Spread of Hemorrhagic Fever Viruses: Predicting Pandemics.
As successive epidemics have swept the world, the scientific community has quickly learned from them about the emergence and transmission of communicable diseases. Epidemics usually occur when health systems are unprepared. During an unexpected epidemic, health authorities engage in damage control, fear drives action, and the desire to understand the threat is greatest. As humanity recovers, policy-makers seek scientific expertise to improve their "preparedness" to face future events.Global spread of disease is exemplified by the spread of yellow fever from Africa to the Americas, by the spread of dengue fever through transcontinental migration of mosquitos, by the relentless influenza virus pandemics, and, most recently, by the unexpected emergence of Ebola virus, spread by motorbike and long haul carriers. Other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (West Nile, chikungunya and Zika) enabled by ecology and vector adaptations. Did we learn from the past epidemics? Are we prepared for the worst?The ultimate goal is to develop a resilient global health infrastructure. Besides acquiring treatments, vaccines, and other preventive medicine, bio-surveillance is critical to preventing disease emergence and to counteracting its spread. So far, only the western hemisphere has a large and established monitoring system; however, diseases continue to emerge sporadically, in particular in Southeast Asia and South America, illuminating the imperfections of our surveillance. Epidemics destabilize fragile governments, ravage the most vulnerable populations, and threaten the global community.Pandemic risk calculations employ new technologies like computerized maintenance of geographical and historical datasets, Geographic Information Systems (GIS), Next Generation sequencing, and Metagenomics to trace the molecular changes in pathogens during their emergence, and mathematical models to assess risk. Predictions help to pinpoint the hot spots of emergence, the populations at risk, and the pathogens under genetic evolution. Preparedness anticipates the risks, the needs of the population, the capacities of infrastructure, the sources of emergency funding, and finally, the international partnerships needed to manage a disaster before it occurs. At present, the world is in an intermediate phase of trying to reduce health disparities despite exponential population growth, political conflicts, migration, global trade, urbanization, and major environmental changes due to global warming. For the sake of humanity, we must focus on developing the necessary capacities for health surveillance, epidemic preparedness, and pandemic response.


Localization of small nuclear RNA by EM autoradiography in Chinese hamster ovary (CHO) cells.
The ultrastructural localization of small nuclear RNA (snRNA) was studied by EM autoradiography in Chinese Hamster Ovary (CHO) cells. Conditions were set where most (greater than 85%) of the nuclear [3H]uridine label consisted of snRNA, the most abundant species being U1, U2 and the nucleolar species U3. The label was found in highest density in the peripheral part of the nucleus, especially over areas of condensed chromatin. A quantitative analysis of grain distribution showed that the enrichment observed in the periphery was significant (P less than 0.001). Labelling was also observed over the nucleolus. Labelling conditions using inhibitors of RNA synthesis provided additional evidence that the precursor was incorporated into snRNA. Our results show that in interphasic CHO cells, the greatest abundance of snRNA is found, in situ, over areas enriched in condensed chromatin. Whereas the nature of this association remains to be elucidated, these findings suggest that some species of snRNA might be involved in the structure of chromatin; among the various species, U2 appears as the best candidate.


Pancreastatin inhibits insulin secretion and stimulates glucagon secretion in mice.
Recently a new peptide, pancreastatin, was isolated from porcine pancreatic extracts. It contains 49 amino acids and shows a structural similarity to chromogranin A, which occurs in secretory granules of the endocrine pancreas. Furthermore, pancreastatin has been found to inhibit glucose-induced insulin secretion in the perfused rat pancreas. However, its effects under in vivo conditions have never been studied. We have therefore investigated the effects of this peptide on insulin and glucagon secretion in vivo in the mouse. We found that an intravenous injection of pancreastatin (4.0 nmol/kg) lowered basal plasma insulin concentration at 6 min from 55 +/- 8 microU/ml in control mice to 21 +/- 7 microU/ml (P less than .01). The peptide also inhibited the plasma insulin response to both glucose (P less than .01) and the cholinergic agonist carbachol (P less than .001). Furthermore, 2 min after injection of pancreastatin, plasma glucagon concentration had increased to 301 +/- 19 pg/ml compared to 190 +/- 12 pg/ml in control mice (P less than .001). The peptide did not, however, affect the carbachol-induced plasma glucagon response. In addition, pancreastatin induced a transient hyperglycemia. Combined adrenergic blockade by means of a pretreatment of phentolamine and propranolol did not prevent pancreastatin from exerting its effects on plasma insulin levels, whereas the increase in plasma glucagon levels was abolished. Thus, in the mouse, the newly discovered intrapancreatic peptide pancreastatin 1) lowers baseline plasma insulin levels, 2) inhibits glucose- and cholinergically induced insulin secretion, 3) stimulates baseline glucagon secretion, and 4) induces hyperglycemia.


Impact of PM2.5 concentration, weather and population on COVID-19 morbidity and mortality in Baghdad and Kuwait cities.
The coronavirus (COVID-19) pandemic is a global health crisis and biggest challenge facing the world. Station measurements of fine particulate matter (PM2.5) concentration in Baghdad and Kuwait during the period January-July 2020 are analyzed as well as assessment of correlation between PM2.5, weather conditions (air temperature, relative humidity, wind speed), population density and COVID-19 morbidity and mortality. A significant improvement (decrease) has observed during total and partial curfew in PM2.5 at Baghdad by 35%, 12.4%, respectively, from PM2.5 mean during the study period that is less than the WHO recommended PM2.5 level especially in total curfew. This decrease in PM2.5 pollution and people's mobility in Baghdad at total and partial curfew contributed to decrease injuries and mortality. PM2.5 during total and partial curfew in Kuwait country witnessed increasing by 38.4% and decreasing by 22.3% from the PM2.5 mean, respectively, but still higher than WHO standard level. This increase in PM2.5 at total curfew was related to burning accidents in the oil wells which caused increasing in PM2.5 pollutant and then an increase in number of injuries and mortality during that time. In general during all study period our research found that PM2.5 and wind speed exhibit weak relation with COVID-19 morbidity and mortality but strong relation with increasing temperature and decreasing humidity. The high population density had a good association with increasing daily new cases, mortality due to COVID-19 pandemic. Thus, these factors may be taken into consideration in policy development for the control and prevention of new chains of the Coronavirus pandemic.


How do environmental stresses accelerate photoinhibition?
Environmental stress enhances the extent of photoinhibition, a process that is determined by the balance between the rate of photodamage to photosystem II (PSII) and the rate of its repair. Recent investigations suggest that exposure to environmental stresses, such as salt, cold, moderate heat and oxidative stress, do not affect photodamage but inhibit the repair of PSII through suppression of the synthesis of PSII proteins. In particular, production of D1 protein is downregulated at the translation step by the direct inactivation of the translation machinery and/or by primarily interrupting the fixation of CO2. The latter results in the creation of reactive oxygen species (ROS), which in turn block the synthesis of PSII proteins in chloroplasts.


Brunner's gland polyp with upper gastrointestinal bleeding managed by endoscopic polypectomy: a report of two cases.
We report 2 rare cases of Brunner's gland adenoma presenting with upper gastrointestinal bleeding. They were removed by endoscopic polypectomy. In skilled hands, this method is safe and effective.


No bilingual advantage in children's attentional disengagement: Congruency and sequential congruency effects in a large sample of monolingual and bilingual children.
According to recent accounts, bilingualism in childhood confers an advantage in a specific domain of executive functioning termed attentional disengagement. The current study tested this hypothesis in 492 children (245 boys; Mage = 10.98 years) from Canada, China, and Lebanon by testing for an association between language status and measures of attentional disengagement. Across the entire sample, monolinguals responded more quickly and accurately than bilinguals on a measure of attentional disengagement but differed in age, socioeconomic status, and general cognitive ability. Differences between monolinguals and bilinguals disappeared when the influence of these confounding variables was controlled using a matched samples analysis (ns = 105). Bayesian analyses further confirmed that the evidence was more likely under the null hypothesis than under the alternative hypothesis. In sum, there was little evidence of an association between language status and attentional disengagement in children.


Integrative analysis identifies two molecular and clinical subsets in Luminal B breast cancer.
Comprehensive multiplatform analysis of Luminal B breast cancer (LBBC) specimens identifies two molecularly distinct, clinically relevant subtypes: Cluster A associated with cell cycle and metabolic signaling and Cluster B with predominant epithelial mesenchymal transition (EMT) and immune response pathways. Whole-exome sequencing identified significantly mutated genes including TP53, PIK3CA, ERBB2, and GATA3 with recurrent somatic mutations. Alterations in DNA methylation or transcriptomic regulation in genes (FN1, ESR1, CCND1, and YAP1) result in tumor microenvironment reprogramming. Integrated analysis revealed enriched biological pathways and unexplored druggable targets (cancer-testis antigens, metabolic enzymes, kinases, and transcription regulators). A systematic comparison between mRNA and protein displayed emerging expression patterns of key therapeutic targets (CD274, YAP1, AKT1, and CDH1). A potential ceRNA network was developed with a significantly different prognosis between the two subtypes. This integrated analysis reveals a complex molecular landscape of LBBC and provides the utility of targets and signaling pathways for precision medicine.


Pediatric deep neck infections: Clinical description and analysis of therapeutic management.
The aim of our study was to describe clinical presentations, bacteriological results, and therapeutic management in a pediatric population presenting with acute pharyngeal suppuration. A further aim was to identify clinical, bacteriological, and radiological predictors of success associated with exclusive medical treatment. A retrospective study was carried out including patients under 18 years of age hospitalized between January 1, 2015 and December 31, 2017 in our center for acute pharyngeal suppuration. We identified three groups of patients: group A, treated with exclusive intravenous antibiotics; group B, surgically treated after 48 h of appropriate antibiotic therapy, due to persistent fever and/or clinical worsening and/or persistence of a collection on follow-up imaging; group C, surgically treated as first-line therapy in association with intravenous antibiotics. A total of 83 patients were included: 36 in group A, 12 in group B, and 35 in group C. These three groups were compared for several variables: age of the patients, polynuclear neutrophil counts, diameter of the collections (the largest diameter found on imaging), duration of antibiotic therapy, delay before return to apyrexia, and hospitalization duration. A neck mass and torticollis were present, respectively, in 48.8 and 47.6% of cases. No breathing difficulties were reported. Streptococcus pyogenes was the most frequently identified microorganism. The average diameter of the collections from patients treated surgically as first-line therapy (group C) was significantly larger than that of the patients treated with antibiotics (group A) (27.89 mm vs. 18.73 mm, respectively, p = 0.0006). All the patients who required surgery despite 48 h of appropriate antibiotic therapy (group B) had collections with diameters greater than or equal to 15 mm. There was no significant difference between the groups concerning hospitalization duration. Exclusive medical treatment is associated with a high cure rate, mainly for collections with small diameter. We recommend special attention to patients treated with first-line exclusive intravenous antibiotic therapy and with a collection diameter greater than or equal to 15 mm.


Chondrosarcoma metastatic to the heart.
This review summarizes the clinical manifestations and results of treatment of chondrosarcoma metastatic to the heart. Including the patient in the present report, a total of 18 patients have been reported. The most common site of cardiac metastasis was the right atrium. Dyspnea and pleuritic chest pain were the most common symptoms associated with cardiac metastases. The median time from the initial diagnosis of primary chondrosarcoma to death was 36 months, and the median time from the initiation of cardiac symptoms to death was 2 months. Treatment of primary chondrosarcoma included local radical resection in 14 patients. Treatment of cardiac metastases consisted of palliative support in 13 patients and surgical resection in 5 patients. Median survival following the development of cardiac symptoms was 2 months for patients treated nonsurgically and 18 months for those who underwent resection of cardiac metastases. The longest survival (24 and 28 months) was obtained in 2 patients with metastases confined to the heart that were successfully resected soon after development of cardiac symptoms. These results suggest that surgical resection of cardiac metastases in patients without widespread other metastases can result in substantial prolongation of life.


Multicenter evaluation of the acid-fast bacillus smear, mycobacterial culture, Xpert MTB/RIF assay, and adenosine deaminase for the diagnosis of tuberculous peritonitis in China.
The aim of this study was to assess the validity of GeneXpert MTB/RIF (Xpert) and adenosine deaminase (ADA) in the diagnosis of tuberculous peritonitis (TBP). The laboratory results of peritoneal effusion (PE) specimens from patients with symptoms suggestive of TBP, attending three TB specialized hospitals between January 2016 and December 2018, were included retrospectively. Clinically diagnosed TBP was set as the gold standard to evaluate the performance of these methods. In total, 191 individuals presenting with symptoms suggestive of TBP were included for analysis. The sensitivities of MGIT culture and Xpert were 17.2% and 18.3%, respectively. In addition, the TBP cases (69.8±6.0U/l) had higher amounts of ADA in their PE samples than the non-TBP cases (12.6±1.6U/l; p<0.01). Using a threshold of 31.5U/l to differentiate the TBP group from non-TBP group, the ADA assay provided a sensitivity of 89.6% and a specificity of 92.1%. The mean ADA concentration was significantly higher in bacteria-positive cases than in bacteria-negative cases (p<0.01). In conclusion, the study data demonstrate the high sensitivity and specificity of the ADA test for the early diagnosis of TBP. In addition, the ADA concentration is directly correlated with the mycobacterial load.


Free triiodothyronine and free thyroxine hormone levels in relation to breast cancer risk: a meta-analysis.
The conflict between breast cancer (BC) and thyroid hormone (TH) has been studied for years. The purpose of the study was to summarise and analyse the available data on the relationship between TH and BC. The PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched to identify relevant studies. The mean difference (MD) with 95% confidence interval (CI) were calculated by fixed or random effects models to assess the effect sizes. Thirteen eligible studies with 5957 participants were included in the meta-analysis. The result of this study indicates that there is a significant risk relationship between BC and thyroid hormones [free triiodothyronine (FT3): MD = 1.01 pmol/L, 95% CI: 0.32-1.70, free thyroxine (FT4): MD = 0.26 ng/dL, 95% CI: 0.13-0.38]. Compared with healthy controls, the positive risk of FT3 and FT4 is higher in BC.


Leuprolide acetate lowers circulating bioactive luteinizing hormone and testosterone concentrations during ovarian stimulation for oocyte retrieval.
Levels of immunoreactive luteinizing hormone (LH), bioactive LH, and testosterone (T) were determined in 52 women receiving human menopausal gonadotropins (hMG). In 26 women receiving leuprolide acetate (LA) preceding hMG, there was a significant suppression of immunoreactive LH and bioactive LH. The characteristic increase in serum levels of bioactive LH and T were absent. Follicular fluid estradiol and T concentrations, and serum progesterone were not different. The lower circulating levels of T may reflect reduced LH-stimulated androgen accumulation in smaller nonaspirated follicles and may account for the enhanced follicle recruitment observed during LA. The lack of premature luteinization despite marked rises of bioactive LH in the absence of LA is consistent with normal events during the menstrual cycle and was due to the early termination of hMG stimulation.


Cycling related traumatic brain injury requiring intensive care: association with non-helmet wearing in young people.
Traumatic injury is the leading cause of death in children after infancy. Almost 25% of all cyclists killed in the UK are children, and two thirds of these will die because of their head injuries. We compared the population of young people wearing helmets whilst cycling, to those admitted with serious post cycling head injuries to our paediatric critical care unit. All children aged 0-18 years admitted to our intensive care following a bicycle accident between the years January 2011-June 2018 were identified and information on the mechanism of injury, and both immediate and long term clinical data were collected. For comparison data, helmet wearing on a random morning was observed from six schools. All pupils arriving at school by bicycle were observed. Data collected included the school year and sex of the child, and whether each child was wearing a helmet or not. Of 28 cases, 22 were admitted due to head injuries. None wore a helmet. 23/133 school pupils wore a helmet. The intensive care population were significantly less likely to be wearing helmets than the general population (p = 0.044, Fisher's exact test). A Chi-Square test for helmet wearing by school year showed a reduction in helmet wearing with increasing school year with a p value of 0.0026. There was no association between helmet wearing and abdominal injury. Young people admitted to a Critical Care Unit with cycling related head trauma are statistically significantly less likely to wear a helmet than the general, age matched cycling population. Helmet wearing decreases as children get older. Outcomes were mixed, but in the head trauma group only 3/18 recovered with no neurological deficit.


Roles of pyrolysis on availability, species and distribution of Cu and Zn in the swine manure: chemical extractions and high-energy synchrotron analyses.
Animal manures generally contain high levels of heavy metals that may pose a significant threat to soil and groundwater qualities. Pyrolysis as means of reducing metal availability in such feed stocks is recently encouraged, but systematic studies are currently lacking. The aim of this study was to assess the impact of pyrolysis temperature on the availability of Cu and Zn by chemical extraction, to determine the speciation of Cu and Zn by synchrotron-based X-ray spectroscopy, and finally to investigate the phase distribution of metal species in the carbonaceous materials by combining acid-base extractions and absorption spectroscopy data. The results showed that both Cu and Zn in the swine manure were mainly bound to organic functional groups. Cu (II) reduction and Cu (I)-S complexes were observed during the pyrolysis process. Zn species resembling ZnAc2 was still dominant, being 60.8-69.2%, and ZnS increased by 6.6-21.8% in the carbonaceous materials. The distribution of Cu and Zn in the mineral, carbonized and non-carbonized organic phases varied greatly with the pyrolysis temperature. The higher the temperature, the more the metals existed in the mineral phase and carbonized organic phase. The decrease of EDTA extractable Cu and Zn with pyrolysis temperature was due to the increase of metals in the carbonized organic phase and mineral phase. It is suggested that pyrolysis at the relatively higher temperature is a better choice for metal-containing manure according to the metal speciation, solubility and availability.


Surface passivation for highly active, selective, stable, and scalable CO2 electroreduction.
Electrochemical conversion of CO2 to formic acid using Bismuth catalysts is one the most promising pathways for industrialization. However, it is still difficult to achieve high formic acid production at wide voltage intervals and industrial current densities because the Bi catalysts are often poisoned by oxygenated species. Herein, we report a Bi3S2 nanowire-ascorbic acid hybrid catalyst that simultaneously improves formic acid selectivity, activity, and stability at high applied voltages. Specifically, a more than 95% faraday efficiency was achieved for the formate formation over a wide potential range above 1.0 V and at ampere-level current densities. The observed excellent catalytic performance was attributable to a unique reconstruction mechanism to form more defective sites while the ascorbic acid layer further stabilized the defective sites by trapping the poisoning hydroxyl groups. When used in an all-solid-state reactor system, the newly developed catalyst achieved efficient production of pure formic acid over 120 hours at 50 mA cm-2 (200 mA cell current).


IL-7 drives T cell-mediated bone loss following ovariectomy.
Ovariectomy-induced bone loss stems in large measure from a realignment of adaptive immune responses leading to the activation and expansion of tumor necrosis factor (TNF)-producing T cells. The mechanisms driving this T cell expansion are complex but we have recently reported that the pro-osteoclastogenic cytokine interleukin (IL)-7 plays a critical role in this process. The mechanisms of IL-7 action are intricate and poorly defined. We present herein an overview of our current understanding of IL-7 action on bone turnover and the role of IL-7 in ovariectomy-induced bone loss.


Improvement of radio frequency (RF) heating-assisted alkaline pretreatment on four categories of lignocellulosic biomass.
Pretreatment plays an important role in making the cellulose accessible for enzyme hydrolysis and subsequent conversion because it destroys more or less resistance and recalcitrance of biomass. Radio frequency (RF)-assisted dielectric heating was utilized in the alkaline pretreatment on agricultural residues (corn stover), herbaceous crops (switchgrass), hardwood (sweetgum) and softwood (loblolly pine). Pretreatment was performed at 90 °C with either RF or traditional water bath (WB) heating for 1 h after overnight soaking in NaOH solution (0.2 g NaOH/g Biomass). Pretreated materials were characterized by chemical compositional analysis, enzyme hydrolysis, scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The glucan yields of RF-heated four categories of hydrolysates were 89.6, 72.6, 21.7, and 9.9 %. Interestingly, RF heating raised glucan yield on switchgrass and sweetgum but not on corn stover or loblolly pine. The SEM images and FTIR spectra agreed with results of composition analysis and hydrolysis. GC-MS detected some compounds only from RF-heated switchgrass. These compounds were found by other researchers only in high-temperature (150-600 °C) and high-pressure pyrolysis processes.


Phoma sorghina infection in human being.
Phoma sorghina is reported for the first time as an opportunistic fungal pathogen. It was repeatedly isolated from patient as well as experimental animal. The identity and taxonomy of the fungus has been discussed.


Stimulation by octopamine of the sodium efflux in barnacle muscle fibres.
The behaviour of the ouabain-insensitive Na efflux in barnacle muscle fibres towards DL-octopamine has been investigated. It is found that these fibres are quite often sensitive to external application of octopamine. A concentration as low as 10(-9) M is effective. The kinetic results indicate that the stimulatory response develops within 5-10 min of exposure of the fibre to octopamine and is transitory in nature. The response to octopamine is greater in size in the presence of 1-isoamyl-3-isobutylxanthine (IAX) than in the presence of 1-propyl-3-methyl-7-(5-hydroxyhexyl)-xanthine (PMX). But neither IAX nor PMX stops the response from decaying. The response to octopamine is highly dependent on the presence of external Ca2+. The provisional conclusion is that the barnacle muscle fibre may be a useful preparation for studying the hormonal function of octopamine.


Correlation of murine susceptibility to tumor, parasite and bacterial challenge with altered cell-mediated immunity following systemic exposure to the tumor promoter phorbol myristate acetate.
Phorbol myristate acetate (PMA), the most potent of the tumor promoting phorbol diesters, modulates function in several immunoresponsive cells following in vitro exposure. Since suppression of cellular mechanisms capable of limiting tumors and infections can adversely affect health, these experiments were designed to evaluate relevant components of cell-mediated immunity (CMI) following in vivo PMA exposure, and to determine the biological significance of any alterations utilizing assays of host resistance. Adult, female B6C3F1 mice were administered 0.2, 2.0, 20.0 or 40.0 micrograms PMA/g body weight subcutaneously over a two-week period. Mechanisms of cell-mediated host resistance were assessed by quantitating natural killer (NK), cytotoxic T-lymphocyte (CTL) and macrophage-mediated lysis of radiolabelled tumor target cells, and macrophage-induced cytostasis in tumor cell populations. Macrophages from PMA-treated mice were cytostatic to tumor cells, inhibiting up to 90% of growth in cultured tumor cells, but were not tumoricidal. Furthermore, pyran-elicited (primed) macrophages, which are activated to fully cytotoxic states by in vitro exposure to lipopolysaccharide, were inhibited in tumoricidal activation by in vivo PMA exposure. The induction of responsive but not cytotoxic macrophages by in vivo PMA exposure is consistent with the enhanced resistance to Listeria bacterial challenge, and increased susceptibility to B16F10 tumor and Trichinella parasitic challenges observed in these mice. Furthermore, previous reports of decreased in vitro NK activity following in vivo PMA exposure and present observations of correlative decreases of in vivo NK activity (55% decrease in mice exposed to 20 micrograms PMA/g) suggest an important role for NK activity in limiting in vivo B16F10 melanoma growth. CTL effector function was less susceptible to PMA-induced suppression than NK function at similar dosages, further supporting a predominant role of macrophages and NK cells or possibly other effector functions in the resistance to Listeria, Trichinella, or B16F10 challenge. Nevertheless, significant suppressive effects of PMA on CTL function at higher dosages cannot be excluded as contributing to altered host resistance to these agents. These studies demonstrate that in vivo exposure to PMA can modify cell-mediated mechanisms of host resistance with coincident alterations in the incidence of infections and tumors.


Drug-related problems in prescribed medicines in Germany at the time of dispensing.
Drug-related problems (DRPs) can have an important impact on the effectiveness and safety of pharmacotherapy. In Germany, the frequency of DRPs in prescribed medicines in ambulatory care is not yet known. Objective To quantify DRPs in prescribed medicines identified by community pharmacists (CPs) at the time the medicine is dispensed. German CPs in four different regions. We invited CPs to document one hundred consecutive patients presenting prescriptions using a standardized documentation form. For each patient, person- and medication-related as well as identified DRP-related data were documented. Data were transcribed electronically, coded if necessary, checked for validity, and analyzed. Nature and frequency of DRPs. In total, 143 CPs documented 14,231 patients with 24,422 prescribed drugs and identified DRPs in 2,556 patients (18.0%). Analyses resulted in 0.23 DRPs per patient and 0.13 DRPs per prescribed medicine. Four DRPs were responsible for almost 70% of all DRPs: Potential drug-drug interaction (22.9%), dose not known to patient (21.7%), patient insecure due to generic substitution (13.5%), and insufficient patient knowledge of correct drug use (10.9%). If a patient's drug file was kept in the pharmacy, specific types of DRPs were detected more frequently e.g., drug-drug interactions (p < 0.001). Interventions primarily comprised counselling, monitoring, and changing drug or instructions for use. The prescribing physician was contacted in 28% of DRPs resulting in a change of these prescriptions in 50% of the cases. Overall and according to the pharmacists, more than 90% of the DRPs detected were partially (10.4%) or completely (85.4%) solved. We quantified DRPs in prescribed medicines in daily ambulatory care practice in Germany. When filling a prescription, in nearly 20% of the patients relevant DRPs were revealed. According to the pharmacists, the majority could be partially or completely solved during the encounter at the pharmacy. Keeping a patient's drug file including patient specific data may facilitate the detection of DRPs and shall, therefore, be offered to patients more often.


Circadian rhythms in sleep-wakefulness and wheel-running activity in a congenitally anophthalmic rat mutant.
Circadian rhythms were examined in a congenitally anophthalmic rat mutant. All bilaterally anophthalmic rats had clear circadian rhythms in sleep-wakefulness as well as in locomotor activity, but the rhythms did not entrain to the light-dark (LD) cycle. However, two unilaterally anophthalmic rats, like sighted rats, reentrained their sleep-wakefulness rhythms to the LD cycle in 4 days after a 6 hr delaying phase-shift. The hypogenesis of the suprachiasmatic nuclei (SCN) that is correlated with absence of circadian activity rhythms in anophthalmic mice was not observed in these anophthalmic rats.


Antibodies for a bespoke plant immunity.
Plants do not have antibodies. However, in a recent Science article, Kourelis and Marchal et al. have demonstrated that plant immune receptors can be retrofitted with animal antibodies to provide plants potentially with hundreds and thousands of options to perceive attacking microbes. This is the dawn of bespoke plant immunity.


MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells.
MiR-214 has been shown to inhibit cell growth, migration and invasion. Here we demonstrate that ectopic expression of miR-214 reduces cell survival, induces apoptosis and enhances sensitivity to cisplatin through directly inhibiting Bcl2l2 expression in cervical cancer HeLa and C-33A cells. Further analysis reveals that apoptosis induced by miR-214 is correlated with increased expression of Bax, caspase-9, caspase-8 and caspase-3. Moreover, we show that miR-214 is regulated by DNA methylation and histone deacetylation. Taken together, these data suggest that miR-214 might be a candidate target for the development of novel therapeutic strategies to treat cervical cancer.


MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma.
MEF2B encodes a transcriptional activator and is mutated in ∼11% of diffuse large B cell lymphomas (DLBCLs) and ∼12% of follicular lymphomas (FLs). Here we found that MEF2B directly activated the transcription of the proto-oncogene BCL6 in normal germinal-center (GC) B cells and was required for DLBCL proliferation. Mutation of MEF2B resulted in enhanced transcriptional activity of MEF2B either through disruption of its interaction with the corepressor CABIN1 or by rendering it insensitive to inhibitory signaling events mediated by phosphorylation and sumoylation. Consequently, the transcriptional activity of Bcl-6 was deregulated in DLBCLs with MEF2B mutations. Thus, somatic mutations of MEF2B may contribute to lymphomagenesis by deregulating BCL6 expression, and MEF2B may represent an alternative target for blocking Bcl-6 activity in DLBCLs.


Housing insecurity among cancer survivors: Results from the 2017 behavioral risk factor surveillance system survey.
Cancer patients and cancer survivors may struggle to pay for housing or fall behind on their monthly bills to pay for out-of-pocket medical costs. Housing insecurity increases the likelihood of poorer health and decreased access to health care. The financial burden of medical care as a cause of poorer health outcomes is worsened by the inability to afford housing. We examined housing insecurity among cancer survivors, using data from the 2017 Behavioral Risk Factor Surveillance System (BRFSS). We compared intensity of housing insecurity across various socioeconomic status indicators and estimated the adjusted odds for housing insecurity for these characteristics. We found that about 16.6 % of the cancer survivors had moderate to increased level of housing insecurity. The intensity of housing insecurity among cancer survivors was significantly associated with being Black, and having lower household income and lower educational attainment. In order to ensure the quality and appropriateness of cancer survivorship care, effective interventions are needed to address housing insecurity in these populations. Policy Summary. A sizeable percentage of cancer survivors have housing insecurity which is likely to complicate their ability to self-manage their disease and navigate the health care system for optimal care.