Small RNA and degradome profiling reveals important roles for microRNAs and their targets in tea plant response to drought stress.
Tea (Camellia sinensis) is a popular beverage worldwide. Drought stress (DS) is a major constraint on the growth, yield and quality of tea plants. MicroRNAs (miRNAs) play important roles in plant responses to DS. We constructed eight small RNA libraries from the drought-tolerant 'Ningzhou 2' (NZ2) and drought-susceptible 'Zhuyeqi' (ZYQ) cultivars during four stages [control (CK), the fourth day of DS, the eighth day of DS and after recovery (RC)]. A total of 268 conserved and 62 novel miRNAs were identified using small RNA sequencing. In total, 139 (52.9%) and 96 (36.0%) conserved miRNAs were differentially expressed during the four stages (P ≤ 0.05) in NZ2 and ZYQ, respectively. A total of 814 predicted target genes were identified as differentially regulated by 199 miRNAs through degradome sequencing. Among them, 201 and 218 genes were specific to the NZ2 and ZYQ cultivars, respectively, and 395 were common to both cultivars. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the biological roles of these targets and showed that some of the targets responded to DS in a stress- and cultivar-dependent manner. Correlated expression patterns between miRNA and their targets showed that specific miRNAs target the miRNA effector Argonaute 1 (AGO1), drought signaling-related receptors and enzymes, transcription factors, and other structural and functional proteins. The predicted regulatory networks provide insights into a potential miRNA-mediated regulatory mechanism. These results will contribute to the breeding of drought-tolerant tea plants and to elucidating miRNA regulation in response to drought.


Response to dehydration and irrigation in invasive and native saplings: osmotic adjustment versus leaf shedding.
To clarify the mechanism underlying successful invasion by tree species into xeric sites on Japan's Bonin Islands, we compared the water use of an alien species, Psidium cattleianum, which is rapidly expanding on ridge sites with shallow soil, with that of a native species, Trema orientalis. We hypothesized that there is a trade-off between leaf shedding with low cavitation resistance (frequent xylem cavitation plus refilling ability) and leaf osmotic adjustment with high cavitation resistance (cessation of xylem cavitation plus canopy leaf retention), indicating contrasting strategies for drought tolerance and water use in semi-arid regions. We examined leaf turnover, leaf gas exchange, leaf water potential and water distribution in stem xylem conduits using cryo-scanning electron microscopy for the saplings of both species under three cycles of artificial drought and sudden pulse irrigation. Invasive P. cattleianum saplings were highly resistant to cavitation in stem xylem conduits, retained their leaves and exhibited effective leaf osmotic adjustment under the drought treatment. In contrast, native T. orientalis saplings exhibited xylem cavitation, conspicuous leaf shedding and less effective leaf osmotic adjustment under the drought treatment. Leaf gas exchange rate recovered more rapidly in P. cattleianum saplings than in T. orientalis saplings immediately following pulse irrigation after a period without irrigation, especially in the first drought cycle. Embolized conduits in T. orientalis were refilled by pulse irrigation, and leaf gas exchange rate recovered following refilling. The two tree species showed contrasting strategies for drought tolerance and water use along a trade-off axis. Cavitation avoidance and effective leaf osmotic adjustment in P. cattleianum saplings under drought conditions partially support their survival at the xeric ridge sites on the Bonin Islands. Our results help to explain the success of P. cattleianum in its invasion of a sub-arid environment.


Dysregulation of renal salt and water transport proteins in diabetic Zucker rats.
Diabetic nephropathy is commonly associated with renal salt and water retention and hypertension. The molecular mechanisms involved and how the kidney responds to this volume expansion, in terms of renal transporter regulation, are not understood. Targeted proteomics employing semiquantitative immunoblotting were used to investigate regulation of abundance of the primary salt and water transport proteins of the kidney, in 6-month-old lean and obese Zucker rats, a model for Type II diabetes. Obese rats were significantly heavier, had larger kidneys, increased plasma creatinine and glucose levels and elevated blood pressures. Furthermore, they had a marked decrease in abundance of many pre-macula densa renal sodium transporters. Mean band densities (% lean) were: in cortex, sodium phosphate cotransporter (NaPi-2), 68%, and sodium hydrogen exchanger (NHE3), 66%; and in outer medulla, NHE3, 39%, and the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), 37%. Collecting duct proteins also were markedly reduced. In inner medulla, aquaporins-2, -3, and -4 were reduced to, 46, 48, and 46%, respectively, and the apical urea transporter, UTA1 to 52%. In contrast, post-macula densa sodium transporters were less affected. The thiazide-sensitive Na-Cl cotransporter (NCC) was 106% and the alpha- beta- and gamma-subunits of the epithelial sodium channel (ENaC), 54, 121, and 84% of lean, respectively. In obese rats, selective decreases for pre-macula densa sodium transporters may reflect decreased glomerular filtration rate and glomerulotubular balance. This potentially could reduce blood pressure by decreasing proximal tubule sodium reabsorption.


Morphological and ultrastructural analysis of the watershed zones after stripping of the vasa nervorum.
Peripheral nerve trunks are well-vascularized structures where a well-developed collateral system may compensate for local vascular damage. Vasculitis in nerve has a predilection for epineurial vessels and causes to the peripheral neuropathy, which is a major clinical feature of primary and secondary systemic vasculitides. In the present study, the goal was to simulate the vasculitic neuropathy in rat sciatic nerve and to investigate the watershed zones after stripping of the epineural vessels of the sciatic nerve. Sciatic function index values, light and electron microscopic evaluations of the experimental sciatic nerve suggested that the sciatic nerve was normal except for some watershed zones located in the peripheral part of the nerve. Although there is abundant collateral circulation in the peripheral nerve, distribution of the vessels of the watershed zones as observed in the present study should be elucidated by further studies.


Store-Operated Ca(2+) Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity.
T follicular helper (Tfh) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (Tfr) cells limit the GC reaction. Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Conditional deletion of Stim1 and Stim2 genes in T cells abolished SOCE and strongly reduced antibody-mediated immune responses following viral infection caused by impaired differentiation and function of Tfh cells. Conversely, aging Stim1Stim2-deficient mice developed humoral autoimmunity with spontaneous autoantibody production due to abolished Tfr cell differentiation in the presence of residual Tfh cells. Mechanistically, SOCE controlled Tfr and Tfh cell differentiation through NFAT-mediated IRF4, BATF, and Bcl-6 transcription-factor expression. SOCE had a dual role in controlling the GC reaction by regulating both Tfh and Tfr cell differentiation, thus enabling protective B cell responses and preventing humoral autoimmunity.


First-line versus second-line use of pralsetinib in treatment of rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer: a cost-effectiveness analysis.
The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) in clinical trials. However, due to the high cost of PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, the aim of this study was to assess the cost-effectiveness characteristics of using PRL as a first-line therapy versus reserving it until the second-line versus solely relying on chemotherapy from the perspective of payers in the United States. A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies. Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year. To ensure the robustness of the model, both probabilistic and univariate sensitivity analyses were performed. The primary endpoints included quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY. Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY. The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY. Univariable sensitivity analyses revealed that the cost of PRL and the utility of progressed disease had the most significant impact on the ICER. To be considered cost-effective at a WTP threshold of $150,000 per QALY, the cost of PRL would need to be reduced by 71.34% in first-line treatment or 84.49% in second-line treatment. Based on current pricing, neither PRL as first-line nor second-line therapy was found to be cost-effective for patients with RET fusion-positive advanced NSCLC compared to chemotherapy. Reserving PRL until second-line therapy may be a compromise approach to maintaining control over healthcare expenses yet still achieving favorable clinical outcomes.


Effects of high-fat diets on body composition, hypothalamus NPY, and plasma leptin and corticosterone levels in rats.
We investigated the adipogenic effects of high-fat diets with different fat sources, as well as their influence on hypothalamus NPY content (NPY) and plasma corticosterone (Cs) and leptin (Lep) concentrations. In a 6-wk experiment performed in 28 male Wistar rats, high-fat diets (approx 60% of energy as fat) containing sunflower oil (S), rapeseed oil (R), palm oil (P), or lard (L) as the fat source were applied. Carcass composition was analyzed by standard methods; NPY, Cs, and Lep were determined by RIA method. Gas chromatography was applied to measure fatty acid composition of dietary fats. S group had the highest body fat content and Lep and the lowest Cs and NPY, while L rats had high Lep and the highest Cs and NPY. We conclude that the fatty acid composition of dietary fat is of high importance where effects of high fat diets on adiposity, as well as on plasma levels of both hormones and hypothalamus NPY content are concerned.


DHF-7 Ameliorates Behavioral Disorders and White Matter Lesions by Regulating BDNF and Fyn in a Mouse Model of Schizophrenia Induced by Cuprizone and MK-801.
Schizophrenia is a psychiatric disorder including multiple clinical symptoms such as severe psychosis and cognitive dysfunction. DHF-7 is a novel dihydroflavanone derivative that was designed and synthesized to treat schizophrenia. This study aimed to investigate the effects and mechanisms of DHF-7 in a mouse model of schizophrenia induced by a combination of cuprizone and MK-801. After intragastric administration of DHF-7 for 7 weeks, open field, Y-maze, and novel object recognition tests were performed to detect behavioral changes in the mouse model. White matter lesions and myelin loss were determined using transmission electron microscopy and oil red O staining. Western blotting and immunohistochemistry were used to detect the expression of the related proteins. The results showed that DHF-7 treatment significantly improved cognitive impairment and positive symptoms in the model mice. Moreover, DHF-7 alleviated white matter lesions and demyelination and promoted the differentiation and maturation of oligodendrocytes for remyelination in the corpus callosum of model mice. The mechanistic study showed that DHF-7 increased the expression of brain-derived neurotrophic factor and phosphorylated Fyn, thus activating the tyrosine kinase receptor B (Trk B)/Fyn/N-methyl-D-aspartate receptor subunit 2 B (NMDAR2B) and Raf/mitogen-activated protein kinase (MEK)/ extracellular signal-related kinase (ERK) signaling pathways. Our results provide an experimental basis for the development of DHF-7 as a novel therapeutic agent for schizophrenia.


[Multifunctional 14-3-3 proteins of plant cell].
The 14-3-3 proteins are a family of highly conserved proteins found in all eukaryotes - from the yeasts to mammals. They regulate several cellular processes recognizing unique conservative, mostly phosphorylated motif of partner proteins. Binding of the 14-3-3 proteins regulates their partners through a variety of mechanisms, such as altering their catalytic activity, subcellular localization, stability or altering their interactions with other protein molecules. The native 14-3-3 proteins are present in form of homo- and hetero-dimers. The most structurally variable N-and C-termini are responsible for isoform specific protein-protein interactions, and cellular localization. In plant cell, 14-3-3 proteins appear to play an important role in regulation of key enzymes of carbon and nitrogen metabolism, modulation ion pumps and channels. They are also involved in signal transduction pathways and even in gene expression.


Mechanisms mediating responsiveness to beta-adrenergic stimulation after coronary reperfusion in conscious dogs.
The goal of this study was to assess beta-adrenergic receptor (beta-AR) signaling mechanisms in mediating physiological responses to sympathomimetic amines after 45 min coronary artery occlusion followed by 45 min reperfusion. At this time, isoproterenol (Iso) infusion (0.1 microgram/kg-1.min-1, n = 5) increased percent wall thickening in previously ischemic subendocardium (Endo) more than in nonischemic Endo (12.6 +/- 1.2 vs. 7.2 +/- 0.6%, P < 0.05), whereas forskolin (25 nmol.kg-1.min-1, n = 6) elicited the opposite effect (3.6 +/- 0.6 vs. 10.4 +/- 2.8%, P < 0.05). During Iso and forskolin infusions increases in regional myocardial blood flow in the previously ischemic zone were similar to the nonischemic zone. In all groups, total beta-AR density was depressed in previously ischemic Endo compared with nonischemic Endo (65 +/- 7 vs. 82 +/- 8 fmol/mg, P < 0.05), but the fraction of beta-AR binding agonist with high affinity increased (82 +/- 4 vs. 49 +/- 1%, P < 0.05). The changes in beta-AR were associated with a decrease in Iso-stimulated adenylyl cyclase (22 +/- 8%), a decrease in guanosine 5'-triphosphate (GTP)-stimulatory protein (Gs) (23 +/- 6%), and a decrease in inhibitory G proteins (16 +/- 4%). However, regional Endo functional responsiveness to beta-AR stimulation was enhanced in reperfused myocardium in response to Iso but not to forskolin. Thus the mechanism of increased number of beta-AR binding agonist with high affinity in previously ischemic myocardium predominated over persistent downregulation of total beta-AR density and reductions in Gs and adenylyl cyclase activity and correlated best with the physiological response to beta-AR stimulation. These data may also suggest that Iso exerts an action distal to adenylyl cyclase in previously ischemic myocardium.


Improved liquid chromatographic determination of nine currently used (fluoro)quinolones with fluorescence and mass spectrometric detection for environmental samples.
An HPLC method using C18-modified silica as stationary phase has been developed for environmental trace analysis of nine (fluoro)quinolones. Detection is done by fluorescence measurement or MS using the modes of SIM and selected reaction monitoring (SRM). Best separation is achieved with a gradient consisting of 50 mM formic acid and methanol, which is fully compatible with MS coupling. LOQs (S/N of 10) for fluorescence detection are between 10 and 60 microg/L, depending on the analyte. MS detection (SIM and SRM) yields LOQs that are better by a factor of at least an order of magnitude. Sample preconcentration and sample clean-up is accomplished by SPE (preconcentration factor of 1000), leading to LOQs in the low ng/L range. Recoveries of the preconcentration procedure are better than 80% for all analytes. The suitability for real samples has been demonstrated by analyzing surface waters, municipal waste waters, sewage treatment plant effluents, sewage sludge, and sediment taken from rivers and fish ponds. The method should also be useful for determination of residues of (fluoro)quinolones in food or other matrices. The degradation of the (fluoro)quinolones has been examined over 5 days in order to get information about the decomposition rate and the degradation products eventually occurring in the environment.


Ethnic and socioeconomic disparities in dermatology.
Ethnic and socioeconomic disparities exist within healthcare. Specifically, minority group members experience more deleterious health outcomes than do majority group members. In this paper, we explore the factors that influence such variety, with a focus on the field of dermatology, in an attempt to understand the ways to improve minority group results. We also highlight how the prevalence of mental health issues within minority group and low socioeconomic status individuals can differentially influence dermatological disease states, such as the relationship between depression and psoriasis.


T cells signaled by NF-kappa B- dendritic cells are sensitized not anergic to subsequent activation.
Paradoxically, while peripheral self-tolerance exists for constitutively presented somatic self Ag, self-peptide recognized in the context of MHC class II has been shown to sensitize T cells for subsequent activation. We have shown that MHC class II(+)CD86(+)CD40(-) DC, which can be generated from bone marrow in the presence of an NF-kappa B inhibitor, and which constitutively populate peripheral tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance. In this study, we show that CD40(-) human monocyte-derived dendritic cells (DC), generated in the presence of an NF-kappa B inhibitor, signal phosphorylation of TCR zeta, but little proliferation or IFN-gamma in vitro. Proliferation is arrested in the G(1)/G(0) phase of the cell cycle. Surprisingly, responding T cells are neither anergic nor regulatory, but are sensitized for subsequent IFN-gamma production. The data indicate that signaling through NF-kappa B determines the capacity of DC to stimulate T cell proliferation. Functionally, NF-kappa B(-)CD40(-)class II(+) DC may either tolerize or sensitize T cells. Thus, while CD40(-) DC appear to "prime" or prepare T cells, the data imply that signals derived from other cells drive the generation either of Ag-specific regulatory or effector cells in vivo.


Making the case for lead safe housing: Downstream effects of lead exposure on outcomes for children and youth.
Lead based paint is a predominate source of lead exposure in children, which has a documented negative effect on their health and development. Despite public health efforts, the housing stock in disinvested neighborhoods in many cities continues to present significant risk of childhood lead exposure. In this article, we describe how a multi-agency integrated data system was used to document the impact of lead exposure on indicators of child and youth development as recorded in educational and human service systems. By tracking administrative data for two cohorts of Cleveland, Ohio children from birth to early adulthood and using rigorous matching methods to reduce confounders when comparing those with and without elevated blood lead levels, we document negative effects on developmental, behavioral and socio-economic outcomes due to early childhood lead exposure. The magnitude of disparities between individuals who had elevated blood lead levels (≥5 μg/dL) in early childhood, compared to their matched counterparts, is in the ranges of 20-40%. The analysis is framed by clarifying the context, assumptions and limitations associated with the use of administrative data. This type of information has been useful in illuminating the burden of lead exposure for children, families and youth serving agencies and engaging public officials, landlords and residents in initiatives to bring housing up to lead safe standards.


Aerobic Exercise Suppresses Atherosclerosis Through Adiponectin-Nuclear Transcription Factor κB Pathway in Apolipoprotein E-deficient Mice.
We aimed to investigate the therapeutic effect of aerobic exercise on atherosclerosis (AS) in apolipoprotein E-deficient mice and the adiponectin (ApN)-nuclear transcription factor κB (NF-κB) pathway involved in the related anti-inflammation. ApoE-deficient mice with AS (AS+C), and ApoE-deficient mice with AS and aerobic exercise (AS+E) were investigated for body weight and visceral fat. Pathomorphology of the aortic vascular wall was qualitatively and quantitatively evaluated with hematoxylin-eosin staining. The ApN messenger RNA level in adipose tissue and ApN level in plasma were determined. The aortic adiponectin receptor 1 (AdipoR1) and NF-κB levels were determined with western blot. There was no significant difference in body weight between the AS+C and the AS+E groups, but visceral fat in the AS+E group was significantly smaller than that in the AS+C group. Aortic vascular wall fiber board in the AS+C group broke, but this aortic disease in the AS+E group was obviously alleviated. The AS+E group showed a smaller neointimal hyperplasia and plaque area compared with AS+C group. After a high-fat diet, the ApN levels in both adipose tissue and plasma were decreased in the AS+C group and returned to a relative high level in the AS+E group. The expression of AdipoR1 protein in the AS+C group was significantly lower than those in the AS+E group. As for NF-κB protein, its enhanced expression in the AS+C group was reversed to a relatively low level in the AS+E group. Aerobic exercise suppressed AS through the ApN-NF-κB pathway in ApoE-deficient mice.


Assessing the Awareness Regarding Osteoarthritis and Its Related Risk Factors Among Women in Aseer Central Hospital.
Background Osteoarthritis (OA) is the most common form of arthritis worldwide and is characterized by the gradual loss of joint cartilage, leading to stiffness, discomfort, and restricted movement. This research aims to assess the knowledge of obese women in the Aseer region regarding OA and its associated risk factors. OA predominantly affects the knees, hands, and hips, with knee OA being particularly significant due to its high incidence rate and early onset in obese women. In Saudi Arabia, there are varying levels of awareness among the population, but no study has focused on obese females. This study seeks to address this gap and enhance the understanding of OA in this demographic. Methodology A cross-sectional research design was employed using a self-administrated questionnaire collected by a group of trained data collectors who distributed the questionnaires throughout the clinics of Aseer central hospital. The questionnaire was divided into two sections. The first section collected demographic data about the participants, and the second section was a 20-item questionnaire about OA and its related risk factors. The study was conducted in the Aseer region. A total of 278 subjects (female) were included in the study. Statistical analysis was performed using SPSS version 18.104.22.168 (IBM Corp., Armonk, NY, USA). Results This study analyzed the sociodemographic characteristics of 278 participants. All participants were female, were young to middle-aged adults, and had a collegiate education. On average, participants were overweight, with varying knowledge levels about OA. While some correctly identified symptoms and risk factors. Many participants responded with "I Don't Know" regarding joint stiffness as a symptom (37.7%). Comparing knowledge among different body mass index groups revealed no significant differences, except for misconceptions about the cause of OA among overweight individuals (39.06%). Conclusions This study's findings underscore the practical implications for patient education and healthcare strategies. The varying levels of awareness among obese women in the Aseer region regarding OA emphasize the need for increased education and targeted health promotion interventions. Addressing misconceptions and improving knowledge can enhance treatment plans and contribute to better patient outcomes. Understanding these knowledge gaps is crucial for improving patient education, healthcare strategies, and OA management.


Role for Functional SOD2 Polymorphism in Pulmonary Arterial Hypertension in a Chinese Population.
The superoxide dismutase 2 (SOD2) gene is a pivotal part of oxidative stress system, which could induce the onset of pulmonary arterial hypertension (PAH). In this study, we quantified the influence of a SOD2exonic polymorphism (rs4880) on PAH susceptibility. We genotyped this single nucleotide polymorphism (SNP) by TaqMan, and evaluated its association with PAH susceptibility in a case-control study of 460 patients and 530 controls in China. There were significant differences between PAH cases and controls in both CC and TC+CC genotypes (p = 0.013 and p = 0.010, respectively). Furthermore, the number of variant alleles followed a dose-response manner (p trend was 0.023). Besides, the mRNA level and protein expression also indicated that the C allele of this variant decreased the expression of SOD2 gene (p = 0.004 in mRNA level and p = 0.012 in protein level) after the transfection of plasmids containing the different genotype of rs4480. There is significant association between SOD rs4880 polymorphism and the PAH susceptibility, and this polymorphism influenced PAH susceptibility by altering the expression of SOD2.


A New Era in Salivary Gland Carcinoma Treatment: A Case Report.
Salivary gland cancers are rare and heterogenous malignancies which makes it hard to standardize treatments with good evidence levels. The localized disease approach is well established, with surgery to the primary site and adjuvant radiation therapy in patients with high-risk features. Treatment of advanced disease should be multidisciplinary. Local approaches, which include radiation therapy, surgery, and thermoablation, among others, have the potential to achieve durable disease control with low toxicity. Chemotherapy has shown disappointing results, so systemic treatment should be guided by actionable genetic alterations, which in salivary gland cancers rely on the histologic type. When directed molecular tests are not useful, a multigene panel should be performed. This case is a good example of how to integrate all these possible tretaments in clinical practice, including molecular testing and target treatment.


[Initial experiences with ambulatory ligament suture of the fresh ligament rupture of the upper ankle joint using local anesthesia].
Reported in this paper is preliminary experience obtained from outpatient suturing in local anaesthesia of recent rupture of fibular ligaments. An indication of this kind is valid for all cases of established rupture of ligaments, with due consideration to be given to individual factors. The method is extensively described. Preliminary short-time results so far recorded from 18 outpatient cases of ligament suturing in local anaesthesia appear to underscore this therapeutic approach as optional in acute situations. Reference is made to early functional therapy to avoid immobilisation damage, and a therapeutic concept is proposed.


Femoroacetabular Impingement in Adolescent Athletes: Outcomes of Arthroscopic Management.
Adolescent athletes with symptomatic femoroacetabular impingement (FAI) may respond well to arthroscopic intervention. This study reports the outcomes of arthroscopic treatment for symptomatic FAI in adolescents. Case series; Level of evidence, 4. Included in this study were 104 consecutive athletes (116 hips) younger than 18 years who underwent arthroscopic correction of symptomatic FAI with a minimum 2-year follow-up. All patients were prospectively assessed with the modified Harris Hip Score (mHHS). Pincer lesions were defined by acetabular overcoverage or retroversion with an accompanying labral injury, and cam lesions were defined by loss of sphericity of the femoral head with associated acetabular articular failure. The average follow-up was 38 months (range, 24-120 months), and the average patient age was 16 years (range, 12-17 years), with 47 male and 57 female patients. There were 67 combined, 33 cam, and 16 pincer lesions. The average improvement on the mHHS was 25 points (average score: 69 preoperatively, 94 postoperatively), with 97% improved and 94% good and excellent results. Athletes returned to their sport after 100 procedures (86%). After 16 procedures, 5 patients were unable to return to sport, 6 chose not to, and 5 had completed their high school athletic careers. There were 2 complications, both transient pudendal nerve neurapraxias, that resolved within 2 weeks. Four patients underwent repeat arthroscopic surgery, and 1 underwent periacetabular osteotomy. This study reports favorable outcomes of arthroscopic treatment of FAI among adolescent athletes. A high proportion improved, although only 87% actually returned to their sport. Return to sport may be influenced by factors other than just the success of the procedures.


The basics of phosphate metabolism.
Phosphorus is an essential mineral that is under the form or inorganic phosphate (Pi) required for building cell membranes, DNA and RNA molecules, for energy metabolism, signal transduction or pH buffering. In bone, Pi is essential for bone stability under the form of apatite. Intestinal absorption of dietary Pi depends on its bioavailability and has two distinct modes of active transcellular and passive paracellular absorption. Active transport is transporter mediated and partly regulated, passive absorption depends mostly on bioavailability. Renal excretion is controlling systemic Pi levels, depends on transporters in the proximal tubule and is highly regulated. Deposition and release of Pi into and from soft tissues and bone has to be also tightly controlled. The endocrine network coordinating intestinal absorption, renal excretion and bone turnover integrates dietary intake, metabolic requirements with renal excretion and is critical for bone stability and cardiovascular health during states of hypophosphatemia or hyperphosphatemia as evident from inborn or acquired diseases. This review provides an integrated overview over the biology of phosphate and Pi in the mammalian organism.


Serratia marcescens osteomyelitis in an infant.
Neutrophil dysfunction can result from oxidative burst defect or from glucose-6-phosphate dehydrogenase (G6PD) deficiency; we noted both in the same patient. A 4-month-old male infant with G6PD deficiency presented with swelling of the left middle finger, left leg, and right big toe. At 5 weeks of age he was hospitalized for fever for 2 days. A maternal uncle died at 5 years of age and a male maternal cousin died at the age of 21 months, both reportedly diagnosed with chronic granulomatous disease (CGD). On physical examination, he had a swollen erythematous left third finger, left distal leg swelling, and right big toe abscess. None of these areas was significantly tender. WBC was 18.7 x 10(3)/mm(3) with 37% PMN and 5% bands. The x-ray films showed osteomyelitis in the left third proximal phalanx and the distal right first metatarsal. Culture from the toe abscess grew Serratia marcescens. His neutrophil oxidative burst was tested by the dihydrorhodamine-123 assay and was markedly suppressed, typical of CGD. The mother and maternal grandmother were found to be CGD carriers. He was treated with i.v. antibiotics for 4 weeks and was discharged on prophylactic trimethoprim, itraconazole and interferon gamma, with substantial reduction in infections. Infection in this infant was unusual in its nature, in affecting multiple sites, and in its causative organism. Immune deficiency was suspected, particularly of the phagocytic component, but could not be attributed to his moderate degree of primary G6PD deficiency. Additional immunologic evaluation and the family history led to the diagnosis of X-linked CGD.


P16INK4A--A possible marker in HPV persistence screening.
The aim of this study was to investigate the correlation of p161NK4a expression levels with the cytological group of cervical carcinogenesis (NILM, ASCUS, LSIL, HSIL, cancer groups), in order to establish its value as potential diagnostic marker. The smears obtained from 50 women with/without suggestive HPV infection pathology were subjected to cytological investigations. The viral testing was based on the detection of HPV DNA using the INNOLIPA kit, while the semiquantitative expression levels of p16INK4a were estimated by RT-PCR. p16INK4a expression level was correlated with the cytological degree of cervical lesions. In LSIL patients, p16INK4a values were 1.36 times greater than in NILM subjects (p = 0.07). In HSIL/cancer patients, p16INK4a values were 2.38 times greater than in NILM patients (p = 0.002). We also noticed significant differences between ASCUS: HSIL group (p = 0.02) and LSIL: HSIL (p = 0.07) group. The p16INK4a expression level was dependent of HPV genotype, p16INK4a mRNA presence being correlated with the presence of hrHPV in low and high risk lesions.


First occurrence of Platycladus from the upper Miocene of Southwest China and its phytogeographic implications.
Platycladus Spach is native to Central China, but its natural occurrences are very difficult to establish. According to molecular phylogenetic data, this genus might have originated since the Oligocene, but no fossil record has been reported. Here, we describe eight foliage branches from the upper Miocene in western Yunnan, Southwest China as a new species, P. yunnanensis sp. nov., which is characterized by foliage branches spread in flattened sprays, and leaves decussate, imbricate, scale-like and dimorphic. The leaves are amphistomatic, and the stomata are elliptical or oblong, haplocheilic, and monocyclic type. Based on a detailed comparison with the extant genera of Cupressaceae sensu lato, our fossils are classified into the genus Platycladus. The occurrence of P. yunnanensis sp. nov. indicates that this genus had a more southernly natural distribution in the late Miocene than at present. Molecular phylogeny and fossil records support a pre-Oligocene common ancestor for the genera Platycladus, Microbiota and Calocedrus. The separation of the three taxa was most likely caused by the arid belt across Central China during the Oligocene. In addition, the cooling down of the global temperature and the strengthening of Asian monsoon since the Miocene will further promote the migration of these genera.


Comparison of radiography and computed tomography in evaluating posterior indirect reduction of spinal canal bone fragment.
This article describes a retrospective study of patients who underwent posterior indirect reduction procedures for thoracolumbar burst fractures. The goal of this study was to explore a simple and effective method for evaluating the reduction of spinal canal fragments during posterior indirect reduction procedures.Sixty-four burst fractures with retropulsed bone fragments encroaching the spinal canal at the thoracolumbar junction were performed. C-arm fluoroscopy was used to evaluate the spinal canal fragments' reduction. A standard lateral view of the thoracolumbar spine was set up. When a continuous and smooth posterior vertebral body line of the injured vertebrae appeared, similar to below and above the vertebrae, the spinal canal bone fragment was considered to be satisfactorily reduced. The midsagittal diameter of the injured segment was measured on preoperative and postoperative computed tomography (CT) scans. Narrowing of the midsagittal diameter of the injured segment was improved from 41.4%+/-15.9% to 13.7%+/-9.7%. The correction value was 27.6%+/-15.6%. All pre- and postoperative outcome variables had statistical significance (P<.01). Forty-two patients experienced a restored posterior vertebral body line with a continuous and smooth vertical line, indicating that the fragment reduction was satisfactory. Post-operative CT showed that the spinal canal compromise was <10% (range, 0%-9.8%; mean, 6.1%+/-2.9%).Continuous and smooth posterior vertebral body line imaging is a simple and effective method to judge the reduction of a bone fragment retropulsed into the spinal canal. It can provide evidence as to whether a laminotomy and pushing the bone fragment are necessary during posterior surgery.


Requirement of Pygopus 2 in breast cancer.
The development of novel therapeutic strategies for breast cancer requires the identification of molecular targets involved in malignancy. Human Pygopus (Pygo)-1 and -2 are recently discovered components of the Wnt signaling pathway required for beta-Catenin/Tcf dependent transcription in embryos and colorectal cancer cells, but the role of these proteins in malignant cell growth and survival has not yet been determined. We report the expression and requirement for proliferation of hPygo2 in breast cancer cells. hPygo2 protein was overexpressed in malignant breast tumors and in the nuclei of five breast cancer cell lines, but was not expressed in the nuclei of non-malignant breast cells. Phosphorothioated antisense oligonucleotides were used to specifically knockdown expression hPygo2 in Mcf-7 and MDA-MB-468 cell lines. hPygo2 was required for the growth, in tissue culture and anchorage-independent assays, of both cell lines and for the expression of the Wnt target gene Cyclin D1. We conclude that hPygo2 is highly expressed in, and required for the growth of breast carcinoma cells.


Combined osteotomy in patients with severe Legg-Calve-Perthes disease.
The purpose of the present study was to describe the clinical and radiographic results obtained with the combined osteotomy in patients with severe Legg-Calve-Perthes disease. During 2000 to 2010 patients with Legg-Calve-Perthes disease who intervened with combined osteotomy at Siriraj Hospital were evaluated. Clinical evaluation was categorized by Ratliff classification and radiographic evaluation was performed by Moss index, Lloyd Roberts classification and Stulberg classification. Twenty patients intervened with combined osteotomy. There were nineteen males and one female with a mean age of 7.7 years. The average follow-up was 49 months. Nine had a Catterall III and eleven had a Catterall IV. According to Herring classification, fourteen patients were Herring B and six were Herring C. In accordance with the Ratliff classification, the postoperative clinical results: fifteen good, three fair and two poor. According to Mose scale, eight patients had good results, nine had fair results and three had poor results. According to the Lloyd-Roberts classification eight patients had good results, nine had fair results and three had poor results. Based on the Stulberg classification, there were ten patients in class II, nine in class III and one in class V. The surgical treatment for severe Perthes disease with the best expected outcome is still a challenge. According to the results reported here, the combined osteotomy is safe and effective procedure for patients with severe Perthes disease in whom the femoral head cannot be contained by conventional forms of treatment.


Oral self-care among adults with diabetes in Finland.
The importance of maintenance and promotion of periodontal health is emphasized among people with diabetes because of their high risk for periodontal diseases. Our aim was to evaluate oral health behavior and its determinants among adults with diabetes in Finland. The population of the questionnaire study consisted of 420 systematically selected adults with diabetes, who were members of a national diabetes register. The response rate was 80%. Questions focused on self-treatment, -prevention, and -diagnosis of oral diseases, utilization of dental services, and knowledge and attitudes toward oral health among adult people with diabetes. Oral self-care was evaluated in the framework of the New Century model of oral health promotion. The proportion of edentulous subjects was 23%, and these were excluded from further analysis. Self-reported twice-a-day brushing among dentate participants was significantly more common among women and the highly educated, but was less common compared with earlier studies among Finnish adults. A quarter of those surveyed reported never cleaning interdental surfaces, with the number of daily cleaners being nearly equal (27%). Age 40 years or over and recent treatment by a private dentist were significant predictors for daily interdental cleaning. The proportion of those who had attended a dental appointment within the last year was 63%, and the main reason for the last dental visit was an emergency among almost one-fifth of those surveyed. A need exists for further promotion of oral self-care among adults with diabetes. Support by dental and other health care professionals involved in diabetes care should be encouraged.


Hypoxia Impairs Mesenchymal Stromal Cell-Induced Macrophage M1 to M2 Transition.
The transition of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype is crucial for the progression of normal wound healing. Persistent M1 macrophages within the injury site may lead to an uncontrolled macrophage-mediated inflammatory response and ultimately a failure of the wound healing cascade, leading to chronic wounds. Mesenchymal stromal cells (MSCs) have been widely reported to promote M1 to M2 macrophage transition; however, it is unclear whether MSCs can drive this transition in the hypoxic environment typically observed in chronic wounds. Here we report on the effect of hypoxia (1% O2) on MSCs' ability to transition macrophages from the M1 to the M2 phenotype. While hypoxia had no effect on MSC secretion, it inhibited MSC-induced M1 to M2 macrophage transition, and suppressed macrophage expression and production of the anti-inflammatory mediator interleukin-10 (IL-10). These results suggest that hypoxic environments may impede the therapeutic effects of MSCs.


Color-discrimination performance of pigeons: effects of reward.
Performance of two pigeons given tasks in discriminating colors was examined on trials before and after they had occasionally received rewards for pecking when exposed to light of specific wavelengths. After a reward, the probability that the birds would respond to light svtimuli that were never rewarded was higher than before the reward was given, but paradoxically the birds showed no general decline in their ability to differentiate between stimuli at wavelengths 1 millimicron apart.


Metamotivational states displayed using differential digital photoplethysmograms while listening to music and noise.
The theory of psychological reversal postulates that individuals switch between paratelic and telic metamotivational states. To observe the paratelic state as an actual phenomenon using a physiological index, a correlation between changes in P-wave amplitudes of differential digital photoplethysmograms (deltaDPG) of 24 undergraduate students while listening to music and changes in mood pre- to postlistening was investigated. Elevation in arousal of the sympathetic nervous system, as indicated by deltaDPG. was related to improvement in mood. It was assumed that the subjects who were aroused more while listening to music enjoyed the high arousal more and were more susceptible to a pleasant state. This was interpreted as a paratelic state. In listening to a noise condition using another 24 undergraduate students, however, the correlation was inverse of that for the music condition. It was assumed that the subjects who spent more effort in identifying stimuli showed more elevation in arousal of the sympathetic nervous system and more aggravation in mood. This was interpreted as a telic state.


Health promotion: preventing unwanted teenage pregnancies.
In the second of two articles looking at health promotion projects addressing targets set out in the Health of the Nation White Paper (1), the author describes the work of a North Staffordshire family planning clinic which specifically targets young people with contraceptive advice and services including pregnancy testing, rubella vaccination and cervical cytology. Hundreds of young people have attended the clinic since it opened in 1990 and the scheme has been so successful that a similar clinic has been opened in another area.


Decompression Sickness Treatment Using a Pressure Suit After Loss of Spacecraft Atmosphere.
BACKGROUND: Loss of spacecraft atmosphere (LOA) during Earth-Moon transit may require up to 144 h of pressure suit operations. This work investigates the feasibility of DCS treatment in this paradigm and discusses the operational and engineering implications.METHODS: Three scenarios of LOA-induced DCS were considered: a permanent LOA secondary to a 0.25-in (0.64 cm) hole (unrecoverable cabin leak), a transient LOA, and a permanent LOA with early suit over-pressurization (beyond suit specification). Each was simulated in the context of the current Orion spacecraft operational concept with regards to atmosphere and anticipated cabin depress profile. Probability of DCS symptom resolution (P(SR)) was estimated using the previously derived Hypobaric DCS Treatment Model, with ΔP calculated from a Three Region Well-Stirred Tissue (3RWT) bubble dynamics model. Analysis was conducted and analogies drawn from experiences with the development and testing of the Orion Crew Survival System (OCSS).RESULTS: Maintaining 8 psia at 100% Fio₂ following LOA resulted in an eventual halt and regression of bubble growth with a P(SR) of 87% (at 8 h, time to symptom onset (Ts) = 105 min, with ambulation). If cabin atmosphere was not restored and psia dropped to 4.3, bubble growth returned, but again eventually slowed and regressed over time (P(SR) = 75% at 21 h). If the leak is repaired within the 8-h period, 8 psid (psia = 22.7) resulted in P(SR) of greater than 95%. Similarly, if the suit was over-pressurized (12 psid/psia) within 3 h after LOA, P(SR) exceeded 95%.DISCUSSION: A launch/entry pressure suit represents a contingency option for DCS management in the event of LOA.Greene MR, Jacobs SE. Decompression sickness treatment using a pressure suit after loss of spacecraft atmosphere. Aerosp Med Hum Perform. 2020; 91(7):571-577.


Psychosis: from mental disorder to disease concept.
This article traces the development of the concept of psychosis from its being coined as a general term for mental disorder in 1845 by the Austrian psychiatrist Ernst von Feuchtersleben until its reification as a disease concept in the twentieth century by the German psychiatrist and pupil of Kraepelin Kurt Schneider.


Nicotine withdrawal disrupts new contextual learning.
Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual fear conditioning. C57BL/6J mice trained in CPP exhibited a significant preference for an initially non-preferred chamber that was paired with 0.35 mg/kg nicotine. Following CPP, mice were implanted with mini-osmotic pumps containing 6.3 mg/kg/d nicotine or saline. Pumps were removed twelve days later and nicotine CPP was retested 24 h later. Mice withdrawn from chronic nicotine exhibited CPP, suggesting that older drug-context associations are not disrupted by nicotine withdrawal. One hour later, the same mice were trained in contextual and cued fear conditioning; nicotine withdrawal disrupted contextual but not cued fear conditioning. A subsequent experiment demonstrated that nicotine withdrawal did not disrupt recall of contextual or cued fear conditioning when acquisition occurred before nicotine withdrawal. These data suggest that nicotine withdrawal disrupts new contextual learning, but does not alter contextual learning that occurred before withdrawal.


Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets.
Insulin secretion from the 2,000-3,000 beta-cells in an islet is a highly synchronized activity with discharge of insulin in coordinate secretory bursts at approximately 4-min intervals. Insulin secretion progressively declines in type 2 diabetes and following islet transplantation. Both are characterized by the presence of islet amyloid derived from islet amyloid polypeptide (IAPP). In the present studies, we examined the action of extracellular human IAPP (h-IAPP) on morphology and function of human islets. Because oligomers of h-IAPP are known to cause membrane disruption, we questioned if application of h-IAPP oligomers to human islets would lead to disruption of islet architecture (specifically cell-to-cell adherence) and a decrease in coordinate function (e.g., increased entropy of insulin secretion and diminished coordinate secretory bursts). Both hypotheses are affirmed, leading to a novel hypothesis for impaired insulin secretion in type 2 diabetes and following islet transplantation, specifically disrupted cell-to-cell adherence in islets through the actions of membrane-disrupting IAPP oligomers.


Pentraxin 3 promotes long-term cerebral blood flow recovery, angiogenesis, and neuronal survival after stroke.
Restoration of cerebral blood flow (CBF) and upregulation of angiogenesis are crucial for brain repair and functional recovery after cerebral ischaemia. Pentraxin 3 (PTX3) is a key regulator of angiogenesis and is emerging as a promising target for cerebrovascular repair after stroke. Here, we investigated for the first time the role of PTX3 in long-term CBF, angiogenesis, and neuronal viability after ischaemic stroke induced by transient middle cerebral artery occlusion (MCAo). Lack of PTX3 had no effect on early brain damage, but significantly impaired restoration of CBF, 14 and 28 days after MCAo, compared to wild-type (WT) mice. Immunohistochemical analysis revealed that PTX3 KO mice have significantly greater neuronal loss, significantly decreased vessel diameter, vessel proliferation, vascular density, and reactive astrocytes and decreased expression of vascular endothelial growth factor receptor 2 (VEGR2), vascular extracellular matrix (ECM)-proteins (collagen IV, laminin), and integrin-β, in the ipsilateral (stroke) hemisphere compared to WT mice, 28 days after MCAo. Therefore, PTX3 promotes sustained long-term recovery of CBF, angiogenesis, and neuronal viability after cerebral ischaemia. Collectively, these findings demonstrate the potential and clinical relevance of PTX3 as a promising therapeutic target, providing sustained long-term post-stroke neurovascular repair and reducing the loss of neurons. KEY MESSAGES: Pentraxin 3 (PTX3) is a key regulator of angiogenesis and is emerging as a promising target for cerebrovascular repair after stroke. Restoration of cerebral blood flow (CBF) and angiogenesis are crucial for brain repair and functional recovery after cerebral ischaemia. PTX3 promotes sustained long-term recovery of CBF, angiogenesis, and neuronal viability after cerebral ischaemia.


Impact of Ketamine on Opioid Use and Persistent Pain After Cytoreductive Surgery with Hyperthermic Chemotherapy.
Persistent pain and opioid use can be devastating after cytoreductive surgery (CRS) and hyperthermic intraoperative chemotherapy (HIPEC). We conducted a retrospective study to investigate the impact of ketamine use on postoperative complications and persistent and chronic pain after CRS-HIPEC. Ketamine reduced perioperative opioid use before and after implementation of recovery after surgery programs. Ketamine did not impact the formation of persistent and chronic pain formation and long-term opioid use. Postoperative complications and postoperative re-operations were independent predictors of persistent pain. Interestingly, the risk of having a complication was increased by 1% for every doubling in opioids used intraoperatively. Ketamine use reduces perioperative opioid consumption in patients undergoing CRS-HIPEC, but it is not associated with improvements in long-term opioid use and chronic pain.


Evidence at time of regulatory approval and cost of new antibiotics in 2016-19: cohort study of FDA approved drugs.
To review the clinical evidence, regulatory background, and cost of antibiotics approved by the US Food and Drug Administration (FDA), 2016-19. Cohort study of FDA approved drugs. FDA databases, ClinicalTrials.gov, and drug labelling. Launch prices were extracted from IBM Micromedex Red Book. Antibiotics approved by the FDA from October 2016 to December 2019 were identified, and key features of their clinical development were extracted from publicly available FDA databases, ClinicalTrials.gov, and drug labelling. Launch prices were extracted from IBM Micromedex Red Book to evaluate the cost of treatment against comparators. 15 new antibiotics received at least one special regulatory designation and were supported by a median of two pivotal trials. More than half of the pivotal trials used an active control non-inferiority design. All drugs were approved based on surrogate outcome measures. 52 postmarketing requirements and commitments were included across the cohort (median 3 for each drug). From January 2021, 27 postmarketing requirements and commitments were listed as pending, seven as ongoing, three as delayed, one as submitted, eight as released, and four as fulfilled. The most expensive new antibiotic was pretomanid at $36 399 (£29 618; €34 582) for a course of treatment, and the least expensive was rifamycin ($176). Cost ratios between study drugs and comparators ranged from 0.48 to 134. New antibiotics have been approved by the FDA in recent years mostly based on fewer, smaller, and non-inferiority pivotal trials that often used surrogate outcome measures but were commonly more costly. Efforts to incentivise the development of antibiotics should balance growing the antibiotic development pipeline with ensuring that clinical trials provide clinically relevant evidence of effectiveness in showing added benefits for the patient.


Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology.
Tularemia is primarily caused by two subspecies of Francisella tularensis worldwide, ssp. tularensis (type A) and ssp. holarctica (type B), which were originally delineated by phenotypic differences. Application of molecular typing methods to investigate population structure of F. tularensis has confirmed that categorizing the two subspecies via phenotypic characteristics corresponds with genotypic differentiation. In addition, genotyping methods have demonstrated that both subspecies, type A and type B, can be further distinguished into subpopulations and, in some cases, biological relevance has been ascribed to these identified subpopulations. Genetic variation among both type A and type B subpopulations has been shown to correlate with differences in geographic distribution and has also been coupled to distinct ecological niches, animal hosts and replication foci. Among type A subpopulations, strain variation is linked to differing clinical manifestations in humans and virulence in mice. This article will highlight our current understanding of F. tularensis subpopulations, including methods for their detection, their observed epidemiologic differences, implications for public health and basic research programs, as well as future challenges yet to be solved.


Newer insulin analogs: advances in basal insulin replacement.
Basal insulin analog therapy is the most common method of introducing insulin replacement therapy for the majority of patients with type 2 diabetes mellitus. Long-acting insulin analogs provide relatively peakless and more physiologic insulin replacement therapy than neutral protaminated Hagedorn insulin. Recently 2 new basal insulin analogs have been developed with superior pharmacokinetic and pharmacodynamics properties; insulin degludec and a pegylated insulin lispro. These agents are generally well tolerated and have been evaluated in both type 1 and type 2 diabetes. In this article we review the results of clinical trials assessing the efficacy, safety and tolerability of these newer longer-acting insulin analogs. In general rates of hypoglycaemia in these trials were low, glucose control was comparable to currently available basal insulin analogs, and rates of nocturnal hypoglycaemia were significantly and substantially lower. While further study will be required, advances in basal insulin replacement may offer important advantages over existing options for starting insulin strategies.


Bacterial Community Associated with the Reef Coral Mussismilia braziliensis's Momentum Boundary Layer over a Diel Cycle.
Corals display circadian physiological cycles, changing from autotrophy during the day to heterotrophy during the night. Such physiological transition offers distinct environments to the microbial community associated with corals: an oxygen-rich environment during daylight hours and an oxygen-depleted environment during the night. Most studies of coral reef microbes have been performed on samples taken during the day, representing a bias in the understanding of the composition and function of these communities. We hypothesized that coral circadian physiology alters the composition and function of microbial communities in reef boundary layers. Here, we analyzed microbial communities associated with the momentum boundary layer (MBL) of the Brazilian endemic reef coral Mussismilia braziliensis during a diurnal cycle, and compared them to the water column. We determined microbial abundance and nutrient concentration in samples taken within a few centimeters of the coral's surface every 6 h for 48 h, and sequenced microbial metagenomes from a subset of the samples. We found that dominant taxa and functions in the coral MBL community were stable over the time scale of our sampling, with no significant shifts between night and day samples. Interestingly, the two water column metagenomes sampled 1 m above the corals were also very similar to the MBL metagenomes. When all samples were analyzed together, nutrient concentration significantly explained 40% of the taxonomic dissimilarity among dominant genera in the community. Functional profiles were highly homogenous and not significantly predicted by any environmental variables measured. Our data indicated that water flow may overrule the effects of coral physiology in the MBL bacterial community, at the scale of centimeters, and suggested that sampling resolution at the scale of millimeters may be necessary to address diurnal variation in community composition.


Prenatal programming of the female reproductive neuroendocrine system by androgens.
It has been clear for several decades that the areas of the brain that control reproductive function are sexually dimorphic and that the 'programming actions' of the male gonadal steroids are responsible for sex-specific release of the gonadotrophins from the pituitary gland. The administration of exogenous steroids to fetal/neonatal animals has pinpointed windows of time in an animals' development when the reproductive neuroendocrine axis is responsive to the organisational influences of androgens. These 'critical' periods for sexual differentiation of the brain are trait- and species-specific. The neural network regulating the activity of the gonadotrophin releasing hormone (GnRH) neurones is vital to the control of reproductive function. It appears that early exposure to androgens does not influence the migratory pathway of the GnRH neurone from the olfactory placode or the size of the population of neurones that colonise the postnatal hypothalamus. However, androgens do influence the number and the nature of connections that these neurones make with other neural phenotypes. Gonadal steroid hormones play key roles in the regulation of GnRH release acting largely via steroid-sensitive intermediary neurones that impinge on the GnRH cells. Certain populations of hormonally responsive neurones have been identified that are sexually dimorphic and project from hypothalamic areas known to be involved in the regulation of GnRH release. These neurones are excellent candidates for the programming actions of male hormones in the reproductive neuroendocrine axis of the developing female.


PUVA Induced Bullous Pemphigoid in a Patient with Mycosis Fungoides.
Background. Bullous pemphigoid is an autoimmune subepidermal blistering skin disease in which autoantibodies are directed against components of the basement membrane. The disease primarily affects the elderly people and in most of the patients inducing factors cannot be identified. Herein, we report a case of BP that occurred in a patient who was receiving PUVA therapy for the treatment of mycosis fungoides. Main Observation. A 26-year-old woman with mycosis fungoides developed blisters while receiving PUVA therapy. On physical examination tense bullae on the normal skin, remnants of blisters, and erosions were observed on her breasts, the chest wall, and the upper abdomen. Histopathological investigations revealed subepidermal blisters with eosinophilic infiltration and in direct immunofluorescence examination linear deposition of IgG along the basement membrane zone was observed. The diagnosis of bullous pemphigoid was also confirmed by ELISA and BIOCHIP mosaic-based indirect immunofluorescence test. Conclusions. PUVA therapy is an extremely rare physical factor capable of inducing bullous pemphigoid. So the development of blistering lesions during PUVA therapy may be suggestive sign of a bullous disease such as bullous pemphigoid and it should be excluded with proper clinical and laboratory approaches immediately after withdrawal of PUVA therapy.


Bryophytes and Organic layers Control Uptake of Airborne Nitrogen in Low-N Environments.
The effects of atmospheric nitrogen (N) deposition on ecosystem functioning largely depend on the retention of N in different ecosystem compartments, but accumulation and partitioning processes have rarely been quantified in long-term field experiments. In the present study we analysed for the first time decadal-scale flows and allocation patterns of N in a heathland ecosystem that has been subject to airborne N inputs over decades. Using a long-term 15N tracer experiment, we quantified N retention and flows to and between ecosystem compartments (above-ground/below-ground vascular biomass, moss layer, soil horizons, leachate). After 9 years, about 60% of the added 15N-tracer remained in the N cycle of the ecosystem. The moss layer proved to be a crucial link between incoming N and its allocation to different ecosystem compartments (in terms of a short-term capture, but long-term release function). However, about 50% of the 15N captured and released by the moss layer was not compensated for by a corresponding increase in recovery rates in any other compartment, probably due to denitrification losses from the moss layer in the case of water saturation after rain events. The O-horizon proved to be the most important long-term sink for added 15N, as reflected by an increase in recovery rates from 18 to 40% within 8 years. Less than 2.1% of 15N were recovered in the podzol-B-horizon, suggesting that only negligible amounts of N were withdrawn from the N cycle of the ecosystem. Moreover, 15N recovery was low in the dwarf shrub above-ground biomass (<3.9% after 9 years) and in the leachate (about 0.03% within 1 year), indicating still conservative N cycles of the ecosystem, even after decades of N inputs beyond critical load thresholds. The continuous accumulation of reactive forms of airborne N suggests that critical load-estimates need to account for cumulative effects of N additions into ecosystems.


[Evaluation of the value of cytological examination of group III, IV or V by comparison of histological examination results].
The agreement was studied of cytological examination of group III, IV, and V with the results of histopathological examination. The material consisted of 289 female patients who were referred to the department with the results of examinations carried out in cytological counselling centres outside the department. The attention was paid to age and obstetric history of the patients. The agreement of results was found in half the total number of cases. In 43.5% cytological evaluation was falsely positive, and in 7% falsely negative. The greatest variety of disease progression was found in the III cytological group.


Goldmine integrates information placing genomic ranges into meaningful biological contexts.
Bioinformatic analysis often produces large sets of genomic ranges that can be difficult to interpret in the absence of genomic context. Goldmine annotates genomic ranges from any source with gene model and feature contexts to facilitate global descriptions and candidate loci discovery. We demonstrate the value of genomic context by using Goldmine to elucidate context dynamics in transcription factor binding and to reveal differentially methylated regions (DMRs) with context-specific functional correlations. The open source R package and documentation for Goldmine are available at http://jeffbhasin.github.io/goldmine.


Diagnosing, Typing, and Staging of Renal Cell Carcinoma by Designer Matrix-Based Urinary Metabolic Analysis.
Molecular diagnosing, typing, and staging have been considered to be the ideal alternatives of imaging-based detection methods in clinics. Designer matrix-based analytical tools, with high speed, throughout, efficiency and low/noninvasiveness, have attracted much attention recently for in vitro metabolite detection. Herein, we develop an advanced metabolic analysis tool based on highly porous metal oxides derived from available metal-organic frameworks (MOFs), which elaborately inherit the morphology and porosity of MOFs and newly incorporate laser adsorption capacity of metal oxides. Through optimized conditions, direct high-quality fingerprinting spectra in 0.5 μL of urine are acquired. Using these fingerprinting spectra, we can discriminate the renal cell carcinoma (RCC) from healthy controls with higher than 0.99 of area under the curve (AUC) values (R2Y(cum) = 0.744, Q2 (cum) = 0.880), as well, from patients with other tumors (R2Y(cum) = 0.748, Q2(cum) = 0.871). We also realize the typing of three RCC subtypes, including clear cell RCC, chromophobe RCC (R2Y(cum) = 0.620, Q2(cum) = 0.656), and the staging of RCC (R2Y(cum) = 0.755, Q2(cum) = 0.857). Moreover, the tumor sizes (threshold value is 3 cm) can be remarkably recognized by this advanced metabolic analysis tool (R2Y(cum) = 0.710, Q2(cum) = 0.787). Our work brings a bright prospect for designer matrix-based analytical tools in disease diagnosis, typing and staging.


Advice, authority and autonomy in shared decision-making in antenatal screening: the importance of context.
Shared decision-making (SDM) has been widely advocated across many branches of healthcare, yet there is considerable debate over both its practical application and how it should be examined or assessed. More recent discussions of SDM have highlighted the important of context, both internal and external to the consultation, with a recognition that decisions cannot be understood in isolation. This paper uses conversation analysis (CA) to examine how decision-making is enacted in the context of antenatal screening consultations in Hong Kong. Building on previous CA work (Collins et al. , Toerien et al. 2013), we show that, whilst previously identified formats are used here to present the need for a decision, the overriding basis professionals suggest for actually making a decision in this context is the level of worry or concern a pregnant woman holds about potential foetal abnormality. Professionals take an unknowing 'epistemic stance' (Heritage ) towards this worry, and hence step back from involvement in decision-making. We argue that this is linked to the non-directive ethos that prevails in antenatal screening services, and suggest that more research is needed to understand how the enactment of SDM is affected by wider professional contexts and parameters.


Bilateral agenesis of the hippocampal dentate gyrus in a neurologically normal adult.
Ontogenic development of granule cells in the hippocampal dentate gyrus is influenced by genes including WNT3, EMX2, NEUROD, and LEF1. Dentate granule cells continue to be generated from stem cell precursors postnatally and during adult life, and are implicated in normal and abnormal neurological function. Developmental privation of dentate granule cells is rare and essentially always occurs in the context of other neurodevelopmental abnormalities. We have found no previous reports of severe, selective agenesis of dentate granule cells in humans. A gross and microscopic examination of the brain included appropriate histochemical and immunohistochemical preparations and examination of the hippocampal formation at multiple levels bilaterally. This neurologically normal 82-year-old man was found to have bilateral agenesis of the hippocampal dentate gyrus, no identifiable dentate granule cells, and moderate disorganization of the pyramidal cell layer of Ammon's horn. We found no neurodevelopmental abnormalities outside the hippocampus. The hippocampal architectural alterations in this patient are similar to those associated with a murine Lef1 mutation, but our human case does not have the other congenital deficits reported in the Lef1-null mouse. Bilateral agenesis of the hippocampal dentate gyrus, and apparent failure of regeneration of dentate granule cells from stem cells in adult life, may occur without overt clinical neurological deficits.


Crystal structure of cytoplasmic acetoacetyl-CoA thiolase from Saccharomyces cerevisiae.
Thiolases are vital enzymes which participate in both degradative and biosynthetic pathways. Biosynthetic thiolases catalyze carbon-carbon bond formation by a Claisen condensation reaction. The cytoplasmic acetoacetyl-CoA thiolase from Saccharomyces cerevisiae, ERG10, catalyses carbon-carbon bond formation in the mevalonate pathway. The structure of a S. cerevisiae biosynthetic thiolase has not previously been reported. Here, crystal structures of apo ERG10 and its Cys91Ala variant were solved at resolutions of 2.2 and 1.95 Å, respectively. The structure determined shows that ERG10 shares the characteristic thiolase superfamily fold, with a similar active-site architecture to those of type II thiolases and a similar binding pocket, apart from Ala159 at the entrance to the pantetheine-binding cavity, which appears to be a determinant of the poor binding ability of the substrate. Moreover, comparative binding-pocket analysis of molecule B in the asymmetric unit of the apo structure with that of the CoA-bound complex of human mitochondrial acetoacetyl-CoA thiolase indicates the canonical binding mode of CoA. Furthermore, the steric hindrance revealed in a structural comparison of molecule A with the CoA-bound form raise the possibility of conformational changes that are associated with substrate binding.


Effects of dissolved organic carbon on sorption and mobility of imidacloprid in soil.
To evaluate the effects of dissolved organic carbon on sorption and mobility of the insecticide imidacloprid [1-(6-chloro-3-pyridinyl) methyl-N-nitro-2-imidazolidinimine] in soils, adsorption and column experiments were performed by using a typical calcareous soil from southeastern Spain and two different types of dissolved organic carbon, that is, dissolved organic carbon extracts from a commercial peat (DOC-PE) and high-purity tannic acid (DOC-TA). The experiments were carried out from a 0.01 M CaCl2 aqueous medium at 25 degrees C. The results obtained from the sorption experiments show that the presence of both DOC-PE and DOC-TA, over a concentration range of 15 to 100 mg L(-1), produces in all cases a decreasing amount of imidacloprid adsorbed in the soil studied. From the column experiments the retardation coefficients (RC) were calculated for imidacloprid by using either 0.01 M CaCl2 aqueous solution (RC = 2.10), 0.01 M CaCl2 DOC-PE solution (RC = 1.65), or 0.01 M CaCl2 DOC-TA solution (RC = 1.87). The results indicate that mobility of imidacloprid is increased 21.4 and 11.0% in the presence of DOC-PE and DOC-TA solutions, respectively. Dissolved organic carbon reduces imidacloprid sorption by competing with the pesticide molecules for sorption sites on the soil surface, allowing enhanced leaching of imidacloprid and potentially increasing ground water contamination.


Laser-induced nuclear magnetic resonance splitting in hydrocarbons.
Irradiation of matter with circularly polarized light (CPL) shifts all nuclear magnetic resonance (NMR) lines. The phenomenon arises from the second-order interaction of the electron cloud with the optical field, combined with the orbital hyperfine interaction. The shift occurs in opposite directions for right and left CPL, and rapid switching between them will split the resonance lines into two. We present ab initio and density functional theory predictions of laser-induced NMR splittings for hydrocarbon systems with different sizes: ethene, benzene, coronene, fullerene, and circumcoronene. Due to the computationally challenging nature of the effect, traditional basis sets could not be used for the larger systems. A novel method for generating basis sets, mathematical completeness optimization, was employed. As expected, the magnitude of the spectral splitting increases with the laser beam frequency and polarizability of the system. Massive amplification of the effect is also observed close to the optical excitation energies. A much larger laser-induced splitting is found for the largest of the present molecules than for the previously investigated noble gas atoms or small molecules. The laser intensity required for experimental detection of the effect is discussed.


Q Fever Severe Pericarditis With Cardiac Tamponade: A Case Report.
Q fever can present in acute or chronic form with a wide range of clinical symptoms and presentations. Here we report severe pericarditis with cardiac tamponade due to a chronic Coxiella burnetii (C. burnetii) infection. Our report emphasizes and justifies the importance of serological testing for chronic Q fever in patients with unexplained pericarditis, particularly in areas where C. burnetii is endemic.


An Optical Fiber Lateral Displacement Measurement Method and Experiments Based on Reflective Grating Panel.
An optical fiber sensing method based on a reflective grating panel is demonstrated for lateral displacement measurement. The reflective panel is a homemade grating with a periodic variation of its refractive index, which is used to modulate the reflected light intensity. The system structure and operation principle are illustrated in detail. The intensity calculation and simulation of the optical path are carried out to theoretically analyze the measurement performance. A distinctive fiber optic grating ruler with a special fiber optic measuring probe and reflective grating panel is set up. Experiments with different grating pitches are conducted, and long-distance measurements are executed to accomplish the functions of counting optical signals, subdivision, and discerning direction. Experimental results show that the proposed measurement method can be used to detect lateral displacement, especially for applications in working environments with high temperatures.


Forkhead Box F2 Suppresses Gastric Cancer through a Novel FOXF2-IRF2BPL-β-Catenin Signaling Axis.
DNA methylation has been identified as a hallmark of gastric cancer (GC). Identifying genes that are repressed by DNA promoter methylation is essential in providing insights into the molecular pathogenesis of gastric cancer. Using genome-wide methylation studies, we identified that transcription factor forkhead box F2 (FOXF2) was preferentially methylated in gastric cancer. We then investigated the functional significance and clinical implication of FOXF2 in gastric cancer. FOXF2 was silenced in gastric cancer cell lines and cancer tissues by promoter methylation, which was negatively associated with mRNA expression. Ectopic expression of FOXF2 inhibited proliferation, colony formation, G1-S cell-cycle transition, induced apoptosis of gastric cancer cell lines, and suppressed growth of xenograft tumors in nude mice; knockdown of FOXF2 elicited opposing effects. FOXF2 inhibited Wnt signaling by inducing β-catenin protein ubiquitination and degradation independently of GSK-3β. FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation. Multivariate Cox regression analysis identified FOXF2 hypermethylation as an independent prognostic factor of poor survival in early-stage gastric cancer patients. In conclusion, FOXF2 is a critical tumor suppressor in gastric carcinogenesis whose methylation status serves as an independent prognostic factor for gastric cancer patients.Significance: FOXF2-mediated upregulation of the E3 ligase IRF2BPL drives ubiquitylation and degradation of β-catenin in gastric cancer, blunting Wnt signaling and suppressing carcinogenesis. Cancer Res; 78(7); 1643-56. ©2018 AACR.


Alcohol intake in social housing and in isolation before puberty and its effects on voluntary alcohol consumption in adulthood.
We assessed the effects of alcohol exposure in social and isolation housing before puberty on the alcohol consumption later in adulthood. From 25 to 35 days of age, Wistar male rats were exposed to either (a) continuous isolation; (b) continuous social housing; (c) continuous isolation, but placed in social housing during 12 hr every other day; or (d) continuous social housing, but placed in isolation during 12 hr every other day (SOIS group). All males were exposed to 8% ethanol as the only available liquid 12 hr/day every other day in this prepubescent period and to continuous free-choice access to 8% ethanol or water in both social and isolation housing when adulthood was reached. Alcohol consumption before puberty was higher in the group permanently housed in isolation. Both voluntary alcohol intake and preference for alcohol in adulthood also were higher during the isolation than in the social condition in all groups, except in the SOIS group. Alcohol consumption was higher in the SOIS group than in the other groups only during social condition in adulthood. Food intake decreased during the social interaction of the groups that changed their condition from isolated to social or from social to isolated. Results support that (a) isolation facilitates alcohol consumption, and (b) rearing characteristics associated to alcohol intake at an early age can play an important role in later alcohol intake.


Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis.
Immune thrombocytopenia (ITP) in children has a varied course and according to duration is distinguished as newly diagnosed (<3 months), persistent (3-12), and chronic (>12) types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and platelets at diagnosis, treatment, disease course, and immunological markers was recorded. 39 children had newly diagnosed, 4 persistent, and 14 chronic disease. Chronic ITP children were more likely to be of age > 10 years (p = 0.015) and have gradual initiation of the disease (p = 0.001), platelets > 10 × 109/L (p = 0.01), and impaired immunological markers (p < 0.003) compared to newly diagnosed/persistent groups. Recent history of infection was found mainly in the newly diagnosed/persistent group (p = 0.013). None of the children exhibited severe spontaneous bleeding. Conclusion. Even though ITP in children usually has a self-limited course, with rare serious bleeding complications, the chronic form of the disease is characterized by different predictive parameters, which can be used in clinical practice.


Sugars-eating habits of 405 11- to 14-year-old English children.
Between September 1979 and July 1981, 405 northern-English children, initially aged 11-12 years, each recorded all food and drink consumed on five occasions on each of three consecutive days. Sugars and nutrient intakes were calculated using food tables. The average total sugars intake was 118 g/d or 21% of the energy intake and 43% of the carbohydrate intake; these percentages were similar for both sexes, all social class groups and surveys. Sugars were found to be derived from a variety of food sources with confectionery being the single largest source. Sugars were fairly evenly consumed over the average day with a high amount in foods eaten between meals. Snacks accounted for 65% of the sugars intake but only 46% of the energy intake. Sugars intake and snacking therefore seem to have been major components of the eating habits of these children. If dietary changes towards lower sugars intakes are to be achieved a vigorous, informed health education campaign is necessary together with effective labelling of manufactured foods, the development of new products and the modification of some existing ones.


Synthesis of potent inhibitors of anthrax toxin based on poly-L-glutamic acid.
We report the synthesis of biodegradable polyvalent inhibitors of anthrax toxin based on poly-L-glutamic acid (PLGA). These biocompatible polyvalent inhibitors are at least 4 orders of magnitude more potent than the corresponding monovalent peptides in vitro and are comparable in potency to polyacrylamide-based inhibitors of anthrax toxin assembly. We have elucidated the influence of peptide density on inhibitory potency and demonstrated that these inhibitory potencies are limited by kinetics, with even higher activities seen when the inhibitors are preincubated with the heptameric receptor-binding subunit of anthrax toxin prior to exposure to cells. These polyvalent inhibitors are also effective at neutralizing anthrax toxin in vivo and represent attractive leads for designing biocompatible anthrax therapeutics.


[Relationship between the retromolar space and the mandibular measurements in Bulgarians].
We examined 412 mandibles from adult males. Using the classic anthropometric methods according to Martin-Saller, we took 17 measurements: length, width, height and angle of the mandible. The data obtained were subjected to variance and correlation analyses. We observed poor correlations for the length of the dental arch, the height of the ascending ramus, the condylar width and the width of the chin; there were medium correlations for the following measurements: mental plane, median plane and angular width in the region of 46, 47, 36, 37 and the thickness of the alveolar portion. The correlations for all the other measurements were high; in some cases, they approximated the normal value.


Genome-based Definition of an Inflammatory Bowel Disease-associated Adherent-Invasive Escherichia coli Pathovar.
Mucosal-associated Escherichia coli are commonly found in inflamed tissues during inflammatory bowel disease (IBD). These bacteria often possess an adherent and invasive phenotype but lack virulence-associated features of well-described intestinal E. coli pathogens, and are of diverse serology and phylotypes, making it difficult to correlate strain characteristics with exacerbations of disease. The genome sequences of 14 phenotypically assigned adherent-invasive Escherichia coli (AIEC) isolates obtained from intestinal biopsies of patients with IBD were compared with the genome sequences of 37 other pathogenic and commensal E. coli available from public databases. Core genome-based phylogenetic analyses and genome-wide comparison of genetic content established the existence of a closely related cluster of AIEC strains with 3 distinct genetic insertions differentiating them from commensal E. coli. These strains are of the B2 phylotype have a variant type VI secretion system (T6SS-1), and are highly related to extraintestinal pathogenic E. coli, suggesting that these 2 clinically distinct pathovars have common virulence strategies. Four other mucosally adherent E. coli strains from patients with IBD were of diverse phylogenetic origins and lacked the 3 genetic features, suggesting that they are not related to the B2 AIEC cluster. Although AIEC are often considered as having a unique association with Crohn's disease, isolates from Crohn's disease and ulcerative colitis were genetically indistinguishable. B2 AIEC thus represent a closely related cluster of IBD-associated E. coli strains that are distinct from normal commensal isolates, and which should be considered separately from the phenotypically similar but genetically distinct non-B2 AIEC strains when considering their association with intestinal pathogenesis.


Siderophores in Cloud Waters and Potential Impact on Atmospheric Chemistry: Production by Microorganisms Isolated at the Puy de Dôme Station.
A total of 450 bacteria and yeast strains isolated from cloud waters sampled at the puy de Dôme station in France (1465 m) were screened for their ability to produce siderophores. To achieve this, a high-throughput method in 96-well plates was adapted from the CAS (chrome azurol S) method. Notably, 42% of the isolates were siderophore producers. This production was examined according to the phyla of the tested strains and the type of chelating functional groups (i.e., hydroxamate, catechol, and mixed type). The most active bacteria in the clouds belong to the γ-Proteobacteria class, among which the Pseudomonas genus is the most frequently encountered. γ-Proteobacteria are produced in the majority of mixed function siderophores, such as pyoverdines, which bear a photoactive group. Finally, siderophore production was shown to vary with the origin of the air masses. The organic speciation of iron remains largely unknown in warm clouds. Our results suggest that siderophores could partly chelate Fe(III) in cloud waters and thus potentially impact the chemistry of the atmospheric aqueous phase.


The effect of applying a pipe-joint lubricant to connect ductile iron pipe on off-flavors in drinking water distribution systems.
This study was used to help define the contribution to taste and odor problems caused by the application of a pipe-joint lubricant to connect ductile iron pipe in drinking water distribution systems. Tyton Joint Lubricant (TJL) was studied. The lubricant produced odors that are continually oxidized by chlorine or oxygen. The mechanism of oxidative rancidity, one of the major causes of food spoilage is the apparent mechanism of oxidation. The odors produced by the lubricant were characterized by a Flavor Profile Analysis (FPA) panel as well as GC/MS and Sensory GC analysis. The most common odors perceived in the TJL water samples for the first six days were waxy/oily and soapy odors with a rancid oil, odor note. The waxy/oily and soapy odors decreased with time in the chlorine medium as the rancid oily odor note increased. Numerous aldehydes, ketones, alcohols and borneol compounds, produced from the lubricants, were tentatively identified and linked to the odors perceived by the FPA panel.


Biomass axial distribution in airlift bioreactor with yeast and plant cells.
This study was aimed at determining the degree of biomass homogeneity in the various parts of an internal loop airlift bioreactor, thus verifying the assumption, often made in bioreactor studies, of a well-mixed liquid-biomass system. Following characterization of the hydrodynamics of the vessel with water, the axial biomass distribution in the riser and downcomer was determined for plant and yeast cell suspensions of 5.8, 8.5, and 12.5 g DW/L Phaseolus vulgaris and of 30 and 46 g DW/L Saccharomyces cerevisiae. The airlift bioreactor with a surface ratio A(D)/A(D) of 1.04 and aspect ratio of 4.95 was investigated under various aeration rates. The yeast cells were found to be distributed practically uniformly throughout the vessel at the aeration rates of 0.1-1.45 vvm. However, in the case of the denser and cluster-forming plant cells, a clear trend of a gradual bio-mass accumulation in the downcomer, a slightly lower but uniform biomass loading in the riser, and a slightly higher biomass concentration in the gas-liquid separator was observed at the lower aeration rates of 0.1-0.61 vvm. In the case of powderized calcium carbonate (55 g/L) often used in fermentations of organic acids, a slight trend of a gradual accumulation of solids towards the bottom parts in both the downcomer and riser was observed. A better representative sampling location, in terms of solids and biomass loading, seems to be in the middle part of the vessel. It is suggested that airlift bioreactors with higher aspect ratios (>5) may be prone to a more significant inhomogeneity of solids (biomass and particles).


Recurrence rates following external valvular stenting of the saphenofemoral junction: a comparison with simultaneous contralateral stripping of the great saphenous vein.
The incidence of recurrent varicose veins remains high despite the development of new ablative treatments for varicose veins associated with incompetence of the saphenofemoral junction. External valvular stenting (EVS) of the terminal and/or subterminal valves of the great saphenous vein (GSV) provides a reparative, physiological approach that requires long-term evaluation. The aim of this study was to compare recurrences following EVS with perforate invaginate (PIN) stripping of the GSV. Included in the study were 193 patients (386 limbs) all of whom underwent simultaneous PIN-stripping of the GSV in one limb and EVS in the contralateral limb. Duplex scanning of the GSV and venous valves established suitability for each procedure. Only valves with visible, mobile cusps on ultrasound imaging are suitable for EVS. Stents were specifically designed Dacron reinforced silicone for left and right saphenofemoral junctions and for the subterminal valve. In a separate group of patients identified from a database where unilateral and bilateral stents had been implanted, 39 limbs with recurrent varices were examined clinically and ultrasonically to determine the aetiology of recurrences. Follow up was available to a maximum of 147 months. The total recurrence rate was 12.4%; stripping (22.2%) and EVS (4.6%) (P<0.01). The residual reflux as measured by postoperative Valsalva on duplex was 9% but rarely was associated with recurrences. The most common cause of recurrence was incompetent perforators and ovarian vein incompetence filling varices of the pudendal veins. This non-randomised study included more severely affected limbs in the PIN stripping limbs, favouring a better outcome in the EVS group. In those patients at an early stage of the disease process where venous valve structure is essentially intact, EVS is a physiological alternative to PIN stripping in the treatment of varicose veins.


Rapid access to the Welwitindolinone alkaloid skeleton by cyclization of indolecarboxaldehyde substituted cyclohexanones.
[reaction: see text] A very rapid access to cyclohexanone-bridged indole systems was established by an acid-mediated ring closure of appropriately substituted indole aldehydes, which involved an apparent disproportionation of an aldol-like intermediate. One of the bridged indole intermediates was further transformed into an oxindole having the essential skeleton of the Welwitindolinone alkaloids.


Pilot study results from a brief intervention to create smoke-free homes.
Very few community-based intervention studies have examined how to effectively increase the adoption of smoke-free homes. A pilot study was conducted to test the feasibility, acceptability, and short-term outcomes of a brief, four-component intervention for promoting smoke-free home policies among low-income households. We recruited forty participants (20 smokers and 20 nonsmokers) to receive the intervention at two-week intervals. The design was a pretest-posttest with follow-up at two weeks after intervention. The primary outcome measure was self-reported presence of a total home smoking ban. At follow-up, 78% of participants reported having tried to establish a smoke-free rule in their home, with significantly more nonsmokers attempting a smoke-free home than smokers (P = .03). These attempts led to increased smoking restrictions, that is, going from no ban to a partial or total ban, or from a partial to a total ban, in 43% of the homes. At follow-up, 33% of the participants reported having made their home totally smoke-free. Additionally, smokers reported smoking fewer cigarettes per day. Results suggest that the intervention is promising and warrants a rigorous efficacy trial.


Diminished brain synaptic plasma membrane Ca(2+)-ATPase activity in rats with streptozocin-induced diabetes: association with reduced anesthetic requirements.
Recent evidence suggests that chronic hyperglycemia may inhibit plasma membrane Ca(2+)-ATPase (PMCA) in cells from several tissues. Inhalational anesthetics (IA) can inhibit brain synaptic PMCA activity. We proposed that diabetic rats may manifest chronic inhibition of brain synaptic PMCA and thus provide a model for testing the hypothesis that synaptic PMCA plays a key role in IA pharmacodynamics. Ca2+ pumping activity of PMCA was measured in cerebral synaptic plasma membrane (SPM) vesicles prepared from rats with streptozocin (STZ)-induced diabetes and from control, normoglycemic rats. Dose requirements for halothane and xenon were estimated in treated and untreated rats. Brain PMCA activity in hyperglycemic rats was depressed by about 8.4%, compared to controls. In vitro glycation also caused a significant decrease in PMCA pumping activity. Halothane requirement for STZ-hyperglycemic rats was dramatically reduced to about 65% of control. Xenon requirement was also significantly reduced, to 88% of control. Correlation of IA dose with percent glycated hemoglobin for each rat revealed a strong association between reduced requirements for halothane or xenon and increased protein glycation. These results indicate that inhibition of brain synaptic PMCA in chronically hyperglycemic rats is associated with a significant reduction in IA requirement.


New insights into the function of a versatile class of membrane molecular motors from studies of Myxococcus xanthus surface (gliding) motility.
Cell motility is a central function of living cells, as it empowers colonization of new environmental niches, cooperation, and development of multicellular organisms. This process is achieved by complex yet precise energy-consuming machineries in both eukaryotes and bacteria. Bacteria move on surfaces using extracellular appendages such as flagella and pili but also by a less-understood process called gliding motility. During this process, rod-shaped bacteria move smoothly along their long axis without any visible morphological changes besides occasional bending. For this reason, the molecular mechanism of gliding motility and its origin have long remained a complete mystery. An important breakthrough in the understanding of gliding motility came from single cell and genetic studies in the delta-proteobacterium Myxococcus xanthus. These early studies revealed, for the first time, the existence of bacterial Focal Adhesion complexes (FA). FAs are formed at the bacterial pole and rapidly move towards the opposite cell pole. Their attachment to the underlying surface is linked to cell propulsion, in a process similar to the rearward translocation of actomyosin complexes in Apicomplexans. The protein machinery that forms at FAs was shown to contain up to seventeen proteins predicted to localize in all layers of the bacterial cell envelope, the cytosolic face, the inner membrane (IM), the periplasmic space and the outer membrane (OM). Among these proteins, a proton-gated channel at the inner membrane was identified as the molecular motor. Thus, thrust generation requires the transduction of traction forces generated at the inner membrane through the cell envelope beyond the rigid barrier of the bacterial peptidoglycan.


Heroin: from drug to ambivalent medicine : on the introduction of medically prescribed heroin and the emergence of a new space for treatment.
This article provides an anthropological analysis of the introduction of medically prescribed heroin as part of official substance abuse treatment. While anthropological inquiries of substance abuse treatment have mainly focused on providing the users perspectives on the (ab)use or unraveling the conflicts and negotiations between users and staff, the present article argues for the merits of paying attention to the spatial dimensions of substance abuse treatment. Focusing on the spatial and material ramification of the treatment can shed a nuanced light on the still vulnerable process of altering the heroin from drug to medicine, and thereby on the attempts to settle heroin in a new practical and semantic landscape. The heroin is anchored in some powerful discourses of crime, death, and pleasure, and the analysis shows how these discourses (re-)appear in the spatial textures of the clinic, contesting the attempts to medicalize the heroin. Further, the article argues that even though the treatment aims at a marginalization of the heroin in the life of the clients, the spatial arrangements and the practices within them simultaneously enforces a centralization of the heroin, making the space for treatment highly ambivalent.