Progress in Development of Interventions to Prevent Birth Defects in Diabetic Pregnancies.
Diabetic embryopathy is a diabetic complication, in which maternal hyperglycemia in early pregnancy causes birth defects in newborn infants. Under maternal diabetic conditions, hyperglycemia disturbs intracellular molecular activities and organelles functions. These include protein misfolding in the endoplasmic reticulum (ER), overproduction of reactive oxygen species (ROS) in mitochondria, and high levels of nitric oxide (NO). The resultant ER, oxidative, and nitrosative stresses activate apoptotic machinery to cause cell death in the embryo, ultimately resulting in developmental malformations. Based on the basic research data, efforts have been made to develop interventional strategies to alleviate the stress conditions and to reduce embryonic malformations. One of the challenges in birth defect prevention is to identify effective and safe agents to be used in pregnancy. One approach is to search and characterize naturally occurring phytochemicals, including flavonoids, curcuminoids and stilbenoids, for use in prevention of diabetic embryopathy.


Metal fume-induced diffuse alveolar damage.
Metal fume fever is a well-defined clinical entity characterized by a self-limited influenza-like illness. Severe and protracted illness related to metal fume exposure is rare. We describe 2 related cases of serious metal fume fever in a 29- and a 51-year-old male precipitated by the use of an acetylene torch to dismantle galvanized steel in a poorly ventilated area. Each case was unusual in both severity and duration of symptoms for metal fume exposure. High-resolution computed tomography scans revealed diffuse alveolar damage in both patients. The 29-year-old male was started on steroids 1-day after exposure and experienced a significantly attenuated course of symptoms compared with the 58-year-old male, who received treatment 3 days after exposure.


The Effect of Lipid Antioxidant α-Tocopherol on Cell Viability and Electrofusion Yield of B16-F1 Cells In Vitro.
Induced cell fusion is a powerful method for production of hybridoma in biotechnology and cell vaccines in medical applications. Among different alternatives, physical methods have an advantage, as they do not require any additives. Among them electrofusion, an electroporation-based cell fusion method holds a great promise. Electric pulses cause cell membrane permeabilization and due to pore formation bring cell membrane into the fusogenic state. At the same time, however, they compromise cell viability. We used a train of 8 × 100 µs electric pulses, delivered at 1 Hz with strengths ranging from 400 to 1600 V/cm. We evaluated electrofusion efficiency by dual color microscopy. We determined cell viability, because during electroporation reactive oxygen species are generated affecting cell survival. The novelty of our study is evaluation of the effect of lipid antioxidant α-tocopherol on cell fusion yield and cell viability on mouse B16-F1 cells. Pretreatment with α-tocopherol slowed down dynamic of cell fusion shortly after electroporation. Twenty-four hours later, fusion yields between α-tocopherol treated and untreated cells were comparable. The viability of α-tocopherol pretreated cells was drastically improved. Pretreatment of cells with α-tocopherol improved whole electrofusion process by more than 60%. We believe that α-tocopherol holds great promise to become an important agent to improve cell electrofusion method.


The preclinical discovery and development of quetiapine for the treatment of mania and depression.
Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.


["... that we are thus not dead." : Unpublished letters addressed by Sigmund Freud to Georg Hermann].
The main reason behind these three letters and these two postcards addressed in 1936 by Sigmund Freud to Georg Hermann (a German realist writer, author of a great number of psychological novels) and that are presented here by Gert Mattenklott, takes root in this Freudian leitmotiv: psychoanalysis can and must speak of the work of art, not so much in relationship to its formal or technical qualities as to the impression it gives the spectator, to its "effects". This brief exchange provided an occasion for Freud to speak of the notion of unconscious guilt when replying to an objection made by Hermann, and then essentially of dreams about travelling and trains that are missed as a defence against the perspective of death. The article and the correspondence with Hermann end in the same manner, with the two last postcards sent by Freud to the German writer who died in 1943 at Auschwitz-Birkenau.


Manganese peroxidase from the white-rot fungus Phanerochaete chrysosporium is enzymatically active and accumulates to high levels in transgenic maize seed.
Manganese peroxidase (MnP) has been implicated in lignin degradation and thus has potential applications in pulp and paper bleaching, enzymatic remediation and the textile industry. Transgenic plants are an emerging protein expression platform that offer many advantages over traditional systems, in particular their potential for large-scale industrial enzyme production. Several plant expression vectors were created to evaluate the accumulation of MnP from the wood-rot fungus Phanerochaete chrysosporium in maize seed. We showed that cell wall targeting yielded full-length MnP, whereas cytoplasmic localization resulted in multiple truncated peroxidase polypeptides as detected by immunoblot analysis. In addition, the use of a seed-preferred promoter dramatically increased the expression levels and reduced the negative effects on plant health. Multiple independent transgenic lines were backcrossed with elite inbred corn lines for several generations with the maintenance of high-level expression, indicating genetic stability of the transgene.


Effect of organic load and nutrient ratio on the operation stability of the moving bed bioreactor for kraft mill wastewater treatment and the incidence of polyhydroxyalkanoate biosynthesis.
This paper studies the effect of organic load rate (OLR) and nutrient ratio on operation stability of the moving bed bioreactor (MBBR) for kraft mill wastewater treatment, analyzing the incidence of polyhydroxyalkanoate (PHA) production. The MBBR operating strategy was to increase OLR from 0.25 ± 0.05 to 2.41 ± 0.19 kg COD m(-3) d(-1) between phases I and IV. The BOD(5):N:P ratio (100:5:1 and 100:1:0.2) was evaluated as an operation strategy for phases IV to V. A stable MBBR operation was found when the OLR was increased during 225 days in five phases. The maximum absolute fluorescence against the proportion of cells accumulating PHA was obtained for an OLR of 2.41 ± 0.19 kg COD m(-3)d(-1) and a BOD(5):N:P relationship of 100:1:0.2. The increase of PHA biosynthesis is due to the increased OLR and is not attributable to the increased cell concentration, which is maintained constant in stationary status during bioreactor biosynthesis.


Epidermal development in the growth retarded fetal rat.
Intrauterine growth retardation (IUGR) due to vascular insufficiency in humans results in newborn infants with marked loss of subcutaneous fat and a poorly characterized "dysmature" appearance of the epidermis. In this study, we examined selected indices of epidermal development in 20 and 21 day old growth retarded fetal rats. IUGR was produced by unilateral ligation of the uterine artery and vein on gestational day 17. Littermate rats from the opposite uterine horn were utilized as pair matched experimental controls. A total of 49 consecutive fetal pairs were examined. Mean body weight (+/- SEM) for controls was 4.2 +/- 0.1 g versus 2.6 +/- 0.2 g for the treatment group on gestational day 20 (n = 74, P less than 0.01) and 6.0 +/- 0.1 versus 4.0 +/- 0.2 g, respectively, on the day 21 (n = 24, P less than 0.01). Examination by light and electron microscopy showed marked diminution in overall epidermal thickness in the growth retarded animals, particularly of the stratum granulosum and stratum corneum. Epidermal DNA content was decreased in IUGR pups on day 20 (0.99 +/- 0.05 versus 1.26 +/- 0.07 micrograms DNA/mg wet weight, P less than 0.05). Soluble epidermal proteins showed a similar reduction in IUGR animals (30.2 + 0.8 versus 34.7 +/- 1.6 micrograms protein/mg wet weight, P less than 0.05). IUGR also decreased the total amount of epidermal protein extractable in 8 M urea. Differentiation-specific epidermal proteins (keratins, filaggrin) were markedly reduced in the growth retarded animals following normalization to epidermal surface area and analysis by polyacrylamide gel electrophoresis. Overall, these changes in the growth retarded fetal rat lead to formation of a thin, hypoplastic, and poorly keratinized epidermal covering.


Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial.
To assess the effectiveness of two mechanical methods of blood conservation in reducing the need for allogeneic red blood cells or coagulation products during cardiac surgery. Randomised controlled trial. Regional cardiac centre in a teaching hospital in Southampton. 263 adults aged 18-80 years undergoing elective coronary artery bypass surgery entered the study, of whom 252 completed the trial. All patients received routine perioperative care. Patients were allocated to one of three treatment groups: intraoperative cell salvage, intraoperative cell salvage with acute perioperative normovolaemic haemodilution, or no mechanical blood conservation. There were 84 patients in each group. Numbers of patients who received allogeneic blood or coagulation products, and the mean number of units of blood transfused per patient. Of the patients in the intraoperative cell salvage group, 26 were given a transfusion of allogeneic blood, compared with 43 in the control group (odds ratio 0.43 (95% confidence interval 0.23 to 0.80)). The mean number of units of allogeneic blood transfused per patient in the intraoperative cell salvage group was 0.68 units (SD=1.55), compared with 1.07 (1.56) units in the control group. 32 of the patients in the intraoperative cell salvage group were given any blood product, compared with 47 in the control group (odds ratio 0.47 (0.25 to 0.89); P=0.019). Combining acute perioperative normovolaemic haemodilution with intraoperative cell salvage conferred no additional benefits. An intraoperative cell salvage device should be used in elective coronary artery bypass grafting. Pharmacological strategies may achieve further reductions in blood transfusions. Yet further reductions in blood transfusions could be achieved if the lower safe limit of haemoglobin concentration in patients undergoing cardiac surgery were known.


Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the 'therapeutic' concentration be reconsidered?
The therapeutic concentration of epsilon-aminocaproic acid (EACA) has been 130 microg/ml or greater for nearly 50 years. We tested the effects on clot growth/disintegration of EACA with a plasmatic model of hyperfibrinolysis in vitro. Human plasma was exposed to 1000 U/ml tissue-type plasminogen activator containing 0, 13, 65 or 130 microg/ml EACA, with clot growth/disintegration kinetics quantified via thrombelastography. Data were analyzed with one-way analysis of variance or Kruskal-Wallis analysis of variance as appropriate. Exposure of plasma to 1000 U/ml tissue-type plasminogen activator resulted in a brief-lived clot, lasting 2 min. EACA at all concentrations tested significantly increased the rate of clot growth compared with samples with 0 microg/ml EACA. Clot strength was significantly increased by EACA in a concentration-dependent fashion. Similarly, EACA significantly prolonged the time of onset of clot lysis and decreased the rate of lysis. Samples with 130 microg/ml EACA had no sign of lysis present for 30 min. Subtherapeutic to therapeutic concentrations of EACA significantly attenuated or abolished fibrinolysis in the presence of a concentration of tissue-type plasminogen activator more than 2000-fold that encountered systemically during cardiopulmonary bypass. Further clinical investigation is warranted to determine whether smaller concentrations of EACA could provide a reduction in bleeding with a concomitant decrease in thrombotic complications.


Association of Dowling-Degos disease and multiple seborrheic keratosis in a "Christmas tree pattern".
Dowling-Degos disease is a rare sporadic or autosomal dominant pigmentary entity, in which clusters of papules and reticulate macules slowly develop with predominance in flexural regions. This entity is due to mutations in the keratin 5 gene, and is related with other cutaneous disorders. We report the sporadic form of Dowling-Degos disease in an elderly man with multiple seborrheic keratosis in a "Christmas tree" pattern. Worthy of note in this case study is the lesions evolved for over than 30 years. The aim is to describe the association of these keratoses with Dowling-Degos disease in a healthy man.


Astaxanthin biosynthesis is enhanced by high carotenogenic gene expression and decrease of fatty acids and ergosterol in a Phaffia rhodozyma mutant strain.
An astaxanthin-overproducing (∼1000 μg g(-1)) strain of Phaffia rhodozyma, termed MK19, was established through 1-methyl-3-nitro-1-nitrosoguanidine and Co60 mutagenesis from wild-type JCM9042 (merely 35-67 μg g(-1)). The total fatty acid content of MK19 was much lower than that of the wild type. Possible causes of the astaxanthin increase were studied at the gene expression level. The expression of the carotenogenic genes crtE, crtI, pbs, and ast, which are responsible for astaxanthin biosynthesis from geranylgeranyl pyrophosphate, was highly induced at the mRNA level, leading to excessive astaxanthin accumulation. In contrast, transcription levels of the genes (hmgs, hmgr, idi, mvk, mpd, fps), responsible for the initial steps in the terpenoid pathway, were essentially the same in wild type and MK19. Although fatty acid and total ergosterol content were reduced by 40-70 mg g(-1) and 760.3 μg g(-1) , respectively, in MK19 as compared with the wild type, but the transcription levels of rate-limiting genes in fatty acid and ergosterol pathways such as acc and sqs were similar. Because fatty acids and ergosterol are two branch pathways of astaxanthin biosynthesis in P. rhodozyma, our findings indicate that enhancement of astaxanthin in MK19 results from decreased fatty acid and ergosterol biosynthesis, leading to precursor accumulation, and transfer to the astaxanthin pathway. Strengthening of the mevalonate pathway is suggested as a promising metabolic engineering approach for further astaxanthin enhancement in MK19.


The Molecular Size of Bioengineered Oxygen Carriers Determines Tissue Oxygenation in a Hypercholesterolemia Guinea Pig Model of Hemorrhagic Shock and Resuscitation.
Polymerized human hemoglobin (PolyhHb) has shown promise in preclinical hemorrhagic shock settings. Different synthetic and purification schemes can control the size of PolyhHbs, yet research is lacking on the impact of polymerized hemoglobin size on tissue oxygenation following hemorrhage and resuscitation in specialized animal models that challenge their resuscitative capabilities. Pre-existing conditions that compromise the vasculature and end organs, such as the liver, may limit the effectiveness of resuscitation and exacerbate the toxicity of these molecules, which is an important but minimally explored therapeutic dimension. In this study, we compared the effective oxygen delivery of intermediate molecular weight PolyhHb (PolyhHb-B3; 500-750 kDa) to high molecular weight PolyhHb (PolyhHb-B4; 750 kDa-0.2 μm) for resuscitative effectiveness in guinea pig models subjected to hemorrhagic shock. We evaluated how the size of PolyhHb impacts hemodynamics and tissue oxygenation in normal guinea pigs and guinea pigs on an atherogenic diet. We observed that while PolyhHb-B3 and -B4 equivalently restore hemodynamic parameters of normal-dieted guinea pigs, high-fat-dieted guinea pigs resuscitated with PolyhHb-B4 have lower mean arterial pressures, impaired tissue oxygenation, and higher plasma lactate levels than those receiving PolyhHb-B3. We characterized the plasma of these animals following resuscitation and found that despite similar oxygen delivery kinetics, circulating PolyhHb-B3 and -B4 demonstrated a size-dependent increase in the plasma viscosity, consistent with impaired perfusion in the PolyhHb-B4 transfusion group. We conclude that intermediate-sized PolyhHbs (such as -B3) are ideal for further research given the effective resuscitation of hemorrhagic shock based on tissue oxygenation in hypercholesterolemic guinea pigs.


Electron microscopic characterization of Rhizobium bacteriophage 16-6-12 and its isolated deoxyribonucleic acid.
Bacteriophage 16-6-12 of Rhizobium lupini has a long, non-contractile tail and a head which is hexagonal in outline. The tail is 140 nm in length, 11 nm in diameter, and carries a short term fiber. Analysis of the tail structure by optical diffraction indicates that it is of the helical "stacked disc" type. After phenol-extraction from purified particles, the DNA of phage 16-6-12 can circularize in vitro. No significant difference in contour length was observed between the linear (14.34 plus or minus 0.28 mum) and circular (14.44 plus or minus 0.24 mum) forms of molecules. After partial denaturation with alkali an AT-GC-map was constructed, which shows an asymmetric distribution of AT- and GC-rich regions. It is concluded that this phage DNA can circularize due to the presence of cohesive ends and that it is not circularly permuted.


Activation of T cells by interleukin 1 involves internalization of interleukin 1.
The cytokine interleukin-1 plays an important role in the induction of IL-2 secretion and IL-2 receptor expression. The events that follow binding of IL-1 to its receptor are not known. We found that in a purified T cell population (comprising the Lyt2- and L3T4- T cells) IL-1 in the absence of antigen or mitogen induced strong proliferation and de novo expression of IL-2R light chain mRNA. This was accompanied by high affinity IL-2 binding. Production of IL-2 or IL-2 mRNA was not detected under these conditions. As a model system for IL-1 action two EL4 subclones were isolated. EL4 5D3 responded to IL-1 by augmentation of PMA induced IL-2 secretion and IL-2R expression. EL4D6/76 bound IL-1 with the same affinity but did not respond. We found that this line was unable to internalize surface bound IL-1. The finding suggests that in T cells internalization of IL-1 is required for its activity.


Differential regulation of mitogen-activated protein kinase pathways by acetaminophen and its nonhepatotoxic regioisomer 3'-hydroxyacetanilide in TAMH cells.
Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States. 3'-Hydroxyacetanilide (AMAP), a regioisomer of APAP, is useful as a comparative tool for studying APAP-induced toxicity because it is nontoxic relative to APAP. Transforming growth factor-alpha transgenic mouse hepatocytes were treated with both isomers to investigate mitogen-activated protein kinase (MAPK) cascades in order to differentiate their toxicological outcomes. Posttranslational modifications of MAPK signaling were assessed using immunoblotting and Bioplex technology, whereas gene expression changes were measured using Affymetrix Mouse Gene 1.0 ST arrays. APAP treatment led to higher levels of glutathione depletion at 6 and 24 h compared with AMAP in mitochondria. Glutathione depletion was preceded by increased levels of c-Jun N-terminal kinase (JNK) phosphorylation at 2 and 6 h after APAP treatment compared with AMAP, whereas AMAP treatment led to increased extracellular signal-regulated protein kinase (ERK) phosphorylation at 2 and 6 h compared with APAP. Furthermore, APAP treatment significantly upregulated jun oncogene (c-Jun) gene expression, which was confirmed by Western blotting for both the phosphorylated and the nonphosphorylated forms of c-Jun protein. Transfection with JNK siRNA attenuated APAP toxicity after 24 h, suggesting that higher levels of APAP-induced activation of JNK were related to higher rates of cell death. In summary, genomic regulation of MAPK-related transcription factors coupled with posttranslational activation of their upstream kinases is critical in differentiating the toxicities of APAP and AMAP.


[The use of "cognitive" in health terminology. A latent controversy].
The adjective «cognitive» has a double meaning and it is used for naming two disciplines with separate activities: Cognitive neuroscience and cognitive psychotherapy. This has an unrecognised impact on the health terminology and the classification systems. The current use of this term is reviewed in a series of key dictionaries, scientific books, databases (OldMedline and PsycINFO) and specific web searchers (Google Scholar). The history of this term and its etymology is also reviewed and compared to other alternatives (i.e. noetic) as well as its use in international classifications (e.g. the International Classification of Functioning - ICF). The modern use of the term «cognitive» in Neurosciences can be traced back to Hebb in a 1955 one year before that recorded at official version. The different meaning of this term in psychology can be traced back to the same decade. Departing from the ICF framework of mental functions, «cognitive» can be regarded as a generic term that encompasses both neurocognitive and meta-cognitive functions and should not be used for classification purposes. A hierarchy is suggested for the use of «neurocognitive» in the classification of mental functions. The polysemic use of this name reveals a latent controversy in health sciences which has implications for its use in the international classification systems. There is an need to improve the standard definition and the semantic hierarchy of the term «cognitive», «neurocognitive» and other related terms within the context of International Health Terminology Standards Development Organisation (IHTSO).


Polypathology-associated neurodegeneration after remote head injury.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. TBI ranges from mild to severe and is a recognized risk factor for later neurodegenerative conditions including chronic traumatic encephalopathy (CTE), Alzheimer disease (AD) and Parkinson disease (PD). The development of CTE is typically associated with repetitive exposure to mild TBI (mTBI), while a single moderate-to-severe TBI is considered a risk factor for AD and PD. Polypathology is common, and the lines between these conditions post TBI can be somewhat blurred. The mechanisms through which TBI leads to future neurodegeneration are not well understood. Heterogeneity and distance from the injury or injuries and individual genetic and environmental factors make clinical studies difficult. We present the case of an 82-year-old man who died 4 years after developing a phenotypically mixed dementia with neuropsychiatric features and parkinsonism. He had a remote history of a severe TBI 40 years prior, following a road traffic accident which caused a large right frontal injury, requiring neurosurgical intervention. Post-mortem neuropathological examination demonstrated abnormal phosphorylated-Tau (p-Tau), beta-amyloid plaques (Aβ) and α-synuclein deposition. Spatial immunohistochemical analysis demonstrated increased perivascular accumulation of p-Tau with blood-brain barrier (BBB) disruption at the site of injury, which decreased with distance from the injury site. The appearances are suggestive of initial vascular disruption with persisting BBB disruption as a driver of the pathology.


Development of cytoplasmic CD3+/T cell receptor-negative cells in the peripheral lymphoid tissues of chickens.
In a study of T cell ontogeny using monoclonal antibodies specific for chicken T cell receptors (TcR) and associated cell surface molecules, we found a subset of lymphocytes that express cytoplasmic CD3 epitopes in the absence of cell surface CD3/TcR complexes. Approximately half of these cells, which were present in the spleen, bursa and intestine of young chick embryos, expressed surface CD8. None expressed CD4, TcR 1 (gamma/delta), TcR 2 (alpha/beta) or TcR 3 (a third CD3-associated heterodimer in the chicken). These cytoplasmic CD3+CD8 +/- cells, tentatively named TcR 0 cells to denote their lack of surface TcR, appeared first in the spleen of 8-day embryos, 4 days before TcR expression begins in the thymus, and reached a peak frequency of approximately 10% of the splenic cell in 14-day embryos. The TcR 0 cells were also present in adult birds, where they comprised only about 1% of the CD3+ spleen cells and approximately 40% of the lymphocytes in the intestinal epithelium. We conclude that the avian TcR 0 cells represent a thymus-independent lineage of lymphocytes which, like natural killer cells in mammals, may play an important role in body defense.


A comparison of different suture techniques for microvascular anastomosis.
Of the various techniques known, simple interrupted sutures remain the gold standard in the microanastomosis of vessels. Tying many knots, however, is time consuming. This may be of more significance with tissue such as the jejunum, which is significantly effected by ischemia time, or when several vessels are to be anastomosed. In this study, 60 femoral arteries of rabbits were divided into three equal groups. The arteries were then divided and repaired using simple interrupted, simple continuous, and continuous locked sutures. Application of the Bonferroni t-test revealed that both groups of arteries repaired using continuous sutures exhibited a statistically significant (p < 0.02) reduction in anastomosis time (50%) compared with interrupted suture techniques. However, there also was a 45% incidence of reduction in flow (9 of 21 anastomoses) when the simple running suture technique was utilized, giving the running locked suture unquestionable superiority.


In vitro comparison of cefoxitin, cefamandole, cephalexin, and cephalothin.
The in vitro effect of cefoxitin, cefamandole, cephalexin, and cephalothin was tested against 645 strains of bacteria recently isolated from clinical sources. Against gram-positive organisms cephalothin and cefamandole were the most effective, generally being three- to fourfold more active than cephalexin or cefoxitin. Enterococci were not inhibited by less than 25 mug of any of the antibiotics per ml. Against Enterobacteriaceae, cefoxitin and cefamandole were the most active. An exception was the Enterobacter strains, against which cefoxitin was the least effective. None of the Pseudomonas aeruginosa strains were susceptible to 100 mug of any of the cephalosporins per ml. Cefamandole was the most active agent against Neisseria meningitidis and Neisseria gonorrhoeae. It was also the most effective agent against Haemophilus influenzae, even when taking into account a threefold inoculum effect.


Thermoelectric properties of monolayer MSe2 (M = Zr, Hf): low lattice thermal conductivity and a promising figure of merit.
Monolayer transition-metal dichalcogenides (TMDCs) MX2 (M = Mo, W, Zr, Hf, etc; X = S, Se, Te) have become well-known in recent times for their promising applications in thermoelectrics and field effect transistors. In this work, we perform a systematic study on the thermoelectric properties of monolayer ZrSe2 and HfSe2 using first-principles calculations combined with Boltzmann transport equations. Our results point to a competitive thermoelectric figure of merit (close to 1 at optimal doping) in both monolayer ZrSe2 and HfSe2, which is markedly higher than previous explored monolayer TMDCs such as MoS2 and MoSe2. We also reveal that the higher figure of merits arise mainly from their low lattice thermal conductivity, and this is partly due to the strong coupling of acoustic modes with low frequency optical modes. It is found that the figure of merits can be better optimized in n-type than in p-type. In particular, the performance of HfSe2 is superior to ZrSe2 at a higher temperature. Our results suggest that monolayer ZrSe2 and HfSe2 with lower lattice thermal conductivity than usual monolayer TMDCs are promising candidates for thermoelectric applications.


[Prevalence of depression, anxiety, and associated factors in residents from hospital centers during COVID-19 pandemic].
To determine anxiety and depression frequency in residents from hospital centers during COVID-19 pandemic. A descriptive, observational, cross-sectional study was carried out from June to December 2020. Residents from hospitals of Secretary of Health, Puebla, were identified. The sample included 247 residents, who had an individual interview and answered a questionnaire through CEMEVI (Virtual Medical Center of High Specialty). 17 % of anxiety and 45 % of depression were reported. The most frequent age group was 26 to 31 years; 124 women and 123 men; anesthesiology, internal medicine and pediatrics were the medical specialties with greater depression; internal medicine and pediatrics were the medical specialties with greater anxiety. The risk factors for depression were anxiety (OR = 36.9), record of contact with COVID-19 patients (OR = 2.49 p = 0.035), and parental anxiety record (OR = 2.6, p = 0.009). The medical history of parents with anxiety was risk factor for anxiety (OR = 2.3, p = 0.031). Prevalence of depression and anxiety should alert to seek answers to the problem.


Thermo-mechanical degradation of composite restoration photoactivated by modulated methods-a SEM study of marginal and internal gap formation.
To evaluate the influence of thermal-mechanical degradation on superficial and internal gap formation of composite restorations photoactivated using modulated methods. An experimental composite was prepared using a resin matrix containing 65wt% Bis-GMA and 35wt% TEGDMA. Camphorquinone (0.5wt%) and dimethylaminoethyl-methacrylate (0.5wt%) were dissolved in the resin as a photo-initiator system and 65wt.% silanized glass fillers were added to the matrix. Ground buccal surfaces of bovine lower incisors were used to make 160 preparations (3 mm × 3 mm × 2 mm in depth). An adhesive system (Adper Single Bond 2) was applied and the specimens were assigned into 16 groups (n = 10), according to the photoactivation method [high intensity (HI), low intensity (LI), soft-start (SS) and pulse-delay (PD)] and the degradation protocol [(control/no degradation; thermal cycling (TC); mechanical loading (ML); thermo-mechanical loading (TC+ML)]. Marginal and internal interfaces of bonded restorations were replicated in epoxy resin and analyzed by SEM. Gaps were expressed as a percentage of the total length of the margins. Data were submitted to 2-way ANOVA and Tukey's test (α = 0.05). For the control group no significance was noted among the photoactivation methods. TC had no effect in gap formation. ML and TC+ML increased the incidence of superficial gaps for both HI and SS groups as well as increased the internal gaps for all groups. Although photoactivation methods do not influence gap formation at first, composite restoration photoactivated by low intensity or modulated methods showed improved resistance to thermo-mechanical degradation. Mechanical loading is determinant for interfacial degradation of composite restorations, while thermal cycling has no effect on gap formation.


New insights into the interaction between polycystic ovary syndrome and psychiatric disorders: A narrative review.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease characterized by hyperandrogenism, ovulatory dysfunction, and ovarian polycystic changes, which combines with reproductive problems, metabolic disorders, and psychological disorders to exhibit a far-reaching impact on the physical and mental health of women. We reviewed previous research and discovered that psychiatric disorders are more common in PCOS patients and their children, potentially exacerbating the condition and creating a vicious loop. To understand the reasons, relevant articles were collected following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines from PubMed, Web of Science, and Cochrane Library, through December 2022. Evidence suggested that PCOS-related clinical manifestations, hyperandrogenism, insulin resistance, obesity, gut dysbiosis, and other variables may increase the risk of psychiatric disorders in patients. In turn, psychiatric disorders may aggravate the pathologic process of PCOS and increase the difficulty of the treatment. We systematically reported the mechanisms underlying the psychiatric disorders-PCOS interactions, intending to provide potential ways to break the vicious cycle and lay the groundwork for future research. However, research on PCOS and psychiatric disorders were still in initial stages, which limited the scope of this review. More studies are needed to further verify our findings.


Reversal of halophilicity in a protein-DNA interaction by limited mutation strategy.
Comparison of the genes of functionally homologous proteins in organisms existing in different environments shows that adaptation is most often accomplished by mutation of an existing protein. However, from such comparisons, the significance of individual residues to the particular environmental adaptation is not generally discernable among the mass of changes that occur over evolutionary time. This can be exemplified by the general transcription factor found in eukaryotes and archaea, the TATA binding protein (TBP). TBP from Pyrococcus woesei is adapted for optimal binding to DNA at high salt and high temperature, with 34% of the amino acids altered in comparison to its nearest known mesophilic counterpart. We demonstrate that the halophilic nature of this protein can be attributed to only three mutations, revealing that the important phenotype of halophilicity could be rapidly acquired in evolutionary time.


Cannabis and Young Users-A Brief Intervention to Reduce Their Consumption (CANABIC): A Cluster Randomized Controlled Trial in Primary Care.
Brief intervention to reduce cannabis is a promising technique that could be adapted for use in primary care, but it has not been well studied in this setting. We tested the efficacy of a brief intervention conducted by general practitioners among cannabis users aged 15 to 25 years. We performed a cluster randomized controlled trial with 77 general practitioners in France. The intervention consisted of an interview designed according to the FRAMES (feedback, responsibility, advice, menu, empathy, self-efficacy) model, while the control condition consisted of routine care. The general practitioners screened and followed up 261 young cannabis users. After 1 year, there was no significant difference between the intervention and control groups in the median number of joints smoked per month among all users (17.5 vs 17.5; P = .13), but there was a difference in favor of the intervention among nondaily users (3 vs 10; P = .01). After 6 months, the intervention was associated with a more favorable change from baseline in the number of joints smoked (-33.3% vs 0%, P = .01) and, among users younger than age of 18, smoking of fewer joints per month (12.5 vs 20, P = .04). Our findings suggest that a brief intervention conducted by general practitioners with French young cannabis users does not affect use overall. They do, however, strongly support use of brief intervention for younger users and for moderate users.


Polycomb group protein Suz12 is regulated by a novel miRNA-like small RNA.
Human mesenchymal stem/stromal cells (hMSCs) provide support for cancer progression, partly through their secretome that includes extracellular vesicles (EVs). Based on deep-sequencing of small RNA from EVs of MSCs, we now report the characterization of novel small RNA, named n-miR-G665, which exhibits typical properties of miRNAs. n-miR-G665 sequence is conserved and expressed in most cell types. Knockdown studies using anti-agomirs and shRNA studies demonstrated that n-miR-G665 plays an important role in cell proliferation. Functional assays to reveal the targets of n-miR-G665 showed that polycomb protein Suz12 is regulated by n-miR-G665, which in turn regulates the expression of n-miR-G665 through feedback loop mechanism. These data shed light on a previously unknown novel feedback regulatory mechanism for controlling Suz12 expression regulated by previously not described miRNA, which may highlight a new therapeutic approach to control the polycomb repressor complex 2 activity in cancers.


Nitric oxide is involved in integration of UV-B absorbing compounds among parts of clonal plants under a heterogeneous UV-B environment.
In nature, ultraviolet-B (UV-B) radiation is highly heterogeneous, both spatially and temporally. Plants exposed to UV-B radiation produce UV-B absorbing compounds that function as a protective filter. For clonal plants under heterogeneous UV-B radiation conditions, integration among ramets can allow irradiated ramets to benefit un-irradiated ramets by causing them to increase their UV-B absorbing compounds content. In this study, we evaluated integration between pairs of clonal ramets of Glechoma longituba under heterogeneous or homogeneous UV-B conditions. We determined the levels of UV-B absorbing compounds, nitric oxide (NO) and hydrogen peroxide (H2 O2 ) and measured the activity of phenylalanine ammonia-lyase (PAL) in connected ramet pairs under homogeneous or heterogeneous UV-B conditions. Under heterogeneous UV-B conditions, the UV-B absorbing compounds content increased in leaves of irradiated and un-irradiated ramets, but not in the connecting stolons. The NO content increased in irradiated and un-irradiated leaves and stolons, but the H2 O2 content did not. Application of NO synthesis inhibitors and an NO blocker to irradiated ramets blocked the increase in UV-B absorbing compounds and PAL activity in un-irradiated ramets. These results suggested that NO is involved in the integration process for UV-B absorbing compounds among ramets. Our findings suggested that a UV-B-induced increase in NO transmits a signal to un-irradiated ramets via the stolon, leading to an increase in PAL activity and UV-B absorbing compounds content. The internal translocation of signal enables members of clonal networks to function as a whole unit and to mount an efficient defensive response to localized UV-B radiation.


Population attributable fractions for risk factors for spontaneous preterm births in 81 low- and middle-income countries: A systematic analysis.
Complications associated with preterm birth (PTB) are the largest contributor to under-five mortality globally. Success in reaching the Sustainable Development Goal target requires identifying potentially modifiable risk factors for PTB, estimating the relative importance of these risk factors, and identifying/implementing effective prevention strategies to address them. We conducted a literature review to define risk relationships and estimate prevalence for established risk factors for spontaneous PTB (sPTB). We then estimated population attributable fractions (PAF) for the sPTB risk factors identified in the review as statistically significant for the 81 low- and middle-income (LMIC) countries included in the Countdown 2030 initiative. We summed country-level findings to produce PAFs for each risk factor and regional estimates for sub-Saharan Africa and South Asia. Forty-four potential sPTB risk factors were identified. and the final analysis included twenty-four risk factors with evidence of significant associations with sPTB. A second model with three additional risk factors with borderline insignificant associations was also run. Taken together, the twenty-four risk factors had a total PAF of 73% for all 81 countries and 77% and 72% of sPTB in sub-Saharan Africa and South Asia, respectively. For all countries, maternal undernutrition had the highest PAF (17.5%), followed by maternal infections (16.6%), environmental exposures (16%) and pregnancy history (8.7%). While multiple risk factors contribute to sPTB, no single risk factor addresses a predominant fraction, and 27% of spontaneous preterm births are not associated with risk factors that we identified. Despite the significant role of preterm birth in child survival, there are major data gaps in LMIC settings. Furthermore, there is a paucity of evidence for effective interventions to prevent preterm birth. Preventing sPTB requires understanding underlying mechanisms leading to sPTB in different populations, and the identification/implementation of effective interventions.


Knowledge, attitudes, and practices regarding cystic echinococcosis and sheep herding in Peru: a mixed-methods approach.
The parasitic disease, cystic echinococcosis (CE), is prevalent in low-income, livestock-raising communities and 2000 new people will be diagnosed this year in South America alone. The disease usually passes from livestock to dogs to humans, making it a zoonotic disease and part of the One Health Initiative. Control of CE has been infamously difficult; no endemic areas of South America have succeeded in maintaining sustainable eradication of the parasite. For the current study, we aimed to gain a better understanding of the knowledge, attitudes, and practices of rural sheep farmers and other community leaders regarding their sheep herding practices and perspectives about a control program for CE. We also hope to identify potential barriers and opportunities that could occur in a control program. The authors conducted Knowledge, Attitude and Practices (KAP) surveys and semi-structured interviews in rural communities in the highlands of Peru. The KAP surveys were administered to 51 local shepherds, and the semi-structured interviews were administered to 40 individuals, including shepherds, community leaders, and health care providers. We found that the shepherds already deworm their sheep at a median of 2 times per year (N = 49, range 2-4) and have a mean willingness-to-pay of U.S. $ 0.60 for dog dewormer medication (N = 20, range = 0.00- $2.00 USD). We were not able to learn the deworming agent or agents that were being used, for neither sheep nor dogs. Additionally, 90% of shepherds slaughter their own sheep (N = 49). We also learned that the main barriers to an effective control program include: lack of education about the cause and control options for CE, accessibility to the distant communities and sparse grazing pastures, and a lack of economic incentive. Findings suggest it may be feasible to develop an effective CE control program which can be used to create an improved protocol to control CE in the region.


Epidemiology and treatment of atraumatic subarachnoid hemorrhage over 10 years in a population-based registry.
Incidence of atraumatic subarachnoid hemorrhage (SAH) is decreasing over time and its treatment is changing. We reported epidemiologic data on aneurysmal (a-) and non-aneurysmal (na-) SAH over 10 years. Our prospective population-based registry included patients with first-ever SAH occurring from January 2011 to December 2020. Clinical and neuroimaging records were screened to evaluate the presence and location of intracranial aneurysms, to identify naSAH subtypes and to retrieve information on surgical treatments. Incidence rates were standardized to the 2011 Italian and European population. We also estimated 30-day and 1-year case-fatality rates after SAH. Multivariate hazard ratios for 30-days and 1-year fatality were estimated with Cox regression analysis. 194 patients (60.8% women; mean age 62.5 ± 16.0 years) were included (76.8% aSAH and 23.2% naSAH). The crude incidence rates per 100,000 person-years of SAH, aSAH, and naSAH were 6.5 (95% CI 5.6-7.5), 5.0 (95% CI 4.2-5.9), and 1.5 (95% CI 1.1-2.0), respectively, and remained stable over time. Compared to aSAH, naSAH patients had higher age (68.8 ± 19.7 yearsvs 60.6 ± 14.2 years; p = 0.012), lower cigarette smoking (17.9%vs 36.4%; p < 0.001) and higher atrial fibrillation (15.7% vs 2.8%; p = 0.005). SAH case-fatality rates within 30-days and 1-year were 28.4% (95% CI 21.4-36.9) and 37.1% (95% CI 29.0-46.7), respectively. The relative proportion of surgically treated patients did not change over time. We found a low and stable incidence of SAH over the 2011-2020 period. naSAH remained rare and deserves further investigation in larger prospective cohorts.


Cardiovascular Magnetic Resonance Detects Myocardial Inflammation in Giant Cell Arteritis.
We describe a patient with GCA and cardiac involvement, presented as myocardial inflammation with reduced biventricular ejection fraction and diagnosed using cardiovascular magnetic resonance (CMR). She was treated successfully with sacubitril/valsartan in parallel with anti-rheumatic medication and the post-treatment CMR showed improvement of biventricular function and disappearance of myocardial inflammation.


Haplorchis infections in intermediate hosts from a clonorchiasis endemic area in Meinung, Taiwan, Republic of China.
Snails and freshwater fish were examined from four ponds in the Meinung township in which Clonorchis sinensis was known to be endemic 18 years ago. No metacercariae were found in 478 Tilapia nilotica, whereas of 451 Ctenopharyngodon idellus examined, 16.2%, 3.3% and 0.9% were found to be infected with Haplorchis pumilio, H. taichui and Clonorchis sinensis, respectively. In addition, there were some unidentified metacercariae in 12.0% of Ctenopharyngodon idellus examined. Overall, no positive correlation between infection rates and sizes of infected fish was shown. Six species of snails were collected in this survey and two frequently-occurring snails, Melanoides tuberculata and Thiara granifera were commonly infected with H. pumilio. Reasons for the prevalence of Haplorchis species and the absence of Clonorchis sinensis in fish and snail hosts in a previously reported endemic area for human clonorchiasis are discussed.


Assessment of Subtle Changes in Diabetes-Associated Arteriosclerosis using Photoplethysmographic Pulse Wave from Index Finger.
Distortions in macro- and microcirculation are principal contributors to diabetes-associated complications. This study aimed at investigating the validity of applying non-invasive photoplethysmographic (PPG) waveform parameters in detecting diabetes-induced subtitle changes in arterial stiffness. Between July 2009 and October 2010, totally 94 middle-aged and elderly subjects were recruited including 48 without diabetes (Group 1) and 46 with the disease (Group 2). Demographic (i.e., age, gender), anthropometric (body-mass index), biochemical (i.e., glycated hemoglobin concentration), and hemodynamic (i.e., systolic blood pressure, heart rate) parameters were obtained. Crest time (CT) and crest time ratio (CTR) computed from PPG signals acquired from left index finger were compared with left index finger pulse wave velocity (PWVfinger) obtained from six-channel ECG-PWV system to investigate the differences between the two groups and the associations of these indices with the parameters of testing subjects. Significant difference was only noted in CTR between the two groups (P < 0.005). Despite correlation of both CT and CTR with age, only CTR demonstrated significant associations with hemodynamic parameters. CTR could differentiate diabetic patients from healthy individuals despite absence of difference in arterial stiffness assessed by conventional PWV, highlighting its superior sensitivity to subtle changes in diabetes-associated arteriosclerosis.


Expected behavior of quantum thermodynamic machines with prior information.
We estimate the expected behavior of the quantum model of a heat engine when we have incomplete information about external macroscopic parameters such as the magnetic field controlling the intrinsic energy scales of the working medium. We explicitly derive the prior probability distribution for these unknown parameters ai (i=1,2). Based on a few simple assumptions, the prior probability distribution is found to be of the form Π(ai)∝1/ai. By calculating the expected values of various physical quantities related to this engine, we find that the expected behavior of the quantum model exhibits thermodynamiclike features. This leads us to a surprising proposal that incomplete information quantified as an appropriate prior distribution can lead us to expect classical thermodynamic behavior in quantum models.


Radiographic and histologic analysis of the tibial tunnel after allograft anterior cruciate ligament reconstruction in goats.
Several problems have been reported with use of allogenic grafts in anterior cruciate ligament reconstruction, including local immune response to allograft tendon within the synovial fluid, delayed maturation and ligamentization, and progressive tibial tunnel enlargement. There is a correlation between the use of allograft and tibial tunnel enlargement. Controlled laboratory study. Twenty healthy adult female goats underwent allograft anterior cruciate ligament reconstruction and were followed with serial radiographs at 6-week intervals. Animals were randomly chosen for sacrifice between 18 and 36 weeks for histologic assessment. Significant radiographic increases in tunnel size were noted within the first 6 weeks of healing and remained up to 36 weeks with no further remodeling noted. Histologic analysis showed progressive ligamentization of the allografts with tendon-to-tunnel wall biologic fixation with dense connective tissue. Remodeling and incorporation of the bone plug was seen in all cases. The allograft tendon underwent early fibrous attachment within the tunnel and remodeled toward ligament histologic structure. Remodeling and incorporation of the bone plug was seen by 18 weeks. Tibial tunnel enlargement, consistent with that seen in humans after allograft anterior cruciate ligament reconstruction, did not appear to affect the ultimate incorporation of the allograft on a histologic level.


Confinement effects on intermediate-state flux patterns in mesoscopic type-I superconductors.
Intermediate-state flux structures in mesoscopic type-I superconductors are studied within the Ginzburg-Landau theory. In addition to well-established tubular and laminar structures, the strong confinement leads to the formation of (i) a phase of singly quantized vortices, which is typical for type-II superconductors and (ii) a ring of a normal domain at equilibrium. The stability region and the formation process of these intermediate-state structures are strongly influenced by the geometry of the sample.


Targeted magnetic resonance imaging (tMRI) of small changes in the T1 and spatial properties of normal or near normal appearing white and gray matter in disease of the brain using divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences.
This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.


Balancing Water Uptake and Loss through the Coordinated Regulation of Stomatal and Root Development.
Root development is influenced by nutrient and water availabilities. Plants are able to adjust many attributes of their root in response to environmental signals including the size and shape of the primary root, lateral roots and root hairs. Here we investigated the response of roots to changes in the levels of leaf transpiration associated with altered stomatal frequency. We found that plants with high stomatal density and conductance produce a larger rooting area and as a result have enhanced phosphate uptake capacity whereas plants with low stomatal conductance produce a smaller root. Manipulating the growth environment of plants indicated that enhanced root growth is most likely a result of an increased demand for water rather than phosphate. Plants manipulated to have an increase or reduction in root hair growth show a reduction or increase respectively, in stomatal conductance and density. Our results demonstrate that plants can balance their water uptake and loss through coordinated regulation of both stomatal and root development.


Effects of radiation therapy on tumor microenvironment: an updated review.
Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.


Use of trabecular bone score for risk stratification of patients with monoclonal gammopathy of undetermined significance.
Monoclonal gammopathy of undetermined significance (MGUS) is a common finding in clinical practice. The risk for developing MGUS increases with aging in parallel with age-associated increases in fracture risk. Although there is good evidence that patients with MGUS suffer from increased fracture risk, no standardized guidelines exist for the evaluation and/or management of skeletal health in patients with MGUS. Trabecular bone score (TBS), a texture index derived from lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) images, provides information about trabecular microarchitecture independent of bone mineral density (BMD). We retrospectively identified 155 adult patients diagnosed with MGUS between 2005 and 2018. This group was matched 1:1 to a control group for sex, age and BMI. TBS was performed retrospectively, and values categorized as low (≤1.23), intermediate (1.23-1.31) or normal (>1.31). Patients had a mean ± SD age of 69.6 ± 10.0. BMD was performed within a median of 28 months (IQR 1-78) of MGUS diagnosis. Cases had a non-statistically significant higher rate of fractures compared to control subjects (27 vs. 17, respectively, p = 0.1). Patients with MGUS had a significantly lower TBS (1.31 ± 0.13 vs. 1.34 ± 0.12, respectively, p < 0.05) and lower LS BMD (1.215 ± 0.223 vs. 1.275 ± 0.247, p < 0.05) compared to controls. Although fractures occurred more commonly in those control subjects with significantly lower TBS values, this was not the case in subjects with MGUS (TBS 1.299 vs. 1.313 in cases with vs. without fractures p = 0.313). Similarly, there was no difference in T-scores in cases with or without fractures (-1.33 vs. -1.37, respectively, p = 0.56). Despite patients with MGUS having a significantly increased fracture risk compared to age-, sex- and BMI-matched control subjects, neither assessment of BMD nor TBS, obtained within two years of MGUS diagnosis, were able to accurately risk stratify MGUS patients. Unlike control subjects, patients with MGUS tend to fracture despite normal BMD and intermediate or normal TBS values, suggesting that deterioration of cortical rather than trabecular skeletal components may be more important for the increased fracture risk seen in MGUS.


The effect of copper deficiency on the induction of tryptophan pyrrolase in chick liver by hydrocortisone.
The induction of tryptophan pyrrolase in chick liver by hydrocortisone was studied in copper- and magnesium-deficient chicks. Magnesium deficiency did not influence the induction of the enzyme, whereas copper deficiency significantly decreased it. These results suggest that tryptophan pyrrolase of chick liver, like that in Pseudomonas, is a copper-containing enzyme.


A challenge for diagnosing acute liver injury with concomitant/sequential exposure to multiple drugs: can causality assessment scales be utilized to identify the offending drug?
Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis.


One-Pot Rapid Access to Benzyl Silanes, Germanes, and Stannanes from Toluenes Mediated by a LiN(SiMe3)2/CsCl System.
Organo-silanes, germanes, and stannanes are considered to be conducive to the development of cross-coupling reactions because they are stable, nontoxic, and easy to handle. Using feedstock toluenes, one-pot direct benzylic C-H silylations, germylations, and stannylations are developed. Simply combining toluenes, LiN(SiMe3)2/CsCl, and R3MCl (M = Si, Ge, Sn) generates a diverse array of bench-stable benzyl silanes, germanes, and stannanes (38 examples, 53-90% yields). The syntheses developed here are easy to access on scale.


Comparison of nutritive and nonnutritive stimuli in intestinal and oral conditioned taste aversion paradigms.
The intestinal taste aversion paradigm has previously demonstrated that animals could orally discriminate between carbohydrate and fat subsequent to pairing a gastrointestinal (GI) infusion of 1 nutrient with lithium chloride (LiCl), whereas they could not discriminate between 2 nonnutritive flavors (A. L. Tracy, R. J. Phillips, M. M. Chi, T. L. Powley, & T. L. Davidson, 2004). The present experiments assessed the relative salience of nutritive and nonnutritive stimuli when presented either intestinally or orally. Two compound stimuli, each comprising 1 nutrient and 1 nonnutritive flavor, were presented in training and were paired with LiCl or saline. Subsequent oral intake of the nutrients alone, the flavors alone, or the compounds was measured. Results showed that rats discriminated both nutrients and flavors independently after GI or oral training, whereas the compounds were discriminated only after oral training, indicating substantive differences in the processing of these stimuli. This suggests that nutrient activation of the GI tract may potentiate learning about nonnutritive flavors analogously to taste-potentiated odor conditioning. The ability to learn about the oral properties of stimuli in the GI tract suggests a new account of delayed taste aversion learning as well as learning about the positive nutritive consequences of food consumption.


Characterization of in vitro oxidative and conjugative metabolic pathways for brevetoxin (PbTx-2).
Brevetoxins are potent marine toxins produced by the dinoflagellate Karenia brevis, the causative organism of Florida red tides. An in vitro metabolism of PbTx-2 was performed using purified cDNA-expressed rat liver cytochrome P-450 (CYP) enzymes and freshly isolated rat hepatocytes. The metabolic activities of six CYP enzymes, CYP1A2, CYP2A2, CYP2C11, CYP2D1, CYP2E1, and CYP3A1, were examined by incubation with PbTx-2 for up to 4 h in the presence of a NADPH-generating system. Further identification of the metabolites produced by CYP1A2 and CYP3A1 was preformed using high performance liquid chromatography-mass spectrometry (LC/MS). Both CYP1A2 and CYP3A1 metabolized PbTx-2 to PbTx-3 (MH+: m/z 897), PbTx-9 (MH+: m/z 899), and a newly recorded diol brevetoxin-2 metabolite (MH+: m/z 929). CYP3A1 also produced a considerably higher amount of BTX-B5 (MH+: m/z 911). Subsequent incubation of PbTx-2 with rat hepatocytes produced additional phase 1 metabolites of MH+: m/z 911, 913, 915, 917, and 931, indicating a CYP-catalyzed epoxidation at H-ring (C27,C28-double bond) and a subsequent A-ring hydrolysis of PbTx-2 metabolic products. A conjugation metabolism was identified by the production of a glutathione-brevetoxin conjugate (MH+: m/z 1222) and a cysteine-brevetoxin conjugate (MH+: m/z 1018). Structures of the new metabolites are postulated, and a likely CYP-catalyzed metabolism pathway of PbTx-2 metabolism are discussed.


Slow photoelectron imaging spectroscopy of CCO- and CCS-.
High-resolution photodetachment spectra of CCO(-) and CCS(-) using slow photoelectron velocity-map imaging spectroscopy are reported. Well-resolved transitions to the neutral X (3)Sigma(-), a (1)Delta, b (1)Sigma(+), and A (3)Pi states are seen for both species. The electron affinities of CCO and CCS are determined to be 2.3107+/-0.0006 and 2.7475+/-0.0006 eV, respectively, and precise term energies for the a (1)Delta, b (1)Sigma(+), and A (3)Pi excited states are also determined. The two low-lying singlet states of CCS are observed for the first time, as are several vibronic transitions within the four bands. Analysis of hot bands finds the spin-orbit orbit splitting in the X (2)Pi ground state of CCO(-) and CCS(-) to be 61 and 195 cm(-1), respectively.


Coffee and tea consumption and cancers of the bladder, colon and rectum.
Coffee has been observed to be associated weakly or not at all with bladder cancer risk, inversely with colon cancer risk, and inconsistently with rectal cancer risk. The association between these cancers and consumption of coffee and tea was examined in a single case-control study conducted in Ontario, Canada from 1992 to 1994. A questionnaire was filled out by 927 bladder cancer cases, 991 colon cancer cases, 875 rectal cancer cases, and 2118 population controls. Although bladder cancer risk was not associated with coffee or tea, risk estimates associated with coffee among subjects who had never smoked were non-significantly increased. Colon cancer risk was inversely associated with coffee. Relative to those drinking less than 1 cup of coffee per day, the odds ratios (OR) for those drinking 1-2 cups was 0.9 (95% CI 0.8-1.1), for those drinking 3-4 cups was 0.8 (95% CI 0.7-1.0), and for those drinking 5 or more cups was 0.7 (95% CI 0.5-0.9); these ORs decreased linearly (P = 0.008). The reduced risk estimates were more pronounced with cancer of the proximal colon than the distal colon. Rectal cancer risk was not associated with either coffee or tea. Coffee consumption was observed to have a different relationship for each of the cancer sites and tea consumption was not related to any cancer site.


Nonnutritive sweetener consumption during pregnancy, adiposity, and adipocyte differentiation in offspring: evidence from humans, mice, and cells.
Obesity often originates in early life, and is linked to excess sugar intake. Nonnutritive sweeteners (NNS) are widely consumed as "healthier" alternatives to sugar, yet recent evidence suggests NNS may adversely influence weight gain and metabolic health. The impact of NNS during critical periods of early development has rarely been studied. We investigated the effect of prenatal NNS exposure on postnatal adiposity and adipocyte development. In the CHILD birth cohort (N = 2298), we assessed maternal NNS beverage intake during pregnancy and child body composition at 3 years, controlling for maternal BMI and other potential confounders. To investigate causal mechanisms, we fed NNS to pregnant C57BL6J mice at doses relevant to human consumption (42 mg/kg/day aspartame or 6.3 mg/kg/day sucralose), and assessed offspring until 12 weeks of age for: body weight, adiposity, adipose tissue morphology and gene expression, glucose and insulin tolerance. We also studied the effect of sucralose on lipid accumulation and gene expression in cultured 3T3-L1 pre-adipocyte cells. In the CHILD cohort, children born to mothers who regularly consumed NNS beverages had elevated body mass index (mean z-score difference +0.23, 95% CI 0.05-0.42 for daily vs. no consumption, adjusted for maternal BMI). In mice, maternal NNS caused elevated body weight, adiposity, and insulin resistance in offspring, especially in males (e.g., 47% and 15% increase in body fat for aspartame and sucralose vs. controls, p < 0.001). In cultured adipocytes, sucralose exposure at early stages of differentiation caused increased lipid accumulation and expression of adipocyte differentiation genes (e.g., C/EBP-α, FABP4, and FASN). These genes were also upregulated in adipose tissue of male mouse offspring born to sucralose-fed dams. By triangulating evidence from humans, mice, and cultured adipocytes, this study provides new evidence that maternal NNS consumption during pregnancy may program obesity risk in offspring through effects on adiposity and adipocyte differentiation.


Medial opening wedge high tibial osteotomy for osteoarthritis of knee: long-term results in 50 knees.
To retrospectively study the long term results of high tibial valgus osteotomy in management of primary medial compartment osteoarthritis, with special reference to patient satisfaction and functional assessment, we conducted this study in radiologically established 50 knees of patients with primary osteoarthrosis of knee. In these patients with medial compartment disease (varus knee), medial open wedge osteotomy was performed using full thickness iliac crest grafts. These were called for follow-up after average 7.5 years and clinico-radiological assessment was done. Although many surgeons of the west do not favour this osteotomy, we found the procedure to be quite acceptable to our patients in whom the primary concerns of cost and squatting habits are well taken care of. The authors feel that this osteotomy is still relevant in the third world. Results do deteriorate with time but most patients consider the surgery satisfactory.


The risk of abscess from sternoclavicular septic arthritis.
From a systematic review of the literature on septic arthritis and our own patient records we found that in a high percentage of cases (20% of those we reviewed) infection of the sternoclavicular joint leads to an abscess. This appears to be true regardless of the presence or absence of a history of intravenous drug abuse or underlying illness compromising the immune system, and regardless of the responsible organism. The predisposing factors must center on the joint itself. The risk from spread of infection should be considered in management of the uncommon but difficult clinical problem of sternoclavicular septic arthritis.


Inulin-whey protein as efficient vehicle carrier system for chlorophyll: Optimization, characterization, and functional food application.
Natural chlorophylls mostly found in vegetables such as spinach (Spinacia oleracea) could be employed as a possible substitute for synthetic colorants because of their intense green properties. However, the stability of natural chlorophyll is a major challenge to its utilization in the food industry. In this study, spray drying as an encapsulation technique was used to improve the stability of natural chlorophyll. Box-Behnken design was utilized to optimize the spray drying conditions for chlorophyll. Optimum conditions were given as inlet temperature, 132°C; inulin-to-whey protein isolate ratio, 61%:39%; pump rate, 25%, resulting in 92.3% encapsulation efficiency, 69.4% solubility, and -13.5 mV zeta potential at a desirability level of 0.901. The particle size, Carr index, bulk and tapped density, polydispersity index, and color showed satisfactory results. Crystallinity, endothermic peak melting temperature, and the enthalpy of chlorophyll-loaded microcapsules increased when compared to the blank microcapsules suggesting decreased hygroscopicity and enhanced thermal stability. In addition, the suitability of fabricated microcapsules using yogurt as a food model was assessed. Yogurt incorporated with chlorophyll-loaded microcapsules showed no significant pH modification with better apparent viscosity than control and sodium copper chlorophyllin (SCC) yogurt after 9 days of refrigerated storage. Based on the studied responses, the spray drying process could be optimized to achieve optimal output and product quality. PRACTICAL APPLICATION: Spray drying is a cheap and convenient approach for microencapsulating bioactive compounds such as chlorophyll. However, the physico-chemical and functional properties of the spray-dried microcapsules are influenced by operating conditions, such as inlet temperature, type and concentration of wall materials, and feed flow rate. Therefore, to maximize and obtain a superior quality of the final product, there is a need to optimize the spray drying process. The Box-Behnken design employed in this study could be utilized as an appropriate technique to design, enhance, and develop process parameters for the fabrication and better retention of the physico-chemical properties of spray-dried chlorophyll microcapsules.


Prognostic Predictors of Tricuspid Regurgitation Worsening after Mitral Regurgitation Surgery with Mild Tricuspid Regurgitation.
We aimed to investigate the prevalence and predictors of postoperative tricuspid regurgitation (TR) worsening in patients with mitral regurgitation (MR) and concomitant ≤mild TR. A total of 620 patients underwent surgery for MR from 2013 to 2017. Of these, 260 had ≤mild preoperative TR and no concomitant tricuspid valve surgery and were enrolled in this single-center retrospective study. The primary endpoint was postoperative worsening of ≥moderate TR. The primary endpoint occurred in 28 of 260 patients (11%) during the follow-up period [median: 4.1 years (interquartile range: 2.9-6.1 years)]. In the multivariable analysis, age, female sex, and left atrial volume index (LAVI) were significant predictors of the primary outcome during intermediate-term follow-up (age: hazard ratio [HR] 1.05 per 1-year increment, 95% confidence interval [CI] 1.02-1.10, P = 0.003; female sex: HR 3.53, 95% CI 1.61-7.72, P = 0.002; LAVI: HR 1.17 per 10-mL/m2 increment, 95% CI 1.07-1.26, P < 0.001). The optimal LAVI cut-off value for predicting postoperative TR worsening was 79 mL/m2 (area under the curve: 0.69). A high LAVI (>79 mL/m²) was significantly associated with a low rate of freedom from postoperative TR worsening compared with a low LAVI (≤79 mL/m²) (82.6% vs 93.9% at 5 years, respectively; log-rank P = 0.008). In patients with ≤mild preoperative TR and no concomitant tricuspid surgery, the rate of postoperative TR worsening was 11% during intermediate-term follow-up. LA enlargement in patients with MR and ≤mild preoperative TR was significantly associated with postoperative TR worsening.


Effect of sociodemographic factors on survival of people living with HIV.
The purpose is to describe and understand the sociodemographic determinants of survival in people living with HIV within high-income countries in the context of the current recommendation of universal antiretroviral therapy for all HIV-infected persons, irrespective of their CD4 cell count. Survival rates in people living with HIV have experienced remarkable increases in the last decade because of more efficacious and well tolerated treatments. Still, these improvements are unevenly distributed between regions across the world as well as within regions. HIV outcomes are heavily influenced by what are known as the 'social determinants' of health which have traditionally encompassed the gender, race/ethnicity, and socioeconomic axes. The evidence that these social determinants are now more important than before (more and earlier interventions are now available), has become stronger in the last 2 years. Because antiretroviral therapy is now recommended for all HIV-infected persons, sociodemographic factors limiting access to testing, treatment, and retention in care will undoubtedly jeopardize the UNAIDS aspirational objective to end AIDS by 2030. Innovative interventions targeting individuals with social vulnerability are urgently needed to ensure that social inequalities do not continue to be linked with higher mortality.


Pemphigus Vegetans Confined to the Face and Scalp.
A 58-year-old man presented to our department with multiple chronic vegetant plaques on the face and scalp that had been present for 4 months. The plaques were well-defined hypertrophic areas, measuring between 3 cm × 3 cm and 3 cm × 4 cm, that were located mainly on the face symmetrically and on the forehead (Figure 1). The patient did not report itching or pain. There were also dry, crusty, well-defined plaques on the scalp. No other lesions were present on the skin or mucous membranes.


Observations on Antricola ticks: small nymphs feed on mammalian hosts and have a salivary gland structure similar to ixodid ticks.
Ticks use bloodmeals as a source of nutrients and energy to molt and survive until the next meal and to oviposit, in the case of females. However, only the larvae of some tick species are known to feed upon bats; females are obligatorily autogenous, and nymphal stages are believed to not feed. We investigated the presence of blood in a natural population of nymphal Antricola delacruzi ticks collected from bat guano; their ability to feed upon laboratory hosts; and the microscopic structure of both salivary glands and gut. DNA amplification of gut contents of freshly collected material was positive for a mammal in 4 of 11 first instar nymphs, but we were unsuccessful in the amplification of host bloodmeal DNA from late instar nymphs. All early nymphal stages (n = 10) fed on rabbits, and host DNA was detected and sequenced from gut contents. However, all the large nymphs (n = 10) rejected feeding, and host DNA remained undetected in these ticks. All stages of A. delacruzi have salivary glands similar in morphology to the ixodid agranular Type I salivary gland acini and to granular Type II or Type B acini. All stages of A. delacruzi had a similar gut structure, consisting of digestive cells in the basal portion that contained hematin granules. Neither regenerative nor secretory cell traces were observed in the sections of gut.


Validity and reliability of a Persian translation of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS).
Cognitive dysfunction is common in multiple sclerosis (MS) and validated batteries are limited in languages other than English. We aimed to translate, cross-culturally adapt, validate, and assess reliability of Minimal Assessment of Cognitive Function in MS (MACFIMS) in Persian. The MACFIMS is a well-constructed battery in the MS literature. The battery was adapted to Persian in accordance with available guidelines. A total of 158 MS patients and 90 controls underwent neuropsychological assessment. For reliability assessment the battery was re-administered in a subset of 41 patients after a short interval using alternate forms to mitigate practice effects (approximately 10 days). Patients performed significantly worse than controls in all cognitive tests, supporting discriminant validity of our adapted battery. Approximately half of patients (46.2%) showed cognitive impairment as defined by the impairment in two or more tests. The Symbol Digit Modalities Test was the most robust test by ROC analysis. All tests showed acceptable to good level of reliability. This is the first validation of gold-standard cognitive testing in Persian. The Persian MACFIMS shows nearly the same psychometrics as its English counterpart.


Nonlinear Poisson-Boltzmann model of charged lipid membranes: Accounting for the presence of zwitterionic lipids.
The nonlinear Poisson-Boltzmann model is used to derive analytical expressions for the free energies of both mixed anionic-zwitterionic and mixed cationic-zwitterionic lipid membranes as function of the mole fraction of charged lipids. Accounting explicitly for the electrostatic properties of the zwitterionic lipid species affects the free energy of anionic and cationic membranes in a qualitatively different way: That of an anionic membrane changes monotonously as a function of the mole fraction of charged lipids, whereas it passes through a pronounced minimum for a cationic membrane.


Ultra-Long Cycle of Prussian Blue Analogs Achieved by Equilibrium Electrolyte for Aqueous Sodium-Ion Batteries.
Aqueous sodium-ion batteries have promising prospects in large-scale electrical energy storage, which lack of suitable cathode with high specific capacity and long cycle lifespan, unfortunately. Manganese-based Prussian blue analogs (PBAs) (KMnHCF/NaMnHCF) are ideal candidates for low-cost and high theoretical specific capacity merits. But the rapid decline hinders their application, due to side reactions caused by water imbalance. Here, an equilibrium strategy, which can balance the interstitial water supplement and water attack, is proposed. As proof of the concept, xCS (x: proportion, CS: co-solvent, such as polyethylene glycol and trimethyl phosphate) equilibrium electrolytes are introduced to solve the rapid decline. Assisting with the electrolyte, KMnHCF realizes excellent performance (10 000 cycles), which is beyond most cathode materials of sodium-ion batteries. The full batteries composed of KMnHCF cathode and NaTi2 (PO4 )3 anode also display outstanding performance (7000 cycles) and promising application prospects at low-temperature and engineering scenes. And then, the equilibrium electrolyte concept is verified by NaMn0.8 Fe0.2 HCF and NaMnHCF, proving its universality for low-cost and long-life manganese based PBAs.


Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits.
The possible activity of ticlopidine and its analogue clopidogrel in early atherogenesis was investigated. Incubation of rabbit platelets with the extracellular matrix produced by endothelial cells in culture induced massive platelet adherence in vitro. This phenomenon was strongly reduced when platelets were isolated from rabbits that had been treated with a single dose of clopidogrel (10 mg/kg PO) or three doses of ticlopidine (each 200 mg/kg PO) (94% and 56% inhibition of platelet adhesion, respectively). Three doses of aspirin (each 200 mg/kg PO) were ineffective. Air-drying injury of the rabbit carotid artery resulted in platelet adherence to the underlying subendothelium. This platelet accumulation on the damaged vessel wall was greatly reduced by clopidogrel: 95% (P < .001) inhibition of platelet adhesion after a single oral dose of 25 mg/kg. Ticlopidine (200 mg/kg) was also effective (71% inhibition; P < .001), whereas aspirin (100 mg/kg PO) failed to reduce platelet adhesion to the subendothelium. The effect of clopidogrel on intimal smooth muscle hyperplasia in rabbit carotid arteries subjected to air-drying endothelial injury was then investigated. After a 16-day treatment, clopidogrel (25 mg/kg per day PO) inhibited the development of intimal thickening (48% inhibition; P < .01). This effect was dose dependent and increased with the duration of the treatment. Under the same experimental conditions, ticlopidine (200 mg/kg per day PO) inhibited myointimal thickening (57%; P < .001), whereas aspirin was ineffective. These results show that clopidogrel and ticlopidine, two ADP-selective antiplatelet agents, can reduce myointimal thickening after endothelial injury. This effect can be due to the inhibition of platelet adhesion and aggregation to the exposed subendothelium.


Investigating the choriocapillaris and choroidal vasculature with new optical coherence tomography technologies.
The body of knowledge of in vivo investigation of the choroid has been markedly enhanced by recent technological advances in optical coherence tomography (OCT). New insights elucidating the morphological features of the choriocapillaris and choroidal vasculature, in both physiological and pathological conditions, indicate that the choroid plays a pivotal role in many posterior segment diseases. In this article, a review of the histological characteristics of the choroid, which must be considered for the proper interpretation of in vivo imaging, is followed by a comprehensive discussion of fundamental principles of the current state-of-the-art in OCT, including cross-sectional OCT, en face OCT, and OCT angiography using both spectral domain OCT and swept source OCT technologies. A detailed review of the tomographic features of the choroid in the normal eye is followed by relevant findings in prevalent chorioretinal diseases, focusing on major causes of vision loss such as typical early and advanced age-related macular degeneration, polypoidal choroidal vasculopathy, central serous chorioretinopathy, pachychoroid spectrum disorders, diabetic choroidopathy, and myopia.


Beta-sitosterol and 17beta-estradiol alter gonadal steroidogenic acute regulatory protein (StAR) expression in goldfish, Carassius auratus.
Fish exposed to the phytosterol beta-sitosterol (beta-sit) have decreased circulating hormone and cholesterol concentrations, and decreased gonadal intra-mitochondrial cholesterol pools. The current study examined the potential for beta-sit to alter abundance of the key cholesterol transport protein, steroidogenic acute regulatory (StAR) protein, which delivers cholesterol to the first and rate-limiting steroidogenic enzyme P450 side chain cleavage (P450(scc)) inside the mitochondria. Plasma testosterone (T) and lipids (cholesterol, lipoproteins and triglycerides) were also measured. Goldfish were exposed to 200 microg/g beta-sit (97% pure or as a 72.6% pure phytosterol mixture) and 10 microg/g 17beta-estradiol (E(2); estrogenic control) by intra-peritoneal Silastic implants for 21-days or for five-months. Plasma T was significantly decreased in male fish exposed to the phytosterol mixture following the long-term exposure (p<0.001). There were no differences in total cholesterol concentrations among treatments in the short- or long-term exposure, but male fish in the long-term exposure had significantly lower HDL as compared to control fish (p<0.025) with a corresponding increase in LDL. StAR transcript levels were unchanged following the short-term exposure, but were reduced after five months in male beta-sit fish (p=0.05) and E(2)-treated female fish (p=0.05). This reduction in StAR transcript abundance in conjunction with decreased plasma T and altered plasma lipoprotein fractions demonstrates a non-estrogenic effect of beta-sit. This is the first study to show that beta-sit has the capacity to alter gonadal StAR transcript abundance, offering a mechanism by which beta-sit disrupts reproductive endocrine endpoints.


Association between atypical parathyroid adenoma and neurofibromatosis.
Primary hyperparathyroidism is a disease characterized by excessive production of parathyroid hormone (PTH), which is due to a parathyroid adenoma in 85% of cases. An atypical parathyroid adenoma, with some histopathological features of parathyroid carcinoma, may be found in some of the cases, although it may not fulfill all the criteria for this diagnosis. Neurofibromatosis type 1 (NF1) is an autosomal dominant systemic disease that may be associated with hyperparathyroidism. We report here the rare combination of a patient with NF1 and clinical manifestations of hyperparathyroidism due to an atypical parathyroid adenoma.


Association between injury severity and amyloid β protein levels in serum and cerebrospinal fluid in rats with traumatic spinal cord injury.
The aim of the present study was to determine whether amyloid-β (Aβ) protein could be detected in the serum and cerebrospinal fluid (CSF) of rats with traumatic spinal cord injury (SCI) and whether Aβ protein levels in serum and CSF correlated with the injury severity. A total of 140 adult female Sprague‑Dawley rats were randomly divided into four groups: Sham, mild injury, moderate injury and severe injury. Serum and CSF samples were collected at 12 h, 1, 3, 7, 14, 21 and 28 days post‑injury. ELISA analysis for serum and CSF Aβ protein was performed. Locomotor function of all animals was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Following SCI, the protein levels of Aβ in serum and CSF samples from SCI groups significantly increased from 12 h (P<0.05) and peaked 3 days after injury. A significant increase of Aβ levels in serum and CSF in the severe SCI group was also observed at 28 days after injury (P<0.05). At 28 days after injury the protein levels of Aβ in serum and CSF were significantly correlated with the severity of injury (serum, R2=‑0.806, P<0.01; CSF, R2=‑0.694, P<0.01). A significant correlation between Aβ protein level in serum and CSF and neurological deficits (BBB score) was also observed (P<0.01). The protein level of Aβ in serum and CSF was severity and time‑dependent during the acute phase in rats with traumatic SCI. Monitoring the level of Aβ protein in serum may improve the evaluation of SCI severity and the neuron functional status following SCI.


Actinomadura montaniterrae sp. nov., isolated from mountain soil.
The taxonomic position of the mountain soil actinomycete, strain CYP1-1BT, was clarified by a polyphasic study. The strain produced a single spore, or occasionally a chain of spores, on aerial mycelium. Chemotaxonomic data supported the classification of CYP1-1BT as representing a member of the genus Actinomadura on the basis of the presence of meso-diaminopimelic acid in the peptidoglycan; galactose, glucose, madurose and ribose as whole cell sugars; MK-9(H6), MK-9(H8) and MK-9(H4) as dominant menaquinones; C16 : 0, 10-methylated C18 : 0 and C18 : 1ω9c as the major cellular fatty acids; and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol manosides as the predominant phospholipids. The DNA G+C content was 74.3 mol%. On the basis of the combination of morphological and chemotaxonomic characteristics, CYP1-1BT was identified as representing a member of the genus Actinomadura. On the basis of the results of 16S rRNA gene analysis, CYP1-1BT, was shown to be closely related to Actinomadura nitritigenes DSM 44137T (98.9 %). Phenotypic, genotypic and DNA-DNA hybridization data supported the hypothesis that CYP1-1BT represents a novel species of the genus Actinomadura for which the name Actinomadura montaniterrae sp. nov. is proposed. The type strain is CYP1-1BT (=JCM 16995T=KCTC 39784T=PCU 349T=TISTR 2400T).


A field trial of ketamine anaesthesia in the horse.
Ketamine was used on 80 occasions to induce anaesthesia in 77 animals. Xylazine premedication was used alone on 75 occasions, in conjunction with methadone once, in conjunction with methadone and acepromazine once and, on three occasions, methadone and acepromazine only were used. Anaesthesia was maintained in seven cases with halothane and oxygen. Premedication with xylazine 5 mins previously or concurrently with ketamine gave similar results but an interval of more than 5 mins between the drugs produced less deep anaesthesia and this protocol is, therefore, not advised. Induction and recovery were judged to be good in 82 per cent and 78 per cent of cases, respectively, and analgesia and muscle relaxation were judged as adequate in 79 per cent of cases.


Pushing the limit. Minnesota probe of Accretive's collection practices raises new questions on hospital billing policies.
The collection practices of hospitals once again grabbed the spotlight, with a report from Minnesota Attorney General Lori Swanson, left, that raises questions about aggressive techniques used by Accretive Health at Fairview Health Services in Minneapolis. While Fairview has already ended its contract with Accretive, a number of large systems still use the Chicago-based billing company.


The conjoint junction of the triceps surae: implications for gastrocnemius tendon lengthening.
Forty embalmed cadaver lower limbs were dissected to identify the morphology of the conjoint junction of the tendons of gastrocnemius and soleus and the location of the gastrocnemius tendon relative to bony landmarks. Five patterns of conjoint junction morphology were found: transverse (25%), oblique passing distally and medially (45%), oblique passing distally and laterally (5%) and arcuate as an inverted U (17.5%) and a U-shape (7.5%). Left-right asymmetry of the junction was observed in 31.6% of 19 paired cadaver legs. On the medial side of the calf the gastrocnemius tendon could be located between 38 and 46% of the proportion of the distance between the upper border of the calcaneus and the fibular head. Corresponding values for the midline and lateral side of the calf were 45-58% and 48-51%. The location of the gastrocnemius tendon relative to bony landmarks may help to guide incision planning for open or endoscopic division of the tendon.


Rapid-sequence orotracheal intubation with rocuronium: a randomized double-blind comparison with suxamethonium--preliminary communication.
Eighty ASA I-III patients were randomly assigned to four groups. Group I patients received rocuronium 0.6 mg kg-1 immediately prior to thiopentone, while patients in group II received the same dose immediately after the induction agent. In groups III and IV a priming dose of rocuronium 0.04 mg kg-1 was administered prior to induction. Group III patients received rocuronium immediately prior to thiopentone. In group IV, suxamethonium 1.5 mg kg-1 was administered immediately after thiopentone. Intubation conditions were scored by a blinded investigator. An intubation time of > 60 s was defined as a failure. All patients could be intubated within 60 s. Priming with rocuronium did not improve intubation conditions. Total intubation scores > 6 occurred significantly more often in group II (P < 0.01 vs. all other groups). A single bolus dose of rocuronium 0.6 mg kg-1 (2 x ED95) administered immediately prior to thiopentone 6 mg kg-1 offers the same intubation conditions as suxamethonium 1.5 mg kg-1.


Fetal mummification in the major domestic species: current perspectives on causes and management.
Fetal mummification is an uncommon condition in most domestic species. While most often seen in multiparous and polytocous species like swine, it is also observed in monotocous species when the fetus is retained for a long time. The low prevalence of the condition may help explain the scarcity of information in the literature. To further complicate the study of this phenomenon, the physiological mechanisms that maintain pregnancy vary between species, implying different pathways for the condition. The exact outcome of early fetal mortality is unpredictable, and is influenced by several factors, including the cause of fetal mortality, differences in pregnancy between species, stage of gestation at fetal death, and number of fetuses. Based on our current knowledge of natural fetal mummification events, there are a number of prerequisites for the process of fetal mummification to occur. Examining the circumstances associated with fetal mummification can help scientists better understand the etiology and clinical situation in different species. The objective of this article is to review fetal mummification in the major domestic species: cattle, goats, sheep, horses, swine, dogs, and cats. This paper discusses the clinical situation, the most common and important etiologies, and the treatment approaches for restoring future pregnancy in the female, and where applicable, herd fertility.


Association of weight at enlistment with enrollment in the Army Weight Control Program and subsequent attrition in the Assessment of Recruit Motivation and Strength Study.
The ongoing obesity epidemic has made recruiting qualified Army applicants increasingly difficult. A cohort of 10,213 Army enlisted subjects was enrolled in the Assessment of Recruit Motivation and Strength (ARMS) study from February 2005 through September 2006. Overweight recruits obtained a waiver for enlistment (n = 990) if they passed a screening physical fitness test. Recruits were evaluated for enrollment into the Army Weight Control Program (AWCP) and discharged during the 15 months following enlistment. Enrollment was higher among overweight recruits than recruits who met entrance standards (men: adjusted OR = 13.3 [95% CI: 10.3, 17.2]; women: adjusted OR = 3.6 [3.3, 3.9]). Although the discharge frequency was higher in the waiver group than in those who met standards (25.4% versus 19.9%, p < 0.001), there were only 10 (0.5% of total) discharges directly attributed to weight. Granting overweight waivers through the ARMS program increases enrollment to the AWCP but has little effect on weight-related attrition.