Relationship of Self-reported and Performance-based Visual Function With Performance-based Measures of Physical Function: The Health ABC Study.
To assess the relationship between self-reported and performance-based visual impairment (VI) and lower extremity physical function. Cross-sectional analysis of 2 219 Health ABC participants who completed vision testing and the Short Physical Performance Battery (SPPB). Linear regression models used either self-reported (weighted visual function question [VFQ] score) or performance-based (visual acuity [VA], log contrast sensitivity [LCS], Frisby stereoacuity [SA]) to predict SPPB or its components-gait speed, chair stands, or standing balance-with and without covariate adjustment. Mean age was 73.5 years (range 69-80); 52.4% were female and 37.4% African American. All VI measures were strongly associated with SPPB in unadjusted and adjusted models (p < .001). A self-reported VFQ score 1 standard deviation lower than the mean (mean 87.8 out of 100) demonstrated a -0.241 (95% confidence interval [CI]: -0.325, -0.156) adjusted difference in SPPB. After controlling for covariates, VA of <20/40 (41%) demonstrated a -0.496 (-0.660, -0.331) lower SPPB score while SA score>85 arcsec (30%) had a -0.449 (-0.627, -0.271) adjusted SPPB score versus those with better visual function. LCS < 1.55 (28.6%) was associated with a -0.759 (-0.938, -0.579) lower and LCS ≤ 1.30 (8%) with a -1.216 (-1.515, -0.918) lower adjusted SPPB score relative to better LCS. In a final multivariable model containing multiple vision measures, LCS remained independently associated with SPPB and all components, while SA remained associated with balance (all p < .05). Both self-reported and performance-based VI are strongly associated with poor lower extremity physical function. These findings may identify a subgroup of older adults with co-existing visual and physical dysfunction who may benefit from targeted screening and intervention to prevent disability.


Vestibulo-ocular reflex from the posterior canal nerve to extraocular motoneurons in the cat.
In the anesthetized cat, the posterior canal nerve (PCN) was stimulated by electric pulses and synaptic responses were recorded intracellularly in the three antagonistic pairs of extraocular motoneurons. Pure reciprocal effects were obtained in the motoneurons innervating the antagonistic pair of ipsilateral oblique muscles and the antagonistic pair of contralateral vertical rectus muscles. These responses consisted of low threshold disynaptic excitatory postsynaptic potentials (EPSPs) in either the contralateral superior oblique (c--SO) (trochlear) or contralateral inferior rectus (c--IR) motoneurons and of disynaptic inhibitory postsynaptic potentials (IPSPs) in either the ipsilateral inferior oblique (i--IO) or ipsilateral superior rectus (i--SR) motoneurons. In addition, disynaptic IPSPs were also found in (i--SO) motoneurons. Mixtures of low threshold (di or trisynaptic) EPSPs and IPSPs were found in all other extraocular motoneurons except for the contralateral lateral rectus (c--LR) motoneurons. These results may afford a basis for the characteristic eye movements induced by vertical canal nerve stimulation.


Predictors of acute myocardial infarction mortality in hypertensive patients treated in primary care: a population-based follow-up study in the Skaraborg Project.
To explore risk factors for acute myocardial infarction (AMI) mortality in hypertensive patients treated in primary care. Community-based cohort study. Hypertension outpatient clinic in primary health care. Patients who consecutively underwent an annual follow-up during 1992-1993 (n =894; 377 men and 517 women). All events of fatal AMI were ascertained by record linkage to the National Mortality Register to December 31, 2002. Gender-specific predictors for AMI mortality were analysed by Cox regression. AMI mortality. During a mean follow-up of 8.7 years 32 cases (8.5%) of fatal AMI were observed in men and 31 cases (6.0%) were observed in women. Most important predictors for AMI mortality in men were microalbuminuria (HR 3.8, CI 1.8-8.0) and left ventricular hypertrophy (HR 4.0, CI 1.7-9.4), whilst in women type 2 diabetes (HR 4.8, CI 2.4-9.8) was an important predictor. In hypertensive patients without diabetes male gender was associated with high AMI mortality (HR 2.7, CI 1.4-5.3), but in patients with both hypertension and type 2 diabetes the higher risk in men disappeared (HR 0.8, CI 0.4-1.7). Cardiovascular disease risk factors remain strong predictors of AMI mortality in hypertensive patients but with a different pattern in the two genders. Markers of organ damage are more important predictors in men, whereas markers of impaired glucose metabolism are more important predictors in women.


Interference effects in a numerical Stroop paradigm in 9- to 12-year-old children with ADHD-C.
Attention deficit hyperactivity disorder (ADHD) is characterized by deficient self-regulation, poor attentional control, and poor response inhibition. To date, however, the extent to which these deficits affect basic interference control remains a matter of controversy. Secondly, ADHD has been reported to be associated with arithmetic deficits. It remains unclear whether such deficits are a secondary consequence of the above-mentioned characteristics of ADHD or whether basic numerical magnitude representations are also affected. In the present study we attempted to investigate these issues using a basic numerical interference paradigm. Nine- to twelve-year-old children with ADHD-C (attention-deficit hyperactivity-disorder combined type) and control children without ADHD (each n = 16) were presented with two digits of possibly different physical sizes (e.g., 3 7). This numerical Stroop task requires subjects to make a magnitude classification concerning either the physical or the numerical stimulus dimension. The irrelevant dimension can be congruent (same response), incongruent (different response), or neutral (no response association). Children with ADHD-C performed worse than control children in most analyses. The most important finding was a significant interaction of congruity effects with group in the numerical comparison task. Children with ADHD-C tended to show larger congruity and interference effects than controls, and these were not attributable to a speed-accuracy trade-off. The results might reflect differential processing speeds, or a different degree of automatic activation of physical and numerical magnitudes in children with and without ADHD-C. Alternative explanations, such as insufficient inhibition of selective (domain-specific) attention are also discussed.


Pregnancy in epilepsy: issues of concern.
Every pregnancy, even under the best of circumstances, carries risks with it. Having epilepsy and taking medications to treat seizures further increase these risks and not all patients are willing to accept risks. The issues related to pregnancy, epilepsy, and antiepileptic drugs and pregnancy are fraught with confusion and misperceptions. Lay publications may misinform the public by assigning risks to drugs not known to be teratogenic in humans. Women report that their physicians have encouraged them to terminate otherwise wanted pregnancies "just to be on the safe side" which is clearly an excess of caution. In this chapter, we review the most common risk factors and divide them in two broad categories: (a) avoidable or modifiable risk factors and (b) unavoidable or non modifiable risk factors. Physicians counseling women with epilepsy who are pregnant or are planning a pregnancy should make every effort to understand the nature and magnitude of the risks associated with epilepsy and antiepileptic drugs in order to ensure the best possible outcomes in these cases. We discuss preventive measures that, when properly followed, can minimize risks and allow the vast majority of women with epilepsy to give birth to normal children.


Mammalian ovary differentiation - a focus on female meiosis.
Over the past 50 years, the ovary development has been subject of fewer studies as compare to the male pathway. Nevertheless due to the advancement of genetics, mouse ES cells and the development of genetic models, studies of ovarian differentiation was boosted. This review emphasizes some of new progresses in the research field of the mammalian ovary differentiation that have occurred in recent years with focuses of the period around prophase I of meiosis and of recent roles of small non-RNAs in the ovarian gene expression.


Quantitative measurements in 3-dimensional datasets of mouse lymph nodes resolve organ-wide functional dependencies.
Deep tissue imaging has become state of the art in biology, but now the problem is to quantify spatial information in a global, organ-wide context. Although access to the raw data is no longer a limitation, the computational tools to extract biologically useful information out of these large data sets is still catching up. In many cases, to understand the mechanism behind a biological process, where molecules or cells interact with each other, it is mandatory to know their mutual positions. We illustrate this principle here with the immune system. Although the general functions of lymph nodes as immune sentinels are well described, many cellular and molecular details governing the interactions of lymphocytes and dendritic cells remain unclear to date and prevent an in-depth mechanistic understanding of the immune system. We imaged ex vivo lymph nodes isolated from both wild-type and transgenic mice lacking key factors for dendritic cell positioning and used software written in MATLAB to determine the spatial distances between the dendritic cells and the internal high endothelial vascular network. This allowed us to quantify the spatial localization of the dendritic cells in the lymph node, which is a critical parameter determining the effectiveness of an adaptive immune response.


Anatomical depth parameters of pronator quadratus: a cadaveric study.
There is a paucity of literature documenting the cadaveric muscle thickness of pronator quadratus. We measured the width and depth of this muscle bilaterally in 15 cadavers. There was a significant difference in thickness between male and female cadavers, but the width was proportional to radius length.


Topology-sensitive weighting model for myocardial segmentation.
Accurate myocardial segmentation is crucial for the diagnosis of various heart diseases. However, segmentation results often suffer from topology structural errors, such as broken connections and holes, especially in cases of poor image quality. These errors are unacceptable in clinical diagnosis. We proposed a Topology-Sensitive Weight (TSW) model to keep both pixel-wise accuracy and topological correctness. Specifically, the Position Weighting Update (PWU) strategy with the Boundary-Sensitive Topology (BST) module can guide the model to focus on positions where topological features are sensitive to pixel values. The Myocardial Integrity Topology (MIT) module can serve as a guide for maintaining myocardial integrity. We evaluate the TSW model on the CAMUS dataset and a private echocardiography myocardial segmentation dataset. The qualitative and quantitative experimental results show that the TSW model significantly enhances topological accuracy while maintaining pixel-wise precision.


Penny wise, dollar foolish approach to antiemetic use may compromise patient care.
A recent coverage determination by National Government Services threatens to compromise the ability of patients to achieve complete control of chemotherapy-induced nausea and vomiting by limiting oncologist discretion in prescribing antiemetics.


Modelling the growth of Leuconostoc mesenteroides by Artificial Neural Networks.
The combined effect of temperature (10.5 to 24.5 degrees C), pH level (5.5 to 7.5), sodium chloride level (0.25% to 6.25%) and sodium nitrite level (0 to 200 ppm) on the predicted specific growth rate (Gr), lag-time (Lag) and maximum population density (yEnd) of Leuconostoc mesenteroides under aerobic and anaerobic conditions, was studied using an Artificial Neural Network-based model (ANN) in comparison with Response Surface Methodology (RS). For both aerobic and anaerobic conditions, two types of ANN model were elaborated, unidimensional for each of the growth parameters, and multidimensional in which the three parameters Gr, Lag, and yEnd are combined. Although in general no significant statistical differences were observed between both types of model, we opted for the unidimensional model, because it obtained the lowest mean value for the standard error of prediction for generalisation. The ANN models developed provided reliable estimates for the three kinetic parameters studied; the SEP values in aerobic conditions ranged from between 2.82% for Gr, 6.05% for Lag and 10% for yEnd, a higher degree accuracy than those of the RS model (Gr: 9.54%; Lag: 8.89%; yEnd: 10.27%). Similar results were observed for anaerobic conditions. During external validation, a higher degree of accuracy (Af) and bias (Bf) were observed for the ANN model compared with the RS model. ANN predictive growth models are a valuable tool, enabling swift determination of L. mesenteroides growth parameters.


Integrated transcriptome sequencing and dynamic analysis reveal carbon source partitioning between terpenoid and oil accumulation in developing Lindera glauca fruits.
Lindera glauca fruits (LGF) with the abundance of terpenoid and oil has emerged as a novel specific material for industrial and medicinal application in China, but the complex regulatory mechanisms of carbon source partitioning into terpenoid biosynthetic pathway (TBP) and oil biosynthetic pathway (OBP) in developing LGF is still unknown. Here we perform the analysis of contents and compositions of terpenoid and oil from 7 stages of developing LGF to characterize a dramatic difference in temporal accumulative patterns. The resulting 3 crucial samples at 50, 125 and 150 days after flowering (DAF) were selected for comparative deep transcriptome analysis. By Illumina sequencing, the obtained approximately 81 million reads are assembled into 69,160 unigenes, among which 174, 71, 81 and 155 unigenes are implicated in glycolysis, pentose phosphate pathway (PPP), TBP and OBP, respectively. Integrated differential expression profiling and qRT-PCR, we specifically characterize the key enzymes and transcription factors (TFs) involved in regulating carbon allocation ratios for terpenoid or oil accumulation in developing LGF. These results contribute to our understanding of the regulatory mechanisms of carbon source partitioning between terpenoid and oil in developing LGF, and to the improvement of resource utilization and molecular breeding for L. glauca.


The impact of setting and agency.
Workers in institutions that deal with loss and bereavement need to be aware of factors that can negatively influence their capability to work effectively. This paper aims to outline the risk factors and details some approaches to remedying the situation. Institutional problems are analysed from a psychoanalytic and systemic perspective. This is followed by a management approach that builds on the importance of multidisciplinary teamwork and the implementation of a regular staff support system. It is proposed that implementation of these ideas and systems would create the most effective and efficient working model to cope with matters of loss and bereavement in organisations. Stresses the value of multidisciplinary teamwork.


Evolution of the chloroplast genome in photosynthetic euglenoids: a comparison of Eutreptia viridis and Euglena gracilis (Euglenophyta).
The chloroplast genome of Eutreptia viridis Perty, a basal taxon in the photosynthetic euglenoid lineage, was sequenced and compared with that of Euglena gracilis Ehrenberg, a crown species. Several common gene clusters were identified and gene order, conservation, and sequence similarity was assessed through comparisons with Euglena gracilis. Significant gene rearrangements were present between Eutreptia viridis and Euglena gracilis chloroplast genomes. In addition, major expansion has occurred in the Euglena gracilis chloroplast accounting for its larger size. However, the key chloroplast genes are present and differ only in the absence of psaM and roaA in Eutreptia viridis, and psaI in Euglena gracilis, suggesting a high level of gene conservation within the euglenoid lineage. Further comparisons with the plastid genomes of closely related green algal taxa have provided additional support for the hypothesis that a Pyramimonas-like alga was the euglenoid chloroplast donor via secondary endosymbiosis.


Lipoprotein(a), metabolic profile and new-onset type 2 diabetes in patients with familial combined hyperlipidemia: A 9 year follow-up study.
Lipoprotein(a) [Lp(a)] appears to have an inverse association with the risk of type 2 diabetes mellitus in the general population. This study aimed to investigate the prognostic role of Lp(a) regarding the development of type 2 diabetes in the special population of subjects with familial combined hyperlipidemia (FCH). This cohort study included 474 patients (mean age 49.7±11.3 years, 64% males) with FCH, without diabetes at baseline who were followed for a mean period of 8.2±6.8 years. At baseline evaluation venous blood samples were obtained for the determination of lipid profile and Lp(a) levels. The endpoint of interest was the development of diabetes. Patients with increased Lp(a) levels ≥30 mg/dl compared to those with low Lp(a) levels <30 mg/dl had lower levels of triglycerides (238±113 vs 268±129 mg/dl, p = 0.01), greater levels of high-density lipoprotein (HDL) cholesterol (44±10 vs 41±10 mg/dl, p = 0.01) and hypertension in a greater percentage (42% vs 32%, p = 0.03). The incidence of new-onset diabetes during the follow-up period was 10.1% (n = 48). Multiple Cox regression analysis revealed that increased Lp(a) is an independent predictor of lower diabetes incidence (HR 0.39, 95% CI 0.17-0.90, p = 0.02) after adjustment for confounders. Among subjects with FCH those with higher Lp(a) levels have lower risk for the development of type 2 diabetes. Moreover, the presence of increased Lp(a) seems to differentiate the expression of metabolic syndrome characteristics in patients with FCH, as increased Lp(a) is related to lower levels of triglycerides, greater prevalence of hypertension and higher levels of HDL cholesterol.


Repeated injections of intradetrusor onabotulinumtoxinA as adjunctive treatment of children with neurogenic bladder.
To evaluate the effects of repeated injections of onabotulinumtoxinA in children with neurogenic bladders refractory to conventional treatment. A total of 26 children with neurogenic bladder were prospectively studied. Some patients received up to four repeat injections. Patients were reinjected if they showed improvement in voiding diary, score of urinary incontinence and/or urodynamic studies; otherwise, augmentation cystoplasty was indicated. Of the 26 patients, 12 were reinjected a second time, 6 patients were reinjected a third time and 2 patients received a repeat injection for the fourth time. Six months after the first, second and third injection, the urinary incontinence score 0 (dry) was 50, 77 and 75 %, respectively. After each injection, the mean bladder capacity in voiding diary and the mean maximum cystometric capacity increased. The mean detrusor pressure at the end of filling decreased. Only compliance after the first injection improved significantly. Detrusor overactivity (n: 4), improved during 3 months and reappeared in three children after the first injection, but at greater cystometric volumes. In the fourth case, it reappeared 11 months after the third injection. Five patients underwent cystoplasty. After treatment with onabotulinumtoxinA, urinary continence achieved was 50-77 %. There were favorable changes in urodynamic variables, but they were insufficient. Detrusor overactivity was attenuated, but did not disappear completely.


Regulation of testosterone hydroxylation by rat liver microsomal cytochrome P-450.
The pathways of testosterone oxidation catalyzed by purified and membrane-bound forms of rat liver microsomal cytochrome P-450 were examined with an HPLC system capable of resolving 14 potential hydroxylated metabolites of testosterone and androstenedione. Seven pathways of testosterone oxidation, namely the 2 alpha-, 2 beta-, 6 beta-, 15 beta-, 16 alpha-, and 18-hydroxylation of testosterone and 17-oxidation to androstenedione, were sexually differentiated in mature rats (male/female = 7-200 fold) but not in immature rats. Developmental changes in two cytochrome P-450 isozymes largely accounted for this sexual differentiation. The selective expression of cytochrome P-450h in mature male rats largely accounted for the male-specific, postpubertal increase in the rate of testosterone 2 alpha-, 16 alpha, and 17-oxidation, whereas the selective repression of cytochrome P-450p in female rats accounted for the female-specific, postpubertal decline in testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylase activity. A variety of cytochrome P-450p inducers, when administered to mature female rats, markedly increased (up to 130-fold) the rate of testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylation. These four pathways of testosterone hydroxylation were catalyzed by partially purified cytochrome P-450p, and were selectively stimulated when liver microsomes from troleandomycin- or erythromycin estolate-induced rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and these macrolide antibiotics. Just as the testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylase activity reflected the levels of cytochrome P-450p in rat liver microsomes, so testosterone 7 alpha-hydroxylase activity reflected the levels of cytochrome P-450a; 16 beta-hydroxylase activity the levels of cytochrome P-450b; and 2 alpha-hydroxylase activity the levels of cytochrome P-450h. It is concluded that the regio- and stereoselective hydroxylation of testosterone provides a functional basis to study simultaneously the regulation of several distinct isozymes of rat liver microsomal cytochrome P-450.


Suppression of the antibody response by phorbol esters in the mouse is due to an effect on the nylon wool adherent cell population.
Phorbol esters, in particular 12-O-tetradecanoyl-phorbol-13-acetate (TPA), have been shown to have profound effects on most biological systems including tumor promotion. Presented here are studies on the acute toxic effects of TPA, and the effects of phorbol esters on the in vivo and in vitro, T cell-dependent, antigen-specific antibody response in the mouse. The LD50 of a single i.v. dose of TPA in the mouse was 309 micrograms/kg. Acute toxic effects included lethargy, hypothermia and enlarged, hemorrhagic spleens at the higher doses. TPA was shown to be a potent inhibitor of the in vivo primary antibody response as measured by the IgM antibody-forming cell (AFC) response to sheep red blood cells (sRBC). The ED50 of a cumulative i.v. dose was 145 micrograms/kg administered the day before and the day of immunization (72.5 micrograms/kg/day). A cumulative dose of 500 micrograms/kg (250 micrograms/kg/day) resulted in a 100% suppression of the response. This in vivo exposure to TPA did not alter B cell/T cell ratio in the spleen. Phorbol ester analogs inactive in other biological systems were also inactive in the in vivo AFC response. The in vitro AFC assay was used to determine what cell type was being affected by TPA. Separation of the adherent spleen cells into B and T cell populations was done using nylon wool columns and anti-theta plus complement treatment. Experiments with these cell populations indicated that TPA produced suppression of the response due to an effect on the nylon wool adherent cell population.


Ultrastructure of gamma-motoneurons after temporary or permanent interruption of peripheral target contact.
The paradigm of nerve crush, vs. nerve transection and ligation, was used to examine the effects of temporary or permanent interruption of peripheral target contact on the ultrastructure of cat thoracic gamma-motoneurons. The normal, highly ordered ultrastructure of Nissl bodies was lost 8 days after axotomy. Nissl bodies remained disorganised up to 305 days after nerve transection and ligation. In contrast, normal ultrastructural orderliness was restored for many of the Nissl bodies of gamma-motoneurons 64 days following nerve crush. A decrease in the area of the Golgi apparatus was found 64 days following both nerve crush and nerve transection with ligation. Other organelles were unaltered.


Calcium dependence of hormone-stimulated cAMP accumulation in intact glial tumor cells.
The Ca2+ content of glial tumor (C6) cells was reduced approximately 5-fold by repeated treatment with media containing ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) without loss of cellular viability. The ability of the cells to accumulate cAMP in response to beta-adrenergic agonists was reduced 60 to 70% following Ca2+ depletion. Ca2+ did not affect the apparent KACT for norepinephrine, nor did it change the concentration of propranolol required to produce 50% inhibition of the maximal norepinephrine response. Phentolamine did not alter the Ca2+ dependence of the response. The binding of dihydroalprenolol by intact C6 cells was not influenced by Ca2+. Furthermore, pretreatment with norepinephrine did not affect the Ca2+ dependence of cAMP accumulation. The effects of Ca2+, therefore, appeared to be exerted on components of the adenylate cyclase system other than the catecholamine receptor. Micromolar free Ca2+ concentration in the extracellular medium were sufficient to restore a maximal norepinephrine response to Ca2+-depeleted cells. The effect of Ca2+ on cAMP accumulation in response to hormone was immediate and was rapidly reversible upon the addition of EGTA in excess of the cation. Cells in media containing Ca2+ exhibited a characteristic biphasic time course of cAMP accumulation; with Ca2+-depleted cells cAMP was accumulated more slowly and the subsequent decline in cAMP content was also reduced. Verapamil, an inhibitor of plasmalemmal Ca2+ influx, decreased the Ca2+-dependent component of the cAMP accumulation when added prior to the cation. The effect of Ca2+ on cAMP accumulation was reduced more extensively by pretreatment of cells at 45 degrees C under Ca2+-depleted (80% loss) than under Ca2+-restored (30% loss) conditions. Trifluoperazine at micromolar concentrations decreased the Ca2+-dependent increment in accumulation of cAMP in Ca2+-restored cells. This inhibition was not overcome by increasing concentrations of norepinephrine or of extracellular Ca2+.


Intestinal excretion of toxic substances.
Chemicals can be eliminated from body via feces by two major mechanisms, namely biliary and intestinal excretion. The relative importance of these processes in the elimination of a highly lipophilic xenobiotic such as hexachlorobenzene (HCB) has been studied. It has been demonstrated that fecal (90%) rather than urinary (10%) excretion is the major route of elimination of HCB in most species. It has been shown also that the bile of HCB dosed animals contained HCB metabolites only whereas fecal excretion consisted primarily of the parent compound. These findings suggested that the bile could not be the source of fecal HCB. Indeed, bile duct ligation in rats increased rather than decreased the fecal excretion of HCB. Experiments in rhesus monkeys with complete biliary bypass confirmed the conclusion that the source of fecal HCB is not the bile, suggesting that most of the fecal HCB originated from intestinal excretion. Exfoliation of intestinal epithelium and exudation across the intestinal mucosa are the two major nonbiliary mechanisms whereby xenobiotics can enter the intestinal lumen. The contribution of desquamation and exudation to fecal excretion of HCB was estimated in jejunectomized and hemicolectomized rats. Removal of 50% of the jejunum did not influence fecal excretion of HCB, whereas excision of 50% of the large intestine reduced it by 40%. These data suggest that the source of fecal HCB is nonbiliary, intestinal transfer (exudation) from blood into the intestinal contents, which occurs primarily in the large intestine. Fecal elimination of HCB is significantly enhanced by dietary treatments with mineral oil or hexadecane.(ABSTRACT TRUNCATED AT 250 WORDS)


Distribution, driving forces, and risk assessment of 2-MIB and its producer in a drinking water source-oriented shallow lake.
Freshwater blooms of harmful cyanobacteria in drinking water source-oriented shallow lakes affect public health and ecosystem services worldwide. Therefore, identifying 2-methylisoborneol (2-MIB)-producing cyanobacteria and predicting the risks of 2-MIB are critical for managing 2-MIB-infected water sources. Previous studies on the potential producers and risks of 2-MIB have focused on reservoirs or have been limited by the ecosystems of phytoplankton-dominated areas. We investigated the producers, distribution, and occurrence of 2-MIB in East Taihu Lake-a drinking water source-oriented shallow lake with macrophyte- and phytoplankton-dominated areas-from August 2020 to November 2021. We observed that Pseudanabaena sp. produces 2-MIB in this lake, as determined by the maximum correlation coefficient (R = 0.71, p < 0.001), maximum detection rate, and minimum false positive/negative ratio exhibited by this genus. Extreme odor events occurred in this lake during late summer and early autumn in 2021, with the mean 2-MIB concentration increasing to 727 ± 426 ng/L and 369 ± 176 ng/L in August and September, respectively. Moreover, the macrophyte-dominated area, particularly the wetland area, exhibited a significant decrease (p < 0.01) in bloom intensity and 2-MIB production during these extreme odor events. Pseudanabaena sp. outbreak was likely owing to eutrophication, seasonal gradients, and macrophyte reduction, considering that temporal trends were consistent with high water temperature, high total phosphorus levels, and low-light conditions. Moreover, 2-MIB production was sensitive to short-term hydrometeorological processes, with high water levels and radiant intensity enhancing 2-MIB production. The risk assessment results showed that the probability of 2-MIB concentration exceeding the odor threshold (10 ng/L) is up to 90% when the cell density of Pseudanabaena sp. reaches 1.8 × 107 cell/L; this risk is reduced to 50 and 25% at densities of < 3.8 × 105 cell/L and 5.6 × 104 cell/L, respectively. Our findings support calls for shallow lake management efforts to maintain a macrophyte-dominated state and control odorous cyanobacteria growth.


Anti-endotoxin antibodies consumption in cardiovascular collapse: Pathophysiological concerns.
Abnormal endotoxin activity in critically ill patients has been described in the absence of Gram-negative bacterial (GNB) infection. As disease severity seems to be crucial in the detection of this phenomenon, we decided to assess and compare endotoxin exposure in those patients representing the critical situation: septic shock and cardiogenic shock. Prospective, observational non intervention study. Critical Care Department of a University tertiary hospital. Cardiogenic shock (CS) and septic shock (SS) patients. None. Follow-up was performed for the first three days. Inflammatory biomarkers (C-reactive protein, procalcitonin and interleuquin-6) and IgM antiendotoxin-core antibodies titter (IgM EndoCAb) were daily analyzed. Sixty-two patients were included; twenty-five patients with SS and thirty-seven with CS. Microbial etiology was established in 23 SS patients (92%) and GNB were present in 13 cases (52%). Although infection was suspected and even treated in 30 CS patients (81%), any episode could be finally confirmed. EndoCAb consumption was more intense in SS patients, although twenty-two CS patients (59.5%) had IgM anti-endotoxin value below 10th percentile range for healthy people. No statistically significant difference in endotoxin exposure was detected between Gram-positive and Gram-negative infections in the SS group. Endotoxin exposure ability to distinguish between SS and CS was moderate (AUC 0.7892, 95% IC: 0.6564-0.9218). In the severely ill patient some mechanisms take place allowing endotoxin incursion and therefore blurring the limits of diseases pathophysiology. Our work representatively shows how exposure to endotoxin was not fully capable of distinguishing between CS and SS.


Nonodontogenic Cysts.
This article focuses on describing nonodontogenic cysts of the oral and maxillofacial region. The lesions described include nasopalatine duct canal cyst, nasolabial cyst, traumatic bone cyst, Stafne bone cyst, aneurysmal bone cyst, focal osteoporotic bone marrow defect, dermoid cyst, epidermoid cyst, pilar cyst, and sebaceous cyst. The intent of this article is to make general dentists aware and knowledgeable of the nonodontogenic cysts they may encounter in everyday practice, so they can adequately manage or make an appropriate referral to improve treatment outcomes and reduce patient morbidity.


Relationship between glomerular dysfunction and left-ventricular mass independent of haemodynamic factors in a community sample.
To evaluate whether the relationship between early glomerular dysfunction and left-ventricular mass (LVM) occurs in a community sample and whether this relationship depends on haemodynamic factors. In 621 randomly selected participants from a community sample (332 were normotensive), estimated glomerular filtration rate (eGFR), LVM and dimensions were determined using echocardiography, and aortic blood pressure (BP) assessed from applanation tonometry and SphygmoCor software. Aortic pulse wave velocity (PWV) and high-quality 24-h BP values were available from 554 and 437 participants, respectively. With adjustments for confounders (including clinic SBP), eGFR was associated with LVM index (LVMI) and LVM in excess of that predicted from stroke work (inappropriate LVM, LVMinappr) in all participants (LVMI: partial r = -0.18, P < 0.0001; LVMinappr: partial r = -0.17, P < 0.0001) and normotensive (LVMI: partial r = -0.23, P < 0.0001; LVMinappr: partial r = -0.22, P < 0.0001) separate from hypertensive patients. Marked differences in LVMinappr were noted in the eGFR range below 132 compared to at least 132 ml/min per 1.73 m (P < 0.0005). When replacing clinic BP with either aortic SBP, 24-h BP, PWV, stroke work (for LVMI), left-ventricular end-diastolic diameter (LVEDD), or circumferential wall stress in the regression models, eGFR retained strong associations with LVMI (P = 0.01 to <0.0001) and LVMinappr (P < 0.005 to <0.0001) and these effects were replicated in normotensive separate from hypertensive patients. Strong relationships between eGFR and LVM occur at a community level irrespective of the presence of hypertension and independent of 24-h and aortic BP, PWV, LVEDD, stroke work and wall stress. Non-haemodynamic factors explain a considerable proportion of the relationship between early glomerular dysfunction and left-ventricular hypertrophy.


Interaction of cortisol and epinephrine in the regulation of leucine kinetics in man.
To assess the interaction of the two major stress hormones epinephrine and cortisol in the regulation of leucine kinetics in man, epinephrine (50 ng/kg/min) was infused either alone or in combination with cortisol (2 micrograms/kg/min) into two groups of 6 postabsorptive normal male subjects during 180 min. Plasma leucine concentrations decreased by 28% (p less than 0.05) from baseline during epinephrine treatment (plasma levels 515 pg/ml); this was due to a decrease of leucine appearance (determined by 1-13C-leucine infusions) by 23% (p less than 0.025); leucine oxidation decreased by 29% (p less than 0.05). However, when plasma cortisol concentrations were elevated to supraphysiological levels (16.3 mumol/l) during epinephrine administration, the decreases of leucine plasma concentrations, appearance and oxidation were abolished. Plasma glucose and FFA concentrations were similarly elevated during both kinds of treatment. Since leucine appearance represents a measurement of total body protein breakdown and leucine disappearance into non-oxidative pathways reflects protein synthesis, the data indicate that plasma epinephrine concentrations during severe stress exert a protein anabolic effect in man which may counteract catabolic properties of elevated plasma cortisol.


Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization.
Iron-sulfur clusters are prosthetic groups that are required for the function of numerous enzymes in the cell, including enzymes important in respiration, photosynthesis, and nitrogen fixation. Here we report cloning of the human homolog of NifS, a cysteine desulfurase that is proposed to supply the inorganic sulfur in iron-sulfur clusters. In human cells, different forms of NifS that localize either to mitochondria or to the cytosol and nucleus are synthesized from a single transcript through initiation at alternative inframe AUGs, and initiation site selection varies according to the pH of the medium or cytosol. Thus, a novel form of translational regulation permits rapid redistribution of NifS proteins into different compartments of the cell in response to changes in metabolic status.


Takayasu arteritis: association with focal segmental glomerulosclerosis.
We herein report on a 29-year-old woman who presented with edema and proteinuria. In light of her blood pressure differences and, finally, with the angiographic findings, Takayasu arteritis (TA) was the diagnosis. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) and other possible etiologic alternatives were excluded. This was a very rare association and we could not find any other cases reported on TA accompanied with FSGS before. A poor treatment response was observed at the end of a 1-year therapy.


Volatile solvents as drugs of abuse: focus on the cortico-mesolimbic circuitry.
Volatile solvents such as those found in fuels, paints, and thinners are found throughout the world and are used in a variety of industrial applications. However, these compounds are also often intentionally inhaled at high concentrations to produce intoxication. While solvent use has been recognized as a potential drug problem for many years, research on the sites and mechanisms of action of these compounds lags behind that of other drugs of abuse. In this review, we first discuss the epidemiology of voluntary solvent use throughout the world and then consider what is known about their basic pharmacology and how this may explain their use as drugs of abuse. We next present data from preclinical and clinical studies indicating that these substances induce common addiction sequelae such as dependence, withdrawal, and cognitive impairments. We describe how toluene, the most commonly studied psychoactive volatile solvent, alters synaptic transmission in key brain circuits such as the mesolimbic dopamine system and medial prefrontal cortex (mPFC) that are thought to underlie addiction pathology. Finally, we make the case that activity in mPFC circuits is a critical regulator of the mesolimbic dopamine system's ability to respond to volatile solvents like toluene. Overall, this review provides evidence that volatile solvents have high abuse liability because of their selective effects on critical nodes of the addiction neurocircuitry, and underscores the need for more research into how these compounds induce adaptations in neural circuits that underlie addiction pathology.


Intercostal neuroma as a source of pain after aesthetic and reconstructive breast implant surgery.
The development of persistent post-operative pain after implant placement for aesthetic or reconstructive breast surgery can lead to significant patient morbidity. Although there are many etiologies for post-operative pain, the diagnosis of an intercostal neuroma is important as this can be treated surgically. We describe three cases of an intercostal neuroma in patients with breast implants. A Tinel's sign can be elicited along the lateral chest wall and a local anesthetic block temporarily alleviates this pain. Surgical management with identification and clipping of the intercostal neuroma and burying into the underlying muscle significantly decreases post-operative pain long term. In patients with persistent pain after breast implant placement, plastic surgeons must be aware of this treatable cause of pain.


Clinical Impact of Pharmacogenetic-Guided Treatment for Patients Exhibiting Neuropsychiatric Disorders: A Randomized Controlled Trial.
Pharmacogenetic testing holds promise as a personalized medicine tool by permitting individualization of pharmacotherapy in accordance with genes influencing therapeutic response, side effects, and adverse events. The authors evaluated the effect on outcomes for patients diagnosed with neuropsychiatric disorders of pharmacogenetics (PGx)-guided treatment compared to usual standard of care. This was a prospective, randomized study of 237 patients at an outpatient community-based psychiatric practice conducted between April 2015 and October 2015. Baseline patient assessments and a buccal swab were collected for pharmacogenetic testing at study initiation. For the experimental group, PGx results were provided to the clinicians as guides to treatment. Control subjects were treated according to the usual standard of care with no clinician reference to their PGx results. Neuropsychiatric Questionnaire (NPQ) and Symbol Digit Coding Test (SDC) scores and adverse drug events, hospitalizations, and medication information were collected at 30, 60, and 90 days. More than half (53%) of patients in the control group reported at least 1 adverse drug event compared to 28% of patients with PGx-guided medication management (P = .001). NPQ and SDC scores improved for both groups, but no statistical difference in efficacy as measured by these assessments was observed within the 90-day observation period. Pharmacogenetic testing may facilitate psychiatric drug therapy with greater tolerability and similar efficacy compared to standard of care. ClinicalTrials.gov Identifier: NCT02411123.


Chlorine: state of the art.
Chlorine is a widely used industrial chemical. Individuals can be exposed to chlorine through transportation accidents, industrial exposures or misuse of domestic cleaners. While most exposed individuals recover normal pulmonary function, chlorine can cause a variety of lung injuries including pulmonary edema, restrictive lung disease, and obstructive disease, including Reactive Airways Dysfunction Syndrome. Residual effects of chlorine exposure are a function of intensity of exposure, minute ventilation during exposure, and host characteristics such as cigarette smoking and atopy. This monograph will summarize uses of chlorine, the potential for accidents, the mechanism of chlorine toxicity in the lung, and review acute and chronic effects of chlorine exposure on the lung, as well as systemic effects of massive chlorine exposure.


Prevalence and risk factors of functional gastrointestinal disorders in early period medical students: a pilot study in Tunisia.
Functional gastrointestinal disorders (FGIDs) are highly prevalent in medical students around the world. However, there is no specific data on FGIDs in Tunisia. The objectives of this study were to evaluate the prevalence of FGIDs in medical students according to the rome III criteria and to identify risk factors associated with these disorders. A self-administered questionnaire survey was carried out among the students from the first and the second year of medical studies. We studied the influence of socio-demographic characteristics, lifestyle, health care seeking, psychosomatic symptoms and hospital anxiety and depression scale on the prevalence of FGIDs among these students. Three hundred and forty-three students (20.3 ± 0.8years) were included in our study. The prevalence of FGIDs was 54.2%. The main FGIDs found were the unspecified functional bowel disorder (46.6%), functional constipation (11.6%), irritable bowel syndrome (7.6%) and functional dyspepsia (6.7%). In logistic regression, abnormal BMI (OR = 2.1, 95% CI= 1-4.3), living in school dormitory (OR = 3.7, 95% CI = 1.7-7.8), low water intake (OR = 2.2, 95% CI = 1.1-4.2), digestive medication use (OR = 3.4, 95% CI= 1.3-8.5), and probable or definite anxiety (OR = 2.5, 95% CI = 1.1-5.8) were the five risk factors associated with FGIDs. We demonstrate a high prevalence of FGIDs (54.2%) among our students. Risk factors for FGIDs were abnormal BMI, living in school dormitory, low water intake, digestive medication use and anxiety.


Prevalence and intensity of Cephalobium microbivorum (Nematoda: Diplogasterida) infection in three species of Gryllus field crickets.
Here we report on the results of a survey for nematode parasites in three species of field cricket, Gryllus integer, Gryllus lineaticeps, and an undescribed Gryllus species. The nematode, Cephalobium microbivorum, was recovered from the intestine of the crickets. To our knowledge, this paper is just one of two to report on the biology of C. microbivorum. This nematode was first described from the cricket, Gryllus assimilis. It has not been documented in any other Gryllus species to date. G. integer were collected from two locations: Aguila, Arizona and Davis, California. G. lineaticeps were collected from Davis, CA and an undescribed species of Gryllus cricket was collected from Aguila, AZ. Results of the survey revealed the presence of nematodes in all three species of Gryllus, at all collection sites. The intensity of infection ranged from 1 to 113 nematodes.


Colorectal cancer and therapy response: a focus on the main mechanisms involved.
The latest GLOBOCAN 2021 reports that colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Most CRC cases are sporadic and associated with several risk factors, including lifestyle habits, gut dysbiosis, chronic inflammation, and oxidative stress. To summarize the biology of CRC and discuss current therapeutic interventions designed to counteract CRC development and to overcome chemoresistance. Literature searches were conducted using PubMed and focusing the attention on the keywords such as "Current treatment of CRC" or "chemoresistance and CRC" or "oxidative stress and CRC" or "novel drug delivery approaches in cancer" or "immunotherapy in CRC" or "gut microbiota in CRC" or "systematic review and meta-analysis of randomized controlled trials" or "CSCs and CRC". The citations included in the search ranged from September 1988 to December 2022. An additional search was carried out using the clinical trial database. Rounds of adjuvant therapies, including radiotherapy, chemotherapy, and immunotherapy are commonly planned to reduce cancer recurrence after surgery (stage II and stage III CRC patients) and to improve overall survival (stage IV). 5-fluorouracil-based chemotherapy in combination with other cytotoxic drugs, is the mainstay to treat CRC. However, the onset of the inherent or acquired resistance and the presence of chemoresistant cancer stem cells drastically reduce the efficacy. On the other hand, the genetic-molecular heterogeneity of CRC often precludes also the efficacy of new therapeutic approaches such as immunotherapies. Therefore, the CRC complexity made of natural or acquired multidrug resistance has made it necessary the search for new druggable targets and new delivery systems. Further knowledge of the underlying CRC mechanisms and a comprehensive overview of current therapeutic opportunities can provide the basis for identifying pharmacological and biological barriers that render therapies ineffective and for identifying new potential biomarkers and therapeutic targets for advanced and aggressive CRC.


Age of Onset of Puberty in Apparently Healthy School Girls from Northern India.
To determine the age of pubertal onset and menarche in school-going girls, and to assess the impact of obesity on pubertal timing. Cross-sectional. Seven schools across Delhi, India. 2010 school girls, aged 6-17 years. Anthropometric measurement and pubertal staging was performed for all subjects. Menarche was recorded by status quo method. Body mass index was used to define overweight/obesity. Serum gonadotropins and serum estradiol were measured in every sixth participant. Age at thelarche and menarche analyzed for entire cohort and stratified based on body mass index. Median (95% CI) ages of thelarche, pubarche and menarche were 10.8 (10.7-10.9) y, 11.0. y (10.8-11.2) y and 12.4 y (12.2-12.5) y. Overweight/obese girls showed six months earlier onset of thelarche and menarche than those with normal BMI (P<0.05). Serum gonadotropins did not vary significantly in overweight/obese subjects. The study provides the normative data for pubertal growth in Indian girls. Pubertal onset occurs earlier in overweight and obese girls.


Prolonged postoperative ileus following right- versus left-sided colectomy: A systematic review and meta-analysis.
Prolonged postoperative ileus (PPOI) is a common complication following colonic surgery, and is associated with longer hospital stay, greater risk of complications and substantial cost for patients and hospitals. Some reports have recently suggested that gastrointestinal (GI) recovery varies based on the side of resection (i.e., right-sided vs. left-sided colectomy). This systematic review and meta-analysis aimed to compare GI recovery by resection side. The MEDLINE, Embase, Cochrane Library and CENTRAL databases were systematically searched for articles reporting GI recovery outcomes in adults undergoing elective right- versus left-sided colectomy (excluding with ileostomy) of any surgical approach. The primary outcome was PPOI, and secondary outcomes included time to first passage of flatus, stool and tolerance of solid diet, and postoperative complications. Subgroup analyses of laparoscopic procedures and cohorts without inflammatory bowel disease and sensitivity analysis of adjusted multivariate results were also performed. Nine studies were identified, of which seven were included in the meta-analysis, comprising 29 068 colectomies (14 581 right-sided; 14 487 left-sided). PPOI was heterogeneously defined and was significantly more likely following right-sided compared to left-sided colectomy regardless of the surgical approach (OR 1.78, 95% CI 1.32-2.39; P < 0.01; I2 = 51%), as well as on subgroup analyses and adjusted multivariate meta-analysis. Secondary outcomes were reported in only a few small studies; hence meta-analysis did not produce reliable results. Based on heterogeneous definitions, consistently higher rates of PPOI were observed following right- versus left-sided colectomy. These differences are currently unexplained and highlight the need for further research into the pathophysiology of ileus.


Cytofluorometric analysis of the DNA content in ovarian carcinoma and its relationship to patient survival.
Forty-one patients with epithelial malignancies of the ovary treated at the Medical College of Wisconsin Affiliated Hospitals from 1976 to 1984 had paraffin embedded tissue available for review. Of the 41 patients, 40 had adequate material to provide 50 micron sections that were evaluated with flow cytometry to determine DNA content. Tumor- and patient-related parameters were then correlated with the results of flow cytometry. Overall survival at 5 years in these patients was 43%, and relapse-free survival was 50%. Forty percent of the tumors were diploid, and 60% were aneuploid. Five-year survival for diploid patients was 74% with a relapse-free survival of 71%. Corresponding overall and relapse-free survivals for aneuploid patients were 22% and 35%, respectively. Distribution of the patients by histology, stage, and grade was equal between the diploid and aneuploid groups. All patients were treated with whole abdominal plus concomitant pelvic boost irradiation; total doses to the whole abdomen ranged from 10 Gy to 46 Gy (1000 to 4600 cGy) with the median dose being 37.5 Gy. Approximately 40% of the patients received chemotherapy, which usually consisted of a single agent (Alkeran, Burroughs Welcome, Research Triangle Park, NC). This retrospective study of patients with ovarian cancer treated with radiation therapy suggests the possibility that determinations of DNA ploidy may be useful in selecting patients whose poor prognosis dictates that a more aggressive therapy be used.


Direct activation of gelatinase B (MMP-9) by hay dust suspension and different components of organic dust.
Matrix metalloproteinases (MMPs) are involved in tissue destruction in allergic airway diseases. We studied the ability of various allergenic substances to directly activate recombinant 92kDa proMMP-9. The substances included hay dust suspension (HDS) and its components (supernatant, particulate matter and wash fluid of particulate matter), storage mite extract and two Aspergillus fumigatus extracts. The allergen suspensions were incubated in vitro with proMMP-9. After incubation the conversion of proMMP-9 to 10kDa lower active forms were studied using gelatin zymography and Western immunoblot quantified by computerized densitometry. All studied allergens except HDS significantly and efficiently activated proMMP-9 as compared to a negative control. At the concentrations employed, the most potent activators were A. fumigatus extracts and mite suspension. The greater potency of mite and fungi as proMMP-9 activators suggests that these allergens may be more damaging to airways even at low concentrations.


Structures, stabilities, electronic, and optical properties of C64 fullerene isomers, anions (C64(2-) and C64(4-)), metallofullerene Sc2@C64, and Sc2C2@C64.
The 3465 classical isomers of C(64) fullerene have been investigated by quantum chemical methods PM3, and the most stable isomers have been refined with HCTH/3-21G//SVWN/STO-3G, B3LYP/6-31G(d)//HCTH/3-21G, and B3LYP/6-311G(d)//B3LYP/6-31G(d) level. C(64)(D(2):0003) with the lowest e(55) (e(55) = 2), the number of pentagon-pentagon fusions, is predicted to be the most stable isomer and it is followed by the C(64)(C(s):0077) and C(64)(C(2):0103) isomers within relative energy of 20.0 kcal/mol. C(64)(D(2):0003) prevails in a wide temperature range according to energy analysis with entropy contribution at B3LYP/6-31G(d) level. The simulated IR spectra and electronic spectra help to identify different fullerene isomers. All the hexagons in the isomers with e(55) = 2 display local aromaticity. The relative stabilities of C(64) isomers change with charging in ionic states. Doping also affects the relative stabilities of fullerene isomers as demonstrated by Sc(2)@C(64)(D(2):0003) and Sc(2)@C(64)(C(s):0077). The bonding of Sc atoms with C(64) elongates the C-C bond of two adjacent pentagons and enhances the local aromaticity of the fullerene cages. Charging, doping, and derativization can be utilized to isolate C(64) isomers through differentiating the electronic and steric effects.


Effects of etomidate use in ICU patients on ventilator therapy: a study of 12,526 patients in an open database from a single center.
There is a debate regarding the safety of etomidate. We evaluated the effects of etomidate on mortality in a large cohort of critical care patients. This retrospective matched-cohort study was performed using the Medical Information Mart for Intensive Care version 3 (MIMIC-III) database. Among 12,526 adult patients who were prescribed etomidate or propofol on the first day of mechanical ventilation, 625 patients administered etomidate were statistically matched with 6,250 patients administered propofol. The primary outcome measures were all-cause in-hospital mortality, 48-hour survival, cardiovascular morbidity, and infectious morbidity. Logistic regression analysis with stepwise selection of variables was performed to examine the dose-mortality relationship of etomidate. All-cause in-hospital mortality was 1.84 times higher in the etomidate cohort (OR, 1.84; 98.75% CI, 1.42, 2.37). Compared to the propofol cohort, the etomidate cohort showed 57% lower odds of 48-hour survival (0.43 [0.27, 0.73]), no difference in odds of cardiovascular morbidity (0.86 [0.66, 1.12]), and 1.77 times higher odds of infectious morbidity (1.77 [1.35, 2.31]). Additionally, the odds of mortality increased by 1.36 times per 0.1 mg/kg of etomidate (1.36 [95% CI: 1.23, 1.49]). Etomidate is a poor choice as a hypnotic drug on the first day of mechanical ventilation, as it is associated with a dose-dependent increase in all-cause mortality, and does not improve survival for the first 48 h.


From psychosomatic medicine to consultation-liaison psychiatry.
To trace the movement from psychosomatic medicine to consultation-liaison psychiatry, the forces at work in shaping the change, and the extent to which the change is reflected in the latest revisions of the International classification of diseases (ICD-10) and the Diagnostic and statistical manual of mental disorders, third revision (DSM-III-R). Identification of important trends in the field was aided by discussions with fellow members of the panel of compilers of the consultation-liaison psychiatry literature review expert list published bi-annually in General Hospital Psychiatry. The expert list is based on appropriate literature searches. Psychosomatic medicine continues as a science, studying the relationships between biological, psychological and social phenomena in health and disease. The main advocates of the clinical application of the concepts and findings of psychosomatic medicine are now the general hospital consultation-liaison psychiatrists and their allied health professional colleagues. The mainstreaming of psychiatry into medicine has accentuated the role of the consultation-liaison psychiatrist. In attempting to translate the advances in the field into a new taxonomy, both ICD-10 and DSM-III-R have created a new language that hinders understanding by a medical profession perhaps now less prone to resistance to holism. There is a need for a valid taxonomy that addresses the most common form of psychiatric presentation in the community, that of physical/psychiatric co-morbidity, and for outcome studies based on such a taxonomy. Consultation-liaison psychiatrists need to educate their colleagues about the changes in concepts and terminology.


Autophagy and Viral Infection.
Autophagy is an intracellular recycling process that maintains cellular homeostasis by orchestrating immunity upon viral infection. Following viral infection, autophagy is often initiated to curtail infection by delivering viral particles for lysosomal degradation and further integrating with innate pattern recognition receptor signaling to induce interferon (IFN)-mediated viral clearance. However, some viruses have evolved anti-autophagy strategies to escape host immunity and to promote viral replication. In this chapter, we illustrate how autophagy prevents viral infection to generate an optimal anti-viral milieu, and then concentrate on how viruses subvert and hijack the autophagic process to evade immunosurveillance, thereby facilitating viral replication and pathogenesis. Understanding the interplays between autophagy and viral infection is anticipated to guide the development of effective anti-viral therapeutics to fight against infectious diseases.


Assessing the effects of Ang-(1-7) therapy following transient middle cerebral artery occlusion.
The counter-regulatory axis, Angiotensin Converting Enzyme 2, Angiotensin-(1-7), Mas receptor (ACE2/Ang-1-7/MasR), of the renin angiotensin system (RAS) is a potential therapeutic target in stroke, with Ang-(1-7) reported to have neuroprotective effects in pre-clinical stroke models. Here, an extensive investigation of the functional and mechanistic effects of Ang-(1-7) was performed in a rodent model of stroke. Using longitudinal magnetic resonance imaging (MRI) it was observed that central administration of Ang-(1-7) following transient middle cerebral artery occlusion (MCAO) increased the amount of tissue salvage compared to reperfusion alone. This protective effect was not due to early changes in blood brain barrier (BBB) permeability, microglia activation or inflammatory gene expression. However, increases in NADPH oxidase 1 (Nox1) mRNA expression were observed in the treatment group compared to control. In order to determine whether Ang-(1-7) has direct cerebrovascular effects, laser speckle contrast imaging (LSCI) was performed to measure dynamic changes in cortical perfusion following reperfusion. Delivery of Ang-(1-7) did not have any effect on cortical perfusion following reperfusion however; it showed an indication to prevent the 'steal phenomenon' within the contralateral hemisphere. The comprehensive series of studies have demonstrated a moderate protective effect of Ang-(1-7) when given alongside reperfusion to increase tissue salvage.


Impact of an easy-access telephonic interpreter program in the acute care setting: an evaluation of a quality improvement intervention.
Language barriers render interaction with the health care system difficult and lead to health disparities for patients with limited English proficiency (LEP). Despite a long-standing legal obligation for large health care organizations in the United States to try to provide free language access services for patients with LEP, professional interpretation is not always widely accessible, and even when it is, its use is often suboptimal. A dual-handset phone with 24-hour access to professional telephonic interpretation was placed at the bedside of all patients admitted to the general medicine floor of a tertiary care academic hospital. Nurses and physicians were surveyed before and after the easy-access interpretation program's implementation. Distribution of pre- and postimplementation surveys to 127 and 122 nurses, respectively, yielded a total of 163 completed surveys (overall participation rate, 65%). Distribution of surveys to 96 and 78 physicians, respectively, yielded 116 completed surveys (overall participation rate, 67%). After implementation, use of professional telephonic interpreters for communication with LEP patients increased fourfold, without a decrease in use of professional in-person interpreters. There were significant increases in professional interpreter use during brief communications with high error potential, including medication administration (odds ratio [OR] = 1.9, 95% confidence interval [CI] 1.1-3.2) and pre-rounding (OR = 3.4, 95% CI 1.2-9.8). Increasing ease of access to dual-handset interpreter telephones promotes use of professional interpreters in the acute care setting. Future hospital policy should focus on further integrating language services into the hospital environment, accompanied by an educational program to assist in shifting professional norms toward use of professional interpreters.


Long-term results of medical and surgical therapy for Japanese patients with moderate carotid stenosis.
To clarify the efficacy of medication versus carotid endarterectomy (CEA), we investigated cardiovascular events and outcomes in Japanese patients with moderate carotid stenosis. We consecutively registered patients with significant carotid stenosis (50%-79%) measured by digital subtraction angiography (DSA) over 10 years and compared the incidences of stroke, myocardial infarction, and death between treatment groups (surgical group vs medical group). Of 406 registered patients, 163 (108 treated surgically and 55 treated medically) with moderate carotid stenosis were analyzed. Complete follow-up data (mean, 4.2 years) were available for 105 patients in the surgical group (97.2%) and 54 patients in the medical group (98.2%). Surgical treatment was associated with lower incidences of any stroke, myocardial infarction, and death compared with medication. Although the incidence rates differed significantly between CEA and medication in the 66 symptomatic patients, there were no significant differences in the 93 asymptomatic patients. The results of this single-center study in Japanese patients suggest that CEA is an acceptable treatment for patients with symptomatic moderate carotid stenosis, but that CEA for asymptomatic moderate carotid stenosis seems to be less effective in Japanese patients.


Oocyte growth.
The main elements of reproduction are exposed with emphasis on its preparation during the larval stage. The system oocyte-nurse cells-follicular cells is described and the principal features of egg morphogenesis are indicated. Two types of problems are concentrated on : 1) sequential determination of growth and evolution of the follicle in the ovarian tube, 2) morphological and biochemical aspects of chorion formation. Variation in the functioning of the oocyte's morphogenetic system is explored with discussion of the role of larval alimentation, temperature, hormonal environment and genetic factors.


Cemented tibial component fixation performs better than cementless fixation: a randomized radiostereometric study comparing porous-coated, hydroxyapatite-coated and cemented tibial components over 5 years.
The question whether the tibial component of a total knee arthroplasty should be fixed to bone with or without bone cement has not yet been definitely answered. We studied movements between the tibial component and bone by radiostereometry (RSA) in total knee replacement (TKR) for 3 different types of fixation: cemented fixation (C-F), uncemented porous fixation (UC-F) and uncemented porous hydroxyapatite fixation (UCHA-F). 116 patients with osteoarthrosis, who had 146 TKRs, were included in 2 randomized series. The first series included 86 unilateral TKRs stratified into 1 of the 3 types of fixation. The second series included 30 patients who had simultaneous bilateral TKR surgery, and who were stratified into 3 subgroups of pairwise comparisons of the 3 types of fixation. After 5 years 2 knees had been revised, neither of which were due to loosening. 1 UCHA-F knee in the unilateral series showed a large and continuous migration and a poor clinical result, and is a pending failure. The C-F knees rotated and migrated less than UC-F and UCHA-F knees over 5 years. UCHA-F migrated less than UC-F after 1 year. Cementing of the tibial component offers more stable bone-implant contact for 5 years compared to uncemented fixation. When using uncemented components, however, there is evidence that augmenting a porous surface with hydroxyapatite may mean less motion between implant and bone after the initial postoperative year.


Mandatory fortification of flour with folic acid: an overdue public health opportunity.
The scientific benefit is clear, but translating this into practice requires advocacy.


The infectivity of surviving Psoroptes ovis (Hering) on cattle treated with ivermectin.
Ivermectin, 22,23-dihydroavermectin B1 (Merck MK-933), injected intramuscularly at the rate of 200 microgram kg-1 body wt., completely eliminated Psoroptes ovis populations from 6 Hereford cattle within 2 weeks after treatment. However, mites surviving 1, 3, and 5 days after treatment were viable and infective when transferred to untreated cattle. Mites surviving 7 days after treatment did not cause scabies or establish a colony of mites when transferred to untreated cattle. These results indicate that cattle treated with ivermectin for control of psoroptic scabies should be isolated from other cattle for at least 5 days after treatment.


α-linolenic acid supplementation prevents exercise-induced improvements in white adipose tissue mitochondrial bioenergetics and whole-body glucose homeostasis in obese Zucker rats.
While the underlying mechanisms in the development of insulin resistance remain inconclusive, metabolic dysfunction in both white adipose tissue (WAT) and skeletal muscle have been implicated in the process. Therefore, we investigated the independent and combined effects of α-linolenic acid (ALA) supplementation and exercise training on whole-body glucose homeostasis and mitochondrial bioenergetics within the WAT and skeletal muscle of obese Zucker rats. We randomly assigned obese Zucker rats to receive a control diet alone or supplemented with ALA and to remain sedentary or undergo exercise training for 4 weeks (CON-Sed, ALA-Sed, CON-Ex and ALA-Ex groups). Whole-body glucose tolerance was determined in response to a glucose load. Mitochondrial content and bioenergetics were examined in skeletal muscle and epididymal WAT (eWAT). Insulin sensitivity and cellular stress were assessed by western blot. Exercise training independently improved whole-body glucose tolerance as well as insulin-induced signalling in muscle and WAT. However, the consumption of ALA during exercise training prevented exercise-mediated improvements in whole-body glucose tolerance. ALA consumption did not influence exercise-induced adaptations within skeletal muscle, insulin sensitivity and mitochondrial bioenergetics. In contrast, within eWAT, ALA supplementation attenuated insulin signalling, decreased mitochondrial respiration and increased the fraction of electron leak to reactive oxygen species (ROS). These findings indicate that, in an obese rodent model, consumption of ALA attenuates the favourable adaptive changes of exercise training within eWAT, which consequently impacts whole-body glucose homeostasis. The direct translation to humans, however, remains to be determined.


Racial and Ethnic Differences in Communication Quality During Family-Centered Rounds.
To evaluate racial and ethnic differences in communication quality during family centered rounds. We conducted an observational study of family-centered rounds on hospital day 1. All enrolled caregivers completed a survey following rounds and a subset consented to audio record their encounter with the medical team. We applied a priori defined codes to transcriptions of the audio-recorded encounters to assess objective communication quality, including medical team behaviors, caregiver participatory behaviors, and global communication scores. The surveys were designed to measure subjective communication quality. Incident Rate Ratios (IRR) were calculated with regression models to compare the relative mean number of behaviors per encounter time minute by race and ethnicity. Overall, 202 of 341 eligible caregivers completed the survey, and 59 had accompanying audio- recorded rounds. We found racial and ethnic differences in participatory behaviors: English-speaking Latinx (IRR 0.5; 95% confidence interval [CI] 0.3-0.8) Black (IRR 0.6; 95% CI 0.4-0.8), and Spanish-speaking Latinx caregivers (IRR 0.3; 95% CI 0.2-0.5) participated less than white caregivers. Coder-rated global ratings of medical team respect and partnership were lower for Black and Spanish-speaking Latinx caregivers than white caregivers (respect 3.1 and 2.9 vs 3.6, P values .03 and .04, respectively: partnership 2.4 and 2.3 vs 3.1, P values .03 and .04 respectively). In surveys, Spanish-speaking caregivers reported lower subjective communication quality in several domains. In this study, Black and Latinx caregivers were treated with less partnership and respect than white caregivers.


A multicountry controlled trial of strategies to promote dissemination and implementation of brief alcohol intervention in primary health care: findings of a World Health Organization collaborative study.
This study examines the impact of marketing strategies on the dissemination of a brief alcohol intervention program to general practitioners (GPs). The marketing strategy was tested to determine the most effective way to promote awareness about and consideration of a brief alcohol intervention program. The study also examines the impact of training and support strategies to promote the program's implementation in routine primary care. A pragmatic trial was carried out in Australia, Belgium (Flanders), Denmark, England, New Zealand and Spain (Catalonia) in which GPs were randomly allocated into one of three marketing conditions (direct mail, telemarketing and academic detailing [personal visits]). The GPs who requested a brief intervention program and agreed to use it were stratified by previous marketing condition and randomly allocated into one of three implementation strategy groups: written guidance, outreach training and outreach training plus ongoing telephone support. Acceptance of the brief intervention program was more effective with use of telemarketing (65%) and academic detailing (67%) than with direct mail (32%) for promoting awareness about and consideration of a brief alcohol intervention program. The median proportion of patients screened was higher for trained GPs (6%) and supported GPs (9%) than for control GPs (1%), who received only written guidance on how to conduct brief intervention. Similarly, the median rate for giving advice to at-risk patients was higher for trained GPs (3%) and supported GPs (3%) than for control GPs (0%). The adoption of more direct approaches for disseminating evidence-based intervention programs to GPs is a necessary first step for changing practice behavior. However, outreach training was required to promote actual use of a new procedure in routine practice.


Withania somnifera extracts induced attenuation of HIV-1: a mechanistic approach to restrict viral infection.
Several anti-retroviral drugs are available against Human immunodeficiency virus type-1, but have multiple adverse side effects. Hence, there is an incessant compulsion for effectual anti-retroviral agents with minimal or no intricacy. Traditionally, natural products have been the most successful source for the development of new medications. Withania somnifera, also known as Ashwagandha, is the utmost treasured medicinal plant used in Ayurveda, which holds the potential to give adaptogenic, immunomodulatory, and antiviral effects. However, its effect on HIV-1 replication at the cellular level has never been explored. Herein, we focused on the anti-HIV-1 activity and the probable mechanism of action of hydroalcoholic and aqueous extracts of Withania somnifera roots and its phytomolecules. The cytotoxicity of the extracts was determined through MTT assay, while the in vitro anti-HIV-1 activity was assessed in TZM-bl cells against the HIV-1 strains of X4 and R5 subtypes. Results were confirmed in peripheral blood mononuclear cells, using the HIV-1 p24 antigen assay. Additionally, the mechanism of action was determined through the Time of Addition assay, which was further validated through the series of enzymatic assays, i.e. HIV-1 Integrase, Reverse transcriptase, and Protease assays. To explore the role of the identified active metabolites of Withania somnifera in antiretroviral activity, molecular docking analyses were performed against these key HIV-1 replication enzymes. The hydroalcoholic and aqueous extracts of Withania somnifera roots were found to be safer at the sub-cytotoxic concentrations and exhibited their ability to inhibit replication of two primary isolates of HIV-1 through cell-associated and cell-free assays, in dose-dependent kinetics. Several active phytomolecules found in Withania somnifera successfully established hydrogens bonds in the active binding pocket site residues responsible for the catalytic activity of HIV replication and therefore, signifying their role in the attenuation of HIV-1 infection as implied through the in silico molecular docking studies. Our research identified both the hydroalcoholic and aqueous extracts of Withania somnifera roots as potent inhibitors of HIV-1 infection. The in silico analyses also indicated the key components of Withania somnifera with the highest binding affinity against the HIV-1 Integrase by 12-Deoxywithastramonolide and 27-Hydroxywithanone, HIV-1 Protease by Ashwagandhanolide and Withacoagin, and HIV-1 Reverse transcriptase by Ashwagandhanolide and Withanolide B, thereby showing possible mechanisms of HIV-1 extenuation. Overall, this study classified the role of Withania somnifera extracts and their active compounds as potential agents against HIV-1 infection.


Combination of withaferin A and X-ray irradiation enhances apoptosis in U937 cells.
Combined treatment with radiation has improved the outcome in various cancers and many radiosensitizers are used to enhance the therapeutic efficiency of radiotherapy. Withaferin A (Wit A), a natural compound derived from the medicinal plant Withania somnifera, has been reported for its anti-inflammatory and anti-tumor effects. In this study, we show that Wit A enhances the ionizing radiation (IR)-induced apoptosis in human lymphoma U937 cells. Wit A-enhanced IR-induced apoptosis is associated with the PARP cleavage, caspase-3 activation, as well as specifically down-regulation of anti-apoptotic protein Bcl-2, suggesting that Wit A may be useful as a potential radiosensitizer. In addition, pretreatment of U937 cells with SP600125 (JNK inhibitor) or SB203589 (p38 MAPK inhibitor) dose-dependently inhibited the proteolytic cleavage of PARP. We provide the evidence here that generation of reactive oxygen species (ROS), Bcl-2 down-regulation and activation of MAPKs pathway are critically involved in the apoptosis induced by Wit A and radiation.


Influences of thyroxine on cell proliferation in the retina of the clawed frog at different ages.
The change in spatial pattern of retinal cell production that occurs after midlarvae stages in Xenopus is shown to occur because of a greater proliferative response to thyroxine in the ventral than in the dorsal margin of the retina. The asymmetry of retinal cell production is not caused by a dorsoventral difference in the duration of the mitotic cycle. It is concluded that the asymmetry is due to differences in the number of proliferative cells in different parts of the retinal margin.


A family of cyclophilin-like molecular chaperones in Plasmodium falciparum.
The cyclophilins are a large family of proteins implicated in folding, transport and regulation of other proteins and are potential drug targets in cancer and in some viral and parasitic infections. The functionality of cyclophilins appears to depend on peptidyl-prolyl cis-trans isomerase (foldase) and/or molecular chaperone activities. In this study we assessed the peptidyl-prolyl isomerase and chaperone activities of 8 members of the Plasmodium falciparum cyclophilin family, all produced recombinantly using a common host/vector system. While only two of these proteins had isomerase activity, all of them displayed chaperone function as judged by the ability to prevent the thermal aggregation of model substrates. We suggest that the cyclophilins constitute a family of molecular chaperones in malarial parasites that complement the functions of other chaperones such as the heat-shock proteins.


Humic acid removal and easy-cleanability using temperature-responsive ZrO2 tubular membranes grafted with poly(N-isopropylacrylamide) brush chains.
New poly(N-isopropylacrylamide) brushes grafted with ZrO2 (PNIPAAm-g-ZrO2) composite membranes, which had been prepared in our laboratory, were used for humic acid (HA) removal. We found that the fluxes associated with such membranes, when compared to those obtained from unmodified ZrO2 membranes, declined slightly at both 25 °C and 35 °C. The PNIPAAm-g-ZrO2 membrane achieved a high rejection, of 98.0%, at a suitable steady flux of 111.9 L m(-2) h(-1) at 25 °C. This membrane exhibited good anti-fouling properties as well as improved membrane performance during filtration of HA. The important role of pH and Ca(2+) concentration in HA removal was also investigated. Lower adsorption fouling and a higher rejection were obtained at higher pH levels. The Ca(2+) ions reduced the electrostatic exclusion and played a cross-linking role between HA and the PNIPAAm-g-ZrO2 membrane surface. Fouling was severe in the presence of Ca(2+). These tests led to the development of an environment-friendly membrane cleaning method, by means of temperature-change water elution around LCST of PNIPAAm-brushes. After the alternate temperature-change (25 °C/35 °C) cleaning, a flux recovery of 98.2% was obtained for the PNIPAAm-g-ZrO2 membrane. Moreover, after four repeated experiments, the anti-fouling and easy-cleaning properties were still maintained. It is implied that PNIPAAm-brushes were firmly "stuck" to the membrane surface, and could not easily be removed by water cleaning or HA filtration. The PNIPAAm-g-ZrO2 membranes exhibited good stability and great potential for HA removal.


Clinical characteristics and epidemiology of pulmonary pseudallescheriasis.
Some members of the Pseudallescheria (anamorph Scedosporium) have emerged as an important cause of life-threatening infections in humans. These fungi may reach the lungs and bronchial tree causing a wide range of manifestations, from colonization of airways to deep pulmonary infections. Frequently, they may also disseminate to other organs, with a predilection for the brain. In otherwise healthy patients, the infection is characterized by non-invasive type involvement, while invasive and/or disseminated infections were mostly seen in immunocompromised patients. We reviewed all the available reports on Pseudallescheria/Scedosporium pulmonary infections, focusing on the geographical distribution, immune status of infected individuals, type of infections, clinical manifestations, treatment and outcome. The main clinical manifestations of the 189 cases of pulmonary pseudallescheriasis reviewed were pneumonia (89), followed by fungus ball (26), and chest abscess (18). Some patients had more than one type of invasive pulmonary manifestations. Among patients with pneumonia, several cases of pneumonia associated with near-drowning (10/89, 11.2%) have also been reported in immunocompetent hosts. Major underlying conditions for non-invasive pulmonary infection were preexisting lung cavities and medical immunosuppression for invasive pulmonary infection. Saprobic airway colonization was mostly seen in patients with mucosal dysfunction, i.e. patients with cystic fibrosis. The mortality rate was closely related to the infection type, being 26.8% in non-invasive type (fungus balls) and 57.2% in invasive type.


Esthetic soft tissue ridge augmentation around dental implant: Case report.
The aim of this case report is to present a method to correct soft tissue ridge deformity around dental implant using acellular dermal matrix (ADM). A 25-year-old female patient presented with a missing maxillary first left premolar, which had class I soft tissue defect. The missing tooth was replaced with single implant supported prosthesis and the soft tissue defect was corrected using ADM utilizing the envelop technique. A 5-years follow-up is presented showing the long-term stability of this technique and the predictability of using the ADM as an alternative method to connective tissue graft to correct the soft tissue defect around dental implant.


The sarcoplasmic calcium pump - a most efficient ion translocating system.
In contrast to the sodium-potassium transporting plasma membranes, the sarcoplasmic membranes (SR) are highly specialized structures into which only two major intrinsic proteins, a calcium transporting protein and a calcium binding protein are embedded. The calcium transporting protein is a highly asymmetric molecule. It binds two calcium ions with a very high affinity at its external, and two calcium ions with low affinity at the internal section of the molecule. ATP is bound with high afffinity to an external binding site, inducing a conformational change. When the vesicular membranes are exposed to solutions containing Ca++, Mg++ and ATP, ATP is hydrolyzed and simultaneously calcium ions are translocated from the external medium into the vesicular space. When calcium ions are translocated in the opposite direction, ATP is synthesized. The calcium-ATP ratio for ATP cleavage as well as for ATP synthesis is 2. Thus, the SR membranes can transform reversibly chemical into osmotical energy. Inward and outward movements of calcium ions are relatively slow processes connected with the appearance and disappearance of different phosphorylated intermediates. One phosphorylated intermediate is formed by phosphoryltransfer from ATP when calcium ions are present in the medium. In contrast, when calcium ions are absent from the external medium, two different intermediates can be formed by the incorporation of inorganic phosphate. Only when calcium ions present in the internal space of the vesicles are released, the incorporation of inorganic phosphate gives rise to an intermediate who phosphoryl group can be transferred to ADP.


Cancer of the anal canal.
Anal cancer is an uncommon tumour that represents 4% of all cancers of the lower gastrointestinal tract. Its pathogenesis and treatment have undergone substantial reassessment over the past two decades, and this is likely to continue. Anal cancer can be cured by synchronous chemoradiotherapy, a treatment that both enables anal continence to be retained and reserves abdominoperineal resection of the rectum and anal canal (with formation of a permanent colostomy) for recurrent or residual disease after primary chemoradiotherapy. Overall, survival from anal cancer is now around 70-80% at 5 years. Future challenges will be influenced by an increasing incidence due to human papillomavirus and HIV infection, more accurate characterisation and treatment of early (in situ) disease, and optimisation of chemoradiation regimens.


Spectroscopic meta-analyses reveal novel metabolite profiles across methamphetamine and cocaine substance use disorder.
Although proton magnetic resonance spectroscopy (MRS) has been used to study metabolite alterations in stimulant (methamphetamine and cocaine) substance use disorders (SUDs) for over 25 years, data-driven consensus regarding the nature and magnitude of these alterations is lacking. In this meta-analysis, we examined associations between SUD and regional metabolites (N-acetyl aspartate (NAA), choline, myo-inositol, creatine, glutamate, and glutamate+glutamine (glx)) in the medial prefrontal cortex (mPFC), frontal white matter (FWM), occipital cortex, and basal ganglia as measured by 1 H-MRS. We also examined moderating effects of MRS acquisition parameters (echo time (TE), field strength), data quality (coefficient of variation (COV)), and demographic/clinical variables. A MEDLINE search revealed 28 articles that met meta-analytic criteria. Significant effects included lower mPFC NAA, higher mPFC myo-inositol, and lower mPFC creatine in SUD relative to people without SUD. mPFC NAA effects were moderated by TE, with larger effects at longer TEs. For choline, although no group effects were observed, effect sizes in the mPFC were related to MRS technical indicators (field strength, COV). No effects of age, sex, primary drug of use (methamphetamine vs. cocaine), duration of use, or duration of abstinence were observed. Evidence for moderating effects of TE and COV may have implications for future MRS studies in SUDs. The observed metabolite profile in methamphetamine and cocaine SUD (lower NAA and creatine with higher myo-inositol) parallels that observed in Alzheimer's disease and mild cognitive impairment, suggesting these drugs are associated with neurometabolic differences similar to those characterizing these neurodegenerative conditions.


Attachment of Acidithiobacillus ferrooxidans onto different solid substrates and fitting through Langmuir and Freundlich equations.
Attachments of Acidithiobacillus ferrooxidans ATCC 23270 onto elemental sulfur, quartz and complex chalcopyrite were investigated by analysis of its extracellular polymeric substances as well as applying Langmuir and Freundlich equations. The two equations fitted the adsorption equilibrium data with significant correlation coefficient over 0.9. This indicated that bacterial attachment is complicated and involves Langmuir and Freundlich characterizations. Sulfur-grown cells showed the highest affinity for the three solid substrates. The investigated complex chalcopyrite possessed a higher maximum adsorption capacity for A. ferrooxidans than elemental sulfur or quartz. The Freundlich fitting parameters suggested that quartz had a weaker adsorption capacity and smaller adsorption areas than elemental sulfur or the complex chalcopyrite. It is not the content of total carbohydrates or proteins in EPS but their ratios that determine the affinity differences between cells and substrates.


Interventions and Therapy in Rheumatology.
Patients affected by rheumatic conditions frequently present with spine degeneration and vertebral compression fractures, mainly related to the long-term therapies with glucocorticosteroids. A mini-invasive approach provided by interventional radiology techniques, especially vertebroplasty, plays a relevant role in the pain management of these patients; vertebroplasty represents the symptomatic treatment of fracture pain, so patients must always be included in a specific therapeutic workup of the rheumatic condition. This article describes patient selection criteria, technique, and outcomes of vertebroplasty in patients affected by rheumatic disease and secondary osteoporosis caused by glucocorticosteroids.


Epidemiology and clinical features of Streptococcus pyogenes bloodstream infections in children in Madrid, Spain.
Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13 years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16 years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1: 2005-June 2011 vs P2: July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI: -2.7, + 15.4]; p = 0.163). Median age was 24.1 months (IQR: 14.0-53.7), peaking during the first four years of life (89/109 cases; 81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7 vs. 13 days; p = 0.003) and received intravenous antibiotics less frequently (72.5% vs. 94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10 vs. 21 days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI: 2.16-29.41]). Two children (1.8%) died. Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).


Reduced gap junctional intercellular communication and altered biological effects in mouse osteoblast and rat liver oval cell lines transfected with dominant-negative connexin 43.
Gap junctional intercellular communication (GJIC) maintains normal growth and differentiation of cells in a tissue. The intercellular molecules traversing gap junctions are largely unknown, but the molecular weight (MW) cutoff is normally 1200 Da. No differences in dye transfer were observed in normal or vector controls of WB-F344 rat liver epithelial or mouse osteoblastic MC3T3-E1 cells with either Lucifer Yellow (LY) with a MW of 457 Da (LY-457) or LY with a MW of 649 Da (LY-649). Transfection of a dominant negative-connexin 43 (Cx43) gene decreased GJIC (>50%) when LY-649 was used, however, normal GJIC was observed in both cell lines when LY-457 was used. Therefore, the MW cut off in these clones was considerably less than the wild type. The dominant negative clones of the MC3T3-E1 cells exhibited over 90% less alkaline phosphatase (ALPase) activity and calcium deposition after the induction of differentiation. Similarly, dominant negative Cx43 inhibited gene expression of ALPase and bone sialoprotein but not osteocalcin in MC3T3-E1. WB-F344 cells normally exhibit a biphasic response to 12-O-tetradecanoylphorbol-13-acetate (TPA) where inhibition of GJIC recovers after 2 h, but the dominant negative clones showed no recovery from inhibition of GJIC by TPA. Dominant negative Cx43 also inhibited the formation of network-like structures by WB-F344 cells on Matrigel. These results demonstrate that the dominant negative gene transfected into cell types containing the wild-type connexins result in diminished channel sizes, thus allowing the determination of whether distinct biological endpoints, i.e., differentiation, are dependent upon either small or high MW intercellular signals.


First Report of Using Portable Unmanned Aircraft Systems (Drones) for Search and Rescue.
Unmanned aircraft systems (UAS), colloquially called drones, are used commonly for military, government, and civilian purposes, including both commercial and consumer applications. During a search and rescue mission in Oregon, a UAS was used to confirm a fatality in a slot canyon; this eliminated the need for a dangerous rappel at night by rescue personnel. A second search mission in Oregon used several UAS to clear terrain. This allowed search of areas that were not accessible or were difficult to clear by ground personnel. UAS with cameras may be useful for searching, observing, and documenting missions. It is possible that UAS might be useful for delivering equipment in difficult areas and in communication.


Predicting Discharge Walking Function With High-Intensity Stepping Training During Inpatient Rehabilitation in Nonambulatory Patients Poststroke.
This cohort investigation identified primary predictors of discharge walking function of nonambulatory individuals poststroke with high-intensity training (HIT) during inpatient rehabilitation. Observational cohort investigation. Inpatient rehabilitation. Data were collected from individuals (N=257) <6 months poststroke who required assistance to walk at admission. Clinical physical therapy interventions attempted to maximize stepping practice at higher intensities. Primary outcomes included the discharge level of assistance required during walking (minimal or no assistance) and attainment of specific gait speed thresholds (0.4 and 0.8 m/s) during the 10-m walk test. Independent predictors were demographics, training interventions (including steps/day), baseline Berg Balance Scale (BBS), and paretic leg strength. Participants performed a median (interquartile range) of 1270 (533-2297) steps per day throughout inpatient rehabilitation, with significant differences between those who walked with versus without assistance at discharge. Logistic regressions indicate steps per day was a primary predictor of unassisted walking recovery; removal of steps per day resulted in primary predictors of baseline BBS and strength. Receiver operating characteristic (ROC) analyses indicate significant areas under the curve for BBS and relatively low cutoff scores of 5.5 points at admission to walk without assistance at any speed. ROC analyses performed using 1-week outcomes indicate BBS scores of 5-17 points were needed to achieve locomotor thresholds. Stepping activity, BBS, and paretic leg strength were primary predictors of walking outcomes in patients performing HIT, and ROC analyses indicated recovery of independent walking could be achieved in low functioning patients early poststroke.


Matrix-based autologous chondrocyte implantation for cartilage repair with HyalograftC: two-year follow-up by magnetic resonance imaging.
Monitoring of articular cartilage repair after matrix-associated autologous chondrocyte implantation with HyalograftC by a new grading system based on non-invasive high-resolution magnetic resonance imaging. In 23 patients, postoperative magnetic resonance imaging (MRI) was performed between 76 and 120 weeks. In nine of these patients, five MRI examinations were performed at 4, 12, 24, 52 and 104 weeks after HyalograftC implant. The repair tissue was described with separate variables: degree of defect repair in width and length, signal intensity of the repair tissue and status of the subchondral bone. For these variables a grading system with point scale evaluation was applied. High-resolution MRI provides a non-invasive tool for monitoring the development of cartilage repair tissue following HyalograftC technology, shows a good correlation with clinical outcome and may help to differentiate abnormal repair tissue from a normal maturation process.