Tibial nonunion treated with direct current, capacitive coupling, or bone graft.
Two hundred seventy-one tibial nonunions of average duration of 23.5 months (range, 9-69 months) were treated with direct current (167 patients), capacitive coupled electrical stimulation (56 patients), or bone graft surgery (48 patients). Logistic regression analysis was used to compare heal rates among the 3 treatment methods, to identify risk factors adversely affecting the heal rate, and to predict the probability of successful healing of a nonunion of any given risk profile treated with each of the 3 forms of therapy. Seven risk factors were identified: duration of nonunion, prior bone graft surgery, prior electrical treatment, open fracture, osteomyelitis, comminuted or oblique fracture, and atrophic nonunion. When no risk factors were present, there were no significant differences among the 3 treatment methods. As progressively more risk factors were present, the predicted heal rates decreased significantly regardless of the treatment method. Some differences among the treatment groups did appear in the heal rates: bone graft surgery yielded a worse heal rate when there was a previous bone graft failure, and capacitive coupling had a worse heal rate in the presence of an atrophic nonunion.


Antikinetoplastid Activity of Sesquiterpenes Isolated from the Zoanthid Palythoa aff. clavata.
Leishmaniasis and Chagas disease are neglected tropical diseases that cause problems in developing countries. The causative agents, Leishmania spp. and Trypanosoma cruzi, produce a clinical picture that can be fatal for the patient, such as Chagas heart disease, visceral leishmaniasis and megacolon, among others. Current treatments for these diseases are not very effective and highly toxic, since they require very prolonged treatments. The development of innovative, effective and safe drugs to fight infections caused by these parasites remains a challenge. For this reason, in recent years, there has been an increase in the search for new therapies. In this study, the antikinetoplastid activity of 13 sesquiterpene lactones obtained from Palythoa aff. clavata was screened against L. amazonensis, L. donovani and T. cruzi. The results revealed that the sesquiterpene lactones anhydroartemorin (2), cis,trans-costunolide-14-acetate (3) and 4-hydroxyarbusculin A (11) were the most selective against the kinetoplastid species studied. These molecules seem to induce the mechanisms involved in an apoptotic-like death or programmed cell death (PCD) in the kinetoplastids, and since they do not cause necrosis, the inflammatory events associated with this type of cell death will not be triggered.


Interethnic marriages in the USSR in the mid-1930s.
"The present article will attempt to determine the extent of interethnic marriage in the Soviet Union in the mid-1930s, utilizing materials from the Central Statistical Administration of the USSR." Interethnic marriage is analyzed according to Union Republic, rural or urban area, and socioeconomic and cultural development.


Diverticular Choledochal Cyst with a Large Impacted Stone Masquerading as Mirizzi's Syndrome.
Choledochal cysts are congenital anomalies of the biliary tract manifested by cystic dilatation of the extrahepatic and intrahepatic bile ducts. Choledochal cyst is not rare in far-East Asian countries. Type II choledochal cysts account for 2% of all such cysts. They are true diverticula of the extrahepatic bile duct and communicate with the bile duct through a narrow stalk. This condition is associated with significant complications, such as ductal strictures, stone formation, cholangitis, rupture and secondary biliary cirrhosis. We describe a case of a huge impacted stone in a diverticular choledochal cyst which masqueraded as an unusual cystic duct stone causing Mirizzi's syndrome.


Therapeutic use of microRNAs in lung cancer.
Lung cancer is a leading cause of cancer deaths worldwide. Although the molecular pathways of lung cancer have been partly known, the high mortality rate is not markedly changed. MicroRNAs (miRNAs) are small noncoding RNAs that actively modulate cell physiological processes as apoptosis, cell-cycle control, cell proliferation, DNA repair, and metabolism. Several studies demonstrated that miRNAs are involved in the pathogenesis of lung diseases including lung cancer and they negatively regulate gene and protein expression by acting as oncogenes or tumor suppressors. In this review we summarize the current knowledge on the role of miRNAs and their target genes in lung tumorigenesis and evaluate their potential use as therapeutic agents in lung cancer. In particular, we describe methodological approaches such as inhibition of oncogenic miRNAs or replacement of tumor suppressor miRNAs, both in in vitro and in vivo assays. Furthermore we discuss new strategies to achieve in vivo tissue specific delivery, potential off-target effects, and safety of miRNAs systemic delivery.


Exposure to Chinese famine in early life and the risk of sensory impairment in adulthood.
Studies have shown that malnutrition in early life has a negative effect on midlife cognitive functions. Little is known, however, about the relationship between early-life malnutrition and visual, hearing or dual sensory impairments in adulthood. This study aims to investigate the association between exposure to the 1959-1961 Chinese famine in early life and sensory impairments in adulthood. A total of 6347 adults born between 1952 and 1964 surveyed in the 2015 China Health and Retirement Longitudinal Study were included in this study. The presence of sensory impairments was identified by self-reported assessment of visual and hearing functions. The associations between multi-stage early-life famine exposure and sensory functions were estimated using the multiple generalised linear model. Compared with the unexposed group, respondents exposed to famine in the fetal period and late childhood had a significantly higher risk of hearing impairment (OR 1.54, 95% CI 1.06 to 2.24; OR 1.75, 95% CI 1.23 to 2.50) and dual sensory impairments (OR 1.45, 95% CI 1.00 to 2.11; OR 1.55, 95% CI 1.09 to 2.21), respectively. Furthermore, in severely famine-affected areas, the early, mid and late childhood-exposed groups were more likely to have hearing and dual sensory impairments than the unexposed group. Those associations were not observed in less famine-affected areas. However, no significant association was found between famine exposure and visual impairment in early-life famine-exposed group. Exposure to Chinese famine in the fetal period and late childhood was linked to hearing and dual sensory impairments in adulthood.


v-Src-mediated phosphorylation of connexin43 on tyrosine disrupts gap junctional communication in mammalian cells.
It is not clear how the v-Src oncoprotein disrupts gap junctional communication (GJC) established by connexin43 (Cx43) in mammalian cells. In this study, an experimental system was established to stably express v-Src and wild type (wt) Cx43, or Y247F, Y265F, or Y247F/Y265F Cx43 mutants in a Cx43 knockout (KO) mouse cell line. When co-expressed with v-Src, the levels of phosphotyrosine (pTyr) from Y247F, Y265F, and Y247F/Y265F Cx43 mutants were reduced to approximately 57%, 10%, and 2% of the level of pTyr from wt Cx43, indicating that Y247 and Y265 were phosphorylation targets of v-Src in vivo. These data also implied that phosphorylation of Cx43 at Y265 was required for efficient phosphorylation of Cx43 at Y247. Most importantly, our measurements of GJC demonstrated that, in contrast to the wt Cx43 gap junction channels, the Y247F, Y265F, and Y247F/Y265F Cx43 channels were resistant to the disruption by v-Src. In conclusion, our studies support a model for processive phosphorylation of Cx43 on tyrosine, at the Y265 site followed by the Y247 site, in mediating the disruption of GJC induced by v-Src in mammalian cells.


Multiple factors in the satiation of salt appetite.
There is evidence in the literature that has been taken to show that, unlike hunger and thirst, salt appetite cannot be satiated in the absence of salt taste stimulation. The present study showed that repletion of body sodium in the absence of taste stimulation, that is, by gavage, can diminish subsequent saline intake. The satiating effects of gavage versus drinking of saline were studied at various intervals after repletion. For the first few hours, gastric loading was constantly less satiating than was drinking. But as the interval between gavage and testing was lengthened beyond 4-8 hr, the satiating effect began to increase until by 16 hr it was equal to that of drinking. The specificity of the satiating effect of saline gavage as a function of time between treatment and testing was also studied. There appeared to be a transient nonspecific blocking effect of solutes on solute intake which had a duration of less than 30 min. The satiating effect of saline gavage became specific after that time. The experiment suggests that there are multiple factors involved in the satiation of salt appetite--a taste factor, a short-latency post ingestional factor, and a long-latency postingestional factor.


Frontal plagiocephaly: synostotic, compensational, or deformational.
Plagiocephaly is a term commonly used to describe congenital forehead asymmetry. Sixty patients with frontal plagiocephaly were evaluated retrospectively and separated into three types: synostotic (N = 24), compensational (N = 3), and deformational (N = 33). Categorization of frontal plagiocephaly as synostotic or deformational was reliably made by physical examination, focusing on the supraorbital rims, nasal root, ears, and malar eminences. Other anatomic parameters useful in the differential diagnosis included chin point, palpebral fissures, and facial height. This study documented that birth histories were similar for synostotic and deformational frontal plagiocephalic infants. However, other deformational anomalies were more common in deformational frontal plagiocephalic infants, whereas malformations had an equal incidence in deformational and synostotic frontal plagiocephalic infants. Torticollis was an associated finding in 64 percent of infants with deformational frontal plagiocephaly; almost all were ipsilateral. In contrast, head tilt, usually to the contralateral side, was noted in 14 percent of patients with synostotic frontal plagiocephaly. Female preponderance was noted in both synostotic (79 percent) and deformational (76 percent) frontal plagiocephaly. Left-sided involvement was seen in 73 percent of patients with deformational frontal plagiocephaly and in 46 percent of patients with synostotic frontal plagiocephaly. Premature pelvic descent, in the left occipital anterior position, may account for the high incidence of left-sided deformational plagiocephaly and ipsilateral torticollis.


A novel minimally occlusive microvascular anastomosis technique using a temporary intraluminal shunt: a prospective technique to minimize brain ischemia time during superficial temporal artery-to-middle cerebral artery bypass.
To describe a new technique of suturing microvessels with persistent perfusion via a temporary intraluminal microshunt. Experiments were conducted in Wistar rats. Abdominal aorta grafts were explanted from donor rats. A soft silicon microcatheter was introduced into the lumen of this graft. The abdominal aorta of a recipient rat was prepared for end-to-side microvascular anastomosis. Acland clamps (S&T AG, Neuhausen, Switzerland) were applied, and a linear arteriotomy was made. One end of the graft-clad microcatheter was introduced into the lumen and occluded with a fenestrated Acland clamp. At a more distal part, a similar arteriotomy was performed, and the other end of the microcatheter was introduced into the lumen and clamped with a fenestrated Acland clip. This created a temporary shunt through the graft-clad microcatheter. Then, the graft was anastomosed to the arteriotomies at both ends, over the microcatheter, in an end-to-side manner. The microcatheter was explanted from the vessel lumen through an arteriotomy in the middle of the graft. The graft was clipped short to close this arteriotomy. The mean total occlusion time before perfusion was reestablished amounted to 3.7 minutes. This experiment was repeated in 12 animals (6 with and 6 without heparin) without technical complications. As controls, conventional anastomoses were made in 2 animals. Suturing microvessels mandates their occlusion during the period of anastomosis. Although ischemia is well tolerated by other tissue types, the brain is quite sensitive to even short windows of ischemia. Nonocclusive anastomotic techniques have been developed recently. These are confined to vessels with luminal diameters greater than 3 mm. We have evolved a novel technique that can be used with microvessels, as pertinent to superficial temporal artery-to-middle cerebral artery bypass. We have described a new technique for performing microvascular anastomoses over a temporary intraluminal microcatheter shunt.


Preferences of patients undergoing hemodialysis - results from a questionnaire-based study with 4,518 patients.
Chronic kidney disease is an increasing health problem worldwide and in its final stage (stage V) can only be treated by renal replacement therapy, mostly hemodialysis. Hemodialysis has a major influence on the everyday life of patients and many patients report dissatisfaction with treatment. Little is known about which aspects of treatment are considered important by hemodialysis patients. The objective of this study was to rate the relative importance of different outcomes for hemodialysis patients and to analyze whether the relative importance differed among subgroups of patients. Within the framework of a yearly questionnaire which is distributed among patients receiving hemodialysis by the largest hemodialysis provider in Germany, we assessed the relative importance of 23 outcomes as rated on a discrete visual analog scale. Descriptive statistics were used to rank the outcomes. Subgroup analyses were performed using Mann-Whitney U or Kruskal-Wallis tests. Questionnaires of 4,518 hemodialysis patients were included in the analysis. The three most important outcomes were safety of treatment, health-related quality of life, and satisfaction with care. Further important outcomes were hospital stays, accompanying symptoms, hemodialysis duration, and the improvement or preservation of a good emotional state. Age, profession, and education had the strongest influence on relevant differences of preferences for outcomes; no relevant influence of sex or comorbidity was observed. Outcomes concerning the delivery or provision of care and aspects influencing quality of life are rated by patients to be at least as important as clinical outcomes. Many of the outcomes judged to be important by the patients are not regularly considered in research, evaluation studies, or quality programs.


Effects of repetitive galvanic vestibular stimulation on spatial neglect and verticality perception-a randomised sham-controlled trial.
Recent evidence shows that bipolar galvanic vestibular stimulation (GVS) with the cathode on the left (CL) or right (CR) mastoid ameliorates spatial neglect, extinction and verticality perception transiently and partly permanently. However, no randomised controlled trial evaluated the long-term effects of repetitive GVS in comparison to sham-GVS on exploration and verticality perception. To compare the effects of CL-GVS, CR-GVS and Sham-GVS on spatial exploration and verticality perception in right-hemispheric stroke patients with left neglect we conducted a randomised controlled trial with minimisation. Twenty-four patients completed 10-12 training sessions on a daily basis, 5 days/week. The CL-and CR-GVS group received 20 min of stimulation at 1.5 mA, the Sham-GVS group only 30 s of CL-GVS. Simultaneously, all patients performed a standard therapy of smooth pursuit eye movement training (SPT) followed by visual scanning training (VST). Outcome measures (Neglect test, visuo-tactile search task, subjective visual and tactile vertical) were assessed before and immediately after the intervention and at 2- and 4-week follow-ups. Our results show that neither our standard therapy nor the combination of standard therapy and GVS improved neglect symptoms significantly. The reasons for our non-significant results are discussed.


Evolution under domestication: ongoing artificial selection and divergence of wild and managed Stenocereus pruinosus (Cactaceae) populations in the Tehuacan Valley, Mexico.
The Tehuacán Valley in Mexico is a principal area of plant domestication in Mesoamerica. There, artificial selection is currently practised on nearly 120 native plant species with coexisting wild, silvicultural and cultivated populations, providing an excellent setting for studying ongoing mechanisms of evolution under domestication. One of these species is the columnar cactus Stenocereus pruinosus, in which we studied how artificial selection is operating through traditional management and whether it has determined morphological and genetic divergence between wild and managed populations. Semi-structured interviews were conducted with 83 households of three villages to investigate motives and mechanisms of artificial selection. Management effects were studied by comparing variation patterns of 14 morphological characters and population genetics (four microsatellite loci) of 264 plants from nine wild, silvicultural and cultivated populations. Variation in fruit characters was recognized by most people, and was the principal target of artificial selection directed to favour larger and sweeter fruits with thinner or thicker peel, fewer spines and pulp colours other than red. Artificial selection operates in agroforestry systems favouring abundance (through not felling plants and planting branches) of the preferred phenotypes, and acts more intensely in household gardens. Significant morphological divergence between wild and managed populations was observed in fruit characters and plant vigour. On average, genetic diversity in silvicultural populations (H(E) = 0.743) was higher than in wild (H(E) = 0.726) and cultivated (H(E) = 0.700) populations. Most of the genetic variation (90.58 %) occurred within populations. High gene flow (Nm(FST) > 2) was identified among almost all populations studied, but was slightly limited by mountains among wild populations, and by artificial selection among wild and managed populations. Traditional management of S. pruinosus involves artificial selection, which, despite the high levels of gene flow, has promoted morphological divergence and moderate genetic structure between wild and managed populations, while conserving genetic diversity.


Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor.
The paradigm for activation of Ras and extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase by extracellular stimuli via tyrosine kinases, Shc, Grb2, and Sos does not encompass an obvious role for phosphoinositide (PI) 3-kinase, and yet inhibitors of this lipid kinase family have been shown to block the ERK/MAP kinase signalling pathway under certain circumstances. Here we show that in COS cells activation of both endogenous ERK2 and Ras by low, but not high, concentrations of epidermal growth factor (EGF) is suppressed by PI 3-kinase inhibitors; since Ras activation is less susceptible than ERK2 activation, PI 3-kinase-sensitive events may occur both upstream of Ras and between Ras and ERK2. However, strong elevation of PI 3-kinase lipid product levels by expression of membrane-targeted p110alpha is by itself never sufficient to activate Ras or ERK2. PI 3-kinase inhibition does not affect EGF-induced receptor autophosphorylation or adapter protein phosphorylation or complex formation. The concentrations of EGF for which PI 3-kinase inhibitors block Ras activation induce formation of Shc-Grb2 complexes but not detectable EGF receptor phosphorylation and do not activate PI 3-kinase. The activation of Ras by low, but mitogenic, concentrations of EGF is therefore dependent on basal, rather than stimulated, PI 3-kinase activity; the inhibitory effects of LY294002 and wortmannin are due to their ability to reduce the activity of PI 3-kinase to below the level in a quiescent cell and reflect a permissive rather than an upstream regulatory role for PI 3-kinase in Ras activation in this system.


A case of mycotic keratitis caused by Fusarium solani.
A 36-year-old black man, without history of systemic disease or ocular trauma developed a corneal infection in his left eye. He was treated with antibacterial antibiotic and corticosteroids for one month prior to diagnosis. Fungal hyphae and chlamydospores were found in a KOH preparation of the corneal scrapings, and positive cultures for Fusarium solani were obtained in Sabouraud dextrose agar. It is emphasized the cautious use of antibiotics and steroids in corneal diseases, and the need of considering the involvement of opportunistic fungi in the etiology of these infections.


Sodium metabisulfite in dried plum and its cytotoxic effects on K-562 and L-929 normal cell lines.
In the present study, the concentration of sodium metabisulfite (SMB) in dried plums and its toxicity effects on the cell lines of K-562 (human leukemia cell line) and L-929 (normal fibroblast cell line) were measured. Samples of dried plums were randomly collected from the shops located in Neyshabur and Mashhad (Iran). SMB residue was measured using iodometric titration and high-performance liquid chromatography. To analyze the cytotoxicity, the cells were treated with various concentrations of SMB, and cell viability was determined by the MTT and LDH methods. The average concentration of SMB in the samples of dried plums was selected to evaluate the apoptosis/necrosis by flow cytometer. The expression analysis of apoptosis marker genes (BAX, Bcl-2, and P53) was also assessed. Results indicated that the average concentration of SMB residue in 12 samples of dried plum was 516 ± 285.39 mg/kg. When K-562 cells were treated with 500 mg/L of SMB, apoptosis increased significantly (p < 0.01). The IC50 of SMB for K-562 and L-929 cells after a 48-h exposure was 200.31 and 257.82 mg/L, respectively. SMB-treated cells showed that cell viability in both cell lines decreased in a dose-dependent manner after 72 h (p < 0.01). The percentage of apoptotic but not necrotic cells was 69.49% for K-562 and 77.32% for L-929 cells, whereas apoptosis of untreated control cells was 0.17%. Our findings also showed an opposite mRNA expression of Bcl-2 (anti-apoptotic marker) and Bax2 (pro-apoptotic marker) when k-562 cells were treated with SMB. The results indicated that the concentration of sulfite residue in some dried plums poses a cell toxicity risk for normal cells. PRACTICAL APPLICATION: The results of current study provide important information concerning the toxicological effects of SMB, and give a warning that it needs to be replaced by natural products for fruit drying processes.


Coherent interaction effects in pulses propagating through a doped nonlinear dispersive medium.
Using a numerical approach we report on the cloning dynamics of simultaneous self-induced transparency (SIT) and nonlinear Schrödinger (NLS) solitons in a doped nonlinear dispersive medium. This technique involves a three-level atomic system interacting resonantly with two optical fields within a Lambda scheme. As a result, a pulse in the signal frequency is transformed into a replica of the pulse in the pump frequency. The atomic population evolution shows that the basic mechanism behind the cloning process is the coherent population trapping effect. Furthermore, it is shown that the signal clone presents characteristics of both the SIT soliton and NLS soliton.


[Research on wavelength matching of therapeutic laser fiber].
Medical laser adopts optical fibers as spread media, using laser energy for the purpose of diagnostics and therapeutics. The corresponding industry standard is YY/T 0758-2009 General requirements for therapeutic laser fiber, which requires manufacturers to offer applicable wave length (or spectrum range) of the fiber, and the corresponding minimum transmission efficiency of the wave length. This research focuses on the matching of therapeutic laser fiber and laser source, to support and emphasize the importance and reasonability of relative requirements in YY/T 0758-2009.


A fundamental measure density functional for fluid and crystal phases of the Asakura-Oosawa model.
We investigate a density functional for the Asakura-Oosawa model of colloid-polymer mixtures, describing both fluid and crystal phases. It is derived by linearizing the two-component fundamental-measure hard sphere tensor functional in the second (polymer) component. We discuss the formulation of an effective density functional for colloids only. For small polymer-colloid size ratios the effective, polymer-induced potential between colloids is short-range attractive and of two-body form but we show that the effective density functional is not equivalent to standard mean-field approaches where attractions are taken into account by terms second order in the colloid density. We calculate numerically free energies and phase diagrams in good agreement with available simulations, furthermore we discuss the colloid and polymer distributions in the crystal and determine equilibrium vacancy concentrations. Numerical results reveal a fairly strong sensitivity to the specific type of underlying fundamental measure hard sphere functional which could aid further development of fundamental measure theory.


In vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic T lymphocytes.
Cytotoxic T lymphocyte (CTL)-mediated cytolysis is induced via the interaction of the specific T-cell antigen receptor and the peptidic viral antigen associated with the major histocompatibility complex class I antigen. Here we demonstrate in vitro that lymphocytic choriomeningitis virus (LCMV) can escape the cytotoxic activity of LCMV-specific cloned CTLs by single amino acid changes within the recognized T-cell epitope defined by residues 275-289 of the LCMV glycoprotein [LCMV-GP-(275-289)]. LCMV-infected fibroblasts at a multiplicity of infection of 10(-3) exposed to virus-specific CTL at an effector-to-target cell ratio of 4:1 4 hr after infection was optimal for virus mutant selection. The selections were carried out with three LCMV-GP-(275-289)-specific CTL clones expressing T-cell antigen receptors containing the identical variable gene segments V alpha 4 and V beta 10 but different junctional regions; selection was also possible with LCMV-GP-(275-289)-specific cytotoxic polyclonal T cells. The most common escape mutation was an amino acid change of asparagine (AAT) to aspartic acid (GAT) at position 280; an additional mutation was glycine (GGT) to aspartic acid (GAT) at position 282. The results presented show that relevant point mutations within the T-cell epitope of LCMV-GP-(275-289) occur frequently and that they are selectable in vitro by CTLs.


Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion.
The vertebrate control of locomotion involves all levels of the nervous system from cortex to the spinal cord. Here, we aim to cover all main aspects of this complex behavior, from the operation of the microcircuits in the spinal cord to the systems and behavioral levels and extend from mammalian locomotion to the basic undulatory movements of lamprey and fish. The cellular basis of propulsion represents the core of the control system, and it involves the spinal central pattern generator networks (CPGs) controlling the timing of different muscles, the sensory compensation for perturbations, and the brain stem command systems controlling the level of activity of the CPGs and the speed of locomotion. The forebrain and in particular the basal ganglia are involved in determining which motor programs should be recruited at a given point of time and can both initiate and stop locomotor activity. The propulsive control system needs to be integrated with the postural control system to maintain body orientation. Moreover, the locomotor movements need to be steered so that the subject approaches the goal of the locomotor episode, or avoids colliding with elements in the environment or simply escapes at high speed. These different aspects will all be covered in the review.


Levels of pro-opiomelanocortin and prolactin mRNA in the fetal sheep pituitary following hypoxaemia and glucocorticoid treatment in late gestation.
It is well established that corticotrophin-releasing hormone and vasopressin can induce both synthesis and release of ACTH from the ovine pituitary gland, and that glucocorticoids can inhibit these responses. Changes in the abundance, localization and distribution of pro-opiomelanocortin (POMC) mRNA and prolactin (PRL) mRNA in the ovine fetal pituitary were examined by in situ hybridization following hypoxaemia applied in the presence or absence of concomitant cortisol in late gestation (day 135). Fetuses were distributed amongst four groups; saline-infused/normoxaemic, cortisol-infused/normoxaemic (0.3 mg/h), saline-infused/hypoxaemic and cortisol-infused/hypoxaemic. Hypoxaemia (6 h) was induced by reducing the maternal PaO2, resulting in a 6-8 mmHg decrease in fetal arterial PO2. Fetal infusions were commenced 5 h prior to and maintained throughout the treatment period. Hypoxaemia, which elevated fetal plasma ACTH and cortisol, caused a significant (P < 0.05) increase in POMC mRNA in the pars distalis (PD), but was without effect on POMC mRNA in the pars intermedia (PI). Cortisol infusion attenuated the hypoxaemia-induced increase in POMC mRNA in the PD, but was without effect on non-stimulated steady-state POMC mRNA levels in either the PD or PI. PRL mRNA was only present in the PD and significantly (P < 0.05) increased after cortisol infusion and hypoxaemia. In conclusion (i) POMC and PRL mRNA in the PD are increased following moderate hypoxaemia, (ii) cortisol attenuates changes in POMC mRNA but not PRL mRNA in the PD following hypoxaemia and (iii) cortisol increases PRL mRNA levels in the PD.(ABSTRACT TRUNCATED AT 250 WORDS)


Reaction Time and Visual Memory in Connection to Hazardous Drinking Polygenic Scores in Schizophrenia, Schizoaffective Disorder and Bipolar Disorder.
The purpose of this study was to explore the association of cognition with hazardous drinking Polygenic Scores (PGS) in 2649 schizophrenia, 558 schizoaffective disorder, and 1125 bipolar disorder patients in Finland. Hazardous drinking PGS was computed using the LDPred program. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: the 5-choice serial reaction time task, or Reaction Time (RT) test, and the Paired Associative Learning (PAL) test. The association between hazardous drinking PGS and cognition was measured using four cognition variables. Log-linear regression was used in Reaction Time (RT) assessment, and logistic regression was used in PAL assessment. All analyses were conducted separately for males and females. After adjustment of age, age of onset, education, household pattern, and depressive symptoms, hazardous drinking PGS was not associated with reaction time or visual memory in male or female patients with schizophrenia, schizoaffective, and bipolar disorder.


Autotaxin: An Early Warning Biomarker for Acute-on-chronic Liver Failure.
Background and Aims: Recent accumulating evidence indicates the biological actions of autotaxin (ATX) in liver disease. However, the relationship between ATX and liver failure has not been reported. The present study aimed to examine alterations of serum ATX in acute-on-chronic liver failure (ACLF) and evaluate whether serum ATX could be useful as an early warning biomarker of ACLF. Methods: Serum ATX was measured in 50 patients with hepatitis B-related ACLF, 14 patients with alcohol-related ACLF, 11 patients with hepatitis B-related pre-ACLF, 11 patients with alcohol-related Child-Pugh A cirrhosis, 39 patients with hepatitis B-related Child-Pugh A cirrhosis, 26 patients with chronic hepatitis B, and 38 healthy volunteers by enzyme-linked immunosorbent assay. Results: Serum ATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group; furthermore, patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF. Serum ATX levels were significantly higher among male ACLF patients with preclinical infection, spontaneous bacterial peritonitis or pneumonia, as compared to patients with ACLF but no spontaneous bacterial peritonitis or pneumonia. Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score. Serum ATX ≥ 584.1 ng/mL was a poor prognostic factor for ACLF (hazard ratio of 4.750, 95% confidence interval of 1.106-20.392, p=0.036). Conclusions: Serum ATX level may be a useful early warning biomarker for ACLF.


Magnetic routing of light-induced waveguides.
Among photofunctional materials that can be employed to control the propagation of light by modifying their properties, soft dielectrics such as nematic liquid crystals (NLCs) stand out for their large all-optical response. Through reorientation, the molecular distribution of NLCs can be modified by the electric field of light, permitting functional operations and supporting self-localized light beams or spatial optical solitons. To date, the generation and routing of such solitons have been limited by the boundary conditions employed to tailor the properties of NLCs in planar cells or capillaries. Here we report on spatial solitons in bulk NLCs with no lateral anchoring, where the application of an external magnetic field effectively controls the direction of propagation and the angular steering of the self-trapped wavepackets. Our results entail a completely new approach to the routing of self-localized beams and light-induced waveguides in three dimensions, without the usual limitations imposed by transverse boundary conditions.


Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome.
Members of the Rho family of small GTPases play an essential role in controlling the motile behaviour of animal cells. Specifically, Cdc42 and Rac have been shown to induce the formation of filopodia and lamellipodia, respectively, at the cell periphery of Swiss 3T3 fibroblasts. In addition, both GTPases are required for progression through G1 phase of the cell cycle, possibly by regulating the activity of the Jun N-terminal kinase (JNK) signalling pathway. In order to examine more closely the mechanisms underlying the diverse functions of Rho GTPases in mammalian cells, we searched for downstream targets of these proteins. A yeast two-hybrid screen for proteins interacting with the human Cdc42 GTPase identified WASP, a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome (WAS). Recombinant WASP, expressed in Escherichia coli, also bound to Cdc42 and weakly to Rac, but not at all to Rho. The Cdc42/Rac-binding domain was identified in a region between amino acids 201-321 of WASP, and binding was dependent on Cdc42 and Rac being in the GTP-bound conformation. Furthermore, WASP did not catalyze GTPase activation or nucleotide exchange activity on Cdc42. Positional cloning has implicated WASP in causing WAS, and the protein is defective in patients suffering from the disease. WASP is expressed exclusively in cells of hematopoietic lineage, and lymphocytes from WAS patients have a distorted cell-surface and exhibit reduced proliferative capacity. WASP has recently been found to bind to the Src-homology 3 (SH3) domain of the adapter protein Nck. This observation, and the results presented here, suggest that WAS is the result of defects in signal transduction pathways regulated by Cdc42/Rac and Nck.


Sigma smooth pursuit eye tracking: constant k values revisited.
Effective sigma tracking, i.e., apparent movement perception when slow eye movements are made across a stationary repetitive pattern under stroboscopic illumination, has been shown to be a function of the distance between sequential stimuli (P(s)) and the flash frequency (f(s)). The relationship between these factors and eye velocity ( V (e)) has been formally specified as V (e)= k P(s)f(s)[deg s(-1)], where it has been argued that the value of k, which defines the rate limit for eye velocity, is normally 1, or exceptionally 2 or 3. However, theoretically the limitations on the maximum value for k are the maximum optimal pursuit speed for eye tracking (V(max)) and the minimum values which P(s) and f(s) can assume while preserving target discrimination, and since the values for V(max) are known to lie well beyond 20 deg/s and those for P(s) and f s) well below 0.3 deg and 10 Hz respectively, it should be possible to demonstrate empirically that k can assume integer values considerably larger than the indicated maximum of 3. To test this prediction, three subjects performed seven series of five EOG-monitored trials producing sigma-pursuit, with values of k ranging from 1 to 7. All subjects evidenced smooth pursuit eye tracking for every condition and reported experiencing sigma-type apparent motion in 95% of the trials. The results confirm theoretical expectations and unequivocally demonstrate that sigma tracking can be readily effected under conditions where k significantly exceeds the maximal values previously reported, in conformity with theory.


Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein.
The proinflammatory cytokine interleukin 1 (IL-1) activates the transcription of many genes encoding acute phase and proinflammatory proteins, a function mediated primarily by the transcription factor NF-kappaB. An early IL-1 signaling event is the recruitment of the Ser/Thr kinase IRAK to the type I IL-1 receptor (IL-1RI). Here we describe the function of a previously identified IL-1 receptor subunit designated IL-1 receptor accessory protein (IL-1RAcP). IL-1 treatment of cells induces the formation of a complex containing both IL-1RI and IL-1RAcP. IRAK is recruited to this complex through its association with IL-1RAcP. Overexpression of an IL-1RAcP mutant lacking its intracellular domain, the IRAK-binding domain, prevented the recruitment of IRAK to the receptor complex and blocked IL-1-induced NF-kappaB activation.


Toxic megacolon in a renal allograft recipient with cytomegalovirus colitis.
We report a 35-year-old man, a renal allograft recipient, who presented with toxic megacolon. Segmental biopsies from the colon were consistent with cytomegalovirus colitis. Serum polymerase chain reaction for cytomegalovirus DNA confirmed the diagnosis. He was treated with ganciclovir but, though his abdominal condition improved initially, he worsened later and succumbed to his illness.


The psychosocial treatment of recurrent diabetic ketoacidosis: an interdisciplinary team approach.
The professional expertise of the diabetes mental health professional is integral to the interdisciplinary team approach to recurrent diabetic ketoacidosis (DKA). A case report provides the context to illustrate the interconnection of concurrent strategies of diabetes management, teaching, and counseling. Specific methods include a practical approach to manipulative behavior in blood glucose monitoring, supervision of insulin administration, education, and intensive psychotherapy. In this case study, the adolescent's removal from her home environment, along with medical supervision and extensive psychosocial support, was instrumental in reversing the pattern of self-destructiveness. Recurrent DKA is a very specific problem for which the mental health professional can play an effective treatment role.


Clinical implications of coronavirus disease 2019 in neonates.
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, a small number of coronavirus disease 2019 (COVID-19) cases in neonates have been reported worldwide. Neonates currently account for only a minor proportion of the pediatric population affected by COVID-19. Thus, data on the epidemiological and clinical features of COVID-19 in neonates are limited. Approximately 3% of neonates born to mothers with COVID-19 reportedly tested positive for SARS-CoV-2. Current limited data on neonates with COVID-19 suggest that neonatal COVID-19 shows a relatively benign course despite a high requirement for mechanical ventilation. However, neonates with pre-existing medical conditions and preterm infants appear to be at a higher risk of developing severe COVID-19. The greatest perinatal concern of the COVID-19 pandemic is the possibility of vertical transmission, especially transplacental transmission of SARS-CoV-2. Although direct evidence of the vertical transmission of SARS-CoV-2 is lacking, its possibility during late pregnancy cannot be ruled out. This review summarizes available case studies on COVID-19 in neonates and introduces what is currently known about neonatal COVID-19 with focus on its vertical transmission.


Finding the molecular basis of quantitative traits: successes and pitfalls.
Understanding the molecular basis of quantitative genetic variation is a principal goal for biomedicine. Although the complex genetic architecture of quantitative traits has so far largely frustrated attempts to identify genes in humans by standard linkage methodologies, quantitative trait loci (QTL) have been mapped in plants, insects and rodents. However, identifying the molecular bases of QTL remains a challenge. Here, we discuss why this is and how new experimental strategies and analytical techniques, combined with the fruits of the genome projects, are beginning to identify candidate genes for QTL studies in several model organisms.


Tyrosinaemia--treatment and outcome.
Tyrosinaemia type I is, untreated, a fatal disease: in the acute form from liver failure, in the chronic form often from hepatocellular carcinoma. Acute neurological crisis is also a cause of death. Traditionally the treatment has been with diet, but for a decade liver transplantation has been the ultimate treatment. The continuous production of the pathological metabolites in the kidneys after transplantation appears to be without significance. Introduction of the enzyme inhibitor NTBC in the treatment of tyrosinaemia has reduced the need for liver transplants. Neonatal screening may be justified as efficient treatment has become available. The complex phenotype of lethal albino mice, with severe alterations in gene expression, has been shown to be caused by fumarylacetoacetase deficiency. Prolonged hypoglycaemia in otherwise adequately treated tyrosinaemia patients may result from depressed expression of genes coding for enzymes in gluconeogenesis, as seen in the mouse model. Self-induced genetic correction in liver tissue that occurs in many tyrosinaemia patients may reduce the risk of liver failure in some patients.


Direct teaching of thinking skills using clinical simulation.
Because of the nursing faculty shortage, many academic leaders hire clinicians who are not formally prepared for an academic role. Novice faculty face an immediate need to develop teaching skills. One of the most crucial areas is the ability to help students develop critical thinking. To address this need, the authors describe how they used clinical simulation to incorporate direct teaching of thinking skills into course content and how this resulted in a faculty mentoring experience.


Immune-mediated protein-losing enteropathy with Down syndrome.
A 28-year-old woman previously diagnosed to have Down syndrome presented with a one-month history of severe hypoalbuminemia, lower extremity edema, and diarrhea. Her urine was negative for protein. She was diagnosed with immune-mediated protein-losing enteropathy (PLE) based on clinical findings, protein loss evident on (99m)Technetium-labeled human serum albumin scintigraphy, and IgM and complement C3 deposition in the duodenum. She did not exhibit any manifestations of collagen diseases. A dramatic remission was achieved and maintained with corticosteroid administration. This is the first report of immune-mediated PLE in a patient with Down syndrome.


Development and Implementation of an HIV Health Care Practice Transformation Model for Latinos.
A Latino Community Health Center in Washington, D.C. implemented and evaluated a practice transformative model to optimize human resources and improve quality health outcomes in HIV service delivery for Latino patients. We conducted a qualitative formative assessment through interviews and focus groups with clinic staff and patients living with HIV/AIDS in order to inform implementation. The formative assessment identified specific training and practice facilitation needs and provided valuable insight for choosing evaluation metrics. Incorporating staff input fostered staff engagement in laying the foundation of the transformation and helped build a sense of ownership of the transformative process. Through the formative assessment process we gained insight into the organization's HIV practice and improved our ability to align practice transformation goals with evaluation metrics to better measure changes resulting from the model implementation. The formative assessment process also highlighted challenges in conducting health systems research with Latino communities in the U.S.


Dynamic alterations of hepatocellular function by on-demand elasticity and roughness modulation.
Temperature-responsive cell culture substrates reported here can be dynamically programmed to induce bulk softening and surface roughness changes in the presence of living cells. Alterations in hepatocellular function following temporally controlled substrate softening depend on the extent of stiff mechanical priming prior to user-induced material transition.


Single cell transcriptomics of human epidermis identifies basal stem cell transition states.
How stem cells give rise to epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find four spatially distinct stem cell populations at the top and bottom of rete ridges and transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling suggests that basal cell populations serve as crucial signaling hubs to maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest that transitional basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed transitional basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.


Toward an Ultralow-Power Onboard Processor for Tongue Drive System.
The Tongue Drive System (TDS) is a new unobtrusive, wireless, and wearable assistive device that allows for real-time tracking of the voluntary tongue motion in the oral space for communication, control, and navigation applications. The latest TDS prototype appears as a wireless headphone and has been tested in human subject trials. However, the robustness of the external TDS (eTDS) in real-life outdoor conditions may not meet safety regulations because of the limited mechanical stability of the headset. The intraoral TDS (iTDS), which is in the shape of a dental retainer, firmly clasps to the upper teeth and resists sensor misplacement. However, the iTDS has more restrictions on its dimensions, limiting the battery size and consequently requiring a considerable reduction in its power consumption to operate over an extended period of two days on a single charge. In this brief, we propose an ultralow-power local processor for the TDS that performs all signal processing on the transmitter side, following the sensors. Assuming the TDS user on average issuing one command/s, implementing the computational engine reduces the data volume that needs to be wirelessly transmitted to a PC or smartphone by a factor of 1500×, from 12 kb/s to ~8 b/s. The proposed design is implemented on an ultralow-power IGLOO nano field-programmable gate array (FPGA) and is tested on AGLN250 prototype board. According to our post-place-and-route results, implementing the engine on the FPGA significantly drops the required data transmission, while an application-specific integrated circuit (ASIC) implementation in a 65-nm CMOS results in a 15× power saving compared to the FPGA solution and occupies a 0.02-mm2 footprint. As a result, the power consumption and size of the iTDS will be significantly reduced through the use of a much smaller rechargeable battery. Moreover, the system can operate longer following every recharge, improving the iTDS usability.


In the interface of caesalpinioids and mimosoids: Comparative floral development elucidates shared characters in Dimorphandra mollis and Pentaclethra macroloba (Leguminosae).
Pentaclethra and Dimorphandra (Leguminosae) have long been considered a possible enigmatic link between caesalpinioids and mimosoids because they both have an imbricate calyx and heteromorphic androecium, floral features that are rare among mimosoids but common among caesalpinioids. This study compared the developing flowers of Dimorphandra mollis and Pentaclethra macroloba to determine whether the shared floral conditions also have the same ontogenetic origin. Buds of different sizes and flowers were processed for surface (scanning electron microscopy) and histological (light microscopy) examination. The floral meristem initiates five sepal primordia in a modified helical order in both species. The median sagittal sepal is adaxial. The overlap of the sepals during elongation culminates with the formation of the imbricate calyx. Heteromorphic androecia arise in the intermediate stages of development. In P. macroloba, the fertile pollen-bearing stamens are antesepalous, robust and short, and the anthers carry a robust apical gland; the staminodes are long and white with a vestigial apical gland. In contrast, in D. mollis the fertile pollen-bearing stamens are antepetalous without glands and as long as the staminodes. The staminodes are thinner with an expanded apical region. The imbricate calyx and the heteromorphic androecium in the studied species originated via distinct pathways, favoring the hypothesis of homoplasy of these conditions. The pathways observed in P. macroloba are more similar to those observed in caesalpinioids than to those observed in mimosoids, indicating that although the floral development differs between the species studied, it supports the basal placement of Pentaclethra among mimosoids.


New and fast method to quantify respiration rates of bacterial and plankton communities in freshwater ecosystems by using optical oxygen sensor spots.
A new method of respiration rate measurement based on oxygen luminescence quenching in sensor spots was evaluated for the first time for aquatic bacterial communities. The commonly used Winkler and Clark electrode methods to quantify oxygen concentration both require long incubation times, and the latter additionally causes signal drift due to oxygen consumption at the cathode. The sensor spots proved to be advantageous over those methods in terms of precise and quick oxygen measurements in natural bacterial communities, guaranteeing a respiration rate estimate during a time interval short enough to neglect variations in organism composition, abundance, and activity. Furthermore, no signal drift occurs during measurements, and respiration rate measurements are reliable even at low temperatures and low oxygen consumption rates. Both a natural bacterioplankton sample and a bacterial isolate from a eutrophic river were evaluated in order to optimize the new method for aquatic microorganisms. A minimum abundance of 2.2 x 10(6) respiring cells ml(-1) of a bacterial isolate was sufficient to obtain a distinct oxygen depletion signal within 20 min at 20 degrees C with the new oxygen sensor spot method. Thus, a culture of a bacterial isolate from a eutrophic river (OW 144; 20 x 10(6) respiring bacteria ml(-1)) decreased the oxygen saturation about 8% within 20 min. The natural bacterioplankton sample respired 2.8% from initially 94% oxygen-saturated water in 30 min. During the growth season in 2005, the planktonic community of a eutrophic river consumed between 0.7 and 15.6 micromol O(2) liter(-1) h(-1). The contribution of bacterial respiration to the total plankton community oxygen consumption varied seasonally between 11 and 100%.


Neuropsychological performance following a history of multiple self-reported concussions: a meta-analysis.
Debate continues about the long-term neuropsychological impact of multiple mild traumatic brain injuries (MTBI). A meta-analysis of the relevant literature was conducted to determine the impact of having a history of more than one self-reported MTBI (versus just one MTBI) across seven cognitive domains, as well as symptom complaints. The analysis was based on 8 studies, all conducted with athletes, involving 614 cases of multiple MTBI and 926 control cases of a single MTBI. The overall effect of multiple MTBI on neuropsychological functioning was minimal and not significant (d = 0.06). However, follow-up analyses revealed that multiple self-reported MTBI was associated with poorer performance on measures of delayed memory and executive functioning. The implications and limitations of these findings are discussed.


Thrombospondin-1, a natural inhibitor of angiogenesis, is present in vitreous and aqueous humor and is modulated by hyperglycemia.
Negative regulators of angiogenesis play a major role in maintaining vascular homeostasis. Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. This report examines the presence of TSP1 in ocular samples and determines whether its production is altered in diabetes. Western blot analysis detected a 140 kDa antiangiogenic fragment of TSP1(gp140) in vitreous samples prepared from normal human and rat eyes. Intact TSP1 was detected in aqueous humor samples prepared from normal rat and bovine eyes. In contrast, TSP1 was virtually absent in vitreous and aqueous humor samples prepared from diabetic rat eyes. Furthermore, production of TSP1 by microvascular endothelial cells in culture was sensitive to high concentrations of glucose. Retinal blood vessels appeared nonuniform and dilated in diabetic animals when compared to control animals. These results demonstrate that TSP1 and its antiangiogenic fragment are present in aqueous humor and vitreous of normal rat eyes and are dramatically reduced in diabetes. Thus, TSP1 may play a role in ocular vascular homeostasis and its absence may contribute to vascular dysfunctions associated with diabetes.


[Medical histories of patients with Marfan's syndrome].
The life expectancy of patients with Marfan's syndrome has been increased by over 30 years by modern medico-surgical management but the diagnostic problems related to the multiplicity of symptoms and the necessity of collaboration by many specialities complicate the medical history of patients, which is largely unknown. The authors sent a self-administered questionnaire to 1 353 patients with Marfan's syndrome to obtain this information. Of the 430 questionnaires returned, as many by men as by women, the diagnosis of the disease was made in less than half the cases by clinical symptoms (42%): the investigation of an unrelated clinical problem (39%) or a family enquiry (19%) also led to the diagnosis. The delay between the first symptoms of the disease and first medical consultation (usually cardiological or ophthalmic) was long (5.2 years) as was the interval between the first consultation and the diagnosis (2.8 years). However, the population could be divided into two groups. one with rapid access to the physician (< 1 year) and to the diagnosis (< 3 years) and the second group in which the delays are long. When the diagnosis of Marfan's syndrome is made following consultation for an unrelated condition, it is more often delayed and the patient is usually older. The delay in diagnosis observed could be shortened by systematic familial enquiries and better information to physicians who could then suspect the diagnosis before the advent of clinical symptoms.


Preparation of CdSe nanocrystals in a micro-flow-reactor.
A micro-reactor was utilized for continuous and controlled CdSe nanocrystal preparation. Effects of reaction conditions on optical properties of the nanocrystals were investigated; in this current system, rapid and exact temperature control of the micro-reactor was beneficial for controlling particle diameter and reproducible preparation of particles; additional effort was made towards narrower particle-size distributions.


Overexpression of Nitrate Transporter OsNRT2.1 Enhances Nitrate-Dependent Root Elongation.
Root morphology is essential for plant survival. NO₃- is not only a nutrient, but also a signal substance affecting root growth in plants. However, the mechanism of NO₃--mediated root growth in rice remains unclear. In this study, we investigated the effect of OsNRT2.1 on root elongation and nitrate signaling-mediated auxin transport using OsNRT2.1 overexpression lines. We observed that the overexpression of OsNRT2.1 increased the total root length in rice, including the seminal root length, total adventitious root length, and total lateral root length in seminal roots and adventitious roots under 0.5-mM NO₃⁻ conditions, but not under 0.5-mM NH₄⁺ conditions. Compared with wild type (WT), the 15NO₃- influx rate of OsNRT2.1 transgenic lines increased by 24.3%, and the expressions of auxin transporter genes (OsPIN1a/b/c and OsPIN2) also increased significantly under 0.5-mM NO₃- conditions. There were no significant differences in root length, ß-glucuronidase (GUS) activity, and the expressions of OsPIN1a/b/c and OsPIN2 in the pDR5::GUS transgenic line between 0.5-mM NO₃- and 0.5-mM NH₄⁺ treatments together with N-1-naphthylphalamic acid (NPA) treatment. When exogenous NPA was added to 0.5-mM NO₃- nutrient solution, there were no significant differences in the total root length and expressions of OsPIN1a/b/c and OsPIN2 between transgenic plants and WT, although the 15NO₃- influx rate of OsNRT2.1 transgenic lines increased by 25.2%. These results indicated that OsNRT2.1 is involved in the pathway of nitrate-dependent root elongation by regulating auxin transport to roots; i.e., overexpressing OsNRT2.1 promotes an effect on root growth upon NO₃- treatment that requires active polar auxin transport.


The impact of Ontario smoke-free legislation on secondhand smoke in enclosed public places.
Many studies have evaluated the impact of indoor smoking bans on secondhand smoke (SHS) exposure. No studies have assessed the impact of a smoking ban on SHS in enclosed areas outside separately ventilated, designated smoking rooms (DSRs). This study evaluated the overall impact of the Smoke-Free Ontario Act implemented May 31, 2006, on SHS in bars and coffee shops and the impact of banning DSRs on SHS outside DSRs. Air particulate matter (PM) and carcinogenic particulate polycyclic aromatic hydrocarbons (PPAH) were measured in May 2006 before the ban inside and outside DSRs in Toronto venues (13 coffee shops and 14 bars) that allowed smoking only in DSRs, and in Windsor venues (10 coffee shops and 10 bars) where smoking was allowed in shared spaces. Measurements were repeated 2 months post-ban. Air quality index values (AQIs) were calculated. Mixed model analysis was applied, taking into account measurement errors for repeated measures. Post ban, mean PM and PPAH levels were reduced by 87% (from 494 to 67 mm(2)/m(3)) and 94% (from 196 to 11 ng/m(3)), respectively, inside Toronto DSRs. Mean PM and PPAH levels were reduced by 10% (from 124 to 111 mm(2)/m(3)) and 46% (from 45 to 24 ng/m(3)), respectively, outside Toronto DSRs. In all Windsor venues, mean PM and PPAH levels were reduced by 83% (from 488 to 81 mm(2)/m(3)) and 90% (from 107 to 10 ng/m(3)), respectively. All reductions were statistically significant (p < 0.0001). In Toronto venues, the AQI was reduced from the "very unhealthy" range inside DSRs and the "moderate" range outside Toronto DSRs to the "good" range, and in Windsor venues from the "unhealthy for sensitive groups" range to the "good" range post-ban. Pre-ban PPAH levels including those outside Toronto DSRs may be associated with cardiovascular injury. DSRs did not provide adequate protection from SHS. The Smoke-Free Ontario Act produced a significant and firm reduction in SHS exposure in venues both with and without DSRs.


Analysis of the epidermal growth factor receptor promoter: the effect of nuclear factor-kappaB.
The epidermal growth factor receptor gene is highly regulated and responsive to extracellular stimuli that control cell growth. We have identified five putative nuclear factor-kappaB (NF-kappaB) binding sites within the epidermal growth factor receptor (EGFR) promoter region by sequence analysis. We have analyzed the potential role of NF-kappaB family members in the regulation of the EGFR transcription. Electrophoretic mobility shift analysis demonstrated that the p50 and p49, subunit proteins of the NF-kappaB, bound to the EGFR promoter at four out of five of these sites. However, it was found that NF-kappaB could not transactivate the EGFR by cotransfection experiments with each NF-kappaB subunit, using p50, p65 and c-Rel and an EGFR promoter luciferase reporter. Treatment of cells with tumor necrosis factor (TNF)-alpha, which could degrade the I-kappaB and then result in translocation of NF-kappaB to nucleus, did not enhance EGFR promoter reporter gene transcription. Also, TNF-alpha did not induce EGFR expression at the protein level. These results indicate that even though purified NF-kappaB can bind to the putative sites, there is no evidence that NF-kappaB transactivates the EGFR promoter region.


Human Beta Defensin 2 Ameliorated Alcohol-Associated Liver Disease in Mice.
Alcohol-associated liver disease (ALD) is a prevalent liver disorder and significant global healthcare burden with limited effective therapeutic options. The gut-liver axis is a critical factor contributing to susceptibility to liver injury due to alcohol consumption. In the current study, we tested whether human beta defensin-2 (hBD-2), a small anti-microbial peptide, attenuates experimental chronic ALD. Male C57Bl/6J mice were fed an ethanol (EtOH)-containing diet for 6 weeks with daily administration of hBD-2 (1.2 mg/kg) by oral gavage during the final week. Two independent cohorts of mice with distinct baseline gut microbiota were used. Oral hBD-2 administration attenuated liver injury in both cohorts as determined by decreased plasma ALT activity. Notably, the degree of hBD-2-mediated reduction of EtOH-associated liver steatosis, hepatocellular death, and inflammation was different between cohorts, suggesting microbiota-specific mechanisms underlying the beneficial effects of hBD-2. Indeed, we observed differential mechanisms of hBD-2 between cohorts, which included an induction of hepatic and small intestinal IL-17A and IL-22, as well as an increase in T regulatory cell abundance in the gut and mesenteric lymph nodes. Lastly, hBD-2 modulated the gut microbiota composition in EtOH-fed mice in both cohorts, with significant decreases in multiple genera including Barnesiella, Parabacteroides, Akkermansia, and Alistipes, as well as altered abundance of several bacteria within the family Ruminococcaceae. Collectively, our results demonstrated a protective effect of hBD-2 in experimental ALD associated with immunomodulation and microbiota alteration. These data suggest that while the beneficial effects of hBD-2 on liver injury are uniform, the specific mechanisms of action are associated with baseline microbiota.


A hematopoietic organ-specific 49-kD nuclear antigen: predominance in immature normal and tumor granulocytes and detection in hematopoietic precursor cells.
A 49-kD protein was specifically detected in hematopoietic organs by Western blotting with a novel mouse monoclonal antibody (B92) raised against stromal cells. The protein was found in the immunizing cells using a sensitive method. However, its detection in the bone marrow by the B92 antibody seemed to stem from the abundance of p49 in immature cells of the myeloid lineage. Study of the bone marrow following in vivo irradiation or 5-fluorouracil (5-FU) treatment, in vitro culture with differentiation-inducing factors and long-term culture, and cell sorting all pointed in the same direction: the protein was found in early myeloid cells and in hematopoietic precursor cells. These results were in accordance with the specific presence of p49 in primary radiation-induced myeloid leukemia and its absence in spontaneous B lymphoma. Immunofluorescent staining using B92 antibody detected a nuclear antigen forming a dotted pattern in early myeloid cells and day 12 colony-forming units-spleen (CFU-S). Nuclear localization of p49 was further demonstrated by subcellular fractionation followed by Western blotting. We thus identified a nuclear protein that within the hematopoietic population is detected in hematopoietic precursor cells, predominates in early myeloid cells, and is reduced following differentiation. These properties imply that p49 might be involved in the regulation of hematopoietic cell growth or differentiation.


Calcium Dobesilate Modulates PKCδ-NADPH Oxidase- MAPK-NF-κB Signaling Pathway to Reduce CD14, TLR4, and MMP9 Expression during Monocyte-to-Macrophage Differentiation: Potential Therapeutic Implications for Atherosclerosis.
Monocyte-to-macrophage differentiation results in the secretion of various inflammatory mediators and oxidative stress molecules necessary for atherosclerosis pathogenesis. Consequently, this differentiation represents a potential clinical target in atherosclerosis. Calcium dobesilate (CaD), an established vasoactive and angioprotective drug in experimental models of diabetic microvascular complications reduces oxidative stress and inhibits inflammation via diverse molecular targets; however, its effect on monocytes/macrophages is poorly understood. In this study, we investigated the anti-inflammatory mechanism of CaD during phorbol 12-myristate 13-acetate (PMA)-induced monocyte-to-macrophage differentiation in in vitro models of sepsis (LPS) and hyperglycemia, using THP-1 monocytic cell line. CaD significantly suppressed CD14, TLR4, and MMP9 expression and activity, lowering pro-inflammatory mediators, such as IL1β, TNFα, and MCP-1. The effects of CaD translated through to studies on primary human macrophages. CaD inhibited reactive oxygen species (ROS) generation, PKCδ, MAPK (ERK1/2 and p38) phosphorylation, NOX2/p47phox expression, and membrane translocation. We used hydrogen peroxide (H2O2) to mimic oxidative stress, demonstrating that CaD suppressed PKCδ activation via its ROS-scavenging properties. Taken together, we demonstrate for the first time that CaD suppresses CD14, TLR4, MMP9, and signature pro-inflammatory cytokines, in human macrophages, via the downregulation of PKCδ/NADPH oxidase/ROS/MAPK/NF-κB-dependent signaling pathways. Our data present novel mechanisms of how CaD alleviates metabolic and infectious inflammation.


Potential Zoonotic Trematodes Recovered in Stray Cats from Kuwait Municipality, Kuwait.
Stray cats are a common feature roaming the streets and alleys of Kuwait; they could be a source of parasites, including trematodes, that affect humans. A survey was conducted to identify feline trematodes and throw the light on their public health significance in Kuwait. Out of 240 stray cats trapped from different localities of Kuwait from June 2011 to May 2012, 59 (24.6%) were found to be infected with 14 species of trematodes. The most common were trematodes of the genus Heterophyes, particularly H. heterophyes and H. dispar that were found in respectively 15.8% and 10.8% of the cats examined. Other trematodes recorded, with lower prevalences, were Heterophyes nocens (2.9%), Haplorchis taichui (3.8%), Stictodora sawakinensis (2.1%), Stellantchasmus falcatus (1.6%), Echinochasmus japonicus (1.6%), and Mesostephanus dottrensi (1.3%). Centrocestus cuspidatus, Galactosomum fregatae, Ascocotyle sp., Mesostephanus appendiculatus, Haplorchis yokogawai, and Pygidiopsis genata showed the lowest prevalence (0.4%) and intensity. The majority of the trematodes are recorded for the first time in Kuwait and even in the Gulf region. The study reveals that stray cats are good indicators of fish-borne trematodes in the environment. As all trematodes recovered are zoonotic, their significance to public health should be considred.


[Echocardiographic diagnosis of fetal heart insufficiency caused by supraventricular tachycardia].
A fetus with hydrops congenitus universalis and congestive heart failure in the 34th week of gestation caused by supraventricular tachycardia was diagnosed by ultrasound. A reanimation in the infant delivery by cesarean section with a heart rate of 360 beats/min was successful. By a weight at birth of 3140 g, pre- and postnatal 930 g edema was found. The postpartal treatment of the supraventricular tachycardia with verapamil, methyldigoxin and propranolol was successful. The child recovered uneventfully.


Effects of Dietary Trans Fatty Acids on Mutagenesis of Known Carcinogens.
The metabolic activating potential of liver homogenates from animals fed a diet containing 46.6% trans fatty acids or a diet containing less than .1% trans fatty acids was compared in the Ames assay with 2-aminofluorene (AF), benzo(a)pyrene (BP), and dimethylbenz(a)anthracene (DMBA). The control fat had a similar fatty acid composition only consisting of cis fatty acid (cis fats). Since both the cis and trans fats contained moderate levels of saturated fatty acids, a comparison was made between these two fats and corn oil. All three fats were incorporated into high fat, 20%, and low fat, 5%, diets and fed to male Sprague-Dawley rats for three weeks. Although the mutagenic potentials of AF and BP increased with increasing mutagen concentration and with increasing level of dietary fat, there was no consistent difference in mutagenic potential between the cis and trans fats. DMBA was mutagenic only at the two highest concentrations with livers from corn oil-fed rats. The mutagenic activating potential of S-9 from animals fed trans fat diets generally was similar to that of animals fed cis fat diets, but did not follow the trend of animals fed corn oil diets. Thus the amount and/or type of polyunsaturated fatty acids (essential fatty acids) present in the diet may be key factors in evaluating the enhancement of mutagenic activity of DMBA by dietary fat.


Coordinated crosstalk between microtubules and actin by a spectraplakin regulates lumen formation and branching.
Subcellular lumen formation by single-cells involves complex cytoskeletal remodelling. We have previously shown that centrosomes are key players in the initiation of subcellular lumen formation in Drosophila melanogaster, but not much is known on the what leads to the growth of these subcellular luminal branches or makes them progress through a particular trajectory within the cytoplasm. Here, we have identified that the spectraplakin Short-stop (Shot) promotes the crosstalk between MTs and actin, which leads to the extension and guidance of the subcellular lumen within the tracheal terminal cell (TC) cytoplasm. Shot is enriched in cells undergoing the initial steps of subcellular branching as a direct response to FGF signalling. An excess of Shot induces ectopic acentrosomal luminal branching points in the embryonic and larval tracheal TC leading to cells with extra-subcellular lumina. These data provide the first evidence for a role for spectraplakins in single-cell lumen formation and branching.


Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin.
Hsp90 is a ubiquitously expressed molecular chaperone that folds, stabilizes, and functionally regulates many cellular proteins. The benzoquinone ansamysin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is an anticancer drug that disrupts Hsp90 binding to its clients, causing their degradation through the ubiquitin-dependent proteasomal pathway. The protein kinase B-RAF is mutated in approximately 7% of human cancers. The most common mutation (approximately 90%) is (V600E)B-RAF, which has constitutively elevated kinase activity, stimulates cancer cell proliferation, and promotes survival. Here, we show that (V600E)B-RAF is an Hsp90 client protein that requires Hsp90 for its folding and stability. (V600E)BRAF is more sensitive to degradation by 17-AAG treatment than (WT)B-RAF and we show that the majority of the other mutant forms of B-RAF are also sensitive to 17-AAG-mediated proteasomal degradation. Our data show that B-RAF is an important target for 17-AAG in human cancer.


Diffraction-limited collimation optics for a channel waveguide Cerenkov frequency doubler for diode lasers.
Optical path analysis applying diffraction theory and geometrical ray tracing, and with collimation experiments shows that a hemiconic lens can convert the arc of blue radiation formed by Cerenkov second-harmonic generation to a parallel plane wave. To obtain an aberration-free plane wave, we modified the apex angle of the cone according to the birefringence of the waveguide. To correct chromatic aberration, we needed to have diode laser wavelength tuning with the aid of an achromatic cone lens doublet.


Evidence for dysregulation of axonal growth and guidance in the etiology of ASD.
Current theories concerning the cause of autism spectrum disorders (ASDs) have converged on the concept of abnormal development of brain connectivity. This concept is supported by accumulating evidence from functional imaging, diffusion tensor imaging, and high definition fiber tracking studies which suggest altered microstructure in the axonal tracts connecting cortical areas may underly many of the cognitive manifestations of ASD. Additionally, large-scale genomic studies implicate numerous gene candidates known or suspected to mediate neuritic outgrowth and axonal guidance in fetal and perinatal life. Neuropathological observations in postmortem ASD brain samples further support this model and include subtle disturbances of cortical lamination and subcortical axonal morphology. Of note is the relatively common finding of poor differentiation of the gray-white junction associated with an excess superficial white matter or "interstitial" neurons (INs). INs are thought to be remnants of the fetal subplate, a transient structure which plays a key role in the guidance and morphogenesis of thalamocortical and cortico-cortical connections and the organization of cortical columnar architecture. While not discounting the importance of synaptic dysfunction in the etiology of ASD, this paper will briefly review the cortical abnormalities and genetic evidence supporting a model of dysregulated axonal growth and guidance as key developmental processes underlying the clinical manifestations of ASD.


Interfacial tension in immiscible mixtures of alkali halides.
The interfacial tension of the liquid-phase interface in seven immiscible reciprocal ternary mixtures of lithium fluoride with the following alkali halides: CsCl, KBr, RbBr, CsBr, KI, RbI, and CsI was measured using the cylinder weighing method over a wide temperature range. It was shown that for all mixtures the interfacial tension gradually decreases with growing temperature. The interfacial tension of the reciprocal ternary mixtures at a given temperature increases both with the alkali cation radius (K(+) < Rb(+) < Cs(+)) and with the radius of the halogen anion (Cl(-) < Br(-) < I(-)).


Prevention and treatment of experimental autoimmune myasthenia gravis with anti-rabbit thymocyte serum and gammaglobulin in rabbits.
Twenty-two rabbits received Torpedo californica acetylcholine receptor (AChR) subcutaneously. Six rabbits were treated with 0.5 ml/kg/day of anti-rabbit thymocyte serum (ARTS), and four were treated with 5.0 mg/kg/day of anti-rabbit thymocyte gammaglobulin (ARTG) subcutaneously beginning concomitantly 1, 2 and 3 weeks after the initial AChR immunization. All 12 control animals died of experimental autoimmune myasthenia gravis (EAMG) within 52 days. None of the 10 treated rabbits developed clinical EAMG. ARTS- and ARTG-treated animals had significantly lower anti-AChR antibody titers than control animals at 3 weeks (pre-AChR booster, p < 0.01). At 6 weeks (post-AChR booster), only ARTS-treated animals had significantly lower titers than controls (p < 0.01). ARTS-treated animals developed sterile abscesses at injection sites, which were minimal in the ARTG-treated group. ARTS and ARTG prevent EAMG.


Building international collaborations from the ground up: Brown University partnerships in Haiti and Ukraine.
The world is becoming more interconnected with a need for a global approach to healthcare. Brown University has remained a leader in global health through clinical service, education, cutting edge research and dedication to the development of sustainable global partnerships. We describe two programs from the ground up in Haiti and Ukraine, and the important lessons learned in their development. The path towards the development of global health programs in Ukraine and Haiti both illustrate that although circumstances may vary between global health programs, the recipe for successful collaboration is the same: identifying specific needs, developing strong and sustained partnerships, and addressing barriers by crafting effective solutions to ongoing challenges.


Socio-economic inequalities in survival from screen-detected breast cancer in South West England: population-based cohort study.
Socio-economic inequalities in breast cancer survival have been reported worldwide, but whether these exist in screen detected as well as symptomatic women has not been established. Making this distinction will allow inferences about the relative contributions of pre- and post-diagnostic delay to these inequalities. Screening-eligible women diagnosed with breast cancer in South West England (2002-06) were followed-up to 2007. Five-year relative survival ratios (RSRs) were calculated for each deprivation quintile, using deprivation-specific life-tables and a period approach. The 'deprivation gap' in survival was calculated as the slope index of inequality between least and most deprived women. The study included 11 018 women, of whom 1176 died during follow-up. Screening status of 54% of women was missing. A clear gradient in survival across deprivation groups ranged from 83.6% [95% confidence interval (CI) 80.0, 86.6] in the most deprived to 90.8% (95% CI 89.0, 92.3) in the least deprived group. Comparing the most deprived to least deprived women, the estimated deprivation gap was -9.42% (95% CI -12.80, -6.04, P = 0.003). Among screen-detected women, inequalities were attenuated, but persisted, ranging from 95.6% (95% CI 90.6, 98.0) in the most deprived to 98.2% (95% CI 95.9, 99.2) in least deprived; the estimated deprivation gap was -3.03% (95% CI -5.75, -0.85, P = 0.023). The deprivation gap in survival does not appear as marked with screen-detected breast cancer as the other groups, though still apparent. Efforts to eliminate inequalities should consider both increasing breast screening participation and ensuring equal access through secondary care systems for women of lower socio-economic position.


Sublethal sensitivity index as an ecotoxicity parameter measuring energy allocation under toxicant stress: application to cadmium in soil arthropods.
Toxic substances may affect the life history of a species in a variety of ways. Different species maintain different priorities in coping with the physiological consequences of toxicant-induced stress. This is expressed by changes in energy allocation to different life-history characteristics which may have great consequences for the response at the population level. In this study the terrestrial invertebrates Platynothrus peltifer (Oribatida), Orchesella cincta, Folsomia candida (Collembola), and Porcellio scaber (Isopoda) were chosen to evaluate species-specific sensitivity of life histories. Effects on reproduction and weight increase under exposure to cadmium in the food were analyzed. The answer to the question of which species is the most sensitive depends on the parameter chosen. A comparison of sensitivity on the basis of sublethal effects showed P. peltifer to be the most sensitive species; on the basis of lethal effects however, the species O. cincta was the most sensitive. This discrepancy between effect parameters resulted in differences between the distance of the concentrations at which lethal and sublethal effects occur for different species. The ratio between the lethal effect concentration and the sublethal effect concentration is called the sublethal sensitivity index (SSI) and is proposed as a parameter expressing maintenance of sublethal functions under toxicant stress. The SSI seems to be a valuable parameter for evaluating the likelihood of population-level effects under toxicant stress. To extrapolate effects found in the laboratory to the field situation, more attention should be paid to the relationships between effects on life-history parameters and effects on population growth.


Impact of Genetic Diversity and Genome Plasticity of Leishmania spp. in Treatment and the Search for Novel Chemotherapeutic Targets.
Leishmaniasis is one of the major public health concerns in Latin America, Africa, Asia, and Europe. The absence of vaccines for human use and the lack of effective vector control programs make chemotherapy the main strategy to control all forms of the disease. However, the high toxicity of available drugs, limited choice of therapeutic agents, and occurrence of drug-resistant parasite strains are the main challenges related to chemotherapy. Currently, only a small number of drugs are available for leishmaniasis treatment, including pentavalent antimonials (SbV), amphotericin B and its formulations, miltefosine, paromomycin sulphate, and pentamidine isethionate. In addition to drug toxicity, therapeutic failure of leishmaniasis is a serious concern. The occurrence of drug-resistant parasites is one of the causes of therapeutic failure and is closely related to the diversity of parasites in this genus. Owing to the enormous plasticity of the genome, resistance can occur by altering different metabolic pathways, demonstrating that resistance mechanisms are multifactorial and extremely complex. Genetic variability and genome plasticity cause not only the available drugs to have limitations, but also make the search for new drugs challenging. Here, we examined the biological characteristics of parasites that hinder drug discovery.


Avoidable mortality in small-for-gestational-age children in the Netherlands.
To analyze avoidable perinatal mortality in small-for-gestational-age (SGA) children. All SGA-children (< or =10(th) percentile) among 22,189 newborns delivered after 24 weeks' gestation (175 days), from three regions of the Netherlands during 2003-2004 were evaluated. Cases of perinatal mortality were identified and assessed in a consensus model by perinatal audit groups for cause of death and the presence of substandard care factors (SSF). We analyzed all singleton SGA-cases with and without SSF for avoidable perinatal mortality. Out of 20,927 singletons, 2396 newborns were SGA. Of those, 59 died perinatally (2.46%), and 55 of which were assessed by perinatal audit groups. SSF by caregivers were found in 22 cases (40%). In 16 of these cases (29%) the relation to the perinatal death was considered possible or (very) probable. Of the cases without SSF by caregivers, 15 cases (25%) could possibly have been avoided: in 13 cases an avoidable condition and in 2 cases avoidable death were identified. Failure in the correct and timely diagnosis of fetal growth restriction appears to be an important issue in all cases of perinatal mortality in SGA-children. Before referral growth restriction was suspected only in 22% of all SGA cases during the third trimester of pregnancy. More adequate action by caregivers could decrease perinatal mortality in nearly 1/3 among SGA-children. Adjustments in pregnancy monitoring, especially in low-risk pregnancies, such as routine ultrasound biometry examination, may improve the accuracy in detecting growth deviations and decreasing the number of possibly avoidable cases of perinatal mortality in this category.


LC3-Dependent Autophagy in Pig 2-Cell Cloned Embryos Could Influence the Degradation of Maternal mRNA and the Regulation of Epigenetic Modification.
In this study, the distribution as well as the effect of autophagy on reprogramming in pig cloned embryos were observed immediately after somatic cell nuclear transfer. Results showed that the LC3 was at the highest level in cloned embryos at 2-cell stage, and it decreased with the development from 2-cell stage to blastocyst. Different to cloned embryos, the intensity of LC3 in parthenogenetic activation (PA) embryos was at the highest level at 4-cell stage. A markedly higher level of Bmp15, H1foo, and Dppa3 was shown in cloned embryos at 2-cell stage (p < 0.05 or p < 0.01), but a significantly lower level of LC3, Sox2, and eIF1A was observed at 4-cell stage (p < 0.05), compared with PA embryos. When the efficient interfering by the LC3 siRNA was performed on the cloned embryos (p < 0.01), not only the mRNA level of maternal Cyclin B, Bmp15, Gdf9, c-mos, H1foo, and Dppa3 was increased significantly (p < 0.05), but also the expression of Dnmt1 and Dnmt3b was obviously upregulated (p < 0.05). Although the expression of Sox2 and Oct4 is not changed, the expression of Stat3 decreased significantly (p < 0.05). Furthermore with the treatment of 200 nM rapamycin, the expression of eIF1A and Stat3 was significantly increased at 4-cell stage. In conclusion, the LC3-dependent autophagy mainly occurred in cloned embryos at 2-cell stage, but at 4-cell stage in PA embryos. In addition, the modulation of autophagy could affect genome activation by influencing the degradation of maternal mRNA and regulating the expression of DNA methyltransferase.


Use and cost of home health agency services under Medicare.
Presented are 1986 data and trend data (1974-86) on the use and cost of home health agency services rendered to aged and disabled Medicare beneficiaries. Since 1974, reimbursements for these services have grown more rapidly than overall Medicare expenditures. From 1974 to 1986, Medicare expenditures for these services increased from $141 million to $1.8 billion, an average annual rate of 24 percent. HHA reimbursements, however, continue to represent only a small proportion (3.6 percent in 1986) of all Medicare expenditures.


Prevalence and Co-Occurrence of Different Types of Body Dysmorphic Disorder Among Men Having Sex with Men.
Body dysmorphic disorder (BDD) is a relatively common psychiatric condition of which the prevalence has not been fully investigated in the non-clinical population, and in particular among men having sex with men (MSM). MSM have proven to be more inclined to develop body dissatisfaction and body image disorders compared to non-MSM. Our study investigates the prevalence of BDD and the prevalence and co-occurrence of muscle dysmorphia (MD) and penile dysmorphic disorder (PDD) in a sample of 261 Italian MSM recruited online. From our data, gathered through self-report measures, the prevalence of BDD, MD, and PDD in our populations was 5.4%, 8.8%, and 4.2%, respectively. Compared to their elders, younger adults (ages 18-34) appear to be at higher risk of BDD and especially of MD. Non-significant differences have been observed for the prevalence of PDD depending on the age range. Our study shows that the risk of body image disorders among MSM is quite common, especially among young adults, and higher than what is found among heterosexual men.


Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination.
To study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD) with deficient haptic perception. Twelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices. We found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients. PD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.


Three cases of Troyer syndrome in two families of Filipino descent.
Troyer syndrome is a complex hereditary spastic paraplegia (HSP) due to a mutation in SPG20 first reported in the Old Amish population. A genetic mutation in SPG20 is responsible for a loss of function of the protein spartin in this disease. Since its initial report, this syndrome has also been reported in Turkish and Omani families. Here we report the case of three patients of Filipino descent with Troyer syndrome. Whole exome sequencing (WES) identified a homozygous mutation c.364_365delAT which predicts p.Met122Valfs*2 in SPG20. This is the same mutation identified in affected patients from the Omani and Turkish families, and is the first report of this syndrome in the Filipino population. Although Troyer syndrome has characteristic phenotypic manifestations it is likely underdiagnosed due to its rarity and we expect that WES will lead to identifying this disease in other individuals. © 2016 Wiley Periodicals, Inc.


Interface engineering in NiSe2/Ni2Co/CoSe2 heterostructures encapsulated in hollow carbon shells for high-rate Li-Se batteries.
The sluggish conversion reaction and the accompanying huge volume fluctuation greatly hinder the application of lithium-selenium (Li-Se) batteries. Therefore, reasonably constructing stable carbonaceous hosts with efficient electrochemically active sites is particularly essential for promoting the development of Se cathodes. Herein, a metal-organic solid derived carbon host with multiple heterogeneous NiSe2/Ni2Co/CoSe2 interfaces was fabricated via in situ selenization. The formation of multiple heterointerfaces introduced subtle atomic array distortions, which provided additional electrochemically active sites compared with single heterointerfaces. Besides, the establishment of a built-in electric field was favorable for electron transfer and the absorption of Li+, thereby accelerating the reaction kinetics. Depending on the hollow structure and the heterogeneous catalysts, Li-Se batteries with NiSe2/Ni2Co/CoSe2@Se cathodes delivered reversible capacities of 503 and 324 mA h g-1 after 900 and 2200 cycles at 1 and 12 C, respectively. This work revealed the synergistic mechanism of multiple heterostructures composed of a Ni2Co alloy and in situ derived bimetallic selenides for Se cathodes and provided new insights into the exploitation of energy storage materials.


Infections of the subcutis and skin of dogs caused by rapidly growing mycobacteria.
Nine dogs with panniculitis due to rapidly growing mycobacteria (RGM) were examined over 17 years. Dogs were two to 15 years; five were male, four were female. All were obese or in good condition. Antecedent injury, typically a dog bite or vehicular trauma, could be identified in some patients, while one bitch had hyperadrenocorticism. Infections involved different locations, although the cervicothoracic region, dorsum or flank were most often affected. Patients were systemically well, apart from one dog with pyrexia and two with pain or lameness. Cytology demonstrated pyogranulomatous inflammation, but in only one case was it possible to see acid-fast bacilli (AFB) in smears. Histology demonstrated chronic active pyogranulomatous panniculitis and dermatitis; AFB could be detected in only four specimens. Culture of aspirates or resected tissues demonstrated RGM in all cases, comprising six Mycobacterium smegmatis group and three Mycobacterium fortuitum group isolates. Resection of infected tissues, perioperative injectable antimicrobials and long courses of oral antimicrobials chosen according to susceptibility data generally effected a cure, although some cases recurred.


Effects of different oral instructions on kinematic and kinetic parameters during drop vertical jump.
[Purpose] This study aimed to examine the impact of changing the drop vertical jump stance time on kinematic and kinetic parameters by ordering to high jump or quick jump for consistent stance time and a more accurate assessment of anterior cruciate ligament injury risk. [Participants and Methods] The participants were 20 healthy female students. The drop vertical jump was started by instructing the participants to stand on a 30-cm platform with both legs stationary. The task was performed while the participants were instructed to perform high jump or quick jump. [Results] Stance time was significantly shorter with quick jump than with high jump. Quick jump showed significantly higher knee abduction angles at initial contact and peak vertical ground reaction force, and lower hip flexion, knee flexion, and ankle dorsiflexion angles at the lowest point of the center of mass. Quick jump showed a significantly higher peak vertical ground reaction force. The knee abduction moment at initial contact was not significantly different between the 2 conditions. [Conclusion] Quick jump was better than high jump for making stance time consistent, and the differences in kinematic and kinetic characteristics by oral instructions should be considered when using drop vertical jump.


New device and method for capture, reverse transcription and nested PCR in a single closed-tube.
A device and improved method based on the use of a compartmentalized Eppendorf tube that allows capture, reverse transcription and nested-PCR in a single closed-tube has been developed and patented. The main advantages of the system are the high sensitivity obtained, the simplicity, the low risk of contamination and the easy establishment of adequate conditions for nested-PCR. The method has been successfully applied to the detection and characterization of citrus tristeza closterovirus and plum pox potyvirus isolates in plant tissues and single aphids squashed on paper. This device and methodology could be easily adapted to the detection of other targets.


A new, facile synthesis of 1,4,7,10-tetraazacyclododecane: cyclen.
This report outlines a new and efficient synthesis of cyclen (1,4,7,10-tetraazacyclododecane, 1) utilizing bis-imidazoline, 6 (1,1'-ethylenedi-2-imidazoline), with 1,2-dibromoethane. General conditions were developed, allowing for the simple, three-step synthesis of 1 at the multigram scale with an isolated overall yield approaching 65%. The cyclization of 6 produced by the condensation of triethylene tetraamine (TETA) with N,N-dimethylformamide dimethyl acetal, gave the twelve-membered, imidazolinium, cyclized intermediate bromide salt, 7 (2,3,4,5,6,7,8,8c-octahydro-1H-4a,6a,8a-triaza-2a-azoniacyclopent[fg]acenaphthylene), which hydrolyzed to 1 with the use of hot, aqueous caustic. Hydrolysis of 7 under milder conditions formed the 1,4,7,10-tetraazabicyclo[8.2.1]tridecan-13-one (20). Mechanistically, the formation of 7 may be rationalized as involving a diaminocarbene that undergoes an intramolecular carbon-hydrogen insertion.