The human papillomavirus type 16 (HPV-16) E5 protein sensitizes human keratinocytes to apoptosis induced by osmotic stress.
We have studied the role of the HPV-16 E5 protein in apoptosis, using HaCaT cell lines stably transfected with either E5 (HaCaT/E5) or the empty vector (HaCaT/pMSG) as control. When subjected to a hyperosmolar concentration of sorbitol, HaCaT/E5 cells respond with cytochrome c release, activation of caspase-3, -8, and -9, and PARP-cleavage, showing that the mitochondria and death-receptor mediated apoptotic pathways are involved in subsequent cell death. Similar effects are observed for the control cells only after extended sorbitol treatment. Thus, E5-expressing cells are more sensitive to osmotic stress, perhaps because of modifications of the cellular membranes caused by this strongly hydrophobic molecule.


[Vascular nephropathies: a fresh look at a systemic disease].
Hypertensive nephropathy represents the most prevalent cause of end-stage renal disease in France. Renal lesions are unspecific. Nephroangiosclerosis diagnosis is overestimated due to non standardized clinical criteria and available histological analysis. Other factors than hypertension contribute to vascular lesions.MYH9 and APOL1 polymorphisms are strongly associated with kidney diseases including hypertensive nephropathy. Elevated blood pressure levels are associated with CKD progression. Treatment includes angiotensin blockers which have a synergic effect on blood pressure reduction and lowering urinary protein excretion with sodium restriction and diuretics.


Investigations on the percutaneous absorption of the antidepressant rolipram in vitro and in vivo.
In vitro experiments using full-thickness human skin showed that it was feasible to deliver therapeutic amounts of the new antidepressant drug rolipram. Simple transdermal devices were constructed, and the presence of isopropyl myristate (IPM) in a silicone adhesive (Dow Corning X7-2920) enhanced the flux across excised human skin. The steady-state fluxes from adhesive mixtures containing 0, 5, and 10% IPM were 3, 5.2, and 6 micrograms/cm2/hr, respectively. The in vitro experiments were confirmed in a clinical study involving six healthy male volunteers. The formulations tested were an alcoholic solution and adhesive patches containing 5 and 10% IPM. The dose of drug administered was 0.5 mg/cm2 and the device size 25 cm2. Blood samples were withdrawn over a 24-hr period and analyzed using radioimmunoassay. The topical applications were well tolerated, with only mild or no side effects. A lag time of approximately 2 hr was found for the detection of rolipram in the plasma (detection limit, 50 pg/ml). Interindividual variations both for the peak drug levels and throughout the delivery were quite high but this magnitude of variation has been observed in many other transdermal studies. Plasma levels between 1 and 2 ng/ml were found for all formulations and the AUC0-30 hr was significantly higher for the patch containing 5% IPM.


Development and validation of a Sarcopenia Geriatric Scale (SARCO-GS): a new short scale for the screening of sarcopenia.
Sarcopenia is a highly prevalent disease associated with adverse outcomes such as falls, disability, and death. The current international consensuses agree that muscle strength, muscle mass, and gait speed must be included in the definition. However, these proposed criteria require objective measurements that are not available for most populations. Since the timely identification of sarcopenia is a priority, several subjective screening scales have been developed; however, they have some limitations due to their low sensitivity. The objective of this work was to develop and validate SARCO-GS, a new short scale to screen sarcopenia that is affordable, easy, and accessible for all clinical care settings. The development of the SARCO-GS included four stages: (1) Review and analysis of documentary sources, (2) Contextualization of the theoretical model of sarcopenia, (3) Scale conformation, and (4) Reliability and validity analyses. SARCO-GS was validated in the FraDySMex study, which is a longitudinal cohort of community-dwelling adults. In the studied population (n=852), the average age was 68.9 years (SD 10.21) and 80.1% of the participants were women. SARCO-GS is a seven-item scale with an innovative structure that included five subjective questions (gait speed, muscular strength, muscle mass) and two measurements of muscular strength and muscle mass (Chair stand test and calf circumference). The results regarding criterion validity showed that the cut-off point ≥ 3 had good sensitivity (77.68%) versus the EWGSOP2 consensus, with an adequate Area Under the Receiver Operating Characteristic (AUC) (0.73), in addition to showing higher values of sensitivity and AUC than SARC-F and SARC-CalF using as reference the same consensus. Furthermore, SARCO-GS presented good predictive validity for functional dependence (HR=2.22, p=0.046) and acceptable correlation with other related measurements (construct validity). Regarding reliability, the scale showed acceptable internal reliability (correlation between items and total score: 0.50 to 0.70). After the validation analysis, the scale was adapted to English. The SARCO-GS is a novel scale to screen sarcopenia with high sensitivity, good construct, predictive validity, and internal reliability that may be useful for health professionals in different clinical settings and for clinical research.


Unusual Pseudomonas corneal ulcers.
Two rare species of Pseudomonas were isolated from corneal ulcers in two patients. In the first case P. acidovorans was isolated and suspected as the primary pathogenic microorganism in human disease. In the second case P. stutzeri was isolated from ocular sources, but this is the first report of its role in causing corneal disease. The patient in the second case had a scarred cornea, possibly caused by a previous herpetic infection, and this may have been a predisposing factor to the development of the infection by P. stutzeri. Susceptibility studies of both organisms revealed sensitivity to a wide range of antibiotics but resistance to carbenicillin, a drug currently used in the treatment of infections from P. aeruginosa.


Pressure-Volume Curve during Capnoperitoneum in Cats.
Laparoscopy is a growing field in veterinary medicine, although guidelines are lacking. The objective of this study was to evaluate the pressure-volume curve during capnoperitoneum in cats. A total of 59 female cats were scheduled for routine laparoscopy. Pressure and volume data were recorded and processed, and the yield point of the curve was calculated using a method based on a capacitor discharging function. For the remaining 40 cats, a linear-like pressure-volume curve was observed until a yield point with a mean cutoff pressure (COP) of 6.44 ± 1.7 mmHg (SD) (range, 2.72-13.00 mmHg) and a mean cutoff volume (COV) of 387 ± 144.35 mL (SD) (range, 178.84-968.43 mL) was reached. The mean mL/kg CO2 value in cats was 208 ± 34.69 mL/kg (range, 100.00-288.46 mL/kg). The COV correlated with COP and body weight but not with body condition score (BCS). COP correlated only with the COV. This study suggests that feline patients have a pressure-volume curve similar to that of canine patients, and the same pressure limit recommendations can be used for both species. After a yield point of 6.44 mmHg is reached, the increment in volume decreases exponentially as the intra-abdominal pressure (IAP) increases.


Neuroblastoma.
The identification of prognostic factors has greatly facilitated the rational choice of therapies in individual patients. Intensive chemotherapy, supplemented with radiation and surgery, has increased the remission rate of patients with widespread disease. The persistence of microscopic foci of malignant cells, however, remains a difficult hurdle for long-term disease-free survival. Highly toxic myeloablative therapies have had at most a modest impact on the overall cure rate of poor-risk patients. The use of novel biological therapies has provided new information on the mechanisms and potentials of immune-mediated tumor cytotoxicity. Timely clinical trials are needed to test their role in adjuvant treatment of occult microscopic disease.


The role of a defined formula diet in the prevention of stress-induced gastric mucosal injury in the rat.
The role of a defined formula diet, Vivonex HN, in the prevention of gastric mucosal injury was evaluated in the cold, restrained rat model. The mean grade of gastric bleeding and mean number of gastric lesions were 3.95 and 7.35 +/- 1.02, respectively, in the stressed, unprotected control group. In four random groups of rats given Vivonex HN, Maalox, Cimetidine (20 mg/kg) and Cimetidine (60 mg/kg) prior to stress, the mean grade of gastric bleeding was 0; 1.55; 2.33; 1.75; and the mean number of gastric lesions was 0; 1.2 +/0 0.31; 2.83 +/0 0.82; 2.2 +/- 0.65, respectively. The differences were statistically significant. Our experiments show that Vivonex HN was more effective than Maalox or Cimetidine in high dose in preventing gastric bleeding and gastric mucosal lesions in the cold, restrained rat. Cimetidine in a standard dose was the least protective. Clinical trials are needed to establish the role of Vivonex HN in the prevention of stress ulcers in patients at risk.


Impact of oncogenic BRAF mutations and p16 expression on the growth rate of early melanomas and naevi in vivo.
It is important to know what drives and arrests melanocytic growth in vivo but observations linking oncogenic mutations to growth rates of melanocytic neoplasms in vivo are sparse. To clarify the relationship between BRAF(V) (600E) mutations and p16 expression and the growth rate of melanocytic neoplasms in vivo. We measured the growth rate of 54 melanocytic lesions (26 melanomas, 28 naevi) in vivo with digital dermatoscopy and correlated it with BRAF(V) (600E) and p16 expression, and with dermatoscopic and histological patterns. Melanomas grew faster than naevi (mean 2·7 vs. 0·8 mm(2) /year; P < 0·001) and the growth rate was faster in lesions with more nests (> 25% nests: 2·0 mm(2) /year vs. < 25% nests: 1·0 mm(2) /year; P = 0·036). Melanomas with the BRAF(V) (600E) mutation grew significantly faster than melanomas without the mutation (mean 3·36 vs. 1·60 mm(2) /year, P = 0·018). This effect of the BRAF(V) (600E) mutation on the growth rate was not observed in melanocytic naevi (mean 1·01 vs. 0·47 mm(2) /year, P = 0·274). Histopathologically, extensive nesting, larger nests and larger cell sizes were more common in melanocytic neoplasms with the BRAF(V) (600E) mutation than in those without the mutation. Melanomas expressing p16 had a slower growth rate than melanomas without p16 expression (2·27 vs. 4·34 mm(2) /year, P = 0·047). This effect was not observed in naevi (0·81 vs. 0·68 mm(2) /year, P = 0·836). The expression of BRAF(V) (600E) and the loss of p16 accelerate the growth rate of early melanomas in vivo but not in melanocytic naevi. In comparison to melanocytic proliferations that lack the mutation, the epidermal melanocytes in lesions that harbour BRAF(V) (600E) mutations are larger and more frequently arranged in large nests.


Recombinant human granulocyte-macrophage colony-stimulating factor induces secretion of autoinhibitory monokines by U-937 cells.
Colony-stimulating factors are required for survival proliferation, differentiation and functional activation of granulocytes, macrophages and their precursor cells. In the present report, however, we demonstrate antiproliferative activity of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) on monoblast cell line U-937 and provide evidence for the involvement of tumor necrosis factor alpha TNF-alpha and interleukin 1 beta (IL 1 beta) in its growth inhibitory action. GM-CSF (but not granulocyte CSF, G-CSF or macrophage CSF, M-CSF) suppressed DNA synthesis and self renewal of U-937 cells. Similarly, medium conditioned by U-937 cells in response to GM-CSF (GM-CSF U-937-CM) was able to reduce clonogenicity and [3H]thymidine uptake by U-937 cells. Since neutralization of GM-CSF present in GM-CSF U-937-CM by monoclonal antibody to GM-CSF did not abrogate the autoinhibitory activity present in GM-CSF U-937-CM, we considered the possibility that other soluble molecules are released by U-937 cells upon GM-CSF stimulation. Neutralization by antibodies to IL 1 beta and TNF-alpha suggested that both monokines could be the antiproliferative principle operating in GM-CSF U-937-CM. Moreover, employing IL 1 beta-specific enzyme-linked immunosorbent assay, TNF-alpha specific radioimmunoassay, Northern analysis using a cloned TNF-alpha-specific cDNA and an oligonucleotide probe for IL 1 beta, we demonstrate GM-CSF-inducible IL 1 beta and TNF-alpha gene expression by U-937 cells at the mRNA and protein level. Although M-CSF expression was induced under similar conditions, M-CSF failed to inhibit growth of U-937 cells.


The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread.
The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry.


Screening for inducers of kinase degradation.
Targeted small molecule-induced protein degradation is a promising approach to inhibit signaling within kinase cascades. In this issue, researchers describe a simple assay for the rapid, high-throughput identification of novel agents that promote degradation of the kinases Her2 and EGFR.


Reversible hypogonadotrophic hypogonadism in sexually infantile male thalassaemic patients with transfusional iron overload.
To determine the severity and reversibility of the lesion in the hypothalamic-pituitary (H-P) axis of male transfusion-dependent thalassaemic patients with failed puberty (FP). The hypothalamic-pituitary axes of 20 male thalassaemic patients (study group) were compared with two male subjects with idiopathic hypogonadotrophic hypogonadism (IHH) and five prepubertal healthy siblings (control group). GnRH-gonadotrophin insufficiency was characterized by nocturnal 12 h ultradian gonadotrophin profiles followed by a 100 microg GnRH bolus test (GBT) 4-6 times at 6 monthly intervals. Thalassaemic and IHH patients were then subjected to pulsatile subcutaneous GnRH infusions every 120 minutes for 3 months. Ultradian gonadotrophin profiles and GBT were repeated after 6 weeks of GnRH infusion and again at 3 months following infusion. FSH and LH were measured by radio-immunoassay. Ferritin was assayed by an immunoradiometric method. Patients with IHH who were apulsatile prior to infusion, developed normal gonadotrophin pulses with marked increment in their gonadotrophin responses to the GBT after 3 months of GnRH infusion. In contrast, the thalassaemic patients with apulsatile failed puberty (AFP) remained apulsatile (nonresponders) and had no increment in their gonadotrophin responses to the GBT after GnRH infusion. All patients with pulsatile failed puberty (PFP) had abnormal gonadotrophin pulses prior to GnRH infusion. Their pulse defects were either totally or partially corrected (responders) following infusion. The serum ferritin levels (9500 +/- 500 microg/l vs. 5966.67 +/- 1139 microg/l; P < 0.01) and percentage of organ dysfunction (87% vs. 17%; P < 0.01) were higher in the nonresponders than the responders. This study shows that thalassaemic patients with severe organ damage and iron overload are likely to be apulsatile with irreversible damage to their hypothalamo-pituitary axis, while those with less severe iron overload are likely to have potentially reversible hypogonadotrophic hypogonadism (HH). Our results also suggest that gonadotrophin pulse parameters, rather than the gonadotrophin response to a GnRH bolus following prolonged pulsatile GnRH infusion, may be more useful in discriminating reversible from irreversible hypogonadotrophic hypogonadism.


Design, synthesis, antimicrobial activity and molecular docking study of cationic bis-benzimidazole-silver(I) complexes.
Two series of bis(1-alkylbenzimidazole)silver(I) nitrate and bis(1-alkyl-5,6-dimethylbenzimidazole)silver(I) nitrate complexes, in which the alkyl substituent is either an allyl, a 2-methylallyl, an isopropyl or a 3-methyloxetan-3-yl-methyl chain, were synthesized and fully characterized. The eight N-coordinated silver(I) complexes were screened for both antimicrobial activities against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii) and Gram-positive (Staphylococcus aureus, Staphylococcus aureus MRSA, and Enterococcus faecalis) bacteria and antifungal activities against Candida albicans and Candida glabrata strains. Moderate minimal inhibitory concentrations (MIC) of 0.087 μmol/mL were found when the Gram-negative and Gram-positive bacteria were treated with the silver complexes. Nevertheless, MIC values of 0.011 μmol/mL, twice lower than for the well-known fluconazole, against the two fungi were measured. In addition, molecular docking was carried out with the structure of Escherichia coli DNA gyrase and CYP51 from the pathogen Candida glabrata with the eight organometallic complexes, and molecular reactivity descriptors were calculated with the density functional theory-based calculation methods.


N alpha-acetyl-[Arg8]vasopressin antagonizes the behavioral effect of [Cyt6]vasopressin-(5-9), but not of vasopressin.
It has been found recently that N alpha-acetyl-[Arg8]vasopressin (Ac-VP) is present in the brain of rats. The physiological significance of this peptide is as yet unknown. Therefore, the central nervous system effects of this peptide were investigated, namely, its effects on passive avoidance behavior, exploratory behavior and body temperature. The interaction of Ac-VP with the central nervous system effects of vasopressin (VP) was also studied. Ac-VP had a slight agonistic effect on passive avoidance behavior, i.e. it facilitated passive avoidance behavior at a dose 100 times higher than that of VP. Relatively low doses (3-10 ng) of Ac-VP attenuated passive avoidance behavior, which suggests that Ac-VP interfered with an endogenous compound involved in the control of passive avoidance responding. Ac-VP was also able, albeit in higher doses (30 ng), to competitively antagonize the effect of [Cyt6]VP-(5-9), a highly potent, putative endogenous metabolite of vasopressin in the rat brain. This antagonism could be due to an interaction of Ac-VP with sites other than the V1 vasopressin receptor. Ac-VP had no significant influence on other central nervous system effects of the hormonally active nonapeptide VP, such as exploratory behavior and body temperature. These effects were readily antagonized by the V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)VP. Ac-VP may be competitive antagonist of behaviorally active vasopressin metabolite(s) in the brain.


Epidermal nevus syndrome: megalencephaly with bihemispheric and cerebellar involvement: imaging and neuropathologic correlation.
Epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder characterized by the combination of epidermal nevi with significant central nervous system, eye, and skeletal abnormalities. Hemimegalencephaly and related brain abnormalities are the dominant neuropathologic abnormalities in ENS. Magnetic resonance imaging features of the case reported here revealed enlargement of both cerebral hemispheres and malformed basal ganglia, with incomplete separation of the caudate nucleus and putamen. In addition, the right cerebellar hemisphere was enlarged, with disorganized folia. None of these findings have been reported previously in this disorder.


Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors.
To develop a population pharmacokinetics (PPK) model for rucaparib, an oral poly(ADP-ribose) polymerase inhibitor. The PPK analysis used PK data from patients in Study 1014 (NCT01009190, n = 35), Study 10 (NCT01482715, n = 123), and ARIEL2 (NCT01891344, n = 300), including intensive intravenous data (12-40 mg), intensive and sparse oral data (12-360 mg single-dose, 40-500 mg once daily, and 240-840 mg twice daily [BID]), and intensive single-dose oral data under fasted conditions and after a high-fat meal (40, 300, and 600 mg). Rucaparib PK was well described by a two-compartment model with sequential zero-order release and first-order absorption and first-order elimination. A high-fat meal slightly increased bioavailability at 600 mg but not at lower doses; this is not considered clinically significant, and rucaparib can be taken with or without food. Covariate effects of baseline creatinine clearance and albumin on rucaparib clearance were identified. Despite numerical increases in exposure with renal impairment, no dose adjustment is recommended for patients with mild or moderate renal impairment. No statistically significant relationships were detected for demographics, hepatic function (normal versus mild impairment), CYP1A2 and CYP2D6 phenotypes, or strong CYP1A2 or CYP2D6 inhibitors. Concomitant proton pump inhibitors showed no clinically significant effect on absorption. External validation of the model with data from ARIEL3 (NCT01968213) and TRITON2 (NCT02952534) studies showed no clinically meaningful PK differences across indications or sex. The PPK model adequately described rucaparib PK, and none of the covariates evaluated had a clinically relevant effect. GOV: Study 1014 (NCT01009190), Study 10 (NCT01482715), ARIEL2 (NCT01891344), ARIEL3 (NCT01968213), and TRITON2 (NCT02952534).


Epidemiology and control of melanoma in white populations and in Japan.
In white populations living at moderate or low latitudes, melanoma has become one of the most common tumors in young adults. Epidemiologic studies show a complex association with sun exposure. Risk is related positively to the levels of exposure typical of the place of residence, and also to personally controlled exposure, with the maximum risk being related to acute intermittent exposure. Risk also varies with pigmentation, family history of melanoma, and the presence of benign and of dysplastic nevi. The following methods of control of melanoma in such populations are discussed: the most effective methods depend on early diagnosis; primary prevention appears difficult and requires evaluation; identification of very high-risk subjects on the basis of family history and dysplastic nevi will affect only a very small proportion of melanomas; the use of simpler methods to identify high-risk subjects is explored. In Japan, melanoma is comparatively rare, but increasing as rapidly as elsewhere. The incidence rate of acral lentiginous melanoma appears similar to that in whites, comprising a large proportion of melanoma in Japan. Control programs cannot be designed rationally, since basic information on the occurrence, presentation, and survival of melanoma in Japan is lacking. Some specific research questions are suggested.


Inherited aplastic anaemia with increased endoreduplications: a new syndrome of Fanconi's anaemia variant?
Two sisters with aplastic anaemia without other congenital anomalies are described. Peripheral blood cytogenetic studies revealed an increase in endoreduplications in the absence of other unstable chromosome anomalies. Increased expression of T-antigen following SV40 virus infection in vitro was demonstrated in both sisters, as well as other normal family members. We feel that these patients represent a variant of Fanconi's anaemia. The importance of performing chromosome studies in idiopathic aplastic anaemia is emphasized.


Endoscopic Treatments for Obesity.
Purpose of review Endoscopic bariatric therapy (EBT) is a rapidly developing area that has now seen FDA approval of six endoscopic bariatric devices and procedures and there are a number of other novel EBTs progressing through various stages of development with newly published findings. This paper aims to assist readers in either selecting an appropriate therapy for their patient or deciding to incorporate these therapies into their practice. This paper provides an updated review of the available data on EBTs, both FDA approved and not, with a particular focus on effectiveness and safety, as well as guidance for discussing with your patient the decision to use endoscopic therapies. Findings The authors of a large meta-analysis of Orbera concluded its ideal balloon volume to be 600-650 mL. AspireAssist has had favorable effectiveness and safety data published in a large RCT. A large study of endoscopic sleeve gastroplasty has published findings at up to 24 months showing promising durability. Elipse, a swallowed intragastric balloon not requiring endoscopy for either insertion or removal, has had early favorable results published. A magnet-based system for creation of a gastrojejunostomy has published favorable findings from its pilot study. Summary EBTs are safe and effective therapies for weight loss when used in conjunction with lifestyle changes and fill an important gap in the management of obesity. There are now six FDA-approved EBTs available and several more in ongoing trials with favorable early findings. More study is needed to understand the role of EBTs used in combination or in sequence with medications and bariatric surgery.


Interactive effects of individuation, family factors, and stress on adolescent alcohol use.
A prospective, school-based study of increasing alcohol use in a multi-ethnic sample of 7,540 adolescents showed that the effects of stress, family conflict, and parental monitoring were differentially moderated by two modes of individuation. The effects of stress were moderated by ethnic status and individuation. Implications for prevention and intervention are discussed.


Co-applying biochar and manganese ore can improve the formation and stability of humic acid during co-composting of sewage sludge and corn straw.
This study examined the effects of corn straw biochar (CSB) and manganese ore (MO) on the abiotic formation and stability of humic acid (HA) during sewage sludge composting. Co-applying CSB and MO (106%) induced a higher increase in HA content of final compost product than those of no or single applications (32.6-85.1%). This positive change was achieved by promoting the conversion of humus precursors and fulvic acid to HA through abiotic pathway, respectively, in the early and later stages of composting. The co-application of CSB and MO also exhibited a higher capacity to improve HA stability than those of single applications. In sum, this study confirmed a clear synergistic effect of CSB and MO on improving the formation and stability of HA in compost product, which could further enhance the multi-benefits (e.g., carbon sequestration and soil quality improvement) of compost soil application.


Paeoniflorin alleviates AngII-induced cardiac hypertrophy in H9c2 cells by regulating oxidative stress and Nrf2 signaling pathway.
Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of paeoniflorin on oxidative stress of cardiac hypertrophy induced by angiotensin II (AngII) in vitro. Using MTS assay, qRT-PCR, WGA staining assay, and western blot, different dosages (50-400 μM) of paeoniflorin were utilized to examine the antihypertrophy effects on H9c2 cells. Western blot examination revealed the presence of apoptosis-related proteins Bax, Bcl2, and Cytc, antioxidative stress-related proteins Nrf2, HO-1, SOD, and CAT, and mitophagy-related proteins PINK1 and Parkin. qRT-PCR was used to detect the mRNA expression of Bax, Bcl2, Nrf2, and HO-1. TUNEL, caspase3/9 enzyme viability, and MDA, T-AOC, and superoxide levels were all evaluated using commercial kits.The fluorescent probes DCFH-DA and JC-1 were employed to measure cellular ROS and MMP levels. Nrf2 siRNA was utilized to investigate Nrf2's role in paeoniflorin-treated cardiac hypertrophy. Paeoniflorin dramatically reduced cell section area (CSA) and hypertrophic marker (ANP, BNP) expression while inhibiting oxidative stress by modulating ROS and MDA, CAT, SOD, and T-AOC levels. Furthermore, in AngII-induced cardiomyocyte hypertrophy, paeoniflorin restores H9c2 apoptosis by restoring Bax, Bcl-2 Cyt-C, Caspase 3, and Caspase 9 levels. Paeoniflorin also restored Nrf2/HO-1 and PINK1/Parkin expression, and its anti-AngII activities were mediated by Nrf2, which was regulated by Nrf2 knockdown. In conclusion, Our data confirm that paeoniflorin alleviates cardiac hypertrophy through modulating oxidative stress and Nrf2 signaling pathway in vitro.


[Flavonols and flavones of vegetables. VIII. Flavones of carrot leaves (author's transl)].
The flavonoid constituents of carrot leaves (Daucus carota L. ssp. sativa) were separated by means of cellulose column chromatography, and the following compounds were obtained crystalline and identified by usual procedures: luteolin 7-beta-D-glucoside as the main flavon, luteolin 4'-beta-D-glucoside, luteolin 7-beta-D-glucuronide, apigenin 7-beta-D-glucoside, apigenin 7-rutinoside, chrysoeriol 7-beta-D-glucoside. Luteolin 7-rutinoside also was identified, but could not be obtained crystalline.


Case report: Hypophosphatemic hemolytic syndrome of alcoholics--a common city hospital problem.
This report describes three male alcoholics with acute hemolytic anemia secondary to hypophosphatemia who were seen within one year at a large city hospital. The basic etiologic association between low serum phosphorus and hemolytic disease was not initially appreciated in each instance.


Risperidone in the treatment of psychoses in the elderly: a case report series.
Risperidone is one of the newer atypical antipsychotic agents, which combines potent serotonin and dopamine receptor antagonism. It shows efficacy against the positive and negative symptoms of schizophrenic psychoses and other psychotic conditions, and has a low propensity to cause extrapyramidal side effects. The aim of these case reports in elderly patients is to provide the benefit of personal experience with risperidone to the body of published literature and to demonstrate the types of patients that may benefit from treatment. These cases were compiled retrospectively from data collected on referral and during routine hospital appointments. This series covers four main areas of concern when treating the elderly: low-maintenance dosing minimising the likelihood of adverse events; successful treatment of patients previously uncontrolled and experiencing side effects with other antipsychotics; the possibility of intermittent rather than continuous treatment; and the benefits to patients, carers and the health services. At low doses, risperidone is an effective and well-tolerated treatment for psychoses in elderly patients that improves the quality of life for both patients and their caregivers.


Selective expression of a unique glutathione S-transferase Yb3 gene in rat brain.
A cDNA clone from a rat brain lambda gt11 expression vector library contained the entire open reading frame, the 3' untranslated sequence, and 18 nucleotides of the 5' untranslated region of a Yb-type glutathione S-transferase that was clearly distinct from previously characterized liver forms. This form was designated as Yb3. Primer extension analysis indicated that the mRNA for Yb3 extends 118 nucleotides upstream of the translation initiation codon, and its total length of 1308 nucleotides is substantially larger than the transcripts of any of the liver glutathione S-transferases described thus far. The open reading frame of 654 nucleotides of Yb3 is the same as that of liver Yb1 and Yb2, with greater than 80% sequence homology. The amino acid sequence derived for Yb3 had regions conserved in all forms of Yb glutathione S-transferase, some other amino acid residues common to either Yb1 or Yb2, and 28 substitutions unique to Yb3. The 533 nucleotides in the 3' untranslated region of Yb3 were longer and not homologous to the 3' noncoding ends of the previously described glutathione S-transferases. A second clone from the brain library was virtually identical to that of the gene encoding the liver Yb1 form of the enzyme. Northern blot analyses of rat brain poly(A)+ RNA with specific Yb1 and Yb3 probes showed that the Yb3 form hybridized with a 1300-nucleotide mRNA, Yb1 with a separate 1100-nucleotide component, and that the two probes did not cross-hybridize. Moreover, while Yb3 is a minor component in liver, testis, and heart with even lesser amounts in spleen, lung, and kidney, it is a major glutathione S-transferase transcript in rat brain.


Graves' Disease Mechanisms: The Role of Stimulating, Blocking, and Cleavage Region TSH Receptor Antibodies.
The immunologic processes involved in Graves' disease (GD) have one unique characteristic--the autoantibodies to the TSH receptor (TSHR)--which have both linear and conformational epitopes. Three types of TSHR antibodies (stimulating, blocking, and cleavage) with different functional capabilities have been described in GD patients, which induce different signaling effects varying from thyroid cell proliferation to thyroid cell death. The establishment of animal models of GD by TSHR antibody transfer or by immunization with TSHR antigen has confirmed its pathogenic role and, therefore, GD is the result of a breakdown in TSHR tolerance. Here we review some of the characteristics of TSHR antibodies with a special emphasis on new developments in our understanding of what were previously called "neutral" antibodies and which we now characterize as autoantibodies to the "cleavage" region of the TSHR ectodomain.


Leveraging Health Care Simulation Technology for Human Factors Research: Closing the Gap Between Lab and Bedside.
We describe health care simulation, designed primarily for training, and provide examples of how human factors experts can collaborate with health care professionals and simulationists-experts in the design and implementation of simulation-to use contemporary simulation to improve health care delivery. The need-and the opportunity-to apply human factors expertise in efforts to achieve improved health outcomes has never been greater. Health care is a complex adaptive system, and simulation is an effective and flexible tool that can be used by human factors experts to better understand and improve individual, team, and system performance within health care. Expert opinion is presented, based on a panel delivered during the 2014 Human Factors and Ergonomics Society Health Care Symposium. Diverse simulators, physically or virtually representing humans or human organs, and simulation applications in education, research, and systems analysis that may be of use to human factors experts are presented. Examples of simulation designed to improve individual, team, and system performance are provided, as are applications in computational modeling, research, and lifelong learning. The adoption or adaptation of current and future training and assessment simulation technologies and facilities provides opportunities for human factors research and engineering, with benefits for health care safety, quality, resilience, and efficiency. Human factors experts, health care providers, and simulationists can use contemporary simulation equipment and techniques to study and improve health care delivery.


Unraveling the mysteries of IGF-1 signaling in melanoma.
The inherent ability of a cell to undergo apoptosis governs a number of developmental processes essential to proper mammalian development. Into adulthood, the pathways that potentiate the apoptotic response are extremely diverse and finely regulated to prevent potential diseases. Of these, cancer is often associated with loss of an apoptotic response. Hanahan and Weinberg (2000) list evasion of apoptosis as a hallmark feature acquired during neoplastic transformation. The impact of this event is dramatic on several levels; avoidance of apoptosis not only prevents programmed cell death in an array of cell types but also promotes chemotherapeutic resistance during anticancer regimens.


Identification by proximity labeling of novel lipidic and proteinaceous potential partners of the dopamine transporter.
Dopamine (DA) transporters (DATs) are regulated by trafficking and modulatory processes that probably rely on stable and transient interactions with neighboring proteins and lipids. Using proximity-dependent biotin identification (BioID), we found novel potential partners for DAT, including several membrane proteins, such as the transmembrane chaperone 4F2hc, the proteolipid M6a and a potential membrane receptor for progesterone (PGRMC2). We also detected two cytoplasmic proteins: a component of the Cullin1-dependent ubiquitination machinery termed F-box/LRR-repeat protein 2 (FBXL2), and the enzyme inositol 5-phosphatase 2 (SHIP2). Immunoprecipitation (IP) and immunofluorescence studies confirmed either a physical association or a close spatial proximity between these proteins and DAT. M6a, SHIP2 and the Cullin1 system were shown to increase DAT activity in coexpression experiments, suggesting a functional role for their association. Deeper analysis revealed that M6a, which is enriched in neuronal protrusions (filopodia or dendritic spines), colocalized with DAT in these structures. In addition, the product of SHIP2 enzymatic activity (phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]) was tightly associated with DAT, as shown by co-IP and by colocalization of mCherry-DAT with a specific biosensor for this phospholipid. PI(3,4)P2 strongly stimulated transport activity in electrophysiological recordings, and conversely, inhibition of SHIP2 reduced DA uptake in several experimental systems including striatal synaptosomes and the dopaminergic cell line SH-SY5Y. In summary, here we report several potential new partners for DAT and a novel regulatory lipid, which may represent new pharmacological targets for DAT, a pivotal protein in dopaminergic function of the brain.


An Automated Breast Volume Scanner-Based Intra- and Peritumoral Radiomics Nomogram for the Preoperative Prediction of Expression of Ki-67 in Breast Malignancy.
This study aimed to create and verify a nomogram for preoperative prediction of Ki-67 expression in breast malignancy to assist in the development of personalized treatment strategies. This retrospective study received approval from the institutional review board and included a cohort of 197 patients with breast malignancy who were admitted to our hospital. Ki-67 expression was divided into two groups based on a 14% threshold: low and high. A radiomics signature was built utilizing 1702 radiomics features based on an intra- and peritumoral (10 mm) regions of interest. Using multivariate logistic regression, radiomics signature, and ultrasound (US) characteristics, the nomogram was developed. To evaluate the model's calibration, clinical application, and predictive ability, decision curve analysis (DCA), the calibration curve, and the receiver operating characteristic curve were used, respectively. The final nomogram included three independent predictors: tumor size (P = .037), radiomics signature (P < .001), and US-reported lymph node status (P = .018). The nomogram exhibited satisfactory performance in the training cohort, demonstrating a specificity of 0.944, a sensitivity of 0.745, and an area under the curve (AUC) of 0.905. The validation cohort recorded a specificity of 0.909, a sensitivity of 0.727, and an AUC of 0.882. The DCA showed the nomogram's clinical utility, and the calibration curve revealed a high consistency among the expected and detected values. The nomogram used in this investigation can accurately predict Ki-67 expression in people with malignant breast tumors, helping to develop personalized treatment approaches.


Memory and exploratory impairment in mice that lack the Park-2 gene and that over-express the human FTDP-17 mutant Tau.
While mutations in the Park-2 gene are the most frequent cause of autosomal-recessive juvenile parkinsonism (AR-JP), they are also present in several forms of tauopathies. Conversely, in some forms of parkinsonism, mutations in the tau gene have also been observed. Deletion of the Park-2 gene and over-expression of mutant tau independently produce mild brain alterations in mice. However, the presence of both mutations simultaneously causes a tau neuropathology, involving reactive astrocytosis, neuron loss in the cortex and hippocampus, and lesions in nigrostriatal and motor neurons. Furthermore, mutant tau over-expression in mice produces important memory impairment. When "parkin" function was abolished in young tau transgenic mice, the memory alterations were exaggerated. Moreover, additional exploratory and motor deficits were observed in older mice, causing the memory alterations to be underestimated. Thus, while memory deficits are more severe in young mice they were somehow attenuated by exploratory impairments in ageing mutants. This double mutant animal will serve as a useful experimental tool to investigate the abnormal processing of hyperphosphorylated tau and its relationship to the development of the cognitive deficits associated with certain neurodegenerative diseases.


Coaching teachers to improve implementation of the good behavior game.
This study explored the association between coaching and the implementation of the Good Behavior Game (GBG) by 129 urban elementary school teachers. Analyses involving longitudinal data on coaching and teacher implementation quality indicated that coaches strategically varied their use of coaching strategies (e.g., modeling, delivery) based on teacher implementation quality and provided additional support to teachers with low implementation quality. Findings suggest that coaching was associated with improved implementation quality of the GBG. This work lays the foundation for future research examining ways to enhance coach decision-making about teacher implementation.


Visual statistical decisions.
To identify variables that underlie intuitive judgments about the sizes of groups of similar objects, we asked people to judge the relative heights of vertical bars briefly shown, two groups at a time, on a computer display. Randomly selected normal deviates determined individual bar height. Average differences in height and group sizes were also randomly varied. Twenty-eight participants judged 250 differences each, which were then submitted to multiple regression analysis and psychophysical inspection. The total number of bars sharpened discrimination, whereas variance dulled it. Critical ratio (CR), the forerunner to the modern t test, emerged as the most important predictor, little additional variance was explained by other factors. The difference in the number of bars was a reliable factor, favoring the greater number of bars. Confidence limits around thresholds, defined as CRs needed to say "possibly greater" surrounded 1.65; as a z value, this corresponded to a one-tailed probability of .05. Judgments about noisy stimuli thus seem to be based on a statistical process and to employ a probability criterion similar to that used in the formal statistical evaluation of experimental findings--namely, p < .05.


Efficacy and safety of repetitive transcranial magnetic stimulation for peripartum depression: A meta-analysis of randomized controlled trials.
This study aims to summarize and systematically review the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for women with peripartum depression (PPD). Several databases (Wanfang, CNKI, VIP, CBM, PubMed, Embase, Cochrane Library, PsyINFO, Web of Science, and Clinical trial) were searched from inception until April 12, 2020. In total, ten randomized controlled trials (RCTs) met the eligibility criteria and were included in this systematic review. We calculated the combined effect size (standardized mean difference [SMD] and odds ratio [OR]) for the corresponding effects models. The aggregated result of 10 trials indicated a significant benefit of rTMS on PPD, and the aggregated result of remission showed significantly positive effects of Test group VS. Control group. In terms of treatment adverse effects, the aggregated result showed no statistical significance of headache and dry mouth between the two groups. The results of the meta-analysis suggest that rTMS is an effective and safe intervention for PPD. Owing to poor methodological quality among the included studies, high-quality multicenter RCTs are needed to further verify the effects of this treatment.


Phytochemical and Bioactivity Studies on Constituents of the Leaves of Vitex Quinata.
A phytochemical investigation of the leaves of Vitex quinata (Lour.) F.N. Williams (Verbenaceae), guided by the MCF-7 human breast cancer cell line, led to the isolation of a new δ-truxinate derivative (1) and a new phytonoic acid derivative (2), together with 12 known compounds. The structures of the new compounds were determined by spectroscopic methods as dimethyl 3,4,3',4'-tetrahydroxy-δ-truxinate (1) and methyl 10R-methoxy-12-oxo-9(13),16E-phytodienoate (2), respectively. In a cytotoxicity assay, (S)-5-hydroxy-7,4'-dimethoxyflavanone (3) was found to be the sole active principle, with ED(50) values of 1.1-6.7 μM, respectively, when tested against a panel of three human cancer cells. Methyl 3,4,5-O-tricaffeoyl quinate (4) showed activity in an enzyme-based ELISA NF-κB p65 assay, with an ED(50) value of 10.3 μM.


Insights into the life-cycle of aerobic granular sludge in a continuous flow membrane bioreactor by tracing its heterogeneous properties at different stages.
This work gave insights into the life-cycle of aerobic granular sludge (AGS) by tracing its heterogeneity in the basic properties at different stages in a closed system (a continuous flow membrane bioreactor, MBR), including physical and chemical characteristics and microbial communities. The results indicate that the entire life-cycle consists of the following four stages, namely, the initial, growing, mature and cleaved stages, where multiple AGS properties synergistically affect the rheological properties of the AGS over its life-cycle. The storage modulus (G') of AGS reached its maximum value at the mature stage, whose value was significantly and positively correlated with the protein (PN) in extracellular polymeric substances (EPS) and granule size, specifically the peak area of granule size distribution, but this value was strongly and negatively correlated with the roughness. The AGS at the mature stage would be more vulnerable to be destroyed than that at other stages under the condition of higher shear strain, such as γ = 50%, which was associated with larger granule size and fewer polysaccharide (PS)-related functional groups (especially in the soluble microbial products (SMPs) in the outermost layer of AGS), and the decrease in PS was correlated with a higher relative abundance of Chloroflexi. Additionally, the value of shear strain that AGS was subjected to had a good linear correlation (R2=0.993) with the Young's modulus, which indicated the ability of AGS to resist deformation improved with increasing values of shear strain.


The use of puppetry for health promotion and suicide prevention among Mi'Kmaq youth.
North American aboriginal youth have been shown to exhibit some of the highest suicide rates in the world. In this article, the authors examine the main factors related to suicide among aboriginal youth and ways to redress what many consider the most important factor. While many factors contribute to suicide plans, the literature would suggest "discontinuity" with heritage to have a particularly negative impact that needs priority redress. A group of Mi'Kmaq elders and an interdisciplinary group of academicians blended traditional Mi'Kmaq knowledge and Western Science knowledge to develop a strategy to address such discontinuity. It involved using puppets made from natural forest materials to promote culture, language, and history. This article describes the strategy, its rationale, as well as its relevance for, and application to, holistic nursing.


Pharmacodynamics of trimethoprim-sulfamethoxazole in Listeria meningitis: a case report.
Infections in the cerebrospinal fluid (CSF) occur in an area of impaired host defenses; therefore, bactericidal antibiotics that reach adequate concentrations in the CSF are necessary for treatment. Measurements of antibiotic penetration into the CSF include CSF inhibitory and bactericidal titers, the absolute antibiotic concentration in the CSF, and the CSF: serum concentration ratio. We present the case of a patient with Listeria monocytogenes meningitis who failed to respond clinically to standard therapy, and whose organism demonstrated tolerance to Ampicillin (MBC: MIC = 258:1) that successfully responded to trimethoprim-sulfamethoxazole (TMP-SMX). The CSF peak bactericidal titer to TMP-SMX was 1:8, corresponding to that reported as necessary for successful outcome in patients with meningitis. The CSF peak: MBC ratios for TMP and SMX were less than 3:1 and equal to 3:1, respectively. These individual ratios are lower than those suggested for successful treatment of meningitis; however, the recommended ratios were established using single agents and did not account for synergistic activity with a drug combination such as TMP-SMX. The failure of standard therapy in this patient underscores the importance of MIC/MBC testing when tolerance is suspected or when CSF penetration of antibiotics is relatively poor. In addition, measurements of CSF inhibitory and bactericidal titers, which incorporate the antibiotic concentration in the CSF, susceptibility of the infecting microorganism, and host defense factors, may be useful in monitoring patients with meningitis.


Overexploitation assessment in an urban karst aquifer: The case of Sete Lagoas (MG), Brazil.
Overexploitation of groundwater in urban karst aquifers can lead to negative consequences such as land subsidence, depletion of springs and lakes, and water pollution. It can also have indirect effects such as environmental, socio-economic, and political instability. In the municipality of Sete Lagoas, Brazil, the long-term effects of extensive groundwater extraction have been observed and studied over the years. This paper analyzes the response of the karst aquifer to urban, industrial, and climatological changes that may have contributed to changes in the aquifer over the last four decades. The results show that groundwater extraction has exceeded the average aquifer recharge since the year 2000. From the 1980s, the number of wells has steadily increased due to unplanned urban development, resulting in higher demand for groundwater. In the 2010s, pumping from tubular wells (7.39 × 107 m3/yr) exceeded the maximum recharge capacity of the aquifer (7.33 × 107 m3/yr). These wells are mainly concentrated in two areas: the central urban zone and the industrial sector. As a result, kilometer-long cones of depression have formed, changing the aquifer from confined to unconfined within these regions. According to the census data, about 67% of the wells remain unidentified. The average annual recharge to the aquifer is estimated to be 5.68 × 107 m3/yr, which accounts for 12% of the average annual rainfall in the region. Climatological trends indicate an incipient decrease in precipitation and an increase in temperature, suggesting a potential decrease in future aquifer recharge. In addition, only 17% of the area has high infiltration rates ranging from 35% to 75%. The current situation in Sete Lagoas is one of overexploitation of groundwater resources, which could be mitigated by localized reduction of groundwater consumption and implementation of effective management strategies to increase aquifer recharge.


Transarterial chemoembolization as the primary treatment for a super-giant hepatic hemangioma.
Hepatic hemangiomas are common benign liver tumors. While the majority are small and require no treatment, giant hemangiomas are characterized as measuring greater than 4-6 cm in size and may require intervention. Surgical resection and enucleation have been described historically as the treatment for giant hemangiomas requiring intervention. Additionally, limited data exists about the treatment of hemangiomas measuring greater than 20 cm, particularly in regards to transarterial chemoembolization. We present a case of a super-giant hemangioma measuring greater than 20 cm treated with transarterial chemoembolization alone.


IMP-GMP 5'-nucleotidase in reptiles: occurrence in a turtle, a tortoise and three species of snakes.
IMP-hydrolyzing activity, which is reactive with goose anti-pig lung IMP-GMP 5'-nucleotidase (c-N-II: EC.188.8.131.52) serum, was detected in extracts from liver, heart, kidney, spleen, stomach, skeletal muscle and lung from several species of reptiles: The values found in liver (U/mg protein) of one animal were: 4.5 for an ammono-ureotelic turtle (Trionyx sinensis japonicus); 3.7 for an ureo-uricotelic tortoise (Testudo elegans); 13-23 for three species of uricotelic snakes: Elaphe quadrivirgata, Elaphe conspicillata and Elaphe climacophora. These findings suggest that in the liver of snakes, c-N-II may participate in the production of uric acid as an end product of amino acid metabolism.


An achiral ferromagnetic/chiral antiferromagnetic bilayer system leading to controllable size and density of skyrmions.
Magnetic skyrmions are topologically protected domain structures related to the Dzyaloshinskii-Moriya interaction (DMI). To understand how magnetic skyrmions occur under different circumstances, we propose a model for skyrmion formation in a bilayer system of ferromagnetic/antiferromagnetic (FM/AFM) films, in which the bulk DMI is only present in the AFM film. Micromagnetic simulations reveal that skyrmions are formed in this system due to the competition between the DMI and demagnetization energies. A critical interfacial exchange energy (Ai = 6.5 mJ/m2) is determined, above which the competition occurs at its full extent. More skyrmions are formed with increasing external magnetic field till a critical value above which the external field is too large and thus leading to the annihilation of skyrmions. The spacing between two skyrmions can be as small as 45 nm. Our results may give technological implications for future skyrmion applications.


From Isocyanides to Iminonitriles via Silver-mediated Sequential Insertion of C(sp3)-H Bond.
Heterocycles are prevalent constituents of many marketing drugs and biologically active molecules to meet modern medical challenges. Isocyanide insertion into C(sp3)-H bonds is challenging especially for the construction of quaternary carbon centers. Herein, we describe an efficient strategy for the synthesis of α-iminonitrile substituted isochromans and tetrahydroisoquinolines (THIQs) with quaternary carbon centers through silver-triflate-mediated sequential isocyanide insertion of C(sp3)-H bonds, where isocyanide acts as the crucial "CN" and "imine" sources. The produced α-iminonitriles have extensive applications as valuable synthetic building blocks for pharmacologically interesting heterocycles. This protocol could be further applied for the synthesis of iminonitrile-decorated phenanthridines and azapyrene. Interestingly, a remarkable aggregation-induced emission (AIE) effect was first observed for an iminonitrile-decorated pyrene derivative, which may open a particular area for iminonitrile applications in materials science.


Description of the male of Laneella perisi (Mariluis) (Diptera: Calliphoridae) n. comb.
The male Laneella perisi (Mariluis) n. comb. is described based on specimens collected in the Cordillera Oriental (1,370-1,450 m asl), Florencia-Suaza, Caquetá, Colombia. A key to separate the two species of the genus Laneella and illustrations of the male genitalia and female abdomen, terminalia, and spermatheca are also presented.


Reliability of nasopharyngeal PCR for the detection of otopathogens in children with uncomplicated acute otitis media compared to culture.
Otopathogens in acute otitis media (AOM) have implications for care because the likelihood of resolution without antibiotics and optimal antibiotic agent varies by microorganism. We aimed to determine the sensitivity, specificity, positive predictive value, and negative predictive value of nasopharyngeal (NP) qualitative polymerase chain reaction (PCR) for common bacterial otopathogens in children with AOM compared to NP culture. NP flocked swabs collected from enrolled children aged 6 to 35 months with uncomplicated AOM in Denver, CO were tested by culture and multiplex PCR. The sensitivity and negative predictive value of PCR using culture as a reference were high (H. influenzae 93.3%, 98.0%; S. pneumoniae 94.2%, 95.1%; M. catarrhalis 92.3%, 86.4%); whereas the specificity and positive predictive value were lower and varied by organism (54.2%-84.1%, 55.1%-69.2%, respectively). PCR detected 1.5 times more organisms than culture. NP PCR has a high predictive value for excluding otopathogens compared to culture and warrants exploration as a diagnostic tool.


Alcohol Use, Hooking-Up, Condom Use: Is There a Sexual Double Standard?
The purposes of the study were to: (1) identify judgments college students make of peers based on descriptions of drinking, hooking-up, and condom use behaviors; and (2) determine whether participants' judgments differed based on the sex of the person described. Participants (N = 574 college students) completed an online questionnaire that included one of 8 different vignettes (4 vignette types, female or male model). Participants evaluated statements, comprising 3 scales (likability, positive character, negative behavior) relative to the model depicted in the vignette. For female participants, significant effects for vignette type for all 3 scales and significant effects for model sex (negative behavior) were revealed. Male participants only showed significant effects for vignette type for positive character traits. Results should be of value to college level health educators and considered by those involved in drinking behavior and sexual health programming on college campuses.


Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma.
To investigate the association between the occurrence of uterine leiomyoma and two SNPs of the CYP 2A13 and CYP 1A1 genes. Prospective case control study with 132 women with clinically and surgically diagnosed uterine leiomyoma and 260 controls. Genotyping was performed by polymerase chain reaction (PCR) based amplification of CYP 2A13 and CYP 1A1 genes, and restriction fragment length polymorphism (RFLP) analysis. Comparing women with uterine leiomyoma and controls, we demonstrate statistical significant differences of allele frequency and genotype distribution for the CYP 1A1 polymorphism (P = 0.025 and P = 0.046, respectively). Furthermore, for the CYP 2A13 polymorphism we found a significant difference concerning allele frequency (P = 0.033). However, for the genotype distribution, only borderline significance was observed (P = 0.064). The CYP 2A13 and CYP 1A1 SNPs are associated with uterine leiomyoma in a Caucasian population and may contribute to the understanding of the pathogenic mechanisms of uterine leiomyoma.


Glucose tolerance and mortality from ischemic heart disease in an elderly population. Impact of repeated glucose measurements.
The impact of glucose tolerance, measured repeatedly, on the mortality from ischemic heart disease (IHD) was assessed in a cohort of 202 elderly patients, aged 64 to 84 years in 1971, from a general practice. During the period from 1971 to 1975 the participants were examined annually. The area under the glucose tolerance curve (AUC) was used as a summary index, and for every subject the mean AUC over the 5-year period was calculated. This index was most strongly correlated with the mean 60-minute glucose level (r = 0.96). Between 1975 and 1987, 125 participants died, 28.8% of whom died from IHD. No association between a single measurement of glucose tolerance and IHD mortality was observed. However, using the mean AUC over the 5-year period, a positive association was observed, independent of age, sex, and other potential confounders (P = 0.04). These results indicate that glucose tolerance independently predicts mortality from coronary heart disease in an elderly cohort, provided that information on repeated measurements is taken into account. A continuous risk gradient is suggested.


Importance of continuing therapy and maintaining one-month relative dose intensity in sunitinib therapy for metastatic renal cell carcinoma.
Sunitinib is a multikinase inhibitor used as first- and second-line treatment of metastatic renal cell carcinoma. However, there are few reports on the necessary doses of sunitinib to get better clinical outcome in general practice with Japanese patients. We examined the relationship between the efficacy and the necessary doses of sunitinib therapy in a multi-institutional retrospective study. A study population of 94 metastatic renal cell carcinoma patients was eligible for this investigation. The most frequent grade 3/4 laboratory adverse events were decreased platelet (31.9 %) and white blood cell (21.3 %) counts. Treatment was discontinued in 18 patients (31.0 %) initially receiving a 50-mg/day dose within only one course, and median 1-month relative dose intensity was 74.3 %. Median progression-free survival time was 2.3 months in patients treated for only one course and 10.8 months in patients treated for more than one course (P < 0.001). Multivariate analysis showed that only one course of treatment and 60 % and less of 1-month relative dose intensity were significantly associated with inferior progression-free survival (P < 0.001 and P = 0.027, respectively). Moreover, modified Memorial Sloan-Kettering Cancer Center poor risk was significantly associated with progression-free survival time. It is difficult for Japanese patients to continue an initial dose of sunitinib therapy without drug withdrawal. Continuing therapy for more than one course and maintaining more than 60 % of 1-month relative dose intensity were very important in the prolongation of progression-free survival time regardless of the initial treatment doses.


Cardiac magnetic resonance for prediction of arrhythmogenic areas.
Catheter ablation has been widely used to manage recurrent atrial and ventricular arrhythmias. It has been established that contrast-enhanced magnetic resonance can accurately characterize the myocardium. In this review, we summarize the role of cardiac magnetic resonance in identification of arrhythmogenic substrates, and the potential utility of cardiac magnetic resonance for catheter ablation of complex atrial and ventricular arrhythmias.


Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
Low-flow orbital or periorbital venous malformation (OVM) is the most common periorbital vascular lesion that may produce an appearance defect, visual dysfunction, internal hemorrhage, and thrombosis. Intralesional injection of pingyangmycin as a minimally invasive, gentle intervention may have better outcomes in treating low-flow OVMs compared with other currently used methods. To investigate the efficacy and safety of intralesional injection of pingyangmycin for treatment of low-flow OVM. A retrospective, noncomparative, interventional case series was conducted in a single medical center. Thirty-three consecutive patients with low-flow OVMs undergoing intralesional injection of pingyangmycin were included in the study. Injections of 1 to 5 mL of a pingyangmycin 1.5-mg/mL mixture with lidocaine hydrochloride, 2%, were given. Each patient received 1 to 4 injections at an interval of 6 to 8 weeks between February 2002 and January 2013. Mixture volume was determined on a basis of 0.5 mL of solution per cubic centimeter of the lesion. The maximum dose for 1 injection was 8 mg. Clinical observations were well documented before and after treatment. Reduction of lesion volume based on ultrasound-measured volume; overall appearance, including blue color and thickness of lesions before and after treatment; and adverse events were evaluated. Patients received a median of 2 (range, 1-4) intralesional injections of pingyangmycin. The mean pretreatment volume was 4.4 cm3 and posttreatment volume was 1.0 cm3 (t = 4.63; P < .001), with a mean decrease of 84% (range, 28%-100%). Marked to moderate improvement in the volume of the lesions was noticed in 31 eyes (94%; 25 of 33 [76%] with marked improvement and 6 of 33 [18%] with moderate improvement). Improvement occurred in 95% (18 of 19) of superficial lesions, 100% (3 of 3) of deep lesions, and 91% (10 of 11) of combined lesions. We noticed significant improvements in blue color and thickness on the basis of investigator scores from clinical photographs taken before and after treatment. None of the patients had recurrence noted at their final follow-up. Adverse events were limited to swelling of the conjunctiva and localized subcutaneous atrophy. The results of intralesional pingyangmycin injection for treatment of low-flow OVM are encouraging and associated with a low risk of adverse events.


Ultrasound assisted combustion synthesis of TiC in Al-Ti-C system.
This research investigated the effects of high-intensity ultrasound on the combustion synthesis of TiC particles in Al-Ti-C system. The process involved that high-intensity ultrasound was applied on the surface of a compacted Al-Ti-C pellet directly through a Nb probe during the thermal explosion reaction. By comparing with the sample without ultrasonic treatment, it was found that the thermal explosion reaction for synthesizing TiC phase could take place thoroughly in the ultrasonically treated sample. During the process of synthesizing TiC phase, the dissolution of solid graphite particles into the Al-Ti melt, as well as the nucleation and growth of TiC particles could be promoted effectively due to the effects of ultrasound, leading to an enhancement of the formation of TiC particles. Ultrasound assisted combustion synthesis as a simple and effective approach was proposed for synthesizing materials in this research.


Quality of life and burden in carers for persons with chronic obstructive pulmonary disease receiving oxygen therapy.
to assess the quality of life and burden of caregivers to Chronic Obstructive Pulmonary Disease patients on Long-Term Oxygen Therapy and to investigate the factors influencing this burden. this is an analytical, cross-sectional study of 80 persons with Chronic Obstructive Pulmonary Disease on Long-Term Oxygen Therapy who used the specialized outpatient center of the Federal University of São Paulo, and their carers. The following instruments were used: Medical Outcomes Studies 36 (SF-36), Caregiver Burden Scale (CBS) and the Katz Index, along with socio-demographic and clinical variables. the most compromised scores on the carers' quality of life questionnaire were for Vitality and Mental Health. On the Caregiver Burden Scale, the domain which created the greatest burden for carers was the Environment. With the exception of Emotional Involvement, all the domains of quality of life were affected negatively by the domains of caregiver burden. it was shown that carers' quality of life was compromised and that they were overburdened with care tasks, confirming that assisting persons with Chronic Obstructive Pulmonary Disease is an important element in carers' quality of life.


Successful treatment of hydrops fetalis caused by fetomaternal hemorrhage: a case report.
Nonimmune hydrops fetalis is a serious perinatal complication with diverse causes but few successful treatment modalities. The first reported case of hydrops fetalis caused by a massive fetomaternal hemorrhage treated successfully prenatally is presented. A modification of the standard intrauterine transfusion technique was used for therapy. Implications of future treatment are discussed.


Practical syntheses of dyes for difference gel electrophoresis.
The three dyes (two indocyanine and one benzoxazolium) useful in difference gel electrophoresis-methyl Cy5 1, propyl Cy3 2, and the benzoxazolium dye Cy2 3--and their NHS esters have been prepared by efficient routes in good overall yield from inexpensive precursors.


Web 2.0 and chronic illness: new horizons, new opportunities.
"Web 2.0" heralds a breakthrough opportunity for empowering healthcare consumers of all types, and especially for those suffering from different forms of chronic illness. As the author shows using some data gathered from a popular social networking website--MySpace.com--this opportunity may be greatest for heavily stigmatized chronic health issues, such as obesity and mental illness.


Development of a method to measure laccase activity on methoxyphenolic food ingredients and isomers.
We studied the laccase-catalysed oxygenation of methoxyphenolic food ingredients, such as 2-methoxyphenol (guaiacol) and 2,6-dimethoxyphenol (syringol), isomers such as 3- and 4-methoxyphenol, and 2,3-, 3,4- and 3,5-dimethoxyphenol. These methoxyphenolic substrates generate unstable free radicals, which leads to the erroneous determination of steady state rates. The addition of small quantities of ascorbic acid as coupling reagent generates a lag period because it reduces free radicals to methoxyphenols. Measurement of the length of the lag period provides the reliable determination of true steady state rates. We describe the application of this chronometric method to the kinetic characterization of the oxidation of the above methoxyphenolic substrates by Trametes versicolor laccase.


Do microspheres with narrow or standard size distributions localize differently in vasculature? An experimental study in sheep kidney and uterus.
To compare standard embolization microspheres (SMS) with microspheres of very narrow size distribution in terms of physical properties and relative distribution within sheep kidney and uterine artery models of embolization. Standard microspheres (SMS; 500-700 mum and 700-900 mum) were compared with narrow microspheres (NMS) of the same material made with a microfluidic method that produced a much narrower size distribution (600 mum and 800 mum). Characterization of both microspheres was performed in vitro (ie, bead size, water content, and compressive modulus). In the sheep model of kidney and uterus embolization, histopathologic analysis was performed to determine the average vessel size occluded, the number of microspheres per vessel, and the deformation in vivo, with a focus on the localization of the products within the different vascular zones of the organ tissues. In vitro testing showed the physical properties of NMS to be similar to those of SMS. SMS and NMS also possessed the same degree of deformation in vivo. In both embolization models, there were no major differences in the localization of SMS compared with NMS of equivalent mean bead diameters. Compared with SMS with a normal distribution in size range, NMS with a narrow size distribution did not exhibit a very different distribution within the vasculature of the sheep kidney or uterus.


Bioluminescence imaging of fibroblast activation protein-alpha in vivo and human plasma with highly sensitive probe.
Fibroblast activation protein-alpha (FAPα) has emerged as a biomarker of tumor stromal fibroblasts. FAP was overexpressed in stromal fibroblasts of human malignancies and positively correlated with the depth of tumor invasion, lymphatic metastasis, distant metastases, high TNM stage and poor prognosis. However, the circulating FAP levels in the plasma of gastric cancer patients and the relationship between FAP levels and gastric cancer remain unknown. Moreover, probes with super selectivity, extremely high sensitivity, and excellent performance in quantitative detection are still lacking. Herein, we developed the bioluminescent probe BL-FAP for sensitive detection and imaging of endogenous FAP in gastric cancer cells and tissues and plasma from gastric cancer patients. The probe exhibited the high signal-to-noise ratio (15000∼fold), the excellent selectivity (FAP/DPP IV ratio and FAP/PREP ratio = 50000∼ fold), and the high sensitivity (18.1 pg/mL). BL-FAP facilitates monitoring of endogenous FAP in living cells and nude mice bearing MGC-803-luc tumors. More importantly, this probe was successfully applied to the measurement of FAP activity levels in plasma from gastric cancer patients for the first time. A significant enhancement in FAP levels was observed in patients with gastric cancer, suggesting that the FAP level may be a potential diagnostic parameter for gastric cancer.


Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions.
Aluminum (Al), oxidative stress and impaired cholinergic functions have all been related to Alzheimer's disease (AD). The present study evaluates the effect of aluminum on acetylcholinesterase (AChE) and lipid peroxidation in the mouse brain. Mice were loaded by gavage with Al 0.1 mmol/kg/day 5 days per week during 12 weeks. The mice were divided into four groups: (1) control; (2) 10 mg/mL of citrate solution; (3) 0.1 mmol/kg of Al solution; (4) 0.1 mmol/kg of Al plus 10 mg/mL of citrate solution. AChE activity was determined in the hippocampus, striatum, cortex, hypothalamus and cerebellum and lipid peroxidation was determined in the hippocampus, striatum and cortex. An increase of AChE activity was observed in the fourth group (Al + Ci) in the hippocampus (36%), striatum (54%), cortex (44%) and hypothalamus (22%) (p<0.01). The third group (Al) presented a decrease of AChE activity in the hypothalamus (20%) and an enhancement in the striatum (27%). Lipid peroxidation, measured by TBARS (thiobarbituric acid reactive substances), was elevated in the hippocampus and cerebral cortex when compared with the control (p < 0.01). The effect of aluminum on AChE activity may be due to a direct neurotoxic effect of the metal or perhaps a disarrangement of the plasmatic membrane caused by increased lipid peroxidation.


Intracellular calcium: molecules and pools.
The complex nature of intracellular calcium storage pools has been examined at many levels in the past year. Additional molecules associated with calcium stores have been identified and their localization examined. The convergence of molecular biology, cell biology and biochemistry has now allowed the details of calcium signalling to be meaningfully explored.


Cut-dip-budding delivery system enables genetic modifications in plants without tissue culture.
Of the more than 370 000 species of higher plants in nature, fewer than 0.1% can be genetically modified due to limitations of the current gene delivery systems. Even for those that can be genetically modified, the modification involves a tedious and costly tissue culture process. Here, we describe an extremely simple cut-dip-budding (CDB) delivery system, which uses Agrobacterium rhizogene to inoculate explants, generating transformed roots that produce transformed buds due to root suckering. We have successfully used CDB to achieve the heritable transformation of plant species in multiple plant families, including two herbaceous plants (Taraxacum kok-saghyz and Coronilla varia), a tuberous root plant (sweet potato), and three woody plant species (Ailanthus altissima, Aralia elata, and Clerodendrum chinense). These plants have previously been difficult or impossible to transform, but the CDB method enabled efficient transformation or gene editing in them using a very simple explant dipping protocol, under non-sterile conditions and without the need for tissue culture. Our work suggests that large numbers of plants could be amenable to genetic modifications using the CDB method.


Lithium Diffusion in Silicon Encapsulated with Graphene.
The model of a graphene (Gr) sheet putting on a silicon (Si) substrate is used to simulate the structures of Si microparticles wrapped up in a graphene cage, which may be the anode of lithium-ion batteries (LIBS) to improve the high-volume expansion of Si anode materials. The common low-energy defective graphene (d-Gr) structures of DV5-8-5, DV555-777 and SV are studied and compared with perfect graphene (p-Gr). First-principles calculations are performed to confirm the stable structures before and after Li penetrating through the Gr sheet or graphene/Si-substrate (Gr/Si) slab. The climbing image nudged elastic band (CI-NEB) method is performed to evaluate the diffusion barrier and seek the saddle point. The calculation results reveal that the d-Gr greatly reduces the energy barriers for Li diffusion in Gr or Gr/Si. The energy stability, structural configuration, bond length between the atoms and layer distances of these structures are also discussed in detail.


The molecular mechanisms of recombinant chromosome 18 with parental pericentric inversions and a review of the literature.
Chromosomal rearrangements mostly result from non-allelic homologous recombination mediated by low-copy repeats (LCRs) or segmental duplications (SDs). Recent studies on recombinant chromosome 18 (rec (18)) have focused on diagnoses and clinical phenotypes. We diagnosed two cases of prenatal rec (18) and identified precise breakpoint intervals using karyotype and chromosomal microarray analyses. We analyzed the distribution characteristics of breakpoint repetitive elements to infer rearrangement mechanisms and reviewed relevant literature to identify genetic trends. Among the 12 families with 25 pregnancies analyzed, 68% rec (18), 24% spontaneous abortions, and 8% normal births were reported. In the 17 rec (18) cases, 65% presented maternal origin and 35% were paternal. Short-arm breakpoints at p11.31 were reported in 10 cases, whereas the long-arm breakpoints were located at q21.3 (6 cases) and q12 (4 cases). Breakpoints of pericentric inversions on chromosome 18 are concentrated in p11.31, q21.3, and q12 regions. Rearrangements at 18p11.31 are non-recurrent events. ALUs, LINE1s, and MIRs were enriched at the breakpoint regions (1.85 to 3.42-fold enrichment over the entire chromosome 18), while SDs and LCRs were absent. ALU subfamilies had sequence identities of 85.94% and 83.01% between two pair breakpoints. Small repetitive elements may mediate recombination-coupled DNA repair processes, facilitating rearrangements on chromosome 18. Maternal inversion carriers are more prone to abnormal recombination in prenatal families with rec (18). Recombinant chromosomes may present preferential segregation during gamete formation.


Why does the healthy cornea resist Pseudomonas aeruginosa infection?
To provide our perspective on why the cornea is resistant to infection based on our research results with Pseudomonas (P) aeruginosa. We focus on our current understanding of the interplay between bacteria, tear fluid, and the corneal epithelium that determines health as the usual outcome, and propose a theoretical model for how contact lens wear might change those interactions to enable susceptibility to P aeruginosa infection. Use of "null-infection" in vivo models, cultured human corneal epithelial cells, contact lens-wearing animal models, and bacterial genetics help to elucidate mechanisms by which P aeruginosa survives at the ocular surface, adheres, and traverses multilayered corneal epithelia. These models also help elucidate the molecular mechanisms of corneal epithelial innate defense. Tear fluid and the corneal epithelium combine to make a formidable defense against P aeruginosa infection of the cornea. Part of that defense involves the expression of antimicrobials such as β-defensins, the cathelicidin LL-37, cytokeratin-derived antimicrobial peptides, and RNase7. Immunomodulators such as SP-D and ST2 also contribute. Innate defenses of the cornea depend in part on MyD88, a key adaptor protein of TLR and IL-1R signaling, but the basal lamina represents the final barrier to bacterial penetration. Overcoming these defenses involves P aeruginosa adaptation, expression of the type III secretion system, proteases, and P aeruginosa biofilm formation on contact lenses. After more than 2 decades of research focused on understanding how contact lens wear predisposes to P aeruginosa infection, our working hypothesis places blame for microbial keratitis on bacterial adaptation to ocular surface defenses, combined with changes to the biochemistry of the corneal surface caused by trapping bacteria and tear fluid against the cornea under the lens.


(3-{[N-(5-Chloro-2-hy-droxy-phen-yl)oxamo-yl]amino}-prop-yl)dimethyl-aza-nium perchlorate.
In the title compound, C(13)H(19)ClN(3)O(3) (+)·ClO(4) (-), the 3-(di-meth-yl-ammonio)-propyl group of the cation is disordered over two sets of sites with occupancies 0.772 (6) and 0.228 (6). The cations are joined by pairs of N-H⋯O hydrogen bonds into centrosymmetric dimers and these dimers are assembled into chains along the a-axis direction, also through N-H⋯O hydrogen bonds. The perchlorate anions are linked to the hy-droxy groups of the cations by O-H⋯O hydrogen bonds. The positively charged ammonium groups and the anions give rise to folded layers parallel to the ab plane.


Functional outcome following excision of a tumour and reconstruction of the distal radius.
We retrospectively studied the functional and oncological results of 15 patients after reconstruction of the distal radius with osteoarticular allograft or non-vascularised fibular graft following wide excision of an aggressive benign or malignant tumour. Eight patients underwent osteoarticular allograft and seven patients had a non-vascularised autogenous fibular graft reconstruction. The average time for incorporation of the graft was 6 and 5 months in each reconstruction respectively. There was no tumour recurrence after follow up over 41.5-95.5 (average 60.5) months. All patients had good and excellent functional results. Three patients in the group reconstructed with osteoarticular allograft had plate loosening and graft fractures which were successfully treated subsequently.


Magnetic resonance imaging evaluation of shoulder joint in patients with early stage of ankylosing spondylitis: A case-control study.
The goal of this prospective study was to determine the prevalence of shoulder abnormalities on magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) who have normal shoulder X-ray examinations and no clinical shoulder abnormalities using a case-control study. Fifty-three patients with AS according to the SpondyloArthritis international Society (ASAS) criteria were enrolled in the study. Fifty-three patients with no AS served as control subjects. Shoulder MRI examinations of patients in the two groups were analyzed and results were compared. In the patient group, 26/53 patients (49.1%) demonstrated one or two of the defined pathological shoulder MRI findings, whereas 5/53 patients (9.4%) had similar findings in the control group. In the patient group, 11/53 patients (20.8%) had enthesal bone marrow edema, 19/53 patients (35.8%) had increased synovial fluid, 8/53 patients (15.1%) had tendinitis, and 2/53 patients (3.8%) had bursitis. There was statistically significant difference between the patient and control groups in terms of prevalence of enthesal bone marrow edema, increase in synovial fluid, and tendinitis. Shoulder involvement is often overlooked in AS. Knowledge of the early-stage findings of the shoulder involvement due to AS is important to establish an early diagnosis and select treatment options.


Clinical significance of 45XX, t(13q14Q) Robertsonian translocation: unexpected triploidy in third abortion of female carrier.
A case report is described of a female t(13q14q) Robertsonian translocation carrier. Her firstborn daughter appeared to be a carrier of the same translocation. Chromosomal investigation of the third of three subsequent spontaneous abortions revealed a triploidy (69XXX). Literature shows discrepancies in the reported abortion rate in the reproductive performance of t(13q14q) carriers. It is concluded that these could in part be explained by heterogenicity of the study groups due to variable presence of other factors known to influence the abortion risk. In our case report treatment for epilepsy, a luteal phase defect and high numbers of spermatozoa in the sperm count of the husband must be considered as contributory factors. It is recommended to perform systematic investigations in all cases of recurrent abortion even when a chromosomal anomaly is found in one of the partners.


Bimanual microincision phacoemulsification in treating hard cataracts using different power modes.
To compare the performance of the Multiburst mode, the Shortpulse mode and the Whitestar technology of the Sovereign platform in treating hard cataracts with bimanual microincision phacoemulsification. 101 eyes with hard cataracts (nuclear density Grade 3 and Grade 4 or above) were randomized into three groups. Bimanual microincision phacoemulsification was performed using the Multiburst mode, the Shortpulse mode and the Whitestar technology of the Sovereign phacoemulsification machine respectively. The average power, total duration of ultrasonic power release (US Time), effective phaco time, complications, best-corrected visual acuity and rate of corneal endothelial cell loss were measured and compared among the study groups. For hard cataracts of various nuclear densities, average ultrasonic power was highest in the Whitestar group followed by the Shortpulse group. The Multiburst group had the highest US Time, effective phaco time and rate of corneal endothelial cell loss whereas the Whitestar Group had the lowest.The differences between the groups were found to be statistically significant by variation analysis and the Fisher's least significant difference procedure. However, there were no significant differences between the USTime values of the Shortpulse Group and the Whitestar Group (P = 0.051). In the Multiburst Group, wound burn occurred in one eye, and three eyes had abnormal fluctuations in the anterior chamber depth. The Whitestar technology showed the best performance in this study.The Multiburst mode was proved to be a relatively unsuitable ultrasonic power mode in treating hard cataracts with bimanual microincision phacoemulsification.


Do police arrestees substitute legal highs for other drugs?
Some commentators have suggested legal highs (LH) might reduce existing illegal drug use and contribute to lower drug-related harm. However, no studies have specifically investigated substitution between LH and other drugs. To explore the extent to which police detainees substitute LH for illegal drugs. A total of 848 detainees at four central police stations were interviewed about their drug and LH use. Detainees were asked what impact their LH use had on their other drug use (i.e., 'no change', 'more', 'less' or 'stopped'). The detainees were placed into four groups: (i) no LH use; (ii) LH use and 'no change' in drug use; (iii) LH use and 'more' drug use; (iv) LH use and 'less' or 'stopped' drug use. Demographics and levels of drug use in the past month were compared between groups. Ninety-six percent of the LH using detainees had used synthetic cannabinoids (SC), and, of those who reported substituting a drug, 94% had substituted (natural) cannabis. Overall, 54% of the detainee sample had not used SC, 34% had used SC but not changed their cannabis use, 9% had used SC and used 'less' or 'stopped' cannabis use, and 3% had used SC and used 'more' cannabis. The SC users were more likely to have recently been in drug treatment. All those who used SC had higher cannabis consumption regardless of substitution behaviour. The SC users who used 'more' cannabis also used more methamphetamine and ecstasy. Twenty percent of those who used SC and cannabis reported reducing or stopping their cannabis use while 6% increased their cannabis use, suggesting a modest overall reduction in cannabis use. Further research is required to quantify the magnitude of substitution changes, the impact on drug-related harm, and extent to which substitution occurs for other LH and other populations.


Rescue Therapies for AKI in Onconephrology: Rasburicase and Glucarpidase.
Tumor lysis syndrome (TLS) and high-dose methotrexate (HD MTX) toxicity can present with potentially severe complications, including acute kidney injury, in patients with malignancy. Guidelines for using rasburicase and glucarpidase as rescue therapies for TLS and HD MTX toxicity, respectively, are widely used by clinicians intending to mitigate organ toxicity and decrease morbidity and mortality as a consequence of cancer therapy. This review discusses the pathogenesis of TLS and HD MTX-associated toxicity, to understand the mechanism of action of these therapeutic agents and to review the currently available evidence supporting their use.


Presence of serotonin in early chick embryos.
With biochemical analysis and with autoradiography based on injection of 5-[3H]hydroxytryptophan, it was possible to demonstrate the presence of serotonin (5-hydroxytryptamine) in early chick embryos as early as the pre-streak stage. The biochemical analysis which covered the early developmental period (0.5-6 days of incubation) revealed an elevated concentration of serotonin at gastrulation; from then it stayed at a lower and fairly even level. Autoradiographs of embryos at the pre-streak stage, the primitive streak stage, the head fold stage and the 4-6 somites stage indicated the presence of serotonin in intracellular yolk granules and in cell nuclei. Moreover, the amine appeared associated with microfilaments and microtubules, particularly in developing neural cells. Notably the elevated concentration of serotonin at gastrulation, but also the intracellular distribution of the amine during early organogenesis, indicates a prominent role for it in cell-shape changes and morphogenesis in the early chick embryo.


Effects of trifluoperazine on synaptically evoked potentials and membrane properties of CA1 pyramidal neurons of rat hippocampus in situ and in vitro.
The effects of trifluoperazine (TFP), a phenothiazine antipsychotic, on hippocampal activity were studied in the CA1 subfield, both in situ and in slices. In the extracellular studies in situ and in vitro, both somatic population spikes and dendritic excitatory postsynaptic potentials (EPSP) fields were depressed reversibly by TFP, applied by microiontophoresis or in the bath (50-100 microM). Similar effects were also seen during iontophoretic applications of sphingosine in situ. Like TFP (at micromolar concentrations) sphingosine is a dual Ca2+/calmodulin-dependent kinase and protein kinase C (PKC) inhibitor. In intracellular recordings from slices, 50-100 microM TFP induced a slow depolarization and a decrease in input resistance (RN), probably through a gamma-aminobutyric acid (GABA)-mediated increase in Cl- conductance (GCl). TFP also reduced the slow afterhyperpolarization (AHP) as well as electrically evoked inhibitory postsynaptic potentials (IPSPs), but EPSPs were augmented in both amplitude and duration. When CA1 neurons were voltage clamped, TFP elicited a corresponding inward current (consistent with depolarization), increased the leak conductance, and enhanced excitatory synaptic currents; whereas inhibitory synaptic currents and high-threshold Ca2+ currents were reduced. In conclusion, these effects of TFP--which cannot be readily explained by its potent antidopamine action--are in keeping with other evidence that both Ca2+/calmodulin-dependent kinase and PKC can modulate GCl-conductance and high-threshold Ca(2+)-conductance, as well as inhibitory and excitatory postsynaptic currents.


Intakes of Calcium and Phosphorus and Calculated Calcium-to-Phosphorus Ratios of Older Adults: NHANES 2005-2006 Data.
High intakes of dietary phosphorus (P), relative to calcium (Ca) intake, are associated with a lower calcium:phosphorus ratio (Ca:P) ratio which potentially has adverse health effects, including arterial calcification, bone loss, and death. A substantial percentage of older adults (50 to 70 and 71 plus years) who have a higher risk of fracture rate than younger adults typically have low intakes of dietary Ca that are dominated by higher intakes of dietary P from natural and fortified foods, and lower Ca:P ratios than desirable. This investigation was undertaken to examine Ca and P intakes and the resulting Ca:P ratios (by mass) across gender and older adult age groups, using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. NHANES data are based on a cross-sectional sample of the non-institutionalized United States (US) population within various regions. This sample is selected to be representative of the entire US population at all ages. National Cancer Institute (NCI) methods and SAS survey procedures were used for analyses. Ca:P ratios were calculated using total Ca from both foods and supplements, whereas P intakes were calculated from food composition values and supplements. The amounts of P additives in processed foods are not available. Mean Ca and P intakes demonstrated lower intakes of Ca and higher intakes of P compared to current Recommended Dietary Allowances (RDAs). The Ca:P ratios in older male and female adults were influenced by both low-Ca and high-P dietary consumption patterns. Both low total Ca intakes and high P amounts contribute to lower Ca:P ratios, i.e., ~0.7:1.0, in the consumption patterns of older adults than is recommended by the RDAs, i.e., ~1.5:1.0. Whether Ca:P ratios lower than recommended contribute to increased risk of bone loss, arterial calcification, and all-cause mortality cannot be inferred from these data. Additional amounts of chemical P additives in the food supply may actually reduce even further the Ca:P ratios of older adults of both genders, but, without P additive data from the food industry, calculation of more precise ratios from NHANES 2005-2006 data is not possible.


Female throat ornamentation does not reflect cell-mediated immune response in bluethroats Luscinia s. svecica.
The brilliantly coloured throat patch in male bluethroats, Luscinia s. svecica, influences their social mating success and both within- and extra-pair paternity. Female bluethroats are highly variable in their extent of throat coloration, from entirely drab to almost male-like. The ornament in females could be due to a genetic correlation between the sexes. However, it has been shown that male bluethroats prefer brightly coloured females, suggesting that female ornamentation has evolved by direct sexual selection on females through male choice. Males may prefer extravagant traits in females if these reliably signal female quality, such as resistance to disease. We investigated whether variation in the extent of structural and melanin plumage ornamentation in female bluethroats reflects cell-mediated immune response. We caught the females at their nests and measured their immune response as a swelling following a challenge by phytohemagglutinin. An analysis of the data from two years of study revealed that the cell-mediated immune response was not related to female ornamentation. However, the immune response was strongly correlated with female body condition. Thus, our results do not support the hypothesis that female ornament expression signals quality in terms of cell-mediated immunity.


To drain or not to drain in thyroid surgery. A controlled clinical study.
Drainage after thyroid surgery is widely used to prevent postoperative complications by evacuation of blood and fluids. However, to our knowledge no study has shown the benefit of drainage. Therefore, we performed a prospective, randomized study on the rate of complications after drainage or no drainage in thyroid surgery. One hundred fifty patients were allocated to drainage or no drainage. No difference was seen between the two groups according to the experience of the surgeon, type of operation, diagnosis, weight of thyroid specimens, operation time, and hospital stay. All complications were recorded and resulted in two patients receiving reoperation because of bleeding, two permanent laryngeal nerve palsies, one case of permanent hypocalcemia, ten minor hematomas, one wound infection, and one lymphatic leakage. No difference was seen between the groups. This study does not support prophylactic routine drainage after uncomplicated thyroid surgery.