Reported rationales for HPV vaccination vs. Non-vaccination among undergraduate and medical students in South Carolina.

Objective: We sought to identify factors that influence Human Papillomavirus (HPV) vaccination rates in individuals at two higher education institutions in South Carolina (SC).Participants: We surveyed 1007 students with a mean age and standard deviation of 20.3 ± 3.3 from September 2018 to December 2018.Methods: Participants answered 13 questions, assessing HPV vaccination rates, demographics, and rationales for vaccination vs. non-vaccination.Results: Of 1007 respondents, 700 received HPV vaccination, 165 were unvaccinated, 75 received partial vaccination and 138 were uncertain. Commonalities in HPV vaccination existed between females (p = 0.037), individuals who received standard childhood vaccinations (p = 0.04), and those not native-born in SC (p < 0.001). Of non-vaccinated individuals, 37% "never thought about vaccination," 32% did not perceive a need for vaccination, and 31% reported vaccine safety as reasons for not receiving the vaccine.Conclusions: Promotion of HPV vaccination may benefit from targeting SC natives, males, and individuals who are under-vaccinated or unvaccinated.

Assessment of the behaviour and welfare of laying hens on free-range units.

The aims of this study were twofold: to develop and test an animal-based protocol for the assessment of the physical and emotional elements of the welfare of laying hens on free-range units and to investigate the effects of different approaches to housing and management on the welfare of the birds. The protocol was tested on 25 free-range units for laying hens, each of which was visited on four occasions by one of five trained observers; further information about husbandry, health and productivity was gathered from interviews with the farmers. Measures of the birds' attitude included arousal, noise, flight distance and response to a novel object, measures of their activity included feather pecking, aggression and use of range, and measures of their physical welfare included mortality, body condition and egg quality. Increased arousal was associated with increased flight distance, greater reluctance to approach a novel object and higher levels of feather pecking and feather loss, but the correlation between pecking and feather loss was low. The birds maintained body condition throughout the period of lay. Neither body condition, feather pecking nor feather loss was affected by the extent of beak trimming. Estimated losses (deaths and culls) ranged from 1.8 to 21.4 per cent (median 6.95 per cent). Few birds showed signs of ill health, limb lesions or red mite infestation. No feature of building design had a significant effect on mortality, but there were consistent differences in the birds' attitude, behaviour and performance attributable to the type of floor and the presence or absence of perches, which suggested that the welfare of the hens was inferior when they were housed on plastic floors with no perches.

Reductive amination of 3-ketoanguidin and antitumor activity of the products.

Amine-containing trichothecanes were prepared by reductive aminations of 3-ketoanguidin. In in vivo tests against P388 leukemia, most of them showed an improved activity compared to anguidin though their potency was decreased. 3-Ketoanguidin also produced some unexpected structures: oxazoline 5, dioxalane 7, and alpha-amino nitrile 13.

Phenylalkylamines with potential psychotherapeutic utility. 2. Nuclear substituted 2-amino-1-phenylbutanes.

A series of 2-amino-1-(4-substituted-2,5-dimethoxyphenyl)butanes (Table V) was prepared as analogues of (R)-2-amino-1-(2,5-dimethoxy-4-methylphenyl)butane (1a). 1-(2,5-Dimethoxyphenyl)-2-(N-phthalimido)butane (7) was utilized as a synthetic intermediate common to many of the target compounds. Animal data are presented indicating that most of these analogues have low hallucinogenic potential. Selected compounds were compared with 1a in an avoidance-response acquisition model which differentiates between 1a and the human hallucinogens DOM (2a) and DOET (2b). Structure-activity relationships of these analogues are discussed.

1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil. A highly selective antiherpes simplex agent.

The protected nucleoside 1-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-beta-D-arabinofuranosyl)-5-ethylura cil (10) was prepared by condensation of 3,5-dibenzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (9) with 2,4-bis-O-(trimethylsilyl)-5-ethyluracil (8). The ratio in this coupling reaction has been raised to 17:1 in favor of the desired beta-anomer. Deprotection by aminolysis gave 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil (FEAU, 1) in 67% isolated yield from the bromo sugar 9. In vitro data show that FEAU has activity against herpes simplex virus types 1 and 2 comparable to that of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU, 2), 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU, 3), and acyclovir (ACV, 12). The cellular toxicity of FEAU was found to be much lower than that of the other nucleoside analogues. Biochemical experiments indicate that FEAU has similar affinity toward thymidine kinases encoded by HSV 1 and 2 and a much lower affinity for cellular thymidine kinase than thymidine. The in vivo antiviral effects of FEAU, FMAU, FIAU, and ACV were evaluated against herpes infection in a systemic mouse encephalitis model and a cutaneous guinea pig model. While FEAU showed activity comparable to that of ACV in the systemic infection model, it was superior in the cutaneous herpes infection model.

Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands.

A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the conclusion that naphthalene is a bioisostere of the indole moiety of melatonin. Moreover it appears that the affinity is strongly affected by the size of the substituent of the nitrogen of the amidic function. Many of these ligands give biphasic dose-response curves which suggests that there may be two melatonin receptor subtypes within the ovine pars tuberalis cells. The replacement of naphthalene by benzofuran or benzothiophene did not strongly alter the affinity for the melatonin receptor. In contrast, the benzimidazole analogue was a poor ligand. Compound 7, the naphthalenic analogue of melatonin, a selective ligand of the melatonin receptor and an agonist derivative, has been selected for clinical development.

Structural modifications of anguidin and antitumor activities of its analogues.

Approximately 60 derivatives of anguidin were prepared for evaluation of antitumor activities. Positions 3, 4, 8-10, and 15 were modified, and the resultant derivatives were screened against P-388 leukemia. It was found that introduction of the C3-keto and C3,C8-diketo groups markedly improved the antileukemic activity, whereas epoxidation of the C9-C10 double bond or oxidation of the C15 position diminished its activity. Selected derivatives were further tested in the L1210, B16, Lewis lung, Colon 36, and Colon 38 tumor lines. Among these compounds, 4 beta, 15-diacetoxyscirpene-3,8-dione (54) and 4 beta-(chloroacetoxy)-15-acetoxyscirpene-3,8-dione (55) were found to be most active in various tumors. Inhibitory action of several analogues on protein synthesis was also examined using H-HeLa cells.

Autoradiographic anomaly in 125I-melatonin binding revealed in ovine adrenal.

Conventional in vitro autoradiographical techniques have been used to screen a number of ovine peripheral tissues for the presence of specific 2-[125I]iodomelatonin binding sites. Intense specific labelling (defined as that displaced by 1 microM melatonin) was observed in the adrenal cortex, and less intense specific binding in the spleen. Subsequent attempts to characterize these adrenal binding sites using in vitro binding assays were unsuccessful. The level of specific binding to both crude membranes and to dispersed whole cell preparations was negligible, and was not correlated with increasing protein or cell concentration. Using quantitative in vitro autoradiography, melatonin was found to competitively inhibit 2-[125I]iodomelatonin binding to sections of the adrenal cortex, but with a considerably lower affinity (IC50 of 1 microM) than that obtained for the ovine pars tuberalis (IC50 of 150 pM) under identical conditions. These results suggest that under the conditions of in vitro autoradiography, 2-[125I]iodomelatonin binds to a finite number of non-receptor sites which are restricted to the ovine adrenal gland. The ability to visualize these sites in the present study may arise through the use of an inappropriately high excess of unlabelled melatonin (1 microM). Consequently to avoid this potential problem, non-specific labelling should perhaps more appropriately be defined as binding in the presence of a concentration of melatonin at approximately 100-fold the value of the Kd (i.e. 10 nM).

Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [|]lodomelatonin*.

Abstract A high-affinity, discretely localized melatonin receptor has been characterized and mapped within the brain and pituitary of the Syrian hamster using the high specific activity ligand [(125)|]iodomelatonin and a combination of in vitro autoradiography and membrane homogenate receptor assays. Specific binding of radioligand was found in regions of the epithalamus and hypothalamus in the brain and the pars tuberalis of the pituitary. Excitatory amino-acid lesions destroyed [(125)|]iodomelatonin binding within the brain, demonstrating that binding sites are located on neurons. Analysis of [(125)|]iodomelatonin binding to membrane homogenates of the pars tuberalis revealed a linear relationship between specific ligand binding and the amount of tissue. The time-course of specific binding at 37 degrees C reached equilibrium after 30 min and remained stable thereafter. The addition of increasing concentrations of [(125)|]iodomelatonin alone and in the presence of 1 muM melatonin showed that specific binding reached equilibrium at 80 to 100 pM. Analysis of the saturation isotherm using a one-site binding model was consistent with a single receptor site with a K(d) of 29.3 (+/-5.9 SEM) pM and B(max) of 2.54 (+/-0.19 SEM) fmol/mg protein.

Melatonin receptors: localization, molecular pharmacology and physiological significance.

A pre-requisite to understanding the physiological mechanisms of action of melatonin is the identification of the target sites where the hormone acts. The radioligand 2-[125I]iodo-melatonin has been used extensively to localize binding sites in both the brain and peripheral tissues. In general these binding sites have been found to be high affinity, with Kd in the low picomolar range, and selective for structural analogues of melatonin. Also the affinity of these sites can generally be modulated by guanine nucleotides, consistent with the notion that they are putative G-protein coupled receptors. However, only a few studies have demonstrated that these putative receptors mediate biochemical and cellular responses. In the pars tuberalis (PT) and pars distalis (PD) of the pituitary, the amphibian melanophore and vertebrate retina, evidence indicates that melatonin acts to inhibit intracellular cyclic AMP through a G-protein coupled mechanism, demonstrating that this is a common signal transduction pathway for many melatonin receptors. However in the pars distalis the inhibition of calcium influx and membrane potential are also important mediators of melatonin effects. How many different forms or states of the melatonin receptor exist is unknown, but clearly the identification of the structure of the melatonin receptor(s) and its ability to interact with different G-proteins and signal transduction pathways are quintessential to our understanding of the physiological mechanisms of action of melatonin. In parallel the recent development of new melatonin analogues will greatly aid our understanding of the pharmacology of the melatonin receptor both in terms of the development of potent melatonin receptor antagonists and for the definition of receptor sub-types. The wide species and phylogenic diversity of melatonin binding sites in the brain has probably generated more questions than answers. Nevertheless the localization of melatonin receptors to the suprachiasmatic nucleus of the hypothalamus is at least consistent with circadian effects within the foetus and the adult. In contrast the PT of the pituitary presents an enigma in relation to the seasonal effects of melatonin. A model of how melatonin might mediate the timing of the circannual events through the PT is proposed.

Mycotic cervical carotid aneurysm.

A case of ruptured mycotic aneurysm involving the extracranial carotid artery is presented. Klebsiella was found to be the responsible pathogen. Carotid artery mycotic aneurysms are discussed with emphysis on the dilemma of surgical treatment. After aneurysm resection the carotid flow either must be re-established or the carotid vessels ligated. A review of the literature reveals that the majority of grafts or arterial repairs fail if reconstruction is carried out in an infected field. The consequences of acute carotid artery ligation are reconsidered.

Characterisation of human melatonin mt(1) and MT(2) receptors by CRE-luciferase reporter assay.

A cyclic AMP response element (CRE)-luciferase reporter gene assay was used to characterise the functional responses of human melatonin mt(1) and human melatonin MT(2) receptors, stably expressed in the human embryonic kidney cell line HEK293, to a series of six naphthalenic analogues of melatonin. By comparison to the observed melatonin-mediated inhibition of stimulated luciferase levels the naphthalenic series was identified as comprising agonists, partial agonists and one antagonist of melatonin mt(1) and melatonin MT(2) receptor function. Three of the agonist/partial agonist members of this series were also identified as displaying a functional selectivity for the melatonin MT(2) receptor. Competitive displacement of 2-[125I]iodomelatonin binding to the ovine pars tuberalis melatonin ML(1) receptor demonstrated a close correlation to the observed functional luciferase responses of the human melatonin mt(1) receptor. We conclude that the CRE-luciferase reporter gene assay provides an effective functional screening method for the pharmacological characterisation of human melatonin receptor subtypes.

Generalized anxiety disorder in women.

Women have a higher prevalence of GAD than do men. This ratio holds true in most clinical and general-population samples. Some variations exist, with evidence to suggest the strong impact of environment and life events. Women are sensitive to lifetime adversity and exacerbation of symptoms in conjunction with their menstrual cycle. Comorbidity is a crucial diagnostic factor when treating anyone with GAD, especially women. Most notably, high comorbidity with other anxiety disorders, MDD and alcohol-abuse disorder occurs for women. Overall, although the prevalence of women with GAD is greater than that of men with GAD, the course of illness and prognosis are not qualitatively different. Across varied methodology, data suggest gender-related differences in the metabolism and potentially in the effects and side effects of the various benzodiazepines and antidepressant psychopharmacologic treatments of GAD. Additional research is needed to better understand these differences.

Surgical significance of extrahepatic biliary tree anomalies.

A patient with an anomalous insertion of the right hepatic duct into the cystic duct was noted during cholecystectomy and confirmed by operative cholangiography. This case and related anomalies of the bile ducts are of sufficient importance that, because of the technical difficulties and dangers incidental to their presence, no surgeon who operates on the gallbladder and bile ducts can afford to be unaware of their existence. Adequate exposure, careful dissection, and accurate knowledge of the regional anatomy plus a realization of the frequency and multiplicity of abnormalities of the extrahepatic biliary tree are requisites for safe biliary tract surgery. In addition, carefully performed operative cholangiography can be an indispensable aid in the clarification of anatomic variations. In case of recognized operative injury to the extrahepatic biliary tree, primary repair or biliary-intestinal anastomosis can usually be carried out with good results.

Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants: 3-year results of a pilot study in humans.

BACKGROUND: This study evaluated patients who had been treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded in an absorbable collagen sponge (ACS) in human extraction sites or in sites that required alveolar ridge augmentation. An earlier report on the same patients revealed that after 4 months, implantation of rhBMP-2/ACS was safe, as determined by clinical, radiographic, systemic, and immunological analyses. In this longer-term follow-up, eligible patients were restored with endosseous dental implants in the area treated with rhBMP-2/ACS and bone biopsy samples were taken for histological analysis of the treated human bone tissue. The primary objective was to monitor the long-term safety of patients treated with rhBMP-2/ACS. Another objective was to evaluate the dental implants placed in the sites treated with rhBMP-2. METHODS: Patient safety was evaluated by clinical examinations, periapical radiographs, and occurrence of adverse experiences. Dental implants were evaluated by radiographic and clinical examination. All 12 patients have been followed for 3 years. RESULTS: Two years following surgical implantation of rhBMP-2/ACS, no serious or unexpected adverse experiences occurred. The adverse experiences that did occur were mostly benign and compatible with the dental implant surgeries performed in these patients. No adverse experiences were deemed as related to the rhBMP-2/ACS. Furthermore, no safety concerns in the local area of rhBMP-2/ACS placement were noted, based on oral wound examinations. In the 10 patients (6 extraction socket patients and 4 augmentation patients) who received endosseous implants, all implants were clinically stable at all assessments and all 10 patients have been functionally restored. Histological evaluation of the human bone core biopsies revealed normal bone tissue formation identical to the surrounding native bone. Three-year follow-up clinical examinations revealed that all implants had stable marginal bone levels and healthy peri-implant tissues. CONCLUSIONS: These 3-year results demonstrate that rhBMP-2/ACS can be used safely in human patients. Human bone biopsies reveal normal bone formation in areas treated with rhBMP-2/ACS. Endosseous implants placed in these areas were all stable with no radiographic or clinical complications. The results from this study suggest that rhBMP-2/ACS (0.43 mg/ml) can be safely used in tooth extraction sites and in local ridge augmentation procedures and that endosseous dental implants placed in bony areas treated with rhBMP-2/ACS are stable and can be functionally restored without complication.

Clinical experience with autogenous ascitic fluid infusion for cirrhotic ascites.

Autogenous ascitic fluid infusion was found to be a safe and practical method in dealing with patients suffering advanced liver cirrhosis complicated by massive ascites.

African hamster lymphocytes as a model for immunologic studies.

The mitogenic response of splenic lymphocytes from Mystromys albicaudatus was studied to evaluate the potential of this animal as a model for immunologic research. In response to phytochemagglutinin and concanavalin A, splenic cells from Mystromys, unlike those from mouse strains, incorporate [3H] thymidine optimally in microculture at 10(5) to 2 X 10(5) cells per microculture. Maximum magnitude of incorporation in response to the same doses of mitogen used in mouse splenic lymphocyte microculture is greater than 10(5) cpm. Moreover, this high incorporation at low cell concentration has been observed in cultures from animals ranging from six to 24 months of age. Splenic cells from Mystromys give little or no incorporation with either LPS or PPD in doses mitogenic to mouse lymphocytes. These features of mitogenic response in Mystromys lymphocyte cultures suggest several useful applications to studies of mechanisms of mitogenesis.

[New naphthalenic ligands of melatoninergic receptors]. / Nouveaux ligands naphtaléniques des récepteurs mélatoninergiques.

Twenty three naphthalenic bio-isosteres of melatonin have been synthesized. The main structural variations concerned the acylamino substituents of the side chain and the alkoxy group on the 7-position of the naphthalene. Some of these compounds show greater affinity than melatonin itself for the melatonin receptor. The results of this study provide new informations on the structure affinity relationships and on the mode of interaction at the melatonin binding site.