Prevalence and whole genome-based phylogenetic, virulence and antibiotic -resistance characteristics of nasal -Staphylococcus aureus in healthy Swiss horses.

INTRODUCTION: A total of 100 nasal swabs were collected from healthy horses in Switzerland between January 2020 and August 2020. The samples were taken from horses at 40 different stables in 12 different cantons and screened for both methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) using selective agar plates. S. aureus were tested for antibiotic susceptibility by measurement of the minimal inhibitory concentration (MIC) and for virulence factors, antibiotic resistance genes and phylogenetic characteristics using whole genome sequence analysis. Ten horses were found to be positive (10 %, CI: 95 %, 0,0552 - 0,1744) for S. aureus, and four of them harboured MRSA (4 %, CI: 95 %, CI: 1,5 % - 9 %). The MRSA were detected in horses from three different stables in the same region of one canton and MSSA were detected in horses from five different cantons. All the MRSA isolates were genetically related (ST398-t011-IVa), while the MSSA were diverse (ST1-t127/t398/t1508, ST816-t1294, ST133-t1403, ST30-t012). MRSA showed resistance to penicillin (blaZ), cefoxitin (mecA), trimethoprim (dfrK), gentamicin, kanamycin (aac(6')-Ie - aph(2'')-Ia), and tetracycline (tet(M)). MSSA were resistant to either none or one of the antibiotics tested like penicillin (blaZ) and erythromycin (erm(T)). Virulence genes were more abundant in MSSA than in MRSA. This study provides first insight into the prevalence and type of S. aureus in healthy Swiss horses and reveals a source of strains, which may cause infections in both horses and humans.

INTRODUCTION: Au total, 100 écouvillons nasaux ont été prélevés sur des chevaux sains en Suisse entre janvier 2020 et août 2020. Les échantillons ont été prélevés sur des chevaux de 40 écuries différentes dans 12 cantons différents et ont été soumis à un dépistage de S. aureus résistant à la méthicilline (MRSA) et de S. aureus sensible à la méthicilline (MSSA) à l'aide de plaques de gélose sélectives. Les S. aureus ont été testés pour leur sensibilité aux antibiotiques en mesurant la concentration minimale inhibitrice (CMI) et pour les facteurs de virulence, les gènes de résistance aux antibiotiques et les caractéristiques phylogénétiques en analysant la séquence du génome entier. Dix chevaux se sont révélés positifs (10 %, IC: 95 %, 0,0552 ­ 0,1744) pour S. aureus, et quatre d'entre eux étaient porteurs de MRSA (4 %, IC: 95 %, IC: 1,5 % ­ 9 %). Les MRSA ont été détectés chez des chevaux provenant de trois écuries différentes de la même région d'un canton et les MSSA ont été détectés chez des chevaux provenant de cinq cantons différents. Tous les isolats de MRSA étaient génétiquement apparentés (ST398-t011-IVa), tandis que les MSSA étaient divers (ST1-t127/t398/t1508, ST816-t1294, ST133-t1403, ST30-t012). Les MRSA étaient résistants à la pénicilline (blaZ), à la céfoxitine (mecA), au triméthoprime (dfrK), à la gentamicine, à la kanamycine (aac(6')-Ie ­ aph(2")-Ia) et à la tétracycline (tet(M)). Les MSSA étaient résistants à aucun ou à un des antibiotiques testés soit à la pénicilline (blaZ) ou à l'érythromycine (erm(T)). Les gènes de virulence étaient plus abondants chez les MSSA que chez les MRSA. Cette étude donne, pour la première fois, un aperçu de la prévalence et du type de S. aureus chez les chevaux suisses en bonne santé et révèle la présence de souches susceptibles de provoquer des infections chez les chevaux et les humains.

Prevalence and characterization of -methicillin-resistant Macrococcus spp. in food producing animals and meat in Switzerland in 2019.

INTRODUCTION: The prevalence of methicillin-resistant Macrococcus spp. in calves and pigs at slaughterhouses and in retail beef and pork meat was determined using samples taken in 2019 within the framework of the national monitoring of methicillin-resistant Staphylococcus aureus in food producing animals in Switzerland. The isolates were submitted to antimicrobial susceptibility testing of 19 antibiotics and to molecular techniques (e.g. PCR, microarray, WGS) for the identification of resistance genes, elements containing the methicillin resistance genes mec and sequence type (ST). Methicillin-resistant Macrococcus spp. (M. caseolyticus (n=38), M. bohemicus (n=4) and Macrococcus spp. (n=2)) were isolated in 40 of 299 nasal swabs from calves representing a prevalence of 13,38 % (95 % CI, 9,98 % - 17,70 %), and in four of 303 nasal swabs from pigs [1,32 % (95 % CI, 0,36 % - 3,35 %)]. One of 311 samples of Swiss pork meat contained a Macrococcus sp. [0,32 % (95 % CI, 0,01 % - 1,78 %)], and four of 309 beef meat samples (260 domestic and 49 imported) contained M. caseolyticus [1,29 % (95 % CI, 0,35 % - 3,28 %)]. The M. caseolyticus strains belonged to diverse STs, with ST21 being the most common in both pigs and calves. The mecD gene was located on Macrococcus resistance island mecD (McRImecD) in 42 strains and on staphylococcal cassette chromosome mec (SCCmecD) in three strains, while mecB was found on plasmids in four strains. In addition to resistance to ß-lactams, the strains also exhibited resistance to tetracycline (n=17; tet(L), tet(K), tet(M)), streptomycin (n=13; str, ant(6)-Ia, rpsL mutation [K56R in ribosomal protein S12]), kanamycin (n=10; aac(6')-Ie - aph(2'')-Ia, aph(2')-Ib, aph(2')-Ic, ant(4')-Ia), clindamycin (n=9; erm(B), erm(45)), erythromycin (n=9; erm(B), msr(G), erm(45)), fusidic acid (n=9; fusC) and gentamicin (n=1; aac(6')-Ie - aph(2'')-Ia). This study represents the first national prevalence study of methicillin-resistant Macrococcus spp. in pigs, calves, pork and beef meat in Switzerland and revealed a reservoir of genetically diverse strains carrying several resistance traits.

INTRODUCTION: La prévalence des macrococques résistants à la méthicilline chez les veaux et les porcs à l'abattoir et dans la viande de bœuf et de porc au détail a été déterminée à partir d'échantillons prélevés en 2019 dans le cadre du monitoring national des Staphylococcus aureus résistants à la méthicilline chez les animaux de rente en Suisse. Les isolats ont été soumis à des tests de sensibilité à 19 antibiotiques et à des techniques moléculaires (par exemple PCR, microarray, WGS) pour l'identification des gènes de résistance, des éléments contenant les gènes mec responsible de la résistance à la méthicilline, ainsi que du type de séquence (ST). Des macocoques résistants à la méthicilline (M. caseolyticus (n=38), M. bohemicus (n=4) et Macrococcus spp. (n=2)) ont été isolés dans 40 des 299 écouvillons nasaux de veaux, ce qui représente une prévalence de 13,38 % (IC 95 %, 9,98 % ­ 17,70 %), et dans quatre des 303 écouvillons nasaux de porcs [1,32 % (IC 95 %, 0,36 % ­ 3,35 %)]. Un des 311 échantillons de viande de porc suisse contenait un Macrococcus sp. [0,32 % (IC 95 %, 0,01 % ­ 1,78 %)], et quatre des 309 échantillons de viande de bœuf (260 domestiques et 49 importés) contenaient M. caseolyticus [1,29 % (IC 95 %, 0,35 % ­ 3,28 %)]. Les souches de M. caseolyticus appartenaient à divers ST, le ST21 étant le plus fréquent chez les porcs et les veaux. Le gène mecD a été localisé sur des éléments du chromosome McRImecD dans 42 souches et SCCmecD dans trois souches, tandis que le gène mecB se trouvait sur des plasmides dans quatre souches. En plus de la résistance aux ß-lactamines, les souches étaient également résistantes à la tétracycline (n=17 ; tet(L), tet(K), tet(M)), à la streptomycine (n=13 ; str, ant(6)-Ia, mutation rpsL [K56R dans la protéine ribosomale S12]), à la kanamycine (n=10 ; aac(6')-Ie ­ aph(2'')-Ia, aph(2')-Ib, aph(2')-Ic, ant(4')-Ia), clindamycine (n=9 ; erm(B), erm(45)), érythromycine (n=9 ; erm(B), msr(G), erm(45)), acide fusidique (n=9 ; fusC) et gentamicine (n=1 ; aac(6')-Ie ­ aph(2'')-Ia). Cette étude est la première à déterminer prévalence des Macrococcus spp. résistants à la méthicilline chez les porcs, les veaux, la viande de porc et de bœuf en Suisse et a révélé un réservoir de souches génétiquement diverses et portant plusieurs traits de résistance.

Implementation of the North Carolina HIV Bridge Counseling Program to Facilitate Linkage and Reengagement in Care for Individuals Infected with HIV/AIDS.

BACKGROUND Statewide interventions are critical to meeting the goals of the National HIV/AIDS Strategy in this country. In 2012, the North Carolina Division of Public Health developed the North Carolina State Bridge Counselor program to improve linkage to and reengagement in care for newly diagnosed persons and persons living with HIV who were out-of-care.METHODS We reviewed the planning process for the North Carolina State Bridge Counselor program, which involved a review of existing strengths-based counseling models for persons living with HIV, implementation of these models, and communication strategies with other providers. State bridge counselor responsibilities were delineated from the role of disease intervention specialists while retaining the fieldwork capability of disease intervention specialists to conduct outreach and provide services for persons living with HIV throughout the state.RESULTS Program implementation required extensive planning with stakeholders, incorporation of strengths-based counseling models, development of performance standards, and utilization of CAREWare, an HIV care software program to document referrals and data-sharing between state bridge counselors and clinics. By the end of 2014, state bridge counselor services were provided to approximately 60 of the 400 persons living with HIV (15%) who are diagnosed each quarter in North Carolina, with increasing utilization of the program.LIMITATIONS We assessed the development of this intervention specific to the North Carolina Division of Public Health, which may limit its generalizability. However, the State Bridge Counselor program was implemented in both urban and rural areas throughout the state, which increases its applicability to different public health programs throughout the country.CONCLUSION We demonstrated that a statewide State Bridge Counselor program for linkage and reengagement activities can be implemented by leveraging existing infrastructures, electronic medical records, HIV care networks, and fieldwork activities.

New equine antitoxins to botulinum neurotoxins serotypes A and B.

Hyperimmune monovalent antitoxins to botulinum neurotoxin serotypes A and B have been produced by immunizing horses with newly developed formalin toxoids. After primary immunization, horses developed acceptable prophylactic antibody titers (1-5 IU/mL). Three horses received additional toxoid booster injections to induce hyperimmune antibody titers with antitoxin-A and antitoxin-B titers reaching peaks of approximately 2000 IU/mL and 150-625 IU/mL, respectively. Titers were quantified throughout the process by antigen-capture ELISA and by in-vivo neutralization. ELISA titers and neutralization titers correlated (R² ∼0.62-0.92), however, unique correlations between in-vitro and in-vivo titers were observed for each horse. Monovalent antitoxin pools were made by combining plasma that had been collected twice via plasmaphoresis several months after primary immunization. Neutralizing units were established for each pool relative to the current US and WHO reference standards. Titers were determined at the L(+)/10 and L(+)/40 toxin dose for Toxin types A and B, respectively, and U.S. and international units were assigned to each monovalent antitoxin. Avidity of the new Anti-A pool was equivalent to the WHO Anti-A reference at the L(+), L(+)/10 and L(+)/30 dose. Each monovalent plasma pool failed to cross-neutralize other botulinum neurotoxin serotypes indicating a high degree of specificity of each antitoxin for the toxin serotype used during immunization.

Recovery from botulinum neurotoxin poisoning in vivo.

Botulinum neurotoxins cause the disease botulism, which is characterized by prolonged muscle paralysis. In contrast, injections of low doses of purified botulinum neurotoxins do not cause systemic illness but produce localized muscle paralysis that is beneficial for treating several human medical disorders involving uncontrollable muscle contraction. Optimizing the therapeutic efficacy while diminishing adverse reactions requires precise knowledge of toxin potency as well as a clear understanding of how each toxin causes disease. A novel in vivo mouse assay has been used to correlate toxin dosage with the duration of muscle paralysis. Voluntary running activity performed by mice was proportional to the amount of toxin injected into the hind limbs and the subsequent rate of recovery over the ensuing days or weeks was a function of botulinum neurotoxin serotype A or B concentration. Botulinum neurotoxin A produced longer paralysis than botulinum neurotoxin B consistent with human observations. A third serotype, botulinum neurotoxin E, had the shortest duration of action, but unlike the other two toxins, dosage did not influence recovery time. Botulinum neurotoxin A recovery appeared biphasic with the initial phase about two-fold faster than the final phase. Over four weeks, muscle activity had gradually improved following the highest botulinum neurotoxin A dose, reaching about half of the normal running activity. Lower botulinum neurotoxin A doses led to incrementally faster and complete recovery. Persistence of maximum paralysis was exponentially related to botulinum neurotoxin A dosage, with a doubling of the paralysis time occurring with every 25% increase of the toxin concentration. In contrast, the rate of recovery from botulinum neurotoxin B was monophasic relative to toxin dosage and the duration of maximum paralysis was linear relative to dosage. Combinations of botulinum neurotoxin A and B and botulinum neurotoxin A and E were tested and shown to exacerbate paralysis compared with individually administered serotypes.

The role of the synaptic protein snap-25 in the potency of botulinum neurotoxin type A.

Botulinum neurotoxin serotype A (BoNT/A) is distinguished from BoNT/E by longer duration of paralysis and greater potency. The proteolytic activity of BoNT/A in cultures of dissociated spinal cord neurons persists beyond 80 days, whereas BoNT/E activity persists for less than 1 day (Keller, J. E., Neale, E. A. Oyler, G., and Adler, M. (1999) FEBS Lett. 456, 137-142). This single quality of toxin activity can account for the differences observed in the duration of muscle block. In the present work we sought to understand the basis for the apparent greater potency of BoNT/A. BoNT/E cleaves a 26-amino acid fragment from the C terminus of the synaptic protein SNAP-25 whereas BoNT/A removes only nine residues creating a 197-amino acid fragment (P197) that is 95% the length of SNAP-25. We show that inhibition of neurotransmitter release by BoNT/E is equivalent to the damage caused to SNAP-25. However, synaptic blockade by BoNT/A is greater than the extent of SNAP-25 proteolysis. These findings can be explained if P197 produces an inhibitory effect on neurotransmitter release. A mathematical model of the experimentally determined relationship between SNAP-25 damage and blockade of neurotransmission supports this interpretation. Furthermore, neurotransmitter release following complete cleavage of SNAP-25 can be achieved by P197, but with about 5-fold less sensitivity to external Ca(2+). In this case, vesicular release is restored by increasing intracellular Ca(2+). These data demonstrate that P197 competes with intact SNAP-25, but is unable to initiate normal synaptic vesicle fusion in physiological concentrations of Ca(2+).

Persistence of botulinum neurotoxin A demonstrated by sequential administration of serotypes A and E in rat EDL muscle.

Botulinum neurotoxin serotypes A (BoNT/A) and E (BoNT/E) inhibit neurotransmitter release from peripheral cholinergic nerve terminals by cleaving different sites on SNAP-25, a protein involved in synaptic vesicle docking and exocytosis. Since recovery from BoNT/A is protracted, but reversal of BoNT/E intoxication is relatively rapid, it was of interest to determine whether sequential exposure to BoNT/A and BoNT/E could provide insight into the factors responsible for persistence of BoNT action. Extensor digitorum longus (EDL) muscles from rats were injected locally with 5 mouse LD(50) units of BoNT/A or 20 mouse LD(50) units of BoNT/E; these doses were selected to produce total paralysis of EDL muscles within 48 hr. Additional groups of rats were injected sequentially with either BoNT/A followed 48 h later by BoNT/E or with BoNT/E followed 48 h later by BoNT/A. Muscle tensions were elicited in situ in response to supramaximal stimulation of the peroneal nerve to monitor recovery from BoNT intoxication. Tensions returned to 53% and 94% of control, respectively, 7 and 15 days after injection of BoNT/E. In contrast, tensions in muscles injected with BoNT/A returned to only 2% and 12% of control at these time points. Preparations injected sequentially with BoNT/A followed by BoNT/E or with BoNT/E followed by BoNT/A exhibited slow recovery times resembling those recorded in the presence of BoNT/A alone. Pronounced atrophy of the EDL muscle was observed in rats injected with BoNT/A or in those receiving serotype combinations in either sequence, whereas no loss of muscle mass was observed in animals treated with BoNT/E alone. Data suggesting that BoNT/E can enter BoNT/A-treated preparations was obtained by findings that 3,4-diaminopyridine, which readily reversed muscle paralysis after BoNT/A exposure, lost this ability within 1 h of BoNT/E addition. Evidence that BoNT/E was able to cleave SNAP-25 at its characteristic site during sequential neurotoxin exposure was demonstrated by western blot analysis of cultured primary cortical neurons. Since the sequential exposure studies indicate that recovery from BoNT intoxication is lengthened by exposure to serotype A, but not shortened by exposure to serotype E, the duration of BoNT/A intoxication appears to be determined predominantly by the intracellular stability of catalytically active BoNT/A light chain.

Modification of cysteines reveals linkage to acetylcholine and vesamicol binding sites in the vesicular acetylcholine transporter of Torpedo californica.

Properties of cysteinyl residues in the vesicular acetylcholine transporter (VAChT) of synaptic vesicles isolated from Torpedo californica were probed. Cysteine-specific reagents of different size and polarity were used and the effects on [3H]vesamicol binding determined. The vesamicol dissociation constant increased 1,000-fold after reaction with p-chloromercuriphenylsulfonate or phenylmercury acetate, but only severalfold after reaction with relatively small methylmercury chloride or methylmethanethiosulfonate (MMTS). Methylmercury chloride, but not MMTS, protected binding from phenylmercury acetate. Thus, two classes of cysteines react to affect vesamicol binding. Class 1 reacts with only organomercurials, and class 2 reacts with both organomercurials and MMTS. Quantitative analysis of the competition between p-chloromercuriphenylsulfonate and VAChT ligands was possible after defining second-order reaction conditions. The results indicate that each cysteinyl class probably contains a single residue. Acetylcholine protects cysteine 1, but apparently does not protect cysteine 2. Vesamicol, which binds to a different site than acetylcholine does, apparently protects both cysteines, suggesting that it induces a conformational change. The relatively large reagent glutathione removes a substituent from cysteine 1, but not cysteine 2, suggesting that cysteine 2 is deeper in the transporter than cysteine 1 is. The complete sequence of T. californica VAChT is given, and possible identities of cysteines 1 and 2 are discussed.

A critical histidine in the vesicular acetylcholine transporter.

The role of proton binding sites in the vesicular acetylcholine transporter was investigated by characterization of the pH dependence for the binding of [3H]vesamicol [(-)-trans-2-(4-phenylpiperidino)cyclohexanol] to Torpedo synaptic vesicles. A single proton binds to a site with pKa 7.1 +/- 0.1, which is characteristic of histidine, to competitively inhibit vesamicol binding. The histidine-selective reagent diethylpyrocarbonate causes time-dependent inhibition of [3H]vesamicol binding with a rate constant only about 20-fold lower than for reaction with free histidine. Because its pH titration has a simple, ideal shape, this residue probably controls all pH effects in the transporter between pH 6-8. Inhibition of [3H]vesamicol binding by diethylpyrocarbonate was slowed by vesamicol but not acetylcholine, which binds to a separate site. The data suggest that a critical histidine with a pKa of 7.1 is unhindered when reacting with diethylpyrocarbonate. A conformational model for the histidine is proposed to explain why acetylcholine competes with protons but not with diethylpyrocarbonate. A conserved histidine in transmembrane helix VIII possibly is the histidine detected here.

Rapid microplate assay for monitoring botulinum neurotoxin B catalytic activity.

The binding activity of a rabbit polyclonal antiserum raised against a 51-residue peptide (P51) homologous to human VAMP2 (residues 44-94) was examined. Human VAMP2 is an 18-kDa protein located on the external membrane of small synaptic vesicles and is targeted by four of the seven botulinum neurotoxin (BoNT) serotypes (B, D, F and G). The antiserum, designated anti-P51, recognized P51 but exhibited little cross-reactivity with the two cleavage products that result from BoNT/B-mediated proteolysis of P51. The larger of these fragments, designated as P33 (residues 44-76), exhibited a weak but measurable interaction with the antiserum. The smaller cleavage product, designated as P18 (residues 77-94), was not recognized by the antiserum. Anti-P51 was used to monitor BoNT/B light chain (LC)-mediated cleavage of P51 using an indirect ELISA. The serine protease inhibitor phenylmethylsulfonyl fluoride did not inhibit BoNT/B activity, but the zinc chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) and the elastase inhibitor 7- N -phenylcarbamoylamino-4-chloro-3-propyloxyisocoumarin (ICD 1578) produced complete blockade of BoNT/B LC action. Under ideal conditions, it will be possible to evaluate up to seven candidate anti-BoNT/B drugs in triplicate at four concentrations using a single 96-well microtiter plate. These findings indicate that the ELISA will be suitable for rapid screening of BoNT/B inhibitors.

Persistence of botulinum neurotoxin action in cultured spinal cord cells.

Primary dissociated fetal mouse spinal cord cultures were used to study the mechanisms underlying the differences in persistence of botulinum neurotoxin A (BoNT/A) and botulinum neurotoxin/E (BoNT/E) activities. Spinal cord cultures were exposed to BoNT/A (0.4 pM) for 2-3 days, which converted approximately half of the SNAP-25 to an altered form lacking the final nine C-terminal residues. The distribution of toxin-damaged to control SNAP-25 remained relatively unchanged for up to 80 days thereafter. Application of a high concentration of BoNT/E (250 pM) either 25 or 60 days following initial intoxication with BoNT/A converted both normal and BoNT/A-truncated SNAP-25 into a single population lacking the final 26 C-terminal residues. Excess BoNT/E was removed by washout, and recovery of intact SNAP-25 was monitored by Western blot analysis. The BoNT/E-truncated species gradually diminished during the ensuing 18 days, accompanied by the reappearance of both normal and BoNT/A-truncated SNAP-25. Return of BoNT/A-truncated SNAP-25 was observed in spite of the absence of BoNT/A in the culture medium during all but the first 3 days of exposure. These results indicate that proteolytic activity associated with the BoNT/A light chain persists inside cells for > 11 weeks, while recovery from BoNT/E is complete in < 3 weeks. This longer duration of enzymatic activity appears to account for the persistence of serotype A action.

Case-control studies of cancer in Illinois farmers using data from the Illinois State Cancer Registry and the U.S. Census of Agriculture.

A series of case-control studies have been carried out to compare farmers reported to the Illinois State Cancer Registry (ISCR) with other males reported to the ISCR between 1986 and 1988. Data on the number of farms in each Illinois county producing given agricultural commodities were obtained from the United States Census of Agriculture and used as surrogate exposure indicators. Employment as a farmer was found to be associated with cancer of the eye [odds ratio (OR) = 6.49, 95% confidence interval (CI) = 1.78, 23.71], lip (OR = 4.42, 95% CI = 2.46, 7.94), prostate (OR = 1.15, 95% CI = 0.99, 1.35) and leukaemia (OR = 1.51, 95% CI = 1.01, 2.25). Wheat and soybean production were found to be positively associated with leukaemia. Hay and beef production were found to be positively associated with cancer of the prostate.

Cancer in Illinois construction workers: a study.

A series of case-control studies using subjects from the Illinois State Cancer Registry have been conducted. Logistic regression was used to control for age and history of tobacco and alcohol use. Construction workers were consistently found to be younger than other subjects and to have used alcohol and tobacco more often. Significant positive associations between cancer of the stomach and welding (odds ratio [OR] = 2.11, 95% confidence interval [CI] = 1.09, 4.09), lung cancer and employment in the construction industry (OR = 1.18, 95% CI = 1.02, 1.26), and lung cancer and welding (OR = 1.68, 95% CI = 1.03, 2.76) were found. Significant negative associations between cancer of the colon and welding (OR = .54, 95% CI = .29, 1.00), cancer of the prostate and employment in the construction industry (OR = .76, 95% CI = .65, .89), cancer of the prostate and plumbing (OR = .44, 95% CI = .38, .50), cancer of the prostate and metal working (OR = .43, 95% CI = .19, .93), and bladder cancer and employment as an electrician (OR = .60, 95% CI = .36, 1.00) suggests that construction workers did not consistently experience excesses of cancers known to be associated with tobacco use, and an overall excess of sites not known to be related to tobacco use may have occurred.

Relation between population density and cancer incidence, Illinois, 1986-1990.

Many investigators have examined urbanization gradients in cancer rates. The authors used incidence data for 1986 through 1990 from the Illinois State Cancer Registry, a large, population-based incidence registry, to identify race-specific, urban-rural trends in cancer rates. Using population density, they categorized an urbanization gradient into four groups. Five-year, average annual age-adjusted, site-specific incidence rates were calculated for all sex-race strata within each population density group. Monotonic and statistically significant cancer incidence trends across all race-sex groups were found for cancers of the esophagus, liver, lung, female breast and cervix, male prostate, nervous system, non-Hodgkin's lymphomas, and all cancers combined. No trend was observed for blacks that was not also seen for whites; however, significant trends for cancer of the pancreas and Hodgkin's disease were seen for whites but not for blacks. Colon cancer in males was the only sex-specific trend in cancer that can occur in both sexes. Analytic studies for sites with consistent urban-rural trends across all race-sex groups may be fruitful in identifying the aspect of population density, or other unmeasured factor, that contribute to these trends.

Risk factors for lung cancer among nonsmoking Illinois residents.

The purpose of this study was to examine possible risk factors for lung cancer among nonsmokers. The Illinois State Cancer Registry was used to identify all nonsmoking lung cancer cases diagnosed between 1985 and 1987. Subjects were classified as nonsmokers only if their medical record specifically stated that they had never smoked during their lifetime. These cases were compared with nonsmoking colon cancer cases. White male nonsmoking lung cancer cases were more likely to have worked in the construction industry than controls [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.3] and to have worked in the bus service and urban transit industry (OR = 2.6, 95% CI = 1.0-6.9), in the trucking service industry (OR = 2.1, 95% CI = 1.3-3.6), and in blast furnaces, steelworks, and rolling and finishing mills (OR = 1.9, 95% CI = 1.0-3.6). White female cases were more likely to have worked as registered nurses than were the controls (OR = 1.9, 95% CI = 1.0-3.5). Negative associations between lung cancer and farming were found in both white males (OR = 0.6, 95% CI = 0.5-0.7) and white females (OR = 0.1, 95% CI = 0.01-0.6). Several other less plausible associations between employment and lung cancer were also found. To determine whether urban residence and associated air pollution increased the risk of lung cancer for nonsmokers, rates among nonsmokers in Cook County were compared with those in the remainder of Illinois. Cook County rates of nonsmoking lung cancer were elevated among white females and nonwhite females, but not among males. Residences of the white female and nonwhite female lung cancer cases were mapped to determine whether clustering within Chicago had occurred. The absence of observable clustering suggests that the excess of female lung cancer cases in Cook County is not attributable to pollution.

An algorithm for matching anonymous hospital discharge records used in occupational disease surveillance: anonymous record matching algorithm.

The expense of collecting primary data, coupled with limited authority to mandate reporting, requires alternative methods of implementing an occupational disease registry in Illinois. One alternative data source for surveillance of some occupational diseases is hospital discharge records. Because these records lack personal identifiers, it has been impossible historically to match records belonging to the same individual and obtain reliable case estimates. To circumvent this difficulty, an algorithm has been developed to match anonymous hospital discharge records collected from all Illinois hospitals. The algorithm was based on the assumption that specific combinations of occupational disease code, sex, zip code, and date of birth would identify an individual to whom multiple hospitalizations belong. Matching with the algorithm reduced the 1986 case estimates from 597 to 499 for all cases of coal workers' pneumoconiosis, asbestosis, and silicosis.

Faeriefungin: a new broad-spectrum antibiotic from Streptomyces griseus var. autotrophicus.

Faeriefungin, a polyol polyene macrolide lactone antibiotic, was isolated from the mycelium of Streptomyces griseus var. autotrophicus, MSU-32058/ATCC 53668, collected from the soil sample of a fairy ring in an old lawn in Lansing, Michigan. Faeriefungin has some properties similar to the previously reported polyene macrolides, mycoticin and flavofungin, but possesses different physiochemical and biological properties. Aspergillus, Fusarium, Microsporum, Trichophyton, and Alternaria spp. were completely inhibited by faeriefungin at 3.2 micrograms/ml, Candida spp. at 5.5 micrograms/ml, and Pythium, Phialophora, Leptosphaeria spp., and some selected Gram-negative penicillin-resistant strains of Neisseria gonorrhoeae at 16.0 micrograms/ml. At a concentration of 100 ppm, it caused 100% mortality of mosquito larvae (Aedes aegypti, Rockefeller strain) and free-living nematodes (Panagrellus redivivus). Unlike the related polyene macrolides, faeriefungin is crystalline and stable with broad-spectrum antimicrobial and insecticidal activity. Preliminary cytotoxicity studies with human erythrocytes and rat liver epithelial cells indicated that faeriefungin and amphotericin B have comparable toxicity. Solution nmr study has indicated that faeriefungin is a mixture of two compounds, faerifungins A [1] and B [2], and that they differ in the attachment of a H or an Me at C-33.

Pungent spices, ground red pepper, and synthetic capsaicin as onion fly ovipositional deterrents.

In laboratory choice experiments, the spices dill, paprika, black pepper, chili powder, ginger, and red pepper deterredDelia antiqua oviposition by 88-100%. Dose-response choice tests demonstrated that 1 mg of ground cayenne pepper (GCP) placed within 1 cm of artificial onion foliage reduced oviposition by 78%. A synthetic analog of capsaicin, the principal flavor ingredient of red peppers, deterred oviposition by 95% when present at 320 ppm in the top centimeter of sand (the ovipositional substrate). However, in no-choice conditions 10 mg GCP was not an effective deterrent. Sevana Bird Repellent and Agrigard Insect Repellent both use red pepper as a principal ingredient; at recommended field rates, neither of these materials was an effective ovipositional deterrent either in laboratory or field. Capsaicin-based materials do not appear to be candidates for onion maggot control via behavioral modification.

Responses ton-dipropyl disulfide by ovipositing onion flies: Effects of concentration and site of release.

Onion fly females,Delia antiqua (Diptera: Anthomyiidae) laid the most eggs on ovipositional dishes havingn-dipropyl disulfide (Pr2S2) release rates of 1-6 ng/sec from polyethylene capsules placed beneath a sand substrate. When dipropyl disulfide was released from the wax coating of surrogate foliage rather than from the substrate, ovipositing females again responded differentially to various concentrations, laying more eggs around stems containing 0.075 and 0.089 mg/stem. Factorial combinations of several concentrations released from surrogate foliage and substrate showed that releases from surrogate foliage stimulated four times more egg-laying than releases from the substrate. Females tended to lay more eggs around surrogate stems having Pr2S2 at the base rather than on the upper half of foliage. Observations of individual females performing preovipositional examining behaviors on Pr2S2-treated surrogate stems indicated that females tended to land on the upper portions of the foliage, but after landing, spent most of their time examining areas of soil and surrogate within 1 cm of the soil-surrogate foliage interface. Surrogate stems provide a realistic context for investigating effects of plant chemicals on host-acceptance behaviors.