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Review. et al., Many infectious diseases originating from, or carried by, wildlife affect wildlife conservation and biodiversity, livestock health, or human health. We provide an update on changes in the epidemiology of 25 selected infectious, wildlife-related diseases in Europe (from 2010–16) that had an impact, or may have a future impact, on the health of wildlife, livestock, and humans. These pathogens were selected based on their: 1) identification in recent Europe-wide projects as important surveillance targets, 2) inclusion in European Union legislation as pathogens requiring obligatory surveillance, 3) presence in recent literature on wildlife-related diseases in Europe since 2010, 4) inclusion in key pathogen lists released by the Office International des Epizooties, 5) identification in conference presentations and informal discussions on a group email list by a European network of wildlife disease scientists from the European Wildlife Disease Association, or 6) identification as pathogens with changes in their epidemiology during 2010–16. The wildlife pathogens or diseases included in this review are: avian influenza virus, seal influenza virus, lagoviruses, rabies virus, bat lyssaviruses, filoviruses, canine distemper virus, morbilliviruses in aquatic mammals, bluetongue virus, West Nile virus, hantaviruses, Schmallenberg virus, Crimean-Congo hemorrhagic fever virus, African swine fever virus, amphibian ranavirus, hepatitis E virus, bovine tuberculosis (Mycobacterium bovis), tularemia (Francisella tularensis), brucellosis (Brucella spp.), salmonellosis (Salmonella spp.), Coxiella burnetii, chytridiomycosis, Echinococcus multilocularis, Leishmania infantum, and chronic wasting disease. Further work is needed to identify all of the key drivers of disease change and emergence, as they appear to be influencing the incidence and spread of these pathogens in Europe. We present a summary of these recent changes during 2010–16 to discuss possible commonalities and drivers of disease change and to identify directions for future work on wildlife-related diseases in Europe. Many of the pathogens are entering Europe from other continents while others are expanding their ranges inside and beyond Europe. Surveillance for these wildlife-related diseases at a continental scale is therefore important for planet-wide assessment, awareness of, and preparedness for the risks they may pose to wildlife, domestic animal, and human health., F.R.F. was funded by the Spanish Ministry for the Economy, Industry and Competitiveness (MINECO) through the ‘Ramon y Cajal program.

Objective: Mandibular distraction osteogenesis (MDO) aims to relieve tongue-based airway obstruction in Robin Sequence (RS). We investigated direct laryngoscopy grade (DLG) improvement and difficult airway (DA) resolution following MDO. Design: Retrospective cohort analysis. Setting: Three tertiary care institutions. Patients: Sixty-four infants with RS who underwent a single MDO procedure in their first year of life were identified from January 2010 to January 2019. Main Outcome Measures: The primary outcome was DLG pre- and post-MDO. Secondary outcomes included DA designation, pre- and post-MDO polysomnographic assessment for obstructive sleep apnea (OSA), length of stay, need for gastrostomy, and major/minor adverse events. Results: Median DLG improved from II pre-MDO to I at the time of distractor removal (n = 43, P < .001). No significant change was seen in patients with a third recorded time point (eg, palatoplasty; n = 78, P = .52). Twenty-six (47%) of 55 patients were designated as DA pre-MDO, and 10 (18%) of 55 patients retained the label post-MDO ( P < .01). Five (50%) of these 10 patients appeared to be inappropriately retained. Median obstructive apnea–hypopnea index improved from 38.6 (range 31.2-62.8) pre-MDO to 2.9 (range 1-3.9) post-MDO (n = 12; P = .002). Conclusion: Mandibular distraction osteogenesis allowed for DLG improvement that was stably maintained as well as functional improvement in OSA, with minimal morbidity. Difficult airway designation persisted in the electronic record of some infants despite clinical resolution.

Allostery is a phenomenon observed in many proteins where binding of a macromolecular partner or a small-molecule ligand at one location leads to specific perturbations at a site not in direct contact with the region where the binding occurs. The list of proteins under allosteric regulation includes AGC protein kinases. AGC kinases have a conserved allosteric site, the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF) pocket, which regulates protein ATP-binding, activity, and interaction with substrates. In this study, we identify small molecules that bind to the ATP-binding site and affect the PIF pocket of AGC kinase family members, PDK1 and Aurora kinase. We describe the mechanistic details and show that although PDK1 and Aurora kinase inhibitors bind to the conserved ATP-binding site, they differentially modulate physiological interactions at the PIF-pocket site. Our work outlines a strategy for developing bidirectional small-molecule allosteric modulators of protein kinases and other signaling proteins. Fil: Schulze, Jörg O.. Goethe Universitat Frankfurt; Alemania Fil: Saladino, Giorgio. University College London; Reino Unido Fil: Busschots, Katrien. Goethe Universitat Frankfurt; Alemania Fil: Neimanis, Sonja. Goethe Universitat Frankfurt; Alemania Fil: Süß, Evelyn. Goethe Universitat Frankfurt; Alemania Fil: Odadzic, Dalibor. Goethe Universitat Frankfurt; Alemania Fil: Zeuzem, Stefan. Goethe Universitat Frankfurt; Alemania Fil: Hindie, Valerie. Goethe Universitat Frankfurt; Alemania Fil: Herbrand, Amanda K.. Goethe Universitat Frankfurt; Alemania Fil: Lisa, María Natalia. Instituto Pasteur; Francia. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Alzari, Pedro M.. Instituto Pasteur; Francia Fil: Gervasio, Francesco L.. University College London; Reino Unido Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Goethe Universitat Frankfurt; Alemania. German Cancer Research Center; Alemania

Alternative oxidase (AOX) is a terminal oxidase within the inner mitochondrial membrane (IMM) present in many organisms where it functions in the electron transport system (ETS). AOX directly accepts electrons from ubiquinol and is therefore capable of bypassing ETS Complexes III and IV. The human genome does not contain a gene coding for AOX, so AOX expression has been suggested as a gene therapy for a range of human mitochondrial diseases caused by genetic mutations that render Complex III and/or IV dysfunctional. An effective means of screening mutations amenable to AOX treatment remains to be devised. We have generated such a tool by heterologously expressing AOX from the Pacific oyster (Crassostrea gigas) in the yeast Saccharomyces cerevisiae under the control of a galactose promoter. Our results show that this animal AOX is monomeric and is correctly targeted to yeast mitochondria. Moreover, when expressed in yeast, Pacific oyster AOX is a functional quinol oxidase, conferring cyanide-resistant growth and myxothiazol-resistant oxygen consumption to yeast cells and isolated mitochondria. This system represents a high-throughput screening tool for determining which Complex III and IV genetic mutations in yeast will be amenable to AOX gene therapy. As many human genes are orthologous to those found in yeast, our invention represents an efficient and cost-effective way to evaluate viable research avenues. In addition, this system provides the opportunity to learn more about the localization, structure, and regulation of AOXs from animals that are not easily reared or manipulated in the lab.

There is a current and pressing need for improved cancer therapies. The use of small molecule kinase inhibitors and their application in combinatorial regimens represent an approach to personalized targeted cancer therapy. A number of AGC kinases, including atypical Protein Kinase C enzymes (PKCs), are validated drug targets for cancer treatment. Most drug development programs for protein kinases focus on the development of drugs that bind at the ATP-binding site. Alternatively, allosteric drugs have great potential for the development of future innovative drugs. However, the rational development of allosteric drugs poses important challenges because the compounds not only must bind to a given site but also must stabilize forms of the protein with a desired effect at a distant site. Here we describe the development of a new class of compounds targeting a regulatory site (PIF-pocket) present in the kinase domain and provide biochemical and crystallographic data showing that these compounds allosterically inhibit the activity of atypical PKCs. PS432, a representative compound, decreased the rate of proliferation of non-small cell lung cancer cells more potently than aurothiomalate, an atypical PKC inhibitor currently under evaluation in clinical trials, and significantly reduced tumor growth without side effects in a mouse xenograft model. The druglike chemical class provides ample possibilities for the synthesis of derivative compounds, with the potential to allosterically modulate the activity of atypical PKCs and other kinases. Fil: Arencibia, Jose M.. Universitätsklinikum Frankfurt; Alemania Fil: Fröhner, Wolfgang. Universitat Saarland; Alemania Fil: Krupa, Magdalena. Universitätsklinikum Frankfurt; Alemania Fil: Pastor Flores, Daniel. Universitätsklinikum Frankfurt; Alemania Fil: Merker, Piotr. Universitätsklinikum Frankfurt; Alemania Fil: Oellerich, Thomas. Goethe Universitat Frankfurt; Alemania Fil: Neimanis, Sonja. Universitätsklinikum Frankfurt; Alemania Fil: Schmithals, Christian. Universitätsklinikum Frankfurt; Alemania Fil: Köberle, Verena. Universitätsklinikum Frankfurt; Alemania Fil: Süß, Evelyn. Universitätsklinikum Frankfurt; Alemania Fil: Zeuzem, Stefan. Universitätsklinikum Frankfurt; Alemania Fil: Stark, Holger. Goethe Universitat Frankfurt; Alemania Fil: Piiper, Albrecht. Universitätsklinikum Frankfurt; Alemania Fil: Odadzic, Dalibor. Goethe Universitat Frankfurt; Alemania Fil: Schulze, Jörg O.. Universitätsklinikum Frankfurt; Alemania Fil: Biondi, Ricardo Miguel. Universitätsklinikum Frankfurt; Alemania. German Cancer Consortium; Alemania. German Cancer Research Center ; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

SummaryProtein kinases play important regulatory roles in cells and organisms. Therefore, they are subject to specific and tight mechanisms of regulation that ultimately converge on the catalytic domain and allow the kinases to be activated or inhibited only upon the appropriate stimuli. AGC protein kinases have a pocket in the catalytic domain, the PDK1-interacting fragment (PIF)-pocket, which is a key mediator of the activation. We show here that helix αC within the PIF-pocket of atypical protein kinase C (aPKC) is the target of the interaction with its inhibitory N-terminal domains. We also provide structural evidence that the small compound PS315 is an allosteric inhibitor that binds to the PIF-pocket of aPKC. PS315 exploits the physiological dynamics of helix αC for its binding and allosteric inhibition. The results will support research on allosteric mechanisms and selective drug development efforts against PKC isoforms.

Protein kinase inhibitors with an allosteric mode of action are expected to reach, in many cases, higher selectivity for the target enzyme than ATP-competitive compounds. Therefore, basic research is aiming at identifying and establishing novel sites on the catalytic domain of protein kinases which might be targeted by allosteric inhibitors. We previously published the first structure-activity relationships (SARs) for allosteric activators of protein kinase PDK1. Here, we present the design, synthesis, and SAR data on a series of novel compounds, 4-benzimidazolyl-3-phenylbutanoic acids, that inhibit the atypical protein kinace C (PKC) ζ via binding to the PIF-pocket. Key positions were identified in the compounds that can be modified to increase potency and selectivity. Some congeners showed a high selectivity toward PKCζ, lacking inhibition of the most closely related isoform, PKCι, and of further AGC kinases. Furthermore, evidence is provided that these compounds are also active toward cellular PKCζ without loss of potency compared to the cell-free assay.

The members of the AGC kinase family frequently exhibit three conserved phosphorylation sites: the activation loop, the hydrophobic motif (HM), and the zipper (Z)/turn-motif (TM) phosphorylation site. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates the activation loop of numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites, the activation loop and the Z/TM in the C-terminal extension. We provide evidence that phosphorylation of the Z/TM site of PRK2 inhibits its interaction with PDK1. Our studies further provide a mechanistic model to explain different steps in the docking interaction and regulation. Interestingly, we found that the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2 and do not apply for other AGC kinases.

DNA cleavage is a biochemical hallmark of apoptosis. In humans, apoptotic DNA cleavage is executed by DNA fragmentation factor (DFF) 40. In proliferating cells DFF40 is expressed in the presence of its chaperone and inhibitor DFF45, which results in the formation of the DFF complex. Here, we present a systematic analysis of the nuclear import of the DFF complex. Our in vitro experiments demonstrate that the importin alpha/beta-heterodimer mediates the translocation of the DFF complex from the cytoplasm to the nucleus. Both DFF subunits interact directly with the importin alpha/beta-heterodimer. However, importin alpha/beta binds more tightly to the DFF complex compared with the individual subunits. Additionally, the isolated C-terminal regions of both DFF subunits together bind importin alpha/beta more strongly than the individual C termini. Our results from in vivo studies reveal that the C-terminal regions of both DFF subunits harbor nuclear localization signals. Furthermore, nuclear import of the DFF complex requires the C-terminal regions of both subunits. In more detail, one basic cluster in the C-terminal region of each subunit, DFF40 (RLKRK) and DFF45 (KRAR), is essential for nuclear accumulation of the DFF complex. Based on these findings two alternative models for the interaction of importin alpha/beta with the DFF complex are presented.

International audience; no abstract

Background: Diagnosis of hypertension, treatment, and follow-up depend on accurate measurement. This research study attempted to determine whether family physicians are all measuring blood pressure (BP) according to Canadian guidelines. Methods: A short survey was mailed to all physicians within the Department of Family Medicine, St. Joseph9s Healthcare, Hamilton, Ontario, Canada. Results: Fifty-one percent of the surveys were completed and returned. Eleven of the recommendations were followed “always or most of the time.” BP is measured manually by 63% of the respondents, and the most frequent barrier to following the recommendations was time. Conclusion: The results of the survey indicated that measurement of BP according to Canadian Hypertension Education Program recommendations was felt to be important and conducted in most cases, but there is room for improvement.

Clinical nursing research is an emerging subspecialty that enhances nursing expertise. In an effort to provide a basic educational curriculum on cancer research and clinical trials, a major academic cancer center launched a novel program titled Clinical Research Nursing Grand Rounds that allowed nurses to receive continuing education units. The purpose of the current article is to describe the development and content of the education model, challenges encountered, and implications for oncology nursing education, practice, and research.

Internal hemipelvectomy may be indicated in the treatment of select tumors of the pelvis and lower extremity, and has become our preferred approach due to favorable outcomes. After such extensive resections, which can involve long operative times and significant blood loss, there are often substantial bony and soft tissue deficits. However, it is unclear whether the benefits of reconstruction in these cases outweigh the risks involved. In the largest series to date of internal hemipelvectomy patients, we evaluate the effect of reconstruction on surgical complications, postoperative function, and survival. A retrospective review was performed of all patients who underwent internal hemipelvectomy between 1998 and 2011. Outcomes for patients who underwent reconstruction were compared to outcomes for those who did not. A total of 111 patients underwent internal hemipelvectomy, of which 51 (45.9%) received reconstruction and 60 (54.1%) did not. In cases of reconstruction, 30 (58.8%) involved placement of mesh for abdominal wall and pelvic floor reconstruction, 27 (52.9%) involved a soft tissue flap, and 15 (29.4%) involved a vascularized bone flap to restore pelvic ring continuity. Two concurrent reconstructive procedures were performed in 22 (43.1%) patients. The overall rate of early complications was 19.8%, which occurred in 15.7% of patients who received reconstruction compared to 23.3% in patients who did not (P = 0.35). Late recipient-site complications occurred significantly less often in patients who underwent reconstruction (7.8% vs 26.7%, respectively; P = 0.01). From a functional standpoint, Musculoskeletal Tumor Society scores were higher in patients who underwent reconstruction, although this was not statistically significant (62.8% vs 48.4%, respectively; P = 0.12). The 2 groups were similar with regard to operative time, blood loss, and hospital stay, as well as overall and disease-free survival rates. Overall, these results indicate that immediate reconstruction of internal hemipelvectomy defects significantly reduces the incidence of late recipient-site complications, without an adverse effect on perioperative course or overall function. An algorithm for reconstruction based on these outcomes is presented.

The purpose of this study was to evaluate the extent to which a new patient information package (NPIP) or a mini version of the same package (mini-NPIP) reduces emotional distress and meets the informational needs of patients arriving at a tertiary cancer centre for the first time. A comprehensive package, NPIP, consisting of procedural information regarding cancer centre location, description of the health care team, treatment services, research, educational activities, accommodation and community services provided at the centre; and a condensed version of the same package, mini-NPIP, were developed. Consecutive patients with newly diagnosed breast, gynaecological, lung and prostate cancer, referred to the centre for the first time were prerandomised to receive NPIP, mini-NPIP or no information package. Patients randomised to NPIP or mini-NPIP were mailed the information package at least one week before their first appointment. On arrival at the centre, patients were administered the Brief Symptom Inventory (BSI) which measures psychological distress, and interviewed regarding preferences for information and acceptability of the information packages. Of 465 randomised patients, 161 were excluded post-randomisation and 304 completed the entire interview: 100 were randomised to the NPIP, 102 to the mini-NPIP and 102 to the control group. Emotional distress as measured by the BSI was similar for all groups (P = 0.98). Most patients preferred to receive the information (98%), receive it before the first appointment (84%) and by mail (79%). These preferences were more evident for those given the information packages. The majority of patients found the information packages easy to understand (88%) and useful (89%), and no differences were detected between packages. The cost of production and dissemination of NPIP was more than double the cost for mini-NPIP: $ 8.93 vs $ 3.98 (Canadian dollars) per patient. For patients presenting to a cancer centre for the first time, packages of procedural information do not appear to reduce psychological distress, but are preferred by patients. Given the cost of producing NPIP, mini-NPIP is the preferred approach.

International audience; The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for substrates and as a switch for the transduction of the conformational changes needed for activation or inhibition. We describe the effects of compounds that bind to the PIF-pocket of PDK1. In vitro, PS210 is a potent activator of PDK1, and the crystal structure of the PDK1-ATP-PS210 complex shows that PS210 stimulates the closure of the kinase domain. However, in cells, the prodrug of PS210 (PS423) acts as a substrate-selective inhibitor of PDK1, inhibiting the phosphorylation and activation of S6K, which requires docking to the PIF-pocket, but not affecting PKB/Akt. This work describes a tool to study the dynamics of PDK1 activity and a potential approach for drug discovery.

Protein kinase C-related protein kinases (PRKs) are effectors of the Rho family of small GTPases and play a role in the development of diseases such as prostate cancer and hepatitis C. Here we examined the mechanism underlying the regulation of PRK2 by its N-terminal region. We show that the N-terminal region of PRK2 prevents the interaction with its upstream kinase, the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2. We confirm that the N-terminal region directly inhibits the kinase activity of PRK2. However, in contrast to previous models, our data indicate that this inhibition is mediated in trans through an intermolecular PRK2-PRK2 interaction. Our results also suggest that amino acids 487–501, located in the linker region between the N-terminal domains and the catalytic domain, contribute to the PRK2-PRK2 dimer formation. This dimerization is further supported by other N-terminal domains. Additionally, we provide evidence that the region C-terminal to the catalytic domain intramolecularly activates PRK2. Finally, we discovered that the catalytic domain mediates a cross-talk between the inhibitory N-terminal region and the activating C-terminal region. The results presented here describe a novel mechanism of regulation among AGC kinases and offer new insights into potential approaches to pharmacologically regulate PRK2.

International audience; Protein kinases are key mediators of cellular signaling, and therefore, their activities are tightly controlled. AGC kinases are regulated by phosphorylation and by N- and C-terminal regions. Here, we studied the molecular mechanism of inhibition of atypical PKCζ and found that the inhibition by the N-terminal region cannot be explained by a simple pseudosubstrate inhibitory mechanism. Notably, we found that the C1 domain allosterically inhibits PKCζ activity and verified an allosteric communication between the PIF-pocket of atypical PKCs and the binding site of the C1 domain. Finally, we developed low-molecular-weight compounds that bind to the PIF-pocket and allosterically inhibit PKCζ activity. This work establishes a central role for the PIF-pocket on the regulation of PKCζ and allows us to envisage development of drugs targeting the PIF-pocket that can either activate or inhibit AGC kinases.

Ethical tensions exist regarding the value and practice of acknowledging Indigenous contributions in community-based participatory research (CBPR). Semistructured phone interviews with researchers documented their perspectives on authorship in the scholarly dissemination of their community-based participatory Indigenous research. Thematic analysis resulted in four key ideas: (1) current practices regarding methods of acknowledging community contributions; (2) requirements for shared authorship with individual versus collective/community partners; (3) benefits to sharing authorship with collective/community partners; and (4) risks to sharing authorship with collective/community partners. Findings suggest an emerging but inconsistent practice.

To examine patients' use of and satisfaction with the nurse-staffed Telephone Health Advisory Service (THAS) and physician after-hours care in a rostered Family Health Organization, as well as physicians' satisfaction with both types of services.Cross-sectional telephone survey.A Family Health Organization in Hamilton, Ont.Nineteen family physicians and their patients who used an after-hours service during 9 selected weeks between March and December of 2007.Distribution of encounters directed to the on-call physician or to the THAS; types of health problems; and patient and physician satisfaction.A total of 817 calls were recorded from 774 patients. Of these patients, 606 were contacted and 94.4% (572/606) completed encounter-specific surveys: 358 completed the on-call physician survey and 214 completed the THAS survey. Mean age of respondents was 40.8 years; most were women, and approximately one-third called on behalf of children. Most calls (66.8%, 546/817) were made directly to the on-call physicians. The most common problems were respiratory (34.3%, 271/789), gastrointestinal (10.1%, 80/789), and genitourinary (9.3%, 73/789). Most patients reported being very satisfied with the after-hours care provided by the THAS (62.5%, 125/200) or the on-call physicians (70.9%, 249/351). Almost all callers who bypassed the THAS knew about it (89.8%, 316/352), but either felt their problems were too serious or wished to talk to a physician. Most physicians agreed or strongly agreed that they were satisfied with their colleagues' on-call care (81.0%, 17/21); 47.6% (10/21) agreed that the THAS was helpful in managing on-call duty.When direct after-hours physician contact is available, a minority of patients uses a nurse-staffed triage. Physicians find the arrangements onerous and would prefer to see after-hours care managed and remunerated differently.

The negative cofactor 2 (NC2) is a protein complex composed of two subunits, NC2alpha and NC2beta, and plays a key role in transcription regulation. Here we investigate whether each subunit contains a nuclear localization signal (NLS) that permits individual crossing of the nuclear membrane or whether nuclear import of NC2alpha and NC2beta depends on heterodimerization. Our results from in vitro binding studies and transfection experiments in cultured cells show that each subunit contains a classical NLS (cNLS) that is recognized by the importin alpha/beta heterodimer. Regardless of the individual cNLSs the two NC2 subunits are translocated as a preassembled complex as co-transfection experiments with wild-type and cNLS-deficient NC2 subunits demonstrate. Ran-dependent binding of the nuclear export receptor Crm1/exportin 1 confirmed the presence of a leucine-rich nuclear export signal (NES) in NC2beta. In contrast, NC2alpha does not exhibit a NES. Our results from interspecies heterokaryon assays suggest that heterodimerization with NC2alpha masks the NES in NC2beta, which prevents nuclear export of the NC2 complex. A mutation in either one of the two cNLSs decreases the extent of importin alpha/beta-mediated nuclear import of the NC2 complex. In addition, the NC2 complex can enter the nucleus via a second pathway, facilitated by importin 13. Because importin 13 binds exclusively to the NC2 complex but not to the individual subunits this alternative import pathway depends on sequence elements distributed among the two subunits.

Universal childhood vaccination programs have been key to reductions in child morbidity and mortality caused by common infectious diseases over the past half century. In Ontario, other than the hepatitis B vaccine (which is funded and administered through school-based programs), routine childhood

BACKGROUND: Recent data suggest that although smoking during pregnancy has declined in North America, this has more to do with falling rates of smoking initiation among women of childbearing age than with increased rates of pregnancy-related smoking cessation. One possible explanation is poor exposure to effective stop-smoking strategies. Better information about women who smoke during pregnancy may help target these interventions more effectively. METHODS: The study was a cross-sectional, self-administered survey of a consecutive sample of 916 (40.4% of eligible) women who delivered healthy babies in 1997–98 at a tertiary teaching hospital in Hamilton, Ontario. Our main focus was on health behaviours (smoking, drinking, eating, and exercise habits) before and during pregnancy; but we also included questions about the presence of (other) children and (other) smokers in the household, perceived health status, the subject’s age and level of education, and whether or not the present pregnancy was planned. Factors associated with pregnancy-related smoking cessation were identified using multiple logistic regression. RESULTS: Respondents were better educated and healthier, but smoked at rates similar to women of childbearing age in Hamilton at the time of the survey. Two thirds of prior smokers or 20% of respondents overall continued to smoke during pregnancy. After adjustment for other factors, three factors were associated with ongoing smoking during pregnancy: having other smokers in the household; having other children in the household; and not having post-secondary education. CONCLUSIONS: Many pregnant smokers are not being reached by current stop-smoking strategies. New ways to help these women and their partners are needed.

OBJECTIVE: To determine physicians' reasons for and against participating in a primary care reform (PCR) pilot project, to identify demographic and practice characteristics associated with participation, to gauge physicians' satisfaction with implementation of the project, and to seek suggestions for change. DESIGN: Cross-sectional mailed survey using a self-administered questionnaire. SETTING: Family practices in Hamilton-Wentworth, Ont. PARTICIPANTS: Eighty-two of 107 (76.6%) physicians who participated in the pilot project and 101 of 150 (67.3% of a 60% random sample of the area's remaining generalist physicians) who chose not to participate. MAIN OUTCOME MEASURES: Physicians' primary and secondary motives for participating or not; comments on the pilot project; and subjects' demographic, professional, and practice characteristics. RESULTS: Despite their experience with capitation practice, after controlling for other factors, physicians from health service organizations were no more likely than their fee-for-service colleagues to join the pilot project. Those in large group practices were more likely to participate. Both participants and non-participants were concerned about disrupting call groups, burdening office staff, not having enough time, and whether the project's objectives were achievable. Other key findings were how few patients declined enrolment and how many physicians had unrealistic ideas about the demands of participation and the capabilities of currently available information technology. CONCLUSION: While many Hamilton-area physicians were eligible and willing to participate in a PCR pilot project, many were not. Our findings suggest that physicians and government should clarify their expectations for PCR and that we need to look for better ways to register patients and select information technology for PCR.

Many cancer centers make available to patients written information material to supplement verbal information provided by clinicians. Randomized trials have demonstrated that providing such information can increase patient knowledge and satisfaction. However, little data are available regarding effective means of dissemination of such materials. The purpose of this study was to determine whether providing patients with a personal file folder after their first clinic appointment would improve the dissemination of written information materials and increase patient satisfaction.A before/after study was performed. Consecutive patients with newly diagnosed cancer attending the Hamilton Regional Cancer Centre were selected randomly and interviewed by telephone within 1-2 weeks of the first clinic appointment regarding the number of information pamphlets received, patient satisfaction, and general preference for written information materials. The preintervention evaluation (T1) occurred over a 4-month period followed by the introduction of the personal file folder into the clinical practice. Six weeks after its introduction, the postintervention (T2) evaluation took place over the ensuing 4 months.A total of 300 patients completed the evaluation (150 each in T1 and T2). Responding patients in the two time periods were comparable with respect to background demographic variables. The mean number of information pamphlets received by patients increased with the introduction of the personal file folder from 2.4+/-2.0 standard deviations (SD) in T1 to 3.6+/-2.5 SD in T2 (P=0.0001). The percentage of patients planned for treatment who received treatment-related information increased from 36% (42 of 116 patients) in T1 to 65% (68 of 105 patients) in T2 (P=0.002). Mean patient satisfaction increased from 3.3+/-1.1 SD to 3.8+/-1.0 SD over the 2 time periods (P=0.0001). The majority of patients (87%) believed it was important to receive written information materials.The patient file folder increased the dissemination of written information materials and currently is being incorporated into routine practice.

This is a descriptive of a census survey of telephone contacts to six unit offices of the Metro Hamilton District Canadian Cancer Society (CCS). The survey instrument was also designed to address two a priori hypotheses: that first-time contacts would be systematically different from the population of other callers; and, that some telephone contacts might represent a disguised need for emotional support. We also assessed satisfaction of CCS personnel with the outcome of telephone contacts. Over a four-day survey period, there were 946 telephone contacts of which 158 (17%) were patient related. First-time telephone contacts were more likely to be spouses or relatives/friends of patients as opposed to non-first-time contacts which were more likely to be patients (P = 0.01). A need for emotional support during telephone contact was more likely to be related to an underlying stressful prompting event for the call (P = 0.002). CCS telephone receptionist personnel were relatively less satisfied that callers' needs were met where emotional support was needed, as opposed to calls for service or information only. The results have implications for the orientation and continuing education of CCS personnel dealing with telephone contacts related to patients.

Glucagon-secreting tumors of the pancreatic islets (glucagonomas) produce a distinctive syndrome in which weight loss, diabetes mellitus, anemia,and prominent mucocutaneous findings occur. The cutaneous component-necrolytic migratory erythema--may be polymorphous, but most commonly manifests as erosions and crusts of the groin, perineum, buttocks, distal part of the extremities, and central area of the face. Alternatively, scaly papules and plaques may predominate in these areas. The eruption may resemble such dermatoses as pemphigus foliaceus, acrodermatitis enteropathica, chronic mucocutaneous candidiasis, psoriasis, and severe seborrheic dermatitis. Two patients with chronic, previously undiagnosed dermatoses had necrolytic migratory erythemia, which led to the discovery of glucagonomas present in each. In one patient surgical resection of the tumor resulted in total clearing of the rash within 48 hours. Awareness of this distinctive entity may lead to early diagnosis and, possibly, cure.

Sulconazole nitrate 1.0 percent cream was compared to miconazole nitrate 2.0 percent cream in a double-blind, parallel study involving ninety-six patients with cutaneous dermatophytosis. Both agents were highly effective, with no statistically significant differences in the parameters studied. Among tinea pedis patients, all of seven treated with sulconazole and six of nine treated with miconazole were mycologically cured (negative culture and potassium hydroxide test) at the end of four weeks of twice a day treatment, and there were no relapses by week 9. Among tinea cruris/corporis patients, the rates of mycological cure after three weeks of twice a day treatment with sulconazole or miconazole were, respectively, twenty-nine of thirty-two (91 percent) and 100 percent of thirty one (accompanied in all cases by complete or significant clearing of signs and symptoms); the respective relapse rates were four of twenty-five (16 percent) and eight of twenty-three (35 percent). Miconazole resulted in two cases of severe irritant dermatitis requiring discontinuation of treatment, whereas sulconazole produced no severe irritant reactions.