Functional Roles of Neuronal Nitric Oxide Synthase in Neurodegenerative Diseases and Mood Disorders.

Nitric oxide synthase (NOS) is well known for its involvement in the regulation of the nervous, cardiovascular, and immune systems. Neuronal NOS (nNOS) is the most characterized NOS among all the isoforms. It accounts for most of the production of nitric oxide (NO) in the nervous system required for synaptic transmission and neuroplasticity. Previous studies have described the localization of nNOS in specific brain regions of interest. There is substantial evidence in the literature suggesting that nNOS signaling has significant involvement in several disease pathologies. However, the association between brain nNOS expression profiles and disease remains largely unknown. In this review, we attempt to delineate the contribution of nNOS signaling in memory and mood disorders in order to achieve a better understanding of nNOS in disease modulation.

Translating facilitated multimodal online learning into effective person-centred practice for the person living with dementia among health care staff in Australia: an observational study.

BACKGROUND: This paper aims to identify whether health care staff perceive a 12-week online facilitated, multimodal, person-centred care, dementia education program influences their knowledge, skills, behaviour and practice improvement activities in dementia care. In particular it will examine a dementia education program 'Positive Approach to Care of the Older Person with Dementia' (The Program). METHODS: Three clusters of online questions were developed. Participants completed the first cluster at course completion (N = 1455;2013-2016). The second cluster was added into the 2015-2016 exit-surveys to measure clinical practice improvement (CPI) activities implementation (N = 520). Thirdly, all participants were invited to a 2018 follow-up survey (N = 343). The Program was also matched with key factors that are likely to result in effective online dementia education programs. RESULTS: The Program had a 78% completion rate. At course completion (2013-2016, N = 1455), 62% felt that the online forums generated useful discussion and 92% thought their work would support implementing their new knowledge and skills. In 2015-16, participants (N = 520) reported that The Program had influenced their practice in terms of new knowledge (87%), understanding (87%), awareness (88%), and new ideas about delivering dementia care (80%). Almost all (95%) participants indicated they had changed 'an aspect of their own professional practice'. Sixty-three percent had planned to develop a CPI activity. Of those (N = 310), 40% developed a new or improved tool and 21% planned to deliver education or create new resources. The most common CPI activities reported in the 2018 follow-up survey (N = 343) included education (49%) and role modelling of new behaviour (47%). Additionally, 75% indicated their CPI influenced their practice and had influenced patients (53%) and colleagues (53%). Fifty-seven percent reported their projects were sustained for 12 months or more. CONCLUSION: The Positive Approach to Care of the Older Person with Dementia education program can potentially improve training the dementia workforce. Participants perceived that a multimodal online platform facilitated by clinical champions influences knowledge transfer, skills and behaviour, encourages workplace CPI activities. Further effort could be directed towards empowering and supporting care staff on system, procedure and practice change and engaging management to translate training activities into practice.

Infectious bursal disease virus tissue tropism and pathogenesis of the infection in chickens by application of in situ PCR, immunoperoxase and HE staining.

Infectious bursal disease is one of an OIE list of notifiable diseases. Chicken is the only host that manifests clinical signs and its pathogenicity is correlated with the distribution of antigens in organs. This study was conducted to determine disease pathogenesis and virus tissue tropism by in situ PCR, immunoperoxidase staining (IPS), and HE staining. Twenty four chickens were infected with very virulent Infectious Bursal Disease Virus (vvIBDV). Fifteen chickens were kept as a control group. Infected chickens were sacrificed at hrs 2, 4, 6, 12, days 1, 2, 4, and 6 post-inoculation (pi). While, control chickens were euthanized on days 0, 1, 2, 4, and 6 pi. Different tissues were collected, fixed in 10% buffered formalin, and processed. At hr 2 pi, virus was detected in intestinal, junction of the proventriculus and gizzard, cecal tonsil, liver, kidney, and bursa of Fabricius. At hr 4 pi, virus reached spleen, and at hr 6 pi, it entered thymus. At hr 12 pi, virus concentration increased in positive tissues. The latest invaded tissue was muscle on day 1 pi. Secondary viraemia occurred during 12-24 h pi. In situ PCR was the most sensitive technique to highlight obscure points of infection in this study.

Publish or perish: strategies to help rural early career researchers increase publication output.

INTRODUCTION: Researchers are challenged to publish or perish. A range of barriers to writing can result in sub-optimal productivity, particularly for early career researchers. Researchers in rural areas may face additional challenges of distance and limited access to colleagues. Implementing strategies to address some of these obstacles was identified as a priority for a group of early career, rural researchers. METHODS: In late 2010, the Wiljo-Piri Writing Group was established, embarking on fortnightly lunch-time meetings for support, networking and the public setting of writing goals; and arranging pairing of 'writing buddies' committed to writing daily, with contact before and/or after each writing session to provide motivation and accountability. Key measures for improvement were publication output (publications per person per year (PPY)) and perceptions of effectiveness of strategies. RESULTS: Publication output varied between individuals and over time; overall PPY rates improved from 0.5 to 1.25. 'Buddy writing' helped facilitate adherence to routine writing sessions and was associated with perceptions of increased creativity, efficiency, confidence and ability to focus. CONCLUSIONS: Structured peer support can be a powerful tool to create and maintain regular writing practices and increase publication output. 'Buddy writing' is applicable to any research or academic setting, and helps maintain commitment to daily writing sessions. Furthermore, such interventions can provide peer support for those working in rural settings, helping to address issues such as geographical and professional isolation. Suggested key steps in establishing structured peer support are provided.

Factors influencing early retirement intentions in Australian rural general practitioners.

BACKGROUND: The Australian general practice workforce is ageing. This and a trend towards higher exit intentions and earlier retirement make it increasingly important to identify those work and personal factors affecting intention to leave, which are amenable to change. AIMS: To assess the various work, occupational and individual health factors associated with early retirement intentions among Australian rural general practitioners (GPs) that may be amenable to intervention. METHODS: A cross-sectional study of GPs practising in rural Australia. Odds ratios of early retirement intentions across work, occupational and individual health factors were calculated. RESULTS: There were 92 participants (response rate 56%), and 47% of responders intended to retire before 65. GPs with medium to high burnout levels had higher odds of intending to retire. Increased job satisfaction and work ability scores were associated with decreased retirement intentions, whereas increased physical and mental work ability demands were associated with an increase in retirement intentions. Absenteeism was not related to retirement intentions but presenteeism was. GPs reporting any work-related sleep problems were found to have a 3-fold increase in the odds of early retirement intentions. The odds of early retirement intentions also increased with higher psychological distress, worsening general health and longer working hours. CONCLUSIONS: From a health policy reform perspective, the greatest impact on reducing early retirement intentions among ageing GPs could potentially be made by intervening in areas of working hours, burnout and work-related sleep issues, followed by job satisfaction, psychological distress, health, general workability and mental and physical work ability.

Partial and complete retirement due to ill-health among mature age Australians.

OBJECTIVES: An ageing population requires governments to keep older people working longer and delay early retirement. This paper investigates the extent to which common health problems and geographical location are associated with full and partial early retirement among mature-age Australians. STUDY DESIGN: Cross sectional. METHODS: Multinomial logistic regression analysis of self-reported data of 21,719 women and 16,393 men from the 45 and Up Study. OUTCOME MEASURE: retirement status. RESULTS: Women who reported ever having been told by a doctor that they had a stroke, cancer (except melanoma and skin and breast cancer), osteoarthritis, depression, osteoporosis, thrombosis, or anxiety were more likely to be fully retired due to ill-health compared to those without these health problems. Those who reported ever having been told by a doctor that they had depression, breast cancer or osteoarthritis were more likely to be partially retired due to ill-health than those without these health problems. Men who reported ever having been told by a doctor that they had cancer, heart disease, anxiety or depression were more likely to be fullyorpartially retired due to ill-health than those without these health problems. Men who reported having had a stroke, diabetes, thyroid problems, osteoarthritis or osteoporosis were more likely to be fully retired due to ill-health compared to those without these health problems. Men and women living outside major cities were more likely to be fully retired due to ill-health. Men from outer regional areas were also more likely to be partially retired due to ill-health. CONCLUSIONS: To reduce early retirement due to ill-health, health practitioners, governments and employers should address targeted health problems, particularly in areas outside capital cities.

Investigating breast symptoms in primary care: enhancing concordance with current best advice.

The purpose of this study was to determine whether a targeted intervention could improve primary care practitioners' concordance with guidelines regarding management of women with breast symptoms. One hundred and twelve practitioners from randomly selected areas around Australia prospectively audited their investigations for each woman with a new breast symptom over two 12-week periods, before and five months after the release of national guidelines. Between the two audits, doctors received feedback on practice in relation to peers and attended one seminar in their local areas led by specialists from the Royal Australasian College of Physicians and the Royal Australasian College of Surgeons. For five recommendations, there were statistically significant improvements at the second audit in line with standard Investigation of a New Breast Symptom (INBS) guidelines. All these were for investigations of breast lumps. At first audit, there were seven recommendations where practitioners were already managing more than 80% of women in accordance with the INBS, and where there were no statistically significant increases in concordance at second audit. Another six recommendations had lower concordance with the recommendations prior to the release of the guidelines and did not significantly improve at second audit. These tended to be for less-common presentations and where clinical findings were not consistent with other test results. We concluded that a targeted intervention improved physician concordance with current best advice for investigating women who present with new breast symptoms in a primary care setting. Further educational programs are needed to improve investigations for rarer symptoms, and to enhance physicians' confidence in the results of their clinical examinations.

Cancer Information Services: a pre-/post-evaluation of training to promote nationwide consistency of information.

The object of this study was to evaluate whether an integrated training package improved the consistency and accuracy of advice about breast cancer to callers of Cancer Information Services (CIS) in Australia. The study followed a pre-/post-evaluation design and the participants were all CIS officers from the state-based CIS. A computerized database was used which contained the current best advice about breast cancer combined with a 1-day interactive training workshop for all officers of participating CIS. The proportion of responses that accorded with predetermined model answers for each of five scenarios employed by simulated callers during normal working hours at pre-and post-evaluation were then calculated. There were 95 simulated calls during pre-evaluation, and 104 calls post-evaluation. In some cases, such as breast reconstruction, accordance with model answers was high at both pre- and post-test. The proportion of responses on an item that related to a description of lymphoedaema differed from pre-to post-test with P = 0.007; while an item on the appropriateness of discussing genetic testing with general practitioners differed from pre-to post-test with P = 0.003. There was less concordance, both pre- and post-test, for issues related to surgery, hospitalization, familial aspects and Tamoxifen. We concluded that the intervention presents a method of disseminating consistent information across a number of independent CIS. Some areas were identified that require more targeted intervention.

Perceptions of screening mammography among women aged 40-49.

OBJECTIVE: The aim of this study was to survey women aged 40 to 49 to determine their perceptions of the benefits and the downsides of screening mammography for women in this age group, and the degree of support for targeting women aged 40 to 49 in the national BreastScreen program. METHOD: Telephone interviews were used in a two-stage survey of 200 women aged 40 to 49 from across Australia in 1997. Information that outlined some of the evidence for costs and effectiveness of screening in this age group was sent to the women after the first survey. RESULTS: Women saw both benefits and downsides of mammography screening in this age group. Although the proportion of women reporting downsides increased from (39%) to (69%), after reading the information most women (62%) still thought the benefits outweigh the downsides of offering a screening program to women aged 40-49 and the majority (66%) supported the notion of government funding for this. Most women agreed that women aged 40 to 49 have to be informed about all the advantages and disadvantages of screening before making a decision to attend. CONCLUSION: If women aged 40-49 were to be actively recruited to a government screening program, an information campaign should be undertaken that outlines the benefits and downsides of screening mammography to foster informed participation. IMPLICATIONS: Community views are a helpful contribution to debates about policy when existing data are ambiguous.

Prescribing behaviour in clinical practice: patients' expectations and doctors' perceptions of patients' expectations--a questionnaire study.

OBJECTIVES: To examine the effect of patients' expectations for medication and doctors' perceptions of patients' expectations on prescribing when patients present with new conditions. DESIGN: Questionnaire study of practitioners and patients. SETTING: General practice in Newcastle, Australia. SUBJECTS: 22 non-randomly selected general practitioners and 336 of their patients with a newly diagnosed medical condition. MAIN OUTCOME MEASURES: Prescription of medication and expectation of it. RESULTS: Medication was prescribed for 169 (50%) patients. After controlling for the presenting condition, patients who expected medication were nearly three times more likely to receive medication (odds ratio = 2.9, 95% confidence interval 1.3 to 6.3). When the general practitioner thought the patient expected medication the patient was 10 times more likely to receive it (odds ratio = 10.1, 5.3 to 19.6). A significant association existed between patients' expectation and doctors' perception of patients' expectation (chi 2 = 52.0, df = 4, P = 0.001). For all categories of patient expectation, however, patients were more likely to receive medication when the practitioner judged the patient to want medication than when the practitioner ascribed no expectation to the patient. CONCLUSIONS: Although patients brought expectations to the consultation regarding medication, the doctors' opinions about their expectations were the strongest determinants of prescribing.

Characterization of group A streptococci isolated in Kuala Lumpur, Malaysia.

T-agglutination patterns of 190 strains of group A streptococci isolated between January 1989 and December 1993 from body fluids (10), throat culture (56), pus (51) and skin lesions (73) were determined. Mucoid colonial morphology was exhibited by 6.3% (12/190) of the strains on initial isolation. Type T-5,11,27,44 comprised 23.7%, followed by T-1,3,13,B3264 (11.1%), T-4,6 (8.4%) and T-8,25, Imp 19 (7.9%). About 42% (80/190) strains could not be characterized by T agglutination pattern. T-typing of 71 selected strains at WHO Collaborating Center, Minneapolis yielded similar results. Nineteen selected strains were further characterized by M-typing; only three strains were M-typeable. These strains were isolated from throat (M1), sputum (M5) and pus (M12). About 68% (48/71) isolates produced serum opacity factor. These data support the existence of as yet uncharacterized group A streptococcal serotypes in this region.

Microbiology of cerebral abscess: a four-year study in Malaysia.

A prospective study was carried out to determine the aetiology of cerebral abscess in relation to the primary source of infections. Seventy-five patients with cerebral abscess were included in the study in the period January 1985 to December 1988. More than half of the patients studied had single lesions and the overall most common sites were in the frontal and parietal regions. Chronic suppurative otitis media, cyanotic congenital heart diseases and meningitis were among the important predisposing conditions in these patients. Approximately 25% of the patients with cerebral abscesses had no documented antecedent infections. Pure cultures were found to be predominant (66.7%) and sterile cultures were obtained from 10 (13.3%) patients. Streptococci were isolated from 23 (30.7%) patients, the commonest species being Streptococcus milleri. Proteus sp, Pseudomonas aeruginosa, Pseudomonas putrifaciens and Bacteroides sp were almost exclusively found in cerebral abscesses secondary to chronic suppurative otitis media; these organisms were found in mixed cultures. Streptococcus milleri, Bacteroides sp and Eikenella corrodens were found in pure cultures in patients with cyanotic congenital heart disease. In patients with ventriculoperitoneal shunts in-situ, Staphylococcus aureus, Staphylococcus epidermidis and diphtheroids were common. Anaerobes were found in 15 (20.0%) patients, the majority in mixed cultures. Culture, as well as gas-liquid chromatographic analysis of volatile fatty acids of cerebral pus, was carried out to enhance the detection of the anaerobes. Based on these findings, an antibiotic regimen consisting of penicillin, chloramphenicol and metronidazole is recommended as an initial therapy while awaiting culture and sensitivity results.

Use of gas liquid chromatography as an adjunct to conventional bacteriological methods in the diagnosis of anaerobic cerebral abscess.

Forty cases of cerebral abscesses were studied prospectively to establish the microbial agents implicated in these cases. Chronic otitis media (14 patients, 35%), congenital heart disease (five patients, 12.5%),a and meningitis (five patients, 12.5%) were among the important predisposing factors. Streptococcus (14 patients, 35%) was the most common causative pre-isolated, the predominant species being Streptococcus milleri (11 patients, 27.5%). Other organisms isolated included Proteus mirabilis in six patients (15%) and Staphylococcus aureus in five patients (12.5%). Anaerobes (12 patients, 30%), predominantly Bacteroides sp. (eight patients, 20%), played an important role in these cases, the majority of which were isolated in mixed cultures. Gas-liquid chromatographic analysis of pus detected the presence of anaerobes in another 11 cases of cerebral abscess, in which cultures of anaerobes were negative. Therefore, gas-liquid chromotography is useful as an adjunct to conventional bacteriological methods in providing a rapid and sensitive means of detecting anaerobes in pus obtained especially from patients who had received antibiotic therapy prior to hospitalization.

Ceftazidime/metronidazole versus netilmicin/metronidazole in the treatment of perforated appendicitis in children.

One hundred children with peritonitis resulting from a perforated appendix were treated with ceftazidime or netilmicin. Metronidazole was added to both groups to treat the anaerobic organisms commonly associated with the infecting aerobic organisms in peritonitis. Escherichia coli was the most common aerobe found in peritoneal pus. Wound infection occurred in nine patients of the netilmicin group and in none treated with ceftazidime (P less than 0.01). No bacterial resistance was evident in the ceftazidime group, but gram-positive streptococci found in eight patients were resistant to netilmicin. Thus it is recommended that an antibiotic of the penicillin group be added if netilmicin is used to treat peritonitis. The results indicate that ceftazidime was more effective than netilmicin in the treatment of children with peritonitis resulting from a perforated appendix.

Melioidosis with brain abscess.

Central nervous system involvement in melioidosis is rare. We describe a 48 year old woman who developed septicaemia and a brain abscess due to Pseudomonas pseudomallei. Since there is a continuing practical problem in bacteriological confirmation of the aetiological agent, diagnosis of melioidosis has to be made on clinical suspicion.

Pneumococcal infection in hospitalized patients: a four-year study in Malaysia.

A total of 90 cases of pneumococcal infections were identified at a major referral hospital in Kuala Lumpur, Malaysia during a study period of four years. Pneumonia was the most common clinical presentation (41 cases) followed by meningitis (19 cases). Of 48 patients who were followed-up during the microbiology consultation round, 11 died, 9 were children below two years old. Capsular typing was carried out on 57 strains of Streptococcus pneumoniae isolated from blood and body fluids of 43 children and 14 adults. 38 strains isolated from pharyngeal specimens were also typed. Types 6A (11 strains), 6B (7 strains), 14 (8 strains) and 19A (8 strains) predominated in children. The strains from older patients comprised 3 isolates from cerebrospinal fluid (types 18B, 6B and 14), five from blood (4 strains, type 1 and 1 strain, type 4) and six from pus (1 strain, type 14, 3 strains type 23F and 2 strains type 34). The isolates from pharyngeal specimens belonged to capsular type similar to those implicated in infections. 90% of the types reported in this study are included in the 23 valent pneumococcal vaccines. Minimum inhibitory concentrations of penicillin, cefuroxime, chloramphenicol and rifampicin were determined for selected strains. 4.1% of isolates were resistant to penicillin (3/74), 4.5% to cefuroxime (2/44), 6.5% to chloramphenicol (3/46) and 14.6% to rifampicin (6/41).