No 'Christmas holiday effect' in Australia for cardiovascular and stroke mortality.

OBJECTIVES: Cardiovascular events and mortality have shown a higher incidence within the Christmas holiday period in previous studies and in the northern and southern hemisphere. Our study aimed to assess changes in cardiovascular and stroke mortality variation around the Christmas period in Australia. STUDY DESIGN: The study design is a population-based case-control study. METHODS: Daily mortality data attributed to stroke and cardiovascular was compiled from Australia between 1989 and 2015, amounting to approximately 700,000 and 250,000 deaths, respectively. A locally weighted polynomial regression line was used to estimate expected mortality rates during that period and compared with actual results. RESULTS: There was a non-significant increase of 1.08% (P = 0.35) and 0.20% (P = 0.87) for coronary heart disease and stroke mortality, respectively, in the Christmas holiday period. CONCLUSIONS: There is no evidence of an increase in cardiovascular and stroke mortality in the Christmas holiday period in Australia.

Metal Incorporated g-C3N4 Nanosheets as Potential Cytotoxic Agents for Promoting Free Radical Scavenging in Cancer Cell Lines.

Besides numerous advantages, poor penetration, larger size and less efficient nanomaterials are the current challenges in nanomedicine-based therapies. Graphitic carbon nitride (g-C3N4) possesses all the constructive features to overcome the hurdles in cancer therapy. This is a detailed study on the prospects of utilizing g-C3N4 as a therapeutic agent and through this study it has been established that metal incorporations have improved their performance at in vitro levels. g-C3N4 nanomaterial was prepared by simple thermal decomposition process. The synthesized nanosheets were characterized by using UV-visible spectrometer, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and thermo-gravimetric analysis (TG/DTA). The incorporation of metal particles also has been confirmed by the above mentioned methods. Dose dependent cytotoxicity studies were performed on three different cell lines such as A549, PC-3 and MCF-7. The free radical scavenging activity of g-C3N4 nanosheets was promising using 1,1'-diphenyl-2-picrylhydrazyl (DPPH) assay. Cell scavenging activity of ˜45% with DPPH was observed at 100 µl concentrations of Ag/g-C3N4, Zn/g-C3N4 and g-C3N4. The cytotoxicity and free radical scavenging of cancer cell lines was better with metal incorporated g-C3N4 than their bare counterparts. Hence the study of these thin sheets of nanomaterial is encouraging to be explored as one of the future tools for biomedical therapeutics.

Porous chitosan-infused graphitic carbon nitride nanosheets for potential microbicidal and photo-catalytic efficacies.

Supply of safe drinking water is a high-risk challenge faced internationally. Hybrid technologies involving nanomaterials can offer possible solutions to this research involving natural biopolymers. Porous chitosan with a high specific surface area has promising properties but its use as a membrane component in water purification is still rarely reported. Graphitic carbon nitride (g-C3N4) is a carbon nitride allotrope with a graphene-like layered structure that gifts unfamiliar physicochemical properties due to the presence of s-triazine fragments. It is a metal-free semiconductor with a band gap of ∼2.7 eV to ∼3.7 eV; which shows better visible light-activated photocatalyst properties. This work aims at synthesizing graphitic carbon nitride-biopolymer composite and exploring its properties in the field of wastewater treatment. The samples were synthesized via a soft chemical process with urea, as the source material. The flake-like morphology is displayed in the microstructural SEM image. The composition of the material was analyzed using EDS. Thermogram shows that the material is stable up to 500 °C and also confirms the formation of graphitic carbon nitride. In XRD spectra the intensity reduction shows the chitosan inclusion at the nitride site. The band gap of the prepared material was identified to be 2.3, 2.4 eV. The structural properties were analyzed using Fourier Transform Infrared Spectrometer and Raman spectroscopy. FTIR spectra and Raman spectra indicate the stretching vibration modes of CN and CN heterocycles and chitosan inclusion in the carbon nitride network. The photocatalytic activity was done in sunlight and a UV lamp with different dyes for doped and undoped g-C3N4. The doped (Porous/Non-porous chitosan) g-C3N4 showed faster dye degradation in sunlight compared to UV light. A biomolecular interaction study was done using Bovine serum albumin. It shows the material interaction with the BSA protein. The anti-microbial activity was performed on the Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli by disk diffusion method, the chitosan doped g-C3N4 showed good inhibitions against bacterial growth. The current work reveals the impact of nanoscale chitosan nanostructures doped on the optical, microstructural, catalytic, and antimicrobial properties of g-C3N4 nanosheets. This work provides new research options for nanocomposite-based photocatalytic nanomaterial g-C3N4 so that the quality of contaminated water could be improved.

Self-monitoring of Blood Pressure in Patients With Hypertension-Related Multi-morbidity: Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

Immunomodulatory properties of a viral homolog of human interleukin-10 expressed by human cytomegalovirus during the latent phase of infection.

Human cytomegalovirus (HCMV) establishes a latent infection in hematopoietic cells, from which it can reactivate to cause significant disease in immunocompromised individuals. HCMV expresses a functional homolog of the immunosuppressive cytokine interleukin-10 (termed cmvIL-10), and alternate splicing of the cmvIL-10 transcript results in expression of a latency-associated cmvIL-10 transcript (LAcmvIL-10). To determine whether LAcmvIL-10 encodes immunosuppressive functions, recombinant LAcmvIL-10 protein was generated, and its impact on major histocompatibility complex class II (MHC-II) expression was examined on granulocyte macrophage progenitor cells (GM-Ps) and monocytes. LAcmvIL-10 (and cmvIL-10) downregulated MHC-II on the surfaces of both cell types. This downregulation was associated with a decrease in total MHC-II protein and transcription of components of the MHC-II biosynthesis pathway. Unlike cmvIL-10, LAcmvIL-10 did not trigger phosphorylation of Stat3, and its ability to downregulate MHC-II was not blocked by neutralizing antibodies to the human IL-10 receptor, suggesting that LAcmvIL-10 either does not engage the cellular IL-10 receptor or utilizes it in a different manner from cmvIL-10. The impact of LAcmvIL-10 on dendritic cell (DC) maturation was also assessed. In contrast to cmvIL-10, LAcmvIL-10 did not inhibit the expression of costimulatory molecules CD40, CD80, and CD86 and the maturation marker CD83 on DCs, nor did it inhibit proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and tumor necrosis factor alpha). Thus, LAcmvIL-10 retains some, but not all, of the immunosuppressive functions of cmvIL-10. As GM-Ps and monocytes support latent infection, expression of LAcmvIL-10 may enable HCMV to avoid immune recognition and clearance during latency.

Prevention and Reduction of Obesity through Active Living (PROACTIVE): rationale, design and methods.

The Prevention and Reduction of Obesity through Active Living (PROACTIVE) is a randomised controlled trial to evaluate the effectiveness of a behaviourally based physical activity and diet composition programme to prevent and reduce obesity and related comorbidities in a primary healthcare setting. 491 abdominally obese men and women 25-75 years of age who were patients of primary care physicians were randomly assigned to either a usual care group (N = 242) or a behavioural intervention group (N = 249). Those in usual care received general advice from the physician regarding the merits of physical activity and a healthy diet as a strategy for obesity reduction. Those in the behavioural intervention group received an individually designed counselling programme from a specially trained health educator, with respect to physical activity, diet and obesity reduction. The study was designed to provide 95% power in both men and women to detect a 2% (2 cm) difference in waist circumference and 80% power to identify a 15% reduction in the prevalence of the metabolic syndrome, the two primary outcomes. PROACTIVE is the first behavioural intervention study to assess the effects of physical activity and diet on abdominal obesity and associated metabolic risk factors in a primary healthcare setting, include a generalised sample of men and women and examine long-term (24 months) effects. PROACTIVE has the potential to provide the basis for changing clinical practice (primary care) with respect to the prevention and reduction of obesity and related health risks. The purpose of this report is to present and discuss the rationale, design and methods of PROACTIVE.

Assessment of routine screening of pediatric contacts of adults with tuberculosis disease in Tanzania.

SETTING: Ten selected healthcare facilities in Tanzania, March-April 2016. OBJECTIVE: To assess the implementation of screening among pediatric contacts of adults with tuberculosis (TB) disease. DESIGN: Using a mixed-methods approach, we conducted a questionnaire study among sputum smear-positive adult TB patients and abstracted data from their patient cards to assess the implementation of a child contact management (CCM) intervention. We also conducted in-depth interviews with healthcare workers (HCWs) to solicit their views on clinical practices and challenges in CCM. RESULTS: A total of 141 adult smear-positive TB patients reported 396 children living in households; detailed information on 346 (87.4%) was available. Only 37 (10.7%) children were clinically assessed for TB, 5 (13.5%) were diagnosed with TB, and 22 started on isoniazid preventive therapy (IPT) (59.0%). Of the 320 children whose caregivers responded to whether their children had undergone human immunodeficiency virus (HIV) testing, 55 (17.2%) had been tested and one (1.8%) was HIV-positive. Forty-one HCWs described passive CCM without use of contact or IPT registers. CONCLUSION: We identified gaps in the implementation of TB screening, IPT provision, and HIV testing in pediatric contacts of adults with sputum smear-positive TB. Systematic efforts, including increasing HCW training and educating the community, may improve implementation.

A multifaceted intervention to improve treatment of osteoporosis in postmenopausal women with wrist fractures: a cluster randomized trial.

UNLABELLED: In a cluster randomized trial, we evaluated the effect of a multifaceted intervention (directed at both patient and primary care physician) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture. Compared to usual care, women in the intervention practices were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments. INTRODUCTION: Postmenopausal women with wrist fractures are at increased risk of future fragility fractures, yet they frequently do not receive evaluation and treatment for osteoporosis. We set out to evaluate a multifaceted intervention designed to improve management of osteoporosis in older women with recent wrist fractures. METHODS: Cluster randomized trial of 270 women cared for in 119 primary care practices. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario, Canada. Family practices were randomly assigned to either the intervention or usual care. The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician, in addition to an educational package and letter to the women. The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture. RESULTS: The mean age of women was 69(10.9) years. The intervention increased the proportion of women started on osteoporosis medications (28% vs. 10%) of controls, adjusted OR 3.45, 95% CI, 1.58-7.56, p = 0.002) and the proportion who had a bone mineral density (BMD) test (53.3% vs. 26%) of controls, OR 3.38, 95% CI, 1.83-6.26, p < 0.001). In addition to the intervention, having a female physician was a predictor of increased testing and treatment rates. CONCLUSION: A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures.

Stimulatory effects of the putative metabotropic glutamate receptor antagonist L-AP3 on phosphoinositide turnover in neonatal rat cerebral cortex.

1. The effects of the metabotropic glutamate receptor (mGluR) antagonist, L-2-amino-3-phosphonopropionate (L-AP3) on phosphoinositide turnover in neonatal rat cerebral cortex slices has been investigated. 2. At concentrations of < or = 300 microM, L-AP3 inhibited total [3H]-inositol phosphate ([3H]-InsPx) and Ins(1,4,5)P3 mass responses stimulated by the selective mGluR agonist, 1-amino-cyclopentane-1S, 3R-dicarboxylic acid (1S, 3R-ACPD). Comparison with the competitive mGluR antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine ((+/-)-MCPG) clearly demonstrated that L-AP3 caused inhibition by a mechanism that was not competitive, as L-AP3 decreased the maximal response to 1S, 3R-ACPD (by approximately 40% at 300 microM L-AP3) without significantly affecting the concentration of 1S, 3R-ACPD required to cause half-maximal stimulation of the [3H]-InsPx response. 3. In contrast, at a higher concentration L-AP3 (1 mM) caused a large increase in [3H]-InsPx accumulation which was similar in magnitude in both the absence and presence of 1S, 3R-ACPD (300 microM). D-AP3 (1 mM) had no stimulatory effect alone and did not affect the response evoked by 1S, 3R-ACPD. L-AP3 (1 mM) also caused a large increase in Ins(1,4,5)P3 accumulation. The magnitude of the response (4-5 fold increase over basal) approached that evoked by a maximally effective concentration of 1S, 3R-ACPD, but differed substantially in the time-course of the response. The stimulatory effects of 1S, 3R-ACPD and L-AP3 on Ins(1,4,5)P3 accumulation were also similarly affected by decreases in extracellular calcium concentration. 4. Detailed analysis of the inositol phospholipid labelling pattern and the inositol (poly)phosphate isomeric species generated following addition of L-AP3 was also performed. In the continued presence of myo-[3H]-inositol, L-AP3 (1 mM) stimulated a significant increase in phosphatidylinositol labelling, but not that of the polyphosphoinositides, and the inositol (poly)phosphate profile suggested that substantial Ins(1,4,5)P3 metabolism occurs via both 5-phosphatase and 3-kinase routes. 5. A significant stimulatory effect of L-AP3 (1 mM) on [3H]-InsPx accumulation was also observed in neonatal rat hippocampus, and cerebral cortex and hippocampus slices prepared from adult rat brain. 6. These data demonstrate that whilst L-AP3 antagonizes mGluR-mediated phosphoinositide responses at concentrations of < or = 300 microM, higher concentrations substantially stimulate this response. The ability of (+/-)-MCPG (1 mM) to attenuate significantly L-AP3-stimulated [3H]-InsPx accumulation, suggests that both the inhibitory and stimulatory effects of L-AP3 may be mediated by mGluRs.

End-stage renal disease: factors affecting referral decisions by family physicians in Canada, the United States, and Britain.

The objective of this study is to determine how patient age, sex, creatinine level, and comorbidity affect referral decisions for the treatment of end-stage renal disease (ESRD) and whether these decisions are affected by physician characteristics in three countries: Canada, the United States, and Britain. A vignette-based questionnaire was mailed to a random sample of family physicians in Ontario, Canada (1,818 physicians); all family physicians in the state of New York (1,814 physicians); and a sample of general practitioners from the south of England (2,228 physicians) in 1996. Physicians were presented with clinical scenarios involving a patient with varying degrees of renal insufficiency and a complicating comorbidity, including angina, diabetes, cancer, mental illness, or socioeconomic circumstances. They were asked to indicate the likelihood of referral. Half the physicians received a questionnaire describing a male patient, and half, a female patient. Mean creatinine levels at which physicians would refer were 260 micromol/L for British physicians, 297 micromol/L for Canadian physicians, and 340 micromol/L for American physicians. No difference in referral rates was found based on the sex of the patient or physician. Sixty-five percent of American and Canadian physicians would refer regardless of patient age, but only 49% of British physicians would do so. Family physicians in the United States, Canada, and Britain function as gatekeepers for patients with ESRD. They are less likely to refer based on increasing severity of comorbid conditions. They also discriminate based on age, but not sex.

Men and women residents' experiences with women's health care in a family medicine center.

PURPOSE: To address the experience in women's health care available at the Queen's University Faculty of Medicine family residency program and to compare the amounts and types of experiences of men and women residents. METHOD: A retrospective analysis was made of 70,805 patient encounters with family medicine residents at the Queen's University Family Medicine Centre over a five-year period (June 1988-May 1993). Patient-encounter files contained patient, staff, and resident information, as well as service and diagnostic codes. Statistical analysis was done using a two-tailed Student's t-test to compare the mean numbers of encounters with the women patients for the men and women residents in ten service and diagnostic categories. RESULTS: Of the 70,805 patients, 65.1% were women. The mean numbers of patients seen by the 45 men residents (534) and the 90 women residents (519) did not differ significantly. The percentages of the women patients seen by the men and the women residents (58.6% and 68.4%, respectively), however, differed significantly. The mean ages of the women patients seen by the men and the women residents (44.5 years and 39.2 years, respectively) also differed significantly. The women had significantly more encounters with the women patients in five of the ten categories studied. CONCLUSION: The differences between the men and women residents' experiences was significant in several areas. A potentially confounding factor is that the women may have been preferentially placed in team areas with all women staff physicians and the men placed in team areas with all men staff physicians. As family medicine programs aim for levels of exposure that are sufficient and similar for men and women residents, it is important that they evaluate the clinical opportunities for residents in women's health and work to ensure that both men and women residents receive adequate exposure in this area. One step in this direction might be gender-balanced patient populations, which might be obtained by ensuring gender-balanced clinical teams.

Prevalence of cervical pathogens in women with and without inflammatory changes on smear testing.

OBJECTIVE: To assess correlation between nonspecific cervicitis, inflammation, or exudate on cervical smears tests and confirmed presence of known cervical pathogens. DESIGN: Investigation of women attending a family practice clinic for smear test by microbiological screening for Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, Candida species, group B streptococcus, Gardnerella vaginalis, and Neisseria gonorrhoeae. SETTING: Family practice teaching clinic in a university hospital. PATIENTS: 411 women presenting for a smear test. MAIN OUTCOME MEASURES: Prevalence of genital infections associated with presence or absence of inflammatory changes on cervical smear. RESULTS: Of the 132 women with inflammatory changes on cervical smear, 64 (48%) had positive cultures. Of the 248 without inflammatory changes, 117 (47%) had positive cultures. Subgroup analysis on individual organisms also showed no significant difference between the two groups. CONCLUSION: Reports of inflammatory changes on cervical smear testing are a poor indicator of infection.

Functional testosterone: biochemical assessment of hypogonadism in men--report from a multidisciplinary workshop hosted by the Ontario Society of Clinical Chemists.

OBJECTIVES: In 2004, the Ontario Society of Clinical Chemists (OSCC) held an invitational multidisciplinary workshop to establish the most reliable, cost-effective approach to the biochemical assessment of hypogonadism in men. METHODS: Specialists across Canada in clinical biochemistry, endocrinology, family medicine and urology were invited to participate in this workshop which included individual presentations and a consensus component addressing two challenge statements: 1) 'Determinations for total testosterone (TT) are equivalent to those for bioavailable testosterone (BAT) or calculated BAT (cBAT) or free testosterone (FT) (by analogue radioimmunoassay or equilibrium dialysis) or calculated FT (cFT)'; 2) 'There is no good evidence that borderline low testosterone concentrations in men should be treated'. The main outcomes were to identify what agreement exists in Canada, what issues were still controversial, and what research remains to be addressed. RESULTS: Six recommendations based on expert opinion addressed these main themes: investigate with morning total testosterone (TT) followed by repetition and reflexive testing of sex hormone binding globulin (SHBG) if testosterone is 8-15 nmol/L with automatic calculation of cBAT; discontinue the use of analogue free testosterone assays; and definitive methods and standards must be available to ensure standardized results. CONCLUSIONS: Total testosterone is a reliable marker for the initial investigation of men presenting with symptoms of hypogonadism; cBAT is a reasonable follow-up test in patients with equivocal biochemical or consistent symptomatic findings.

Treating urinary-tract infections: which antibiotic?

Family physicians often start antibiotic treatment for urinary-tract infections (UTI) before they have a urine-culture report. Which is the most appropriate antibiotic to prescribe in this situation? The author of this study reviewed a random sample of charts in a rural Newfoundland clinic and analysed results of urine-culture and sensitivity reports. Certain conclusions were based on the infecting organisms' sensitivity to the various antibiotics and on the cost of the antibiotics. In particular, it would seem that ampicillin is of very limited value in treating urinary-tract infections, and the most appropriate antibiotic for treating a UTI when the culture result is not known is a trimethoprimsulfamethoxazole combination.