Muscle specific kinase protects dystrophic mdx mouse muscles from eccentric contraction-induced loss of force-producing capacity.

KEY POINTS: Adeno-associated viral vector was used to elevate the expression of muscle specific kinase (MuSK) and rapsyn (a cytoplasmic MuSK effector protein) in the tibialis anterior muscle of wild-type and dystrophic (mdx) mice. In mdx mice, enhanced expression of either MuSK or rapsyn ameliorated the acute loss of muscle force associated with strain injury. Increases in sarcolemmal immunolabelling for utrophin and ß-dystroglycan suggest a mechanism for the protective effect of MuSK in mdx muscles. MuSK also caused subtle changes to the structure and function of the neuromuscular junction, suggesting novel roles for MuSK in muscle physiology and pathophysiology. ABSTRACT: Muscle specific kinase (MuSK) has a well-defined role in stabilizing the developing mammalian neuromuscular junction, but MuSK might also be protective in some neuromuscular diseases. In the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy, limb muscles are especially fragile. We injected the tibialis anterior muscle of 8-week-old mdx and wild-type (C57BL10) mice with adeno-associated viral vectors encoding either MuSK or rapsyn (a cytoplasmic MuSK effector protein) fused to green fluorescent protein (MuSK-GFP and rapsyn-GFP, respectively). Contralateral muscles injected with empty vector served as controls. One month later mice were anaesthetized with isoflurane and isometric force-producing capacity was recorded from the distal tendon. MuSK-GFP caused an unexpected decay in nerve-evoked tetanic force, both in wild-type and mdx muscles, without affecting contraction elicited by direct electrical stimulation of the muscle. Muscle fragility was probed by challenging muscles with a strain injury protocol consisting of a series of four strain-producing eccentric contractions in vivo. When applied to muscles of mdx mice, eccentric contraction produced an acute 27% reduction in directly evoked muscle force output, affirming the susceptibility of mdx muscles to strain injury. mdx muscles overexpressing MuSK-GFP or rapsyn-GFP exhibited significantly milder force deficits after the eccentric contraction challenge (15% and 14%, respectively). The protective effect of MuSK-GFP in muscles of mdx mice was associated with increased immunolabelling for utrophin and ß-dystroglycan in the sarcolemma. Elevating the expression of MuSK or rapsyn revealed several distinct synaptic and extrasynaptic effects, suggesting novel roles for MuSK signalling in muscle physiology and pathophysiology.

Denosumab utilization among older adults in Ontario: patient characteristics, persistence with therapy, and return to therapy after an extended gap.

We studied 46,797 older adults who initiated denosumab in Ontario, Canada. Patient characteristics remained relatively stable over time and aligned with public reimbursement restrictions. Almost half of patients persisted with therapy for at least 3 years. Fifty-nine percent of patients who discontinued denosumab returned to treatment within 3.6 years. INTRODUCTION: The purpose of this study was to describe the characteristics of patients who initiated denosumab and estimate persistence with therapy. METHODS: We identified older adults (aged ≥ 66 years) in Ontario who initiated denosumab between 2012/02 and 2015/03 and followed them to 2016/03. Patient characteristics were summarized using medical and pharmacy claims in the year before starting denosumab and osteoporosis drug use considered since 1996/10. Persistence with denosumab and return after discontinuation (> 90-day gap) were estimated using Kaplan-Meier curves. Analyses were stratified by community and long-term care (LTC) residence. RESULTS: We identified 46,797 patients (monthly mean = 1263, SD = 187); 97% female, 13% LTC. Community-dwelling patients had a higher prevalence of bone mineral density testing (62% vs. 5%), yet were younger (mean age 78.5 vs. 86.6 years) and had lower prevalence of hip fractures (3% vs. 10%) compared to LTC patients. Eighty-two percent of patients had used osteoporosis medications in the past; 99% of whom took an oral bisphosphonate. Persistence was similar between community-dwelling and LTC patients: 59% persisted ≥ 2 years, 48% ≥ 3 years, and 38% ≥ 4 years, yet a larger proportion of LTC patients returned to denosumab after discontinuation (76% vs. 57%). CONCLUSIONS: Denosumab utilization is increasing at a steady rate in Ontario. However, persistence remains a concern given the highly reversible pharmacokinetic profile of denosumab that results in a rapid increased fracture risk following discontinuation. Over 80% of patients had a history of oral bisphosphonate therapy, which may persist in bone despite discontinuing denosumab. Consequently, better understanding of denosumab safety and effectiveness among real-world users is important.

Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes.

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered. INTRODUCTION: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time. METHODS: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex. RESULTS: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%). CONCLUSIONS: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.

[The impact of persistent high ambient fine particulate matters exposures on mortality in the 40 districts/counties of China, 2013-2015].

Objective: To investigate the impact of persistent high ambient fine particulate matters (PM(2.5)) exposures on mortality in the polluted areas of 40 districts/counties in China. Methods: Using a convenient sampling method, we selected 40 districts/counties as research sites from the Beijing-Tianjin-Hebei Metropolitan Region, the Yangtze River Delta, the Pearl River Delta, and Heilongjiang, Shanxi, and Sichuan province. The daily concentrations of PM(2.5), meteorological data and population death data from January 1, 2013 to December 31, 2015 were collected. The six persistent PM(2).5 pollution episode scenarios were defined by the average daily concentration of PM(2.5) (75 µg/m(3), P(75) and P(90) of the average daily concentration of each district/county respectively) and the duration (≥2 days or 3 days). Generalized linear models and meta analyses were used to explore the impact of PM(2.5) pollution episodes on mortality in 40 districts/counties. Results: The mean±SD and P(50) (P(25), P(75)) of average daily temperature, relative humidity and PM(2.5) were (15.26±10.48) ℃, 17.20 (7.50, 23.70) ℃, (67.31±19.26)%, 72.00% (57.00%, 81.00%), (72.81±60.93) µg/m(3) and 55.38 (33.77, 91.45) µg/m(3), respectively in 40 districts/counties during 2013-2015. The average number of non-accidental, cardiovascular and cerebrovascular diseases deaths per day were (12±7), (5±4) and (2±2) in each district/county, respectively. When the daily concentrations of PM(2.5) were ≥75 µg/m(3) (≥2 days), ≥P(75) (≥2 days), ≥P(90) (≥2 days), ≥75 µg/m(3) (≥3 days), and ≥P(75) (≥3 days), the excess risk (95%CI) of the total non-accidental deaths and cardiovascular diseases deaths were 1.77% (0.89%,2.66%), 2.69% (1.06%,4.35%), 1.67% (0.59%,2.76%), 2.31% (0.67%, 3.97%), 0.71% (-0.75%, 2.20%), 1.95% (0.08%, 3.86%), 1.15% (0.12%, 2.18%), 1.85% (0.25%, 3.47%), 1.39% (0.15%, 2.64%), 2.29% (0.39%, 4.23%), respectively. Conclusion: Persistently high PM(2.5) exposures were associated with total non-accidental deaths and cardiovascular disease deaths.

[Association of ambient fine particulate matters with anxiety in middle-aged and elderly people].

Objective: To investigate the association of ambient fine particulate matters (PM(2.5)) exposure with anxiety in middle-aged and elderly people in China. Methods: Using a stratified random sampling method, 5 997 middle-aged and elderly people (aged 40-89) who resided in the region for more than 2 years and had no hearing or language impairment were selected from 32 districts/counties in the key areas for air pollution prevention and control in China from October 10(th), 2017 to February 7(th), 2018. Information about demographic characteristics, socioeconomic factors and health status were collected by questionnaire survey and physical examination. The anxiety symptoms were assessed by 7-item Generalized Anxiety Disorder Scales. Three-year moving average concentrations of PM(2.5) were calculated to estimate exposure level. The multivariate logistic regression model was conducted to assess the association between PM(2.5) exposure and anxiety. The interaction of age, gender, overweight, education, smoking, drinking and chronic diseases was also analyzed by likelihood ratio test. Results: There were 2 995 (49.94%) males subjects, 4 092 (68.23%) subjects with education of secondary school or above and 2 576 (42.95%) subjects with self-reported chronic diseases among the 5 997 middle-aged and elder participants. The prevalence of anxiety was 6.64% (n=398). The mean±SD of 3-year moving average concentrations of PM(2.5), O(3) and SO(2) were (53.50±13.38), (90.58±13.26) and (40.29±12.56) µg/m(3), respectively. PM(2.5) had significantly association with anxiety, and the corresponding OR value was 1.17 (95%CI: 1.05,1.31) with a 10 µg/m(3) increment of 3-year moving average concentrations of PM(2.5). Compared with female (OR (95%CI)=1.07 (0.93,1.23)), those with no chronic diseases (OR (95%CI)=1.06 (0.93,1.20)) and those with primary school degree or below (OR (95% CI)=0.90 (0.75,1.09)), the association between PM(2.5) and anxiety was stronger among male (OR (95%CI)=1.35 (1.12,1.63)) and those with chronic diseases (OR (95%CI)=1.77 (1.31,2.38)), middle school education (OR (95%CI)=1.43 (1.22,1.67)), college education and above (OR (95%CI)=1.68 (1.05, 2.67)), all the P interaction values were <0.05. Conclusion: PM(2.5) exposure has significantly positive association with anxiety. The associations are stronger in male, people with higher educational qualifications and patients with chronic diseases.

Acute effect of multiple ozone metrics on mortality by season in 34 Chinese counties in 2013-2015.

BACKGROUND: Although numerous multicentre studies have estimated the association between ozone exposure and mortality, there are currently no nationally representative multicentre studies of the ozone-mortality relationship in China. OBJECTIVE: To investigate the effect on total (nonaccidental) and cause-specific mortality of short-term exposure to ambient ozone, and examine different exposure metrics. METHODS: The effects of short-term exposure to ozone were analysed using various metrics (daily 1-h maximum, daily 8-h maximum and daily average) on total (nonaccidental) and cause-specific (circulatory and respiratory) mortality from 2013 to 2015 in 34 counties in 10 cities across China. We used distributed lag nonlinear models for estimating county-specific relative risk of mortality and combined the county-specific relative rates by conducting a random-effects meta-analysis. RESULTS: In all-year analyses, a 10 µg m-3 increase in daily average, daily 1-h maximum and daily 8-h maximum ozone at lag02 corresponded to an increase of 0.6% (95% CI: 0.33, 0.88), 0.26% (95% CI: 0.12, 0.39) and 0.37% (95% CI: 0.2, 0.55) in total (nonaccidental) mortality, 0.66% (95% CI: 0.28, 1.04), 0.31% (95% CI: 0.11, 0.51) and 0.39% (95% CI: 0.16, 0.62) in circulatory mortality, and 0.57% (95% CI: -0.09, 1.23), 0.11% (95% CI: -0.22, 0.44) and 0.22% (95% CI: -0.28, 0.72) in respiratory mortality, respectively. These estimates had a different seasonal pattern by cause of death. In general, the seasonal patterns were consistent with the times of year when ozone concentrations are highest. CONCLUSIONS: Our findings suggest that in China, the acute effects of ozone are more closely related to daily average exposure than any other metric.

Association of cigarette smoking with a past history and incidence of herpes zoster in the general Japanese population: the SHEZ Study.

Few studies have examined the impact of cigarette smoking on the risk for herpes zoster. The Shozu Herpes Zoster (SHEZ) Study is a community-based prospective cohort study over 3 years in Japan aiming to clarify the incidence and predictive and immunological factors for herpes zoster. We investigated the associations of smoking status with past history and incidence of herpes zoster. A total of 12 351 participants provided valid information on smoking status and past history of herpes zoster at baseline survey. Smoking status was classified into three categories (current, former, never smoker), and if currently smoking, the number of cigarettes consumed per day was recorded. The participants were under the active surveillance for first-ever incident herpes zoster for 3 years. We used a logistic regression model for the cross-sectional study on the association between smoking status and past history of herpes zoster, and a Cox proportional hazards regression model for the cohort study on the association with risk of incidence. The multivariable adjusted odd ratios (95% CI) of past history of herpes zoster for current vs. never smokers were 0·67 (0·54-0·80) for total subjects, 0·72 (0·56-0·93) for men and 0·65 (0·44-0·96) for women. The multivariable adjusted hazard ratios (95% CI) of incident herpes zoster for current vs. never smokers were 0·52 (0·33-0·81) for total subjects, 0·49 (0·29-0·83) for men and 0·52 (0·19-1·39) for women. Smoking status was inversely associated with the prevalence and incidence of herpes zoster in the general population of men and women aged ⩾50 years.

Vascular endothelial growth factor -634 G/C polymorphism and risk of cancer: an updated meta-analysis.

The association between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of cancer has been investigated in several studies published previously; however, the individual results are inconclusive. Therefore, we performed a meta-analysis to establish evidence for an association between the VEGF -634 G/C polymorphism and risk of cancer. We searched PubMed, Medline, and Korean Studies Information Service System databases and identified 29 case-control studies, containing data of 25,324 individuals, for this meta-analysis. The odds ratio (OR) and 95% confidence interval (95%CI) were used to determine the strength of the association. Overall, no significant association was detected in the allele model (G allele vs C allele, OR = 0.98, 95%CI = 0.93-1.03), dominant model (G/G+G/C vs C/C, OR = 1.00, 95%CI = 0.90-1.11), or recessive model (G/G vs G/C+C/C, OR = 0.96, 95%CI = 0.89-1.03). The meta-analysis results suggest that the VEGF -634 G/C polymorphism may not be related to the development of cancer. However, additional studies with larger sample size are required in order to provide supporting evidence.

Assessment of CASP gene polymorphisms in periodontal disease.

Caspases (CASP) are intracellular proteases that play roles as mediators of apoptosis. Activation of caspase 3 is enhanced in chronic periodontitis. Thus, we hypothesized that single nucleotide polymorphisms (SNPs) of CASP genes might be associated with this condition in the Korean population. To investigate whether such polymorphisms might be involved in the development of periodontal disease, 51 patients and 33 control subjects were assessed. A total of 201 CASP gene SNPs were analyzed with genotypes being determined using and Axiom(TM) genome-wide human assay. SNPStats and SPSS 18.0 were used for the analysis of genetic data and logistic regression models were utilized to evaluate odds ratios, 95% confidence intervals, and P values. Of the 201 SNPs, only three (rs12108497, rs4647602, and rs113420705, all in the CASP3 gene) were significantly associated with chronic periodontitis (P < 0.05). The minor allele frequencies of these SNPs were higher in the patient group than in the control group. In addition, the TC and GT haplotypes formed by rs4647602 and rs113420705 were found to be associated with chronic this disease (TC haplotype, P = 0.0039; GT haplotype, P = 0.002). These results suggest that CASP3 gene polymorphisms may be associated with susceptibility to periodontal disease in the Korean population.

Variability in functional p53 reactivation by PRIMA-1(Met)/APR-246 in Ewing sarcoma.

BACKGROUND: Though p53 mutations are rare in ES, there is a strong indication that p53 mutant tumours form a particularly bad prognostic group. As such, novel treatment strategies are warranted that would specifically target and eradicate tumour cells containing mutant p53 in this subset of ES patients. METHODS: PRIMA-1(Met), also known as APR-246, is a small organic molecule that has been shown to restore tumour-suppressor function primarily to mutant p53 and also to induce cell death in various cancer types. In this study, we interrogated the ability of APR-246 to induce apoptosis and inhibit tumour growth in ES cells with different p53 mutations. RESULTS: APR-246 variably induced apoptosis, associated with Noxa, Puma or p21(WAF1) upregulation, in both mutant and wild-type p53 harbouring cells. The apoptosis-inducing capability of APR-246 was markedly reduced in ES cell lines transfected with p53 siRNA. Three ES cell lines established from the same patient at different stages of the disease and two cell lines of different patients with identical p53 mutations all exhibited different sensitivities to APR-246, indicating cellular context dependency. Comparative transcriptome analysis on the three cell lines established from the same patient identified differential expression levels of several TP53 and apoptosis-associated genes such as APOL6, PENK, PCDH7 and MST4 in the APR-246-sensitive cell line relative to the less APR-246-sensitive cell lines. CONCLUSION: This is the first study reporting the biological response of Ewing sarcoma cells to APR-246 exposure and shows gross variability in responses. Our study also proposes candidate genes whose expression might be associated with ES cells' sensitivity to APR-246. With APR-246 currently in early-phase clinical trials, our findings call for caution in considering it as a potential adjuvant to conventional ES-specific chemotherapeutics.

The injury patterns, management and outcomes of retroperitoneal haemorrhage caused by lumbar arterial bleeding at a Level-1 Trauma Centre: A 10-year retrospective review.

PURPOSE: Haemorrhagic shock remains a leading preventable cause of death amongst trauma patients. Failure to identify retroperitoneal haemorrhage (RPH) can lead to irreversible haemorrhagic shock. The arteries of the middle retroperitoneal region (i.e., the 1st to 4th lumbar arteries) are complicit in haemorrhage into the retroperitoneal space. However, predictive injury patterns and subsequent management implications of haemorrhage secondary to bleeding of these arteries is lacking. MATERIALS AND METHODS: We performed a retrospective cohort study of patients diagnosed with retroperitoneal haemorrhage who presented to our Level-1 Trauma Centre (2009-2019). We described the associated injuries, management and outcomes relating to haemorrhage of lumbar arteries (L1-4) from this cohort to assess risk and management priorities in non-cavitary haemorrhage compared to RPH due to other causes. RESULTS: Haemorrhage of the lumbar arteries (LA) is associated with a higher proportion of lumbar transverse process (TP) fractures. Bleeding from branches of these vessels is associated with lower systolic blood pressure, increased incidence of massive transfusion, higher shock index, and a higher Injury Severity Score (ISS). A higher proportion of patients in the LA group underwent angioembolisation when compared to other causes of RPH. CONCLUSION: This study highlights the injury patterns, particularly TP fractures, in the prediction, early detection and management of haemorrhage from the lumbar arteries (L1-4). Compared to other causes of RPH, bleeding of the LA responds to early, aggressive haemorrhage control through angioembolisation. These injuries are likely best treated in Level-1 or Level-2 trauma facilities that are equipped with angioembolisation facilities or hybrid theatres to facilitate early identification and management of thoracolumbar bleeds.

Utility of healthcare-worker-targeted antimicrobial stewardship interventions in hospitals of low- and lower-middle-income countries: a scoping review of systematic reviews.

BACKGROUND: Antimicrobial stewardship (AMS) initiatives in hospitals often include the implementation of clustered intervention components to improve the surveillance and targeting of antibiotics. However, impacts of the individual components of AMS interventions are not well known, especially in low- and lower-middle-income countries (LLMICs). OBJECTIVE: A scoping review was conducted to summarize evidence from systematic reviews (SRs) on the impact of common hospital-implemented healthcare-worker-targeted components of AMS interventions that may be appropriate for LLMICs. METHODS: Major databases were searched systematically for SRs of AMS interventions that were evaluated in hospitals. For SRs to be eligible, they had to report on at least one intervention that could be categorized according to the Effective Practice and Organisation of Care taxonomy. Clinical and process outcomes were considered. Primary studies from LLMICs were consulted for additional information. RESULTS: Eighteen SRs of the evaluation of intervention components met the inclusion criteria. The evidence shows that audit and feedback, and clinical practice guidelines improved several clinical and process outcomes in hospitals. An unintended consequence of interventions was an increase in the use of antibiotics. There was a cumulative total of 547 unique studies, but only 2% (N=12) were conducted in hospitals in LLMICs. Two studies in LLMICs reported that guidelines and educational meetings were effective in hospitals. CONCLUSION: Evidence from high- and upper-middle-income countries suggests that audit and feedback, and clinical practice guidelines have the potential to improve various clinical and process outcomes in hospitals. The lack of evidence in LLMIC settings prevents firm conclusions from being drawn, and highlights the need for further research.

A selective inhibitor of the immunoproteasome subunit LMP2 induces apoptosis in PC-3 cells and suppresses tumour growth in nude mice.

BACKGROUND: Although the proteasome is a validated anticancer target, the clinical application of its inhibitors has been limited because of inherent systemic toxicity. To broaden clinical utility of proteasome inhibitors as anticancer agents, it is critical to develop strategies to selectively target proteasomes in cancer cells. The immunoproteasome is an alternative form of the constitutive proteasome that is expressed at high levels in cancer tissues, but not in most normal cells in the body. METHODS: To validate the immunoproteasome as a chemotherapeutic target, an immunoproteasome catalytic subunit LMP2-targeting inhibitor and siRNA were used. The sensitivity of PC-3 prostate cancer cells to these reagents was investigated using viability assays. Further, a xenograft model of prostate cancer was studied to test the in vivo effects of LMP2 inhibition. RESULTS: A small molecule inhibitor of the immunoproteasome subunit LMP2, UK-101, induced apoptosis of PC-3 cells and resulted in significant inhibition (~50-60%) of tumour growth in vivo. Interestingly, UK-101 did not block degradation of IκBα in PC-3 cells treated with TNF-α, suggesting that its mode of action may be different from that of general proteasome inhibitors, such as bortezomib, which block IκBα degradation. CONCLUSION: These results strongly suggest that the immunoproteasome has important roles in cancer cell growth and thus provide a rationale for targeting the immunoproteasome in the treatment of prostate cancer.

A comparison of computer- and hand-generated clinical dental notes with statutory regulations in record keeping.

INTRODUCTION: Dental patient records should be of high quality, contain information to allow for good continuity of care and clinical defence (should the need ever arise) and, ideally, facilitate clinical audit. Handwritten dental records have been assessed for their compliance to statutory regulations, but the same cannot be levelled at computer-generated notes. This study aimed to compare and analyse the compliance of both methods of data recording with statutory regulations. METHOD: Fifty consecutive sets of handwritten notes and 50 sets of computer-generated notes were audited for compliance with a number of legal requirements and desirable characteristics for dental records and the results compared. The standard set for compliance with all characteristics was 100%. RESULTS: The computer-generated notes satisfied the set standard for 8 of the 11 legal requirements and three of six desirable characteristics. The handwritten notes satisfied the set standard for 1 of 11 legal requirements and none of the desirable characteristics. A statistical difference (using a 95% confidence interval) between the two methods was observed in 5 of 11 legal characteristics and three of six desirable characteristics, all of which were in favour of computer-generated notes. CONCLUSIONS: Within the limitations of this study, computer-generated notes achieved a much higher compliance rate with the set parameters, making defence in cases of litigation, continuity of care and clinical audit easier and more efficient.

Glutathione S-transferase M1 (GSTM1) polymorphism is associated with atopic dermatitis susceptibility in a Korean population.

Atopic dermatitis (AD) is a chronic pruritic skin condition affecting as much as 15% of children in industrialized countries. While the underlying pathophysiology of AD is not entirely understood, several studies have suggested that AD may mediated by oxidative stress. Glutathione S-transferases (GSTs) are a class of polymorphic enzymes that function to protect against oxidative stress. To identify any possible associations between GSTs polymorphisms and AD susceptibility, the prevalence of two specific polymorphisms -GSTM1 and GSTT1 (homozygous deletion vs. undeleted) - were quantified by multiplex PCR in 145 patients with AD and 267 healthy controls. In individuals with AD, GSTM1/GSTT1 polymorphisms were compared with family history of AD, age of disease onset, disease severity [per SCORing Atopic Dermatitis (SCORAD)], serum IgE level and presence of other allergic diseases. While the GSTM1-null genotype was found to be significantly associated with AD (P = 0.033, OR = 1.579, 95% CI = 1.037-2.403), the correlation between the GSTT1-null genotype and AD did not reach statistical significance (P = 0.577, OR = 1.125, 95% CI = 0.744-1.702). The GSTM1-null genotype was also found to be significantly associated with a childhood onset of AD, the absence of other allergic diseases, and a family history of AD. In combination, these results suggest that GSTM1 is associated with AD susceptibility in Korean subjects.

Outcomes of endoscopic sinus surgery in an elderly population: comparison with those in an adult population.

OBJECTIVE: The aim of this study was to compare the surgical outcomes of endoscopic sinus surgery in two patient groups: adults younger than 65 years of age and adults aged 65 years or older. DESIGN: A retrospective study. SETTING: This study was conducted at an academic tertiary referral centre. PARTICIPANTS: One hundred and eighty consecutive older patients (> or =65 years), and 180 adult patients (>15, <65 years) with chronic rhinosinusitis who underwent endoscopic sinus surgery under local anaesthesia between 1997 and 2007 were enrolled in this study. MAIN OUTCOME MEASURES: Recurrence and complication rates were analyzed. Data were analyzed using the Mann-Whitney test, Fisher's Exact test, the Pearson Chi-Square test, and univariate and multivariate logistic regression. P < 0.05 was considered statistically significant. RESULTS: When looked at without control for other factors the surgical complication rates were higher in the older group patients (31%) compared with the younger patients (11%). However, multivariate logistic regression analysis showed that preoperative duration of symptoms, length of follow-up, and diabetes mellitus were positively correlated with complications. In this analysis, the older patients, once controlled for these factors, were less likely to have complications. Regarding recurrence, in multivariate analysis there was no difference between the older and the younger group with preoperative duration and length of postoperative follow-up having a small effect. CONCLUSIONS: Comorbidity especially diabetes mellitus and duration of the condition should be the factors considered preoperatively to predict the likely hood of complications rather than whether the patient is younger or older that 65 years of age.

[A review on the research progress related to ambient air pollution and depression].

It is reported that depression has caused heavy disease burden across the world, with an possible association between ambient air pollution and depressive symptoms. In this paper, we reviewed relative literature in this field and summarized the research events on association between ambient air pollution and depression, both in China and abroad and found that the results of the existed studies were inconsistent, with most studies showing that there existed a positive correlation between the exposure of air pollution and depression, but few studies showing the negative correlation or no correlation between the two.

Estimation of Day-Specific Probabilities of Conception during Natural Cycle in Women from Babylon.

BACKGROUND: Identifying predictors of the probabilities of conception related to the timing and frequency of intercourse in the menstrual cycle is essential for couples attempting pregnancy, users of natural family planning methods, and clinicians diagnosing for possible causes of infertility. The aim of this study is to estimate the days in which the likelihood of conception happened by using first trimester ultrasound fetal biometry in natural cycles and spontaneous pregnancy, and to explore some factors that may affect them. MATERIALS AND METHODS: This study is retrospective cohort study, with random sampling. It involved 60 pregnant ladies at first trimester; the date of conception was estimated using: i. Crown-rump length biometry (routine ultrasound examinations were performed at a median of 70 days following Last menstrual period or equivalently 10 weeks), ii. Date of last menstrual cycle. Only women with previous infertility and now conceiving naturally with a certain date of Last menstrual period were selected. RESULTS: The distribution of conception showed a sharp rise from day 8 onwards, reaching its maximum at day 13 and decreasing to zero by day 30 of Last menstrual period. The older and obese women had conceive earlier than younger women but there was insignificants difference between the two groups (P>0.05). According to the type of infertility, the women with secondary infertility had conceived earlier than those with primary infertility. There was a significant difference between the two groups (P<0.05). CONCLUSION: Day specific of conception may be affected by factors such as age, BMI, and type of infertility. This may be confirmed by larger sample size in metacentric study.

[Air pollution and adverse birth outcome in China: a comprehensive review].

Objective: To summarize the progress in the research of the association between air pollution and adverse birth outcomes in China. Methods: A literature retrieval was conducted by using the databases of CNKI, Wanfang, Pubmed, Science Direct, and Web of Science to select relevant research papers published before 30(th), June 2016 in China according to inclusion criteria. Finally, 27 papers were included in analysis. Results: Exposure to particulate matter (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), total suspended particles (TSP) during pregnancy might increase risk for low birth weight; exposure to PM(10), SO(2), NO(2) during pregnancy might increase risk for premature birth; and exposure to SO(2), NO(2), ozone (O(3)), and PM(10) during pregnancy might increase risk for congenital heart diseases and other birth defects. Conclusion: Exposure to air pollutants during pregnancy might increase the risk for adverse birth outcomes, and further studies are needed to prove the association.