Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study

<p>Abstract</p> <p>Background</p> <p>The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood.</p> <p>Methods</p> <p>Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia.</p> <p>Results</p> <p>Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms.</p> <p>Conclusions</p> <p>The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.</p

Identification of Colorectal Cancer Related Genes with mRMR and Shortest Path in Protein-Protein Interaction Network

One of the most important and challenging problems in biomedicine and genomics is how to identify the disease genes. In this study, we developed a computational method to identify colorectal cancer-related genes based on (i) the gene expression profiles, and (ii) the shortest path analysis of functional protein association networks. The former has been used to select differentially expressed genes as disease genes for quite a long time, while the latter has been widely used to study the mechanism of diseases. With the existing protein-protein interaction data from STRING (Search Tool for the Retrieval of Interacting Genes), a weighted functional protein association network was constructed. By means of the mRMR (Maximum Relevance Minimum Redundancy) approach, six genes were identified that can distinguish the colorectal tumors and normal adjacent colonic tissues from their gene expression profiles. Meanwhile, according to the shortest path approach, we further found an additional 35 genes, of which some have been reported to be relevant to colorectal cancer and some are very likely to be relevant to it. Interestingly, the genes we identified from both the gene expression profiles and the functional protein association network have more cancer genes than the genes identified from the gene expression profiles alone. Besides, these genes also had greater functional similarity with the reported colorectal cancer genes than the genes identified from the gene expression profiles alone. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying colorectal cancer genes. It has not escaped our notice that the method can be applied to identify the genes of other diseases as well

Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: A randomized controlled trial

Context Sexually transmitted infections (STIs) are common in female sex workers (FSWs) and may enhance susceptibility to infection with human immunodeficiency virus type 1 (HIV-1). Objective To examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1. Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted between 1998-2002 among FSWs in an urban slum area of Nairobi, Kenya. Of 890 FSWs screened, 466 who were seronegative for HIV-1 infection were enrolled and randomly assigned to receive azithromycin (n = 230) or placebo (n = 236). Groups were well matched at baseline for sexual risk taking and STI rates. Intervention Monthly oral administration of 1 g of azithromycin or identical placebo, as directly observed therapy. All participants were provided with free condoms, risk-reduction counseling, and STI case management. Main Outcome Measures The primary study end point was incidence of HIV-1 infection. Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, and Haemophilus ducreyi, as well as bacterial vaginosis. Analysis of herpes simplex virus type 2 (HSV-2) infection was performed post hoc. Results Seventy-three percent of participants (n = 341) were followed up for 2 or more years or until they reached an administrative trial end point. Incidence of HIV-1 did not differ between treatment and placebo groups (4% [19 cases per 473 person-years of follow-up] vs 3.2% [16 cases per 495 person-years of follow-up] rate ratio [RR], 1.2; 95% CI, 0.6-2.5). Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae (rate ratio [RR], 4.9; 95% CI, 1.7-14.3) or C trachomatis (RR, 3.0; 95% CI, 1.1-8.9). There was a reduced incidence in the treatment group of infection with N gonorrhoeae (RR, 0.46; 95% CI, 0.31-0.68), C trachomatis (RR, 0.38; 95% CI, 0.26-0.57), and T vaginalis (RR, 0.56; 95% CI, 0.40-0.78). The seroprevalence of HSV-2 infection at enrollment was 72.7%, and HSV-2 infection at baseline was independently associated with HIV-1 acquisition (RR, 6.3; 95% CI, 1.5-27.1). Conclusions Despite an association between bacterial STIs and acquisition of HIV-1 infection, the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1. Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1. Sexually transmitted infections (STIs) are important cofactors in the human immunodeficiency virus type 1 (HIV-1)/AIDS pandemic. In HIV-infected individuals, not only may symptomatic and asymptomatic STIs enhance sexual transmission of HIV-1 by increasing virus shedding from the genital tract,1-3 but at the same time HIV-1 infection itself increases susceptibility to STIs.4 There is also considerable evidence that STIs may increase HIV-1 susceptibility in uninfected individuals,5,6 although differentiating cause from effect is more difficult in this situation.7 Prevention or control of STIs as a strategy for preventing HIV-1 transmission has met with mixed success. Improved syndromic management of STIs reduced HIV-1 incidence in communities in Mwanza, Tanzania,8 but in Uganda neither a similar strategy nor antibiotic mass-treatment of whole communities had an impact on HIV-1 incidence.9,10 Factors contributing to the lack of efficacy in the Uganda trials may have included the greater effectiveness of continuously available STI treatment services11 and the reduction in spread of HIV-1 during primary infection due to counseling given at the time of STI therapy.12 Another important factor may be that the Tanzanian study was performed early in the epidemic, when community prevalence of HIV-1 was below 5%. The Ugandan studies, by contrast, were performed later, in communities with much higher prevalences of HIV-1 (range, 10%-16%).11,13 Curable STIs may play a lesser role in HIV-1 transmission in the context of a mature epidemic, because most transmission occurs in the context of stable partnerships, reducing the potential impact of STI prevention and treatment.14 Interventions based on prevention or control of STIs may therefore be more effective in communities in the early stages of an epidemic13 or in subgroups at high risk of STIs.3 Female sex workers (FSWs) constitute an important vulnerable group in the acquisition and transmission of both HIV-1 infection and STIs15 but may be excluded from household-based community studies of STI control.16 It has therefore been suggested that interventions for control of STIs should target these women specifically.17 Studies in Kenya have shown that certain FSW cohorts have an annual HIV incidence of 16% to 50%18,19 and a high incidence of cervicitis due to infection with Neisseria gonorrhoeae and Chlamydia trachomatis.18 This may be partly attributed to low levels of condom use and poor access to STI counseling and treatment services.20 We hypothesized that these high rates of bacterial STI and HIV-1 infection would make FSWs an ideal population in which to test antibiotic prophylaxis of common genital tract infections as an HIV-1 prevention strategy. Since the use of prophylactic antibiotics by FSWs has been associated with increased sexual risk taking,21 we elected to test this intervention in a blinded fashion

Nutritional management of persistent diarrhea: factors predicting clinical outcome

In a prospective study we randomized 102 male children (age 6-36 months) with persistent diarrhea to receive a traditional rice-lentil (Khitchri) diet and yogurt (K-Y) or a soy formula (alone for seven days and then in combination with K-Y for seven days). Of 73 children satisfying the study criteria, 66 were successfully treated and there were 7 treatment failures. There was poor concordance between parental accounts of severity of diarrhea or vomiting and that observed after admission. Significant risk factors associated with treatment failure included younger age (p \u3c 0.005) and vomiting at presentation (p \u3c 0.02). The greatest number of risk factors associated with delayed recovery (\u3e 10 days) were identified during an initial evaluation period (the first 8 h after admission). These included greater severity of watery diarrhoea (p \u3c 0.01) and increased ORS intake (p \u3c 0.02). Our data suggest that an initial evaluation period, including objective observations, may identify children with persistent diarrhea who are at greatest need of hospitalization