bluuebunny/crossref_metadata_2025 huggingface dataset:
A microfluidic device to acquire high-magnification microphotographs of yeast cells
Authors: Ohnuki Shinsuke , Nogami Satoru , Ohya Yoshikazu
Published: March 2009

Background

Yeast cell morphology was investigated to reveal the molecular mechanisms of cell morphogenesis and to identify key factors of other processes such as cell cycle progression. We recently developed a semi-automatic image processing program called CalMorph, which allows us to quantitatively analyze yeast cell morphology with the 501 parameters as biological traits and uncover statistical relationships between cell morphological phenotypes and genotypes. However, the current semi-automatic method is not suitable for morphological analysis of large-scale yeast mutants for the reliable prediction of gene functions because of its low-throughput especially at the manual image-acquiring process.

Results

In this study, we developed a microfluidic chip designed to acquire successive microscopic images of yeast cells suitable for CalMorph image analysis. With the microfluidic chip, the morphology of living cells and morphological changes that occur during the cell cycle were successfully characterized.

Conclusion

The microfluidic chip enabled us to acquire the images faster than the conventional method. We speculate that the use of microfluidic chip is effective in acquiring images of large-scale for automated analysis of yeast strains.
In vivo and in vitro evaluation of an Acetobacter xylinum synthesized microbial cellulose membrane intended for guided tissue repair
Authors: Mendes Péricles Nóbrega , Rahal Sheila Canevese , Pereira-Junior Oduvaldo Câmara Marques , Fabris Viciany Erique , Lenharo Sara Lais Rahal , de Lima-Neto João Ferreira , da Cruz Landim-Alvarenga Fernanda
Published: March 2009

Background

Barrier materials as cellulose membranes are used for guided tissue repair. However, it is essential that the surrounding tissues accept the device. The present study histologically evaluated tissue reaction to a microbial cellulose membrane after subcutaneous implantation in mice. Furthermore, the interaction between mesenchymal stem cells and the biomaterial was studied in vitro to evaluate its ability to act as cellular scaffold for tissue engineering.

Methods

Twenty-five Swiss Albino mice were used. A 10 × 10 mm cellulose membrane obtained through biosynthesis using Acetobacter xylinum bacteria was implanted into the lumbar subcutaneous tissue of each mouse. The mice were euthanatized at seven, 15, 30, 60, and 90 days, and the membrane and surrounding tissues were collected and examined by histology.

Results

A mild inflammatory response without foreign body reaction was observed until 30 days post-surgery around the implanted membrane. Polarized microscopy revealed that the membrane remained intact at all evaluation points. Scanning electron microscopy of the cellulose membrane surface showed absence of pores. The in vitro evaluation of the interaction between cells and biomaterial was performed through viability staining analysis of the cells over the biomaterial, which showed that 95% of the mesenchymal stem cells aggregating to the cellulose membrane were alive and that 5% were necrotic. Scanning electron microscopy showed mesenchymal stem cells with normal morphology and attached to the cellulose membrane surface.

Conclusion

The microbial cellulose membrane evaluated was found to be nonresorbable, induced a mild inflammatory response and may prove useful as a scaffold for mesenchymal stem cells.
Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study
Authors: de Grauw Janny C , van de Lest Chris HA , van Weeren Paul René
Published: March 2009

Introduction

Inflammation is an important feature of many joint diseases, and levels of cartilage biomarkers measured in synovial fluid may be influenced by local inflammatory status. Little is known about the magnitude and time course of inflammation-induced changes in cartilage tissue turnover as measured in vivo by synovial fluid markers. We aimed to study temporal changes in concentrations of inflammatory mediators, matrix metalloproteinase activity and cartilage biomarkers over 1 week in joints with experimentally induced inflammation.

Methods

Localized inflammation was induced in the intercarpal joint of six horses by sterile injection of 0.5 ng lipopolysaccharide, and synovial fluid was collected at post-injection hours (PIH) 0, 8, 24 and 168. Concentrations of inflammatory mediators (prostaglandin E2, substance P, and bradykinin), general matrix metalloproteinase activity and markers of collagen II turnover (CPII and C2C) as well as aggrecan turnover (CS846 and glycosaminoglycans) were measured with appropriate assays. One-way analysis of variance on repeated measures was used to analyze differences in synovial fluid marker levels over time.

Results

Lipopolysaccharide-injection led to a sharp rise in prostaglandin E2 at PIH 8, while substance P, bradykinin and matrix metalloproteinase activity showed more sustained increases at PIH 8 and 24. Glycosaminoglycan release paralleled changes in the CS846 epitope, with an increase by PIH 8, a peak at PIH 24, and return to baseline by PIH 168. For type II collagen, a parallel time course between catabolic (C2C) and anabolic (CPII) markers was also observed, but the time course differed from that seen for proteoglycan markers: collagen II markers peaked later, at PIH 24, and were still elevated over baseline at PIH 168.

Conclusions

A primary intra-articular inflammatory insult, characterized by local release of peptide and lipid mediators and matrix metalloproteinase activation, can alter synovial fluid levels of proteoglycan biomarkers as early as 8 hours post-induction, and can lead to sustained rises in collagen II biomarkers during at least 1 week after onset.
Crystalloids versus colloids for goal-directed fluid therapy in major surgery
Authors: Hiltebrand Luzius B , Kimberger Oliver , Arnberger Michael , Brandt Sebastian , Kurz Andrea , Sigurdsson Gisli H
Published: March 2009

Introduction

Perioperative hypovolemia arises frequently and contributes to intestinal hypoperfusion and subsequent postoperative complications. Goal-directed fluid therapy might reduce these complications. The aim of this study was to compare the effects of goal-directed administration of crystalloids and colloids on the distribution of systemic, hepatosplanchnic, and microcirculatory (small intestine) blood flow after major abdominal surgery in a clinically relevant pig model.

Methods

Twenty-seven pigs were anesthetized and mechanically ventilated and underwent open laparotomy. They were randomly assigned to one of three treatment groups: the restricted Ringer lactate (R-RL) group (n = 9) received 3 mL/kg per hour of RL, the goal-directed RL (GD-RL) group (n = 9) received 3 mL/kg per hour of RL and intermittent boluses of 250 mL of RL, and the goal-directed colloid (GD-C) group (n = 9) received 3 mL/kg per hour of RL and boluses of 250 mL of 6% hydroxyethyl starch (130/0.4). The latter two groups received a bolus infusion when mixed venous oxygen saturation was below 60% ('lockout' time of 30 minutes). Regional blood flow was measured in the superior mesenteric artery and the celiac trunk. In the small bowel, microcirculatory blood flow was measured using laser Doppler flowmetry. Intestinal tissue oxygen tension was measured with intramural Clark-type electrodes.

Results

After 4 hours of treatment, arterial blood pressure, cardiac output, mesenteric artery flow, and mixed oxygen saturation were significantly higher in the GD-C and GD-RL groups than in the R-RL group. Microcirculatory flow in the intestinal mucosa increased by 50% in the GD-C group but remained unchanged in the other two groups. Likewise, tissue oxygen tension in the intestine increased by 30% in the GD-C group but remained unchanged in the GD-RL group and decreased by 18% in the R-RL group. Mesenteric venous glucose concentrations were higher and lactate levels were lower in the GD-C group compared with the two crystalloid groups.

Conclusions

Goal-directed colloid administration markedly increased microcirculatory blood flow in the small intestine and intestinal tissue oxygen tension after abdominal surgery. In contrast, goal-directed crystalloid and restricted crystalloid administrations had no such effects. Additionally, mesenteric venous glucose and lactate concentrations suggest that intestinal cellular substrate levels were higher in the colloid-treated than in the crystalloid-treated animals. These results support the notion that perioperative goal-directed therapy with colloids might be beneficial during major abdominal surgery.
Interferon-λs: the modulators of antivirus, antitumor, and immune responses
Authors: Li Mingcai , Liu Xiaojin , Zhou Yanchun , Su Shao Bo
Published: March 2009

Recent findings concerning the biology of IFN-λs and their pathophysiological roles in viral infection, cancer, and immune responses of the innate and adaptive arms are summarized.

IFN-λs, including IFN-λ1, IFN-λ2, and IFN-λ3, also known as IL-29, IL-28A, or IL-28B, are a newly described group of cytokines distantly related to the type I IFNs and IL-10 family members. The IFN-λR complex consists of a unique ligand-binding chain, IFN-λR1 (also designated IL-28Rα), and an accessory chain, IL-10R2, which is shared with receptors for IL-10-related cytokines. IFN-λs signal through the IFN-λR and activate pathways of JAK-STATs and MAPKs to induce antiviral, antiproliferative, antitumor, and immune responses. In this review, we summarize recent findings about the biology of IFN-λs and their pathophysiological roles in viral infection, cancer, and immune responses of the innate and adaptive arms.
Interpreting Trial Results in Light of Conflicting Evidence: A Bayesian Analysis of Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer
Authors: Miksad Rebecca A. , Gönen Mithat , Lynch Thomas J. , Roberts Thomas G.
Published: March 2009

Purpose

When successive randomized trials contradict prior evidence, clinicians may be unsure how to evaluate them: Does accumulating evidence warrant changing practice? An increasingly popular solution, Bayesian statistics quantitatively evaluate new results in context. This study provides a clinically relevant example of Bayesian methods.

Methods

Three recent non–small-cell lung cancer adjuvant chemotherapy trials were evaluated in light of prior conflicting data. Results were used from International Adjuvant Lung Trial (IALT), JBR.10, and Adjuvant Navelbine International Trialist Association (ANITA). Prior evidence was sequentially updated to calculate the probability of each survival benefit level (overall and by stage) and variance. Sensitivity analysis was performed using expert opinion and uninformed estimates of survival benefit prior probability.

Results

The probability of a 4% survival benefit increased from 33% before IALT to 64% after IALT. After sequential updating with JBR.10 and ANITA, this probability was 82% (hazard ratio = 0.84; 95% CI, 0.77 to 0.91). IALT produced the largest decrease in variance (61%) and decreased the chance of survival decrement to 0%. Sensitivity analysis did not support a survival benefit after IALT. However, sequential updating substantiated a 4% survival benefit and, for stage II and III, more than 90% probability of a 6% benefit and 50% probability of a 12% benefit.

Conclusion

When evaluated in context with prior data, IALT did not support a 4% survival benefit. However, sequential updating with JBR.10 and ANITA did. A model for future assessments, this study demonstrates the unique ability of Bayesian analysis to evaluate results that contradict prior evidence.
Impact of the Duration of Adjuvant Hormonal Therapy in Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy: A Secondary Analysis of RTOG 85-31
Authors: Souhami Luis , Bae Kyounghwa , Pilepich Miljenko , Sandler Howard
Published: March 2009

Purpose

Radiation Therapy Oncology Group 85-31 was a randomized trial of androgen suppression for life for patients with locally advanced prostate cancer. However, not all patients continued on the protocol-mandated long-term hormonal therapy despite no evidence of recurrence. We correlated duration of adjuvant hormonal therapy and outcomes among patients who prematurely discontinued hormonal therapy.

Patients and Methods

The protocol mandated pelvic radiotherapy followed by goserelin given indefinitely or until disease progression. There were 189 analyzable patients. Patients were divided in groups based on the tertile of hormonal therapy duration (HTD) as follows: ≤ 1 year, more than 1 year and ≤ 5 years, and more than 5 years. Overall survival (OS), disease-free survival (DFS), cause-specific mortality, local failure (LF), and distant metastasis (DM) were studied. Kaplan-Meier estimation and Cox proportional hazards regression model were used for OS and DFS, and Fine and Gray's regression model was used for the other outcomes.

Results

The median follow-up for surviving patients is 9.6 years. The median duration of adjuvant hormonal therapy was 2.2 years. The HTD more than 5 years group is significantly associated with an improved survival and DFS and fewer DMs than other HTD groups. After adjustment for age, radical prostatectomy, nodal status, Gleason score, and stage variables, the HTD more than 5 years group remains significantly associated with better OS and DFS than other HTD groups.

Conclusion

In this hypothesis-generating analysis, prolonged HTD of more than 5 years seems significantly associated with improvements in most outcomes. Given these data, decreasing HTD to ≤ 5 years may have a detrimental effect on patients with locally advanced prostate cancer. Only a randomized trial will conclusively clarify this issue.
Treatment Quality and Outcomes of African American Versus White Breast Cancer Patients: Retrospective Analysis of Southwest Oncology Studies S8814/S8897
Authors: Hershman Dawn L. , Unger Joseph M. , Barlow William E. , Hutchins Laura F. , Martino Silvana , Osborne C. Kent , Livingston Robert B. , Albain Kathy S.
Published: March 2009

Purpose

Women of African ancestry (AA) have lower WBC counts and are more likely to have treatment delays and discontinue adjuvant breast cancer therapy early compared with white women. We assessed the association between race and treatment discontinuation/delay, WBC counts, and survival in women enrolled onto breast cancer clinical trials.

Patients and Methods

AA and white women from Southwest Oncology Group adjuvant breast cancer trials (S8814/S8897) were matched by age and protocol. Only the treatment arms in which patients were scheduled to receive six cycles of chemotherapy were analyzed.

Results

A total of 317 pairs of patients (n = 634) were analyzed. At baseline, AA women had higher body-surface area (P < .0001) and lower WBC (P = .0009). AA women were more likely to have tumors that were ≥ 2 cm (P = .01) and hormone receptor negative (P < .0001). AA women, versus white women, were marginally more likely to discontinue treatment early (11% v 7%, respectively; P = .07) or have one or more treatment delays (85% v 79%, respectively; P = .07) and were significantly more likely to experience the combined end point (discontinuation/delay; 87% v 81%, respectively; P = .04). The mean relative dose-intensity (RDI) was similar for both groups (87% in AA women v 86% in white women); however, overall, 43% had an RDI of less than 85%. After adjusting for baseline WBC and prognostic factors in a multivariate model, AA women had worse disease-free survival (hazard ratio [HR] = 1.56; 95% CI, 1.15 to 2.11; P = .005) and overall survival (HR = 1.95; 95% CI, 1.36 to 2.78; P = .0002). The inclusion of RDI and treatment delivery/quality in the regression had little impact on the results.

Conclusion

On cooperative group breast cancer trials, AA and white women had similar RDIs, but AA women were more likely to experience early discontinuation or treatment delay. Despite correcting for these factors and known predictors of outcome, AA women still had worse survival.
Traffic pattern analysis for spur lines
Authors: Kwok E C S , Sung M W H , Ng S H S
Published: March 2009

In a mass transit railway environment with spur lines, the interleaving of trains along different branches and the layover time at different termini could have a significant impact on fleet size and hence cost. These operational parameters could be systematically optimized without affecting the planned service levels.
Assessment of grounding, bonding, and insulation on rail potential and stray currents in a direct current transit system
Authors: Tzeng Y-S , Lee C-H
Published: March 2009

This article presents the effects of different grounding strategies (ungrounded, direct grounded, and diode grounded), bonding, and insulation on rail potential and stray currents in the Taipei rapid transit systems (TRTSs). The TRTS is a direct current transit railway and its running rails are used as the return conductor for traction currents. The advantage is that no dedicated return conductor is required, whereas the disadvantages are rail potential and stray-current problems. Thus, the analysis of grounding strategies is important and necessary. Moreover, the effects of cross-bonding of the running rails and stray-current collector cables (traction earth conductors) are investigated since bonding is usually used to balance traction negative return currents, to reduce resistances of the negative return circuit, as well as to decrease rail potential. Meanwhile, the effects of insulation on stray currents are also described. Simulation results for the Blue line are presented in TRTS.
Measuring axial forces in rail by forced vibrations: experiences from a full-scale laboratory experiment
Authors: Kjell G , Johnson E
Published: March 2009

The longitudinal load in rail caused by thermal expansion must be regularly monitored in order to avoid buckling or rail fracture. Different methods of monitoring with benefits and drawbacks are used or suggested. In this paper one of the proposed methods is investigated by a full-scale experiment. The aim is to measure the change in wavelength of the bending wave caused by the longitudinal load. In contrast to other vibration methods, this method does not require knowledge of the boundary conditions. However, it requires very accurate measurements, advanced finite element (FE) calculations, and sophisticated data analyses. The full-scale experiment shows that this is a method with potential. On the basis of the results of the full-scale experiment the required accuracy of the different steps in the method are clarified. Influence of measurement accuracy, loosened clamps at the sleepers, FE mesh size, degree of wear of the rail, and inaccuracy in the material parameters is considered.
Some comments on stress intensity factor calculation using different mechanisms and procedures for rolling contact fatigue cracks
Authors: Akama M , Nagashima T
Published: March 2009

Recently, attempts have been underway to simulate rolling contact fatigue (RCF) crack growth in the railhead, including also the effect of wear on maintaining the integrity of the rail and saving cost. At this juncture, it is essential to confirm whether the past analyses are adequate and what extent of differences exists when the different mechanisms or numerical procedures are applied to the same conditions in the RCF problem. Therefore, boundary-element analyses of stress intensity factors (SIFs) at the inclined surface crack tip under RCF conditions have been performed. Comparisons were made between SIFs calculated by the present analyses and those done by the numerical procedures of other researchers in the RCF problem. From this study, it was recognized that a special program should be developed to analyse the SIFs when the fluid pressure is taken into account. It was also found out that, for the analyses of SIFs, the iteration procedure with convergence calculation to specify the extent and location of locked, slipped, and separated regions on the crack faces should be used.
Should syphilis be treated differently in HIV-positive and HIV-negative individuals? Treatment outcomes at a university hospital, Brighton, UK
Authors: Warwick Z , Dean G , Fisher M
Published: March 2009

There has been much debate regarding the optimum treatment for syphilis in HIV-positive patients. There has been a shift in expert opinion in the UK towards using two doses of benzathine penicillin G one week apart regardless of HIV status. We report our experience using a 17-day course of daily procaine penicillin plus probenecid in HIV-positive individuals and two doses of benzathine in HIV-negative patients. Of 350 cases of early syphilis, 37% were in HIV-positive individuals. Ninety-eight percent of HIV-positive patients completing the treatment were followed up for at least six months and met the criteria for treatment success. The treatment response was equally good (98%) for HIV-negative patients using these different schedules. It is currently unclear which patients require an extended course of treatment for syphilis. We have demonstrated that patients adhere well to this regimen, and significantly we have shown comparable treatment success rates in HIV-positive and -negative individuals.
Time taken to undetectable viral load, following the initiation of HAART
Authors: Currie S , Rogstad K E , Piyadigamage A , Herman S
Published: March 2009

The notes of all HIV patients in Sheffield, registered at the Department of Genitourinary Medicine at the Royal Hallamshire Hospital, who had initiated HAART in 2005 and 2006, were audited. The aim was to determine what percentage of these patients acquired an undetectable viral load within 24 weeks and whether this was greater than 75% in accordance with the BHIVA guidelines. Twenty-nine (78.4%) of the 37 patients who were initiating treatment for the first time had an undetectable viral load after 24 weeks.
Chylous ascites: a late complication of intra-abdominal Mycobacterium avium complex immune reconstitution syndrome in HIV-infected patients
Authors: Phillips P , Lee J K , Wang C , Yoshida E , Lima V D , Montaner J
Published: March 2009

Chylous ascites related to Mycobacterium avium complex (MAC) in HIV-infected patients is rare, with only six cases reported in the English literature. We report a series of six cases from a single institution. During the past six years, chylous ascites was diagnosed in six (35%) of 17 AIDS patients, all of whom had previously been diagnosed with intra-abdominal MAC immune reconstitution syndrome (MAC-IRS). A review of medical records identified no other cases of chylous ascites among HIV-positive patients over the past 13 years (1994–2007), and the incidence was estimated at one in 2248 HIV-positive admissions. The ascitic fluid had a milky appearance and a median triglyceride level of 4.07 mmol/L (range 3.19–29.6 mmol/L) (360 mg/dL, range 282–2620 mg/dL). After a median follow-up of 20 months, five (83%) of six patients survived. Chylous ascites is a late complication of intra-abdominal MAC-IRS, and is usually associated with a favourable prognosis.
Suboptimal therapy and clinical management of gonorrhoea in an area with high-level antimicrobial resistance
Authors: Chen P-L , Hsieh Y-H , Lee H-C , Ko N-Y , Lee N-Y , Wu C-J , Chang C-M , Lee C-C , Ko W-C
Published: March 2009

The choice of antimicrobial agents for the treatment of gonorrhoea is critical in areas where the prevalence of drug resistance is high. This study aimed to evaluate the antibiotic treatment of gonorrhoea in endemic areas. During 1999–2004, all Neisseria gonorrhoeae infections ( n = 90) were evaluated. Patients' medical records and antibiotic treatment regimens were retrospectively reviewed if their isolates were viable ( n = 65). In vitro antimicrobial susceptibility of N. gonorrhoeae isolates was performed.

Urethritis (89%) and pelvic inflammatory disease (42%) were the most common presentations among men ( n = 53) and women ( n = 12), respectively. Of 54 patients with uncomplicated N. gonorrhoeae infection, 32 of them received appropriate antibiotics, including cefuroxime ( n = 20), ceftriaxone ( n = 10), ciprofloxacin ( n = 1) and azithromycin ( n = 1) during follow-ups. Among 65 patients, 53.8% were notified to the health authority. Check-ups of other sexually transmitted diseases were carried out in only 46% of patients. Not all isolates were susceptible to penicillin, 96.9% were resistant to tetracycline and 86% were resistant to ciprofloxacin. Ceftriaxone, cefixime, spectinomycin and azithromycin were active in vitro against all isolates. In conclusion, It is crucial to develop treatment guidelines according to regional antimicrobial resistances and educational programmes to improve clinical care for genital gonococcal diseases.
Predictors for casual sex and/or infection among sexually transmitted disease clinic attendees in China
Authors: Lu F , Jia Y , Bin S , Li C , Limei S , Kristensen S , Sun X , Xiao Y , Liu J , Li D , Qu S , Vermund S H
Published: March 2009

To assess the risk factors for casual sex and infections among the sexually transmitted disease (STD) clinic attendees in two disparate Chinese cities, an STD clinic-based cross-sectional study was conducted to provide demographic and sexual behaviour information. Participants were recruited from nine STD clinics selected by mapping strategy. STD prevalence was 69.4% (68.6% of men and 65.2% of women). The most common diagnoses were non-gonococcal urethritis (22.2%), genital warts (13.2%), syphilis (11.6%), gonorrhoea (8.4%), chlamydia (6.3%) and herpes simplex virus type 2 (HSV-2) (5.8%). Of 536 participants, 22.5% reported having casual sex in the last three months, younger age, less education, unawareness of transmission routes and having had casual sex in the last three months were independent risk factors for acquisition of an STD. Single or separated marital status, non-local residency and STD diagnoses were independently associated with having had casual sex. After decades of exceedingly low STD rates in China, a full panoply of STD diagnoses are now evident. Both for reproductive health concerns and for stemming the expansion of HIV spread, STD control and prevention must be revitalized as a priority for China's public health and medical institutions. Effective training is a priority, given the dearth of STD-experienced health-care workers.
Association of Mycoplasma genitalium with acute non-gonococcal urethritis in Russian men: a comparison with gonococcal and chlamydial urethritis
Authors: Taylor-Robinson D , Renton A , Jensen J S , Ison C A , Filatova E , Dmitriev G , Akovbian V
Published: March 2009

Urethral specimens from 172 men who attended sexually transmitted disease clinics in the Moscow Oblast were examined for Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium by nucleic acid amplification tests. N. gonorrhoeae was detected in the urethra of 41 (24%) of the 172 men and C. trachomatis in 57 (33%). The latter occurred in 15 (36%) of the 41 men who were infected by N. gonorrhoeae and in 42 (32%) of 131 uninfected by gonococci. Of the 42 men uninfected by gonococci but chlamydia infected, 39 (93%) had symptoms and/or signs of urethritis. M. genitalium was detected in 45 (26%) of the 172 men, in nine (22%) of the 41 men infected with N. gonorrhoeae and in 12 (21%) infected with C. trachomatis. M. genitalium was detected alone in 25 (28%) of the 89 men uninfected by either gonococci or C. trachomatis. Of these 25 men, 24 (96%) had urethral symptoms and signs of inflammation, a proportion significantly more than experienced by the 64 men uninfected by any of the microorganisms. Of the 31 men who apparently had no symptoms or signs of urethritis, only three (10%) were infected by M. genitalium. The data provide evidence for the pathogenicity and frequent occurrence of M. genitalium in men in Moscow and presumably elsewhere in Russia.
Unusual late nodular presentation of secondary syphilis
Authors: Lanjouw E , van der Meijden W I , den Hollander J C , Neumann H A M
Published: March 2009

A 20-year-old man presented with a five-week history of an eruption of papules and nodules disseminated over his body and face. We propose that this patient has a late form of secondary syphilis with a nodular, granulomatous inflammation in urgent need of treatment. Otherwise late irreversible sequelae could develop and unwanted possible further sexual transmission could take place.
Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution
Authors: Seddon J , Mangeya N , Miller R F , Corbett E L , Ferrand R A
Published: March 2009

Two HIV-infected patients had recurrent cryptococcal meningitis (CM) despite treatment with fluconazole and immune reconstitution with combination antiretroviral therapy (CART). Following treatment of CM with fluconazole, lumbar puncture should be performed either after completion of induction treatment for CM or before starting CART, in order to confirm cerebrospinal fluid sterility.
Haemophilus ducreyi detection by polymerase chain reaction in oesophageal lesions of HIV patients
Authors: Borges M C , Colares J K B , Lima D M , Fonseca B A L
Published: March 2009

HIV patients frequently have opportunistic oesophageal infections. We report Haemophilus ducreyi genetic material detected by polymerase chain reaction in biopsies of oesophageal lesions in three HIV-1-infected patients. This finding may be an indication of its aetiopathological role in oesophageal lesions of HIV patients.
Abacavir-induced reaction with fever and severe skin rash in a patient tested human leukocyte antigen-B*5701 negative
Authors: Calza L , Rosseti N , Biagetti C , Pocaterra D , Colangeli V , Manfredi R
Published: March 2009

The most serious adverse event caused by abacavir is the hypersensitivity reaction, which is usually associated with the presence of the human leukocyte antigen (HLA) subtype B*5701, as shown in recent studies. We describe the case of a 41-year-old Caucasian female patient, who tested HLA-B*5701 negative and developed fever and severe skin rash 10 weeks after the start of abacavir therapy. Similar reports suggest that not all severe abacavir-induced adverse events occur as a result of classic hypersensitivity reactions, and can present also in HLA-B*5701-negative patients.
Syphilitic hepatitis among HIV-infected patients
Authors: Crum-Cianflone N , Weekes J , Bavaro M
Published: March 2009

Syphilis is an important public health issue and continues to occur at high rates among HIV-infected patients. Although abnormal liver function tests are common among HIV-infected persons, the incidence of syphilitic hepatitis in this population is currently unknown. We present two cases of syphilitic hepatitis and performed a retrospective study to determine the incidence of hepatitis during early syphilis infections among HIV-infected persons. Our study showed that syphilitic hepatitis is common, occurring in 38% (12/32) of HIV-positive patients with early stages of syphilis infection. Most cases occurred during secondary syphilis, with the most common finding being a maculopapular rash. Syphilis should be included in the differential diagnosis of HIV patients presenting with liver test abnormalities, rash and/or sexual risk factors.
A delayed hypersensitivity reaction to enfuvirtide after rechallenge
Authors: Emerson C R , Post J J , Workman C
Published: March 2009

Enfuvirtide is beneficial in patients with limited treatment options. We report this case to highlight the possibility of a delayed hypersensitivity reaction as an important potential side-effect of enfuvirtide treatment. A highly antiretroviral treatment-experienced man was commenced on a new regimen containing enfuvirtide. Prophylaxis for Pneumocystis jirovecii pneumonia was started using trimethoprim/sulphamethoxazole (TMP-STX) simultaneously. Ten days later, he developed a maculopapular rash on the chest and abdomen without any systemic features. Both enfuvirtide and TMP-STX were discontinued. Re-introduction of enfuvirtide occurred in a hospital setting. Before re-challenge, haemodynamic observations were stable. The rash re-appeared involving the whole body 5 hours post-dose and was associated with fever (temperature 38.4), nausea and a presyncopal episode.

Hypersensitivity to this drug occurred immediately post-dose in phase III trials. Enfuvirtide is a useful drug in those with reduced drug options. The possibility of delayed hypersensitivity has not been reported previously.
The Internet as a diagnostic aid: the patients' perspective
Authors: Schembri G , Schober P
Published: March 2009

A questionnaire-based cross-sectional study was conducted in order to determine how frequently patients attending a genitourinary (GU) medicine clinic use the Internet to diagnose their own symptoms, and to assess the accuracy of their diagnosis. Out of 223 symptomatic patients attending a GU clinic, 101 (45.3%) looked up their symptoms on the Internet. The age difference between those who looked up their symptoms and those who did not was not statistically significant ( P = 0.77). Twenty (19.8%) out of 101 patients diagnosed their own symptoms, and 14 (13.9%) patients made the correct diagnosis. Ninety-one (90.1%) patients used the Google® search engine as the starting point for their search.

Although the Internet plays an important role in providing health information, the variable quality of health information available limits its use as a diagnostic tool by patients.
Loneliness, social support and family function of people living with HIV/AIDS in Anhui rural area, China
Authors: Sun Y-H , Sun L , Wu H-Y , Zhang Z-K , Wang B , Yu C , Cao H-Y
Published: March 2009

The main purpose of this study was to investigate how loneliness was associated with social support and family function among people living with HIV/AIDS (PLWHA) in an HIV-stricken area of China. Two hundred and nineteen PLWHA were surveyed using the UCLA (University of California at Los Angeles)-Loneliness Scale, the Social Support Rate Scale and the Family APGAR (Adaptability, Partnership, Growth, Affection and Resolve) Index. The results indicated that the majority (84.5%) of PLWHA had moderate to high levels of loneliness, with a mean score of 47.62 and a standardized score of 59.53. The level of loneliness was significantly different in subjects' occupations, but not in other sociodemographic variables. Social support, family function and all dimensions except utilizations of support were significantly negatively associated with loneliness. Multiple regression revealed that less social support and poor family function were associated with more loneliness. In conclusion, loneliness prevails among PLWHA. It may limit PLWHA's ability or access to social relationship. These findings support the hypothesis that if PLWHA are better supported and cared for, their negative psychosocial consequences might be prevented or at least reduced.
Identification of oral candidosis, hairy leukoplakia and recurrent oral ulcers as distinct cases of immune reconstitution inflammatory syndrome
Authors: Ramírez-Amador V A , Espinosa E , González-Ramírez I , Anaya-Saavedra G , Ormsby C E , Reyes-Terán G
Published: March 2009

Oral lesions such as candidosis, hairy leukoplakia (HL) and oral ulcers are strikingly absent in the numerous reports of immune reconstitution inflammatory syndrome (IRIS). To document oral manifestations attributable to immune reconstitution, we conducted a longitudinal follow-up of a cohort of HIV+ individuals starting highly active antiretroviral therapy (HAART) and completing oral pathology follow-up up to 12 weeks after treatment initiation. HIV-infected patients had oral examinations, CD4+ T-cell count and viral load determinations performed at baseline, and at weeks 4, 8 and 12 after HAART initiation. Among individuals with satisfactory viral response and recovery of ≥50 CD4+ T-cell/µL, eight patients complied with strict IRIS criteria: two developed clinical signs of oral candidosis (OC), two oral ulcers, three HL and one Kaposi's sarcoma. CD4+ T-cell counts at symptom onset suggested no remaining immune suppression. Our findings show that cases of OC, HL and recurrent ulcers can be instances of IRIS.
Effect of HIV viral load, CD4 cell count and antiretroviral therapy on human papillomavirus prevalence in urine samples of HIV-infected men
Authors: Jong E , van Gorp E C M , Mulder J W , Tol A , Smits P H M
Published: March 2009

HIV-infected patients are at increased risk for persistent human papillomavirus (HPV) infection, the major cause of anogenital cancer. The present study describes the HPV prevalence in urine samples of 243 HIV-infected men and a control group of 231 men. HPV DNA was amplified by the SPF10 polymerase chain reaction primer set. The overall HPV prevalence in HIV-infected men was 27.5% compared with 12.6% in controls ( P < 0.01). Infections with high-risk and multiple HPV genotypes were present in both groups. Differences were not statistically significant. A multivariate logistic regression model showed a decreased HPV prevalence associated with use of a nucleoside and a non-nucleoside reverse transcriptase inhibitor combination ( P = 0.03). A trend was observed towards a higher HPV prevalence and a lower CD4 cell count. Further prospective studies are needed to determine the role of HPV DNA testing in urine in future screening programmes for anal cancer in men.
Documentation of advice regarding safer sexual practices and partner notification within an HIV clinic
Authors: McNulty M , Kingston M
Published: March 2009

Guidelines for the sexual health care of our HIV patients and provision of post-exposure prophylaxis following sexual exposure have been produced by both British Association of Sexual Health & HIV and British HIV Association (BHIVA). In the light of recent criminal prosecutions, BHIVA produced guidance for HIV clinical teams regarding discussions with patients about HIV transmission and reducing the risk to sexual partners. This audit examined the advice given to HIV patients with regard to safer sexual practices, sexually transmitted infection screening and partner notification and found that, on the whole, the standards set by national guidelines were adhered to, although areas for improvement were identified. We hope that the introduction of proformas with specific prompts for these subjects for HIV clinic visits will improve clinical standards in this area.
How many cases of chlamydial infection would we miss by not testing partners for infection?
Authors: Forbes G , Clutterbuck D J
Published: March 2009

Quality Improvement Scotland standards for sexual health services require that 0.64 contacts per case should be verified as having attended within 90 days of the first partner notification interview. Partner delivered therapy results in more patients being treated than when patients are given information for partners but removes the possibility of further cases of Chlamydia trachomatis being diagnosed through the tracing of secondary contacts. An audit was performed to estimate the impact of removing secondary contacts on the number of chlamydial infections identified in our service. Patients who were not known to be contacts of chlamydial infection were included. One hundred and twenty-seven index cases generated 189 contacts, of which 100 were confirmed as tested and treated. Sixty-four were C. trachomatis positive, who in turn generated 36 new contacts. Fourteen of these were positive. Secondary contact tracing identified 22–28% more cases of chlamydial infection in our service than if all partners were treated without testing.
Immune reconstitution inflammatory syndrome
Authors: Elston J W T , Thaker H
Published: March 2009

Antiretroviral therapy (ART) inhibits HIV replication, allowing recovery of CD4+ T cell numbers and the restoration of immune function; its introduction has led to improved outcomes for individuals with HIV infection. However, it has been observed that some individuals responding to ART experience a clinical deterioration with symptoms and signs of an inflammatory illness. Immune reconstitution inflammatory syndrome (IRIS) results from pathological immune responses occurring during immune reconstitution. IRIS is best considered a group of disorders with a wide range of clinical manifestations, incorporating disease resulting from pathological inflammation to pathogens, immune-mediated inflammatory disease and autoimmune disease. Clinical effects range from a mild, self-limiting illness to severe morbidity and mortality. Clinicians working in the field of HIV medicine can expect to encounter individuals with IRIS. In this review, we discuss definitions, describe clinical presentations, summarize research relating to pathogenesis and identify risk factors, preventive and management strategies.
Resistance mutations in HIV-1 infected pregnant women and their infants receiving antiretrovirals to prevent HIV-1 vertical transmission in China
Authors: Han J , Wang L , Jiang Y , Zhang Q , Fang L , Yao J , Wang Q
Published: March 2009

The objective of this study was to assess the resistance baseline in HIV-1-infected pregnant women in China and the emergence of drug resistance (DR) among them and their infants after receiving single-dose nevirapine (sdNVP) or zidovudine plus sdNVP (ZDV-sdNVP) for the prevention of mother-to-child transmission (PMTCT). The prospective study followed 62 drug-naïve HIV-1-infected mothers and their infants who received sdNVP for PMTCT and 18 who received ZDV-sdNVP. Primary DR was detected in 8.8% (7/80) of pregnant women at baseline. Two (2.5%) women had mutations associated with nucleoside reverse transcriptase inhibitors (NRTI). Six (7.5%) women harboured mutations associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). No protease inhibitor (PI) DR was detected. The DR rates in infected mothers selected by sdNVP and ZDV-sdNVP regimen were 16.3% and 0%, respectively. Women with the emergence of DR after sdNVP had lower CD4 cell counts at delivery than women without DR after sdNVP (178 vs.364 cells/mm3, P < 0.05). The vertical transmission rate in women with baseline resistance was similar to that in women without baseline resistance (1/7 vs. 3/73, P > 0.05). The study indicates that NVP resistance after sdNVP was associated with CD4 cell count at delivery. ZDV-sdNVP regimen was of more significance in the prevention of the emergence of NNRTI-related DR than sdNVP.
Expanded hammerhead ribozymes containing addressable three-way junctions
Authors: Wieland Markus , Gfell Manuela , Hartig Jörg S.
Published: March 2009

Recently, hammerhead ribozyme (HHR) motifs have been utilized as powerful tools for gene regulation. Here we present a novel design of expanded full-length HHRs that allows attaching additional functionalities to the ribozyme. These features allowed us to construct a very efficient artificial riboswitch in bacteria. Following the design of naturally occurring three-way junctions we attached an additional helix (IV) to stem I of the HHR while maintaining very fast cleavage rates. We found that the cleavage activity strongly depends on the exact design of the junction site. Incorporation of the novel ribozyme scaffold into a bacterial mRNA allowed the control of gene expression mediated by autocatalytic cleavage of the ribozyme. Appending an aptamer to the newly introduced stem enabled the identification of very powerful theophylline-inducible RNA switches by in vivo screening. Further investigations revealed a cascading system operating beyond the ribozyme-dependent mechanism. In conclusion, we extended the hammerhead toolbox for synthetic biology applications by providing an additional position for the attachment of regulatory modules for in vivo control of gene expression.
Multiple independent domains of dGW182 function in miRNA-mediated repression in Drosophila
Authors: Chekulaeva Marina , Filipowicz Witold , Parker Roy
Published: March 2009

miRNA-mediated repression affects a wide range of biological processes including development and human pathologies. The GW182 protein is a key component of miRNA repression complex, recruited by Argonaute and functioning downstream to repress translation and accelerate mRNA degradation, but little is known about how GW182 proteins act. Using both tethered function and complementation assays, we identify three independent domains of the Drosophila GW182 protein (also termed Gawky) that are sufficient to repress mRNA. Each of these domains also functions independently of poly(A) tails. These results indicate that miRNA-mediated repression is facilitated by multiple domains of GW182.
Polyadenylation releases mRNA from RNA polymerase II in a process that is licensed by splicing
Authors: Rigo Frank , Martinson Harold G.
Published: March 2009

When transcription is coupled to pre-mRNA processing in HeLa nuclear extracts nascent transcripts become attached to RNA polymerase II during assembly of the cleavage/polyadenylation apparatus (CPA), and are not released even after cleavage at the poly(A) site. Here we show that these cleaved transcripts are anchored to the polymerase at their 3′ ends by the CPA or, when introns are present, by the larger 3′-terminal exon definition complex (EDC), which consists of splicing factors complexed with the CPA. Poly(A) addition releases the RNA from the polymerase when the RNA is anchored only by the CPA. When anchored by the EDC, poly(A) addition remains a requirement, but it triggers release only after being licensed by splicing. The process by which RNA must first be attached to the polymerase by the EDC, and then can only be released following dual inputs from splicing and polyadenylation, provides an obvious opportunity for surveillance as the RNA enters the transport pathway.
Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression
Authors: Zipprich Jakob T. , Bhattacharyya Sankar , Mathys Hansruedi , Filipowicz Witold
Published: March 2009

Proteins of the GW182 family play an important role in the execution of microRNA repression in metazoa. They interact directly with Argonaute proteins, components of microRNPs, and also form part of P-bodies, structures implicated in translational repression and mRNA degradation. Recent results demonstrated that Drosophila GW182 has the potential to both repress translation and accelerate mRNA deadenylation and decay. In contrast to a single GW182 protein in Drosophila, the three GW182 paralogs TNRC6A, TNRC6B, and TNRC6C are encoded in mammalian genomes. In this study, we provide evidence that TNRC6C, like TNRC6A and TNRC6B, is important for efficient miRNA repression. We further demonstrate that tethering of each of the human TNRC6 proteins to a reporter mRNA has a dramatic inhibitory effect on protein synthesis. The repression is due to a combination of effects on the mRNA level and mRNA translation. Through deletion and mutagenesis, we identified the C-terminal part of TNRC6C encompassing the RRM RNA-binding motif as a key effector domain mediating protein synthesis repression by TNRC6C.