Does high body mass index (>25 kg/m2) or weight (>80 kg) reduce the effectiveness of anti-D prophylaxis in Rh(D)-negative pregnant women? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haemolytic disease of the foetus and newborn (HDFN) occurs when maternal antibodies, often triggered by foetal antigens, destroy foetal and neonatal red blood cells. Factors like antibody strength, quantity and gestational age influence HDFN severity. Routine antenatal anti-D prophylaxis (RAADP) has significantly reduced HDFN cases. However, the effect of overweight/obesity (body mass index [BMI] > 25/30 kg/m2) on anti-D prophylaxis efficacy remains unclear. This systematic review will examine the impact of BMI on anti D prophylaxis effectiveness in Rh(D) negative pregnant women. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. We searched databases from 1996 to 2023, focusing on studies exploring the link between high BMI/weight and anti-D serum levels in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. Ten eligible studies were included, three suitable for meta-analysis. Study quality was assessed using the Strengthening the Reporting Observation Studies in Epidemiology (STROBE) checklist. Statistical analyses included Pearson correlation coefficients and risk differences. RESULTS: Our meta-analysis revealed a significant negative correlation (r = -0.59, 95% confidence interval [CI]: -0.83 to -0.35, p = 0.007) between high BMI/weight and serial anti-D levels in in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. High BMI/weight had lower odds of serial anti-D level exceeding 30 ng/mL (arcsine risk difference [ARD] = 0.376, 95% CI: 0.143-0.610, p = 0.002). Heterogeneity among studies was low (I2 = 0). CONCLUSION: While our analysis suggests a potential linkage between high BMI/weight and reduced efficacy of anti-D prophylaxis, caution is warranted due to study limitations. Variability in study design and confounding factors necessitate careful interpretation. Further research is needed to confirm these findings and refine clinical recommendations.

Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma.

The mitochondrion is a gatekeeper of apoptotic processes, and mediates drug resistance to several chemotherapy agents used to treat cancer. Neuroblastoma is a common solid cancer in young children with poor clinical outcomes following conventional chemotherapy. We sought druggable mitochondrial protein targets in neuroblastoma cells. Among mitochondria-associated gene targets, we found that high expression of the mitochondrial adenine nucleotide translocase 2 (SLC25A5/ANT2), was a strong predictor of poor neuroblastoma patient prognosis and contributed to a more malignant phenotype in pre-clinical models. Inhibiting this transporter with PENAO reduced cell viability in a panel of neuroblastoma cell lines in a TP53-status-dependant manner. We identified the histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), as the most effective drug in clinical use against mutant TP53 neuroblastoma cells. SAHA and PENAO synergistically reduced cell viability, and induced apoptosis, in neuroblastoma cells independent of TP53-status. The SAHA and PENAO drug combination significantly delayed tumour progression in pre-clinical neuroblastoma mouse models, suggesting that these clinically advanced inhibitors may be effective in treating the disease.

Optimising the biocompatibility of 3D printed photopolymer constructs in vitro and in vivo.

3D printing is a rapid and accessible fabrication technology that engenders creative custom design solutions for cell scaffolds, perfusion systems and cell culture systems for tissue engineering. Critical to its success is the biocompatibility of the materials used, which should allow long-term tissue culture without affecting cell viability or inducing an inflammatory response for in vitro and in vivo applications. Polyjet 3D printers offer arguably the highest resolution with the fewest design constraints of any commercially available 3D printing systems. Although widely used for rapid-prototyping of medical devices and 3D anatomical modelling, polyjet printing has not been adopted by the tissue engineering field, largely due to the cytotoxicity of leachates from the printed parts. Biocompatibility in the context of cell culture is not commonly addressed for polyjet materials, as they tend to be optimised for their ability to fabricate complex structures. In order to study the potential issues surrounding the leaching of toxins, we prepared cell culture substrates using the commercially available MED610 photopolymer. The substrates were cleaned using either the manufacturer-specified 'biocompatible' washing procedures, or a novel protocol incorporating a sonication in isopropanol and water step. We then compared the effectiveness of these both in vitro and in vivo. Using primary mouse myoblast cultures, the manufacturer's protocol led to inconsistent and poorer cell viability when compared to the sonication protocol (p = 0.0002 at 48 h after indirect exposure). Subdermal implantation of MED610 into nude rats demonstrated a significant foreign body response with a greater number of giant cells (p = 0.0161) and foreign bodies (p = 0.0368) when compared to the sonication protocol, which was comparable to the control (sham) groups. These results present an improved, cytocompatible cleaning protocol of printable photopolymers to facilitate creative 3D-printed custom designs for cell culture systems for both in vitro and in vivo tissue engineering applications.

Biological false-positive venereal disease research laboratory test in cerebrospinal fluid in the diagnosis of neurosyphilis - a case-control study.

BACKGROUND: There is no clear consensus on the diagnosis of neurosyphilis. The Venereal Disease Research Laboratory (VDRL) test from cerebrospinal fluid (CSF) has traditionally been considered the gold standard for diagnosing neurosyphilis but is widely known to be insensitive. OBJECTIVE: In this study, we compared the clinical and laboratory characteristics of true-positive VDRL-CSF cases with biological false-positive VDRL-CSF cases. METHODS: We retrospectively identified cases of true and false-positive VDRL-CSF across a 3-year period received by the Immunology and Serology Laboratory, Singapore General Hospital. A biological false-positive VDRL-CSF is defined as a reactive VDRL-CSF with a non-reactive Treponema pallidum particle agglutination (TPPA)-CSF and/or negative Line Immuno Assay (LIA)-CSF IgG. A true-positive VDRL-CSF is a reactive VDRL-CSF with a concordant reactive TPPA-CSF and/or positive LIA-CSF IgG. RESULTS: During the study period, a total of 1254 specimens underwent VDRL-CSF examination. Amongst these, 60 specimens from 53 patients tested positive for VDRL-CSF. Of the 53 patients, 42 (79.2%) were true-positive cases and 11 (20.8%) were false-positive cases. In our setting, a positive non-treponemal serology has 97.6% sensitivity, 100% specificity, 100% positive predictive value and 91.7% negative predictive value for a true-positive VDRL-CSF based on our laboratory definition. HIV seropositivity was an independent predictor of a true-positive VDRL-CSF. CONCLUSION: Biological false-positive VDRL-CSF is common in a setting where patients are tested without first establishing a serological diagnosis of syphilis. Serological testing should be performed prior to CSF evaluation for neurosyphilis.

Correction to: mouse mammary tumour virus (MMTV) and human breast cancer with neuroendocrine differentiation.

[This corrects the article DOI: 10.1186/s13027-017-0135-8.].

Interferon-gamma release assay as a diagnostic test for tuberculosis-associated uveitis.

BACKGROUND: To study the use of interferon-gamma release assay (IFN-γ) (IGRAs) as a diagnostic test for tuberculosis (TB)-associated uveitis (TAU). DESIGN: Prospective cohort study. PARTICIPANTS: Consecutive new patients (n=162) with clinical ocular signs suggestive of TAU, seen >1 year period at a single tertiary center. METHODS: All subjects underwent investigations to rule out underlying disease, including T-SPOT.TB and tuberculin skin test (TST). Twenty-one subjects with underlying disease and three with interdeterminate T-SPOT.TB results were excluded. Those with T-SPOT.TB- or TST-positive results were referred to infectious diseases physician for evaluation. Anti-TB therapy (ATT) was prescribed if required. Patients' treatment response and recurrence were monitored for six months after completion of ATT, if given; or 1 year if no ATT was given. MAIN OUTCOME MEASURE: Diagnosis of TAU. RESULTS: Mean age of study cohort (n=138) was 46.8 ± 15.3 years. Majority were Chinese (n=80, 58.0%) and female (n=75, 54.3%). TST was more sensitive than T-SPOT.TB (72.0% vs 36.0%); but T-SPOT.TB was more specific (75.0% vs 51.1%) for diagnosing TAU. Patients with either a T-SPOT.TB (1.44; 95% confidence intervals (CI), 0.86-2.42) or TST (1.47; 95% CI, 1.12-1.94)-positive result are more likely to have TAU. The accuracy of diagnosing TAU increases when both tests are used in combination (area under the receiver operator curve=0.665; 95% CI, 0.533-0.795). Patients with both tests positive are 2.16 (95% CI, 1.23-3.80) times more likely to have TAU. Negative T-SPOT.TB or TST results do not exclude TAU (negative likelihood ratios <1.0). CONCLUSIONS: We recommend using a combination of clinical signs, IGRA, and TST to diagnose TAU.

Under-recognition and reporting of dengue in Cambodia: a capture-recapture analysis of the National Dengue Surveillance System.

Robust disease burden estimates are important for decision-making concerning introduction of new vaccines. Dengue is a major public health problem in the tropics but robust disease burden estimates are lacking. We conducted a two-sample, capture-recapture study in the largest province in Cambodia to determine disease under-recognition to the National Dengue Surveillance System (NDSS). During 2006-2008, community-based active surveillance for acute febrile illness was conducted in 0- to 19-year-olds in rural and urban areas combined with testing for dengue virus infection. Of 14 354 individuals under active surveillance (22 498 person-seasons), the annual incidence ranged from 13·4 to 57·8/1000 person-seasons. During the same period, NDSS incidence rates ranged from 1·1/1000 to 5·7/1000, which was 3·9- to 29·0-fold lower than found in the capture-recapture study. In hospitalized cases, the rate of under-recognition was 1·1- to 2·4-fold. This study shows the substantial degree of under-recognition/reporting of dengue and that reported hospitalized cases are not a good surrogate for estimating dengue disease burden.

Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian regions, 2007-2008.

Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. In 2007 and 2008, this Gonococcal Antimicrobial Surveillance Programme (GASP) was enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres within the WPR. Approximately 17,450 N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea by external quality controlled methods in 24 reporting centres in 20 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR, but much lower rates of penicillin resistance and little quinolone resistance was present in most of the Pacific Island countries. The proportion of gonococci reported as 'resistant', 'less susceptible' or 'non-susceptible' gonococci to the third-generation cephalosporin antibiotic ceftriaxone lay in a wide range, but no major changes were evident in cephalosporin minimal inhibitory concentration (MIC) patterns in 2007-2008. Altered cephalosporin susceptibility was associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit a form of plasmid mediated high level resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR supports the need for gonococcal antimicrobial resistance surveillance programs such as GASP to be maintained and potentially expanded.

Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer.

Recent studies have identified vimentin, a type III intermediate filament, among genes differentially expressed in tumours with more invasive features, suggesting an association between vimentin and tumour progression. The aim of this study, was to investigate whether vimentin expression in colon cancer tissue is of clinical relevance. We performed immunostaining in 142 colorectal cancer (CRC) samples and quantified the amount of vimentin expression using computer-assisted image analysis. Vimentin expression in the tumour stroma of CRC was associated with shorter survival. Overall survival in the high vimentin expression group was 71.2% compared with 90.4% in the low-expression group (P=0.002), whereas disease-free survival for the high-expression group was 62.7% compared with 86.7% for the low-expression group (P=0.001). Furthermore, the prognostic power of vimentin for disease recurrence was maintained in both stage II and III CRC. Multivariate analysis suggested that vimentin was a better prognostic indicator for disease recurrence (risk ratio=3.5) than the widely used lymph node status (risk ratio=2.2). Vimentin expression in the tumour stroma may reflect a higher malignant potential of the tumour and may be a useful predictive marker for disease recurrence in CRC patients.

Expression of PPARdelta in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology.

Whether peroxisome proliferator-activated receptor (PPAR) delta is a good target for the chemoprevention and/or treatment of colorectal cancer (CRC) remains controversial. Our goal was to examine PPARdelta expression in multistage carcinogenesis of the colorectum and to assess the relevance of PPARdelta in CRC. Immunohistochemical analysis indicated that PPARdelta expression increased from normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPARdelta protein was accumulated only in those cancer cells with highly malignant morphology, as represented by a large-sized nucleus, round-shaped nucleus, and presence of clear nucleoli. Interestingly, the cancer tissue often contained both PPARdelta-positive and -negative areas, each retaining their respective specific morphological features. Moreover, this pattern persisted even when PPARdelta-positive and -negative cells were aligned next to each other within a single cancer nest or gland and was present in the majority of CRC cases. Immunohistochemistry for Ki-67 proliferation marker showed no significant correlation between Ki-67 and PPARdelta in CRC samples. Based on Western blot analysis and quantitative RT-PCR, high PPARdelta protein expression correlated with high PPARdelta mRNA levels. Peroxisome proliferator-activated receptor delta may have a supporting role in tumorigenesis, and the close association between PPARdelta expression and malignant morphology of CRC cells suggests a pivotal role in cancer tissue.

Dissipation of chlorothalonil, chlorpyrifos, and profenofos in a Malaysian agricultural soil: a comparison between the field experiment and simulation by the PERSIST model.

A comparison of dissipation of chlorothalonil, chlorpyrifos, and profenofos in a Malaysian agricultural soil between the field experiment and simulation by the PERSIST model was studied. A plot of sweet pea (Pisum sativum) from a farm in the Cameron Highlands was selected for the field experiment. The plot was treated with chlorothalonil, chlorpyrifos, and profenofos. Core soil collection was conducted according to the sampling schedule. Residues of the three pesticides were analyzed in the laboratory. Simulations of the three pesticides' persistency were also conducted using a computer-run software PERSIST. Generally, predicted data obtained using PERSIST were found to be high for the three pesticides except for one field measurement of chlorpyrifos. The predicted data for profenofos, which is the most mobile of the three pesticides tested, was not well matched with the observed data compared to chlorothalonil and chlorpyrifos.

Eikenella corrodens discitis after spinal surgery: case report and literature review.

Eikenella corrodens is part of the normal flora of the mouth and upper respiratory tract and is usually associated with dental and head and neck infections. We report a case of Eikenella discitis occurring soon after spinal surgery in an otherwise healthy patient, review the literature on bone and joint infections unrelated to human bites and fist-fight injuries, and stress the importance of definitive diagnosis in post-operative spinal infections.

Epidemiology of beta-haemolytic group G streptococcal bacteraemia in Singapore (1996 to 1998).

INTRODUCTION: Group G streptococcus (GGS) accounted for 8% to 44% of all bacteraemias due to beta-haemolytic streptococci according to various reports. The aims of this study were 1) to describe the epidemiology of GGS bacteraemia in Singapore for which local data are lacking and 2) to compare its frequency of isolation to the other Lancefield groups. PATIENTS AND METHODS: The study period was from 1 January 1996 to 30 June 1998. The laboratory records of 2 large acute care hospitals were examined. There was a total of 85 patients. The medical records of 52 patients were available for analysis. In addition, laboratory microbiological data from 1993 to 1999 were reviewed and the number of blood cultures that were positive for beta-haemolytic streptococci groups A, B, C and G was collated. RESULTS: The majority involved the elderly. The mean age was 67 years. The skin was the major portal of entry. Local conditions predisposing the skin to infection occurred in 40.4%. Co-morbidity included malignancies in 28.8% of patients, diabetes mellitus in 11.5% and liver disease in 9.6%. Mortality was 15.4% including fatal septic shock. Recurrent bacteraemia occurred in 5.8% of the patients. The majority (90.4%) were community-acquired infections. GGS, along with group B streptococcus (GBS), was the most common streptococcus among the beta-haemolytic streptococci causing bacteraemia in these 2 hospitals.

Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice.

Fanconi anemia (FA) is a heterogeneous autosomal recessive chromosomal instability syndrome associated with diverse developmental abnormalities, progressive bone marrow failure and a predisposition to cancer. Spontaneous chromosomal breakage and hypersensitivity to DNA cross-linking agents characterize the cellular FA phenotype. The gene affected in FA complementation group G patients was initially identified as XRCC9, for its ability to partially correct the cellular phenotype of the Chinese hamster ovary (CHO) cell mutant UV40. By targeted disruption we generated Fancg/Xrcc9 null mice. Fancg knock-out (KO) mice were born at expected Mendelian frequencies and showed normal viability. In mice, functional loss of Fancg did not result in developmental abnormalities or a pronounced incidence of malignancies. During a 1 year follow-up, blood cell parameters of Fancg KO mice remained within normal values, revealing no signs of anemia. Male and female mice deficient in Fancg showed hypogonadism and impaired fertility, consistent with the phenotype of FA patients. Mouse embryonic fibroblasts (MEFs) from the KO animals exhibited the FA characteristic cellular response in showing enhanced spontaneous chromosomal instability and a hyper-responsiveness to the clastogenic and antiproliferative effects of the cross-linking agent mitomycin C (MMC). The sensitivity to UV, X-rays and methyl methanesulfonate, reported for the CHO mutant cell line UV40, was not observed in Fancg(-/-) MEFs. Despite a lack of hematopoietic failure in the KO mice, clonogenic survival of bone marrow cells in vitro was strongly reduced in the presence of MMC. The characteristics of the Fancg(-/-) mice closely resemble those reported for Fancc and Fanca null mice, supporting a tight interdependence of the corresponding gene products in a common pathway.

Laser in situ keratomileusis enhancement after radial keratotomy.

PURPOSE: To present results of laser in situ keratomileusis (LASIK) enhancement after radial keratotomy (RK). METHODS: Sixteen eyes of 10 patients were treated with LASIK for residual myopia and hyperopia after RK. Mean preoperative spherical equivalent refraction was -3.14+/-3.04 D (range, -6.675 to +6.00 D). Best spectacle-corrected visual acuity was 20/20 in 9 eyes, 20/25 in 6 eyes, and 20/30 in 1 eye. Uncorrected visual acuity was better than 20/40 in only 2 eyes. Patients were followed at 1 day, 1 week, 1, 3, and 6 months, and 1 year. Mean follow-up was 8.3 months (range, 1 to 17 mo). RESULTS: All eyes received one LASIK enhancement. Mean final spherical equivalent refraction was +0.16+/-0.68 D (range, -1.00 to +1.75 D). No eyes experienced any visual loss. Five eyes gained 1 line of best spectacle-corrected visual acuity. Uncorrected visual acuity was 20/20 in 9 eyes, 20/25 in 6 eyes, and 20/30 in 1 eye. Two eyes of one patient had the previous RK incisions open. CONCLUSION: LASIK was an effective treatment for correction of residual myopia and hyperopia after RK.

Molecular typing of multiresistant Streptococcus pneumoniae serogroup 19 in Singapore.

The prevalence of penicillin-resistant Streptococcus pneumoniae in clinical isolates from the Pathology Department of the Singapore General Hospital, in 1995, was 25%. Most of the resistant isolates belonged to serogroup 19 and were resistant to multiple antibiotics. Field-inversion gel electrophoresis (FIGE), after chromosomal digestion with the restriction enzymes Apal and Smal, was performed on all isolates of multiresistant serogroup 19 S. pneumoniae so as to determine whether they were of clonal origin. Twenty-six isolates, including six controls, were studied. Analysis of the FIGE patterns revealed three distinct clusters of closely related strains. The predominant clone comprised ten isolates of multiresistant serogroup 19 S. pneumoniae and also included two controls of a different serogroup. The presence of multiresistant serogroup 19 S. pneumoniae in Singapore, appears to be due to the spread of a small number of clones.

The effect of polyethylene glycol (PEG) on the isolation of Chlamydia trachomatis in H-1 HeLa cells.

One hundred and ninety-six urethral and endocervical swabs were processed for isolation of C. trachomatis, using H-1 HeLa cells on shell vials, in the presence and absence of 7% PEG in the chlamydial overlay medium. The results were divided into three evaluable groups based on the number of inclusions per coverslip in the shell vials without PEG. The number of inclusions were compared with that of PEG-treated cultures using the paired t-test. The ranges for the three evaluable groups were one to ten, 11-100 and 101-1000 inclusions per coverslip. All three groups showed a significant increase (2.8- to 3.8-fold) in the number of inclusion bodies in the PEG-treated cultures compared to the untreated cultures.