Wnt and SHH in prostate cancer: trouble mongers occupy the TRAIL towards apoptosis

Prostate cancer is a serious molecular disorder that arises because of reduction in tumour suppressors and overexpression of oncogenes. The malignant cells survive within the context of a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. These signals are, nonetheless, deregulated through perturbations to mechanotransduction, from the nanoscale level to the tissue level. Increasingly sophisticated interpretations have uncovered significant contributions of signal transduction cascades in governing prostate cancer progression. To dismantle the major determinants that lie beneath disruption of spatiotemporal patterns of activity, crosstalk between various signalling cascades and their opposing and promoting effects on TRAIL-mediated activities cannot be ruled out. It is important to focus on that molecular multiplicity of cancer cells, various phenotypes reflecting expression of a variety of target oncogenes, reversible to irreversible, exclusive, overlapping or linked, coexist and compete with each other. Comprehensive investigations into TRAIL-mediated mitochondrial dynamics will remain a worthwhile area for underlining causes of tumourigenesis and for unravelling interference options.     

Imaging and artificial intelligence for progression of age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of severe vision loss. With our aging population, it may affect 288 million people globally by the year 2040. AMD progresses from an early and intermediate dry form to an advanced one, which manifests as choroidal neovascularization and geographic atrophy. Conversion to AMD-related exudation is known as progression to neovascular AMD, and presence of geographic atrophy is known as progression to advanced dry AMD. AMD progression predictions could enable timely monitoring, earlier detection and treatment, improving vision outcomes. Machine learning approaches, a subset of artificial intelligence applications, applied on imaging data are showing promising results in predicting progression. Extracted biomarkers, specifically from optical coherence tomography scans, are informative in predicting progression events. The purpose of this mini review is to provide an overview about current machine learning applications in artificial intelligence for predicting AMD progression, and describe the various methods, data-input types, and imaging modalities used to identify high-risk patients. With advances in computational capabilities, artificial intelligence applications are likely to transform patient care and management in AMD. External validation studies that improve generalizability to populations and devices, as well as evaluating systems in real-world clinical settings are needed to improve the clinical translations of artificial intelligence AMD applications.     

Parthenogenesis-derived multipotent stem cells adapted for tissue engineering applications

Embryonic stem cells are envisioned as a viable source of pluripotent cells for use in regenerative medicine applications when donor tissue is not available. However, most current harvest techniques for embryonic stem cells require the destruction of embryos, which has led to significant political and ethical limitations on their usage. Parthenogenesis, the process by which an egg can develop into an embryo in the absence of sperm, may be a potential source of embryonic stem cells that may avoid some of the political and ethical concerns surrounding embryonic stem cells. Here we provide the technical aspects of embryonic stem cell isolation and expansion from the parthenogenetic activation of oocytes. These cells were characterized for their stem-cell properties. In addition, these cells were induced to differentiate to the myogenic, osteogenic, adipogenic, and endothelial lineages, and were able to form muscle-like and bony-like tissue in vivo. Furthermore, parthenogenetic stem cells were able to integrate into injured muscle tissue. Together, these results demonstrate that parthenogenetic stem cells can be successfully isolated and utilized for various tissue engineering applications.     

Optimization of culture media for enhanced chitinase production from a novel strain of Stenotrophomonas maltophilia using response surface methodology

Chitinase is one of the most important mycolytic enzymes with industrial significance. This enzyme is produced by a number of organisms including bacteria. In this study we describe optimization of media components with increased production of chitinase for selected bacteria Stenotrophomonas maltophilia isolated from the soil. Different components of the defined media responsible for influencing chitinase secretion by the bacterial isolate were screened using Plackett-Burman experimental design and were further optimized by Box-Behnken factorial design of response surface methodology (RSM) in liquid culture. Maximum chitinase production was predicted in medium containing chitin 4.94 g/l, maltose 5.56 g/l, yeast extract 0.62 g/l, KH2PO4 1.33 g/l and MgSO4.7H2O 0.65 g/l using Response surface plots and point prediction tool of DESIGN EXPERT 7.1.6 (Statease, USA) software.     

Triple combination antibiotic therapy for carbapenemase-producing <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis>: a systematic review

Background

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections.

Methods

The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2.

Results

Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients).

Conclusions

Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

     

Care-seeking patterns for fatal malaria in Tanzania

Background

Once malaria occurs, deaths can be prevented by prompt treatment with relatively affordable and efficacious drugs. Yet this goal is elusive in Africa. The paradox of a continuing but easily preventable cause of high mortality raises important questions for policy makers concerning care-seeking and access to health systems. Although patterns of care-seeking during uncomplicated malaria episodes are well known, studies in cases of fatal malaria are rare. Care-seeking behaviours may differ between these groups.

Methods

This study documents care-seeking events in 320 children less than five years of age with fatal malaria seen between 1999 and 2001 during over 240,000 person-years of follow-up in a stable perennial malaria transmission setting in southern Tanzania. Accounts of care-seeking recorded in verbal autopsy histories were analysed to determine providers attended and the sequence of choices made as the patients' condition deteriorated.

Results

As first resort to care, 78.7% of malaria-attributable deaths used modern biomedical care in the form of antimalarial pharmaceuticals from shops or government or non-governmental heath facilities, 9.4% used initial traditional care at home or from traditional practitioners and 11.9% sought no care of any kind. There were no differences in patterns of choice by sex of the child, sex of the head of the household, socioeconomic status of the household or presence or absence of convulsions. In malaria deaths of all ages who sought care more than once, modern care was included in the first or second resort to care in 90.0% and 99.4% with and without convulsions respectively.

Conclusions

In this study of fatal malaria in southern Tanzania, biomedical care is the preferred choice of an overwhelming majority of suspected malaria cases, even those complicated by convulsions. Traditional care is no longer a significant delaying factor. To reduce mortality further will require greater emphasis on recognizing danger signs at home, prompter care-seeking, improved quality of care at health facilities and better adherence to treatment.     

Comparison of high-performance liquid chromatography with fluorescence polarization immunoassay for the analysis of vancomycin in patients with chronic renal failure

Eighty-two plasma samples from patients with chronic renal failure undergoing vancomycin treatment and hemodialysis (HD) were analyzed with fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC). Vancomycin was infused once and the samples were collected during three subsequent HD sessions at 2 h, 3 days and 5 days post-infusion. The HPLC method, modified from an earlier assay, was simple. There was a wide variation in the estimated concentration between the two assay methods. The results obtained by HPLC were 69% lower than those obtained by FPIA. This difference in vancomycin concentration was independent of the sampling time after vancomycin infusion. HPLC analysis commenced approximately 1.5 year after that of FPIA. To study the effect of in vitro degradation, the vancomycin concentration in ten of the samples was redetermined with FPIA during HPLC analysis. The concentrations of those samples decreased to 78–98% (average 92%) of the original concentration. Because FPIA appears to lack specificity, there is a need of other methods such as HPLC for vancomycin measurements, particularly in samples from patients with end-stage renal failure.     

Pulsatility and interrelationships of 13,14-dihydro-15-keto-PGF2alpha (PGFM), luteinizing hormone, progesterone, and estradiol in heifers

Temporality among episodes of a prostaglandin F2alpha metabolite (PGFM), progesterone (P4), luteinizing hormone (LH), and estradiol (E2) were studied during preluteolysis and luteolysis. A vehicle group (n = 10) and a group with an E2-induced PGFM pulse (n = 10) were used. Blood sampling was done every 0.25 h for 8 h. An episode was identified by comparing its coefficient of variation (CV) with the intra-assay CV. Pulsatility of PGFM, P4, LH, and E2 in individual heifers was inferred if the autocorrelation functions were different (P < 0.05) from zero. About four nonrhythmic fluctuations of PGFM/8 h were superimposed on PGFM pulses. Pulsatility was detected for LH but not for P4 and E2. A transient increase in P4 was not detected during the ascending portion of a PGFM pulse. Progesterone decreased (P < 0.003) during Hours -1.25 to -0.50 of the PGFM pulse (Hour 0 = peak) and ceased to decrease temporally with an increase (P < 0.05) in LH. Maximum P4 concentration occurred 0.25 h after an LH pulse peak, and an increase (P < 0.005) in E2 began at the LH peak. Nadirs of LH pulses were greater (P < 0.05) and the nadir-to-nadir interval was shorter (P < 0.003) in the E2 group, which is consistent with reported characteristics during luteolysis. The results did not support the hypothesis of a transient P4 increase early in a PGFM pulse and indicated a balance between a luteolytic effect of PGF and a luteotropic effect of LH within the hours of a PGFM pulse.     

What Point-of-Use Water Treatment Products Do Consumers Use? Evidence from a Randomized Controlled Trial among the Urban Poor in Bangladesh

Background

There is evidence that household point-of-use (POU) water treatment products can reduce the enormous burden of water-borne illness. Nevertheless, adoption among the global poor is very low, and little evidence exists on why.

Methods

We gave 600 households in poor communities in Dhaka, Bangladesh randomly-ordered two-month free trials of four water treatment products: dilute liquid chlorine (sodium hypochlorite solution, marketed locally as Water Guard), sodium dichloroisocyanurate tablets (branded as Aquatabs), a combined flocculant-disinfectant powdered mixture (the PUR Purifier of Water), and a silver-coated ceramic siphon filter. Consumers also received education on the dangers of untreated drinking water. We measured which products consumers used with self-reports, observation (for the filter), and chlorine tests (for the other products). We also measured drinking water''s contamination with E. coli (compared to 200 control households).

Findings

Households reported highest usage of the filter, although no product had even 30% usage. E. coli concentrations in stored drinking water were generally lowest when households had Water Guard. Households that self-reported product usage had large reductions in E. coli concentrations with any product as compared to controls.

Conclusion

Traditional arguments for the low adoption of POU products focus on affordability, consumers'' lack of information about germs and the dangers of unsafe water, and specific products not meshing with a household''s preferences. In this study we provided free trials, repeated informational messages explaining the dangers of untreated water, and a variety of product designs. The low usage of all products despite such efforts makes clear that important barriers exist beyond cost, information, and variation among these four product designs. Without a better understanding of the choices and aspirations of the target end-users, household-based water treatment is unlikely to reduce morbidity and mortality substantially in urban Bangladesh and similar populations.