Transient deformation and swelling of paper by aqueous co-solvent solutions.

Inkjet printing inks frequently contain polar liquids of low volatility such as glycerol or poly(ethylene glycols) in addition to the main solvent water. The deposition of these liquids on paper sheets induces swelling of the cellulose fibers, which leads to an overall, anisotropic deformation of the sheet. We characterized the corresponding strain components by means of a grid projection method and white light interferometry. For pure water, most of the hydroexpansion strain vanishes again after drying is complete. However, for aqueous solutions of non-volatile co-solvents, a large fraction of the deformation persists after the water has evaporated. Because swelling occurs only after liquid enters the cellulose fibers, monitoring the dynamics of expansion provides insight into the pore-fiber distribution of co-solvents. The corresponding timescales of pore-fiber transport strongly depend on the co-solvent concentration, as a sufficient quantity of water is needed to plasticize the fiber walls.

Recombinant turnip yellow mosaic virus coat protein as a potential nanocarrier.

AIMS: To display a short peptide (GSRSHHHHHH) at the C-terminal end of turnip yellow mosaic virus coat protein (TYMVc) and to study its assembly into virus-like particles (TYMVcHis6 VLPs). METHODS AND RESULTS: In this study, recombinant TYMVcHis6 expressed in Escherichia coli self-assembled into VLPs of approximately 30-32 nm. SDS-PAGE and Western blot analysis of protein fractions from the immobilized metal affinity chromatography (IMAC) showed that TYMVcHis6 VLPs interacted strongly with nickel ligands in IMAC column, suggesting that the fusion peptide is protruding out from the surface of VLPs. These VLPs are highly stable over a wide pH range from 3·0 to 11·0 at different temperatures. At pH 11·0, specifically, the VLPs remained intact up to 75°C. Additionally, the disassembly and reassembly of TYMVcHis6 VLPs were studied in vitro. Dynamic light scattering and transmission electron microscopy analysis revealed that TYMVcHis6 VLPs were dissociated by 7 mol l-1 urea and 2 mol l-1 guanidine hydrochloride (GdnHCl) without impairing their reassembly property. CONCLUSIONS: A 10-residue peptide was successfully displayed on the surface of TYMVcHis6 VLPs. This chimera demonstrated high stability under extreme thermal conditions with varying pH and was able to dissociate and reassociate into VLPs by chemical denaturants. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first C-terminally modified TYMVc produced in E. coli. The C-terminal tail which is exposed on the surface can be exploited as a useful site to display multiple copies of functional ligands. The ability of the chimeric VLPs to self-assemble after undergo chemical denaturation indicates its potential role to serve as a nanocarrier for use in targeted drug delivery.

The Scope of Family-Centred Care Practices, and the Facilitators and Barriers to Implementation of Family-Centred Care for Hospitalised Children and their Families in Developing Countries: An Integrative Review.

PROBLEM: Limited knowledge exists regarding the scope practices and implementation from developing countries. This integrative review aims to report research on the scope of FCC practices, facilitators and barriers to the FCC implementation for hospitalised children and their families in developing countries. ELIGIBILITY CRITERIA: Qualitative, quantitative, mixed-method studies, reports, systematic reviews and integrative reviews reporting implementation, barriers and facilitators of FCC, published in English between 2008 and 2018, from developing countries were evaluated. Joanna Briggs Institute Appraisal Tools were used for methodological assessment. SAMPLE: Eleven studies from developing countries met the inclusion criteria. Four studies were randomised controlled trials, five were cross-sectional, one was a quasi-experimental while one was a qualitative study. RESULTS: The scope of FCC research focuses on information sharing, family participation, and respect and dignity and FCC implementation focuses on practices and perceptions, measurement and impact of FCC. Both personal and health system facilitators and barriers exist but their influence on FCC implementation is limited. Research on needs of families and hospitalised children is also limited. CONCLUSION: FCC practice and research are still in infancy stage in developing countries. There is limited understanding on scope of FCC practices, the needs of parents and children, and the influence of facilitators and barriers. IMPLICATIONS: The limited findings reported in this review support the need for international collaboration to FCC to critique FCC research and integrate it with other philosophies such as child and family centred care and child centred care as is the case in some developed countries.

Questionnaire survey on medical futility and termination of resuscitation in cardiac arrest patients among emergency physicians in Hong Kong.

INTRODUCTION: The perceptions of medical futility and decisions about termination of resuscitation (TOR) for out-of-hospital cardiac arrest (OHCA) are highly heterogeneous and dependent on the practice of the attending emergency physicians. The objective of this study was to report and investigate the knowledge, attitudes, and practices regarding medical futility and TOR during management of OHCA in Hong Kong. METHODS: A cross-sectional survey was conducted among emergency medicine physicians in Hong Kong. The questionnaire assessed participants' background, knowledge, attitudes, and behaviours concerning medical futility and TOR in management of OHCA. Composite scores were calculated to reflect knowledge, attitudes, and practices of OHCA treatment. Subgroup analysis and multiple regression analysis were used to explore the relationship between participants' background, knowledge, attitudes, and behaviours. RESULTS: The response rate to this survey was 57% (140/247). Independent predictors of less aggressive resuscitation in OHCA patients included status as a Fellow of the Hong Kong College of Emergency Medicine (ß= -0.314, P=0.028) and being an Advanced Cardiac Life Support instructor (ß= -0.217, P=0.032). There was no difference in aggressiveness of resuscitation in terms of years of clinical experience (ß=0.015, P=0.921), knowledge of TOR (ß=0.057, P=0.509), or attitudes about TOR (ß= -0.103, P=0.214). The correlation between knowledge and attitudes was low (Spearman's coefficient=0.02, P=0.795). CONCLUSION: Clinical practice and behaviour of TOR was not demonstrated to have associations with knowledge or attitude. Status as a Fellow of the Hong Kong College of Emergency Medicine or Advanced Cardiac Life Support instructor were the only two parameters identified that had significant relationships with earlier TOR in medically futile patients with OHCA.

Plasma-derived microparticles in polycythaemia vera.

INTRODUCTION: Microparticles are membrane bound vesicles, measuring less than 1.0 um, which are released during cellular activation or during apoptosis. Studies have shown that these circulating microparticles play a role in coagulation, cell signaling and cellular interactions. Increased levels of circulating microparticles have been observed in a number of conditions where there is vascular dysfunction, thrombosis and inflammation. The objective of this study was to determine the various plasma-derived microparticles in patients with polycythaemia vera (PV) in Universiti Kebangsaan Malaysia Medical Centre and to compare them with normal control. METHODS: A total of 15 patients with PV and 15 healthy volunteers were included in this cross-sectional descriptive study. Plasma samples from both patients and healthy volunteers were prepared and further processed for isolation of microparticles. Flow cytometry analyses were then carried out in all samples to determine the cellular origin of the microparticles. Full blood count parameters for both groups were also collected. Data collected were analyzed using SPSS version 12.0. RESULTS: Patients with PV had a significantly higher percentage of platelet derived microparticles compared to healthy controls (P <0.05). The control group had a higher level of endothelial derived microparticles but the differences were not statistically significant (P > 0.05). CONCLUSION: The median percentage of positive events for platelet derived microparticles was higher in patients with PV compared to normal healthy controls.

Unusual presentation of severe dengue: Dengue maculopathy.

Dengue infection is epidemic but ocular complications of dengue are less reported. We report a case of dengueinfected patient with disturbing ocular symptoms. He was admitted for severe dengue. Subsequently, he presented with symptoms of bilateral central scotoma with metamorphosia. Fundus examination revealed cotton wool spots and flame-shaped haemorrhages at the macula, with dull foveal light reflex. He was diagnosed with bilateral dengue maculopathy. The patient was managed conservatively with surveillance. One week later, his eye symptoms improved and were resolved six months later. Early recognition and close monitoring remains the key to successful management and interventions are rarely needed.

Primary imatinib resistance in chronic myeloid leukemia patients in a developing country: BCR-ABL kinase domain mutations or BCR-ABL independent mechanisms?

Clinical resistance to imatinib (IM) in chronic myeloid leukemia (CML) carries adverse consequences. We investigated 22 CML patients who developed IM-resistance for BCR-ABL kinase domain (KD) mutations. The median follow-up for this study was 101.9 months (range: 22.2 to 176.5 months) and the estimated mean overall survival was 150.87 months (95% CI: 130.0 to 171.0). Five out of 22 patients tested positive for BCR-ABL KD mutations: 2 had T315I, 2 had E255K and 1 had V289F mutations. Of the remaining 17 patients who did not harbor BCR-ABL KD mutations, 11 patients received nilotinib while the rest continued on IM. All 17 achieved haematological remission but only 5 patients achieved complete cytogenetic remission, 4 of whom did so after switching to nilotinib. Our study shows that most of our IM-resistant patients do not test positive for BCR-ABL KD mutations by available testing methods and the role of second generation tyrosine kinase inhibitors remains undetermined. A critical analysis of the BCR-ABL KD mutations and the underlying mechanisms/ pathways of BCR-ABL independent IM-resistance along with potential treatments in the horizon will be discussed.

Dismal outcome of therapy-related myeloid neoplasm associated with complex aberrant karyotypes and monosomal karyotype: a case report.

INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis. DISCUSSION AND CONCLUSION: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

Detection of B-mode polarization at degree angular scales by BICEP2.

We report results from the BICEP2 experiment, a cosmic microwave background (CMB) polarimeter specifically designed to search for the signal of inflationary gravitational waves in the B-mode power spectrum around ℓ∼80. The telescope comprised a 26 cm aperture all-cold refracting optical system equipped with a focal plane of 512 antenna coupled transition edge sensor 150 GHz bolometers each with temperature sensitivity of ≈300 µK(CMB)√s. BICEP2 observed from the South Pole for three seasons from 2010 to 2012. A low-foreground region of sky with an effective area of 380 square deg was observed to a depth of 87 nK deg in Stokes Q and U. In this paper we describe the observations, data reduction, maps, simulations, and results. We find an excess of B-mode power over the base lensed-ΛCDM expectation in the range 30 < ℓ < 150, inconsistent with the null hypothesis at a significance of >5σ. Through jackknife tests and simulations based on detailed calibration measurements we show that systematic contamination is much smaller than the observed excess. Cross correlating against WMAP 23 GHz maps we find that Galactic synchrotron makes a negligible contribution to the observed signal. We also examine a number of available models of polarized dust emission and find that at their default parameter values they predict power ∼(5-10)× smaller than the observed excess signal (with no significant cross-correlation with our maps). However, these models are not sufficiently constrained by external public data to exclude the possibility of dust emission bright enough to explain the entire excess signal. Cross correlating BICEP2 against 100 GHz maps from the BICEP1 experiment, the excess signal is confirmed with 3σ significance and its spectral index is found to be consistent with that of the CMB, disfavoring dust at 1.7σ. The observed B-mode power spectrum is well fit by a lensed-ΛCDM+tensor theoretical model with tensor-to-scalar ratio r = 0.20_(-0.05)(+0.07), with r = 0 disfavored at 7.0σ. Accounting for the contribution of foreground, dust will shift this value downward by an amount which will be better constrained with upcoming data sets.

Uptake of breast screening and associated factors among Hong Kong women aged ≥50 years: a population-based survey.

OBJECTIVE: To examine the uptake of breast screening and its associated factors among Hong Kong Chinese women aged ≥50 years. STUDY DESIGN: Cross-sectional population-based survey. METHODS: A sample of Hong Kong Chinese women was recruited through telephone random-digit dialling. The survey consisted of six sections: perceived health status, use of complementary medicine, uptake of breast screening, perceived susceptibility to cancer, family history of cancer and demographic data. The factors associated with uptake of breast screening were analysed using logistic regression analysis. RESULTS: In total, 1002 women completed the (anonymous) telephone survey. The mean age was 63.5 (standard deviation 10.6) years. The uptake rate of breast screening among Hong Kong Chinese women aged ≥50 years was 34%. The primary reasons for undertaking breast screening were as part of a regular medical check-up (74%), prompted by local signs and symptoms (11%) and a physician's recommendation (7%). Higher educational level, married or cohabiting, family history of cancer, frequent use of complementary therapies, regular visits to a doctor or Chinese herbalist, and the recommendation of a health professional were all independently and significantly associated with increased odds of having had a mammogram. CONCLUSIONS: This study provides community-based evidence of the need for public health policy to promote broader use of mammography services among this target population, with emphasis on the active involvement of health care professionals, through the development and implementation of appropriate evidence-based and resource-sensitive strategies.

A Prospective Longitudinal Study of Early Childhood Caries Onset in Initially Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex oral disease that is prevalent in US children. OBJECTIVES: The purpose of this 2-y prospective cohort study was to examine baseline and time-dependent risk factors for ECC onset in initially caries-free preschool children. METHODS: A cohort of 189 initially caries-free children aged 1 to 3 y was recruited. At each 6-mo study visit, children were examined using the ICDAS index; salivary samples were collected to assess mutans streptococci (MS), lactobacilli, Candida species, salivary cortisol (prior and after a stressor), and salivary IgA. Diet and oral health behavior were assessed from parent report. Child and family stress exposure was assessed from measures of psychological symptoms, stressful life event exposure, family organization and violence exposure, and social support. Sociodemographic factors were also considered. A Kaplan-Meier estimator of survival function of time to ECC and a Cox proportional hazards model were used to identify predictors of ECC onset. RESULTS: Onset of ECC was associated with high salivary MS levels at baseline (log-rank test, P < 0.0001). Cox proportional hazards regression showed that the risk of dental caries significantly increased with salivary MS in log scale over the 6-mo period (hazard ratio, 1.08; P = 0.01). Other risk factors in the model did not reach statistical significance. CONCLUSION: Our results provide prospective evidence that an increase in salivary MS predicts ECC onset in young, initially caries-free children, confirming that a high salivary MS count likely plays a causal role in ECC onset, independent of covariates. KNOWLEDGE TRANSFER STATEMENT: These results suggest that we must focus on reducing salivary MS counts in young children and preventing or delaying MS colonization in infants and young children determined to be at risk for ECC.

The acute effects of a pulse-containing meal on glycaemic responses and measures of satiety and satiation within and at a later meal.

Pulses are low glycaemic foods; however, their effect on satiation is unknown. The objective was to determine the effects of an ad libitum pulse meal on food intake (FI), appetite and blood glucose (BG) before and after a test meal (4 h later) and on FI at the test meal. Males (n 24, 22·8 kg/m2) received one of four treatments or control. The pulse treatments contained pasta and tomato sauce and 44 % of energy from: (1) chickpeas, (2) lentils, (3) navy beans or (4) yellow peas. The control was pasta and tomato sauce (pasta and sauce). FI (satiation) was measured at the treatment meal (0-20 min) and at an ad libitum pizza meal 4 h later. BG and appetite were measured from 0 to 340 min. At the treatment meal, lentils led to lower FI compared to chickpeas and pasta and sauce, whereas navy beans led to lower FI compared to chickpeas. Also, lentils led to lower cumulative FI compared to pasta and sauce. All pulses led to lower BG peak and cumulative area under the curve (AUC; 0-340 min); however, only chickpeas, lentils and navy beans reduced pre-pizza meal BG AUC (0-260 min) relative to pasta and sauce. Chickpeas led to lower post-pizza meal BG AUC (260-340 min) compared to navy beans and yellow peas. Consumption of pulses in a high-glycaemic meal contributes to earlier satiation, lower BG following the meal and after a later meal, but these effects are specific to pulse type and cannot be explained by their glycaemic properties alone.

Social, Psychological, and Behavioral Predictors of Salivary Bacteria, Yeast in Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex, multifactorial oral disease that is a major public health concern because it is prevalent, profoundly alters a child's quality of life, is difficult to treat effectively, and has a distressing tendency to recur following treatment. OBJECTIVES: The purpose of the study was to examine social, psychological, and behavioral predictors of salivary bacteria and yeast in young children at risk for ECC. METHODS: A sample of 189 initially caries-free preschool children was assessed for child stress physiology from salivary cortisol, child and family stress exposure, diet, oral health behaviors, and sociodemographic risks. Multiple logistic regression analysis was implemented to examine the associations between these risk factors and cariogenic microorganisms: mutans streptococci (MS), lactobacilli (LB), and Candida species. RESULTS: Higher baseline salivary cortisol (odds ratio [OR] = 6.26; 95% confidence level [CL], 1.69-23.16) and a blunted response to an acute laboratory stressor (OR = .56; 95% CL, .37-.83) were associated with an increased likelihood of elevated salivary MS (≥105 colony-forming units/mL) in caries-free children. Sociodemographic risk for cariogenic microorganisms was also found. Specifically, lower education attainment of the parent/primary caregiver was associated with children being more likely to carry salivary Candida species and elevated salivary MS; in addition, children from households with an unemployed parent/primary caregiver were more likely (OR = 3.13; 95% CL, 1.2-8.05) to carry salivary Candida species and more likely (OR = 3.03; 95% CL, 1.25-7.33) to carry elevated levels of MS and/or salivary Candida and/or LB. CONCLUSIONS: The impact of sociodemographic risk and stress physiology on cariogenic disease processes are evident prior to ECC onset. The findings provide novel data on the early onset of cariogenic processes in children and the importance of considering sociodemographic, psychosocial, and behavioral factors when judging ECC risk. KNOWLEDGE TRANSFER STATEMENT: The findings provide valuable and novel findings that, pre-ECC onset, the caries disease process is explicable from a detailed assessment of behavioral, sociodemographic, and psychosocial stress variables.

Association between Dental Anomalies and Orofacial Clefts: A Meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess whether individuals with nonsyndromic orofacial clefts (OCs) display a higher frequency of dental anomalies (DAs) when compared with individuals without OCs. METHODS: A literature search of indexed databases (PubMed, Cochrane, Web of Science, Embase, Scopus, and LILACS) was conducted without language restriction up to and including February 1, 2020. Cross-referencing was used to further identify articles. Several cleft teams across the United States and Europe were contacted to obtain unpublished data. The eligibility criteria were observational studies with original data that statistically compared individuals with OC without syndromes and those without OC on any type of DA in primary and/or permanent dentition. Random effects meta-analysis through the Mantel-Haenszel estimator was used to evaluate the association between OC and DA based on odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The literature search generated 933 records, and 75 full-text articles were reviewed. Twenty-six studies encompassing 15,213 individuals met the inclusion criteria. The meta-analysis revealed statistically significant associations between OC and agenesis (OR, 14.2; 95% CI, 9.4 to 21.3), supernumerary teeth (OR, 5.7; 95% CI, 3.3 to 9.7), developmental enamel defects (OR, 5.6; 95% CI, 3.5 to 9.0), microdontia (OR, 14.8; 95% CI, 4.0 to 54.6), peg-shaped anterior teeth (OR, 12.2; 95% CI, 3.6 to 41.2), taurodontism (OR, 1.7; 95% CI, 1.0 to 2.7), tooth malposition and/or transposition (OR, 5.6; 95% CI, 2.8 to 11.5), tooth rotation (OR, 3.2; 95% CI, 1.3 to 8.2), and tooth impaction (OR, 3.6; 95% CI, 1.1 to 12.2). The OR estimates of the reviewed studies exhibited significant heterogeneity (P < 0.0001). No association was observed between OC and fusion and/or gemination. CONCLUSION: Within the limitations of this study, the available evidence suggests that individuals with OCs are more likely to present with a range of DAs than their unaffected peers. KNOWLEDGE TRANSFER STATEMENT: The findings of the current review suggest that individuals with orofacial clefts (OCs) are more likely to present with a range of dental anomalies than their unaffected peers. Understanding the association between OCs and dental anomalies is essential in guiding clinicians during treatment-planning procedures and is important in raising our awareness of the possible need for future dental treatment for patients with OCs.

Absence of paternal accessory sex gland secretions disturbs epigenetic reprogramming and expression of Igf2 and Dlk1 in golden hamster embryos.

Accessory sex gland (ASG) secretion is known to exert an effect on sperm that is heritable in hamster embryos. We hypothesized that ASG secretion changes the sperm epigenome, which in turn is propagated in sired embryos. To test our hypothesis, we produced male hamsters that were devoid of either all ASG (TX) or only the ventral lobe of the prostate gland (VPX). A sham-operated control group (SH) was also established. These males were mated with normal females; uterine sperm, fertilized oocytes, and pre-implantation embryos were harvested from the females after mating. Epididymal sperm were collected at the end of experiments. Immunofluorescent staining was performed on these harvested specimens using antibodies against 5-methylcytosine, Dnmt1, Dnmt3a, Dnmt3b, protamine 1, protamine 2, and aectyl-H4K5. Expression of Igf2 and Dlk1 were analyzed by real-time RT PCR and in situ hybridization. We demonstrated that the DNA methylation pattern changed dynamically in SH, TX, and VPX fertilized oocytes. In VPX and TX embryos, DNA demethylation was slower and remethylation was delayed when compared with SH embryos. In addition, Dnmt3b expression was also abnormal. When sperm from VPX and TX males were exposed to whole ASG secretion in vivo, the resulting embryos all methylated normally. Immunofluorescent staining revealed that there was no difference in protamine packaging of uterine sperm from VPX and TX males. The staining also showed a lower level of acetyl-H4K5 expression in the male pronuclei of TX produced embryos. Furthermore, the VPX and TX embryos also expressed higher levels Igf2, and Dlk1. We concluded that interactions between ASG and sperm affected: (1) histone acetylation in male pronuclei; (2) DNA methylation in fertilized oocytes; and (3) Igf2 and Dlk1 expression embryos.

Ablation of paternal accessory sex glands imparts physical and behavioural abnormalities to the progeny: an in vivo study in the golden hamster.

The functional significance of male accessory sex glands (ASG) remains unclear. This study explored their importance in reproduction. In previous investigations, embryos sired by males with ASG either totally or partially removed had a shift in the cell cycle and delayed cleavage during preimplantation development, higher incidence of apoptosis, early oviductal-uterine transit, higher proportion of embryo degeneration, lower implantation rate, and ultimately reduced fertility and fecundity. Some pups were born alive; but would they be normal? We hypothesized that the first generation offspring (F1) could also bear undesirable traits. To test our hypothesis, we raised and studied these F1 pups from birth to 8 weeks. We monitored physical growth and assessed behaviour such as nest patch odor preference, acoustic startle response (ASR) and exploratory activity. We detected deviations from the norm in physical growth, a premature cessation of nest patch odor preferences, accelerated acoustic startle habituation and more frequent rearing when exposed to a novel environment. In terms of structure, we found one incidence of diphallus with duplicated urethra. We concluded that sperm lacking contact with ASG secretions gave rise to progeny with abnormal traits.

MicroRNAs that affect the Fanconi Anemia/BRCA pathway are downregulated in imatinib-resistant chronic myeloid leukemia patients without detectable BCR-ABL kinase domain mutations.

Chronic myeloid leukemia (CML) patients who do not achieve landmark responses following treatment with imatinib mesylate (IM) are considered IM-resistant. Although IM-resistance can be due to BCR-ABL kinase domain (KD) mutations, many IM-resistant patients do not have detectable BCR-ABL KD mutations. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression. To investigate the role of miRNAs in IM-resistance, we recruited 8 chronic phase CML patients with IM-resistance who tested negative for BCR-ABL KD mutations and 2 healthy normal controls. Using miRNA sequencing, we identified 54 differentially expressed miRNAs; 43 of them downregulated. The 3 most differentially downregulated miRNAs were miR-146a-5p, miR-99b-5p and miR-151a-5p. Using real-time quantitative reverse transcriptase-polymerase chain reaction, the expression patterns of the 3 miRNAs were validated on the same cohort of 8 patients in addition to 3 other IM-resistant CML patients. In-silico analysis showed that the predicted gene targets are ATRIP, ATR, WDR48, RAD51C and FANCA genes which are involved in the Fanconi Anemia/BRCA pathway. This pathway regulates DNA damage response (DDR) and influences disease response to chemotherapy. Thus it is conceivable that DDR constitutes a key component in IM-resistance. Further research is needed to elucidate miRNA modulation of the predicted gene targets.

Canalicular function during herpetic keratoconjunctivitis in rabbits.

Canalicular function during acute herpetic keratoconjunctivitis was investigated in rabbits. Evidence of partial obstruction of the duct was obtained in the infected as compared with the mock-infected eyes. Direct damage of the ductal epithelium by virus could not be demonstrated by histologic and immunofluorescent studies. Our findings suggest that canalicular dysfunction associated with viral infection may result from accompanying inflammatory changes.