Search

Purpose: We aim to investigate the effect of sustained hyperglycemia on corneal epithelial wound healing, ocular surface and systemic immune response, and microbiome indices in diabetic mice compared to controls after alkaline chemical injury of the eye., Methods: Corneal alkaline injury was induced in the right eye of Ins2 Akita (Akita) mice and wild-type mice. The groups were observed at baseline and subsequently days 0, 3, and 7 after injury. Corneal re-epithelialization was observed under slit lamp with fluorescein staining using a cobalt blue light filter. Enucleated cornea specimens were compared at baseline and after injury for changes in cornea thickness under hematoxylin and eosin staining. Tear cytokine and growth factor levels were measured using protein microarray assay and compared between groups and time points. Flow cytometry was conducted on peripheral blood and ocular surface samples to determine CD3+CD4+ cell count. Fecal samples were collected, and gut microbiota composition and diversity pattern were measured using shotgun sequencing., Results: Akita mice had significantly delayed corneal wound healing compared to controls. This was associated with a reduction in tear levels of vascular endothelial growth factor A, angiopoietin 2, and insulin growth factor 1 on days 0, 3, and 7 after injury. Furthermore, there was a distinct lack of upregulation of peripheral blood and ocular surface CD3+CD4+ cell counts in response to injury in Akita mice compared to controls. This was associated with a reduction in intestinal microbiome diversity indices in Akita mice compared to controls after injury. Specifically, there was a lower abundance of Firmicutes bacterium M10-2 in Akita mice compared to controls after injury., Conclusion: In diabetic mice, impaired cornea wound healing was associated with an inability to mount systemic and local immune response to ocular chemical injury. Baseline and post-injury differences in intestinal microbial diversity and abundance patterns between diabetic mice and controls may potentially play a role in this altered response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bu, Shih, Wong, Kwok, Lo, Chan, Ng, Chan, Jhanji and Tong.)

Importance: Gliomas, tumors of the central nervous system, are classically diagnosed through invasive surgical biopsy and subsequent histopathological study. Innovations in ultra-high field (UHF) imaging, namely 7-Tesla magnetic resonance imaging (7T MRI) are advancing preoperative tumor grading, visualization of intratumoral structures, and appreciation of small brain structures and lesions., Objective: Summarize current innovative uses of UHF imaging techniques in glioma diagnostics and treatment., Methods: A systematic review in accordance with PRISMA guidelines was performed utilizing PubMed. Case reports and series, observational clinical trials, and randomized clinical trials written in English were included. After removing unrelated studies and those with non-human subjects, only those related to 7T MRI were independently reviewed and summarized for data extraction. Some preclinical animal models are briefly described to demonstrate future usages of ultra-high-field imaging., Results: We reviewed 46 studies (43 human and 3 animal models) which reported clinical usages of UHF MRI in the diagnosis and management of gliomas. Current literature generally supports greater resolution imaging from 7T compared to 1.5T or 3T MRI, improving visualization of cerebral microbleeds and white and gray matter, and providing more precise localization for radiotherapy targeting. Additionally, studies found that diffusion or susceptibility-weighted imaging techniques applied to 7T MRI, may be used to predict tumor grade, reveal intratumoral structures such as neovasculature and microstructures like axons, and indicate isocitrate dehydrogenase 1 mutation status in preoperative imaging. Similarly, newer imaging techniques such as magnetic resonance spectroscopy and chemical exchange saturation transfer imaging can be performed on 7T MRI to predict tumor grading and treatment efficacy. Geometrical distortion, a known challenge of 7T MRI, was at a tolerable level in all included studies., Conclusion: UHF imaging has the potential to preoperatively and non-invasively grade gliomas, provide precise therapy target areas, and visualize lesions not seen on conventional MRI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shaffer, Kwok, Naik, Anderson, Lam, Wszalek, Arnold and Hassaneen.)

Background: Treatment of metastatic brain tumors often involves radiotherapy with or without surgical resection as the first step. However, the indications for when to use surgery are not clearly defined for certain tumor sizes and multiplicity. This study seeks to determine whether resection of brain metastases versus exclusive radiotherapy provided improved survival and local control in cases where metastases are limited in number and diameter., Methods: According to PRISMA guidelines, this meta-analysis compares outcomes from treatment of a median number of brain metastases ≤ 4 with a median diameter ≤ 4 cm with exclusive radiotherapy versus surgery followed by radiotherapy. Four randomized control trials and 11 observational studies (1693 patients) met inclusion criteria. For analysis, studies were grouped based on whether radiation involved stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT)., Results: In both analyses, there was no difference in survival between surgery ± SRS versus SRS alone two years after treatment (OR 1.89 (95% CI: 0.47-7.55, P = .23) or surgery + WBRT versus radiotherapy alone (either WBRT and/or SRS) (OR 1.18 (95% CI: 0.76-1.84, P = .46). However, surgical patients demonstrated greater risk for local tumor recurrence compared to SRS alone (OR 2.20 (95% CI: 1.49-3.25, P < .0001)) and compared to WBRT/SRS (OR 2.93; 95% CI: 1.68-5.13, P = .0002)., Conclusion: The higher incidence of local tumor recurrence for surgical patients suggests that more prospective studies are needed to clarify outcomes for treatment of 1-4 metastasis less than 4 cm diameter., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

An association between age-related hearing loss (ARHL) and Alzheimer's Disease (AD) has been widely reported. However, the nature of this relationship remains poorly understood. Quantification of hearing loss as it relates to AD is imperative for the creation of reliable, hearing-related biomarkers for earlier diagnosis and development of ARHL treatments that may slow the progression of AD. Previous studies that have measured the association between peripheral hearing function and AD have yielded mixed results. Most of these studies have been small and underpowered to reveal an association. Therefore, in the current report, we sought to estimate the degree to which AD patients have impaired hearing by performing a meta-analysis to increase statistical power. We reviewed 248 published studies that quantified peripheral hearing function using pure-tone audiometry for subjects with AD. Six studies, with a combined total of 171 subjects with AD compared to 222 age-matched controls, met inclusion criteria. We found a statistically significant increase in hearing threshold as measured by pure tone audiometry for subjects with AD compared to controls. For a three-frequency pure tone average calculated for air conduction thresholds at 500-1,000-2,000 Hz (0.5-2 kHz PTA), an increase of 2.3 decibel hearing level (dB HL) was found in subjects with AD compared to controls ( p = 0.001). Likewise, for a four-frequency pure tone average calculated at 500-1,000-2,000-4,000 (0.5-4 kHz PTA), an increase of 4.5 dB HL was measured ( p = 0.002), and this increase was significantly greater than that seen for 0.5-2 kHz PTA. There was no difference in the average age of the control and AD subjects. These data confirm the presence of poorer hearing ability in AD subjects, provided a quantitative estimate of the magnitude of hearing loss, and suggest that the magnitude of the effect is greater at higher sound frequencies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021288280., Competing Interests: DL has consulted for Eisai Pharmaceuticals in the past year. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kwok, Nguyen, Wu, Mudar and Llano.)

Purpose: Cornea epithelial-stromal scarring is related to the differentiation of fibroblasts into opaque myofibroblasts. Our study aims to assess the effectiveness of Lycium barbarum polysaccharide (LBP) solution as a pre-treatment in minimizing corneal scarring., Methods: Human corneal fibroblasts were cultured in a three-dimensional collagen type I-based hydrogel in an eye-on-a-chip model. Fibroblasts were pre-treated with 2 mg/mL LBP for 24 h, followed by another 24-h incubation with 10 ng/mL transforming growth factor-beta 1 (TGF-β1) to induce relevant physiological events after stromal injury. Intracellular pro-fibrotic proteins, extracellular matrix proteins, and pro-inflammatory cytokines that involved in fibrosis, were assessed using immunocytochemistry and enzyme-linked immunosorbent assays., Results: Compared to the positive control TGF-β1 group, LBP pre-treated cells had a significantly lower expression of alpha-smooth muscle actin, marker of myofibroblasts, vimentin (p < 0.05), and also extracellular matrix proteins both collagen type II and type III (p < 0.05) that can be found in scar tissues. Moreover, LBP pre-treated cells had a significantly lower secretion of pro-inflammatory cytokines interleukin-6 and interleukin-8 (p < 0.05). The cell-laden hydrogel contraction and stiffness showed no significant difference between LBP pre-treatment and control groups. Fibroblasts pretreated with LBP as well had reduced angiogenic factors expression and suppression of undesired proliferation (p < 0.05)., Conclusion: Our results showed that LBP reduced both pro-fibrotic proteins and pro-inflammatory cytokines on corneal injury in vitro. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option prior to corneal refractive surgeries with an improved prognosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Multiple epidemiological studies have revealed an association between presbycusis and Alzheimer's Disease (AD). Unfortunately, the neurobiological underpinnings of this relationship are not clear. It is possible that the two disorders share a common, as yet unidentified, risk factor, or that hearing loss may independently accelerate AD pathology. Here, we examined the relationship between reported hearing loss and brain volumes in normal, mild cognitive impairment (MCI) and AD subjects using a publicly available database. We found that among subjects with AD, individuals that reported hearing loss had smaller brainstem and cerebellar volumes in both hemispheres than individuals without hearing loss. In addition, we found that these brain volumes diminish in size more rapidly among normal subjects with reported hearing loss and that there was a significant interaction between cognitive diagnosis and the relationship between reported hearing loss and these brain volumes. These data suggest that hearing loss is linked to brainstem and cerebellar pathology, but only in the context of the pathological state of AD. We hypothesize that the presence of AD-related pathology in both the brainstem and cerebellum creates vulnerabilities in these brain regions to auditory deafferentation-related atrophy. These data have implications for our understanding of the potential neural substrates for interactions between hearing loss and AD., Competing Interests: VD was an employee of Eisai Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Llano, Kwok, Devanarayan and The Alzheimer’s Disease Neuroimaging Initiative (ADNI).)

(1) Objective: To study the anti-fibrotic effects of Lycium barbarum polysaccharides (LBP) on corneal stromal fibroblasts and assess LBP's effect on cell viability. (2) Methods: Primary human corneal keratocytes of passage 3 to 6 were used for all experiments. Cells are pretreated with LBP solution for 24 h and then transforming growth factor beta 1 (TGFβ1) for 48 h and collected for experiments. Fibrotic protein analysis was performed using immunofluorescence and Western blot. The effect of LBP on cell viability was assessed using the MTS assay. (3) Results: LBP significantly reduced the expression of fibrotic proteins, including α-SMA and extracellular matrix proteins (collagen type I and III). LBP significantly decreased the viability of myofibroblasts but not the fibroblasts. Conclusions: In this study, LBP was effective in the prevention of fibrosis gene expression. Further studies to assess the underlying mechanism and pharmacological properties will facilitate the formation of a topical LBP solution for in vivo studies.

Diabetes mellitus is the most common cause of blindness in working age populations worldwide. While much of the focus for public health has been on secondary prevention in sight-threatening diabetic retinopathy, the cornea, including its epithelium and nerves, represents a major site of damage by chronic hyperglycemia. On injury, the diabetic cornea exhibits a delayed wound-healing response, as well as an altered ocular surface immune response. This suggests a potential association between the dysfunctional wound healing response and altered inflammation on the ocular surface. However, the presence of potential confounders makes this association difficult to investigate in human epidemiological studies. Thus, we turn to animal diabetic models for a better understanding. In this review, 20 original studies, published between 2008 and 2018, describe in vivo and in vitro models of diabetic cornea disease. We compared different models of diabetic cornea wound healing and discussed the relative strengths and drawbacks of each model. A number of molecular and cellular components involved in the corneal wound healing response that are altered in the presence of diabetes have been identified in the reviewed studies. Particularly, altered corneal epithelial protein concentrations of lumician and occludin were detected in diabetic eyes compared with controls. Additionally, the importance of IL-1β in modulating the inflammatory response after corneal injury in patients with diabetes and controls was further elucidated. Meanwhile, abnormal P2×7 receptor localization and decreased corneal sub-basal nerve density in diabetic eyes were shown to contribute to altered corneal nerve signaling after injury and thus affecting the wound healing response. Finally, the discovery of the therapeutic effects of topically administered aloe vera, Serpine 1, Resolvin D1 (RvD1), pigment epithelium-derived factor (PEDF) and Pro-His-Ser-Arg-Asn in diabetic animal models of cornea epithelial and nerve injury provide encouraging evidence for the future availability of effective treatment for diabetic keratopathy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Retinal ganglion cell (RGC) death is the central and irreversible endpoint of optic neuropathies. Current management of optic neuropathies and glaucoma focuses on intraocular pressure-lowering treatment which is insufficient. As such, patients are effectively condemned to irreversible visual impairment. This review summarizes experimental treatments targeting RGCs over the last decade. In particular, we examine the various treatment modalities and determine their viability and limitations in translation to clinical practice. Experimental RGC treatment can be divided into (1) cell replacement therapy, (2) neuroprotection, and (3) gene therapy. For cell replacement therapy, difficulties remain in successfully integrating transplanted RGCs from various sources into the complex neural network of the human retina. However, there is significant potential for achieving full visual restoration with this technique. Neuroprotective strategies, in the form of pharmacological agents, nutritional supplementation, and neurotrophic factors, are viable strategies with encouraging results from preliminary noncomparative interventional case series. It is important to note, however, that most published studies are focused on glaucoma, with few treating optic neuropathies of other etiologies. Gene therapy, through the use of viral vectors, has shown promising results in clinical trials, particularly for diseases with specific genetic mutations like Leber's hereditary optic neuropathy. This treatment technique can be further extended to nonhereditary diseases, through transfer of genes promoting cell survival and neuroprotection. Crucially though, for gene therapy, teratogenicity remains a significant issue in translation to clinical practice., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Lin Fu et al.)

Objectives: To evaluate recent studies on available and experimental therapies in preventing or minimizing corneal stromal scarring after injury., Methods: We performed an Entrez PubMed literature search using keywords "cornea," "scarring," "haze," "opacity," "ulcer," "treatments," "therapies," "treatment complications," and "pathophysiology" resulting in 390 articles of which 12 were analyzed after filtering, based on English language and publication within 8 years, and curation for relevance by the authors., Results: The 12 articles selected included four randomized control trials (RCTs) (two were double-blinded placebo-controlled RCTs, one was a prospective partially masked RCT, and one was an open-label RCT), two retrospective observational studies, and six laboratory-based studies including two studies having in vivo and in vitro experiments, one was in vivo study, one was ex vivo study, and the last two were in vitro studies. The current mainstay for preventing or minimizing corneal scarring involves the use of topical corticosteroids and local application of mitomycin C. However, supportive evidence for their use in clinical practice from well-designed RCTs is lacking. Laboratory studies on topical rosiglitazone therapy, vitamin C prophylaxis, gene therapy, and stem cell therapy have shown promising results but have yet to be translated to clinical research., Conclusion: There is a need for more robust randomized controlled trials to support treatments using topical corticosteroids and mitomycin C. Furthermore, their clinical efficacy and safety profile should be compared with new treatments that have shown promising results in the laboratory setting. Ultimately, the goal should be to personalize cornea scarring treatment according to the most effective treatment for the specific underlying pathology.

Objective: To evaluate the effect of Lycium barbarum polysaccharides in the treatment and/or prevention of diseases of different etiologies and systems., Methods: We performed an Entrez PubMed literature search using keywords "lycium", "barbarum", "polysaccharides", "anti-fibrotic", "anti-apoptotic", "anti-oxidizing", "anti-aging", "neuroprotection", "metabolism", "diabetes", "hyperlipidemia", "neuroprotection", and "immunomodulation" on the 14 th of August 2018, resulting in 207 papers, of which 20 were chosen after filtering for 'English language' and 'published within 10 years' as well as curation for relevance by the authors., Results: The 20 selected papers included 2 randomized control trials (1 double-blinded RCT and 1 double-blinded placebo-controlled RCT), 11 in vivo studies, 5 in vitro studies, 1 study with both in vivo and in vitro results, and 1 chemical study. There is good evidence from existing studies on the antifibrotic, antioxidizing, neuroprotective, anticancer, and anti-inflammatory effects of Lycium barbarum polysaccharides. However, there is a need for further studies in the form of large-scale clinical trials to support its use in humans. There is also significant potential for LBP as a safe and effective topical treatment in ocular surface diseases, owing to promising in vitro results and a lack of demonstrated toxic effects to corneal epithelial cells., Conclusion: Results from existing studies suggest that LBP is a promising therapeutic agent, particularly in the management of liver disease, hyperlipidemia, and diabetes. One major limitation of current research is a lack of standardization and quality control for the LBP used. The availability of research-grade LBP will inevitably promote future research in this field worldwide.

Neural cell grafting is a promising therapy for stroke, but the optimal differentiation status of the cells prior to grafting is unclear. We grafted cells at different maturity stages (days 28, 42, or 56 of in vitro neural differentiation) into the brains of eight-week-old rats one week after subcortical ischemic stroke, and assessed motor and sensory behavioral recovery over one month. We did not find a difference between the grafted or control groups on behavioral recovery, or on brain tissue outcomes including infarct size, microgliosis, or astrocytosis. Further research is needed into mechanisms of benefit of neural cell grafting for stroke., Competing Interests: The authors declare no conflicts of interest.

Self-discrepancy occurs when a person feels the failure to fulfill one's hopes or responsibilities. Although self-discrepancy has been widely examined to elucidate patients' chronic pain adjustment, the underlying mechanism is unclear. The present study proposes that the effect of self-discrepancy on pain outcomes is accounted for by psychological inflexibility, which involves the psychological processes that guide behaviors in the pursuit of goals and values. One-hundred patients with chronic pain were recruited from a public hospital. They were invited to participate in a semi-structured interview regarding their self-discrepancy and complete self-reported questionnaires regarding their psychological inflexibility and pain outcomes. The results confirmed that psychological inflexibility partly accounts for the variance observed between self-discrepancy and pain outcomes. The current study provides additional insight into the mechanism underpinning the impact of self-discrepancy on patients' pain adjustment and offers clinical implications regarding the use of acceptance commitment therapy for chronic pain management.

Purpose: To determine the most effective method of dissociating neural stem and progenitor cells into a single-cell suspension., Materials/methods: Induced pluripotent stem cells were differentiated toward the neural fate for 4 weeks before clusters were subjected to enzymatic (Accutase, trypsin, TrypLE, dispase, or DNase I) or mechanical (trituration with pipettes of varying size) or combined dissociation. Images of cells were analyzed for cluster size using ImageJ., Results: Cells treated with the enzymes Accutase, TrypLE, or trypsin/EDTA, these enzymes followed by trituration, or a combination one of these enzymes followed by incubation with another enzyme, including DNase I, were more likely to be dissociated into a single-cell suspension., Conclusions: Cells treated with enzymes or combinations of methods were more likely to be dissociated into a single-cell suspension., (Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Purpose: Some East/Southeast Asian countries have experienced a rapid increase in suicide by charcoal burning over the past decade. Media reporting and Internet use were thought to contribute to the epidemic. We investigated the association between method-specific suicide incidence and both Internet search volume and newspaper reporting in Taiwan., Method: Weekly data for suicide, suicide-related Google search volume, and the number of articles reporting suicide in four major newspapers in Taiwan during 2008-2011 were obtained. Poisson autoregressive regression models were used to examine the associations between these variables., Results: In the fully adjusted models, every 10 % increase in Google searches was associated with a 4.3 % [95 % confidence interval (CI) 1.1-7.6 %] increase in charcoal-burning suicide incidence in the same week, and a 3.8 % (95 % CI 0.4-7.2 %) increase in the following week. A one-article increase in the United Daily was associated with a 3.6 % (95 % CI 1.5-5.8 %) increase in charcoal-burning suicide in the same week. By contrast, non-charcoal-burning suicide was not associated with Google search volume, but was associated with the Apple Daily's reporting in the preceding week., Conclusions: We found that increased Internet searches for charcoal-burning suicide appeared to be associated with a subsequent increase in suicide by this method. The prevention of suicide using emerging methods may include monitoring and regulating online information that provides details of these methods as well as encouraging Internet service providers to provide help-seeking information.

Background & Aims: Patients undergoing gastrointestinal operations are at risk of malnutrition which may increase the chance of adverse surgical outcomes. This prospective study aimed at correlating nutritional status of patients having gastrointestinal operations with their short-term surgical outcomes captured by a territory-wide Surgical Outcomes Monitoring and Improvement Program., Methods: The preoperative malnutrition risk of Chinese adult patients undergoing elective/emergency ultra-major/major gastrointestinal operations in two surgical departments over a 12-month period were assessed by Chinese version of Malnutrition Universal Screening Tool. Their perioperative risk factors and clinical outcomes, including length of hospital stay, mortality and morbidity, were retrieved from the above mentioned program. Correlation of malnutrition risk with clinical outcomes was assessed by logistic regression analysis after controlling for known confounders., Results: 943 patients (58% male; mean age 65.9 ± 14.8 years) underwent gastrointestinal operations (40.3% emergency operation; 52.7% ultra-major procedures; 66.9% bowel resections) had analyzable data. 15.8% and 17.1% of patients were at medium and high risk of malnutrition, respectively. Malnutrition risk score according to the screening tool was an independent predictor of length of hospital stay, 30-day mortality, 60-day mortality and minor medical complications. Similar correlations were found for various sub-scores of malnutrition risk. Weight loss sub-score was predictive of 30-day mortality, 60-day mortality and minor medical complications. Body mass index was predictive of mortality (30- and 60- day) whereas the acute disease sub-score was predictive of length of hospital stay., Conclusions: Preoperative malnutrition was an important predictor of poor clinical outcomes in patients undergoing gastrointestinal operations in Hong Kong., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Neural culture of human pluripotent stem cells is useful for neuroscience research, but the optimal feeding schedule for these in vitro systems is unclear. We evaluated the survival and neural differentiation profiles of human embryonic and induced pluripotent stem cells cultured with medium exchange schedules of five, six, or seven days weekly through two months of differentiation. No significant differences were seen in cell numbers or neural differentiation markers through this culture interval with either human pluripotent cell type. We conclude that there is unlikely to be an advantage of feeding more than five days weekly for this culture system.

Background: Little research has been done on the complex relationships between the effect of news reporting on suicide incidence and vice versa (i.e., mutual causation). Furthermore, few studies have examined whether the entry of a new media outlet into a market changes the media dynamics in that market., Methods: A recursive two-way feedback model was used to test for mutual causation between suicide reporting and suicide incidence on a daily basis. We applied the model to examine the effect of the arrival of the Apple Daily (AD) newspaper in Taiwan and whether its suicide reporting affected the suicide incidence and suicide reporting of two other newspapers, the United Daily (UD) and the China Times (CT)., Results: The AD's entry into Taiwan led to a major shift in the relationship between suicide incidence and suicide reporting. The AD stimulated more suicide coverage by the UD and the CT the following day; conversely, the UD and the CT had no such impact on the AD. Before the entry of the AD, there was little correlation between daily suicide incidence and suicide reporting, but the suicide reporting of the UD and CT correlated significantly with daily suicide incidence after the entry of the AD., Limitations: Media impact was assessed by number of news items; detailed content analysis of the reporting was not conducted., Conclusions: The vicious business competition facing new dailies in Taiwan's media market has changed the mass media ecology. Efforts to prevent suicide by regulating the media should closely monitor not only the behavior of newcomers, but also the established news media's reaction to new competitors., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Melamine can be transferred to fetus in utero through placenta and to infant ex utero by breast feeding. In this study, we characterized the pharmacokinetics of melamine in prenatal and postnatal organs in rats. Single bolus of melamine was administered to pregnant rats at different gestational stages and to infants at different postnatal stages. Distribution of melamine in maternal serum was about 30% higher in late pregnancy than that in early pregnancy; and it was 2 folds higher in postnatal serum in early infants in young adulthood. Distribution of melamine in all postnatal organs was higher than that in prenatal organs. Postnatal kidneys in early infants had the highest maximum concentration and the lowest clearance of melamine than the other postnatal organs. It may relate to the high vulnerability to the toxicity of melamine in this population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

For the analysis of cancer, there is great interest in rapid and accurate detection of cancer genome amplifications containing oncogenes that are potential therapeutic targets. The vast majority of cancer tissue samples are formalin fixed and paraffin embedded (FFPE) which enables histopathological examination and long term archiving. However, FFPE cancer genomic DNA is oftentimes degraded and generally a poor substrate for many molecular biology assays. To overcome the issues of poor DNA quality from FFPE samples and detect oncogenic copy number amplifications with high accuracy and sensitivity, we developed a novel approach. Our assay requires nanogram amounts of genomic DNA, thus facilitating study of small amounts of clinical samples. Using droplet digital PCR (ddPCR), we can determine the relative copy number of specific genomic loci even in the presence of intermingled normal tissue. We used a control dilution series to determine the limits of detection for the ddPCR assay and report its improved sensitivity on minimal amounts of DNA compared to standard real-time PCR. To develop this approach, we designed an assay for the fibroblast growth factor receptor 2 gene ( FGFR2 ) that is amplified in a gastric and breast cancers as well as others. We successfully utilized ddPCR to ascertain FGFR2 amplifications from FFPE-preserved gastrointestinal adenocarcinomas.

A Chinese woman had a first-episode of psychosis in the second trimester of pregnancy. The sudden onset of psychotic symptoms and fluctuating mental condition with visual hallucinations suggested an organic origin for the psychosis. Antipsychotic medication was started. Ultrasound investigation at 19 weeks of gestation revealed intrauterine growth retardation and she decided to terminate the pregnancy. Positive blood test results for antiphospholipid antibodies confirmed a diagnosis of systemic lupus erythematosus with antiphospholipid syndrome. Psychosis is one of the neuropsychiatric syndromes in systemic lupus erythematosus and can sometimes be the primary manifestation, antedating other evidence of the disease. Pregnancy can exacerbate systemic lupus erythematosus. This report highlights the importance of considering an organic cause for psychosis, including systemic lupus erythematosus, especially when it occurs for the first time during pregnancy in a previously healthy woman.