Micronesian Migrants in Hawaii: Health Issues and Culturally Appropriate, Community-Based Solutions

More than 20,000 Micronesians have migrated to Guam, Hawaii, or the Commonwealth of the Northern Mariana Islands. Of these migrants, more than 8,000 now live in Hawaii. Factors in their home islands driving the recent emigration include the limited economic resources and struggling health care systems. Education systems in Micronesia are inadequate, and there are few job opportunities. The rates of infectious diseases remain high while at the same time, the epidemiologic transition in health has led to an explosion of non-communicable diseases. In Hawaii, the impact of the Micronesians emigration has been significant with most health and education expenses un-reimbursed. The health care costs alone are substantial as many Micronesians travel to Guam or Hawaii for medical treatment unavailable in their home islands. At the same time, Micronesians have difficulty accessing and navigating the health care system. While governmental, private, and academic programs already provide innovative and communitybased services to the Micronesian population, more work remains to be done. Not only are additional services, tailored to the culture and needs of Micronesian migrants, needed but a keener awareness and understanding of the issues surrounding Hawaii’s migrant population must be promoted among all public health stakeholders to ensure that the priority necessary to successfully address these challenges is recognized

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal splenic-placenta-fetal brain axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (IL-6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of IL-6 in Chrna7 mutant mice. We found that the basal level of IL-6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7+/− offspring. The Chrna7+/− offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after maternal infection

Ocular Penetration of N-Formimidoyl Thienamycin (MK-787) and Potentiation by Dipeptidase Inhibitor (MK-791)

N-formimidoyl thienamycin (MK-787) is a new /?-lactam with potent activity against both aerobic and anaerobic gram-positive and gram-negative bacteria. Its spectrum and activity suggest it may be useful in treatment of complicated intraocular infections. Its ocular penetration was studied in New Zealand white rabbits immediately before and after the third dose of 40 mg/kg administered intravenously at q6h intervals. Plasma, aqueous humor, and vitreous humor were obtained by direct aspiration, and antibiotic levels were asayed using an agar well diffusion method. MK-787 penetrated uninflamed intraocular fluids, including vitreous humor, although vitreous concentrations achieved (0.1-0.2 Mg/ml) were significantly lower than the mean peak plasma (15 Mg/ml) and aqueous concentrations (7 Mg/ml). Nevertheless, the intraocular levels attained approached or exceeded the MIC 90 and markedly enhanced spectrum of activity against both gram-positive and gram-negative bacteria

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Sub-tenon Anaesthesia versus Intracameral Anaesthesia in Patients Undergoing Cataract Extraction: A Comparative Study of the Level of Pain, Visual Perception and Anxiety

Background: Phacoemulsification is a modern method of cataract extraction. Sub-tenon anaesthesia used to be the preferred anaesthetic technique for this procedure before intracameral anaesthesia gained its popularity in recent years. Nevertheless, many surgeons still believe that sub-tenon anaesthesia is better than topical anaesthesia. This study aimed to evaluate and compare the experiences of patients who were treated for cataract by phacoemulsification surgery using either sub-tenon or intracameral anaesthesia. Methods: Cross-sectional study conducted at Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia. Participants were asked to complete a questionnaire within 1-2 hours following surgery. The questionnaires were designed to gather information on the patient’s level of anxiety, visual perception and amount of pain experienced during cataract surgery. Results: A total of 62 patients were included in the study. Thirty-one patients received anaesthesia by sub-tenon injection, whereas another 31 patients received anaesthesia by intracameral injection. There were no significant differences in the level of pain experienced by the two groups of patients during instillation of anaesthesia and during surgery (p=0.205 and p=0.592, respectively). There were also no significant differences in terms of visual perception and anxiety levels during surgery between the two groups (p=0.178 and p=0.731, respectively). Conclusion: Intracameral anaesthesia obviates the need for an injection during cataract surgery and is as comfortable for patients as sub-tenon anaesthesia in terms of visual perception, level of pain, and anxiety

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome

Phase I Trial of the Cyclin-Dependent Kinase Inhibitor Flavopiridol in Combination with Docetaxel in Patients with Metastatic Breast Cancer

Abstract Purpose: The purpose of this study was to determine the toxicities and characterize the pharmacokinetics of docetaxel and flavopiridol in patients with metastatic breast cancer. Experimental Design: Docetaxel was administered at an initial dose of 60 mg/m2 followed in 24 hours by a 72-hour infusion of flavopiridol at 50 mg/m2/d every 3 weeks. Because dose-limiting myelosuppression occurred, the schedule was amended to docetaxel, 50 mg/m2, followed by escalating doses of flavopiridol (starting dose, 26 mg/m2/d) as a 1-hour infusion daily for 3 days. Pharmacokinetic studies were performed. Ki67, p53, and phosphorylated retinoblastoma protein (phospho-Rb) in paired tumor and buccal mucosa biopsies (obtained pre- and posttreatment) were examined by immunohistochemistry. Results: Eleven patients were enrolled. Five patients received docetaxel and 72-hour flavopiridol. Dose-limiting toxicity was grade 4 neutropenia. Six patients received docetaxel and 1-hour flavopiridol, and the dose-limiting toxicity was grade 3 hypotension. Pharmacokinetics of flavopiridol and docetaxel were consistent with historical data. Nuclear staining with p53 increased and phospho-Rb decreased in 10 pairs of buccal mucosa biopsies posttreatment (P = 0.002 and P = 0.04, respectively). No significant changes in Ki67, p53, or phospho-Rb were detected in six paired tumors. Two patients sustained stable disease for >3 months (72-hour flavopiridol), and one partial response was observed (1-hour flavopiridol). Conclusions: Docetaxel combined with 72-hour flavopiridol was not feasible because of dose-limiting neutropenia. Dose escalation of a 1-hour infusion of flavopiridol with docetaxel was also not possible. The changes in p53 and phospho-Rb in buccal mucosa suggest that a biological effect with flavopiridol was achieved

G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum.

Funder: Hong Kong PhD Fellowship SchemeFunder: Hong Kong Special Administrative Region GovernmentG-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.UK Medical Research Council [grants MR/K000535/1 and MR/L008823/1] to CJM. Shenzhen Basic Research Project [JCYJ20180507181642811], Research Grants Council of the Hong Kong SAR, China Projects [CityU 11100421, CityU 11101519, CityU 11100218, N_CityU110/17, CityU 21302317], Croucher Foundation [Project No. 9500030, 9509003], State Key Laboratory of Marine Pollution Director Discretionary Fund, City University of Hong Kong [projects 6000711, 7005503, 9667222, 9680261] to CKK. A generous donation from Mr. and Mrs. Sunny Yang, the University Grants Committee Area of Excellence Scheme (AoE/M-403/16), and the Innovation and Technology Commission, Hong Kong Special Administrative Region Government to the State Key Laboratory of Agrobiotechnology (CUHK) to TFC. EYCC was supported by the Hong Kong PhD Fellowship Scheme