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Biomedical subjects

Matthew Lynch

Publications and source records attributed to Matthew Lynch.

6 recordsLinked to original sources
PubMed2024

Upregulation versus loss of function of NTRK2 in 44 affected individuals leads to 2 distinct neurodevelopmental disorders.

PURPOSE: Heterozygous pathogenic variants in NTRK2 (HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation. METHODS: We reported an extended cohort of 44 affected individuals, of whom 19 are from the literature and 25 were previously unreported. RESULTS: Our analysis led to splitting the cohort into 2 entities. CONCLUSION: One group had variants in the cholesterol-binding motif of the transmembrane domain, with most of these being the recurrent variant c.1301A>G p.(Tyr434Cys). These variants probably lead to upregulation of tropomyosin receptor kinase B activity and to a severe phenotype of developmental delay/intellectual disability, muscular hypotonia, therapy-refractory epilepsy, visual impairment and blindness, and feeding difficulties. The second group had truncating variants or variants that presumably disturb the 3D structure of the protein leading to loss of function. These individuals had a remarkably milder phenotype of developmental delay, obesity, and hyperphagia.

Humans↗
PubMed2005

Malaria prevalence and associated risk factors in Eritrea.

A parasitological cross-sectional survey was undertaken from September 2000 through February 2001 to estimate the prevalence of malaria parasitemia in Eritrea. A total of 12,937 individuals from 176 villages were screened for both Plasmodium falciparum and Plasmodium vivax parasite species using the OptiMal Rapid Diagnostic Test. Malaria prevalence was generally low but highly focal and variable with the proportion of parasitemia at 2.2% (range: 0.4% to 6.5%). Despite no significant differences in age or sex-specific prevalence rates, 7% of households accounted for the positive cases and 90% of these were P. falciparum. Multivariate regression analyses revealed that mud walls were positively associated with malaria infection (OR [odds ratio] = 1.6 [95% CI: 1.2, 2.2], P < 0.008). For countries with low and seasonal malaria transmission, such information can help programs design improved strategic interventions.

Eritrea↗
PubMed2004

New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells.

In this report, four new poly(d-glucaramidoamine)s (1-4) have been designed to lower the toxicity of conventional polymeric nucleic acid delivery vehicles by incorporating a carbohydrate comonomer within a polyethylenimine (PEI)-like backbone. Polymers 1-4 were synthesized via polycondensation of esterified d-glucaric acid and four different amine-containing comonomers [diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and pentaethylenehexamine (4)] in methanol. Viscometry and NMR studies suggest that the polymers are mostly linear (for 1-4, the alpha value in the Mark-Houwink-Sakurada equation = 0.6-0.7), thus indicating that polymerization occurs predominantly through the primary amines with a low degree of branching off the secondary amines. Results of gel electrophoresis shift assays show that polymers 1-4 bind pDNA at N/P ratios of 5, 3, 2, and 2, respectively. Also, dynamic light scattering and TEM experiments indicate that 1-4 compact DNA into nanoparticles (polyplexes) between 140 and 440 nm at an N/P ratio of 30. Furthermore, polyplexes formed with 1-4 deliver pDNA (plasmid DNA) containing the firefly luciferase reporter gene to BHK-21 cells in a nontoxic and highly efficient manner (as determined by luciferase gene expression). In particular, polymer 4 reveals very high delivery efficiency (equivalent to linear PEI). This result may be due in part to the "proton sponge" hypothesis proposed by Behr et al. Polymers containing amines that are protonated in the endosomal pH range (between about 7.4-5.0) reveal enhanced gene delivery profiles.

Animals↗
PubMed2003

Household willingness to pay for azithromycin treatment for trachoma control in the United Republic of Tanzania.

OBJECTIVE: Household willingness to pay for treatment provides important information for programme planning. We tested for relationships between socioeconomic status, risk of trachoma, perceptions of the effects of azithromycin, and the household willingness to pay for future mass treatment with azithromycin. METHODS: We surveyed 394 households in 6 villages located in central United Republic of Tanzania regarding their willingness to pay for future azithromycin treatment. A random sample of households with children under 8 years of age was selected and interviewed following an initial treatment programme in each village. Data were gathered on risk factors for trachoma, socioeconomic status, and the perceived effect of the initial azithromycin treatment. Ordered probit regression analysis was used to test for statistically significant relationships. FINDINGS: 38% of responding households stated that they would not be willing to pay anything for future azithromycin treatment, although they would be willing to participate in the treatment. A proxy for cash availability was positively associated with household willingness to pay for future antibiotic treatment. Cattle ownership (a risk factor) and being a household headed by a female not in a polygamous marriage (lower socioeconomic status) were associated with a lower willingness to pay for future treatment. A perceived benefit from the initial treatment was marginally associated with a willingness to pay a higher amount. CONCLUSIONS: As those at greatest risk of active trachoma indicated the lowest willingness to pay, imposing a cost recovery fee for azithromycin treatment would likely reduce coverage and could prevent control of the disease at the community level.

Adult↗
PubMed2003

Azithromycin treatment coverage in Tanzanian children using community volunteers.

PURPOSE: To determine which of two village-based strategies was more effective at recruiting residents for a trachoma mass treatment campaign. METHODS: The two strategies were to use either village government personnel to recruit residents for treatment, or to solicit interested community volunteers to recruit residents. Three were villages assigned to each strategy, and the outcome measured was treatment coverage of individuals, group and the villages. RESULTS: Self-selected community volunteers were significantly more effective than village government personnel in recruiting villagers for antibiotic treatment (p <.0001). The differences were strongest for the group at highest risk for active trachoma, pre-school children; 73% of children in community volunteer villages were treated, compared to 63% in village government villages (p <.05). Children in villages using community volunteers and from larger families were more likely to be treated. CONCLUSION: These findings support using motivated community volunteers, rather than traditional government workers, for mass treatment campaigns where high coverage is necessary.

Adolescent↗