The X-linked dystonia-parkinsonism (XDP) is a severe progressive, adult-onset X-linked endemic disorder in Filipinos, which is characterized by dystonic movements that start in the third of fourth decade, and replaced by parkinsonism beyond the 10th year of illness. Understanding the pathophysiology of XDP and development of rational therapies will depend on observations from imaging pathological and genetic studies. In this paper we summarize the results of these studies on patients with XDP. The cranial magnetic resonance imaging shows hy-perintense putaminal rim in both dystonic and parkinsonian stages, and atrophy of the caudate head or putamen in the parkinsonian stage. Neuropathological findings show atrophy of the caudate nucleus and putamen, with mild to severe neuronal loss and gliosis. In the neostriatum, the dystonic phase of XDP shows the involvement of striosomes and matrix sparing, while the later, i.e., p[arkinsonian phase, shows matrix involvement as well. In the dystonic phase, the loss of striosomal inhibitory projections lead to disinhibition of nigral dopaminergic neurons, perhaps resulting in a hyperkinetic state; while in the parkinsonian phase, severe and critical reduction of matrix-based projection may result in extranigral parkinsonism. Genetic sequencing of the XDP critical region in Xq13.1 has revealed an SVA retronsposon insertion in an intron of TAF1. This may reduce neuron-specific expression of the TAF1 isoform in the caudade nucleus, and subsequently interfere with the transcription of many neuronal genes, including DRD2. Findings from imaging, pahtology, and genetics studies are gradually shedding light on the pathophysiology of XDP, which hopefully will lead to mare rational and directed therapies.

Human ; Adult ; Atrophy ; Caudate Nucleus ; Dopaminergic Neurons ; Dystonic Disorders ; Genetic Diseases, X-linked ; Gliosis ; Introns ; Parkinsonian Disorders ; Protein Isoforms ; Putamen

Unrecognized gender issues in TB prevention and management in the community and the resulting lack of mechanisms to address these poses as barrier in the success of TB control. Results from two projects on gender responsiveness in TB prevention and management in the community conducted in 2020-2023 contributed to the development of a checklist that can be used as guide to make TB control measures gender-responsive. The checklist used the basic elements of a public health program as framework. This was enhanced by measures to address gender issues which surfaced from KAPcommunity surveys on TB and Gender, in-depth interviews of TB program implementers, and FGDs with women and men who had lived with TB, including their families.
Public Health ; Sexism