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H3Africa is developing capacity for health-related genomics research in Africa

This study aimed to assess the prevalence of neuropsychiatric sequelae following traumatic brain injury (TBI) among the Western Asian, South Asian and African regions of the global south. All studies on psychiatric disturbances or cognitive impairment following TBI conducted (until August 2021) in the 83 countries that constitute the aforementioned regions were reviewed; 6 databases were selected for the literature search. After evaluating the articles using the Joanna Briggs Institute guidelines, the random effects model was used to estimate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), TBI-related sleep disturbance (TBISD), obsessive-compulsive disorder (OCD) and cognitive impairment. Of 56 non-duplicated studies identified in the initial search, 27 were eligible for systematic review and 23 for meta-analysis. The pooled prevalence of depression in 1,882 samples was 35.35%, that of anxiety in 1,211 samples was 28.64%, that of PTSD in 426 samples was 19.94%, that of OCD in 313 samples was 19.48%, that of TBI-SD in 562 samples was 26.67% and that of cognitive impairment in 941 samples was 49.10%. To date, this is the first critical review to examine the spectrum of postTBI neuropsychiatric sequelae in the specified regions. Although existing studies lack homogeneous data due to variability in the diagnostic tools and outcome measures utilised, the reported prevalence rates are significant and comparable to statistics from the global north. [ABSTRACT FROM AUTHOR]

Post-transcriptional RNA processing is an important regulatory control mechanism for determining the phenotype of eukaryotic cells. The processing of a transcribed RNA species into alternative splice isoforms yields products that can perform different functions. Each type of cell in a multi-cellular organism is presumed to actively control the relative quantities of alternative splice isoforms. In this study, the alternatively spliced isoforms of five mRNA transcription units were examined by quantitative reverse transcription-PCR amplification. We show that interindividual variation in splice-isoform selection is very highly constrained when measured in a large population of genetically diverse mice (i.e., full siblings; N=150). Remarkably, splice-isoform ratios are among the most invariant phenotypes measured in this population and are confirmed in a second, genetically distinct population. In addition, the patterns of splice-isoform selection show tissue-specific and age-related changes. We propose that splice-isoform selection is exceptionally robust to genetic and environmental variability and may provide a control point for cellular homeostasis. As a consequence, splice-isoform ratios may be useful as a practical quantitative measure of the physiological status of cells and tissues.

Fraction collection following eleetrophoresis is of major importance for a variety of biological analyses. These assays typically need to identify specific fractions in the separated sample for further processing and require extraction of one or a group of fragments. In this paper, we have developed and characterized a technique to generate addressable electric fields for improved extraction during electrophoresis in microfluidic devices. The addressable electric field is achieved by applying a low bias voltage (1-2 V) to microelectrode pairs within the electrophoresis microchannel. Theoretical analysis shows the purity of the extracted sample can be improved as much as 30% over extraction without the shaped electric fields, and nearly 100% predicted yield can be achieved. We also describe the theoretical design of shaped electric fields by characterizing the optimal electrode geometry, field strength, channel configuration, and electrophoretic migration behavior needed for efficient band extraction.

We have performed the Taqman [beta]-actin PCR system in high-surface-to-volume ratio (0.02-0.13/[micro][m.sup.-1]) Si[O.sub.2] microchannels and observed the reaction yield and uniformity. The concentrations of the enzyme, magnesium chloride, and reaction template were varied in the reaction mix, and PCR amplification was performed in devices of various surface-to-volume ratios. We found that microchannels with higher surface-to-volume ratios required higher enzyme concentrations to achieve the same amplification efficiency. We investigated the possibility that the observed reaction nonuniformity was related to the specific adsorption of magnesium ions to the negatively charged Si[O.sub.2] surface. The effect of several modifications to the reaction chemistry, the addition of the caged-magnesium dye DM-Nitrophen, the replacement of human DNA template with PCR product, and the coating of the microchannel surface with Teflon were all studied. These modifications resulted in improved reaction uniformity in the microchannels and present opportunities for further studies on enhancing the efficiency and uniformity of PCR in high surface-to-volume ratio Si[O.sub.2] microchannels.

A genome scan was conducted to seek evidence for polymorphic genes that influence cause of death in mice produced by a cross between CB6F1 females and C3D2F1 males. Loci on chromosomes 1 and 4 were found to modulate risk of lymphoma. A locus on chromosome 4 influenced risk of mammary adenocarcinoma among multiparous female mice, but had no significant effect in virgin females. A chromosome 4 locus was found to modulate risk of death from either hemangiosarcoma or fibrosarcoma. A suggestive linkage was noted (at p = .09) between a marker on chromosome 11 and hepatocellular carcinoma. Lastly, a locus on chromosome 6 was noted to influence the likelihood that pulmonary adenocarcinoma would be present at death. The collection of normal and neoplastic tissues from 1004 terminal necropsies. together with genetic information, provides a valuable resource for further studies of the genetic influences on late-life diseases in mice.

An active microvalve that uses a meltable piston in place of a conventional solid material to obstruct fluid flow in a microfluidic channel has been developed. This phase change valve is simple to operate and requires no additional fabrication steps. The valve is inherently latched, reusable, and leak-proof (to at least 250 psi) and can be electronically addressed using resistive heaters. The valve has been characterized for a range of operational parameters that will serve as a design guide. For the designs tested, piston displacements of 5 mm or more in 1 s have been achieved. Valves 1.4 mm in length in a 50 [micro]m x 200 [micro]m channel have been integrated on a biochemical reaction device, and successful DNA amplification using PCR has been achieved. The phase change valve can be easily implemented in an array format that can be used to realize complex microfluidic circuits.

Epigenetic control of gene expression is a consistent feature of differentiated mammalian cell types. Epigenetic expression patterns are mitotically heritable and are stably maintained in adult cells. However, unlike somatic DNA mutation, little is known about the occurrence of epigenetic change, or epimutation, during normal adult life. We have monitored the age-associated maintenance of two epigenetic systems--X inactivation and genomic imprinting--using the genes Atp7a and Igf2, respectively. Quantitative measurements of RNA transcripts from the inactive and active alleles were performed in mice from 2 to 24 months of age. For both genes, older animal cohorts showed reproducible increases in transcripts expressed from the silenced alleles. Loss of X chromosome silencing showed cohort mean increases of up to 2.2%, while imprinted-gene activation increased up to 6.7%. The results support the hypothesis that epigenetic loss of gene repression occurs in normal tissues and may be a contributing factor in progressive physiological dysfunction seen during mammalian aging. Quantitatively, the loss of epigenetic control may be one to two orders of magnitude greater than previously determined somatic DNA mutation.

A short focused pulse of light was used to selectively cut lambda-phage DNA molecules at specific restriction sites. Lambda DNA (48.5 kbp) was stretched and placed in a solution containing a restriction enzyme (Sma 1), caged magnesium ions (using a DM-Nitrophen complex), and a chelating agent (EDTA). When a pulse of UV light was directed at a particular location on the stretched DNA molecule, magnesium ions were released into solution. A series of binding reactions then occur in which the enzyme and the chelating agent compete for free [Mg.sup.2+] ions. Since Sma 1 functions only in the presence of [Mg.sup.2+], as is true of most endonucleases, the site(s) in the vicinity of the pulse (typically ~6 [micro]m) were cut while other sites (three total for this DNA/enzyme pair) were not. The ratio of the concentration of the chelating agent to that of the magnesium ions was used to control the radius of this reaction zone with higher ratios leading to smaller, localized reaction areas. This optically based reaction mechanism could be useful to understand single molecule enzymatic kinetics, and when coupled with other DNA analysis techniques, this could be used to construct complex genotyping and sequencing devices that would analyze parts of single DNA molecules.

This study tests the relation between eye-movements and thought processing. Subjects were given specific modality tasks (visual, gustatory, kinesthetic) and assessed on whether they responded with distinct eye-movements. Some subjects' eye-movements reflected ongoing thought processing. Instead of a universal pattern, as suggested by the neurolinguistic programming hypothesis, this study yielded subject-specific idiosyncratic eye-movements across all modalities. Included is a discussion of the neurolinguistic programming hypothesis regarding eye-movements and its implications for the eye-movement desensitization and reprocessing theory.

Background: As conceptions of mental illness are often dictated by prevailing socio-cultural factors and the philosophy of the time, there is little research to substantiate how mental illness is perceived in the Arab world in the light of both traditional and more recent modernization and acculturation processes. Aims: To examine whether social factors exert an influence on a person's attitude towards people with mental illness (PWMI) in the rapidly changing country of Oman. Methods: This study compares the response elicited from medical students, relatives of psychiatric patients and the general Omani public on the causes of mental illness, attitudes toward PWMI and the care and management of people with mental illness. Results: This study found no relationship between attitudes towards PWMI, and demographic variables such as age, educational level, marital status, sex and personal exposure to people with mental illness. Both medical students and the public rejected a genetic factor as the cause of mental illness; instead they favoured the role of spirits as the aetiological factor for mental illness. There were favourable responses on statements regarding value of life, family life, decision-making ability, and the management and care of mental illness. However, both medical students and the public thought that PWMI tend to have peculiar and stereotypical appearances and the majority preferred that facilities for psychiatric care should be located away from the community. Although the relatives of psychiatric patients were concerned about the welfare of mental patients, their responses varied and were often contingent upon their expectations. Conclusions: The data suggest that neither socio-demographic factors nor previous exposure to PWMI was related to attitudes towards PWMI. Although the attitudes of Omanis toward PWMI appear to fluctuate in complex ways, traditional beliefs on mental illness have yet to be eroded by exposure to a biomedical model of mental illness. This study largely supports the view that the extent of stigma varies according to the cultural and sociological backgrounds of each society.

In this paper, we demonstrate immobilization and stretching of single [lambda]-phage DNA molecules within microfluidic systems using ac fields. We present a novel 'thiol-on-gold'-based immobilization technique for fixing one specific end (3' end) of a DNA molecule onto a gold electrode. A polymer-enhanced medium (~3.75 wt % linear polyacrylamide in Tris-HCl) is used to obtain fully stretched configurations (21 [micro]m) of fluorescently stained [lambda]-DNA molecules. We also present an optimized microelectrode design with pointed electrodes and an electrode spacing of 20 [micro]m for stretching DNA molecules with an ac field (1 MHz, 3 x [10.sup.5] V/m). Finally, using these techniques, we immobilize a single DNA molecule at one electrode edge, stretch the molecule, and fix the other end at an adjacent electrode edge, forming a bridge between two electrodes within a microfabricated device.

We have looked for genetic predictors of life span in a sibship of mice created as a four-way cross among inbred grandparental strains BALB/cJ, C57BL/6J, C3H/HeJ, and DBA/2J. To minimize the potential confounding effects of loci that influence early-life illnesses only, we conducted two analyses: one involving all the mice, and the other using a data set from which the first 20% of the deaths were excluded. The two strongest associations reach experimentwise significance levels (p < .01) when tested on the 80% of the mice with the longest life spans. Surprisingly, three of the four strongest associations showed sex-specific effects, with an influence on life span of either male or female mice, but not both. Epistatic interactions among the loci were also identified. The life-span effect of a locus on chromosome 10 (D10Mit15) exhibited epistatic interactions with loci on chromosomes 9 and 16 (D9Mit10 and D16Mit182). In a second example, a locus on chromosome 12 (D12Mit167) depended on the specific combination of alleles inherited from both male and female parents. Our results show that the common laboratory mouse strains are polymorphic at loci that produce substantial differences in life span and that these effects can be sex specific and conditional on alleles inherited at other loci.

Some models of aging imply that late-life diseases, though roughly synchronous, are the result of distinct pathophysiological processes, each in turn influenced by polymorphisms at multiple loci. Other models suggest that the dramatic increase in later life of multiple forms of illness might reflect the outcome of a unitary process, of so-far unknown biochemical nature, that proceeds at a species-specific rate to increase the risk of many forms of disease and disability in parallel. We have previously reported the results of genetic linkage analyses documenting the ability of alleles at D9Mit110, D10Mit15, and D12Mit167, and an allele pair at D2Mit58 and D16Mit182 to predict longevity in mice bred as the progeny of (BALB/cJ x C57BL/6J)F1 mothers and (C3H/HeJ x DBA/2J)F1 fathers (the UM-HET3 stock). Here we report the results of post hoc analyses to test the hypothesis that the genes that extend the life span of mice dying of neoplastic diseases also extend the life span of mice that die of nonneoplastic causes. In all four cases we find that the genotype associated with increased survival in mice dying of cancer is also associated for a similar degree of life span extension in mice dying of other causes. For D9Mit110 and the combination of D2Mit58 and D16Mit182, the difference is statistically significant in both the neoplastic and nonneoplastic mouse groups. The data support the hypothesis that many forms of late-life disease may be influenced by shared pathophysiologic mechanisms that are under coordinated genetic control.