Climate change, malaria and neglected tropical diseases: a scoping review.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

Disaggregating Asian-American Mortality in Drug-Related Overdoses and Behavioral Disorders: A Cross-Sectional Study.

Asian Americans have been historically underrepresented in the national drug overdose discourse due to their lower substance use and overdose rates compared to other racial/ethnic groups. However, aggregated analyses fail to capture the vast diversity among Asian-American subgroups, obscuring critical disparities. We conducted a cross-sectional study between 2018 and 2021 examining Asian-American individuals within the CDC WONDER database with drug overdoses as the underlying cause of death (n = 3195; ICD-10 codes X40-X44, X60-X64, X85, and Y10-Y14) or psychoactive substance-related mental and behavioral disorders as one of multiple causes of death (n = 15,513; ICD-10 codes F10-F19). Proportional mortality ratios were calculated, comparing disaggregated Asian-American subgroups to the reference group (Asian Americans as a single aggregate group). Z-tests identified significant differences between subgroups. Compared to the reference group (0.99%), drug overdose deaths were less prevalent among Japanese (0.46%; p < 0.001), Chinese (0.47%; p < 0.001), and Filipino (0.82%; p < 0.001) subgroups, contrasting with a higher prevalence among Asian Indian (1.20%; p < 0.001), Vietnamese (1.35%; p < 0.001), Korean (1.36%; p < 0.001), and other Asian (1.79%; p < 0.001) subgroups. Similarly, compared to the reference group (4.80%), deaths from mental and behavioral disorders were less prevalent among Chinese (3.18%; p < 0.001), Filipino (4.52%; p < 0.001), and Asian Indian (4.56%; p < 0.001) subgroups, while more prevalent among Korean (5.60%; p < 0.001), Vietnamese (5.64%; p < 0.001), Japanese (5.81%; p < 0.001), and other Asian (6.14%; p < 0.001) subgroups. Disaggregated data also revealed substantial geographical variations in these deaths obscured by aggregated analyses. Our findings revealed pronounced intra-racial disparities, underscoring the importance of data disaggregation to inform targeted clinical and public health interventions.

Estimating kidney function in HIV-infected adults in Kenya: comparison to a direct measure of glomerular filtration rate by iohexol clearance.

BACKGROUND: More than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population. METHODS: We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated. RESULTS: The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm(3). Median measured GFR was 115 mL/min/1.73 m(2). Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60-90 mL/min/1.73 m(2) (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions. CONCLUSIONS: Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m(2), in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.

Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated gene, TSC-36, inhibits invasion.

The transcription factor AP-1 (activator protein-1) is required for transformation by many oncogenes, which function upstream of it in the growth factor-ras signal transduction pathway. Previously, we proposed that one role of AP-1 in transformation is to regulate the expression of a multigenic invasion programme. As a test of this proposal we sought to identify AP-1 regulated genes based upon their differential expression in 208F rat fibroblasts transformed by FBR-v-fos (FBR), and to determine if they functioned in the invasion programme. Subtracted cDNA libraries specific for up- or down-regulated genes in FBRs compared to 208Fs were constructed and analysed. Northern analysis revealed that the cDNAs in both libraries represented differentially expressed genes. Nucleic acid sequence analysis of randomly selected cDNA clones from each library coupled with searches of nucleic acid and amino acid sequence databases determined that many of the cDNAs represented proteins that function in various aspects of the invasion process. Functional analysis of one the down-regulated genes, TSC-36/follistatin-related protein (TSC-36/Frp), which has not previously been associated with invasion, demonstrated that its expression in FBRs inhibited in vitro invasion. These results support the proposal that AP-1 in transformed cells regulates a multigenic invasion programme.

Transcriptional regulation of cell invasion: AP-1 regulation of a multigenic invasion programme.

The focus of this review will be on the regulation of the multigenic invasion programme by activator protein-1 (AP-1). Investigation of AP-1-regulated gene expression in transformed cells can be used to identify the genes in the multigenic invasion programme and to validate them as targets for diagnosis or therapy.

Differentiation stage-specific expression of a gene during granulopoiesis.

Differential screening of a recombinant cDNA library using cDNAs transcribed from poly(A)+ RNA of normal or leukemic leukocytes revealed a number of recombinants homologous to mRNAs characteristic of particular leukemias. The occurrence of one of these (pCG14) in high abundance was shown to be sufficiently characteristic of the circulating leukocyte population of chronic granulocytic leukemia (CGL) patients to distinguish them from all other populations of leukocytes. We have now characterized the gene encoding this mRNA and shown that its expression is specific to the granulocyte lineage in hemopoietic cells and is, moreover, limited to a narrow stage of differentiation during granulopoiesis. Our results explain why high levels of pCG14 RNA are characteristic of chronic granulocytic leukemia peripheral blood leukocytes.

The nucleotide sequence of the mercuric resistance operons of plasmid R100 and transposon Tn501: further evidence for mer genes which enhance the activity of the mercuric ion detoxification system.

The DNA sequences of the mercuric resistance determinants of plasmid R100 and transposon Tn501 distal to the gene (merA) coding for mercuric reductase have been determined. These 1.4 kilobase (kb) regions show 79% identity in their nucleotide sequence, and in both sequences two common potential coding sequences have been identified. In R100, the end of the homologous sequence is disrupted by an 11.2 kb segment of DNA which encodes the sulfonamide and streptomycin resistance determinants of Tn21. This insert contains terminal inverted repeat sequences and is flanked by a 5 base pair (bp) direct repeat. The first of the common potential coding sequences is likely to be that of the merD gene. Induction experiments and mercury volatilization studies demonstrate an enhancing but non-essential role for these merA-distal coding sequences in mercury resistance and volatilization. The potential coding sequences have predicted codon usages similar to those found in other Tn501 and R100 mer genes.

The nucleotide sequence of the tnpA gene completes the sequence of the Pseudomonas transposon Tn501.

The nucleotide sequence of the gene (tnpA) which codes for the transposase of transposon Tn501 has been determined. It contains an open reading frame for a polypeptide of Mr = 111,500, which terminates within the inverted repeat sequence of the transposon. The reading frame would be transcribed in the same direction as the mercury-resistance genes and the tnpR gene. The amino acid sequence predicted from this reading frame shows 32% identity with that of the transposase of the related transposon Tn3. The C-terminal regions of these two polypeptides show slightly greater homology than the N-terminal regions when conservative amino acid substitutions are considered. With this sequence determination, the nucleotide sequence of Tn501 is fully defined. The main features of the sequence are briefly presented.