Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76

Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre- and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The pfcrt codon 72 to 76 haplotype SVMNT was present in all samples tested, both before and after treatment. Amodiaquine did not clearly select for any pfmdr1 genotype, but a novel mutation, pfmdr1 N86F, was detected in four samples. We provide in vivo data to support the in vitro correlation between pfcrt SVMNT and increased resistance to the metabolite of amodiaquine.Amodiaquine (AQ), a 4-aminoquinoline related to chloroquine (CQ), has been used commonly as a monotherapy and now as a partner drug in artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated Plasmodium falciparum malaria. In many countries, predominantly in Africa, the in vivo efficacy of AQ was found to be good even in the face of increasing CQ resistance (12). However, reports of AQ resistance have come from South America, Asia, and East Africa (7, 8, 10).Mutations in the P. falciparum chloroquine resistance transporter gene (pfcrt) and multidrug resistance gene 1 (pfmdr1) have been associated with clinical resistance to both CQ and AQ (13). The presence of the pfcrt codon 72 to 76 haplotype SVMNT (Ser-Val-Met-Asn-Thr) correlates with high-level resistance to the AQ metabolite desethylamodiaquine (DEAQ) in in vitro tests (14) and has been detected with a high prevalence in parasite populations from Brazil, Papua New Guinea, Laos, Iran, and India (9, 18). Clinical trials in East Africa have also demonstrated high levels of in vivo resistance to AQ; in those studies, the parasites carried pfcrt codon 72 to 76 haplotype CVIET, and pfmdr1 polymorphisms 86Y, 184Y, and 1246Y were found to be selected after AQ treatment failure (5, 6, 11).A clinical trial performed in Nangahar Province, East Afghanistan, in 2002 and 2003 to explore possible replacement treatments for CQ showed very poor efficacies of both CQ and AQ monotherapy (adequate clinical and parasitological responses were seen in 11% and 9% of cases, respectively, by day 42) (4). Our aim in this study was to evaluate pre- and posttreatment samples from patients treated with AQ for pfcrt and pfmdr1 mutations and to determine which, if any, polymorphisms are associated with AQ treatment failure in Afghanistan.     

Janus transition metal dichalcogenides in combination with MoS2 for high-efficiency photovoltaic applications: a DFT study

Exotic features of two-dimensional materials have been demonstrated, making them particularly appealing for both photocatalytic and photovoltaic applications. van der Waals corrected density functional theory calculations were performed on AAII-Se MoSSe, AAII-Te MoSTe, and AAII-Se WSSe heterostructures in this study. Our findings reveal that the heterostructures have high stability due to the tiny lattice mismatch and binding energy, which is extremely favorable for epitaxial growth of these heterostructures. According to the electronic band gap calculation, AAII-Se MoSSe and AAII-Se WSSe are semiconducting materials, while AAII-Te MoSTe has metallic properties. Interestingly, all three heterostructures have type II band gap alignment, which is advantageous for photovoltaic and photocatalytic applications. Furthermore, it was discovered that AAII-Se MoSSe and AAII-Se WSSe heterostructures exhibit high power conversion efficiency of up to 12.15% and 9.37%, respectively. Based on these intriguing features, the two heterostructures are excellent prospects for photovoltaic applications. The heterostructures have no appropriate band edge sites for overall water splitting at pH = 0, but they are good for the oxygen evolution process. It is feasible to alter the position of the band edges using strain resulting in improved overall water splitting by the heterostructures.

MoS₂/Janus TMDC heterostructure stacking patterns with different stacking orientations.     

Case-Case-Control Study of Patients with Carbapenem-Resistant and Third-Generation-Cephalosporin-Resistant Klebsiella pneumoniae Bloodstream Infections

Strains of third-generation-cephalosporin-resistant Klebsiella pneumoniae (3GCRKP) and carbapenem-resistant K. pneumoniae (CRKP) are rapidly spreading. Evidence is needed to establish whether differences exist between patients at risk for 3GCRKP and those at risk for CRKP bloodstream infections (BSIs); thus, this retrospective case-case-control study was conducted to determine if the risk factors for these two infections differ. The inclusion criteria for cases were positive blood cultures for K. pneumoniae, first episode of BSI, age of ≥18 years, and susceptibility results indicating resistance to either third-generation cephalosporins (3GCRKP group) or carbapenems and cephalosporins (CRKP group). Controls were patients admitted for ≥72 h and were matched to cases by month/year and medical unit. Variables of interest were analyzed by univariate analysis, and those of significance were analyzed by logistic regression. In total, 111 patients with 3GCRKP BSIs and 43 patients with CRKP BSIs were matched to 154 controls. Multivariate analyses of 3GCRKP case and control groups demonstrated that a length of stay (LOS) of >40 days (odds ratio [OR], 17.7; 95% confidence interval [CI], 3.7 to 84.3), the use of antibiotics in the past 90 days (OR, 4.3; 95% CI, 1.5 to 11.9), and the presence of a central venous catheter (OR, 4.1; 95% CI, 1.3 to 13.4) were independent risk factors. Multivariate analyses of the CRKP case and control groups demonstrated that a LOS of >40 days (OR, 13.5; 95% CI, 2.9 to 62.8) and the use of antibiotics in the past 90 days (OR, 5.9; 95% CI, 1.3 to 26.5) were independent risk factors. Similar factors put patients at risk for these two types of K. pneumoniae BSIs.     

Cloning the shared components of complex DNA resources

The complex and repetitive nature of mammalian genomes limitsthe ability of conventional molecular techniques to recoversequences of interest. Here we describe a rapid and simple procedurefor the direct cloning of sequences which are coincident betweenDNA mixtures of whole genome complexity. The system, calledend ligation coincident sequence cloning (EL-CSC), can enrichcoincident DNA by greater than 10⁶-fold and overcomes problemsassociated with repetitive elements. Applying EL-CSC to variouspaired DNA resources enables the facile cloning of both genomicmarkers and novel genes. To demonstrate the power of the methodwe have 1) selectively purified single copy sequences from acomplete genome, and II) isolated gene fragments from 260 kbof cloned genomic DNA.     

Histopathological and histochemical effects of Naja haje venom on kidney tissue of mice

Naja haje venom in a lethal dose caused focal tubular degenerative lesions with intact glomeruli. The tubular basement membrane was intact. The brush border of the proximal convoluted tubules was only destroyed in the markedly degenerated tubules. The activity of both alkaline phosphatase and succinic dehydrogenase enzymes was decreased. Vacuolization and shading of the epithelial lining of the cells of Henle's loop and the distal convoluted tubules was observed. Cases were found in the collecting tubules. Minimal tubular damage with normal enzymatic activity followed the injection of a single sublethal dose of the venom. Multiple sublethal doses caused mainly glomerular changes with almost normal tubules. Hypertrophy of the cells of the parietal layer of Bowman's capsule appeared. The cells acquired as a PAS positive free border similar to that of the proximal convoluted tubules. The thickened empty rings of basement membrane were suggestive of endothelial damage. Distortion of some of the glomeruli with obliteration of the capsular space at certain points was observed. The cells of the proximal convoluted tubules showed double nuclei and prominent nucleoli with normal enzymatic activity of both succinic dehydrogenase and alkaline phosphatase.     

Trans-cultural comparison of disordered eating in Korean women

OBJECTIVE: The presence of eating disorders in non-Western cultures is often attributed to the export of Western ideals. This study examines this hypothesis by comparing disordered eating attitudes and behaviors in Korean women with differing levels of exposure to Western culture. METHOD: Second-generation Korean-Americans (n=167) and Korean immigrants (n=37) completed the Eating Attitudes Test (EAT-26), and data from native Koreans (n=937) were obtained from a previous epidemiological study, using a Korean-translated version of the EAT-26 (K-EAT-26). Korean-American and immigrant women completed the Suinn-Lew Asian Self-Identity Acculturation Scale (SL-ASIA). RESULTS: Korean-American women scored significantly lower on the EAT-26 than Korean immigrants and native Koreans, who did not differ from each other. Korean-Americans were more Western-oriented than Korean immigrants, and acculturation levels were not correlated with EAT-26 scores in either group. CONCLUSION: This study supports the importance of native cultural factors in the development of eating disorders in non-Western contexts.     

Strategic memory in adults with anorexia nervosa: Are there similarities to obsessive compulsive spectrum disorders?

OBJECTIVE: There is growing interest in the relationship between anorexia nervosa (AN) and obsessive-compulsive (OC) spectrum disorders (e.g., OCD, body dysmorphic disorder [BDD]). Previous neuropsychological investigations of OC spectrum disorders have identified problems with the efficient use of strategy on complex measures of learning and memory. This study evaluated nonverbal strategic memory in AN outpatients using an approach previously applied to OC spectrum disorders. METHOD: Eighteen patients with AN and 19 healthy control participants completed the Rey-Osterrieth Complex Figure Test (RCFT), a widely used measure of nonverbal strategic planning, learning, and memory. RESULTS: Individuals with AN differed significantly from healthy controls in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in learning were mediated by copy organizational strategies. CONCLUSION: These results are identical to study findings in OCD and BDD, indicating important shared neuropsychological features among AN and these OC spectrum disorders. As in OCD and BDD, the essential cognitive deficit in AN was impaired use of organizational strategies, which may inform our understanding of the pathophysiology of AN and potentially offer treatment implications.