A Systematic Literature Review of 3D Deep Learning Techniques in Computed Tomography Reconstruction.

Computed tomography (CT) is used in a wide range of medical imaging diagnoses. However, the reconstruction of CT images from raw projection data is inherently complex and is subject to artifacts and noise, which compromises image quality and accuracy. In order to address these challenges, deep learning developments have the potential to improve the reconstruction of computed tomography images. In this regard, our research aim is to determine the techniques that are used for 3D deep learning in CT reconstruction and to identify the training and validation datasets that are accessible. This research was performed on five databases. After a careful assessment of each record based on the objective and scope of the study, we selected 60 research articles for this review. This systematic literature review revealed that convolutional neural networks (CNNs), 3D convolutional neural networks (3D CNNs), and deep learning reconstruction (DLR) were the most suitable deep learning algorithms for CT reconstruction. Additionally, two major datasets appropriate for training and developing deep learning systems were identified: 2016 NIH-AAPM-Mayo and MSCT. These datasets are important resources for the creation and assessment of CT reconstruction models. According to the results, 3D deep learning may increase the effectiveness of CT image reconstruction, boost image quality, and lower radiation exposure. By using these deep learning approaches, CT image reconstruction may be made more precise and effective, improving patient outcomes, diagnostic accuracy, and healthcare system productivity.

Comparative functional and structural analysis of Pseudomonas aeruginosa d-alanine-d-alanine ligase isoforms as prospective antibiotic targets.

Pseudomonas aeruginosa is a major human pathogen in the healthcare setting. The emergence of multi-drug-resistant and extensive drug-resistant P. aeruginosa is of great concern, and clearly indicates that new alternatives to current first-line antibiotics are required in the future. Inhibition of d-alanine-d-alanine production presents as a promising avenue as it is a key component in the essential process of cell wall biosynthesis. In P. aeruginosa, d-alanine-d-alanine production is facilitated by two isoforms, d-alanine-d-alanine ligase A (PaDdlA) and d-alanine-d-alanine ligase B (PaDdlA), but neither enzyme has been individually characterised to date. Here, we present the functional and structural characterisation of PaDdlA and PaDdlB, and assess their potential as antibiotic targets. This was achieved using a combination of in vitro enzyme-activity assays and X-ray crystallography. The former revealed that both isoforms effectively catalyse d-alanine-d-alanine production with near identical efficiency, and that this is effectively disrupted by the model d-alanine-d-alanine ligase inhibitor, d-cycloserine. Next, each isoform was co-crystallised with ATP and either d-alanine-d-alanine or d-cycloserine, allowing direct comparison of the key structural features. Both isoforms possess the same structural architecture and share a high level of conservation within the active site. Although residues forming the d-alanine pocket are completely conserved, the ATP-binding pocket possesses several amino acid substitutions resulting in a differing chemical environment around the ATP adenine base. Together, these findings support that the discovery of dual PaDdlA/PaDdlB competitive inhibitors is a viable approach for developing new antibiotics against P. aeruginosa.

Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data.

Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.

Gongying-Jiedu-Xiji recipe promotes the healing of venous ulcers by inhibiting ferroptosis via the CoQ-FSP1 axis.

Objective: Gongying-Jiedu-Xiji recipe (DDL, batch number Z01080175) reduces body temperature, detoxifies, activates the blood circulation, reduces swelling, and dispels decay and pus. The aim of this study was to investigate the mechanism of action by which DDL functions in the treatment of venous ulcers (VUs). Methods: Normal tissues as well as VU tissues before and after DDL treatment were collected from nine VU patients in the hospital with ethical approval. These three tissues were subjected to Prussian blue iron staining, immunoblotting, immunohistochemistry, immunofluorescence, and quantitative real-time PCR to detect the expression of ferroptosis suppressor protein 1 (FSP1), coenzyme Q (CoQ), 4-hydroxynonenal (4-HNE), and glutathione peroxidase 4 (GPX4). After successful validation of the heme-induced human foreskin fibroblast (HFF) ferroptosis model, lyophilized DDL powder was added to the cells, and the cells were subjected to viability assays, immunoblotting, flow cytometry, glutathione (GSH) and malonaldehyde (MDA) assays, electron microscopy and qPCR assays. Results: Ferroptosis in VU tissues was stronger than that in normal tissues, and ferroptosis in VU tissues after DDL treatment was weaker than that before treatment. Inhibition of CoQ and FSP1 and transfection of FSP1 influenced the effects of DDL. Conclusion: Our results suggest that DDL may promote healing by attenuating ferroptosis in VUs and that DDL may promote VU healing by modulating the CoQ-FSP1 axis.

Classroom Concordancing and Second Language Motivational Self-System: A Data-Driven Learning Approach.

Research shows that exploring language corpora through data-driven learning (DDL) plays a significant role in language learning. Nevertheless, it is not clear if using concordancing as an application of DDL affects the learners' second language motivation. To address this gap, the current study adopted a triangulation design, validating quantitative data model, and a quasi-experimental (comparison group, pretest-posttest) design. Ninety English-major university students with an intermediate level of English language proficiency, divided into control and experimental groups, took part in the study. Drawing on a second language motivational self-system questionnaire, the findings of the study did not result in any statistically significant differences between the students in their second language motivational self-system. Altogether, the students found learning English through a DDL approach with concordancing less motivating than receiving explicit instruction. The study has implications for language teaching and learning.

In Silico-Based Discovery of Natural Anthraquinones with Potential against Multidrug-Resistant E. coli.

E. coli is a Gram-negative bacterium that causes different human infections. Additionally, it resists common antibiotics due to its outer protective membrane. Natural products have been proven to be efficient antibiotics. However, plant natural products are far less explored in this regard. Accordingly, over 16,000 structures covering almost all African medicinal plants in AfroDb in a structural-based virtual screening were used to find efficient anti-E. coli candidates. These drug-like structures were docked into the active sites of two important molecular targets (i.e., E. coli's Ddl-B and Gyr-B). The top-scoring hits (i.e., got docking scores < -10 kcal/mol) produced in the initial virtual screening (0.15% of the database structures for Ddl-B and 0.17% of the database structures for Gyr-B in the database) were further refined using molecular dynamic simulation-based binding free energy (ΔG) calculation. Anthraquinones were found to prevail among the retrieved hits. Accordingly, readily available anthraquinone derivatives (10 hits) were selected, prepared, and tested in vitro against Ddl-B, Gyr-B, multidrug-resistant (MDR) E. coli, MRSA, and VRSA. A number of the tested derivatives demonstrated strong micromolar enzyme inhibition and antibacterial activity against E. coli, MRSA, and VRSA, with MIC values ranging from 2 to 64 µg/mL. Moreover, both E. coli's Ddl-B and Gyr-B were inhibited by emodin and chrysophanol with IC50 values comparable to the reference inhibitors (IC50 = 216 ± 5.6, 236 ± 8.9 and 0.81 ± 0.3, 1.5 ± 0.5 µM for Ddl-B and Gyr-B, respectively). All of the active antibacterial anthraquinone hits showed low to moderate cellular cytotoxicity (CC50 > 50 µM) against human normal fibroblasts (WI-38). Furthermore, molecular dynamic simulation (MDS) experiments were carried out to reveal the binding modes of these inhibitors inside the active site of each enzyme. The findings presented in this study are regarded as a significant step toward developing novel antibacterial agents against MDR strains.

Discovery of novel antibacterial agents: Recent developments in D-alanyl-D-alanine ligase inhibitors.

Bacterial infections can cause serious problems that threaten public health over a long period of time. Moreover, the continuous emergence of drug-resistant bacteria necessitates the development of novel antibacterial agents. D-alanyl-D-alanine ligase (Ddl) is an indispensable adenosine triphosphate-dependent bacterial enzyme involved in the biosynthesis of peptidoglycan precursor, which catalyzes the ligation of two D-alanine molecules into one D-alanyl-D-alanine dipeptide. This dipeptide is an essential component of the intracellular peptidoglycan precursor, uridine diphospho-N-acetylmuramic acid (UDP-MurNAc)-pentapeptide, that maintains the integrity of the bacterial cell wall by cross-linking the peptidoglycan chain, and is crucial for the survival of pathogens. Consequently, Ddl is expected to be a promising target for the development of antibacterial agents. In this review, we present a brief introduction regarding the structure and function of Ddl, as well as an overview of the various Ddl inhibitors currently being used as antibacterial agents, specifically highlighting their inhibitory activities, structure-activity relationships and mechanisms of action.

Effect of D-Ala-Ended Peptidoglycan Precursors on the Immune Regulation of Lactobacillus plantarum Strains.

The resistance of Lactobacillus plantarum to vancomycin depends on its peptidoglycan composition. Vancomycin has poor binding affinity with peptidoglycan precursors ending in D-alanyl-D-lactate (D-Ala-D-Lac) but binds strongly to peptidoglycan precursors ending in D-alanyl-D-alanine (D-Ala-D-Ala), resulting in resistance and sensitivity, respectively. The ligase Ddl, which generates D-Ala-D-Lac or D-Ala-D-Ala incorporated into the peptidoglycan precursor chain, is responsible for this specificity. To study the effect of peptidoglycan precursors on immunity, we constructed several strains of L. plantarum expressing the ddl gene of Lactococcus lactis to change their peptidoglycan precursors. The change in the termini of the peptidoglycan precursors was determined by the sensitivity of the strains to vancomycin. The overexpression of ddl increased the susceptibility of the strains to vancomycin. We further explored the regulation of the macrophage inflammatory response pathway by the wild-type and constructed strains, and found that these strains induced the MyD88-dependent TRAF6/MAPK pathway, and the increase in D-Ala L. plantarum peptidoglycan precursors increased the secretion of the inflammatory factors IL-6, IL-1ß and TNF-α. These results indicate that D-Ala-ended peptidoglycan precursors play a central role in the variable immunomodulatory ability of L. plantarum.

Optofluidic Formaldehyde Sensing: Towards On-Chip Integration.

Formaldehyde (HCHO), a chemical compound used in the fabrication process of a broad range of household products, is present indoors as an airborne pollutant due to its high volatility caused by its low boiling point ( T = - 19 °C). Miniaturization of analytical systems towards palm-held devices has the potential to provide more efficient and more sensitive tools for real-time monitoring of this hazardous air pollutant. This work presents the initial steps and results of the prototyping process towards on-chip integration of HCHO sensing, based on the Hantzsch reaction coupled to the fluorescence optical sensing methodology. This challenge was divided into two individually addressed problems: (1) efficient airborne HCHO trapping into a microfluidic context and (2) 3,5-diacetyl-1,4-dihydrolutidine (DDL) molecular sensing in low interrogation volumes. Part (2) was addressed in this paper by proposing, fabricating, and testing a fluorescence detection system based on an ultra-low light Complementary metal-oxide-semiconductor (CMOS) image sensor. Two three-layer fluidic cell configurations (quartz-SU-8-quartz and silicon-SU-8-quartz) were tested, with both possessing a 3.5 µL interrogation volume. Finally, the CMOS-based fluorescence system proved the capability to detect an initial 10 µg/L formaldehyde concentration fully derivatized into DDL for both the quartz and silicon fluidic cells, but with a higher signal-to-noise ratio (SNR) for the silicon fluidic cell ( S N R s i l i c o n = 6.1 ) when compared to the quartz fluidic cell ( S N R q u a r t z = 4.9 ). The signal intensity enhancement in the silicon fluidic cell was mainly due to the silicon absorption coefficient at the excitation wavelength,   a ( λ a b s = 420   nm ) = 5 × 10 4   cm - 1 , which is approximately five times higher than the absorption coefficient at the fluorescence emission wavelength, a ( λ e m = 515   nm ) = 9.25 × 10 3   cm - 1 .

d-Alanine-d-alanine ligase as a model for the activation of ATP-grasp enzymes by monovalent cations.

The ATP-grasp superfamily of enzymes shares an atypical nucleotide-binding site known as the ATP-grasp fold. These enzymes are involved in many biological pathways in all domains of life. One ATP-grasp enzyme, d-alanine-d-alanine ligase (Ddl), catalyzes ATP-dependent formation of the d-alanyl-d-alanine dipeptide essential for bacterial cell wall biosynthesis and is therefore an important antibiotic drug target. Ddl is activated by the monovalent cation (MVC) K+, but despite its clinical relevance and decades of research, how this activation occurs has not been elucidated. We demonstrate here that activating MVCs bind adjacent to the active site of Ddl from Thermus thermophilus and used a combined biochemical and structural approach to characterize MVC activation. We found that TtDdl is a type II MVC-activated enzyme, retaining activity in the absence of MVCs. However, the efficiency of TtDdl increased ∼20-fold in the presence of activating MVCs, and it was maximally activated by K+ and Rb+ ions. A strict dependence on ionic radius of the MVC was observed, with Li+ and Na+ providing little to no TtDdl activation. To understand the mechanism of MVC activation, we solved crystal structures of TtDdl representing distinct catalytic stages in complex with K+, Rb+, or Cs+ Comparison of these structures with apo TtDdl revealed no evident conformational change on MVC binding. Of note, the identified MVC binding site is structurally conserved within the ATP-grasp superfamily. We propose that MVCs activate Ddl by altering the charge distribution of its active site. These findings provide insight into the catalytic mechanism of ATP-grasp enzymes.

Molecular Evolution and Diversification of Proteins Involved in miRNA Maturation Pathway.

Small RNAs (smRNA, 19-25 nucleotides long), which are transcribed by RNA polymerase II, regulate the expression of genes involved in a multitude of processes in eukaryotes. miRNA biogenesis and the proteins involved in the biogenesis pathway differ across plant and animal lineages. The major proteins constituting the biogenesis pathway, namely, the Dicers (DCL/DCR) and Argonautes (AGOs), have been extensively studied. However, the accessory proteins (DAWDLE (DDL), SERRATE (SE), and TOUGH (TGH)) of the pathway that differs across the two lineages remain largely uncharacterized. We present the first detailed report on the molecular evolution and divergence of these proteins across eukaryotes. Although DDL is present in eukaryotes and prokaryotes, SE and TGH appear to be specific to eukaryotes. The addition/deletion of specific domains and/or domain-specific sequence divergence in the three proteins points to the observed functional divergence of these proteins across the two lineages, which correlates with the differences in miRNA length across the two lineages. Our data enhance the current understanding of the structure-function relationship of these proteins and reveals previous unexplored crucial residues in the three proteins that can be used as a basis for further functional characterization. The data presented here on the number of miRNAs in crown eukaryotic lineages are consistent with the notion of the expansion of the number of miRNA-coding genes in animal and plant lineages correlating with organismal complexity. Whether this difference in functionally correlates with the diversification (or presence/absence) of the three proteins studied here or the miRNA signaling in the plant and animal lineages is unclear. Based on our results of the three proteins studied here and previously available data concerning the evolution of miRNA genes in the plant and animal lineages, we believe that miRNAs probably evolved once in the ancestor to crown eukaryotes and have diversified independently in the eukaryotes.

d-Alanyl-d-Alanine Ligase as a Broad-Host-Range Counterselection Marker in Vancomycin-Resistant Lactic Acid Bacteria.

The peptidoglycan composition in lactic acid bacteria dictates vancomycin resistance. Vancomycin binds relatively poorly to peptidoglycan ending in d-alanyl-d-lactate and binds with high affinity to peptidoglycan ending in d-alanyl-d-alanine (d-Ala-d-Ala), which results in vancomycin resistance and sensitivity, respectively. The enzyme responsible for generating these peptidoglycan precursors is dipeptide ligase (Ddl). A single amino acid in the Ddl active site, phenylalanine or tyrosine, determines depsipeptide or dipeptide activity, respectively. Here, we established that heterologous expression of dipeptide ligase in vancomycin-resistant lactobacilli increases their sensitivity to vancomycin in a dose-dependent manner and overcomes the effects of the presence of a native d-Ala-d-Ala dipeptidase. We incorporated the dipeptide ligase gene on a suicide vector and demonstrated that it functions as a counterselection marker (CSM) in lactobacilli; vancomycin selection allows only those cells to grow in which the suicide vector has been lost. Subsequently, we developed a liquid-based approach to identify recombinants in only 5 days, which is approximately half the time required by conventional approaches. Phylogenetic analysis revealed that Ddl serves as a marker to predict vancomycin resistance and consequently indicated the broad applicability of the use of Ddl as a counterselection marker in the genus Lactobacillus Finally, our system represents the first "plug and play" counterselection system in lactic acid bacteria that does not require prior genome editing and/or synthetic medium.IMPORTANCE The genus Lactobacillus contains more than 200 species, many of which are exploited in the food and biotechnology industries and in medicine. Prediction of intrinsic vancomycin resistance has thus far been limited to selected Lactobacillus species. Here, we show that heterologous expression of the enzyme Ddl (dipeptide ligase)-an essential enzyme involved in peptidoglycan synthesis-increases sensitivity to vancomycin in a dose-dependent manner. We exploited this to develop a counterselection marker for use in vancomycin-resistant lactobacilli, thereby expanding the poorly developed genome editing toolbox that is currently available for most strains. Also, we showed that Ddl is a phylogenetic marker that can be used to predict vancomycin resistance in Lactobacillus; 81% of Lactobacillus species are intrinsically resistant to vancomycin, which makes our tool broadly applicable.

Edge-oriented dual-dictionary guided enrichment (EDGE) for MRI-CT image reconstruction.

In this paper, we formulate the joint/simultaneous X-ray CT and MRI image reconstruction. In particular, a novel algorithm is proposed for MRI image reconstruction from highly under-sampled MRI data and CT images. It consists of two steps. First, a training dataset is generated from a series of well-registered MRI and CT images on the same patients. Then, an initial MRI image of a patient can be reconstructed via edge-oriented dual-dictionary guided enrichment (EDGE) based on the training dataset and a CT image of the patient. Second, an MRI image is reconstructed using the dictionary learning (DL) algorithm from highly under-sampled k-space data and the initial MRI image. Our algorithm can establish a one-to-one correspondence between the two imaging modalities, and obtain a good initial MRI estimation. Both noise-free and noisy simulation studies were performed to evaluate and validate the proposed algorithm. The results with different under-sampling factors show that the proposed algorithm performed significantly better than those reconstructed using the DL algorithm from MRI data alone.

Crystal structures of d-alanine-d-alanine ligase from Xanthomonas oryzae pv. oryzae alone and in complex with nucleotides.

D-Alanine-D-alanine ligase (DDL) catalyzes the biosynthesis of d-alanyl-d-alanine, an essential bacterial peptidoglycan precursor, and is an important drug target for the development of antibacterials. We determined four different crystal structures of DDL from Xanthomonas oryzae pv. oryzae (Xoo) causing Bacteria Blight (BB), which include apo, ADP-bound, ATP-bound, and AMPPNP-bound structures at the resolution between 2.3 and 2.0 Å. Similarly with other DDLs, the active site of XoDDL is formed by three loops from three domains at the center of enzyme. Compared with d-alanyl-d-alanine and ATP-bound TtDDL structure, the γ-phosphate of ATP in XoDDL structure was shifted outside toward solution. We swapped the ω-loop (loop3) of XoDDL with those of Escherichia coli and Helicobacter pylori DDLs, and measured the enzymatic kinetics of wild-type XoDDL and two mutant XoDDLs with the swapped ω-loops. Results showed that the direct interactions between ω-loop and other two loops are essential for the active ATP conformation for D-ala-phosphate formation.

Role of DDL processes during electrolytic reduction of Cu(II) in a low oxygen environment.

Heavy metals typically accumulate in reduced bottom sediments after being discharged into waterways by industrial and municipal processes. A laboratory experiment was conducted in order to determine if abundance of clay in the bottom sediments of a Cu-contaminated aqueous ecosystem could enhance electrolytic reduction of the heavy metal. Cu(NO3)2 · 2.5H2O was added to simulate a moderately contaminated system with 650 µg Cu/ml kaolinite clay-water slurry. A constant electrical potential of 1.0 V/cm was applied across platinum wire electrodes inserted into the continuously stirred system for four days while the system ORP(2) was monitored and periodic sub-samples were taken for analysis. The electrical as well as the chemical results indicate that the quantity of Cu(II) being reduced to Cu(I), especially within the aqueous phase, is increased within the first 48 h of experimentation by the presence of kaolinite clay up to 0.05 mg clay/l slurry.

Crystal structure of Arabidopsis thaliana Dawdle forkhead-associated domain reveals a conserved phospho-threonine recognition cleft for dicer-like 1 binding.

Dawdle (DDL) is a microRNA processing protein essential for the development of Arabidopsis. DDL contains a putative nuclear localization signal at its amino-terminus and forkhead-associated (FHA) domain at the carboxyl-terminus. Here, we report the crystal structure of the FHA domain of Arabidopsis Dawdle, determined by multiple-wavelength anomalous dispersion method at 1.7-Å resolution. DDL FHA structure displays a seven-stranded ß-sandwich architecture that contains a unique structural motif comprising two long anti-parallel strands. Strikingly, crystal packing of the DDL FHA domain reveals that a glutamate residue from the symmetry-related DDL FHA domain, a structural mimic of the phospho-threonine, is specifically recognized by the structurally conserved phospho-threonine binding cleft. Consistently with the structural observations, co-immuno-precipitation experiments performed in Nicotiana benthamiana show that the DDL FHA domain co-immuno-precipitates with DCL1 fragments containing the predicted pThr+3(Ile/Val/Leu/Asp) motif. Taken together, we count the recognition of the target residue by the canonical binding cleft of the DDL FHA domain as the key molecular event to instate FHA domain-mediated protein-protein interaction in plant miRNA processing.

Critical roles of RNA-binding proteins in miRNA biogenesis in Arabidopsis.

MicroRNAs (miRNAs) are key regulators of gene expression and play critical roles in modulating metabolism, development and physiology in animals and plants. miRNA levels are transcriptionally and post-transcriptionally controlled for their proper function. Recent studies have shown that RNA-binding proteins play important roles in producing miRNAs by affecting the accurate and/or efficient processing of precursors of miRNAs. Many of these RNA-binding proteins also have roles in general RNA metabolism, indicating potential connections between miRNA biogenesis and other RNA metabolism. Here, we focus on the function of several RNA-binding proteins in miRNA biogenesis in Arabidopsis.

Toxicidade dose e tempo dependente da 2', 3' - didesoxiinosina em pâncreas, linfonodo e timo de rato / Toxicity dose-and time-dependent 2 ', 3'- dideoxyinosine in pancreas, lymph node and thymus mouse

O anti-retroviral análogo de nucleosídeo 2',3' - didesoxiinosina (ddl) tem uma ampla utilização clínica no tratamento de pacientes com AIDS iu HIV positivos. Apesar da toxicidade reduzida, alguns problemas tem sido levantados com a utilização da ddl em tratamento a longo prazo. Vários estudo clínicos tem associado a pancreatite com a terapia prolongada de ddl em pacientes infectados com o HIV...Nenhum tratamento com ddl modificou a amilase sérica determinada na época do sacrifício dos animais. Nos ratos tratados com ddl, 600 mg kg -1 dia -1, por mais de 28 dias foi observada uma marcada hipoglicemia (i.p. = 34,7 +- 7,4 mgdL-1 p,,0,05, s.c.= 45,0 +- 7,5 mg dL -1, p,,0,05). Conclui-se que a ddl induz um efeito tóxico direto dose e tempo dependente nos tecidos pancreático e linfóide de rato. Os resultados suportam o envolvimento da ddl na pancreatite relatada em pacientes com AIDS tratados com ddl e são compatíveis com a hipótese de que esse anti-retroviral pode afetar a resposta imune humoral. No conjunto, este estudo indica que a toxicidade potencial do tratamento crônico com ddl deve ser mais profundamente examinada.