Although the dd-CPases are usually the most abundant PBPs in the cell, they are not essential for bacterial survival (Denome et al., 1999) and the in vivo purposes of these seemingly nonessential and redundant enzymes are mostly unknown. The

exception to the above statement is the E. coli protein PBP 5, which helps maintain the normal morphology of this organism even in the absence of seven other PBPs (Nelson & Young, 2001). In the absence of PBP 5 by itself, the cells exhibit small morphological aberrations, but as more PBPs are deleted, the cells become considerably misshapen (Nelson & Young, 2000, 2001). PBP 5 consists of two major domains, I and II, oriented almost at right angles to one another (Davies et al., 2001; Nicholas et al., 2003). The dd-CPase active Roxadustat purchase site selleck products is located in domain I and is responsible for maintaining normal cell shape (Nelson et al., 2002; Ghosh & Young, 2003). Domain II is composed mostly of β-sheets and may lift the enzymatic domain away from the inner membrane and into the periplasm toward the peptidoglycan

substrate (Nelson et al., 2002; Ghosh & Young, 2003). At its extreme carboxyl terminus, at the base of domain II, PBP 5 has a short 18-amino acid (Jackson & Pratt, 1987) amphipathic helix that tethers the protein to the outer face of the inner membrane (Nelson et al., 2002; Ghosh & Young, 2003). The closest homologue to PBP 5 from any organism is PBP 6, from E. coli itself. Interestingly, PBP 6, although ∼65% identical to PBP 5, cannot restore normal shape to aberrant cells, as can PBP 5 (Ghosh & Young, 2003). Domain swap and mutagenesis experiments indicate that the relevant differences

between the two enzymes localize to domain I, and, in fact, to a small stretch of 20 amino acids that surrounds the canonical KTG motif of the active site (Nelson et al., 2002; Ghosh & Young, 2003). For convenience, we will refer to this 20-amino acid segment as the ‘morphology maintenance domain’ (MMD) (Ghosh & Young, 2003) (Fig. 1). When PBP 6 is engineered so that its MMD is replaced by that from PBP 5, the mosaic protein (PBP 656) complements the shape defects of the E. coli mutants as well as wild-type PBP 5 (Ghosh Erythromycin & Young, 2003). Conversely, replacing the MMD of PBP 5 with that from PBP 6 (generating PBP 565) eliminates the ability to complement. PBPs 5 and 6 differ by seven residues in this peptide fragment, but only two, Asp 218 and Lys 219, seem to be necessary to confer on PBP 656 the complementation attributes of PBP 5 (Ghosh & Young, 2003) (Fig. 1). However, mutation of these two amino acids does not eliminate the ability of PBP 5 to complement shape defects, suggesting that other structural features blunt the effects of these changes in the wild-type protein.

We have previously introduced mutations into the aprN gene using site-directed mutagenesis to probe the importance of hydrogen bonds in the active site of the NK (Zheng et al., 2006), increase the oxidative stability of NK (Weng et al., 2009), and investigate the function of the propeptide of NK (Jia et al., 2010).

DNA family shuffling is a simple and efficient method for molecular-directed evolution by mimicking and accelerating the process of sexual recombination (Crameri et al., 1998). This approach involves the recombination of homologous sequences, which are the same gene from related species or related genes from a single species to create a library of chimeras. A library of chimeric subtilisins has been created by DNA family shuffling and the mutants have improved properties compared to the parental enzymes (Ness et al., 1999). NK belongs to the subtilisin family of serine protease, has the same conserved catalytic triad (D32, H64, S221) and substrate binding sites www.selleckchem.com/products/CAL-101.html (S125, L126, G127) (Bryan,

2000). The homology of the encoding gene sequence between NK and subtilisin BPN′ (SB) from Bacillus amyloliquefaciens or NK and subtilisin Carlsberg (SC) from Selleckchem Sirolimus Bacillus licheniformis was 80% or 69%, respectively (Nakamura et al., 1992). Therefore, we introduced random mutagenesis in the aprN gene using the DNA family shuffling method. The three encoding genes were recombined and shuffled to establish chimeric gene libraries. Combined with a high-throughput plate-based screening method, mutants that had the desired properties were selected, purified Anacetrapib and characterized. In the current study, we reported for the first time the application of directed evolution to improve the fibrinolytic activity of subtilisin NAT from Bacillus natto. Bacillus subtilis var. natto strain AS 1.107 (Institute of Microbiology, Chinese Academy of Sciences, Beijing, China),

B. amyloliquefaciens strain CICC 20164 and B. licheniformis strain CICC 10092 (China Center of Industrial Culture Collection, Beijing, China) were used to isolate the genomic DNA. Escherichia coli BL21(DE3)pLysS and the plasmid pET-26b+ (Novagen) were used as the host-vector system for the cloning and expression of the gene encoding the enzymes. All of the enzymes for DNA manipulations were purchased from TaKaRa (Dalian). Thrombin and urokinase were purchased from the Chinese Medicine Testing Institute. Human fibrinogen and succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (suc-AAPF-pNA) were purchased from Sigma (St. Louis, MO). The oligonucleotide primers and plasmids used in the current study are listed in Table 1. The gene encoding the precursor NK was amplified by PCR from genomic DNA of B. subtilis var. natto using the primers PNB and PNX. Similarly, the gene encoding the precursor SB from B. amyloliquefaciens (Vasantha et al., 1984) or Carlsberg from B. licheniformis (Jacobs et al., 1985) were also obtained by PCR using the two sets of primer PBB and PBX or PCB and PCX, respectively.

e. bactericidal vs. bacteriostatic) (von Ah et al., 2009). In addition, the bacterial growth-related heat flow patterns observed by IMC can allow rapid discrimination of medically important microorganisms. For example, IMC can be used to differentiate methicillin-susceptible Staphylococcus aureus from methicillin-resistant selleck chemical S. aureus within 5 h (von Ah et al., 2008; Baldoni et al., 2009). Finally, in connection with dentistry, it has been shown that IMC can measure the growth and the heat of adsorption of mouth bacteria on surfaces (Hauser-Gerspach et al., 2008). In addition to detection and evaluation of bacterial infection and antimicrobial agents, IMC has proven to be an effective tool in studying viral infections

and activities of antiviral compounds (Tan & Lu, 1999; Heng et al., 2005). Heng et al. (2005) emphasize that the change in the metabolism of BHK-21 cells infected by the foot and mouth disease virus was easily indicated by the strong heat production of these infected cells LY294002 mw compared with uninfected controls. For environmental microbiology, IMC is of great value in assessing bacterial activities directly without

the need to separately culture organisms or add radiolabelled, fluorescent or chromogenic substrates. Therefore, IMC is an excellent complement to molecular studies. For example, early observations of lake and marine sediments have shown that there was a linear relation between the dehydrogenase activity assayed using triphenyltetrazolium chloride (TTC) or iodonitrotetrazolium chloride (INT) and sediment heat production (Pamatmat & Bhagwat, 1973; Pamatmat et al., 1981). In addition, Pamatmat et al. (1981) also found a strong correlation between the concentration of ATP in the sediment and the heat production. Similarly, a more recent study on lake sediments has concluded that heat production followed the same trend as radiolabelled

leucine and thymidine incorporation. This study concludes that IMC is especially useful with sediments that contain mixed communities of anaerobes, fermenters and aerobes (Haglund et al., 2003). However, it must be noted that the method is somewhat unspecific in distinguishing between metabolic heat and chemical heat, and therefore several controls are required to determine the quantity of chemical heat. The relationships Janus kinase (JAK) between heat production, ATP and dehydrogenases assay (TTC or INT) have also been observed for larger organisms such as the nematode Caenorhabditis elegans (Braeckman et al., 2002). With respect to the size of the aquatic microorganisms considered, IMC has also been useful in investigating allometric relations between mass, surface area and metabolic rate (measured as heat production) of aquatic protists ranging from 1 to 106 μm3 in size (Johnson et al., 2009). In addition, based on their microcalorimetry results, the authors hypothesized that for these organisms, the cost of motility was low.

In contrast, other-body judgments showed pre-supplementary motor and superior parietal activity. Expansion in the

dorsoventral direction was associated with the left fusiform gyrus and the right inferior parietal lobule, whereas horizontal expansions were associated with activity in the bilateral somatosensory area. These results suggest neural dissociations between the two body axes: dorsoventral images of thickness may require visual processing, whereas bodily sensations are involved in horizontal body-size perception. Somatosensory rather than visual processes can be critical for the assessment of frontal own-body appearance. Visual body thickness Bortezomib solubility dmso and somatosensory body width may be integrated to construct a whole-body representation. “
“Activity-dependent gene expression depends, in part, on transcriptional regulation that is coordinated by rapid changes in the chromatin landscape as well as the covalent modification of DNA. Here we demonstrate that the expression of brain-derived neurotrophic factor (BDNF), a gene that is critically involved in neural

plasticity and subject to epigenetic regulation, is regulated by the RNA/DNA editing enzyme, activation-induced cytidine deaminase (AID). Similar to previous reports, we observed an activity-dependent induction of BDNF exon IV mRNA expression, which correlated with a reduction in DNA methylation within the BDNF P4 promoter. Lentiviral-mediated knockdown of AID disrupted these effects and inhibited BDNF exon IV mRNA expression, Selleck CB-839 an effect that was associated with decreased cAMP response element-binding protein occupancy within the BDNF P4 promoter. Thus, together with other nearly epigenetic mechanisms, AID plays a key role in regulating activity-dependent BDNF expression in post-mitotic cortical neurons. “
“Listeria monocytogenes is a Gram positive pathogen that is ubiquitous in the environment. It is a facultative anaerobic rod that causes listeriosis, a disease with potentially lethal consequences for susceptible individuals.

During infection, the pathogen is capable of sequestering metal ions to act as vital biocatalysts in cellular processes. The zinc uptake regulator (ZurR) is predicted to coordinate uptake of zinc from the external environment. An in-frame deletion of the zurR gene resulted in a mutant exhibiting a small colony phenotype and a smaller cell size. The zurR mutant was unaffected under conditions of zinc limitation but demonstrated increased sensitivity to toxic levels of zinc. The mutant also demonstrated a significant (1-log) reduction in virulence potential in the murine model of infection. Using a bioinformatic approach, we identified a number of potentially Zur-regulated genes in the genome of L. monocytogenes. Quantitative RT-PCR demonstrated significant de-repression of zurA,lmo0153, and lmo1671 in the zurR mutant background indicating that these putative transporters are ZurR regulated.

In cases in which the onset period exceeds 1 month, clinicians should consider the possibility of reinfection and begin empiric antibiotic administration for a different S. pyogenes strain. Macrolide administration is recommended as an alternative treatment for patients who are GSK2126458 order allergic to penicillin (Bisno et al., 2002). However, worldwide emergence of macrolide resistance among pharyngeal isolates of S. pyogenes has been reported in recent years (Martin et al., 2002; Richter et al., 2008; Michos et al., 2009). In a survey of strains obtained from recurrent and reinfection pharyngitis cases, we

observed a much higher rate of antibiotic resistance than reported in several previous studies. Furthermore, there was a higher proportion of strains that showed antibiotic resistance toward erythromycin and azithromycin among those obtained from recurrent cases as compared with initial Androgen Receptor Antagonist purchase onset and reinfection cases, which was associated with possession of the erm and mef genes. In addition, our results strongly indicate that it is essential to examine the sensitivity of target bacteria to antibiotics in patients

receiving therapy. We thank Drs Murai T, Irie M, Myokai M, Nakano M, and Honma N for providing the S. pyogenes strains, and Hashimoto S for his technical assistance. This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas, Young Scientists (A), Scientific Research (B), and Challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology, and Japan Society for the Promotion of Science, as well as grants from the Takeda Science Foundation and Iwadare Scholarship Foundation. “
“This study reports the Idelalisib in vivo first successful application of real-time PCR for the detection of Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), in Ghana, a BU-endemic country. Environmental samples and organs of small mammals

were analyzed. The real-time PCR assays confirmed the presence of M. ulcerans in a water sample collected in a BU-endemic village in the Ashanti Region. Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a severe disease of the skin (Portaels, 1995; Portaels et al., 2009). The disease is mainly endemic in Central and West Africa, where it affects mostly poor rural communities (Portaels, 1995; Debacker et al., 2004). Epidemiological evidence strongly associates BU with aquatic ecosystems and M. ulcerans is considered an environmental pathogen (Portaels, 1995; Stinear et al., 2007). However, its reservoir and mode(s) of transmission are not yet determined (Duker et al., 2006). Presently, detection of M. ulcerans in the environment is based on demonstrating by PCR the presence of IS2404 (Ross et al., 1997), an insertion sequence with >200 copies in M. ulcerans (Stinear et al., 2007).

In cases in which the onset period exceeds 1 month, clinicians should consider the possibility of reinfection and begin empiric antibiotic administration for a different S. pyogenes strain. Macrolide administration is recommended as an alternative treatment for patients who are selleck kinase inhibitor allergic to penicillin (Bisno et al., 2002). However, worldwide emergence of macrolide resistance among pharyngeal isolates of S. pyogenes has been reported in recent years (Martin et al., 2002; Richter et al., 2008; Michos et al., 2009). In a survey of strains obtained from recurrent and reinfection pharyngitis cases, we

observed a much higher rate of antibiotic resistance than reported in several previous studies. Furthermore, there was a higher proportion of strains that showed antibiotic resistance toward erythromycin and azithromycin among those obtained from recurrent cases as compared with initial www.selleckchem.com/products/SRT1720.html onset and reinfection cases, which was associated with possession of the erm and mef genes. In addition, our results strongly indicate that it is essential to examine the sensitivity of target bacteria to antibiotics in patients

receiving therapy. We thank Drs Murai T, Irie M, Myokai M, Nakano M, and Honma N for providing the S. pyogenes strains, and Hashimoto S for his technical assistance. This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas, Young Scientists (A), Scientific Research (B), and Challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology, and Japan Society for the Promotion of Science, as well as grants from the Takeda Science Foundation and Iwadare Scholarship Foundation. “
“This study reports the enough first successful application of real-time PCR for the detection of Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), in Ghana, a BU-endemic country. Environmental samples and organs of small mammals

were analyzed. The real-time PCR assays confirmed the presence of M. ulcerans in a water sample collected in a BU-endemic village in the Ashanti Region. Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a severe disease of the skin (Portaels, 1995; Portaels et al., 2009). The disease is mainly endemic in Central and West Africa, where it affects mostly poor rural communities (Portaels, 1995; Debacker et al., 2004). Epidemiological evidence strongly associates BU with aquatic ecosystems and M. ulcerans is considered an environmental pathogen (Portaels, 1995; Stinear et al., 2007). However, its reservoir and mode(s) of transmission are not yet determined (Duker et al., 2006). Presently, detection of M. ulcerans in the environment is based on demonstrating by PCR the presence of IS2404 (Ross et al., 1997), an insertion sequence with >200 copies in M. ulcerans (Stinear et al., 2007).

Acidipila

[A.ci.di.pi'la N.L. n. acidum (from L. adj. acidus, sour] an acid; L. fem. n. pila a ball or sphere; N.L. fem. n. Acidipila acid sphere). Cells stain Gram-negative and are nonmotile cocci and coccobacilli. Aerobic, acidophilic, and chemoorganotrophic. Good carbon sources for growth are sugars, gluconate, and some amino acids. The main components of cellular fatty acids are C15:0 iso and C16:1ω7c. Menaquinone-8 is the major quinone. The phylogenetic position is in subdivision 1 of the phylum Acidobacteria. Habitats: AMD and acidic soil. The type species is A. rosea. Acidipila rosea (ro’se.a L. fem. adj. rosea rose colored, pink). In addition to GSK1120212 nmr the characteristics shown in the description of the genus, the following are observed. Cells are cocci and coccobacilli measuring 0.5–0.8 μm in diameter. Cells are capsulated. Colonies on solid media are circular, smooth, translucent, mucous, and pink. The temperature range MS-275 cost for growth is 22–37 °C (optimum 30 °C). The pH range for growth is 3.0–6.0 (optimum pH 4.5). Usable carbon and electron donor sources are l-arabinose, d-xylose, d-fructose, d-glucose, d-galactose, d-mannose, glycerol, cellobiose, d-lactose, maltose, trehalose, gluconate, myo-inositol, sucrose, l-glutamate, histidine, casamino acids, yeast

extract, and peptone. Those not utilized are d-mannitol, d-sorbitol, methanol, ethanol, acetate, propionate, butyrate, caprylate, lactate, succinate, fumarate, malate, tartrate, benzoate, aminobutyrate, malonate, oxalate, p-hydroxybenzoate, alanine, l-aspartate, leucine, or serine. The G+C content of the DNA is 59.5 mol% (by HPLC). The type strain is strain AP8T (=NBRC 107607T=KCTC 23427T). We are grateful to Prof. Norio Wakao, Faculty of Agriculture, Iwate University, for supplying us with acid mine water samples. This work was carried

out as a part of the 21st Century COE Program ‘Ecological Engineering and Homeostatic Human Activities’ founded by the Ministry of Education, Sports, Culture, Science and Technology, Japan. The GenBank/EMBL/DDBJ accession number for the Phenylethanolamine N-methyltransferase 16S rRNA gene sequence of strain AP8T is AB561884. Fig. S1. Phase-contrast and transmission electron micrographs of cells of strain AP8T. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“In this work, we analyzed motility and the flagellar systems of the marine bacterium Vibrio shilonii. We show that this bacterium produces lateral flagella when seeded on soft agar plates at concentrations of 0.5% or 0.6%. However, at agar concentrations of 0.7%, cells become round and lose their flagella. The sodium channel blocker amiloride inhibits swimming of V.

[35] The completion of TABS involves the patient answering two sets of four questions using a five-point Likert scale. Answers from the first set give an adherence behaviour score (ABS) and answers from the second set give a non-adherence behaviour score (NABS). ABS of less than 19 out of 20 denote a lack of adherence behaviour whereas NABS of more than eight out of 20 can be defined as non-adherence behaviour.[35] Low scores for ABS are

suggestive of intentional non-adherence whereas low scores for question 5 (NABS) suggest unintentional non-adherence. It should be noted that although TABS comprises ABS and NABS, cumulative totals of the scores are unable to be given due to the inverse relationship between the scoring for ABS and NABS. Descriptive statistics were used to characterise the sample. A semi-structured AZD4547 purchase interview was selected as the most appropriate methodology to explore patients’ ideas, concerns and expectations about adherence to medication. Interviews were conducted by the corresponding author over a 7-week period from May 2010. The topic guide for semi-structured interviews PLX3397 in vitro was adapted from another study of medication adherence in patients with chronic illness.[22] This was reviewed for appropriateness

by the team prior to use. All interviews were digitally recorded before being transcribed by cardiology secretarial staff. Once the interviews were transcribed the accuracy of the transcriptions was scrutinised by the corresponding author. Patient confidentiality was maintained by omitting all names and identifiers, and patient approval for the use of direct quotations was obtained. Once the qualitative data had been transcribed Edoxaban the transcripts were loaded into computer-assisted qualitative data analysis software (Atlas.ti version 6.0.1; Atlas.ti GmbH, Berlin, Germany) which expedited analysis and enhanced ‘closeness’ with the data. A thematic framework was developed to code the transcripts. The original coding framework was agreed upon by GFR and SJL. GFR completed the coding

and SJL verified the accuracy of each applied code on all transcripts. Initially there was a process of familiarisation by listening/re-listening to the recorded interviews while reading/re-reading the transcripts, which allowed immersion in the data. A process of ‘coding’ was applied to the transcripts and these codes allowed for themes to be identified. The construction of the initial thematic framework was guided by the research aims and objectives and questions introduced to participants from the topic guides. However, the framework analysis could also be used to identify emergent themes expressed during the interviews, offering a unique flexibility to realise themes from outwith the topic guide. Contextual meaning for each quote and code were then indexed before being displayed in a process called charting.

[35] The completion of TABS involves the patient answering two sets of four questions using a five-point Likert scale. Answers from the first set give an adherence behaviour score (ABS) and answers from the second set give a non-adherence behaviour score (NABS). ABS of less than 19 out of 20 denote a lack of adherence behaviour whereas NABS of more than eight out of 20 can be defined as non-adherence behaviour.[35] Low scores for ABS are

suggestive of intentional non-adherence whereas low scores for question 5 (NABS) suggest unintentional non-adherence. It should be noted that although TABS comprises ABS and NABS, cumulative totals of the scores are unable to be given due to the inverse relationship between the scoring for ABS and NABS. Descriptive statistics were used to characterise the sample. A semi-structured Screening Library interview was selected as the most appropriate methodology to explore patients’ ideas, concerns and expectations about adherence to medication. Interviews were conducted by the corresponding author over a 7-week period from May 2010. The topic guide for semi-structured interviews this website was adapted from another study of medication adherence in patients with chronic illness.[22] This was reviewed for appropriateness

by the team prior to use. All interviews were digitally recorded before being transcribed by cardiology secretarial staff. Once the interviews were transcribed the accuracy of the transcriptions was scrutinised by the corresponding author. Patient confidentiality was maintained by omitting all names and identifiers, and patient approval for the use of direct quotations was obtained. Once the qualitative data had been transcribed CYTH4 the transcripts were loaded into computer-assisted qualitative data analysis software (Atlas.ti version 6.0.1; Atlas.ti GmbH, Berlin, Germany) which expedited analysis and enhanced ‘closeness’ with the data. A thematic framework was developed to code the transcripts. The original coding framework was agreed upon by GFR and SJL. GFR completed the coding

and SJL verified the accuracy of each applied code on all transcripts. Initially there was a process of familiarisation by listening/re-listening to the recorded interviews while reading/re-reading the transcripts, which allowed immersion in the data. A process of ‘coding’ was applied to the transcripts and these codes allowed for themes to be identified. The construction of the initial thematic framework was guided by the research aims and objectives and questions introduced to participants from the topic guides. However, the framework analysis could also be used to identify emergent themes expressed during the interviews, offering a unique flexibility to realise themes from outwith the topic guide. Contextual meaning for each quote and code were then indexed before being displayed in a process called charting.

Whether it is advisable to use MVC 150 mg once daily in this context or for how long a twice-daily dose should be used after the switch remains unknown. In patients on fully virally suppressive regimens, switching individual components of the ART combination regimen is frequently considered for several reasons, including: management of ARV drug toxicity or intolerance, desire for once-daily dosing and reduced pill burden, management of potential DDIs, patient preference and cost [65]. Guidance on the management of drug toxicity of individual ARVs is not within the scope of these guidelines. Guidance on interventions to support adherence, including once-daily dosing and FDCs is addressed

in Section 6.1 (Adherence) and pharmacological considerations on switching ARVs is discussed Nutlin-3a purchase in Section 6.2.4 (Switching therapy: pharmacological considerations). Switching individual components of an ART regimen may well improve adherence and tolerability, but should not be at the cost of virological efficacy. The following guidance concerns the impact on virological efficacy of either

switching the third agent or the NRTI backbone in a combination ART regimen or simplifying to boosted PI monotherapy. Evidence from a systematic literature review (Appendix 2) was evaluated as well as the impact on critical treatment outcomes of the different switching strategies assessed. Critical outcomes included virological suppression at 48 weeks, virological failure and discontinuation selleck products from grade 3/4 events. We Bacterial neuraminidase recommend, in patients on suppressive ART regimens, consideration is given to differences in side effect profile, DDIs and drug resistance patterns before switching any ARV component (GPP). We recommend in

patients with previous NRTI resistance mutations, against switching a PI/r to either an NNRTI or an INI as the third agent (1B). Number of patients with an undetectable VL on current regimen and documented previous NRTI resistance who have switched a PI/r to either an NNRTI or INI as the third agent. Within-class switches are usually undertaken to improve ARV tolerability. The available evidence for current recommended third agents is limited but switching PI/r or NNRTIs in virologically suppressed patients has, in a small number of studies, not been associated with loss of virological efficacy [66-68]. Consideration should, however, be given to differences in side effect profiles, DDIs and food effect and for switching between different PIs to the previous history of major PI mutations, as this may potentially have an adverse effect on the virological efficacy of the new PI/r. For NRTIs, recent studies have mainly evaluated switching from a thymidine analogue to either TDF or ABC to manage patients with lipoatrophy or have investigated switching to one of two available NRTI FDCs (TDF and FTC or ABC and 3TC).