Oral manifestations of E. faecalis infections include persistent periapical periodontitis in endodontically treated teeth (Stuart et al., 2006), and the presence of this organism in the subgingival plaque of 5% of teeth with severe periodontitis (Rams et al., 1992). This pathogenic potential has led to concern over the fact that increasingly,

strains of E. faecalis have been found to be resistant to currently available antibiotics. In this regard, strains of E. faecalis have recently been found to be resistant to vancomycin, one of the last antibiotics previously thought to be reliably effective against this organism (Bonten et al., 2001). The genome of one such vancomycin-resistant E. faecalis strain check details (strain V583) has been sequenced, JQ1 and within this genome, seven integrated prophage regions were detected (Paulsen et al., 2003). Along with numerous insertion elements, transposons, and integrated plasmid genes, these seven integrated prophage regions comprise over 25% of the total E. faecalis chromosome (Paulsen et al., 2003). Although the degree to which the E. faecalis chromosome is inhabited by exogenous/mobile genetic elements such as prophages is quite remarkable (and unique among sequenced bacterial genomes), the existence of these E. faecalis bacteriophage genomes is not surprising. Enterococcus faecalis bacteriophages

have been known for >70 years (Evans, 1934; Bleiweis & Zimmerman, 1961), and their inducibility from lysogenic E. faecalis strains has similarly been well established (Kjems, 1955). Enterococcus faecalis phages have been isolated directly, or induced from E. faecalis lysogens, from a variety of sources such as fresh water streams (Paisano et al., 2004), sewage (Evans, 1934; Bleiweis & Zimmerman, 1961; Uchiyama et al., 2008), rat intestinal contents (Rogers & Sarles, 1963), human urogential secretions (Ackermann et al., 1975), human saliva

(Bachrach et al., Dipeptidyl peptidase 2003), and human oral mucosae (Natkin, 1967). Recently, we isolated temperate bacteriophages that were induced from E. faecalis strains recovered from the infected root canals of teeth that had previously undergone endodontic treatment (Stevens et al., 2009). One of the isolates, designated phage φEf11, was characterized as a Siphoviridae morphotype, with a spherical head and a long noncontactile tail. Analysis of NdeI and NsiI restriction fragments indicated a DNA length of approximately 41 kb. To further our understanding of this virus, and explore its potential for either contributing to or mitigating against the pathogenicity of its host cell, we undertook the sequencing and functional analysis of its complete genome. TUSoD11 is a lysogenic strain of E. faecalis that was originally isolated from an infected human root canal (Stevens et al., 2009). Enterococcus faecalis JH2-2 (originally generously provided by Dr Nathan Shankar, University of Oklahoma Health Science Center) served as an indicator strain in plaque assays.

, 2000, 2004, 2008; Starkey et al., 2007; Yli-Mattila et al., 2009; Sarver et al., 2011). All F. graminearum sensu stricto strains (lineage 7) can produce PLX4032 sexual progeny (ascospores) without contact with a sexual partner, which is known to be important for initiating the disease cycle (Trail et al., 2002). However, this self-fertility varies among the other members of the Fg complex. For

example, Fusarium asiaticum (lineage 6), which is widely distributed in Asia, exhibited a lower self-fertility than the highly fertile F. graminearum strains (Lee et al., 2012). The sexual ability of the Fg complex is controlled by master regulators called mating-type (MAT) loci (Debuchy & Turgeon, 2006). Unlike their heterothallic relatives, the Fg complex strains carry two MAT loci (MAT1-1 and MAT1-2) in a single nucleus for controlling sexual development, but the structural organization of individual MAT genes is similar to those in Sordariomycetes fungi (e.g. Neurospora crassa, Podospora

anserina, and Sordaria macrospora; Yun et al., 2000; Debuchy & Turgeon, 2006). Three (MAT1-1-1, MAT1-1-2, and MAT1-1-3) and one (MAT1-2-1) transcripts are located at both loci, among which the deduced product of MAT1-1-1 carries a DNA-binding motif called the alpha box, buy ERK inhibitor those of MAT1-1-3 and MAT1-2-1 contain an HMG box domain, and that of MAT1-1-2 includes a newly proposed DNA-binding PHP domain (Yun et al., 2000; Debuchy & Turgeon, 2006). An additional transcript, MAT1-2-3, has been proposed as a new MAT gene at the MAT1-2 locus in the heterothallic Fusarium verticillioides and F. graminearum (Martin et al., 2011). However, it contains no known DNA-binding motifs and its role(s) in sexual development are unknown. To date, gene deletion analyses have confirmed that both MAT loci are essential for sexual development in F. graminearum for (Lee et al., 2003; Desjardins et al., 2004) but the functional requirement for the individual MAT genes, except MAT1-2-1, has not been intensively demonstrated.

Recently, the transgenic strains deleted for MAT1-1-1 and MAT1-1-3, respectively, have become available (Son et al., 2011). Despite the importance of MAT loci in sexual development, transcriptional expression or regulation of MAT genes has remained largely unknown in filamentous fungi. Only a few reports are available (Leubner-Metzger et al., 1997; Czaja et al., 2011), and only the expression pattern of MAT1-1-2 is available from microarray analysis in F. graminearum (Hallen et al., 2007). The functions of each MAT gene in a self-fertile S. macrospora have been determined; Smt A-1 and Smt A-3, which are comparable to MAT1-1-1 and MAT1-1-3, respectively, are dispensable for fruiting body formation (Klix et al., 2010).

, 2009; Semrau et al., 2010). The latter issue may play a role in the ability of some methanotrophs to utilize multicarbon compounds, with alphaproteobacterial and verrucomicrobial methanotrophs utilizing the serine pathway for carbon assimilation, while Gammaproteobacteria methanotrophs utilize the ribulose monophosphate (RuMP) Daporinad cell line pathway (as discussed in more detail below). As comprehensively reported in several recent reviews (Trotsenko & Murrell, 2008; Op den Camp et al., 2009; Semrau et al., 2010), methanotrophs were initially characterized over 100 years ago, and subsequent studies in the 1950s

and 1960s indicated that these strains could only utilize methane or methanol for growth (Dworkin & Foster, 1956; Leadbetter & Foster, 1958; Brown et al., 1964; Foster & Davis, 1966). In 1970, however, a first indication that methanotrophs could utilize multicarbon compounds to accentuate growth was reported (Whittenbury et al., 1970). In this classic manuscript

describing the isolation and characterization of methanotrophs from sites around the world, a wide variety of methanotrophs were reported to show enhanced growth on methane when malate, acetate, or succinate was also present in the culture medium. Such findings suggested that facultative methanotrophs may exist, i.e., strains that could utilize multicarbon compounds as well as methane as a sole growth substrate. DZNeP order Shortly thereafter, the first facultative methanotrophic isolates from freshwater lake sediments and water were reported. These could utilize a wide range of multicarbon compounds as growth substrates, including many organic acids (malate, succinate, fumarate, and acetate) and sugars (glucose, galactose, sucrose, lactose, and ribose) (Patt et al., 1974). One strain, later described as Methylobacterium organophilum (belonging to the Alphaproteobacteria), was further characterized, and had the complete tricarboxylic

acid (TCA) cycle (Patt et al., 1976). This strain, however, lost the ability to oxidize methane when grown repeatedly on glucose, and other workers subsequently did not succeed in growing the strain ioxilan on methane (Green & Bousfield, 1983; Urakami et al., 1993). Collectively, these findings suggested that these isolates were not facultative methanotrophs as originally surmised. Other early studies reported the isolation of facultative methanotrophs from a rice paddy in South China, as well as from soils collected from an oil refinery in the Northeastern United States (Patel et al., 1978; Zhao & Hanson, 1984a, b). These strains were found to have the complete TCA cycle and two of them, strains R6 and 761H, were able to grow solely on glucose, but not with other sugars such as fructose, galactose, or sucrose. In addition, a variant of strain 761H, strain 761M, could not grow on glucose as the sole carbon source, but glucose, as well as acetate and malate, were reported to enhance its growth on methane.

These effects after 6 h could be partially correlated with the nonmotile phenotype of the ompR mutant, because a similar biofilm structure was observed with the nonmotile flhDC mutant. Furthermore, the reduction in the biofilm formation capacity of the ompR strain after 24 h might be correlated with the low adhesion abilities of this mutant. Reduced

adherence could be responsible for the less efficient attachment of cells and the loose structure of the biofilm. These results also suggest that the loss of YompC from the outer membrane NVP-BKM120 of the ompR mutant contributed to the reduced biofilm formation by this strain. The regulation of motility and biofilm development by OmpR in strain Ye9 (serotype O9, biotype 2) seems to be different from that in Y. enterocolitica JB580v (serotype O8 biovar 1B). Kim et al. (2008) demonstrated the importance of OmpR in the motility of JB580v, but the ompR mutant of this strain, unlike that of Ye9, showed no impairment in flagella production. In addition, contrary to our findings, the OmpR of JB580v appeared not to perform a regulatory function in biofilm initiation and production. The Y. enterocolitica species find more is quite heterogeneous with six distinct biovars (1A, 1B, 2, 3, 4 and 5) distinguished according to their pathogenicity, geographic distribution and ecological

niche (Bottone, 1999). It has been shown that the highly pathogenic strain 8081 of Y. enterocolitica biovar 1B contains an assortment enough of genes not present in the biovar 2 and vice versa (Thomson et al., 2006). The results of the present study and those of Kim et al. (2008) suggest that genetic variation in separate

biovars of Y. enterocolitica may lead to different flagella and biofilm production phenotypes. In addition, this study shows that merely recording the many phenotypic changes caused by mutation of OmpR is insufficient to discern which of the functions of this regulator are responsible for certain behaviors of Y. enterocolitica cells that confer an advantage in a particular ecological niche. This work was supported by Warsaw University (grant BW 2007) and by the Polish Ministry of Science and Higher Education (grant N303 009 32/0537). “
“Kochi Core Center, Japan Agency for Marine – Earth Science and Technology (JAMSTEC), Nankoku, Kochi, Japan A total of 71 isolates were collected from lake sediment and soil surrounding lakes in the Skarvsnes area, Antarctica. Based on ITS region sequence similarity, these isolates were classified to 10 genera. Twenty-three isolates were categorized as ascomycetous fungi from five genera (Embellisia, Phoma, Geomyces, Tetracladium or Thelebolus) and 48 isolates were categorized as basidiomycetous fungi in five genera (Mrakia, Cryptococcus, Dioszegia, Rhodotorula or Leucosporidium). Thirty-five percent of culturable fungi were of the genus Mrakia. Eighteen isolates from eight genera were selected and tested for both antifreeze activity and capacity for growth under temperatures ranging from −1 to 25 °C.

“
“Prediction errors are central to modern learning theories. While brain regions contributing to reward prediction errors have been uncovered, the sources of aversive prediction errors remain largely unknown. Here we used probabilistic and deterministic reinforcement procedures, followed by extinction, to examine the contribution of the dorsal raphe nucleus to negative, aversive prediction errors in Pavlovian fear. Rats with dorsal raphe lesions were able to acquire fear and reduce fear to a non-reinforced deterministic cue. However, dorsal raphe lesions impaired the reduction of fear to a probabilistic cue and fear extinction to a deterministic cue, both of which involve the use

of negative prediction errors. The results point to an integral role for the dorsal raphe nucleus in negative prediction

error signaling in Pavlovian fear. “
“This proof-of-concept, double-blind study was designed to determine the effects of transcranial selleck products direct current stimulation (tDCS) on the ‘cost’ of performing a secondary cognitive task on gait and postural control in healthy young adults. Twenty adults aged 22 ± 2 years completed two separate double-blind visits in which gait and postural control were assessed immediately before and after a 20 min session of either real or sham tDCS (1.5 mA) targeting INCB018424 chemical structure the left dorsolateral prefrontal cortex. Gait speed and stride duration variability, along with standing postural sway speed and area, were recorded under normal conditions and while simultaneously performing a serial-subtraction cognitive task. The dual task cost was calculated as the percent change in Terminal deoxynucleotidyl transferase each outcome from normal to dual task conditions. tDCS was well tolerated by all subjects. Stimulation did not alter gait or postural control under normal conditions. As compared with sham stimulation, real tDCS led to increased gait speed (P = 0.006), as well as decreased standing postural sway speed (P = 0.01) and area (P = 0.01), when performing the serial-subtraction task. Real tDCS also diminished (P < 0.01) the dual task cost on each of these outcomes. No effects of tDCS were observed

for stride duration variability. A single session of tDCS targeting the left dorsolateral prefrontal cortex improved the ability to adapt gait and postural control to a concurrent cognitive task and reduced the cost normally associated with such dual tasking. These results highlight the involvement of cortical brain networks in gait and postural control, and implicate the modulation of prefrontal cortical excitability as a potential therapeutic intervention. “
“We used magnetoencephalography (MEG) to determine whether increasingly complex forms constituted from the same elements (lines) activate visual cortex with the same or different latencies. Twenty right-handed healthy adult volunteers viewed two different forms, lines and rhomboids, representing two levels of complexity.

“
“Prediction errors are central to modern learning theories. While brain regions contributing to reward prediction errors have been uncovered, the sources of aversive prediction errors remain largely unknown. Here we used probabilistic and deterministic reinforcement procedures, followed by extinction, to examine the contribution of the dorsal raphe nucleus to negative, aversive prediction errors in Pavlovian fear. Rats with dorsal raphe lesions were able to acquire fear and reduce fear to a non-reinforced deterministic cue. However, dorsal raphe lesions impaired the reduction of fear to a probabilistic cue and fear extinction to a deterministic cue, both of which involve the use

of negative prediction errors. The results point to an integral role for the dorsal raphe nucleus in negative prediction

error signaling in Pavlovian fear. “
“This proof-of-concept, double-blind study was designed to determine the effects of transcranial Selleck Talazoparib direct current stimulation (tDCS) on the ‘cost’ of performing a secondary cognitive task on gait and postural control in healthy young adults. Twenty adults aged 22 ± 2 years completed two separate double-blind visits in which gait and postural control were assessed immediately before and after a 20 min session of either real or sham tDCS (1.5 mA) targeting Epigenetics inhibitor the left dorsolateral prefrontal cortex. Gait speed and stride duration variability, along with standing postural sway speed and area, were recorded under normal conditions and while simultaneously performing a serial-subtraction cognitive task. The dual task cost was calculated as the percent change in Idoxuridine each outcome from normal to dual task conditions. tDCS was well tolerated by all subjects. Stimulation did not alter gait or postural control under normal conditions. As compared with sham stimulation, real tDCS led to increased gait speed (P = 0.006), as well as decreased standing postural sway speed (P = 0.01) and area (P = 0.01), when performing the serial-subtraction task. Real tDCS also diminished (P < 0.01) the dual task cost on each of these outcomes. No effects of tDCS were observed

for stride duration variability. A single session of tDCS targeting the left dorsolateral prefrontal cortex improved the ability to adapt gait and postural control to a concurrent cognitive task and reduced the cost normally associated with such dual tasking. These results highlight the involvement of cortical brain networks in gait and postural control, and implicate the modulation of prefrontal cortical excitability as a potential therapeutic intervention. “
“We used magnetoencephalography (MEG) to determine whether increasingly complex forms constituted from the same elements (lines) activate visual cortex with the same or different latencies. Twenty right-handed healthy adult volunteers viewed two different forms, lines and rhomboids, representing two levels of complexity.

With improved turnaround times for VL testing, a woman presenting Stem Cells inhibitor beyond 28 weeks may still be managed with a view to a possible vaginal delivery if she commences HAART and achieves a VL <50

HIV RNA copies/mL by 36 weeks. Where women present between 24 and 28 weeks, the advantages of more detailed assessment and tailoring of the regimen should be weighed against the advantages of initiating HAART immediately. The turnaround time for CD4 cell counts, VL and viral resistance tests will impact on this choice. 5.4.2 If the VL is unknown or >100 000 copies/mL a three- or four-drug regimen that includes raltegravir is suggested. Grading: 2D Where the VL is unknown or >100 000 HIV RNA copies/mL, a fourth drug, raltegravir, may be added to this regimen. Raltegravir has significantly higher first- and second-phase viral decay rates when used as monotherapy (vs. efavirenz) or in combination with other ARVs [134],[135]. It is important

to note that no adequate or well-controlled studies of raltegravir have been conducted in pregnant women. Pharmacokinetic data presented in Recommendation 5.2.4 indicate that no dose change is required in the third trimester. 5.4.3 An untreated woman presenting in labour at term should be given a stat dose of nevirapine 200 mg (Grading: 1B) and commence fixed-dose zidovudine with lamivudine (Grading: 1B) and raltegravir. Grading: 2D 5.4.4 It is suggested that intravenous zidovudine be infused for the duration of labour and delivery. Grading: 2C A single dose of nevirapine, regardless of CD4 cell count (even if available), should be given immediately as this rapidly crosses the placenta and within 2 h achieves, RG7204 concentration and then maintains, effective concentrations in the neonate for up to 10 days [73],[136]. HAART should be commenced immediately with fixed-dose zidovudine and lamivudine and with raltegravir as the preferred additional agent because it also rapidly crosses the placenta [137]. Intravenous zidovudine can be administered

for the duration of labour and delivery [138]. If delivery is not imminent, CS should be considered. If delivery occurs <2 h post-maternal nevirapine, the ifenprodil neonate should also be dosed with nevirapine immediately. 5.4.5 In preterm labour, if the infant is unlikely to be able to absorb oral medications consider the addition of double-dose tenofovir (to the treatment described in Recommendation 5.4.2) to further load the baby. Grading: 2C If the mother is drug naïve, take baseline bloods for CD4 cell count and VL if not known, and commence HAART as per Recommendation 5.4.2. Nevirapine and raltegravir should be included in the regimen as they cross the placenta rapidly (see above). In addition, double-dose tenofovir has been shown to cross the placenta rapidly to preload the infant and should be considered where the prematurity is such that the infant is likely to have difficulty taking PEP in the first few days of life [139]. 5.4.

A cumulative total of 124 days off duty was reported for the whole 5-month study period. Among the 240 cases reported, only 196 patients provided stool samples (81.7%), the remainder

failed to return samples. Pathogenic agents were identified in 78 stool samples (39.8%), 7 of which had dual infections. Enteric viruses were the most common pathogens identified (28.1%), alone or in coinfection (Table 1). Norovirus was found in 14.3% of the samples, three times in coinfection with respectively Salmonella spp, Shigella spp, and Ankylostomiasis. Rotavirus was found in 10.2% of the samples, three times in coinfection with Shigella spp and once in coinfection with astrovirus. In January 2008, an outbreak was observed (second peak, Figure 3) where rotaviruses represented 29.5% (13/44)

of tested stools. Among the 240 cases of diarrhea, 70 were excluded from case-crossover Epigenetic inhibitor analysis: 34 due to a diarrheal episode occurring before a minimum of 10 days of stay in N’Djamena, 25 due to a diarrheic episode occurring in the 10 days following a previous diarrheic episode, and 12 due to missing data for one of these two criteria. The case-crossover analysis included 170 diarrheic episodes (170 case–control pairs). By univariate analysis, the significant risk factors for acute diarrhea were (1) ice in drinks, (2) presence of a diarrheal case in the close circle, (3) eating at local restaurants, and (4) eating in a field kitchen (Table 2). Always

eating at the mess was protective. No interaction Doramapimod concentration was observed between the presence of diarrhea in the close circle and places to eat, thus ruling out a group effect due to Rucaparib order a food-borne disease outbreak. The conditional multivariate logistic regression analysis confirmed that the presence of diarrhea in the close circle was a risk factor for acute diarrhea (Table 2), while always eating at the mess conferred a protective effect. Moreover, sometimes eating in a temporary encampment was also protective (Table 2). Our study is the first to evaluate etiology and risk of TD in Chad. We observed substantial implication of viruses and a high risk of person-to-person transmission for diarrhea among French forces deployed to Chad. Enteric viruses were the most frequently observed pathogens (28.1%), ahead of bacteria (12.8%) in stool samples. However, no pathogen was identified in 60% of stool samples. This rate is slightly higher than that in others’ studies reporting rates of around 50% of no pathogen identification in TD.8–10 This difference may be partly explained by the fact that our study failed to identify the most frequent pathogens usually involved in TD, namely enterotoxigenic E coli and enteroaggregative E coli.8–11 This is undoubtedly related to the fact that the local French field laboratory in N’Djamena did not perform analyses for E coli for want of suitable technical facilities.

During February 25 to April 14, 14 additional rash illness cases were detected only among crew members: one through medical record review and 13 through passive surveillance in the ship’s infirmary (Figure 1). During the onboard medical log review, a case of probable varicella was identified in a 23-year-old Filipino crew member, who boarded the ship to work in food services, and 22 days Selleckchem AZD2281 later was diagnosed with varicella

in the ship’s infirmary. Thirteen crew members visited the infirmary with a rash illness. Of these, two met the case definition for confirmed measles (one by serology, and one by clinical diagnosis by the ship’s physician and epidemiologic link to the confirmed case); ten met the Council of State and Territorial Epidemiologists case definition for varicella[8] (six were confirmed by clinical characteristics and an epidemiologic link, and the remaining four were probable cases by clinical diagnosis only); and one case of rash illness remained undiagnosed and did not have laboratory evidence of acute rubella or measles and did not meet the case definition for measles, rubella, or varicella (Figure 1). The two additional cases of measles were among crew members employed in food services or entertainment;

the additional varicella cases occurred among crew members from various shipboard occupations (ie, food services, galley, housekeeping, engineering, and entertainment). All these cases were among crew members who had been aboard the ship for at least one incubation period of either measles or varicella. Of 1,197 crew members evaluated for proof of Cyclopamine purchase immunity, 3 had proof of immunity to measles and rubella based on vaccination records. During pre-immunization counseling, three crew members were found to be pregnant; of those, one had serological evidence of immunity to rubella and measles and two were susceptible Hydroxychloroquine molecular weight and disembarked for clinical monitoring because of their exposure to rubella.

The remaining 1,191 crew members received the MMR vaccine after giving informed consent. The MMR vaccine was supplied by BCHD (with cost reimbursement from the cruise line), whose nursing staff performed counseling and administration of the vaccine. Close contacts of varicella cases were defined as those having ≥ 5 minutes of face-to-face contact with the case during the infectious period (1–2 d before rash onset until lesions crust or 6 d after rash onset).[9] Contacts meeting this definition were identified only among crew members (eg, crew roommate and workmates) and those who were susceptible[9] were monitored for onset of fever or rash for 21 days after their last exposure to a varicella case. To suspend continued varicella transmission, with the detection of third generation cases, the cruise line also offered the varicella vaccine to susceptible contacts.

In the ongoing UK PIVOT study, detailed neuropsychological testing is being assessed prospectively in subjects on PI monotherapy vs. standard therapy, the results of which

will be of great interest to this field. Given the above theoretical concerns regarding the CNS activity of PI monotherapy, and for the majority of HIV-positive subjects FXR agonist it may be possible to select other ARV regimens, we suggest this approach is currently avoided in neurologically symptomatic subjects. In patients with ongoing or worsening NC impairment despite ART, we recommend the following best practice management (GPP): Reassessment for confounding conditions. Assessment of CSF HIV RNA, CSF HIV genotropism and genotyping of CSF HIV RNA. In subjects with detectable CSF HIV RNA, modifications to ART should be based on plasma and CSF genotypic and genotropism results. Several published randomized

controlled studies, assessing both intensification of ART with a new ARV agent [131] and with adjunctive therapies [132-135] have been published. Unfortunately, Selleck Caspase inhibitor none of these studies describe improvements in cognition subsequent to the study interventions. Without evidence-based interventions, the Writing Group outlines below a best practice approach based on the current literature. As HIV-associated NC disorders are a diagnosis of exclusion, re-evaluation of subjects with ongoing NC impairment despite ART for confounding conditions, with expert input from other clinical specialties such as psychiatry, neurology and neuropsychology, is recommended and, where possible, input from an HIV neurology service. Assessment of CSF HIV RNA, CSF HIV genotropism and genotypic analysis of CSF RNA may be useful tools in the management of subjects with ongoing NC for the following reasons. First, data from cohorts of untreated HIV-positive subjects would suggest

CSF HIV RNA to be greater in subjects with HIV-associated dementia and cognitive decline [136, 137] and therefore suppression of CSF HIV RNA may be beneficial for cognitive function. Secondly, in subjects with ongoing NC impairment, higher degrees of genetic diversity between HIV viral strains in the CSF and plasma compartment may exist [138], even in subjects with undetectable plasma HIV RNA [139]. Therefore, Sirolimus assessment for CSF HIV resistance may be worthwhile to tailor ART. We recommend patients with HIVAN start ART immediately irrespective of CD4 cell count (1C). We recommend patients with end-stage kidney disease who are suitable candidates for renal transplantation start ART irrespective of CD4 cell count (1C). Proportion of patients with HIVAN started on ART within 2 weeks of diagnosis of CKD. The use of ART has been associated with a decline in the incidence of HIVAN in HIV cohort studies [140], with renal histological improvement in case reports [141, 142], and with delayed progression to end-stage kidney disease in case series [143, 144].