Surprisingly, expression of Lkt was found to be elevated in MhΔNarP7 regardless of the presence or absence of additional NaNO3. This suggests that NarP functions, either directly or indirectly, to repress expression of Lkt. In the parent strain, the presence of NaNO3 relieved this repression and higher expression of Lkt can be achieved. Because the lkt promoter does not contain any NarP-binding sequences, it is likely that the repression of the lkt promoter acts through an intermediate molecule. The initial analysis of protein expression in MhΔNarP7 revealed some unexpected observations

regarding regulation of FbpA and Lkt. Our results suggest the role of NarQ/P TCS in regulating genes that may be important for the pathogenesis of this PD-0332991 clinical trial microorganism. Analysis of the expression profile of this system with has been initiated with a proteomic approach using 2D gel electrophoresis, and preliminary data have shown a number of protein levels with significant alterations in response to NaNO3. Further research will shed light on the panel of protein expression regulated by NarP in M. haemolytica A1 as well as in other microorganisms.

This work is funded by a grant from the Natural Science and Engineering Research see more Council of Canada. We thank Drs Dyanne Brewer and Armen Charcholyan for their assistance with the MS MALDI-TOF analysis. Fig. S1. (a) this website Alignment of NarQ proteins. (b) Alignment of NarP proteins. Appendix S1. Construction of narP knock-out mutant. 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. “
“Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that infects pigs and sporadically

causes serious infections in humans. Two recent large-scale outbreaks of human streptococcal toxic-shock-like syndrome with high mortality occurred in China, posing new challenges for global public health. However, the global regulation of the virulence of epidemic SS2 isolates lacks a systematic understanding. In this study, we performed a mutational and functional analysis of an SS2 two-component system that is orthologous to the VirR/VirS regulatory system of Clostridium perfringens. An isogenic knockout mutant of VirR/VirS (ΔvirRS) was found to exhibit marked phenotypic changes, including the formation of shorter chains and thinner capsular walls, more easily cleared in whole blood, and decreased oxidative stress tolerance. Furthermore, the ΔvirRS mutant was greatly attenuated in a mouse model.

31–33 Due to these immunologically mediated differences, the diagnostic methods and the treatment and follow-up strategy can differ significantly. Regarding diagnosis, highly

specific and sensitive assays enabling to detect patients with very low microfilaremias have been developed recently.34,35 Regarding treatment, there is no indication that expatriates and natives from endemic areas with similar microfilaremias respond differently to treatment in terms of efficacy32 but as the latter harbor sometimes very high microfilarial densities, particular attention should be given when managing these cases in order to prevent possible serious adverse events. The author Alectinib molecular weight states he has no conflicts of interest to declare. “
“Our survey1 showed more than 99% of refugees in the Asylum FK228 purchase Seeker Center in Bari with protective antibodies for poliovirus 1, 2, and 3; then, a very little number of seronegatives were offered inactivated poliovirus vaccine (IPV). In Italy, since the 1970s the number of immigrants has increased yearly. Checking immunization

status for poliomyelitis in all migrants coming seems rather hard, as the accredited laboratories for the detection of antibodies for poliovirus are just 20 nationwide.2 Fortunately, the high level of immunity showed in our survey supports the Centers for Disease Control and Prevention’s current recommendation that foreign-born persons without a vaccination record documenting receipt of recommended immunizations or other evidence of immunity should receive age-appropriate vaccines.3 Arya and Agarwal

suggest to investigate immunity status of migrants coming from polio-endemic countries in the seventh or higher decades, but in Italy the average age of foreign residents is 31 years and only 2% of them are over 65.4 Usually they are young people in good health in their country of origin who are able to address major problems related to travel and adapt in a foreign country. Chlormezanone They are people asking for asylum and refugee status, not tourists. As surveillance for poliomylietis is crucial in countries declared polio-free, our hope is that the sensitivity of surveillance system of acute flaccid paralysis in Italy remains optimal as the current state, with a number of notified cases threefold the expected value and adequate specimen sampling. Silvio Tafuri 1 and Rosa Prato 1 “
“We compliment Dr Webb and Professor Russell for their meticulous review of different insecticide formulations offered in Australia against mosquito bites.

The spores of A. niger were counted in a Neubauer chamber and cells of the B. cepacia were quantified using a spectrophotometer (600 nm), using a previously established growth curve. Serial dilutions of the suspensions were made to obtain 22.3 × 106 spores mL−1 and 4.6 × 109 bacteria mL−1, and these were used as inoculum for the growth assays. The inocula concentrations were based on previous works (Barroso & Nahas, 2006; Park et al., 2010). The spore suspension (0.5 mL) and the cell suspension (0.75 mL) were inoculated into 50 mL sterile liquid media in Petri dishes (150 mm diameter) and incubated at 30 °C for 9 days without agitation. Both spore and cell suspensions were inoculated into co-cultures. Cultures were harvested

at 3-day Ceritinib intervals by filtration or centrifugation. The mycelia were filtrated using Whatman No. 1 filter paper, preweighed, and dried; the filtrate was used for subsequent chemical analysis. The mycelium retained on the filter

paper was washed see more with 50 mL of 1 M HCl to remove any undissolved CaP, followed by 50 mL of water and subsequently weighed; after which, the mycelia were dried in an oven at 105 °C for 24 h. The B. cepacia culture was centrifuged for 15 min at 10 000 r.p.m., and the supernatant was removed for chemical analysis. After removing the supernatant, the cells were washed with 10 mL of HCl 1 M. The pellet was resuspended in 10 mL of water; the dry weight of cell was assayed after drying at 105 °C for 24 h. The dry weight of a co-culture of A. niger–B. cepacia was obtained after centrifugation, using the same protocol described previously for the bacterial culture. Each treatment was replicated three times. The cell-free filtrates were used for chemical analysis. Soluble phosphate was determined using the Ames

(1966) method and quantified spectrophotometrically at 820 nm based on a standard curve. Titratable acidity and pH values were determined by titration of 10 mL of culture Thymidine kinase medium with 0.02 M NaOH using an automatic Titration Manager. Residual sugar was determined spectrophotometrically at 607 nm using anthrone solution. The efficiency of solubilization (ES) of CaPO4 (expressed as a percentage) was determined by the relationship between the amount of phosphate solubilized and the amount added to the culture medium. Acid phosphatase activity was determined using 4 mM p-nitrophenylphosphate in 0.1 M acetate buffer (pH 5.4) as substrate (Nahas et al., 1982). The reaction mixture contained 0.2 mL of culture medium and 1.8 mL of substrate solution. The mixture was stirred and incubated for 20 min at 37 °C. The p-nitrophenol released was measured using a spectrophotometer at 405 nm. One unit of phosphatase activity was defined as the amount of enzyme required to liberate 1 μmol p-nitrophenol per hour under the assay conditions. Specific activity was expressed as units per mg dry biomass. All chemical analysis was performed in duplicate.

3a). Because gingipain activity can be regulated at the transcriptional and post-transcriptional levels (Tokuda et al., 1998), oligonucleotide primers, as described previously

(Vanterpool et al., 2005a), were used in RT-PCR analysis to determine whether these two sigma factors were involved in the transcriptional regulation of gingipain-encoding Y27632 genes. As shown in Fig. 3b, the inactivation of PG0162 and PG1660 had no effect on the expression of rgpA, rgpB, or kgp at the transcriptional level. In FLL355 (PG1827∷ermF), the Kgp activity showed a 25% increase over the wild type. No change was observed in the transcription of the kgp gene in FLL355 (data not shown). Taken together, these results suggest that ECF sigma factors may be involved in the post-transcriptional regulation of gingipains. Post-transcriptional regulation of the gingipains in P. gingivalis is associated with its maturation pathway, which is linked to the biosynthesis Panobinostat mw of surface carbohydrates (Shoji et al., 2002; Paramonov et al., 2005) and several other proteins including the PorR (Shoji et al., 2002), PorT (Sato et al., 2005; Nguyen et al., 2009),

Sov (Saiki & Konishi, 2010), and VimA (Vanterpool et al., 2006). It is unclear how these factors are modulated by the ECF sigma factors and is an active area of further exploration in the laboratory. The correlation between gingipain activity and hemagglutination in P. gingivalis (Lewis et al., 1999; Shi et al., 1999; Vanterpool et al., 2005a) is related to the similar adhesion domains encoded by the hagA, rgpA, and kgp genes (Chen & Duncan, 2004). The hemagglutination potential of ECF sigma factor-defective mutants was assessed. In comparison with the wild-type strain, there was a decrease Aprepitant in the hemagglutination activity in all the mutants. In FLL350, the level of hemagglutination activity was comparable

to the negative control. This is in contrast to FLL354, which showed the greatest reduction in gingipain activity, but a higher hemagglutination activity. RT-PCR using hagA-specific primers indicated no change in the expression of that gene in FLL350 (Fig. 4c). While gingipains have been observed to have hemolytic activity (Shah & Gharbia, 1989; Lewis et al., 1999), hemolysin can be independent of their catalytic association (Deshpande & Khan, 1999). Several putative hemolysin genes have been identified in the P. gingivalis genome (Nelson et al., 2003) and cloned in E. coli (Karunakaran & Holt, 1993). The hemolysins produced by P. gingivalis provide the bacterium with heme-containing molecules that are required for their in vivo survival. Hemolytic activities of all the ECF-defective mutants in this study were similar to those of the wild type, except for FLL350 (Fig. 4d). The FLL350 mutant showed a 50% reduction in those activities compared with the parent strain.

Interpatient variability during pregnancy is, however, high [82, 122]. A study from Italy reported similar third-trimester and postpartum atazanavir concentrations at standard 300 mg dose with 100 mg ritonavir once daily [123]. However, recently third-trimester 24 h area under the curve (AUC) concentrations 28% lower than postpartum concentrations were reported from North America. Gefitinib Third trimester concentrations of atazanavir in women taking tenofovir were lower still, being approximately 50% of the postpartum values of women

on atazanavir without tenofovir, and 55% of women in the study taking tenofovir failed to achieve the target atazanavir concentration. The study authors therefore recommended that it may be necessary to increase the dose of atazanavir to 400 mg (when given with ritonavir 100 mg once daily) during the third trimester [124]. Data from the Europe-based PANNA study also reveals a 33% reduction in third trimester AUC and Clast atazanavir concentrations compared with postpartum. However, all drug concentrations measured, including with co-administered tenofovir, were above the recommended minimum plasma concentration for wild-type virus

[125]. When prescribed with zidovudine/lamivudine, plasma concentrations achieved with atazanavir 300 mg plus ritonavir 100 mg once daily are only 21% less (by AUC) than historic controls while trough concentrations were reported to be comparable to these controls. Increasing the dose of atazanavir to 400 mg Thymidylate synthase daily during the third trimester selleck chemicals increased trough concentrations by 39% and doubled the risk of hyperbilirubinaemia [126]. A case note review of 155 women in London receiving atazanavir did not report virological failure during pregnancy despite 96% receiving standard dosing of 300 mg with ritonavir

100 mg. Therapeutic drug monitoring was rarely performed and mostly if virological control was considered suboptimal [81]. For darunavir, a study from the USA reported reduced troughs and AUC24h with once-daily dosing in pregnancy, whilst dosing twice a day produced levels more comparable to those in non-pregnant individuals [127]. They concluded that twice-daily dosing should be used in pregnancy and higher doses may be required. For women receiving darunavir/ritonavir 800/100 mg the mean trough level (C24h) in the third trimester and postpartum was 1.37 (0.15–3.49) μg/mL and 2.59 (< 0.09–3.96) μg/mL respectively. Similar findings have been reported from the PANNA network with sub-therapeutic trough concentrations reported with once-daily 800/100 mg dosing and no detectable darunavir in any of the cord blood samples [125]. Zorrilla et al. reported that although total darunavir exposure decreases during pregnancy, there were no significant changes in unbound darunavir concentration compared with postpartum and conclude that no dose adjustment is required when darunavir is prescribed at 600mg/ritonavir 100mg bd [128].

Precise statistical distribution theory then determines the reliable P-values for making the decision. design-island runs in two phases, namely first phase and refinement phase. In the first phase, it identifies islands at different locations of the chromosome and to determine the stretches of those islands, and carries out statistical analysis using a probing window.

This leads to the identification of some ‘putative GIs’ having varying sizes and locations in the chromosome that are identifiable with P-values generated using Monte–Carlo tests carried out at variable locations of the probing window with a fixed size. Following the first phase, the refinement phase commences, which takes random samples of genomic segments excluding the regions detected in the first phase. Some of the putative GIs identified in the first phase are further

refined into smaller segments containing BIBF 1120 concentration horizontally acquired genes in the refinement phase. design-island was implemented on the chromosomes of three completely sequenced genomes of V. cholerae under study in order to identify the putative GIs in their genomes. In the first phase, design-island was run using P0=0.05, word size of 4 and initial window size of 5000 with consequent window increment of 500. Two hundred randomly selected fragments small molecule library screening were tested for each window with a sliding window 500. In the refinement phase or the second phase design-island was run with the same parameter values as used in the first phase, except for the initial window size, which was reduced to 2000 and the sliding window increased to 1000. The statistical analysis in the refinement phase is similar to that used in the first phase except the P0 was set to 0.001. The results thus obtained were tabulated using customized perl scripts where

the cut-off E-value was set to 0.001. The final results obtained from design-island were fed into another perl program to generate a circular map of the chromosome indicating the putative GIs GNA12 as identified by design-island in separate phases using different colors. The algorithm is described in Fig. 1. Coordinates of statistically significant genomic segments of three V. cholerae strains under study were determined by design-island from two separate phases. From these predicted regions of three V. cholerae strains the coding regions were marked out with the protein table as the reference available at the NCBI database using a customized perl script. The results show that among the three strains under study, the maximum coverage by the GIs after the refinement phase was found to be 50.90% in the case of V. cholerae MJ1236 (large chromosome) while the least coverage was 33.11%, as in case of V. cholerae El Tor N16961 (small chromosome) as evident from Table 1. design-island identified all the known GIs of V.

, 2011). Even though a number of studies exploring the asymmetry of the EMG mirroring in healthy humans reported stronger EMG mirroring during voluntary movements of the non-dominant hand (Armatas et al., 1996; Uttner et al., 2007), no difference between the two hands (Hübers et al., 2008) has also been described. Because motor training-related after-effects Obeticholic Acid have been studied more often at the level of the dominant M1 (Classen et al., 1998; Muellbacher et al., 2001, 2002; Agostino et al.,

2007, 2008), we selected the dominant M1 as the M1TASK and the non-dominant M1 as M1MIRROR, respectively. TMS was delivered to both M1s [i.e. the dominant (M1TASK) and non-dominant (M1MIRROR), respectively; Fig. 1] using two Magstim 2002 magnetic stimulators with a monophasic current waveform (Magstim, Carmarthenshire, Wales, UK). Each magnetic stimulator was connected to a focal figure-of-eight-shaped coil (outer diameter of each wing, 70 mm). The intersections of the coils were placed tangentially to the scalp with the handles pointing backward

and laterally at ~45 ° angle away from the midline, in this way the monophasic current induced in both M1s was approximately FK866 perpendicular to the line of the central sulcus resulting in a predominantly trans-synaptic activation of the corticospinal system (Kaneko et al., 1996; Di Lazzaro et al., 2004). During the experiments, participants wore a swimming cap and the hot spot positions of both FDIs, i.e. the optimal scalp positions for eliciting MEPs of maximal amplitudes in the contralateral FDI, defined as the M1TASK and the M1MIRROR respectively, were marked on it. TMS was delivered with the FDIs at complete rest as confirmed by visual inspection of the EMG record in the 200-ms preceding stimulation. Traces with background EMG activity exceeding 50 μV in this 200-ms window

were excluded from analysis (~1% of trials). Corticospinal excitability was tested delivering single-pulse TMS, on both the M1TASK and the M1MIRROR hot spots (Fig. 1). As a measure of corticospinal excitability C1GALT1 on the M1TASK we used the resting motor threshold (RMT), determined to the nearest 1% of the maximum stimulator output (MSO), defined as the minimal stimulus intensity required to produce MEPs larger than 50 μV peak-to-peak amplitude, in the contralateral FDITASK, in at least five out of 10 consecutive trials. As a measure of corticospinal excitability on the M1MIRROR, we adjusted the stimulator intensity to produce, at rest, MEPs of ~1 mV in peak-to-peak amplitude (1 mV-MEP) in the contralateral FDI MIRROR. The measurements of RMT and 1 mV-MEP, over the M1TASK and M1MIRROR, respectively, were followed by measurement of IHI targeting M1MIRROR. IHI was measured by means of a standard paired-pulse TMS protocol (Ferbert et al., 1992; Hübers et al., 2008; Ni et al., 2009).

, 2011). Even though a number of studies exploring the asymmetry of the EMG mirroring in healthy humans reported stronger EMG mirroring during voluntary movements of the non-dominant hand (Armatas et al., 1996; Uttner et al., 2007), no difference between the two hands (Hübers et al., 2008) has also been described. Because motor training-related after-effects www.selleckchem.com/products/byl719.html have been studied more often at the level of the dominant M1 (Classen et al., 1998; Muellbacher et al., 2001, 2002; Agostino et al.,

2007, 2008), we selected the dominant M1 as the M1TASK and the non-dominant M1 as M1MIRROR, respectively. TMS was delivered to both M1s [i.e. the dominant (M1TASK) and non-dominant (M1MIRROR), respectively; Fig. 1] using two Magstim 2002 magnetic stimulators with a monophasic current waveform (Magstim, Carmarthenshire, Wales, UK). Each magnetic stimulator was connected to a focal figure-of-eight-shaped coil (outer diameter of each wing, 70 mm). The intersections of the coils were placed tangentially to the scalp with the handles pointing backward

and laterally at ~45 ° angle away from the midline, in this way the monophasic current induced in both M1s was approximately Forskolin nmr perpendicular to the line of the central sulcus resulting in a predominantly trans-synaptic activation of the corticospinal system (Kaneko et al., 1996; Di Lazzaro et al., 2004). During the experiments, participants wore a swimming cap and the hot spot positions of both FDIs, i.e. the optimal scalp positions for eliciting MEPs of maximal amplitudes in the contralateral FDI, defined as the M1TASK and the M1MIRROR respectively, were marked on it. TMS was delivered with the FDIs at complete rest as confirmed by visual inspection of the EMG record in the 200-ms preceding stimulation. Traces with background EMG activity exceeding 50 μV in this 200-ms window

were excluded from analysis (~1% of trials). Corticospinal excitability was tested delivering single-pulse TMS, on both the M1TASK and the M1MIRROR hot spots (Fig. 1). As a measure of corticospinal excitability Pyruvate dehydrogenase lipoamide kinase isozyme 1 on the M1TASK we used the resting motor threshold (RMT), determined to the nearest 1% of the maximum stimulator output (MSO), defined as the minimal stimulus intensity required to produce MEPs larger than 50 μV peak-to-peak amplitude, in the contralateral FDITASK, in at least five out of 10 consecutive trials. As a measure of corticospinal excitability on the M1MIRROR, we adjusted the stimulator intensity to produce, at rest, MEPs of ~1 mV in peak-to-peak amplitude (1 mV-MEP) in the contralateral FDI MIRROR. The measurements of RMT and 1 mV-MEP, over the M1TASK and M1MIRROR, respectively, were followed by measurement of IHI targeting M1MIRROR. IHI was measured by means of a standard paired-pulse TMS protocol (Ferbert et al., 1992; Hübers et al., 2008; Ni et al., 2009).

Degradation of heptachlor by white rot fungi was also reported (Arisoy, 1998; Nwachukwu & Osuji, 2007). However, metabolites and metabolic pathways of heptachlor by white rot fungi have not yet been reported. Recently, we reported

on several white rot fungi belonging to the genus Phlebia that are capable of degrading polychlorinated dibenzo-p-dioxins (PCDDs). Mori & Kondo (2002a, b) reported that several white rot fungi could mineralize 2,7-dichlorodibenzo-p-dioxin, and that 2,7-dichlorodibenzo-p-dioxin and 2,8-dichlorodibenzofuran were hydroxylated by Phlebia lindtneri. It was also reported that P. lindtneri and Phlebia brevispora are capable of hydroxylating and methoxylating 2,3,7-trichlorodibenzo-p-dioxin, 1,2,8,9-tetrachlorodibenzo-p-dioxin, 1,2,6,7-tetrachlorodibenzo-p-dioxin and 1,3,6,8-tetrachlorodibenzo-p-dioxin find more (Kamei & Kondo, 2005; Kamei et al., 2005). Additionally, chloronaphthalene and polychlorinated biphenyls were metabolized to hydroxylated products by P. lindtneri and P. brevispora, respectively (Mori et al., 2003; Kamei et al., 2006). These results suggested that Phlebia species have specific activity in the biotransformation of organohalogen compounds, and led us to pay attention to Phlebia species in selecting heptachlor- and heptachlor epoxide-degrading fungi. In this paper, we evaluate the ability of genus Phlebia to degrade heptachlor

and heptachlor epoxide, and we describe new hydroxylated metabolites of heptachlor epoxide by Protirelin microorganisms. Adriamycin We also propose metabolic pathways of heptachlor and heptachlor epoxide in this genus. This is the first report describing the metabolites of heptachlor and heptachlor epoxide by white rot fungi. Heptachlor, heptachlor epoxide, 1-hydroxychlordene, N,N-dimethylformamide, phenanthrene, acetic anhydride, pyridin and all organic solvents were purchased from Wako Pure Chemical Industries

(Osaka, Japan). Eighteen species belonging to the genus Phlebia were used for degradation experiments. Phlebia acanthocystis TMIC34875, Phlebia tremellosa TMIC30511, Phlebia aurea TMIC33908, Phlebia radiata TMIC34599, Phlebia nitidula TMIC32286 and Phlebia tremellosus TMIC31235 were obtained from the Tottori Mycological Institute (Tottori, Japan). Phlebia lindtneri GB1027, Phlebia acerina HHB11146, Phlebia setulosa HHB12067, Phlebia rufa HHB14924, Phlebia ludoviciana HHB9640, Phlebia subochracea HHB8494, Phlebia livida HHB4609, Phlebia subserialis HHB9768, Phlebia bresadolae RLG10795 and Phlebia uda Kropp-1 were obtained from the Forest Products Laboratory of the United States Department of Agriculture (Washington, DC). Phlebia ochraceofulva ATCC96119 was obtained from the American Type Culture Collection (Manassas, VA). Phlebia brevispora TMIC34596 was identified using molecular approach in a previous study (Suhara et al., 2002).

g. anti-cancer and other types of chemotherapy with bone marrow suppressive potential) may experience a temporary drop in CD4 cell count. If such a confirmatory CD4 cell count measurement is performed, both measurements should be below the threshold for the patient to fulfil the definition. The consensus definitions of persons presenting late for HIV care and presenting with advanced HIV diseases given in this paper will hopefully end the long-standing debate and the subsequent confusion regarding what is actually meant by a ‘late presenter’. Such

a central concept in public health is best served when a common definition exists. A similar definition has recently been proposed by a group of UK investigators [23], and hence this report selleck products confirms that a consensus has been reached – in a parallel process – also on a European level. Europe-wide consensus on this issue is critical in formulating a continent-wide response to this public health crisis. Current guidance on the use of ART is of utmost importance in our consensus definition of a late presenter. Until 2007, ART was recommended to be deferred in asymptomatic persons until their CD4 count reached 200 cells/μL [24], but the guidelines then changed MK-2206 order when multiple studies demonstrated that persons living with HIV and with a current CD4 count in the range of 200–350 cells/μL

remained at significant risk of contracting opportunistic diseases [25, 26]. The findings from the SMART trial strongly supported this policy of initiating therapy in people with CD4 count <350 cells/μL. Therefore, initiation of ART when the CD4 count nears 350 cells/μL would reduce the incidence of such events. Serious non-AIDS events are observed at a higher incidence than AIDS events in persons living with CD4 counts >350 cells/μL,

particularly among those with an elevated underlying risk of such events [18, 27]. The December 2009 Department Coproporphyrinogen III oxidase of Health and Human Services Antiretroviral (ARV) Guidelines for Adults and Adolescents recommend starting ARV therapy for patients with a CD4 count <500 cells/μL [28]. This controversial recommendation has not received general support across Europe at the present time. However, while our proposed threshold value of 350 cells/μL corresponds to the level at which ART is currently recommended in Europe, our proposed definition will not automatically change if future European guidelines change. Even if there is shown to be a relative benefit of starting ART at higher levels than at a CD4 count of 350 cells/μL (a point currently disputed), it is not evident that the definition of late presentation should change. This is because of the low risk of disease progression in people with CD4 counts >350 cells/μL and the fact that the time from infection to, for example, a CD4 count <500 cells/μL is relatively short, diluting the concept of ‘late presentation’ as a public health issue.