In fungal cells, there is evidence of some functions of ecto-ATPase (Zhong et al., 2000; Junior et al., 2005; Collopy-Junior et al., 2006; Kiffer-Moreira et al., 2010), but little information is available about the activity of ecto-5′-nucleotidase and its product, adenosine. Identification of the physiological role of this enzyme would contribute to understanding the biochemical aspects of host–parasite interactions involving C. parapsilosis. We would like to thank PLX3397 cost Ms Fatima Regina de Vasconcelos Goulart for preparation of fungal cultures and Mr Fabiano Ferreira Esteves and Ms Rosangela Rosa de Arau´jo for excellent technical assistance. This work was supported by grants from the Brazilian

Agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). “
“The main α-glucan synthesized by lichens of the genera Ramalina in the symbiotic state is isolichenan. This polysaccharide was not found in the aposymbiotically cultivated symbionts. It is still unknown if this glucan is produced by the mycobiont only in the presence of a photobiont, in a lichen thallus, or if the isolichenan suppression is influenced by the composition of

culture medium used in its aposymbiotic cultive. Consequently, the latter hypothesis is tested in this study. Cultures of the mycobiont Ramalina complanata were obtained from germinated ascospores and cultivated on 4% glucose Lilly and Barnett medium. Freeze-dried Carfilzomib mouse colonies were defatted and their carbohydrates extracted successively with hot water and aqueous 10% KOH, each at 100 °C. The polysaccharides nigeran, laminaran and galactomannan were liberated, along

with a lentinan-type β-glucan and a heteropolysaccharide (Man : Gal : Glc, 21 : 28 : 51). Nevertheless, the α-glucan isolichenan was not found in the extracts. It follows that it was probably a symbiotic product, synthesized Farnesyltransferase by the mycobiont only in this particular microenvironment, in the presence of the photobiont in the lichen thallus. A discussion about polysaccharides found in the symbiotic thallus as well as in other aposymbiotic cultivated Ramalina mycobionts is also included. The lichen thallus, the symbiotic phenotype of lichen-forming fungi in association with their photobiont (algae and/or cyanobacteria), contains considerable amounts of polysaccharide. Although this symbiotic nature was first revealed in 1867, the development of a lichen thallus is often so integrated that it has been perceived and studied as a single organism until quite recently (Nash, 2008; Lutzoni & Miadlikowska, 2009). Investigations on lichen polysaccharides were carried out using material extracted from the entire thallus (Gorin & Iacomini, 1984, 1985; Gorin et al., 1993; Teixeira et al., 1995; Olafsdottir & Ingólfsdottir, 2001), with no mention of the origin of component polymers (fungal partner or photobiont).

The median duration of NRTI use was 77 (IQR 20–149) months, that of NNRTI use was 17 (IQR 0–51) months, and that of PI use was 26 (IQR 0–75) months. Nineteen per cent of participants were currently receiving abacavir. Seventy-five participants (34%) had a positive CAC score and 17 (8%) had a CAC score of >100, indicating significant atherosclerotic disease (Fig. 1). Fatty liver disease on selleck compound CT imaging was diagnosed in 29 HIV-infected persons (13%). The prevalence of fatty liver disease among those without CAC, those with a CAC score of 1–100, and those with a score >100 was 8, 18 and 41%, respectively (P=0.001). Of those with fatty liver disease, 59% (17

of 29) also had coronary atherosclerosis as determined by CAC>0, and these two conditions were significantly correlated (r=0.21, P=0.002). The prevalence of a positive Dabrafenib ic50 CAC score among those 35–49 years of age in our cohort was 31% (36 of 116), with 6% having a CAC score of >100 (Fig. 1). Similar relationships between fatty liver disease and a positive CAC score were also noted in this age group. Regarding clinical symptoms, participants with a positive CAC score were not significantly more likely to report a history of chest pain or dyspnoea compared with those without CAC (21%vs. 17%, respectively; P=0.46). For HIV-infected persons with low (<10%), moderate (10–20%)

and high (>20%) FRSs, a positive CAC scan was noted in 27, 63 and 60% of patients, respectively (P<0.01) (Table 2). The median FRS for those with a positive

CAC was 8 (IQR 3–12), while those without CAC had a median oxyclozanide score of 3 (IQR 1–6) (P<0.01). Of note, the majority (64%) of those with a positive CAC score had a low FRS. We assessed the utility of the FRS for predicting positive CAC scores (it should be noted that the CAC test is a noninvasive test for detecting calcified coronary disease, and, unlike the gold standard diagnostic test, coronary catheterization, it may miss noncalcified plaque). The sensitivity, specificity, and positive and negative predictive value of the FRS in predicting a positive CAC score in HIV-infected persons were 36%, 89%, 63% and 73%, respectively. In the univariate analyses, HIV-infected persons with CAC compared with those without CAC were older (median 49 vs. 40 years old, respectively; OR 1.2; P<0.01), were more likely to be Caucasian (64%vs. 42%, respectively; OR 2.0; P=0.04), had a longer duration of tobacco use (median 18 vs. 10 years, respectively; OR 1.1 per year; P<0.01), were more likely to be receiving lipid-lowering medication (51%vs. 22%, respectively; OR 3.7; P<0.01) and were more likely to have diabetes (13%vs. 3%, respectively; OR 5.5; P<0.01), hypertension (49%vs. 20%, respectively; OR 4.0; P<0.01), the metabolic syndrome (35%vs. 16%, respectively; OR 2.8; P<0.

The aim of this study is to investigate whether risk-taking attitudes of youths are associated with travel characteristics and

likelihood of experiencing illness or injury while traveling to nonindustrialized countries. Methods. Data were analyzed learn more from the 2008 YouthStyles survey, an annual mail survey gathering demographics and health knowledge, attitudes, and practices of individuals from 9 through 18 years of age. Travelers were defined as respondents who reported traveling in the last 12 months to a destination other than the United States, Canada, Europe, Japan, Australia, or New Zealand. Risk-taking attitude was measured by using a four-item Brief Sensation-Seeking Scale. All Erastin purchase p values ≤0.05 were considered significant. Results. Of 1,704 respondents, 131 (7.7%) traveled in the last 12 months. Females and those with higher household income were more likely to travel (odds ratio = 1.6,1.1). Of those who traveled, 16.7% reported seeking pretravel medical care, with

most visiting a family doctor for that care (84.0%). However, one-fifth of respondents reported illness and injury during travel; of these, 83.3% traveled with their parents. Males and older youths had higher mean sensation-seeking scores. Further, travelers had a higher mean sensation-seeking score than nontravelers. Those who did not seek pretravel medical care also had higher mean sensation-seeking scores (p = 0.1, not significant). Conclusions. Our results show an association between risk-taking attitudes and youth travel behavior. However, adult supervision during travel and parental directives prior to travel

should be taken into consideration. Communication messages should emphasize the importance of pretravel advice, target parents of children who are traveling, and be communicated through family doctors. The arrivals of international tourists grew from 25 to 903 million worldwide between 1950 to 2007, and are expected by 2010 to reach 1 billion.1 In 2007, approximately 31 million US residents traveled to an overseas destination for different travel reasons.2 This trend is not only seen in adults, but also in youths as well. American students are increasingly participating in study-abroad from programs to unconventional destinations, with strong increases in students going to China, India, South Africa, Argentina, and Ecuador.3 Though still largely occurring in industrialized countries, international travel has shown fast growth in developing economies in Asia, Central and Eastern Europe, Middle East, Southern Africa, and South America.1 Travel to developing destinations presents different health risks and is found to be associated with the likelihood of diagnoses of certain diseases.4 In a study of those who traveled to a developing destination, 64% reported an illness after returning.

The aim of this study is to investigate whether risk-taking attitudes of youths are associated with travel characteristics and

likelihood of experiencing illness or injury while traveling to nonindustrialized countries. Methods. Data were analyzed Afatinib from the 2008 YouthStyles survey, an annual mail survey gathering demographics and health knowledge, attitudes, and practices of individuals from 9 through 18 years of age. Travelers were defined as respondents who reported traveling in the last 12 months to a destination other than the United States, Canada, Europe, Japan, Australia, or New Zealand. Risk-taking attitude was measured by using a four-item Brief Sensation-Seeking Scale. All find more p values ≤0.05 were considered significant. Results. Of 1,704 respondents, 131 (7.7%) traveled in the last 12 months. Females and those with higher household income were more likely to travel (odds ratio = 1.6,1.1). Of those who traveled, 16.7% reported seeking pretravel medical care, with

most visiting a family doctor for that care (84.0%). However, one-fifth of respondents reported illness and injury during travel; of these, 83.3% traveled with their parents. Males and older youths had higher mean sensation-seeking scores. Further, travelers had a higher mean sensation-seeking score than nontravelers. Those who did not seek pretravel medical care also had higher mean sensation-seeking scores (p = 0.1, not significant). Conclusions. Our results show an association between risk-taking attitudes and youth travel behavior. However, adult supervision during travel and parental directives prior to travel

should be taken into consideration. Communication messages should emphasize the importance of pretravel advice, target parents of children who are traveling, and be communicated through family doctors. The arrivals of international tourists grew from 25 to 903 million worldwide between 1950 to 2007, and are expected by 2010 to reach 1 billion.1 In 2007, approximately 31 million US residents traveled to an overseas destination for different travel reasons.2 This trend is not only seen in adults, but also in youths as well. American students are increasingly participating in study-abroad check details programs to unconventional destinations, with strong increases in students going to China, India, South Africa, Argentina, and Ecuador.3 Though still largely occurring in industrialized countries, international travel has shown fast growth in developing economies in Asia, Central and Eastern Europe, Middle East, Southern Africa, and South America.1 Travel to developing destinations presents different health risks and is found to be associated with the likelihood of diagnoses of certain diseases.4 In a study of those who traveled to a developing destination, 64% reported an illness after returning.

As the hospital

grounds were regularly sprayed with insecticides, all apartments were air-conditioned and all windows screened, malaria was probably transmitted when mosquitoes gained access to the buildings through the main entrance doors. The substantial risk associated with living on the ground floor of a modern apartment building in sub-Saharan Africa has implications Selleckchem 3Methyladenine for the local population, as well as for long-term nonimmune residents in the region. As far as we know there are no studies which investigated the relationship between the floor level and the risk of contracting malaria. It is worth noting that the hospital grounds were regularly sprayed with insecticides. This protective measure is not included in the standard recommendations for the prevention of malaria, but it probably does not explain the increased risk of acquiring malaria in workers living on the ground floor. We initially expected to find an inverse relationship between malaria incidence and the distance from the different apartment buildings to the presumed mosquito breeding area. The lack of such association might be explained by the relatively small total area of the hospital grounds.

Also unexpected was the association found between age and smoking status, and the risk of acquiring malaria. It should be noted that only the association between age and an increased risk of infection ioxilan Olaparib order with malaria was significant in a multivariate analysis. Older age has been reported to be a risk factor for the development of severe malaria, but is not considered to be independently associated with an increased risk of contracting malaria.8 One possible explanation is that younger workers simply spent more time outdoors. As smoking was prohibited in the hospital building, exposure to mosquitoes theoretically increased when staff members went out to smoke or

when window screens were purposely opened to ventilate closed rooms. Strict bite avoidance behavior and chemoprophylaxis were practiced by very few participants. Such poor compliance of well-informed healthcare personnel with relatively simple measures to avoid malaria is disappointing. Not only had most workers received detailed information about malaria prophylaxis in specialized pre-travel clinics, but they also were regularly exposed to patients with malaria and were informed of the high incidence of malaria in sub-Saharan Africa. Immediate access to healthcare within the hospital may have led to a belief that malaria can be easily cured if diagnosed and treated early. Most workers initially used malaria chemoprophylaxis, but stopped all antimalarial medications within 3 months of their arrival in Equatorial Guinea.

, 1997; Miller & Bassler, 2001; Henke & Bassler, 2004a), single-species co-cultures (Hammer & Bassler, 2007), or co-cultures of Vibrios with other bacteria unlikely to occupy the same environmental niches (Xavier

& Bassler, 2005). These studies were not designed to reflect natural environmental setting that Vibrios typically encounter, such as the chitinous surfaces of animals (Lipp et al., 2002). However, mutants of V. cholerae (ΔhapR and ΔluxO), which regulate QS-controlled genes irrespective of autoinducer accumulation, provided the first demonstration of the role of QS in an animal model of cholera (Zhu et al., 2002), but do not directly demonstrate the role of extracellular autoinducer molecules. Only recently has secreted CAI-1 been shown to repress virulence in vivo (Duan OSI-906 supplier & March, 2010). In a similar manner,

we show here for the first time that extracellular CAI-1 and AI-2 molecules directly activate DNA uptake within a mixed-species environmental biofilm. Vibrio-specific CAI-1 appears to play a major role and interspecies AI-2 a minor role, suggesting that induction of DNA uptake may not be restricted exclusively to a response to autoinducers produced by Vibrio species, but that HGT may also be promoted by AI-2 derived from non-Vibrio members of a biofilm. Addition studies will be necessary to determine whether the behavior described here is cooperative selleck chemicals ‘cross-talk’ between bacteria or whether V. cholerae simply uses the autoinducer molecules derived from others as a cue to alter gene expression (Diggle et al., 2007). It will also be interesting to determine whether additional chitinous materials that support growth of Vibrios and other bacteria in marine environments (Kaneko & Colwell, 1975; Sochard et al., 1979; Davis & Sizemore, 1982; Huq et al., 1983; http://www.selleck.co.jp/products/azd9291.html Bartlett & Azam, 2005; Lyons et al., 2007) also stimulate autoinducer-induced DNA uptake (Bartlett & Azam, 2005). Recent genomic comparison studies of multiple V. cholerae isolates suggest that substantial HGT events among Vibrio species may account for the presence of large ‘genomic islands’ of transferred DNA (Chun

et al., 2009). Transduction of the cholera toxin genes encoded within a filamentous phage (CTXΦ) permits exchange of virulence factors among V. cholerae (Waldor & Mekalanos, 1996). In laboratory microcosms, DNA encoding antigenic determinants and also carrying CTXΦ occurs via chitin-induced HGT (Blokesch & Schoolnik, 2007; Udden et al., 2008) between V. cholerae. It is proposed that HGT among Vibrio species likely explains the current genome structures, but it has yet to be demonstrated whether chitin-induced HGT can promote DNA exchange among different Vibrios in environmental microcosms. We are currently performing experiments to test a model that autoinducers may promote interspecies HGT and emergence of genetic diversity in Vibrios.

Advances in genomic tools such as tiling arrays, comparative PD-0332991 manufacturer genome hybridization microarrays (array CGH), and ultra-high-throughput sequencing

are now allowing researchers to have a better understanding of the genotypic changes associated with adaptation [for review see (Dettman et al., 2012)], such as drug resistance (Selmecki et al., 2010). The applications of these tools to time-course isolates obtained in vitro and in vivo will yield the necessary correlations between genotypic and phenotypic changes in resistant strains and help researchers to gain a firmer grasp on the evolutionary trajectories of fungal pathogens during exposure INCB024360 to antifungal agents. In addition to the aforementioned factors (e.g. population size, relative fitness coefficients, rate of beneficial mutations, etc.)

that contribute to the population dynamics during adaptive evolution, additional factors such as dosing regimens and the mode of action of the antifungal agent may also contribute to the population dynamics during the emergence of drug resistance in C. albicans. A series of in vivo studies in murine model shed some light on the importance of some of these factors on antifungal drug resistance in C. albicans (Andes et al., 2006). Andes et al. (2006) investigated the impact of different fluconazole (a fungistatic agent) dosing regimens, using different dose levels and dosing intervals, on the outgrowth of resistant strain with different initial ratios of drug-resistant and susceptible strains in a murine model; they found a lower but more frequent dosage of fluconazole led to less frequent outgrowth of the resistant strain compared with higher but more infrequent dosage. Another study by the same

group revealed a similar effect of dosing regimen on drug resistance emergence when they evolved an initially drug-susceptible strain of C. albicans in a murine model (Andes et al., 2006). Results from these studies suggest different selection strategies may have different impacts on the expansion of drug-resistant genotypes Niclosamide within the population, leading to different population dynamics and ultimately to different evolutionary outcomes. In addition, they found that if the initial population contained at least 10% of the drug-resistant clone, the evolving population behaved phenotypically as entirely drug resistant, suggesting that the population structure prior to drug exposure is an important factor in determining the evolutionary outcome of the population (Andes et al., 2006). The mode of action of the antifungal agent may also be a contributing factor on the emergence of drug resistance.

5 years; IQR 41.6–58.6 years), but higher than in the IDU HIV-infected group (38.6 years; IQR 34.2–42.4 years) (Table 2). HIV-infected patients in the non-IDU group had a higher CD4 cell count and more patients were on HAART at the time of VTE diagnosis than in the IDU group (72.8% in the non-IDU group and 42.9% in the IDU group). The incidences of VTE in non-IDU and IDU HIV-infected patients as well as in the population cohort are illustrated in Figure 1. The overall incidence of VTE was 3.2 per 1000 PYR (95% CI 2.6–3.9) for non-IDU HIV-infected patients, 16.1 per 1000 PYR (95% CI 12.4–21.0) for IDU HIV-infected patients, and 0.9 per 1000 PYR (95%

CI 0.9–1.0) for population selleck monoclonal humanized antibody inhibitor controls. The risks of VTE at 5 and 10 years after the index date are shown in Table 1. As illustrated in Table 3, the risk of VTE was higher in the non-IDU group of HIV-infected individuals compared with the population cohort. However, the risk was substantially

Selleck Antiinfection Compound Library higher in the IDU group than in the non-IDU group (Table 3). For non-IDU patients we observed a slightly higher risk of provoked VTE than unprovoked VTE. This was not observed for patients reporting IDU as the route of infection (Table 3). To estimate the impact of immunodeficiency on VTE risk, we introduced CD4 as a time-dependent variable and found a slightly higher risk of VTE in patients with a CD4 count below 200 cells/μL, although the results were not statistically significant. In the non-IDU group, HAART nearly doubled the risk of VTE, while this effect was not observed in the IDU group (Table 4). Although not statistically significant, the greatest impact of HAART was on risk of provoked VTE in non-IDU patients. In this cohort study we found an increased risk of VTE in HIV-infected patients compared with the general population comparison cohort. The risk was mainly attributable to HIV infection and IDU. A low CD4 cell count seemed to increase the risk of VTE, and Atezolizumab use of HAART almost doubled the risk of VTE in the non-IDU group. The main strengths of the study are its nationwide population-based design with long and complete follow-up. Furthermore, access to Danish

national registries allowed us to identify a well-matched population comparison cohort to obtain data on diagnoses of VTE and comorbidity (including cancers and surgical procedures) for the HIV-infected and general population cohorts from the same accurate data sources. Because the definition of provoked and unprovoked VTE has been shown previously to be important in understanding VTE, we assessed the risk of VTE according to overall, provoked and unprovoked VTE [34,35]. We were able to control the analysis not only for age, gender and calendar time, but importantly also for comorbidity. Because of the strong association between IDU and VTE, stratification according to IDU/non-IDU status was crucial. We are not aware of other studies with a similar design. We used hospital registry-based discharge diagnoses to identify VTEs.

97, P = 0.0003) rhythm, with an

estimated acrophase at 5.48 h (Fig. 2). HNMT showed almost equal activity in all brain structures at all times examined (Fig. 2). The enzymatic activity in the hypothalamus showed no 24-h periodicity, but had near 12-h oscillations (F2,33 = 10.93, P = 0.0002; Table 1), with an estimated acrophase at 11.64 h (Fig. 2), see more which was opposite to that of HDC. Histamine levels were assayed in homogenates of hypothalamic, striatal and cortical samples of both CBA/J and C57BL/6J strains (Table 2). In CBA/J mice, only hypothalamic samples showed significant 24-h rhythmicity (F2,29 = 9.42, P = 0.0005), with an acrophase at 22.72 h (Fig. 3), whereas C57BL/6J mice did not show any changes in histamine content in any of the structures examined. Additionally, no periodicity in histamine levels was detected in the medulla, pons, midbrain, thalamus GSK2118436 molecular weight or hippocampus of CBA mice (data not shown). The mean levels of histamine in CBA/J mice

were significantly lower than those in C57BL/6J mice in all three brain regions, as determined by two-way anova (Table 2). Analysis of the 1-methylhistamine content in the hypothalamus, cortex and striatum revealed clear-cut periodic changes, with a 24-h period and a calculated maximum near ZT 20.5 for both mouse strains. CBA/J mice showed significantly lower levels of 1-methylhistamine than C57BL/6J mice (Table 2; Fig. 4). The location of microdialysis probes is shown in Fig. 5. Representative data on histamine release superimposed with the percentage of motor activity Thalidomide and wakefulness data, respectively, from the same mouse (mouse no. 1; full data in Table 3) are shown in Fig. 6A and B. Group cosinor analysis revealed 24-h and overlaid 8-h periodicities in histamine release, with an orthophase at 17.63 h (Table 3). Cross-correlation analysis

revealed the highest correlation of histamine release with percentage wakefulness and a lower correlation with motor activity (Table 3) at a time lag of 0. In order to test for a relationship between histamine release and the occurrence of specific frequencies in the EEG activity, the histamine level in dialysates was correlated with the EEG power spectra in the 1–45-Hz frequency range (0.5-Hz bins) calculated for wakefulness in 30-min epochs. The strongest positive correlation between histamine release and the EEG power spectra was found in the high θ-range (7.5–9.1 Hz) and the γ-range (> 35 Hz), which are indicative of active and attentive wakefulness in rodents (mean ± SD, 0.83 ± 0.22; Spearman correlation, n = 5, P < 0.05; Fig. 6C). No correlation was found with the low θ-range (4–7 Hz), which indicates quiet wakefulness. A strong negative correlation was observed with the δ-range (1–4 Hz), which is associated with sleep pressure/sleepiness during the awake state (mean ± SD, −0.83 ± 0.3; Spearman correlation, n = 5, P < 0.05). In this study, we analysed the biochemical properties of the brain histaminergic system of mice.

Seventy-five patients (29.6%) were taking ART at the time at which their CD4 count first fell to <200 cells/μL in this immunosuppressive episode. Of these, two-thirds (50 of 75) had documented PLX4032 good adherence to ART. Reasons for the decrease in CD4 cell count included: transient decrease in CD4 count (CD4 counts prior and subsequently >200 cells/μL) (n=31), decrease in CD4 count despite maintaining a VL<50 HIV-1 RNA copies/mL (n=10) and ART failure (n=9). Poor adherence (25 of 75 patients) was documented in the remainder of patients and reasons included: difficulty taking tablets/medication side effects

(n=6), social issues (n=6), mental health issues (n=2), ‘feeling well’ (n=2), travel (n=1) and not documented (n=8). There were no significant associations between all reasons for decrease in CD4 cell count and sex, ethnicity or risk factor for HIV acquisition. Poor adherence was more frequently documented among heterosexuals [15.7% (16 of 102) vs. 5.1% (7 of 137) of MSM], patients of black ethnicity [17.3% (17 of 98) vs. 5.9% (6 of 102) Pexidartinib solubility dmso of white UK-born patients vs. 7.5% (4 of 53) of other patients] and women [18.2% (12 of 66) vs. 7.0% (13 of 187) of men]. Patients

in centre 1 were more likely to have interrupted or declined ART compared with patients in centre 2 who were more likely to be poor attendees (P<0.001). The median time from first presentation to the most recent CD4 <200 cells/μL (t1 to t3) was 36 weeks (IQR 17–81 weeks). There were 155 of 168 patients (92.3%) taking ART at the time of the most recent CD4 count <200 cells/μL. Virological suppression (VL<50 copies/mL) had been achieved in 77.8% of patients (70 of 90) treated for at least 3 months. The median time to the patient starting ART after

first presentation was 5 weeks (IQR 3–10 weeks). Patients taking ART Dichloromethane dehalogenase had done so for a median of 43 weeks (IQR 16–99 weeks). In this time, the median CD4 count increased from 47 cells/μL (IQR 19–90 cells/μL) to 140 cells/μL (IQR 89–171 cells/μL). Thirteen patients were not taking ART. Of these, five declined treatment. Reasons included: mental health issues (n=2), social issues (n=2) and ‘feels well’ (n=1). The remainder first presented in the last 2 weeks of the study period and had not yet started treatment. The rate of hospitalizations for all patients in the year preceding the most recent CD4 <200 cells/μL (t3) was 44.9 per 100 person-years of follow-up (group A, 43.1/100 person-years of follow-up; group B, 48.8/100 person-years of follow-up). All patients had attended the out-patient service a median of four times (IQR 2–6 times) in that year. The proportion of patients with AIDS-defining illnesses in the year preceding the decrease in the CD4 count to <200 cells/μL (t2) was 12.6% (32 of 253) for patients in group A and 33.3% (56 of 168) for patients in group B (P<0.