Association between antiretroviral therapy and antitubercular drug resistance in TB treatment outcome among Kazakh TB/HIV co-infected patients.

OBJECTIVES: Drug-resistant tuberculosis (TB) poses a serious threat to public health in Kazakhstan. This paper presents findings related to TB treatment outcome and drug resistance status among people co-infected with human immunodeficiency virus (HIV) and TB in Kazakhstan. METHODS: A cohort study using data provided by the Kazakhstan Ministry of Health's National Tuberculosis Program for 2014 and 2015 was performed. The χ2 test and logistical regression were performed to understand factors associated with drug-resistant TB status and TB treatment outcome. RESULTS: In the bivariate analysis, drug-resistant TB status was significantly associated with year of TB diagnosis (P=0.001) and viral load (P=0.03). TB treatment outcome was significantly associated with age at diagnosis (p=0.01), antiretroviral (ARV) treatment (P<0.0001) and drug-resistant TB status (P=0.02). In the adjusted analysis, drug-resistant TB status was associated with an increased likelihood of successful completion of treatment with a successful outcome compared with treatment failure (odds ratio=6.94, 95% confidence interval 1.39-34.44). CONCLUSIONS: These results suggest that having drug-resistant TB is associated with a higher likelihood of completing treatment with successful outcome, even when controlling for receipt of ARV therapy.

Cortical Networks Involved in Memory for Temporal Order.

We examined the neurobiological basis of temporal resetting, an aspect of temporal order memory, using a version of the delayed-match-to-multiple-sample task. While in an fMRI scanner, participants evaluated whether an item was novel or whether it had appeared before or after a reset event that signified the start of a new block of trials. Participants responded "old" to items that were repeated within the current block and "new" to both novel items and items that had last appeared before the reset event (pseudonew items). Medial-temporal, prefrontal, and occipital regions responded to absolute novelty of the stimulus-they differentiated between novel items and previously seen items, but not between old and pseudonew items. Activation for pseudonew items in the frontopolar and parietal regions, in contrast, was intermediate between old and new items. The posterior cingulate cortex extending to precuneus was the only region that showed complete temporal resetting, and its activation reflected whether an item was new or old according to the task instructions regardless of its familiarity. There was also a significant Condition (old/pseudonew) × Familiarity (second/third presentations) interaction effect on behavioral and neural measures. For pseudonew items, greater familiarity decreased response accuracy, increased RTs, increased ACC activation, and increased functional connectivity between ACC and the left frontal pole. The reverse was observed for old items. On the basis of these results, we propose a theoretical framework in which temporal resetting relies on an episodic retrieval network that is modulated by cognitive control and conflict resolution.

Hitting the reset button: An ERP investigation of memory for temporal context.

This study explored how temporal context influences recognition. In an ERP experiment, subjects were asked to judge whether pictures, presented one at a time, had been seen since the previous appearance of a special reset screen. The reset screen separated sequences of successively presented stimuli and signaled a change in temporal context. A "new-repeat" picture was one that had been seen before but was to be called "new" because it had not appeared since the previous reset screen. New-repeat pictures elicited a more negative FN400 component than did "old" pictures even though both had seen before during the experiment. This suggests that familiarity, as indexed by the FN400, is sensitive to temporal context. An earlier frontopolar old/new effect distinguished pictures that were seen for the first time in the experiment from all other pictures. The late positive component (LPC), which is typically greater for old stimuli, was smaller for new-repeat pictures than for pictures seen for the first time in the experiment. Finally, individual differences in task performance were predicted by the differences in amplitude of P3b that was evoked by the onset of the reset screen.

Associations between prior HPV4 vaccine doses and cervical cancer screening participation.

BACKGROUND: Cervical cancer screening, regardless of HPV vaccination, is a cornerstone of cancer prevention. This study evaluated associations between prior HPV vaccine doses and initiation and continued participation of screening by age at vaccination. METHODS: Using electronic medical records for a safety net healthcare system (Truman Medical Center), women aged 14-26y vaccinated (n=1123) between 07/01/2006 and 10/1/2009 were randomly selected and matched on birth year and health campus to unvaccinated (n=1123) women. Frequency of screening was determined through 07/01/2013. Hazard ratios (HR) for screening were estimated using Cox proportional hazards regression. RESULTS: Screening rates were higher after vaccination: unvaccinated (53%), first (62%), second (59%) or third (61%) doses. Women who initiated screening were less likely to complete the vaccine series, regardless of age. Women receiving one dose were more likely than unvaccinated women to initiate screening (HR=2.98 95% Confidence Interval (CI):2.45-3.61) and were more likely to screen than those receiving two (1 vs. 2, HR=2.94 95% CI:2.09-4.14) or three doses (1 vs. 3, HR=3.15 95% CI:2.21-4.48). Compared to unvaccinated women, women <21y who completed 3-doses were 1.8-times more likely to screen at ≥21y, whereas vaccinated women ≥21y were more likely to screen regardless of number of doses (p<0.0001). CONCLUSIONS: Women who were vaccinated were more likely to screen than unvaccinated women; screening rate was highest after and occurred closest to the first vaccine dose. Research evaluating the efficacy of a one-dose vaccine is warranted and may provide both higher vaccination and screening rates.

Effects of Exercise During Pregnancy on Maternal Heart Rate and Heart Rate Variability.

BACKGROUND: Pregnancy is associated with an increased sympathetic state, which can be exacerbated by gestational conditions. Research has shown that exercise during pregnancy lowers heart rate (HR) and can attenuate the symptoms of gestational conditions associated with increased sympathetic control. However, changes in maternal heart autonomic function in response to exercise have not been reported across multiple time points during pregnancy. This analysis is designed to address this gap. OBJECTIVE: To determine if exercise throughout gestation improves maternal cardiac autonomic nervous system functioning, as evidenced by decreased HR and increased heart rate variability (HRV) indices. DESIGN: Case control study. SETTING: Academic medical institution. PARTICIPANTS: A total of 56 women with healthy, singleton, low-risk pregnancies. METHODS: Participants were asked to complete 3 resting 18-minute HRV recordings at 28, 32, and 36 weeks' gestation, along with a physical activity questionnaire. MAIN OUTCOME MEASURES: HRV indices were calculated for time (R peak to R peak interval standard deviation and root mean squared of successive differences) and frequency (very low, low, and high frequency) domain measures. The differences between groups were compared for HRV indices at 28, 32, and 36 weeks. RESULTS: Resting HR was significantly lower in the exercise group at 28 weeks (P < .01) compared with the control group. The exercise group had significantly (P < .05) increased measures of resting HRV time domain measures at 28, 32, and 36 weeks' gestation compared with the control group. Resting HRV power was significantly increased (P < .05) in all frequency domain measures at 32 weeks in the exercise group relative to the control group. No differences occurred in sympathovagal balance (low frequency/high frequency ratio) between groups. CONCLUSION: Exercise throughout pregnancy can significantly improve cardiac autonomic control. More research is needed to determine if this adaptation to exercise may reduce the risk of adverse outcomes associated with gestational conditions with poor autonomic control, such as diabetes, hypertension, pre-eclampsia, and excessive weight gain.

Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population.

Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine) participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14-26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00). Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35). Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.

In a safety net population HPV4 vaccine adherence worsens as BMI increases.

OBJECTIVES: Obesity adversely inhibits antibody response to vaccination. Three doses of HPV4 may or may not provide adequate long term protection against HPV 16/18 in obese females. The aim of this study was to determine whether adherence to HPV4 vaccination in a safety net population was reduced with increasing body mass index (BMI). METHODS: We designed a historical prospective study evaluating the number and dates of HPV4 dosing that occurred from July 1, 2006 through October 1, 2009 by the demographic characteristics of the 10-26 year old recipient females. The defined dosing intervals were adapted from the literature and obesity categories were defined by the WHO. RESULTS: 1240 females with BMI measurements received at least one dose of HPV4; 38% were obese (class I, II and III) and 25% were overweight. Females with normal BMI received on-time triplet dosing significantly more often than did the obese class II and III females (30% vs. 18%, p<0.001). Obese class II/III females have a significant 45% less chance of completing the on-time triplet HPV4 series than normal women (OR = 0.55, 95% CI: 0.37, 0.83). Pregnancy history has a significant influence on BMI and HPV4 dosing compliance in this safety net population where 71% had been gravid. Hispanic females were less likely to complete HPV4 dosing regardless of BMI (aOR = 0.39, 95% CI: 0.16, 0.95). CONCLUSIONS: Obesity, as well as gravidity and Hispanic race, are risk factors for lack of HPV4 vaccine adherence among young females in a safety net population.

Urban and rural safety net health care system clinics: no disparity in HPV4 vaccine completion rates.

OBJECTIVE: Safety net health care centers in the US serve vulnerable and underinsured females. The primary aim of this work was to determine if HPV4 dosing compliance differs between females who receive doses at rural vs. urban core safety net health care locations. METHODS: Females exclusively receiving health care in the Truman Medical Center (TMC) safety net system at the urban core and rural locations were identified by their HPV4 vaccine records. Dates and number of HPV4 doses as well as age, gravidity, parity and race/ethnicity were recorded from the electronic medical record (EMR). Appropriate HPV4 dosing intervals were referenced from the literature. RESULTS: 1259 females, 10-26 years of age, received HPV4 vaccination at either the rural (23%) or urban core location (77%). At the rural location, 23% received three doses on time, equal to the 24% at the urban core. Females seen in the urban core were more likely to receive on-time doublet dosing than on-time triplet dosing (82% vs. 67%, p<0.001). Mistimed doses occurred equally often among females receiving only two doses, as well as those receiving three doses. CONCLUSIONS: Compliance with on-time HPV4 triplet dose completion was low at rural and urban core safety net health clinics, but did not differ by location.

Repetition related changes in activation and functional connectivity in hippocampus predict subsequent memory.

Using fMRI, this study examined the relationship between repetition-related changes in the medial temporal lobe (MTL) activation during encoding and subsequent memory for similarity of repetitions. During scanning, subjects classified pictures of objects as natural or man-made. Each object-type was judged twice with presentations of either identical pictures or pictures of different exemplars of the same object. After scanning, a surprise recognition test required subjects to decide whether a probe word corresponded to pictures judged previously. When a subject judged the word as "old," a second judgment was made concerning the physical similarity of the two pictures. Repetition related changes in MTL activation varied depending on whether or not subjects could correctly state that pictures were different. Moreover, psychophysiological interactions analyses showed that accuracy in recalling whether the two pictures were different was predicted by repetition-related changes in the functional connectivity of MTL with frontal regions. Specifically, correct recollection was predicted by increased connectivity between the left posterior hippocampus and the right inferior frontal gyrus, and also by decreased connectivity between the left posterior hippocampus and the left precentral gyrus on the second stimulus presentation. The opposite pattern was found for trials that were incorrectly judged on the nature of the repetition. These results suggest that successful encoding is predicted by a combination of increases and decreases in both the MTL activation and functional connectivity, and not merely by increases in activation and connectivity as suggested previously.

Opposing patterns of neural priming in same-exemplar vs. different-exemplar repetition predict subsequent memory.

The present neuroimaging study examines how repetition-related neural attenuation effects differ as a function of the perceptual similarity of the repetition and subsequent memory. One previous study (Turk-Browne et al., 2006) reported greater attenuation effects for subsequent hits than for misses. Another study (Wagner et al., 2000) found that neural attenuation is negatively correlated with subsequent memory. These opposing results suggest that repetition-related neural attenuation for subsequent hits and misses may be driven by different factors. In order to investigate the factors that affect the degree of neural attenuation, we varied perceptual similarity between repetitions in a scanned encoding phase that was followed by a subsequent memory test outside the scanner. We demonstrated that the degree of neural attenuation in the object processing regions depends on the interaction between perceptual similarity across repeated presentations and the quality their encodings. Specifically, the same areas that decreased neural signal for repetitions of same exemplars that were subsequently recognized with confidence that the repetitions were identical showed a decrease in neural signal for different-exemplar misses but not for the corresponding subsequently recognized hits. Our results imply that repetition-related neural attenuation should be related to the more efficient processing of perceptual properties of the stimuli only if subjects are able to subsequently remember the stimuli. Otherwise, the cause of attenuation may be in the failure to encode the stimuli on the second presentation as shown by the pattern of neural attenuation for the different-exemplar misses.

Problem-solving without awareness: an ERP investigation.

When subjects are given the balls-and-boxes problem-solving task (Kotovsky & Simon, 1990), they move rapidly towards the goal after an extended exploratory phase, despite having no awareness of how to solve the task. We investigated possible non-conscious learning mechanisms by giving subjects three runs of the task while recording ERPs. Subjects showed significant differences in their ERP components during the exploratory phase between correct and incorrect moves. Exploratory incorrect moves were associated with a shallower response-locked N1 component and a larger response-locked P3 component compared with exploratory correct moves. Subjects who solved the task more quickly exhibited a trend towards larger N1 and P3 components. These results suggest that the brain processes information about the correctness of a move well before subjects are aware of move correctness. They further suggest that relatively simple attentional and error-monitoring processes play an important role in complex problem-solving.

Knowing we know before we know: ERP correlates of initial feeling-of-knowing.

Subjects performed a rapid feeling-of-knowing task developed by (Reder, L. M., & Ritter, F. (1992). What determines initial feeling of knowing? Familiarity with question terms, not with the answer. Journal of Experimental Psychology: Learning, Memory, and Cognition, 18, 435-451), while event-related potentials (ERPs) were recorded to identify the time course of "feeling-of-knowing" signals. Subjects were shown a series of math problems, some of which were repeated multiple times during the course of the experiment, and subjects had to rapidly decide whether the answer to a given problem could be quickly retrieved from memory (retrieval trials) or had to be calculated on scrap paper (calculate trials). Behavioral results replicated the 1992 study, showing that subjects can estimate whether the answer is known much faster than the answer can be retrieved. ERPs time-locked to the onset of the math problem showed that accurate retrieval trials were associated with greater positivity for an early frontal P2 component (epoched from 180 to 280ms) and a frontal-central P3 component (epoched from 300 to 550ms). Moreover, this feeling-of-knowing signal was not found for subjects who never obtained a successful on-time retrieval. We interpret these findings as suggesting that initial feeling-of-knowing relies on a rapid assessment of the "perceptual fluency" with which the stimulus is processed. If a stimulus is deemed sufficiently familiar, the activation level of an internal problem representation is used to arrive at a decision of whether to search for the answer or to calculate it.

The impact of synthetic pyrethroid and organophosphate sheep dip formulations on microbial activity in soil.

Sheep dip formulations containing organophosphates (OPs) or synthetic pyrethroids (SPs) have been widely used in UK, and their spreading onto land has been identified as the most practical disposal method. In this study, the impact of two sheep dip formulations on the microbial activity of a soil was investigated over a 35-d incubation. Microbial utilisation of [1-(14)C] glucose, uptake of (14)C-activity into the microbial biomass and microbial numbers (CFUs g(-1) soil) were investigated. In control soils and soils amended with 0.01% sheep dip, after 7d a larger proportion of added glucose was allocated to microbial biomass rather than respired to CO(2). No clear temporal trends were found in soils amended with 0.1% and 1% sheep dips. Both sheep dip formulations at 0.1% and 1% concentrations resulted in a significant increase in CFUs g(-1) soil and [1-(14)C] glucose mineralisation rates, as well as a decline in microbial uptake of [1-(14)C] glucose, compared to control and 0.01% SP- or OP-amended soils. This study suggests that the growth, activity, physiological status and/or structure of soil microbial community may be affected by sheep dips.