Microarray Analysis of Microbiota of Gingival Lesions in Noma Patients

Noma (cancrum oris) is a gangrenous disease of unknown etiology affecting the maxillo-facial region of young children in extremely limited resource countries. In an attempt to better understand the microbiological events occurring during this disease, we used phylogenetic and low-density microarrays targeting the 16S rRNA gene to characterize the gingival flora of acute noma and acute necrotizing gingivitis (ANG) lesions, and compared them to healthy control subjects of the same geographical and social background. Our observations raise doubts about Fusobacterium necrophorum, a previously suspected causative agent of noma, as this species was not associated with noma lesions. Various oral pathogens were more abundant in noma lesions, notably Atopobium spp., Prevotella intermedia, Peptostreptococcus spp., Streptococcus pyogenes and Streptococcus anginosus. On the other hand, pathogens associated with periodontal diseases such as Aggregatibacter actinomycetemcomitans, Capnocytophaga spp., Porphyromonas spp. and Fusobacteriales were more abundant in healthy controls. Importantly, the overall loss of bacterial diversity observed in noma samples as well as its homology to that of ANG microbiota supports the hypothesis that ANG might be the immediate step preceding noma.     

Genetic variation in oxytocin rs2740210 and early adversity associated with postpartum depression and breastfeeding duration

Mothers vary in duration of breastfeeding. These individual differences are related to a variety of demographic and individual maternal factors including maternal hormones, mood and early experiences. However, little is known about the role of genetic factors. We studied single‐nucleotide polymorphisms (SNPs) in the OXT peptide gene (rs2740210; rs4813627) and the OXT receptor gene (OXTR rs237885) in two samples of mothers from the Maternal adversity, Vulnerability and Neurodevelopment study (MAVAN), a multicenter (Hamilton and Montreal, Canada) study following mothers and their children from pregnancy until 7 years of age. Data from the Hamilton site was the primary sample (n = 201) and data from Montreal was the replication sample (n = 151). Breastfeeding duration, maternal mood (measured by the CES‐D scale) and early life adversity (measured by the CTQ scale) were established during 12 months postpartum. In our primary sample, polymorphisms in OXT rs2740210, but not the other SNPs, interacted with early life adversity to predict variation in breastfeeding duration (overall F_8,125 = 2.361, P = 0.021; interaction effect b = ?8.12, t = ?2.3, P = 0.023) and depression (overall F_8,118 = 5.751, P ≤ 0.001; interaction effect b = 6.06, t = 3.13, P = 0.002). A moderated mediation model showed that higher levels of depression mediated the inverse relation of high levels of early life adversity to breastfeeding duration, but only in women possessing the CC genotype [effect a′ = ?3.3401, 95% confidence interval (CI) = ?7.9466 to ?0.0015] of the OXT SNP and not in women with the AA/AC genotype (a′ = ?1.2942, ns). The latter findings (moderated mediation model) were replicated in our Montreal sample (a′ = ?0.277, 95% CI = ?0.7987 to ?0.0348 for CC; a′ = ?0.1820, ns for AA/AC) .     

Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies

Background

Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.

Methods and Findings

Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.

Conclusions

South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors'' Summary     

Associations between Active Travel to Work and Overweight,Hypertension, and Diabetes in India: A Cross-Sectional Study

Background

Increasing active travel (walking, bicycling, and public transport) is promoted as a key strategy to increase physical activity and reduce the growing burden of noncommunicable diseases (NCDs) globally. Little is known about patterns of active travel or associated cardiovascular health benefits in low- and middle-income countries. This study examines mode and duration of travel to work in rural and urban India and associations between active travel and overweight, hypertension, and diabetes.

Methods and Findings

Cross-sectional study of 3,902 participants (1,366 rural, 2,536 urban) in the Indian Migration Study. Associations between mode and duration of active travel and cardiovascular risk factors were assessed using random-effect logistic regression models adjusting for age, sex, caste, standard of living, occupation, factory location, leisure time physical activity, daily fat intake, smoking status, and alcohol use. Rural dwellers were significantly more likely to bicycle (68.3% versus 15.9%; p<0.001) to work than urban dwellers. The prevalence of overweight or obesity was 50.0%, 37.6%, 24.2%, 24.9%; hypertension was 17.7%, 11.8%, 6.5%, 9.8%; and diabetes was 10.8%, 7.4%, 3.8%, 7.3% in participants who travelled to work by private transport, public transport, bicycling, and walking, respectively. In the adjusted analysis, those walking (adjusted risk ratio [ARR] 0.72; 95% CI 0.58–0.88) or bicycling to work (ARR 0.66; 95% CI 0.55–0.77) were significantly less likely to be overweight or obese than those travelling by private transport. Those bicycling to work were significantly less likely to have hypertension (ARR 0.51; 95% CI 0.36–0.71) or diabetes (ARR 0.65; 95% CI 0.44–0.95). There was evidence of a dose-response relationship between duration of bicycling to work and being overweight, having hypertension or diabetes. The main limitation of the study is the cross-sectional design, which limits causal inference for the associations found.

Conclusions

Walking and bicycling to work was associated with reduced cardiovascular risk in the Indian population. Efforts to increase active travel in urban areas and halt declines in rural areas should be integral to strategies to maintain healthy weight and prevent NCDs in India. Please see later in the article for the Editors'' Summary     

Generative FDG-PET and MRI Model of Aging and Disease Progression in Alzheimer's Disease

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer''s Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.     

Decision-Making in Multiple Sclerosis Consultations in Italy: Third Observer and Patient Assessments

Objective

To assess decision-making in multiple sclerosis (MS) from third observer and patient perspectives.

Method

Audio recordings of first-ever consultations with a participating physician (88 outpatients, 10 physicians) at four tertiary MS care clinics in Italy, were rated by a third observer using the Observing Patient Involvement in Shared Decision Making (OPTION) and by patients using the Perceived Involvement in Care Scale (PICS).

Results

Mean patient age was 37.5, 66% were women, 72% had MS, and 28% had possible MS or other disease. Mean PICS subscale scores (range 0 poor, 100 best possible) were 71.9 (SD 24.3) for "physician facilitation" (PICS-F); 74.6 (SD 22.9) for "patient information exchange" (PICS-I); and only 22.5 (SD 16.2) for "patient decision making" (PICS-DM). Mean OPTION total score (0 poor, 100 best possible) was 29.6 (SD 10.3). Poorest OPTION scores were found for items assessing “preferred patient approach to receiving information” and “preferred patient level of involvement.” Highest scores were for “clinician drawing attention to identified problem”, “indicating need for decision making,” and “need to review the decision.” Consultation time, woman physician, patient-physician gender concordance and PICS-F were associated with higher OPTION total score; older physician and second opinion consultation were associated with lower OPTION score.

Conclusions

In line with findings in other settings, our third observer findings indicated limited patient involvement abilities of MS physicians during first consultations. Patient perceptions of physician skills were better than third observers’, although they correlated. Consultations with women physicians, and younger physicians, were associated with higher third observer and patient-based scores. Our findings reveal a need to empower Italian MS physicians with better communication and shared decision-making skills, and show in particular that attention to MS patient preferences for reception of information and involvement in health decisions, need to be improved.     

Effectiveness of a Government-Organized and Hospital-Initiated Treatment for Multidrug-Resistant Tuberculosis Patients-A Retrospective Cohort Study

Background

In contrast to the conventional model of hospital-treated and government directly observed treatment (DOT) for multidrug-resistant tuberculosis (MDR-TB) patient care, the Taiwan MDR-TB Consortium (TMTC) was launched in May 2007 with the collaboration of five medical care groups that have provided both care and DOT. This study aimed to determine whether the TMTC provided a better care model for MDR-TB patients than the conventional model.

Methods and Findings

A total of 651 pulmonary MDR-TB patients that were diagnosed nation-wide from January 2000-August 2008 were enrolled. Of those, 290 (45%) MDR-TB patients whose initial sputum sample was taken in January 2007 or later were classified as patients in the TMTC era. All others were classified as patients in the pre-TMTC era. The treatment success rate at 36 months was better in the TMTC era group (82%) than in the pre-TMTC era group (61%) (p<0.001). With multiple logistic regressions, diagnosis in the TMTC era (adjusted odds ratio (aOR) 2.8, 95% confidence interval (CI) 1.9–4.2) was an independent predictor of a higher treatment success rate at 36 months. With the time-dependent proportional hazards method, a higher treatment success rate was still observed in the TMTC era group compared to the pre-TMTC era group (adjusted hazard ratio 6.3, 95% CI 4.2–9.5).

Conclusion

The improved treatment success observed in the TMTC era compared to the pre-TMTC era is encouraging. The detailed TMTC components that contribute the most to the improved outcome will need confirmation in follow-up studies with large numbers of MDR-TB patients.     

Ocular Hypertension after Pediatric Cataract Surgery: Baseline Characteristics and First-Year Report

Monitoring intraocular pressure (IOP) is essential for pediatric cataract treatment but always difficult due to lack of cooperation in young children. We present the baseline characteristics and the first-year results of a long-term prospective cohort study, which are aimed to determine the relationship of the incidence of ocular hypertension (OH) in children after cataract surgery during the first-year period and the risk of developing late-onset glaucoma. Children were included with the following criteria: they were≤10 years old and scheduled to undergo cataract surgery with/without intraocular lens implantation; they were compliant with our follow-up protocol, which included monitoring IOP using a Tono-Pen under sedation or anesthesia. Incidence of OH, peak OH value, OH onset time and OH duration within a 12-month period following surgery were measured. In brief, 206 patients (379 eyes) were included and OH developed in 66 of 379 (17.4%) eyes. The mean follow-up period was 14.0±3.2 months (median, 12 months; range, 10–16 months). Moreover, 33 of 196 (16.8%) aphakic eyes and 33 of 183 (18.0%) IOL eyes were diagnosed with OH. The peak OH onset times were at 1-week (34/66, 51.5%) and 1-month (14/66, 21.2%) appointments postsurgery. The peak IOP value in the OH eyes was 29.9±7.5 mmHg (median, 29 mmHg; range, 21–48 mmHg). The duration of OH was 30.9±31.2 days (median, 30 days; range, 3–150 days). OH recurred in 13 eyes with a history of OH diagnosed within 1 month postsurgery (13/54, 24.1%), which needed temporary or long term use of antiglaucoma medications. In conclusion, the incidence of OH in children after cataract surgery was 17.4% during the first-year period. Children who have suffered elevated IOP in the first year after cataract surgery should be followed closely to determine if there is an increased risk of developing late-onset glaucoma.     

Reliability of FEV1/FEV6 to Diagnose Airflow Obstruction Compared with FEV1/FVC: The PLATINO Longitudinal Study

QUESTION

A 6-second spirometry test is easier than full exhalations. We compared the reliability of the ratio of the Forced expiratory volume in 1 second/Forced expiratory volume in 6 seconds (FEV₁/FEV₆) to the ratio of the FEV₁/Forced vital capacity (FEV₁/FVC) for the detection of airway obstruction.

METHODS

The PLATINO population-based survey in individuals aged 40 years and over designed to estimate the prevalence of post-Bronchodilator airway obstruction repeated for the same study participants after 5–9 years in three Latin-American cities.

RESULTS

Using the FEV₁/FVC<Lower limit of normal (LLN) index, COPD prevalence apparently changed from 9.8 to 13.2% in Montevideo, from 9.7 to 6.0% in São Paulo and from 8.5 to 6.6% in Santiago, despite only slight declines in smoking prevalence (from 30.8% to 24.3%). These changes were associated with differences in Forced expiratory time (FET) between the two surveys. In contrast, by using the FEV₁/FEV₆ to define airway obstruction, the changes in prevalence were smaller: 9.7 to 10.6% in Montevideo, 8.6 to 9.0% in São Paulo, and 7.5 to 7.9% in Santiago. Changes in the prevalence of COPD with criteria based on FEV₁/FVC correlated strongly with changes in the FET of the tests (R² 0.92) unlike the prevalence based on a low FEV₁/FEV₆ (R² = 0.40).

CONCLUSION

The FEV₁/FEV₆ is a more reliable index than FEV₁/FVC because FVC varies with the duration of the forced exhalation. Reporting FET and FEV₁/FEV₆<LLN helps to understand differences in prevalence of COPD obtained from FEV₁/FVC-derived indices.