Constant peptidoglycan density in the sacculus of escherichia coli B/r growing at different rates

The determination and maintenance of bacterial cell shape are problems still far from being understood (reviewed [ 1,2]). Several models have been advanced during the last decade, for mechanisms governing th

Using a Body-Fixed Sensor to Identify Subclinical Gait Difficulties in Older Adults with IADL Disability: Maximizing the Output of the Timed Up and Go

Objective: The identification and documentation of subclinical gait impairments in older adults may facilitate the appropriate use of interventions for preventing or delaying mobility disability. We tested whether measures derived from a single body-fixed sensor worn during traditional Timed Up and Go (TUG) testing could identify subclinical gait impairments in community dwelling older adults without mobility disability. Methods: We used data from 432 older adults without dementia (mean age 83.30±7.04 yrs, 76.62% female) participating in the Rush Memory and Aging Project. The traditional TUG was conducted while subjects wore a body-fixed sensor. We derived measures of overall TUG performance and different subtasks including transitions (sit-to-stand, stand-to-sit), walking, and turning. Multivariate analysis was used to compare persons with and without mobility disability and to compare individuals with and without Instrumental Activities of Daily Living disability (IADL-disability), all of whom did not have mobility disability. Results: As expected, individuals with mobility disability performed worse on all TUG subtasks (p<0.03), compared to those who had no mobility disability. Individuals without mobility disability but with IADL disability had difficulties with turns, had lower yaw amplitude (p<0.004) during turns, were slower (p<0.001), and had less consistent gait (p<0.02). Conclusions: A single body-worn sensor can be employed in the community-setting to complement conventional gait testing. It provides a wide range of quantitative gait measures that appear to help to identify subclinical gait impairments in older adults

The relationship between non-communicable disease occurrence and poverty—evidence from demographic surveillance in Matlab, Bangladesh

In low-income countries, a growing proportion of the disease burden is attributable to non- communicable diseases (NCDs). There is little knowledge, however, of their impact on wealth, human capital, economic growth or household poverty. This article estimates the risk of being poor after an NCD death in the rural, low-income area of Matlab, Bangladesh. In a matched cohort study, we estimated the 2-year relative risk (RR) of being poor in Matlab households with an NCD death in 2010. Three separate measures of household economic status were used as outcomes: an asset-based index, self-rated household economic condition and total household landholding. Several estimation methods were used including contingency tables, log-binomial regression and regression standardization and machine learning. Households with an NCD death had a large and significant risk of being poor. The unadjusted RR of being poor after death was 1.19, 1.14 and 1.10 for the asset quintile, self-rated condition and landholding outcomes. Adjusting for household and individual level independent variables with log-binomial regression gave RRs of 1.19 [standard error (SE) 0.09], 1.16 (SE 0.07) and 1.14 (SE 0.06), which were found to be exactly the same using regression standardization (SE: 0.09, 0.05, 0.03). Machine learning-based standardization produced slightly smaller RRs though still in the same order of magnitude. The findings show that efforts to address the burden of NCD may also combat household poverty and provide a return beyond improved health. Future work should attempt to disentangle the mechanisms through which economic impacts from an NCD death occur

Associations between Quantitative Mobility Measures Derived from Components of Conventional Mobility Testing and Parkinsonian Gait in Older Adults

Objective: To provide objective measures which characterize mobility in older adults assessed in the community setting and to examine the extent to which these measures are associated with parkinsonian gait. Methods: During conventional mobility testing in the community-setting, 351 ambulatory non-demented Memory and Aging Project participants wore a belt with a whole body sensor that recorded both acceleration and angular velocity in 3 directions. We used measures derived from these recordings to quantify 5 subtasks including a) walking, b) transition from sit to stand, c) transition from stand to sit, d) turning and e) standing posture. Parkinsonian gait and other mild parkinsonian signs were assessed with a modified version of the original Unified Parkinson’s Disease Rating Scale (mUPDRS). Results: In a series of separate regression models which adjusted for age and sex, all 5 mobility subtask measures were associated with parkinsonian gait and accounted for 2% to 32% of its variance. When all 5 subtask measures were considered in a single model, backward elimination showed that measures of walking sit to stand and turning showed independent associations with parkinsonian gait and together accounted for more than 35% of its variance. Cross-validation using data from a 2nd group of 258 older adults showed similar results. In similar analyses, only walking was associated with bradykinesia and sway with tremor. Interpretation Quantitative mobility subtask measures vary in their associations with parkinsonian gait scores and other parkinsonian signs in older adults. Quantifying the different facets of mobility has the potential to facilitate the clinical characterization and understanding the biologic basis for impaired mobility in older adults

Transcriptional Silencing of Multiple Genes in Trophozoites of Entamoeba histolytica

In a previous work we described the transcriptional silencing of the amoebapore A (AP-A) gene (Ehap-a) of Entamoeba histolytica strain HM-1:IMSS. The silencing occurred following transfection with a plasmid containing a 5′ upstream region (473 bp) of Ehap-a that included a truncated segment (140 bp) of a short interspersed nuclear element (SINE1). Silencing remained in effect even after removal of the plasmid (clone G3). Neither short interfering RNA nor methylated DNA were detected, but the chromatin domain of Ehap-a in the gene-silenced trophozoites was modified. Two other similar genes (Ehap-b and one encoding a Saposin-like protein, SAPLIP 1) also became silenced. In the present work we demonstrate the silencing of a second gene of choice, one that encodes the light subunit of the Gal/GalNAc inhibitable lectin (Ehlgl1) and the other, the cysteine proteinase 5 (EhCP-5). This silencing occurred in G3 trophozoites transfected with a plasmid in which the 473 bp 5′ upstream Ehap-a fragment was directly ligated to the second gene. Transcriptional silencing occurred in both the transgene and the chromosomal gene. SINE1 sequences were essential, as was a direct connection between the Ehap-a upstream region and the beginning of the open reading frame of the second gene. Gene silencing did not occur in strain HM-1:IMSS with any of these plasmid constructs. The trophozoites with two silenced genes were virulence-attenuated as were those of clone G3. In addition, trophozoites not expressing Lgl1 and AP-A proteins had a significantly reduced ability to cap the Gal/GalNAc-lectin to the uroid region when incubated with antibodies against the heavy (170 kDa) subunit of the lectin. Lysates of trophozoites lacking cysteine proteinase 5 and AP-A proteins had 30% less cysteine proteinase activity than those of HM-1:IMSS strain or the G3 clone. Silencing of other genes in G3 amoebae could provide a model to study their various functions. In addition, double gene-silenced, virulence-attenuated trophozoites may be an important tool in vaccine development

Tackling socioeconomic inequalities and non-communicable diseases in low-income and middle-income countries under the Sustainable Development agenda

Five Sustainable Development Goals (SDGs) set targets that relate to the reduction of health inequalities nationally and worldwide. These targets are poverty reduction, health and wellbeing for all, equitable education, gender equality, and reduction of inequalities within and between countries. The interaction between inequalities and health is complex: better economic and educational outcomes for households enhance health, low socioeconomic status leads to chronic ill health, and non-communicable diseases (NCDs) reduce income status of households. NCDs account for most causes of early death and disability worldwide, so it is alarming that strong scientific evidence suggests an increase in the clustering of non-communicable conditions with low socioeconomic status in low-income and middle-income countries since 2000, as previously seen in high-income settings. These conditions include tobacco use, obesity, hypertension, cancer, and diabetes. Strong evidence from 283 studies overwhelmingly supports a positive association between low-income, low socioeconomic status, or low educational status and NCDs. The associations have been differentiated by sex in only four studies. Health is a key driver in the SDGs, and reduction of health inequalities and NCDs should become key in the promotion of the overall SDG agenda. A sustained reduction of general inequalities in income status, education, and gender within and between countries would enhance worldwide equality in health. To end poverty through elimination of its causes, NCD programmes should be included in the development agenda. National programmes should mitigate social and health shocks to protect the poor from events that worsen their frail socioeconomic condition and health status. Programmes related to universal health coverage of NCDs should specifically target susceptible populations, such as elderly people, who are most at risk. Growing inequalities in access to resources for prevention and treatment need to be addressed through improved international regulations across jurisdictions that eliminate the legal and practical barriers in the implementation of non-communicable disease control

Voluntary Medical Male Circumcision: Strategies for Meeting the Human Resource Needs of Scale-Up in Southern and Eastern Africa

Kelly Curran and colleagues conducted a program review to identify human resource approaches that are being used to improve voluntary medical male circumcision volume and efficiency, identifying several innovative responses to human resource challenges

An ex-vivo Human Intestinal Model to Study Entamoeba histolytica Pathogenesis

Amoebiasis (a human intestinal infection affecting 50 million people every year) is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase) and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor) were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon) was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5), which have major roles in cell death, adhesion (to target cells or mucus) and mucus degradation, respectively) were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion