A study of amylolytic streptococci from the rumen of the sheep

Ruminants comprise a large class of mammals distributed over the greater part of the earth's surface. The digestive system of these animals has been adapted for the digestion of grass and other cellulosic materials which form the natural diet of the group as a whole. Since this diet is both bulky and indigestible it is to be expected that the ratio of the capacity of the digestive system to body weight is higher in ruminants than it is for example in carnivorous animals. For this purpose the lower part of the oesophagus in the ruminant forms a large sac or rumen. The ingested food passes into the rumen and is mixed with the dense rumen microbial population. It is in the rumen that the digestion of cellulose by rumen bacteria takes place. The relationship between the rumen microflora and the host is thought to be symbiotic and since a large percentage of the world's human population is dependent directly or indirectly upon ruminants for food the economic importance of this symbiotic relationship cannot be over emphasised. Especially asp but for these animals much of the yearly crop of grass and other cellulosic material would not be converted into protein but broken down by soil bacteria and so be lost to man.In most parts of the world the continuous growth of plants is not possible, due to the sequence of the seasons or to the alternation of wet and dry periods. Thus, at intervals, herbivores must live on vegetation which has completed its growth cycle and has become dry, woody and resistant to digestion. The digestive system of the ruminant can utilise such material and as a result these animals are not seriously affected by drought and other inclement weather conditions. This may account for the success of the group in the modern world. In addition it is this ability to utilise cellulose efficiently that has led to the domestication and breeding of the ruminant

Studies on the Microbiology of Early Enamel Demineralisation

Two theories exist regarding the microbial aetiology of dented caries, namely the Specific and Non Specific Plaque Hypotheses. Almost all human studies have involved either cross-sectional or longitudinal designs, with consequent limitations associated with both techniques. Therefore, an in situ model was designed to overcome some of these problems, and while most studies have examined only the relationship between plaque microflora and enamel demineralisation, in this study, many other factors thought to influence the development of caries were also investigated. These included diet, salivary counts of Strep. mutans and lactobacilli, salivary flow rate and buffering capacity, as well as previous caries experience. Preliminary studies examined the reproducibility of experimental methods, compared plaque microflora obtained from enamel specimens mounted on an intra-oral appliance to that from the natural dentition, and examined the susceptibility of enamel to demineralisation. Results showed little variation between repeat identifications from numerous sub-divisions of one original plaque sample. Further, no qualitative difference in microflora between plaques associated with natural and exogenously derived tooth surfaces was found. Since enamel susceptibility was found to be as variable within one tooth as between teeth, it was considered appropriate to employ sections from different teeth in subsequent studies. As the initial work showed that factors such as subject and sequence of experimental runs affected the results to some extent, the statistical package chosen for analysis of the effect of different treatment protocols and plaque microflora on enamel demineralisation, took these other variables into account. The in situ study was performed using seven volunteers, and attempted to determine the relationship between plaque microflora and enamel demineralisation, under normal conditions and with extra-oral sucrose stressing, both with and without inoculation of the subject's own Strep. mutans. Results showed that considerable inter-subject variation existed, in terms of plaque microflora and demineralisation. Sucrose caused no significant effect on plaque microflora composition but, overall, was associated with a slight increase in demineralisation, compared to unstressed plaque. Success of Strep. mutans implantation was very variable, as shown by proportional counts of this organism in plaque samples, although in all subjects, isolation frequency rose following implantation. Overall, the combination of implantation and sucrose application resulted in significantly greater demineralisation. In general, the isolation frequency of Strep. mutans was significantly higher in plaque associated with greater amounts of mineral loss, with mean and median proportions showing a similar trend. Lactobacillus spp. proportions were significantly higher in plaque associated with the greatest amount of demineralisation. Veillonella fell in mean proportion with increasing demineralisation, and no trend was seen, in this regard, in relation to Actinomyces. However, these results relate only to microbial counts at the end of the three week experimental period. Hence, a study on the microflora of developing plaque during this period was performed. As the total microbial count increases during the early stage of plaque growth, enamel slabs, from which absolute counts can be obtained, were used, as proportional counts alone can be misleading when the total count is varying. These early studies showed a change from a Streptococcus - to an Actinomyces - dominated plaque with time, and found no difference between sucrose and unstressed plaque with regard to proportional and final absolute bacterial counts, but demonstrated that the maximum bacterial mass was achieved more rapidly in sucrose plaque. The results of the studies in this thesis are in keeping with those of other workers, and suggest that Strep. mutans has a major role in initiation of demineralisation, while lactobacilli are associated with more extensive lesions, and may be important in the progression of established lesions. (Abstract shortened by ProQuest.)

Integrating contextual and online self-reported data for personalized healthcare: a tennis elbow case study

Advances in sensors and mobile technology have helped evolve the use of eHealth, especially in the field of Chronic Pain. Chronic pain is a widespread problem where self-management is important. Current studies tend to collect data at sparse intervals due to the cost involved in collecting data using traditional instruments. We demonstrate how technology enables richer data collection frequencies to analyse the influence of patients’ context on their pain levels. In this paper, we present a case study as an add-on analysis to a clinical trial for Tennis Elbow. We explore the usefulness of on-line key data collected at higher frequencies in explaining or discovering changes in pain. This dataset allowed us to learn that there are no associations with temperature and humidity to this type of pain, that patients tend to have different pain experiences, and that pain at night tends to be higher than overall or activity-related pain

Maternal Personality Traits Moderate Treatment Response in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder

Background: Some mothers of children with attention-deficit/hyperactivity disorder (ADHD) present with maladaptive personality profiles (high neuroticism, low conscientiousness). The moderating effect of maternal personality traits on treatment outcomes for childhood ADHD has not been examined. We evaluate whether maternal neuroticism and conscientiousness moderated response in the Multimodal Treatment Study of Children with ADHD. This is one of the first study of this type. Methods: In a randomized controlled trial (RCT), 579 children ages 7-10 (M=8.5); 19.7% female; 60.8% White with combined-type ADHD were randomly assigned to systematic medication management (MedMgt) alone, comprehensive multicomponent behavioral treatment (Beh), their combination (Comb), or community comparison treatment-as-usual (CC). Latent Class Analysis and Linear Mixed Effects Models included 437 children whose biological mothers completed the NEO Five-Factor Inventory at baseline. Results: A 3-class solution demonstrated best fit for the NEO: MN&MC=moderate neuroticism and conscientiousness (n=284); HN&LC=high neuroticism, low conscientiousness (n=83); LN&HC=low neuroticism, high conscientiousness (n=70). Per parent-reported symptoms: children of mothers with HN&LC, but not LN&HC, had a significantly better response to Beh than to CC; Children of mothers with MN&MC and LN&HC, but not HN&LC, responded better to Comb&MedMgt than to Beh&CC. Per teacher-reported symptoms, children of mothers with HN&LC, but not LN&HC, responded significantly better to Comb than to MedMgt. Conclusions: Children of mothers with high neuroticism and low conscientiousness benefited more from behavioral treatments (Beh vs. CC; Comb vs. MedMgt) than other children. Evaluation of maternal personality may aid treatment selection for children with ADHD, though additional research on this topic is needed

Improving pathways to care through interventions cocreated with communities: a qualitative investigation of men’s barriers to tuberculosis care-seeking in an informal settlement in Blantyre, Malawi

Introduction Men have a higher prevalence of undiagnosed tuberculosis (TB) than women and can spend up to a year longer contributing to ongoing transmission in the community before receiving treatment. Health outcomes are often worse for patients with TB living in informal settlements especially men. This study aimed to understand the barriers preventing men from seeking care for TB and cocreate interventions to address these barriers. Methods We used qualitative research methods including in-depth interviews and participatory workshops. Researchers worked with women and men living in Bangwe, an informal settlement in Blantyre, Malawi to develop interventions that reflected their lived realities. The study took place over two phases, in the first phase we undertook interviews with men and women to explore barrier to care seeking, in the second phase we used participatory workshops to cocreate interventions to address barriers and followed up on issues emerging from the workshops with further interviews. In total, 30 interviews were conducted, and 23 participants joined participatory workshops. The team used a thematic analysis to analyse the data. Results Three interconnected thematic areas shaped men’s health TB seeking behaviour: precarious socioeconomic conditions; gendered social norms; and constraints in the health system. Insecurity of day labour with no provision for sick leave; pressure to provide for the household and a gendered desire not to appear weak and a severely under-resourced health system all contributed to men delaying care in this context. Identified interventions included improved patient–provider relations within the health-system, improved workers’ health rights and broader social support for households. Conclusion Improving mens’ pathways to care requires interventions that consider contextual issues by addressing individual level socioeconomic factors but also broader structural factors of gendered social dynamics and health systems environment

Gendered endings: Narratives of male and female suicides in the South African Lowveld

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11013-012-9258-y. Copyright @ Springer Science+Business Media, LLC 2012.Durkheim’s classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu’s concepts of ‘symbolic violence’ and ‘masculine domination’ provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu’s concept of ‘habitus’, the narrators of suicide stories did reflect critically upon gender constructs

Different responses of the blockade of the P2Y1 receptor with BPTU in human and porcine intestinal tissues and in cell cultures

Background: Gastrointestinal smooth muscle relaxation is accomplished by activation of P2Y 1 receptors, therefore this receptor plays an important role in regulation of gut motility. Recently, BPTU was developed as a negative allosteric modulator of the P2Y 1 receptor. Accordingly, the aim of this study was to assess the effect of BPTU on purinergic neurotransmission in pig and human gastrointestinal tissues. Methods: Ca 2+ imaging in tSA201 cells that express the human P2Y 1 receptor, organ bath and microelectrodes in tissues were used to evaluate the effects of BPTU on purinergic responses. Key results: BPTU concentration dependently (0.1 and 1 µmol L −1) inhibited the rise in intracellular Ca 2+ evoked by ADP in tSA201 cells. In the pig small intestine, 30 µmol L −1 BPTU reduced the fast inhibitory junction potential by 80%. Smooth muscle relaxations induced by electrical field stimulation were reduced both in pig ileum (EC 50 = 6 µmol L −1) and colon (EC 50 = 35 µmol L −1), but high concentrations of BPTU (up to 100 µmol L −1) had no effect on human colonic muscle. MRS2500 (1 µmol L −1) abolished all responses. Finally, 10 µmol L −1 ADPβS inhibited spontaneous motility and this was partially reversed by 30 µmol L −1 BPTU in pig, but not human colonic tissue and abolished by MRS2500 (1 µmol L −1). Conclusions & inferences: BPTU blocks purinergic responses elicited via P2Y 1 receptors in cell cultures and in pig gastrointestinal tissue. However, the concentrations needed are higher in pig tissue compared to cell cultures and BPTU was ineffective in human colonic tissue

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Transfusion Volume for Children with Severe Anemia in Africa

BACKGROUND Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level. METHODS In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim–sulfamethoxazole. The primary outcome was 28-day mortality. RESULTS A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P=0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days. CONCLUSIONS Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.

Immediate Transfusion in African Children with Uncomplicated Severe Anemia

Background The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. Methods In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim–sulfamethoxazole. Results A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P=0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. Conclusions There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring