Can Adults with Mild Cognitive Impairment Build Cognitive Reserve and Learn Mindfulness Meditation? Qualitative Theme Analyses from a Small Pilot Study.

BACKGROUND/OBJECTIVE: High levels of chronic stress negatively impact the hippocampus and are associated with increased incidence of mild cognitive impairment (MCI) and Alzheimer's disease. While mindfulness meditation may mitigate the effects of chronic stress, it is uncertain if adults with MCI have the capacity to learn mindfulness meditation. METHODS: 14 adults with MCI were randomized 2:1 to Mindfulness Based Stress Reduction (MBSR) or a wait-list control group. We conducted qualitative interviews with those who completed MBSR. Transcribed interviews were: a) coded using an emergent themes inductive approach informed by grounded theory; b) rated 0-10, with higher scores reflecting greater perceived benefit from, and understanding of, mindfulness meditation. Ratings were correlated with daily home practice times and baseline level of cognitive function. RESULTS: Seven themes emerged from the interviews: positive perceptions of class; development of mindfulness skills, including meta-cognition; importance of the group experience; enhanced well-being; shift in MCI perspective; decreased stress reactivity and increased relaxation; improvement in interpersonal skills. Ratings of perceived benefit and understanding ranged from 2-10 (mean = 7) and of 0-9.5 (mean = 6), respectively. Many participants experienced substantial benefit/understanding, some had moderate, and a few had minimal benefit/understanding. Understanding the key concepts of mindfulness was highly positively correlated with ≥20 minutes/day of home practice (r = 0.90) but not with baseline cognitive function (r = 0.13). CONCLUSIONS: Most adults with MCI were able to learn mindfulness meditation and had improved MCI acceptance, self-efficacy, and social engagement. Cognitive reserve may be enhanced through a mindfulness meditation program even in patients with MCI.

Meditation's impact on default mode network and hippocampus in mild cognitive impairment: a pilot study.

Those with high baseline stress levels are more likely to develop mild cognitive impairment (MCI) and Alzheimer's Disease (AD). While meditation may reduce stress and alter the hippocampus and default mode network (DMN), little is known about its impact in these populations. Our objective was to conduct a "proof of concept" trial to determine whether Mindfulness Based Stress Reduction (MBSR) would improve DMN connectivity and reduce hippocampal atrophy among adults with MCI. 14 adults with MCI were randomized to MBSR vs. usual care and underwent resting state fMRI at baseline and follow-up. Seed based functional connectivity was applied using posterior cingulate cortex as seed. Brain morphometry analyses were performed using FreeSurfer. The results showed that after the intervention, MBSR participants had increased functional connectivity between the posterior cingulate cortex and bilateral medial prefrontal cortex and left hippocampus compared to controls. In addition, MBSR participants had trends of less bilateral hippocampal volume atrophy than control participants. These preliminary results indicate that in adults with MCI, MBSR may have a positive impact on the regions of the brain most related to MCI and AD. Further research with larger sample sizes and longer-follow-up are needed to further investigate the results from this pilot study.

Variation in the genetic environments of bla(CTX-M-15) in Escherichia coli from the faeces of travellers returning to the United Kingdom.

OBJECTIVE: The genetic surroundings of bla(CTX-M-15) in Escherichia coli recovered from faeces of travellers returning to the UK from overseas were compared with those among established UK strains to provide further insights into the spread of bla(CTX-M-15) in the UK. METHODS: From August 2006 to January 2008, 1031 faecal specimens were collected at the North West London NHS Trust from general practice patients with a clinical history of diarrhoea following recent international travel. Cefuroxime-resistant E. coli were isolated on cystine-lactose-electrolyte deficient agar and those that produced extended-spectrum ß-lactamases (ESBLs) were identified by double disc synergy test (DDST). The molecular environments surrounding bla(CTX-M-15) were investigated by PCR, DNA sequencing, gene cloning and northern blotting. RESULTS: 182/1031 (18%) E. coli isolated from returning travellers gave a positive DDST, and were confirmed by PCR to produce CTX-M ESBLs; 174 (96%) had bla(CTX-M-15), including 21 belonging to clone ST131. Among these 174 isolates, the environment upstream of bla(CTX-M-15) consisted of either: (i) an intact ISEcp1 (n = 108); (ii) various lengths of truncated ISEcp1 (n = 58); or (iii) a 24 bp remnant of ISEcp1 (n = 8). Two different promoters were found to transcribe bla(CTX-M-15), resulting in different levels of cephalosporin resistance. CONCLUSION: E. coli with CTX-M-15 ESBL from returning travellers harboured previously seen UK bla(CTX-M-15) genetic environments (intact or 24 bp remnant of ISEcp1) as well as bla(CTX-M-15) genetic environments previously unseen in the UK (various lengths of truncated ISEcp1), which suggest overseas acquisition and highlight the difficulty of control in a time of population mobility and travel.

Brucellosis acquired by eating imported cheese.

Pyrexia of unknown origin is an important clinical presentation in both paediatric and adult medicine. We present a case of pyrexia of unknown origin in a 14 year-old boy which turned out to be due to infection with Brucella melitensis, despite the patient not having left Great Britain - an officially brucellosis-free country - in six years. Repeated history-taking provided a clue to the diagnosis.

Coordinated patterns of gene expressions for adult muscle build-up in transgenic mice expressing myostatin propeptide.

BACKGROUND: Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-beta, plays a dominant role in the genetic control of muscle mass. Myostatin is synthesized as a precursor protein, which generates the N-terminal propeptide and the C-terminal mature myostatin peptide by a post-translational cleavage event. Previously, transgenic over-expression of myostatin propeptide in skeletal muscle results in significant muscle growth in early stages of development. The objectives of present study were to further characterize muscle growth in later stages of life and to identify genes and their expression patterns that are responsible for adult muscle build-up by myostatin propeptide. RESULTS: Immunohistochemical staining with an antibody to the N-terminus indicates a high level of myostatin propeptide present in the muscles of transgenic mice while there were no apparent differences in myostatin protein distribution in the muscle fibers between the transgenic and wild-type mice. Main individual muscles increased by 76-152% in the transgenic mice over their wild-type littermate mice at 12 months of age. A large number of nuclei were localized in the central and basal lamina of the myofibers in the transgenic mice as the number of nuclei per fiber and 100 microm(2) area was significantly higher in transgenic mice than wild-type mice. By systemic comparisons of global mRNA expression patterns between transgenic mice and wild-type littermates using microarray and qRT-PCR techniques, we have identified distinct gene expression patterns to support adult muscle build-up by myostatin propeptide, which are comprised of enhanced expressions of myogenic regulatory factors and extracelullar matrix components, and differentially down-regulated expressions of genes related to protein degradation and mitochondrial ATP synthesis. CONCLUSION: The results present a coordinated pattern of gene expressions for reduced energy utilization during muscle build-up in adult stage. Enhanced muscle buildup by myostatin propeptide is sustained by reduced ATP synthesis as a result of a decreased activity of protein degradation. Myostatin propeptide may have a therapeutic application to the treatment of clinical muscle wasting problems by depressing myostatin activity.

Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.

BACKGROUND: Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions. METHODOLOGY/PRINCIPAL FINDINGS: This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing. CONCLUSIONS/SIGNIFICANCE: MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.

Teaching Tai Chi with mindfulness-based stress reduction to middle school children in the inner city: a review of the literature and approaches.

Tai Chi (TC) is the focus of a growing body of literature both qualitative and empirical. Yet there is a paucity of literature on teaching TC to either adolescents or children ages 10-13 presumably because of the level of attention and concentration TC requires. In the pediatric setting, TC appears best combined with other practice activities like mindfulness-based stress reduction (MBSR) that complement the practice of TC, sustain interest and synergistically enhance the benefits TC has been shown to produce in older populations. The literature on the effects of (MBSR) practices with children and teens are also limited. However, the corpus of TC studies suggests significant benefits could be transgenerational if presented in novel ways and taught in developmentally appropriate approaches to children. This chapter explores combining MBSR exercises with TC as one practice that can potentially accomplish this synergy. The chapter includes recommendations for a course design based on two projects created by the author integrating TC and MBSR for ages 11-14 in the inner city of Boston, Mass., USA.

Prospective study of sputum induction, gastric washing, and bronchoalveolar lavage for the diagnosis of pulmonary tuberculosis in patients who are unable to expectorate.

BACKGROUND: Many adults with pulmonary tuberculosis are unable to expectorate. Gastric washing, sputum induction using nebulized hypertonic saline, and bronchoscopy with bronchoalveolar lavage have all been used to obtain specimens for diagnosis, but to our knowledge, the timing and volume of induced sputum have not been well studied, and these 3 methods have not been compared. METHODS: The study recruited consecutive adult inpatients with chest radiography findings suggestive of tuberculosis who were unable to expectorate. Subjects provided 3 induced sputum samples for culture on day 1 and additional samples on days 2 and 3. In addition, gastric washing specimens were collected on days 1, 2, and 3. A proportion of subjects with negative smear results underwent bronchoalveolar lavage. RESULTS: The study recruited 140 subjects. Among 107 subjects who provided 3 gastric washing specimens and at least 3 induced sputum specimens, 43% had cultures positive for Mycobacterium tuberculosis. Use of 3 induced sputum samples detected more cases than did use of 3 gastric washings (39% vs. 30%; P=.03). Among 79 subjects with culture results for all 5 induced sputum specimens, there was no difference in yield between samples obtained by induced sputum induction performed in a single day or that performed over 3 days (34% vs. 37%; P=.63). There was no association between sputum volume and positive culture results. No additional cases were diagnosed in the 21 patients who underwent bronchoscopy. CONCLUSIONS: Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously. Use of bronchoscopy with bronchoalveolar lavage did not increase diagnostic sensitivity. Samples could be collected in 1 day, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay.

Lactation induction as a predictor of post-parturition transgene expression in bovine milk.

The bovine's long generation interval results in a delay of several years when evaluating mammary specific transgenes in genetically engineered animals. This experiment was conducted to evaluate the feasibility of reducing that waiting period. Lactation was induced in prepubertal bull and heifer calves as a means of predicting transgene behaviour during subsequent post-parturient lactations in the heifers themselves, and in daughters sired by the bulls. The animals carry a lactation-specific transgene encoding lysostaphin, an antimicrobial protein that kills Staphlococcus aureus, a mastitis-causing pathogen. Oestrogen, progesterone and dexamethasone were administered as previously described (Ball et al. 2000) to nine heifers (five transgenics) ranging in weight from 80 to 145 kg. Eight bull calves (seven transgenics) weighing 81-178 kg received additional oestrogen and progesterone injection prior to dexamethasone treatment. All nine heifers responded to the milk induction scheme yielding between 19 ml and 4.5 l over 5 d. Milk volume from the four responding males (30 microl to 2.5 ml) was significantly less than that harvested from females (P=0.025). Only bull calves >117 kg had a positive response. Lysostaphin was detected in all transgenic prepubertal heifers and in two transgenic prepubertal bull calves induced. A positive relationship was observed between lysostaphin's stapholytic activity in the two types of lactations (r2=0.907, P<0.001) thus providing a useful means of predicting subsequent lysostaphin production in post-partum milk.

Engineering disease resistant cattle.

Mastitis is a disease of the mammary gland caused by pathogens that find their way into the lumen of the gland through the teat canal. Mammary gland infections cost the US dairy industry approximately $2 billion dollars annually and have a similar impact in Europe. In the absence of effective treatments or breeding strategies to enhance mastitis resistance, we have created transgenic dairy cows that express lysostaphin in their mammary epithelium and secrete the antimicrobial peptide into milk. Staphylococcus aureus, a major mastitis pathogen, is exquisitely sensitive to lysostaphin. The transgenic cattle resist S. aureus mammary gland challenges, and their milk kills the bacteria, in a dose dependent manner. This first step in protecting cattle against mastitis will be followed by introduction of other genes to deal with potential resistance issues and other mastitis causing organisms. Care will be taken to avoid altering milk's nutritional and manufacturing properties. Multi-cistronic constructs may be required to achieve our goals as will other strategies possibly involving RNAi and gene targeting technology. This work demonstrates the possibility of using transgenic technology to address disease problems in agriculturally important species.

Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance.

Obesity and insulin resistance cause serious consequences to human health. To study effects of skeletal muscle growth on obesity prevention, we focused on a key gene of skeletal muscle named myostatin, which plays an inhibitory role in muscle growth and development. We generated transgenic mice through muscle-specific expression of the cDNA sequence (5'-region 886 nucleotides) encoding for the propeptide of myostatin. The transgene effectively depressed myostatin function. Transgenic mice showed dramatic growth and muscle mass by 9 weeks of age. Here we reported that individual major muscles of transgenic mice were 45-115% heavier than those of wild-type mice, maintained normal blood glucose, insulin sensitivity, and fat mass after a 2-month regimen with a high-fat diet (45% kcal fat). In contrast, high-fat diet induced wild-type mice with 170-214% more fat mass than transgenic mice and developed impaired glucose tolerance and insulin resistance. Insulin signaling, measured by Akt phosphorylation, was significantly elevated by 144% in transgenic mice over wild-type mice fed a high-fat diet. Interestingly, high-fat diet significantly increased adiponectin secretion while blood insulin, resistin, and leptin levels remained normal in the transgenic mice. The results suggest that disruption of myostatin function by its propeptide favours dietary fat utilization for muscle growth and maintenance. An increased secretion of adiponectin may promote energy partition toward skeletal muscles, suggesting that a beneficial interaction between muscle and adipose tissue play a role in preventing obesity and insulin resistance.

Blind and sighted pedestrians' judgments of gaps in traffic at roundabouts.

This paper reports two experiments about street crossing under conditions of free flowing traffic, with a focus on modem roundabout intersections. Experiment 1 was conducted at three roundabouts varying in size and traffic volume. Six totally blind and six sighted adults judged whether gaps in traffic were long enough to permit crossing to the median (splitter) island before the next vehicle arrived. Gap distributions and measures of judgment quality are reported. Overall, blind participants were about 2.5 times less likely to make correct judgments than sighted participants, took longer to detect crossable gaps, and were more likely to miss crossable gaps altogether. However, the differences were significant only at the two higher volume roundabouts. In Experiment 2, we evaluated the response of drivers to pedestrians with and without mobility devices (i.e., long canes, dog guides). The experiment was conducted at a single-lane roundabout, a midblock crossing, and a two-way-stop-controlled intersection. Site-specific characteristics appeared to have a greater impact on drivers' yielding than did a mobility device. Actual or potential applications of this research include the development of methods for assessing pedestrian safety and driver behavior as well as identifying intersections that may require modification in order to be accessible to blind pedestrians.

Tai Chi and mindfulness-based stress reduction in a Boston Public Middle School.

This article provides a description of a clinical project that used combined Tai Chi and mindfulness-based stress reduction as an educational program. The 5-week program demonstrated that sustained interest in this material in middle school-aged boys and girls is possible. Statements the boys and girls made in the process suggested that they experienced well-being, calmness, relaxation, improved sleep, less reactivity, increased self-care, self-awareness, and a sense of interconnection or interdependence with nature. The curriculum is described in detail for nurses, teachers, and counselors who want to replicate this type of instruction for adolescent children. This project infers that Tai Chi and mindfulness-based stress reduction may be transformational tools that can be used in educational programs appropriate for middle school-aged children. Recommendations are made for further study in schools and other pediatric settings.

Comparison of gene expression in individual preimplantation bovine embryos produced by in vitro fertilisation or somatic cell nuclear transfer.

In vitro fertilisation (IVF) and somatic cell nuclear transfer (SCNT) have been implicated in a variety of developmental abnormalities. Aberrant gene expression is likely to account for much of the diminished viability and developmental abnormalities observed. In the present study, the expression of multiple genes in IVF and SCNT bovine blastocyst-stage embryos were evaluated and compared with in vivo-produced embryos. Eleven genes expressed at and following maternal-zygotic transcription transition were evaluated in individual blastocysts by real-time polymerase chain reaction following RNA amplification. A subset of those genes was also evaluated in individual IVF and SCNT eight-cell embryos. A fibroblast-specific gene, expressed by nuclear donor cells, was also evaluated in IVF and SCNT embryos. The observed gene expression pattern at the eight-cell stage was not different between IVF and SCNT embryos (P > 0.05). In vitro fertilisation and SCNT blastocyst expression was lower (P < 0.01) for all genes compared with their in vivo-produced counterparts, except for lactate dehydrogenase isoenzyme A (P < 0.001). The patterns of gene expression of the IVF and SCNT blastocysts were indistinguishable. Neither SCNT eight-cell nor blastocyst-stage embryos expressed the gene used as a fibroblast marker (collagen VIalpha1). For the genes evaluated, the level of expression was influenced more by the environment than by the method used to produce the embryos. These results support the notion that if developmental differences observed in IVF- and SCNT-produced fetuses and neonates are the result of aberrant gene expression during the preimplantation stage, those differences in expression are subtle.

Characterization and management of paradoxical upgrading reactions in HIV-uninfected patients with lymph node tuberculosis.

In a retrospective analysis, paradoxical deterioration of lymph node tuberculosis in human immunodeficiency virus-uninfected patients was common, occurring in 25 (23%) of 109 patients after treatment had been given for a median of 46 days (interquartile range, 21-139 days) and persisting for a median of 67.5 days (interquartile range, 34-111 days). We found no association between the use of steroids and the duration of reaction.

Genetically enhanced cows resist intramammary Staphylococcus aureus infection.

Mastitis, the most consequential disease in dairy cattle, costs the US dairy industry billions of dollars annually. To test the feasibility of protecting animals through genetic engineering, transgenic cows secreting lysostaphin at concentrations ranging from 0.9 to 14 micrograms/ml [corrected] in their milk were produced. In vitro assays demonstrated the milk's ability to kill Staphylococcus aureus. Intramammary infusions of S. aureus were administered to three transgenic and ten nontransgenic cows. Increases in milk somatic cells, elevated body temperatures and induced acute phase proteins, each indicative of infection, were observed in all of the nontransgenic cows but in none of the transgenic animals. Protection against S. aureus mastitis appears to be achievable with as little as 3 micrograms/ml [corrected] of lysostaphin in milk. Our results indicate that genetic engineering can provide a viable tool for enhancing resistance to disease and improve the well-being of livestock.

Directional guidance from audible pedestrian signals for street crossing.

Typical audible pedestrian signals indicate when the pedestrian walk interval is in effect but provide little, or even misleading information for directional alignment. In three experiments, blind and blindfolded sighted adults crossed a simulated crossing with recorded traffic noise to approximate street sounds. This was done to investigate how characteristics of signal presentation affected usefulness of the auditory signal for guiding crossing behaviour. Crossing was more accurate when signals came only from the far end of the crossing rather than the typical practice of presenting signals simultaneously from both ends. Alternating the signal between ends of the crossing was not helpful. Also, the customary practice of signalling two parallel crossings at the same time drew participants somewhat toward the opposite crossing. Providing a locator tone at the end of the crossing during the pedestrian clearance interval improved crossing accuracy. These findings provide a basis for designing audible pedestrian signals to enhance directional guidance. The principal findings were the same for blind and sighted participants and applied across a range of specific signals (e.g. chirps, clicks, voices).

Comparison of bronchoscopy and gastric washings in the investigation of smear-negative pulmonary tuberculosis.

This study compares the utility of gastric washings (GWs) and bronchoscopy in the diagnosis of smear-negative pulmonary tuberculosis (TB). The aim of the study was to identify which investigation or combination of investigations provided the greatest yield of positive Mycobacterium tuberculosis cultures of samples from patients with smear-negative pulmonary TB. We retrospectively analyzed the medical records of 180 patients with smear-negative pulmonary TB. The positive culture yield for bronchoalveolar lavage fluid (62 [34%] of 180 patients) was significantly greater than that for specimens from 3 GWs (32 [21%] of 149 patients) (P=.02). Combining GW and bronchoscopy increased the positive culture yield: bronchoscopy combined with 2 GWs resulted in a positive culture rate of 38%. Bronchoscopy is superior to GW in the diagnosis of smear-negative pulmonary TB; however, the combination of bronchoscopy and 2 GWs should be regarded as optimal for the diagnosis of smear-negative pulmonary TB.

Expression of lysostaphin in milk of transgenic mice affects the growth of neonates.

As an initial step towards enhancing mastitis resistance in dairy animals, we generated BLG-Lys transgenic mice that secrete lysostaphin, a potent antistaphylococcal protein, in their milk. In the current study, we continue our assessment of lysostaphin as a suitable antimicrobial protein for mastitis resistance and have investigated mammary gland development and function in three lines of transgenic mice. As the lines were propagated, there was a tendency for fewer BLG-Lys litters to survive to weaning (51% as compared to 90% for nontransgenic lines, p = 0.080). Nontransgenic pups fostered on dams from these three lines exhibited diminished growth rates during the first week of lactation. Rates of gain became comparable to pups on nontransgenic dams at later time points. Initial slow growth also resulted in decreased weaning weights for pups nursed by transgenic dams (15.35 +/- 0.27 g) when compared to pups delivered and nursed by nontransgenic dams (18.61 +/- 0.61 g; p < 0.001), but the effect was temporary, as similar weights were attained by adulthood. Milk yield at peak lactation was not different between BLG-Lys (0.79 +/- 0.33 g) and nontransgenic (0.91 +/- 0.38 g; p = 0.166) dams. Histological examination of the transgenic mammary glands during gestation revealed no differences when compared to control glands; however, at early lactational stages, the BLG-Lys glands exhibited less alveolar area than control glands and a delay in lobulo-alveolar maturation. The results clearly demonstrate reduced growth of neonates on BLG-Lys dams; whether the poor pup performance can be attributed to delayed mammary development or the gland development merely reflects reduced suckling stimuli from the pups remains to be determined.