Vaccines for preventing influenza in the elderly.
Influenza vaccination of elderly individuals is recommended worldwide and has been targeted toward the elderly and those at serious risk of complications. Our aim was to review the evidence of efficacy, effectiveness and safety of influenza vaccines in individuals aged 65 years or older. We searched the following databases on The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness (Issue 1, 2006); MEDLINE (January 1966 to March Week 3 2006); EMBASE (Dialog 1974 to 1979; SilverPlatter 1980 to December 2005); Biological Abstracts (SilverPlatter 1969 to December 2004); and Science Citation Index (Web of Science 1974 to December 2004). We considered randomised, quasi-randomised, cohort and case-control studies assessing efficacy against influenza (laboratory-confirmed cases) or effectiveness against influenza-like illness (ILI) or safety. Any influenza vaccine given independently, in any dose, preparation or time schedule, compared with placebo or with no intervention was considered. We grouped reports first according to the setting of the study (community or long-term care facilities) and then by level of viral circulation and vaccine matching. We further stratified by co-administration of pneumococcal polysaccharide vaccine (PPV) and by different types of influenza vaccines. We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications and deaths. Sixty-four studies were included in the efficacy / effectiveness assessment, resulting in 96 data sets. In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against ILI was 23% (6% to 36%) and non-significant against influenza (RR 1.04: 95% CI 0.43 to 2.51). We found no correlation between vaccine coverage and ILI attack rate. Well matched vaccines prevented pneumonia (VE 46%; 30% to 58%), hospital admission (VE 45%; 16% to 64%) and deaths from influenza or pneumonia (VE 42%, 17% to 59%). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19; 95% CI 0.02 to 2.01), ILI (RR 1.05: 95% CI 0.58 to 1.89), or pneumonia (RR 0.88; 95% CI 0.64 to 1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%; 12% to 38%) and all-cause mortality (VE 42%; 24% to 55%). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%; 21% to 33%), respiratory diseases (VE* 22%; 15% to 28%) and cardiac disease (VE* 24%; 18% to 30%); and for all-cause mortality (VE* 47%; 39% to 54%). The public health safety profiles of the vaccines appear to be acceptable. In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest. The apparent high effectiveness of the vaccines in preventing death from all causes may reflect a baseline imbalance in health status and other systematic differences in the two groups of participants.


Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer care.
This study was conducted to evaluate the effect of stage at diagnosis, age, and level of comorbidity (presence of other illness) on the costs of treating three types of cancer among members of a health maintenance organization. Among 388,000 members enrolled anytime during 1990 and 1991 in Group Health Cooperative (GHC) of Puget Sound (Washington State), we estimated the total and net direct costs of medical care for colon, prostate, and breast cancers, including both incident (290, 554, and 645 patients, respectively) and prevalent (1046, 1295, and 2299 patients, respectively) cases. We summarized costs for initial, continuing, and terminal phases of care. Net costs were the difference between the costs of the care of each case subject and the average costs of the care for all enrollees without the cancer of interest who were of the same sex and in the same 5-year age group. Differences in estimated total and net costs by stage at diagnosis, age, and comorbidity were separately evaluated using multivariate regression modeling. All P values were two-sided. Comorbidity was based on a score calculated from 1988 pharmacy data. Total costs of initial care increased with stage at diagnosis for colon (P = .0013) and breast (P < .0001) cancer cases, but not for prostate cancer cases. Total initial costs decreased with age for prostate (P = .0225) and breast (P = .0002) cancers but did not change with degree of comorbidity for any of the three cancers. Total continuing medical care costs increased with stage at diagnosis for colon (P < .0001) and breast (P < .0001) cancer cases but not for prostate cancer cases. Total terminal care costs were similar by stage for all three cancers. Net initial costs differed with stage for all three cancers (P < .05). Net continuing care costs increased with stage (P < .0001) and decreased with age (P < .001) for colon and breast cancers but not for prostate cancer. Net continuing care costs decreased with comorbidity for all three cancers (P = .004, P = .011, and P < .0001 for colon, prostate, and breast cancers, respectively). Among regional stage cancers, continuing care costs decreased with age for colon (P < .0017) and breast (P = .033) cancers but not for prostate cancers. The results show that total costs vary by stage at diagnosis and age, but the patterns of variation differ for each cancer. Costs of cancer are not simply additive to costs of other conditions. More needs to be done to explore the reasons and implications of age-related cost differences. Cost-effectiveness analyses of cancer control interventions that shift cancer stage distributions may need to consider both the age and comorbidity of the target populations.


Nucleostemin rejuvenates cardiac progenitor cells and antagonizes myocardial aging.
Functional decline in stem cell-mediated regeneration contributes to aging associated with cellular senescence in c-kit+ cardiac progenitor cells (CPCs). Clinical implementation of CPC-based therapy in elderly patients would benefit tremendously from understanding molecular characteristics of senescence to antagonize aging. Nucleostemin (NS) is a nucleolar protein regulating stem cell proliferation and pluripotency. This study sought to demonstrate that NS preserves characteristics associated with "stemness" in CPCs and antagonizes myocardial senescence and aging. CPCs isolated from human fetal (fetal human cardiac progenitor cell [FhCPC]) and adult failing (adult human cardiac progenitor cell [AhCPC]) hearts, as well as young (young cardiac progenitor cell [YCPC]) and old mice (old cardiac progenitor cell [OCPC]), were studied for senescence characteristics and NS expression. Heterozygous knockout mice with 1 functional allele of NS (NS+/-) were used to demonstrate that NS preserves myocardial structure and function and slows characteristics of aging. NS expression is decreased in AhCPCs relative to FhCPCs, correlating with lowered proliferation potential and shortened telomere length. AhCPC characteristics resemble those of OCPCs, which have a phenotype induced by NS silencing, resulting in cell flattening, senescence, multinucleated cells, decreased S-phase progression, diminished expression of stemness markers, and up-regulation of p53 and p16. CPC senescence resulting from NS loss is partially p53 dependent and is rescued by concurrent silencing of p53. Mechanistically, NS induction correlates with Pim-1 kinase-mediated stabilization of c-Myc. Engineering OCPCs and AhCPCs to overexpress NS decreases senescent and multinucleated cells, restores morphology, and antagonizes senescence, thereby preserving phenotypic properties of "stemness." Early cardiac aging with a decline in cardiac function, an increase in senescence markers p53 and p16, telomere attrition, and accompanied CPC exhaustion is evident in NS+/- mice. Youthful properties and antagonism of senescence in CPCs and the myocardium are consistent with a role for NS downstream from Pim-1 signaling that enhances cardiac regeneration.


Exercise interval training: an improved stimulus for improving the physiology of pre-diabetes.
Current reports estimate that type II diabetes (T2D) affects 5-8% of adults. Also recognized is a transitional group of patients whose fasting blood glucose is abnormal; yet, not considered high enough to be diagnosed as diabetes. Defined as "pre-diabetes" these individuals have impaired fasting glucose (IFG; fasting glucose 100-125 mg/dL), impaired glucose tolerance (IGT; 2 h glucose 140-199 mg/dL) or both. Two unifying features associated with IFG and IGT are their strong links to obesity and physical inactivity, which lead independently and collectively toward the erosion of various cellular processes affecting glucose control. In contrast, regular exercise positively influences IFG/IGT and obesity, thus representing an important therapy for preventing diabetes via the enhancement of several mechanisms of action. These include improved glucose metabolism, muscle respiratory capacity, mitochondrial respiratory chain activity and beta-oxidation. Contemporary exercise guidelines provided by various organizations recommend that exercise be performed at intensities ranging from 40% to 85% of maximal aerobic capacity. Unfortunately, little is known regarding the optimal intensity to best facilitate the physiological benefits associated with exercise. An evolving body of research shows that interval training produces greater changes in exercise capacity than traditional aerobic training. Interval training involves bouts of high exercise intensity (15s to 4 min; >90% VO(2max)) followed by a recovery period (40-50% VO(2max)) of equal or longer duration than the associated work interval. Though the net effect of interval training is aerobic, periodic excursions involving anaerobic energy pathways theoretically "push" the mitochondria to greater improvements in exercise capacity, mitochondrial biogenesis, enzymatic markers associated with glycolysis, aerobic metabolism and beta (beta)-oxidation. Though traditionally viewed as a training modality for athletes, a recent report has demonstrated that interval training is more effective than traditional aerobic exercise training in patients up to approximately 75 y of age and with low functional capacities (VO(2max) 13 ml/kg/min) by producing superior improvements in VO(2max), sub-maximal exercise tolerance, levels of peroxisome proliferator activator protein-gamma co-activator1alpha (PGC-1alpha), and quality of life indices more so than traditional aerobic exercise training. Erosion in these same markers is present in populations with pre-diabetes and T2D. The principal hypothesis of this paper is that interval training will provide a more powerful stimulus for improving insulin sensitivity than traditional low-to-moderate intensity aerobic conditioning. This theory further proposes that these affects will be due to greater changes in specific metabolic pathways associated with glycolysis, aerobic metabolism, beta-oxidation, and mitochondrial biogenesis.


Under Reporting of Suicide Ideation in US Army Population Screening: An Ongoing Challenge.
Previous research in US Army Soldiers shows rates of mental health concerns as two to four times higher on anonymous surveys than on postdeployment health assessments. In this study, Soldiers presenting for health reassessment completed two questionnaires on suicide risk factors: one linked to the health assessment and one anonymous. About 5.1% of respondents reported suicide ideation on the anonymous questionnaire, 3.0% on the linked questionnaire, and 0.9% on the health reassessment. About 56.4% who reported suicide ideation anonymously told nobody of their thoughts. Current screening procedures identify only one in seven Soldiers experiencing suicide ideation and highlight the need for alternative risk-detection strategies.


Do price subsidies on artemisinin combination therapy for malaria increase household use? Evidence from a repeated cross-sectional study in remote regions of Tanzania.
The Affordable Medicines Facility-malaria (AMFm) is a pilot program that uses price subsidies to increase access to Artemisinin Combination Therapies (ACTs), currently the most effective malaria treatment. Recent evidence suggests that availability and affordability of ACTs in retail sector drug shops (where many people treat malaria) has increased under the AMFm, but it is unclear whether household level ACT use has increased. household surveys were conducted in two remote regions of Tanzania (Mtwara and Rukwa) in three waves: March 2011, December 2011 and March 2012, corresponding to 3, 13 and 16 months into the AMFm implementation respectively. Information about suspected malaria episodes including treatment location and medications taken was collected. Respondents were also asked about antimalarial preferences and perceptions about the availability of these medications. Significant increases in ACT use, preference and perceived availability were found between Rounds 1 and 3 though not for all measures between Rounds 1 and 2. ACT use among suspected malaria episodes was 51.1% in March 2011 and increased by 10.9 percentage points by Round 3 (p = .017). The greatest increase was among retail sector patients, where ACT use increased from 31% in Round 1 to 49% in Round 2 (p = .037) and to 61% (p<.0001) by Round 3. The fraction of suspected malaria episodes treated in the retail sector increased from 30.2% in Round 1 to 46.7% in Round 3 (p = .0009), mostly due to a decrease in patients who sought no treatment at all. No significant changes in public sector treatment seeking were found. The AMFm has led to significant increases in ACT use for suspected malaria, especially in the retail sector. No evidence is found supporting the concerns that the AMFm would crowd out public sector treatment or neglect patients in remote areas and from low SES groups.


Single-stage Transpedicular Vertebrectomy and Expandable Cage Placement for Treatment of Unstable Mid and Lower Lumbar Burst Fractures.
Retrospective clinical and radiographic study. To examine the efficacy and safety of vertebrectomy and expandable cage placement by a single-stage posterior approach for unstable mid and lower lumbar burst fractures (below the L3). Patients with unstable mid and lower lumbar burst fractures require surgical treatment to relieve pain, address paralysis, and stabilize the spine to prevent further segmental deformity. However, controversy remains regarding the optimal surgical treatment. Eleven patients underwent single-stage posterior-only vertebral column resection and vertebral body reconstruction using an expandable cage. Neurological status was classified using the American Spinal Injury Association (ASIA) Impairment Scale, whereas functional outcome was analyzed using a visual analog scale for back pain. Segmental Cobb angles were measured above and below the fractured vertebral body preoperatively, immediate postoperatively, and at the last follow-up. The preoperative neurological status was ASIA grade E in 2 patients, grade D in 5 patients, grade C in 2 patients, and grade B in 2 patients. Postoperatively, neurological stability was demonstrated in 3 patients (27%), and 8 (73%) showed improvement in the ASIA grade. The mean preoperative visual analog scale score was 8.3, which decreased to 4.5 postoperatively, and to 1.8 at the final follow-up. The mean preoperative segmental lordotic angle was 9.2 degrees, which increased to 16.9 degrees postoperatively, and decreased to 15.1 degrees at the last follow-up. The mean operating time was 208.8 minutes, and the mean blood loss was 1006.3 mL. Regarding surgical complications, 1 patient experienced a dural tear and 1 patient demonstrated cage subsidence. The results of this small series suggest the feasibility, efficacy, and safety of this surgical option for unstable mid and lower lumbar burst fractures. This technique from a single posterior approach offers several advantages over traditional anterior or combined approaches using strut graft or nonexpandable implants.


Use of online promotion to encourage patient awareness of aspirin use to prevent heart attack and stroke.
Literature on health promotion evaluation and public understanding of health suggests the importance of investigating behaviour over time in conjunction with information environment trends as a way of understanding programme impact. We analysed population response to online promotion of an educational tool built by the Ask About Aspirin campaign in the USA to inform people about aspirin as a preventive aid. We collected 156 weeks of time series data on audience behaviour, namely use of a self-assessment tool. We then used the Autoregressive Integrated Moving Average (ARIMA) modelling to predict that outcome as a function of paid search engine advertising, paid social media promotion and general search interest in aspirin. Through ARIMA modelling of tool engagement data adjusted for outcome series autocorrelation, we found a significant effect of online promotional effort on audience behaviour. Total paid search advertising positively predicted weekly total of individuals who started using the self-assessment tool, coefficient=0.023, t=3.28, p=0.001. This effect did not appear to be an artefact of broader secular trends, as Google search data on the topic of aspirin use did not add explanatory power in the final model nor did controlling for general search interest eliminate the significant coefficient for paid search promotion. Results hold implications both for educational tool development and for understanding health promotion campaign effects. We witnessed substantial but ephemeral effects on tool use as a function of paid search efforts, suggesting prioritisation of efforts to affect search engine results as a dissemination tactic.


Third-harmonic generation imaging of laser-induced breakdown in glass.
We present the results of three-dimensional third-harmonic generation imaging of laser-induced breakdown in glass by focused microjoule femtosecond near-IR pulses. This technique has the potential to resolve three dimensionally microstructures that result from laser-induced breakdown. As a potential optical data storage approach it is shown that the same IR laser beam can be used for writing and, at a lower power, for reading. The induced microdamage is shown to be three dimensionally confined and to depend on the write power.


Determinants of health after hospital discharge: rationale and design of the Vanderbilt Inpatient Cohort Study (VICS).
The period following hospital discharge is a vulnerable time for patients when errors and poorly coordinated care are common. Suboptimal care transitions for patients admitted with cardiovascular conditions can contribute to readmission and other adverse health outcomes. Little research has examined the role of health literacy and other social determinants of health in predicting post-discharge outcomes. The Vanderbilt Inpatient Cohort Study (VICS), funded by the National Institutes of Health, is a prospective longitudinal study of 3,000 patients hospitalized with acute coronary syndromes or acute decompensated heart failure. Enrollment began in October 2011 and is planned through October 2015. During hospitalization, a set of validated demographic, cognitive, psychological, social, behavioral, and functional measures are administered, and health status and comorbidities are assessed. Patients are interviewed by phone during the first week after discharge to assess the quality of hospital discharge, communication, and initial medication management. At approximately 30 and 90 days post-discharge, interviewers collect additional data on medication adherence, social support, functional status, quality of life, and health care utilization. Mortality will be determined with up to 3.5 years follow-up. Statistical models will examine hypothesized relationships of health literacy and other social determinants on medication management, functional status, quality of life, utilization, and mortality. In this paper, we describe recruitment, eligibility, follow-up, data collection, and analysis plans for VICS, as well as characteristics of the accruing patient cohort. This research will enhance understanding of how health literacy and other patient factors affect the quality of care transitions and outcomes after hospitalization. Findings will help inform the design of interventions to improve care transitions and post-discharge outcomes.


The emerging quest for the optimal angiostatic combination therapy.
Angiostatic therapies are now routinely embedded in the daily clinical management of cancer. Although these agents clearly benefit patient survival rates, the effect is only moderate with sometimes considerable side effects. A major cause of failure in this respect is the induction of resistance and tolerability against these drugs. Most angiostatic drugs are tyrosine kinase inhibitors that aim to inhibit or neutralize the activity of tumour-produced growth factors. Frustrating the tumour cells in this way results in genetic adaptations in the cells, turning them into mutants that are dependent on other growth mechanisms. It may therefore be necessary to shift to another class of drugs that directly target the tumour vasculature. It is evident that improvement of future angiogenesis inhibitors can only arise from two efforts. First, through the identification of better targets, preferably specifically expressed in the tumour vasculature. Secondly, through the development of combination therapies. The present review highlights the current efforts and challenges in trying to develop effective angiostatic combination therapies.


Improvement of penile erection, sperm count and seminal fructose levels in vivo and nitric oxide release in vitro by ayurvedic herbs.
In the present study, the effect of four Vajikaran Rasayana herbs on penile erection, sperm count, seminal fructose content in vivo and nitric oxide (NO) release in vitro was assessed. Lyophilised aqueous extracts of Asparagus racemosus Willd. (AR), Chlorophytum borivilianum Sant. F. (CB), Curculigo orchioides Gaertn. (CO), and Dactylorhiza hatagirea (D. Don) Soo (DH) were orally administered at 100 mg/kg body weight to Wistar strain male albino rats. Penile erection index and sperm count were determined by visual observation; the seminal fructose concentration was measured spectrophotometrically using resorcinol reagent; and NO release was assessed in a mouse macrophage cell line (RAW264) spectrophotometrically using a commercial Griess reagent kit. Penile erection index, sperm count, seminal fructose concentration and in vitro NO release were the parameters measured. A significant effect on the sperm count, seminal fructose content and penile erection index was observed upon treatment with the extracts. The effect of extracts on inducible NO release in vitro directly correlated with the enhanced erectile function in vivo. The aphrodisiac claims attributed to the four Vajikaran Rasayana herbs were tested and a distinctive effect of all extracts tested was observed, with C. borivilianum showing a highly significant response for all parameters measured in vivo and in vitro. The present study also provides a good correlation between the in vivo improvement of penile erection and in vitro NO releasing activity of the extracts. Increase in seminal fructose levels and sperm count further validates the role of these herbs in improving reproductive function.


Socioeconomic status and objectively measured physical activity in Thai adolescents.
The impact of socioeconomic status (SES) on objective measures of physical activity (PA) in adolescence is poorly understood. The purpose of this cross-sectional study was to evaluate the association between SES and objectively measured PA in Thai adolescents. PA was objectively measured every 30 seconds for 7 consecutive days using ActiGraph GT1M uniaxial accelerometers in 177 secondary-school adolescents aged 13 to 18 years that were classified into 3 SES groups (low, middle, and high). The associations between SES and adolescents' PA were examined using 1-way ANOVA with multiple comparisons and Chi-square test. Adolescents of low-SES accumulated more minutes of PA and less of sedentary behavior than those of high-SES, Additionally, low-SES adolescents tended to meet the daily PA guidelines more than other groups, particularly in girls (P < .01). This study evidences an inverse relationship between SES and PA levels, and shows the importance of targeting high SES adolescents in intervention programs to enhance health behaviors. Based on these findings, we also suggest that SES must be considered as an important determinant in promoting regular PA and in increasing proportions of adolescents meeting current health-related PA guidelines.


An orthodontic oral appliance.
This pilot study was performed to test the hypothesis that an orthodontic oral appliance (OA) that is designed to work against the backwardly directed forces on the upper incisors may counteract the reduction in overjet from these devices. Thirty patients with normal bites, good oral health, and milder sleep apnea were randomized to treatment with either OAs or orthodontic OAs. Bite changes were evaluated on plaster casts and radiographs and by questionnaires after a mean of 2.4 years in 19 frequent users. Four of nine patients in the orthodontic OA group increased their overjet by > or =0.4 mm, while none of the 10 patients in the OA group experienced that effect. Only the orthodontic OA increases the overjet; this design may therefore be beneficial to patients at risk of negative effects on their bite during OA treatment.


Mothers' perceptions of child care assistance: the impact of a child's disability.
This study examined and compared mothers' perceptions of child care assistance provided by fathers and other caregivers. Awareness of child care division of labor will assist occupational therapists in addressing the needs of children with disabilities within the family context. One hundred and thirty-five mothers living in two-parent households kept a time diary of their daily activities for 7 consecutive days using the Caregiver's Activity and Recording of Events Inventory and estimated the percentage of child care their partners performed, the amount of child care their partners performed, and their satisfaction with this division of labor. One third of the women had children with multiple disabilities, one third had children with Down syndrome, and one third had children who were typically developing. The majority of mothers in all three groups perceived that they were responsible for the majority of child care. There were no significant differences between groups in terms of mothers' perceptions of the amount of child care provided by fathers and other caregivers, including relatives, childsitters, nurses, school personnel, and neighbors. However, there were wide variations among families concerning child care arrangements and division of labor. Seventy-five percent of mothers indicated that they were satisfied with the division of child care labor between mothers and fathers, and no significant correlation was found between perceived percentage of child care performed and satisfaction with the division of labor. Mothers in this study were responsible for the majority of child care whether their child had a disability. The variation in number of hours that others spent performing child care activities within individual families suggests that there is no "best" or typical pattern. Occupational therapists need to collaborate with families to determine a system of accommodations to manage their daily routine that most effectively meets the family's needs.


Primary structure of lymphocyte function-associated antigen 3 (LFA-3). The ligand of the T lymphocyte CD2 glycoprotein.
We have isolated the cDNA for human lymphocyte function-associated antigen 3 (LFA-3), the ligand of the T lymphocyte CD2 molecule. The identity of the clones was established by comparison of the deduced amino acid sequence to the LFA-3 NH2-terminal and tryptic peptide sequences. The cDNA defines a mature protein of 222 amino acids that structurally resembles typical membrane-anchored proteins. An extracellular domain with six N-linked glycosylation sites is followed by a hydrophobic putative transmembrane region and a short cytoplasmic domain. The mature glycoprotein is estimated to be 44-68% carbohydrate. Southern blots of human genomic DNA indicate that only one gene codes for human LFA-3. Northern blot analysis demonstrates that the LFA-3 mRNA of 1.3 kb is widely distributed in human tissues and cell lines.


A sensorimotor program for improving writing readiness skills in elementary-age children.
This article discusses a writing readiness program used with three groups of children aged 5 to 7 years. The program combines occupational therapy treatment with a supplementary program implemented by school personnel or parents. The Developmental Test of Visual-Motor Integration-Revised (Beery, 1982) was used to measure the developmental level of the children's writing readiness skills before and after treatment. The group of children with a significant verbal performance IQ discrepancy (greater than 15 points) showed a 17-month growth in readiness skills within 1 year. The group of children with mental retardation (IQ less than 80) showed a significant sex effect: The boys showed more gains than the girls. Implications of these findings are discussed.


Contributions of intrinsic membrane dynamics to fast network oscillations with irregular neuronal discharges.
During fast oscillations in the local field potential (40-100 Hz gamma, 100-200 Hz sharp-wave ripples) single cortical neurons typically fire irregularly at rates that are much lower than the oscillation frequency. Recent computational studies have provided a mathematical description of such fast oscillations, using the leaky integrate-and-fire (LIF) neuron model. Here, we extend this theoretical framework to populations of more realistic Hodgkin-Huxley-type conductance-based neurons. In a noisy network of GABAergic neurons that are connected randomly and sparsely by chemical synapses, coherent oscillations emerge with a frequency that depends sensitively on the single cell's membrane dynamics. The population frequency can be predicted analytically from the synaptic time constants and the preferred phase of discharge during the oscillatory cycle of a single cell subjected to noisy sinusoidal input. The latter depends significantly on the single cell's membrane properties and can be understood in the context of the simplified exponential integrate-and-fire (EIF) neuron. We find that 200-Hz oscillations can be generated, provided the effective input conductance of single cells is large, so that the single neuron's phase shift is sufficiently small. In a two-population network of excitatory pyramidal cells and inhibitory neurons, recurrent excitation can either decrease or increase the population rhythmic frequency, depending on whether in a neuron the excitatory synaptic current follows or precedes the inhibitory synaptic current in an oscillatory cycle. Detailed single-cell properties have a substantial impact on population oscillations, even though rhythmicity does not originate from pacemaker neurons and is an emergent network phenomenon.


Informal payments for health care: definitions, distinctions, and dilemmas.
There is increasing interest in the issue of informal payments for health care in low- and middle-income countries. Emerging evidence suggests that the phenomenon is both diverse, including many variants from cash payments to in-kind contributions and from gift giving to informal charging, and widespread, reported from countries in at least three continents. However, cross-national research is hampered by the lack of consensus among researchers on the definition of informal payments, and the definitions that have been proposed are unable to incorporate all forms of the phenomenon that have been described so far. This article aims to overcome this limitation by proposing a new definition based on the concept of entitlement for services. First, the various forms of informal payment observed in practice are reviewed briefly. Then, some of the proposed definitions are discussed, pointing out that none of the distinctive characteristics implied by these definitions, including illegality, informality, and corruption, is adequate to capture all varieties of the phenomenon. Next, an alternative definition is formulated, which identifies the distinctive feature common to all forms of informal payments as something that is contributed in addition to the terms of entitlement. Then, the boundaries implied by this definition are explored and, finally, the implications for research and policy making are discussed with reference to the lessons developed countries can learn from the experiences of transitional countries.


Risk factors for neurological worsening and symptomatic watershed infarction in internal carotid artery aneurysm treated by extracranial-intracranial bypass using radial artery graft.
OBJECT The revascularization technique, including bypass created using the external carotid artery (ECA), radial artery (RA), and M2 portion of middle cerebral artery (MCA), has remained indispensable for treatment of complex aneurysms. To date, it remains unknown whether diameters of the RA, superficial temporal artery (STA), and C2 portion of the internal carotid artery (ICA) and intraoperative MCA blood pressure have influences on the outcome and the symptomatic watershed infarction (WI). The aim of the present study was to evaluate the factors for the symptomatic WI and neurological worsening in patients treated by ECA-RA-M2 bypass for complex ICA aneurysm with therapeutic ICA occlusion. METHODS The authors measured the sizes of vessels (RA, C2, M2, and STA) and intraoperative MCA blood pressure (initial, after ICA occlusion, and after releasing the RA graft bypass) in 37 patients. Symptomatic WI was defined as presence of the following: postoperative new neurological deficits, WI on postoperative diffusion-weighted imaging, and ipsilateral cerebral blood flow reduction on SPECT. Neurological worsening was defined as the increase in 1 or more modified Rankin Scale scores. First, the authors performed receiver operating characteristic curve analysis for continuous variables and the binary end point of the symptomatic WI. The clinical, radiological, and physiological characteristics of patients with and without the symptomatic WI were compared using the log-rank test. Then, the authors compared the variables between patients with and without neurological worsening at discharge and at the 12-month follow-up examination or last hospital visit. RESULTS Symptomatic WI was observed in 2 (5.4%) patients. The mean MCA pressure after releasing the RA graft (< 55 mm Hg; p = 0.017), mean (MCA pressure after releasing the RA graft)/(initial MCA pressure) (< 0.70 mm Hg; p = 0.032), and mean cross-sectional area ratio ([RA/C2 diameter](2) < 0.40 mm [p < 0.0001] and [STA/C2 diameter](2) < 0.044 mm [p < 0.0001]) were related to the symptomatic WI. All preoperatively independent patients remained independent (modified Rankin Scale score < 3). After adjusting for age and sex, left operative side (p = 0.0090 and 0.038) and perforating artery ischemia (p = 0.0050 and 0.022) were related to neurological worsening at discharge (11 [29%] patients) and at the 12-month follow-up or last hospital visit (8 [22%] patients). CONCLUSIONS Results of the present study showed that the vessel diameter and intraoperative MCA pressure had impacts on the symptomatic WI and that operative side and perforating artery ischemia were related to neurological worsening in patients with complex ICA aneurysms treated by ECA-RA-M2 bypass.


Altered mental status in older adults with histamine2-receptor antagonists: a population-based study.
Standard doses of histamine2-receptor antagonists (H2RAs) may induce altered mental status in older adults, especially in those with chronic kidney disease (CKD). Population-based cohort study of older adults who started a new H2RA between 2002 and 2011 was conducted. Ninety percent received the current standard H2RA dose in routine care. There was no significant difference in 27 baseline patient characteristics. The primary outcome was hospitalization with an urgent head computed tomography (CT) scan (proxy for altered mental status), and the secondary outcome was all-cause mortality also within 30days of a new H2RA prescription. Standard vs. low H2RA dose was associated with a higher risk of hospitalization with an urgent head CT scan (0.98% vs. 0.74%, absolute risk difference 0.24% [95% CI 0.11% to 0.36%], relative risk 1.33 [95% CI 1.12 to 1.58]). This risk was not modified by the presence of CKD (interaction P value=0.71). Standard vs. low H2RA dose was associated with a higher risk of mortality (1.07% vs.0.74%; absolute risk difference 0.34% [95% CI 0.20% to 0.46%], relative risk 1.46 [95% CI 1.23 to 1.73]). Compared to a lower dose, initiation of the current standard dose of H2RA in older adults is associated with a small absolute increase in the 30-day risk of altered mental status (using neuroimaging as a proxy), even in the absence of CKD. This risk may be avoided by initiating older adults on low doses of H2RAs for gastroesophogeal reflux disease, and increasing dosing as necessary for symptom control.


No increase in global temperature variability despite changing regional patterns.
Evidence from Greenland ice cores shows that year-to-year temperature variability was probably higher in some past cold periods, but there is considerable interest in determining whether global warming is increasing climate variability at present. This interest is motivated by an understanding that increased variability and resulting extreme weather conditions may be more difficult for society to adapt to than altered mean conditions. So far, however, in spite of suggestions of increased variability, there is considerable uncertainty as to whether it is occurring. Here we show that although fluctuations in annual temperature have indeed shown substantial geographical variation over the past few decades, the time-evolving standard deviation of globally averaged temperature anomalies has been stable. A feature of the changes has been a tendency for many regions of low variability to experience increases, which might contribute to the perception of increased climate volatility. The normalization of temperature anomalies creates the impression of larger relative overall increases, but our use of absolute values, which we argue is a more appropriate approach, reveals little change. Regionally, greater year-to-year changes recently occurred in much of North America and Europe. Many climate models predict that total variability will ultimately decrease under high greenhouse gas concentrations, possibly associated with reductions in sea-ice cover. Our findings contradict the view that a warming world will automatically be one of more overall climatic variation.


Genotoxicity evaluation of two kinds of smoke-water and 3,7-dimethyl-2H-furo[2,3-c]pyran-2-one.
Smoke, smoke-water and aerosols have a stimulatory effect on seed germination and growth vigour of many seedlings, making them potentially useful for different purposes, provided they do not pose a health risk. Therefore, the genotoxicity of two kinds of smoke-water and 3,7-dimethyl-2H-furo[2,3-c]pyran-2-one, a variant of the most active smoke compound (3-methyl-2H-furo[2,3-c]pyran-2-one) was evaluated using the Vitotox assay. Smoke-water extracts were obtained from burning leaves: Themeda triandra (smoke-water Tt) and a mix of Themeda triandra and Passerina vulgaris (smoke-water Kb). No genotoxic effect was observed for any of the three samples. However, the three samples are toxic at the highest concentrations (3,7-dimethyl-2H-furo[2,3-c]pyran-2-one, 2 ppm; smoke-water Tt, dilutions 1 : 1, 1 : 2, 1 : 4; smoke-water Kb, dilution 1 : 1) without addition of S9 mix. Both the butenolide 3,7-dimethyl-2H-furo[2,3-c]pyran-2-one and smoke-water Tt are also toxic at high doses in the presence of S9 (2 ppm and dilutions 1 : 1 and 1 : 2, respectively), but not smoke-water Kb. Thus, from these results, no genotoxicity of these three samples can be assumed, which is accordance with the previous tests performed with 3-methyl-2H-furo[2,3-c]pyran-2-one and a smoke-water.


Bipolar medication use and adherence to antiretroviral therapy among patients with HIV-AIDS and bipolar disorder.
The study examined relationships between adherence to bipolar medication and to antiretroviral therapy, measured by medication fills, among patients with diagnoses of bipolar disorder and HIV infection. A retrospective study was conducted of Medicaid claims data (2001-2004) from eight states, focusing on antiretroviral adherence. The unit of analysis was person-month (N=53,971). The average observation period for the 1,687 patients was 32 months. Analyses controlled for several patient characteristics. Patients possessed antiretroviral drugs in 72% of the person-months. When a bipolar medication prescription was filled in the prior month, the rate of antiretroviral possession in the subsequent month was 78%, compared with 65% when bipolar medication was not filled in the prior month (p<.001). Odds of antiretroviral possession were 66% higher in months when patients had a prior-month supply of bipolar medication. Bipolar medication adherence may improve antiretroviral adherence among patients with bipolar disorder and HIV infection.


The homeobox gene EMX2 is a prognostic and predictive marker in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm with a poor prognosis and limited treatment options. EMX2 is a homeobox transcription factor that may regulate key developmental pathways known to promote tumorigenesis. In this study, we evaluated the prognostic and predictive significance of EMX2 expression in MPM. Fifty surgically resected MPM specimens were studied. Quantitative real-time RT-PCR was used to analyze EMX2 mRNA expression. Association of EMX2 levels with clinical outcomes was evaluated with using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. EMX2 expression was significantly associated with IMIG stage (p<0.001) and smoking history (p=0.006). Cox hazard regression modeling identified low-EMX2 expression as a negative prognostic factor in progression-free survival by both univariate (p=0.002) and multivariate analysis (p=0.002). Kaplan-Meier analysis revealed significant differences in progression-free survival between low- and high-EMX expressing groups in all patients (p=0.001), and also when grouped by early (I/II) stage disease (p<0.001), patients undergoing pleurectomy (p<0.001) and patients with an epitheliod subtype (p<0.004). Furthermore, EMX2 expression predicted response to neoadjuvant chemotherapy. High-EMX2 expression was associated with decreased progression-free survival after neoadjuvant therapy, suggesting that induction therapy should be avoided in these patients. EMX2 expression is downregulated in advanced cases of malignant pleural mesothelioma and may serve as an important prognostic and predictive molecular biomarker of progression-free survival.


Bone biomechanical properties in LRP5 mutant mice.
The mutation responsible for the high bone mass (HBM) phenotype has been postulated to act through the adaptive response of bone to mechanical load resulting in denser and stronger skeletons in humans and animals. The bone phenotype of members of a HBM family is characterized by normally shaped bones that are exceptionally dense, particularly at load bearing sites [Cancer Res. 59 (1999) 1572]. The high bone mass (HBM) mutation was identified as a glycine to valine substitution at amino acid residue 171 in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) [Bone Miner. Res. 16(4) (2001) 758]. Thus, efforts have focused on the examination of the role of LRP5 and the G171V mutation in bone mechanotransduction responses [J. Bone Miner. Res 18 (2002) 960]. Transgenic mice expressing the human G171V mutation have been shown to have skeletal phenotypes remarkably similar to those seen in affected individuals. In this study, we have identified differences in biomechanical (structural and apparent material) properties, bone mass/ash, and bone stiffness of cortical and cancellous bone driven by the G171V mutation in LRP5. As in humans, the LRP5 G171V plays an important role in regulating bone structural phenotypes in mice. These bone phenotypes include greater structural and apparent material properties in HBM HET as compared to non-transgenic littermates (NTG) mice. Body size and weight in HBM HET were similar to that in NTG control mice. However, the LRP5 G171V mutation in HET mice results in a skeleton that has greater structural (femoral shaft, femoral neck, tibiae, vertebral body) and apparent material (vertebral body) strength, percent bone ash weight (ulnae), and tibial stiffness. Despite similar body weight to NTG mice, the denser and stiffer bones in G171V mice may represent greater bone formation sensitivity to normal mechanical stimuli resulting in an overadaptation of skeleton to weight-related forces.


Indices of Glucose Homeostasis in Cord Blood in Term and Preterm Newborns.
According to the thrifty phenotype hypothesis, intrauterine malnutrition has a role in the etiology of type 2 diabetes. This study was planned to determine the early alterations in indices of glucose homeostasis (glucose, insulin, and cortisol) in term and preterm newborns and the correlations of glucose, insulin, and cortisol levels with insulin resistance indices. A descriptive study comprising 35 term and 35 preterm newborns was carried out from December 2013 to June 2015. Venous cord blood was collected and plasma glucose was analyzed by the glucose oxidase-peroxidase method in an auto analyzer. Serum insulin and cortisol levels were assessed by the enzyme-linked immunosorbent assay. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index and glucose insulin ratio were calculated to assess insulin resistance. The data on physical and metabolic parameters were analyzed using standard tests for statistical significance. In term newborns, mean glucose and cortisol levels (83.6±17.4 mg/dL and 11.88±5.78 µg/dL, respectively) were significantly higher than those in preterm infants (70.4±15.8 mg/dL and 8.9±4.6 µg/dL, respectively). Insulin and HOMA-IR levels were found higher in preterm newborns (10.8±4.8 µIU/mL and 1.52±0.66, respectively) than in term newborns (7.9±2.7 µIU/mL and 1.19±0.29, respectively). Insulin was found to positively correlate with HOMA-IR, whereas cortisol was negatively correlated with HOMA-IR in both term and preterm newborns. Higher insulin levels and HOMA-IR values in the cord blood of preterm newborns support the theory of intrauterine origin of metabolic diseases.


Geometrically induced force interaction for three-dimensional deformable models.
In this paper, we propose a novel 3-D deformable model that is based upon a geometrically induced external force field which can be conveniently generalized to arbitrary dimensions. This external force field is based upon hypothesized interactions between the relative geometries of the deformable model and the object boundary characterized by image gradient. The evolution of the deformable model is solved using the level set method so that topological changes are handled automatically. The relative geometrical configurations between the deformable model and the object boundaries contribute to a dynamic vector force field that changes accordingly as the deformable model evolves. The geometrically induced dynamic interaction force has been shown to greatly improve the deformable model performance in acquiring complex geometries and highly concave boundaries, and it gives the deformable model a high invariancy in initialization configurations. The voxel interactions across the whole image domain provide a global view of the object boundary representation, giving the external force a long attraction range. The bidirectionality of the external force field allows the new deformable model to deal with arbitrary cross-boundary initializations, and facilitates the handling of weak edges and broken boundaries. In addition, we show that by enhancing the geometrical interaction field with a nonlocal edge-preserving algorithm, the new deformable model can effectively overcome image noise. We provide a comparative study on the segmentation of various geometries with different topologies from both synthetic and real images, and show that the proposed method achieves significant improvements against existing image gradient techniques.


Exercise training for intermittent claudication: a narrative review and summary of guidelines for practitioners.
Peripheral artery disease (PAD) is caused by atherosclerotic narrowing of the arteries supplying the lower limbs often resulting in intermittent claudication, evident as pain or cramping while walking. Supervised exercise training elicits clinically meaningful benefits in walking ability and quality of life. Walking is the modality of exercise with the strongest evidence and is recommended in several national and international guidelines. Alternate forms of exercise such as upper- or lower-body cycling may be used, if required by certain patients, although there is less evidence for these types of programmes. The evidence for progressive resistance training is growing and patients can also engage in strength-based training alongside a walking programme. For those unable to attend a supervised class (strongest evidence), home-based or 'self-facilitated' exercise programmes are known to improve walking distance when compared to simple advice. All exercise programmes, independent of the mode of delivery, should be progressive and individually prescribed where possible, considering disease severity, comorbidities and initial exercise capacity. All patients should aim to accumulate at least 30 min of aerobic activity, at least three times a week, for at least 3 months, ideally in the form of walking exercise to near-maximal claudication pain.


Review: Antiurolithiatic plants: Formulations used in different countries and cultures.
About 12% of world population is affected by different forms of urolithiasis in which the recurrence rate in female is 47-60% and in male is 70-80%. According to WHO 75% people rely on traditional medicines for the prevention and cure of different ailments. Similarly, the majority of the world population use a number of plants to treat problems related to the urinary tract system in which urolithiasis is the major cause. The aim of the review is to collect the data of the plants used in different parts and cultures of the world against urolithiasis with their parts, mode of preparation, dosage and administration. A literature review was conducted for traditionally used antiurolithiatic plants. The articles mentioning plant, parts, mode of preparation, dose and route of administration were selected. This information was extracted to compose Mono and Poly herbal antiurolithiatic formulations used in Appalachia (region in Eastern United States), Canada, India, Iran, Israel, Italy, Jordan, Latin America, Pakistan, Turkey and Yemen. The review provides an important data about plants used as antiurolithiatic in different parts of the world. The information not only useful for common people, but also for the scientific community to carry out further phytochemical, pharmacological and toxicological studies for the discovery of new, effective and safer molecules against urolithiasis.


Alpha-tocopheryl succinate sensitises a T lymphoma cell line to TRAIL-induced apoptosis by suppressing NF-kappaB activation.
Activation of nuclear factor-kappaB (NF-kappaB) can interfere with induction of apoptosis triggered by the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL; Apo2L). Therefore, agents that suppress NF-kappaB activation may sensitise cells to TRAIL-dependent apoptosis. Exposure of Jurkat cells to TRAIL resulted in massive and saturable apoptosis induction, following an initial lag time. This lag was abolished by pretreatment of the cells with subapoptotic doses of alpha-tocopheryl succinate (alpha-TOS) or the proteasome inhibitor MG132. Exposure of the cells to TRAIL led to a rapid, transient activation of NF-kappaB, a process that was suppressed by cell pretreatment with alpha-TOS or MG132. Activation of NF-kappaB by TNF-alpha prior to TRAIL exposure increased resistance of the cells to TRAIL-mediated apoptosis. We conclude that alpha-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-kappaB activation. This further supports the possibility that this semisynthetic analogue of vitamin E is a potential adjuvant in cancer treatment, such as in the case of TRAIL-mediated inhibition of cancer.


Self-management interventions in pediatric epilepsy: What is the level of evidence?
To respond to recommendations put forth by the Institute of Medicine to improve self-management resources for youth with epilepsy by conducting a systematic review of the self-management literature in pediatric epilepsy. Inclusion criteria: youth birth to 18 years with a seizure disorder or an epilepsy diagnosis and/or their caregivers, published 1985-2014 in English, and conducted in countries with a very high human development index. Abstract and keywords had to explicitly refer to "self-care" (pre-1996) and/or self-management (post-1996). The review was conducted in seven phases: (1) identification of bibliographical search criteria and databases; (2) abstract assessment; (3) full article review; (4) organization of final citations into instrument development, intervention, factors associated with self-management categories; (5) American Academy of Neurology level of evidence (LOE) assessment for intervention studies; (6) CONsolidated Standards of Reporting Trials (CONSORT) evaluation of LOE level III articles utilizing a control group; and (7) categorization of intervention outcomes across four self-management domains. Of the 87 articles that met eligibility criteria, 24 were interventions and received LOE scores of level III or IV. Most studies (n = 20, 80%) were scored at level III; however, only eight had a control group and adhered to CONSORT guidelines. They largely neglected information on intervention components (e.g., implementation, treatment fidelity), randomization, participant flow, missing data, and effect size or confidence intervals. The 24 intervention studies reported significant impact in four domains: individual (n = 13), family (n = 6), health care system (n = 3), and community (n = 2). There are no level I or II studies. No study met full CONSORT guidelines. Outcomes were well described; however, the nature of self-management interventions (e.g., multiple foci, skills targeted) and the observed heterogeneity in outcomes complicates comparisons across studies. Randomized controlled trials (RCTs) that include large sample sizes, impact of the intervention, treatment fidelity, and power analyses are necessary to further this evidence base.


A matrix-induced ion suppression method to normalize concentration in urinary metabolomics studies using flow injection analysis electrospray ionization mass spectrometry.
Normalizing the total urine concentration is important for minimizing bias in urinary metabolomics analysis comparisons. In this study, we report a matrix-induced ion suppression (MIIS)-based method to normalize concentration using flow injection analysis coupled with electrospray ionization mass spectrometry (FIA-ESI-MS). An ion suppression indicator (ISI) was spiked into urine samples, and the intensity of the extracted ion chromatogram (EIC) for ISI in a urine matrix was subtracted by the EIC for a blank solution and used to calculate the extent to which the signal was reduced by the urine matrix. A series dilution of pooled urine samples was used to correlate the urine concentration and level of ion suppression for ISI. A regression equation was used to estimate the relative concentration of unknown urine samples. The MIIS method was validated for linearity, precision and accuracy. We obtained a good correlation using a quadratic regression model for 1- to 32-fold urine dilutions (R(2)=0.998). The reproducibility (n=4) and intermediate precision (n=3) were below 5% RSD, and the accuracy ranged from 97.15% to 102.10%. The established method was used to estimate the relative concentrations of 16 urine samples, and the results were compared with commonly used normalization methods. Pearson's correlation test was used to demonstrate that the MIIS method correlated highly with the creatinine and osmolarity methods; the correlation coefficients were 0.93 and 0.99, respectively. We successfully applied this method to a urinary metabolomics study on breast cancer. This study demonstrated the MIIS method is simple, accurate and can contribute to data integrity in urinary metabolomics studies.


A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging.
To compare the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging procedures. Sixty children between the age of 1 to 7 years were randomly distributed into two groups: The dexmedetomidine (D) group received 1 μg/kg initial dose followed by continuous infusion of 0.5 μg/kg/h, and the propofol group (P) received 3 mg/kg initial dose, followed by a continuous infusion of 100 μg/kg/min. Inadequate sedation was defined as difficulty in completing the procedure because of the child's movement during magnetic resonance imaging. Mean arterial pressure (MAP), heart rate, peripheral oxygen saturation, and respiratory rate (RR) were recorded during the study. The onset of sedation, recovery, and discharge time were significantly shorter in group P than in group D. MAP, heart rate, and RR decreased during sedation from the baseline values in both groups. MAP and RR were significantly lower in group P than in group D during sedation. Dexmedetomidine and propofol provided adequate sedation in most of the children. We conclude that although propofol provided faster anesthetic induction and recovery times, it caused hypotension and desaturation. Dexmedetomidine could be an alternative, reliable sedative drug to propofol in selected patients.


Projected impact of travoprost versus both timolol and latanoprost on visual field deficit progression and costs among black glaucoma subjects.
We compared differences associated with use of travoprost and latanoprost on both progression of perimetric loss over time and associated costs among black patients. Patients with primary open-angle glaucome or ocular hypertension were randomly assigned to one of four arms in a 12-month, double-masked study: travoprost (0.004% or 0.0015%), latanoprost (0.005%), or timolol (0.5%). Forty-nine patients received 0.004% travoprost, 43 received latanoprost, and 40 received timolol. We applied algorithms found in published studies that link intraocular pressure (IOP) control to visual field progression and calculated the likelihood of visual field deterioration based on IOP data. This was used to estimate differences in medical care costs. The average IOP was lower for patients receiving travoprost than for patients receiving latanoprost or timolol (17.3 versus 18.7 versus 20.5 mm Hg respectively, P < .05). Travoprost-treated patients had a smaller predicted change in visual field defect score (VFDS) than latanoprost-treated patients and timolol-treated patients, and significantly fewer were expected to demonstrate visual field progression. Medical care costs would be higher for latanoprost-treated and timolol-treated patients. Recent studies have provided algorithms linking IOP control to changes in visual fields. We found that treatment with travoprost was associated with less visual field progression and potential cost savings.


Low-density three-dimensional foam using self-reinforced hybrid two-dimensional atomic layers.
Low-density nanostructured foams are often limited in applications due to their low mechanical and thermal stabilities. Here we report an approach of building the structural units of three-dimensional (3D) foams using hybrid two-dimensional (2D) atomic layers made of stacked graphene oxide layers reinforced with conformal hexagonal boron nitride (h-BN) platelets. The ultra-low density (1/400 times density of graphite) 3D porous structures are scalably synthesized using solution processing method. A layered 3D foam structure forms due to presence of h-BN and significant improvements in the mechanical properties are observed for the hybrid foam structures, over a range of temperatures, compared with pristine graphene oxide or reduced graphene oxide foams. It is found that domains of h-BN layers on the graphene oxide framework help to reinforce the 2D structural units, providing the observed improvement in mechanical integrity of the 3D foam structure.


A simple method for freeze-fracture of monolayer cultures.
A simple method is described for the freeze-fracture in situ of monolayer cultures grown on gold carriers coated with a thin layer of silicon monoxide. Preliminary observations on 3T3 mouse embryo fibroblasts indicate that this technique exposes large areas of cell membrane, making it possible to determine how areas of membrane specialization are related to the cell as a whole and to regions of cellular interaction. 3T3 cells cultured on silicon monoxide show no modification of growth properties compared to cells growing on Falcon plastic, and other cell lines also appear to grow well on this substrate.


Resource allocation to brain research in Switzerland.
This study represents a first attempt at estimating Swiss resource allocation to brain research including both public and private spending. In order to estimate public spending (by governments and charities) a survey was conducted to evaluate the way brain research is funded across Europe and especially in Switzerland. Industry funding was measured using different approaches including a survey of pharmaceutical expenditures and the costs of developing new drugs. Private spending is at a reasonable level because a highly developed Swiss pharmaceutical industry invests significantly in this branch of science. However, public spending is at a low level compared to other European countries, although Switzerland is the only European country where the total funding per capita exceeds that of US funding. A detailed investigation of Swiss resource allocation to different branches of biomedical research is warranted. Brain research should be an important part of such a study. The United States and the European Union have selected brain research as one of their priority areas within health related research. The present figures indicate that this may also be justified in Switzerland.


Plant functional traits mediate reproductive phenology and success in response to experimental warming and snow addition in Tibet.
Global climate change is predicted to have large impacts on the phenology and reproduction of alpine plants, which will have important implications for plant demography and community interactions, trophic dynamics, ecosystem energy balance, and human livelihoods. In this article we report results of a 3-year, fully factorial experimental study exploring how warming, snow addition, and their combination affect reproductive phenology, effort, and success of four alpine plant species belonging to three different life forms in a semiarid, alpine meadow ecosystem on the central Tibetan Plateau. Our results indicate that warming and snow addition change reproductive phenology and success, but responses are not uniform across species. Moreover, traits associated with resource acquisition, such as rooting depth and life history (early vs. late flowering), mediate plant phenology, and reproductive responses to changing climatic conditions. Specifically, we found that warming delayed the reproductive phenology and decreased number of inflorescences of Kobresia pygmaea C. B. Clarke, a shallow-rooted, early-flowering plant, which may be mainly constrained by upper-soil moisture availability. Because K. pygmaea is the dominant species in the alpine meadow ecosystem, these results may have important implications for ecosystem dynamics and for pastoralists and wildlife in the region.


Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells.
We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1), a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM) and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT) markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated N-cadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT). Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.


Expression profiling of Oryza sativa metal homeostasis genes in different rice cultivars using a cDNA macroarray.
Rice is an important food crop, but it is a poor source of essential micronutrients such as iron and zinc. In order to improve the metal ion content of rice grains through breeding or biotechnology, more information is needed on the molecular players that help mobilize metals from leaves to developing seeds. To profile several genes simultaneously, a cDNA macroarray was developed using 36 metal-related genes from rice, including ZIPs, NRAMPs, and YSLs (coding for known or potential metal transporters), as well as NAS, FER, FRO, NAAT, FDH, GSTU, and PDR (involved in metal homeostasis). Because flag leaves are the major source of phloem-delivered photoassimilates and remobilized metals for developing seeds, we analyzed the expression of these metal-related genes in flag and non-flag leaves of four different rice cultivars (Cocodrie, Taipei 309, IR58, and IR68144) during the period of mid-grain fill. Genes (24 of 36) exhibited low to non-detectable signals in the macroarray, while 12 genes (OsIRT1, OsZIP1, OsZIP5, OsZIP8, OsYSL5, OsYSL6, OsYSL7, OsYSL8, OsYSL18, OsNRAMP2, OsNRAMP4 and OsNRAMP7) were found to be highly expressed in both flag and non-flag leaves of all four cultivars. Additional expression analysis using semi-quantitative or quantitative PCR provided results that were generally consistent with the macroarray, but semi-quantitative PCR confirmed that OsFDH, OsFER1, OsNAAT, OsNAS1, OsPDR9, OsYSL12, OsYSL13, OsZIP7, and OsZIP10 were also expressed in leaves. This specialized macroarray has provided a short list of potential candidate genes, expressed in leaves, which might contribute to the process of metal transport to distant sinks, such as seeds.


Smyd1 facilitates heart development by antagonizing oxidative and ER stress responses.
Smyd1/Bop is an evolutionary conserved histone methyltransferase previously shown by conventional knockout to be critical for embryonic heart development. To further explore the mechanism(s) in a cell autonomous context, we conditionally ablated Smyd1 in the first and second heart fields of mice using a knock-in (KI) Nkx2.5-cre driver. Robust deletion of floxed-Smyd1 in cardiomyocytes and the outflow tract (OFT) resulted in embryonic lethality at E9.5, truncation of the OFT and right ventricle, and additional defects consistent with impaired expansion and proliferation of the second heart field (SHF). Using a transgenic (Tg) Nkx2.5-cre driver previously shown to not delete in the SHF and OFT, early embryonic lethality was bypassed and both ventricular chambers were formed; however, reduced cardiomyocyte proliferation and other heart defects resulted in later embryonic death at E11.5-12.5. Proliferative impairment prior to both early and mid-gestational lethality was accompanied by dysregulation of transcripts critical for endoplasmic reticulum (ER) stress. Mid-gestational death was also associated with impairment of oxidative stress defense-a phenotype highly similar to the previously characterized knockout of the Smyd1-interacting transcription factor, skNAC. We describe a potential feedback mechanism in which the stress response factor Tribbles3/TRB3, when directly methylated by Smyd1, acts as a co-repressor of Smyd1-mediated transcription. Our findings suggest that Smyd1 is required for maintaining cardiomyocyte proliferation at minimally two different embryonic heart developmental stages, and its loss leads to linked stress responses that signal ensuing lethality.


A Cas9 with PAM recognition for adenine dinucleotides.
CRISPR-associated (Cas) DNA-endonucleases are remarkably effective tools for genome engineering, but have limited target ranges due to their protospacer adjacent motif (PAM) requirements. We demonstrate a critical expansion of the targetable sequence space for a type II-A CRISPR-associated enzyme through identification of the natural 5[Formula: see text]-NAAN-3[Formula: see text] PAM preference of Streptococcus macacae Cas9 (SmacCas9). To achieve efficient editing activity, we graft the PAM-interacting domain of SmacCas9 to its well-established ortholog from Streptococcus pyogenes (SpyCas9), and further engineer an increased efficiency variant (iSpyMac) for robust genome editing activity. We establish that our hybrids can target all adenine dinucleotide PAM sequences and possess robust and accurate editing capabilities in human cells.


A reproducible approach to high-throughput biological data acquisition and integration.
Modern biological research requires rapid, complex, and reproducible integration of multiple experimental results generated both internally and externally (e.g., from public repositories). Although large systematic meta-analyses are among the most effective approaches both for clinical biomarker discovery and for computational inference of biomolecular mechanisms, identifying, acquiring, and integrating relevant experimental results from multiple sources for a given study can be time-consuming and error-prone. To enable efficient and reproducible integration of diverse experimental results, we developed a novel approach for standardized acquisition and analysis of high-throughput and heterogeneous biological data. This allowed, first, novel biomolecular network reconstruction in human prostate cancer, which correctly recovered and extended the NFκB signaling pathway. Next, we investigated host-microbiome interactions. In less than an hour of analysis time, the system retrieved data and integrated six germ-free murine intestinal gene expression datasets to identify the genes most influenced by the gut microbiota, which comprised a set of immune-response and carbohydrate metabolism processes. Finally, we constructed integrated functional interaction networks to compare connectivity of peptide secretion pathways in the model organisms Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa.


Daily Exposure to a Cranberry Polyphenol Oral Rinse Alters the Oral Microbiome but Not Taste Perception in PROP Taster Status Classified Individuals.
Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline (p = 0.012) but not after the intervention (p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs (p = 0.023) but not in STs (p = 0.096). The intervention also altered specific salivary protein levels (α-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.


A fluorometric skin-interfaced microfluidic device and smartphone imaging module for in situ quantitative analysis of sweat chemistry.
The rich composition of solutes and metabolites in sweat and its relative ease of collection upon excretion from skin pores make this class of biofluid an attractive candidate for point of care analysis. Wearable technologies that combine electrochemical sensors with conventional or emerging semiconductor device technologies offer valuable capabilities in sweat sensing, but they are limited to assays that support amperometric, potentiometric, and colorimetric analyses. Here, we present a complementary approach that exploits fluorometric sensing modalities integrated into a soft, skin-interfaced microfluidic system which, when paired with a simple smartphone-based imaging module, allows for in situ measurement of important biomarkers in sweat. A network array of microchannels and a collection of microreservoirs pre-filled with fluorescent probes that selectively react with target analytes in sweat (e.g. probes), enable quantitative, rapid analysis. Field studies on human subjects demonstrate the ability to measure the concentrations of chloride, sodium and zinc in sweat, with accuracy that matches that of conventional laboratory techniques. The results highlight the versatility of advanced fluorescent-based imaging modalities in body-worn sweat microfluidics platforms, and they suggest some practical potential for these ideas.


Biodemographic analysis of male honey bee mortality.
Biodemographic studies of insects have significantly enhanced our understanding of the biology of aging. Eusocial insects have evolved to form different groups of colony members that are specialized for particular tasks and highly dependent on each other. These different groups (castes and sexes) also differ strongly in their life expectancy but relatively little is known about their mortality dynamics. In this study we present data on the age-specific flight activity and mortality of male honey bees from two different genetic lines that are exclusively dedicated to reproduction. We show that males initiating flight at a young age experience more flight events during their lifetime. No (negative) relation between the age at flight initiation and lifespan exists, as might be predicted on the basis of the antagonistic pleiotropy theory of aging. Furthermore, we fit our data to different aging models and conclude that overall a slight deceleration of the age-dependent mortality increase at advanced ages occurs. However, mortality risk increases according to the Gompertz-Makeham model when only days with flight activity (active days) are taken into account. Our interpretation of the latter is that two mortality components act on honey bee males during flight: increasing, age-dependent deaths (possibly from wear-and-tear), and age-independent deaths (possibly due to predation). The overall mortality curve is caused by the interaction of the distribution of age at foraging initiation and the mortality function during the active (flight) lifespan.


Thorium- and uranium-azide reductions: a transient dithorium-nitride versus isolable diuranium-nitrides.
Molecular uranium-nitrides are now well known, but there are no isolable molecular thorium-nitrides outside of cryogenic matrix isolation experiments. We report that treatment of [M(TrenDMBS)(I)] (M = U, 1; Th, 2; TrenDMBS = {N(CH2CH2NSiMe2Bu t )3}3-) with NaN3 or KN3, respectively, affords very rare examples of actinide molecular square and triangle complexes [{M(TrenDMBS)(μ-N3)} n ] (M = U, n = 4, 3; Th, n = 3, 4). Chemical reduction of 3 produces [{U(TrenDMBS)}2(μ-N)][K(THF)6] (5) and [{U(TrenDMBS)}2(μ-N)] (6), whereas photolysis produces exclusively 6. Complexes 5 and 6 can be reversibly inter-converted by oxidation and reduction, respectively, showing that these UNU cores are robust with no evidence for any C-H bond activations being observed. In contrast, reductions of 4 in arene or ethereal solvents gives [{Th(TrenDMBS)}2(μ-NH)] (7) or [{Th(TrenDMBS)}{Th(N[CH2CH2NSiMe2Bu t ]2CH2CH2NSi[μ-CH2]MeBu t )}(μ-NH)][K(DME)4] (8), respectively, providing evidence unprecedented outside of matrix isolation for a transient dithorium-nitride. This suggests that thorium-nitrides are intrinsically much more reactive than uranium-nitrides, since they consistently activate C-H bonds to form rare examples of Th-N(H)-Th linkages with alkyl by-products. The conversion here of a bridging thorium(iv)-nitride to imido-alkyl combination by 1,2-addition parallels the reactivity of transient terminal uranium(iv)-nitrides, but contrasts to terminal uranium(vi)-nitrides that produce alkyl-amides by 1,1-insertion, suggesting a systematic general pattern of C-H activation chemistry for metal(iv)- vs. metal(vi)-nitrides. Surprisingly, computational studies reveal a σ > π energy ordering for all these bridging nitride bonds, a phenomenon for actinides only observed before in terminal uranium nitrides and uranyl with very short U-N or U-O distances.


Fertility Assessment in Sorraia Stallions by Sperm-Fish and Fkbp6 Genotyping.
The Sorraia, a critically endangered indigenous Iberian horse breed, is characterized by low genetic variability, high rate of inbreeding, bad sperm quality and subfertility. Here, we studied 11 phenotypically normal but subfertile Sorraia stallions by karyotyping, sex chromosome sperm-FISH and molecular analysis of FKBP6 - a susceptibility locus for impaired acrosome reaction (IAR). The stallions had normal sperm concentration (>300 million cells/ml), but the numbers of progressively motile sperm (21%) and morphologically normal sperm (28%) were invariably low. All stallions had a normal 64,XY karyotype. The majority of sperm (89%) had normal haploid sex chromosome content, although 11% of sperm carried various sex chromosome aneuploidies. No correlation was found between the percentage of sperm sex chromosome abnormalities and inbreeding, sperm morphology or stallion age. Direct sequencing of FKBP6 exon 4 for SNPs g.11040315G>A and g.11040379C>A revealed that none of the stallions had the susceptibility genotype (A/A-A/A) for IAR. Instead, all animals had a G/G-A/A genotype - a testimony of low genetic variability. The findings ruled out chromosomal abnormalities and genetic predisposition for IAR as contributing factors for subfertility. However, low fertility of the Sorraia stallions could be partly attributed to relatively higher rate of sex chromosome aneuploidies in the sperm.


Improved VO(2) thin films for infrared switching.
Vanadium dioxide (VO(2),) undergoes a thermally induced phase transition from a semiconductor to a metal near 68 degrees C. The deposition of VO(2), thin films by using a process of activated-reactive evaporation provides high-quality VO(2)-film material; specifically, the semiconducting phase-extinction coefficient in the infrared is reduced by an order of magnitude without detrimental effect on the corresponding metal phase coefficient. The materials improvement significantly enhances accessible performance limits for optical switching devices, as compared with VO(2) thin films deposited by both standard reactive and ion-assisted reactive evaporation.


Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.
Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.


Significance of bacteria in oviposition and larval development of the sand fly Lutzomyia longipalpis.
Microbial ecology of phlebotomine sand flies is not well understood although bacteria likely play an important role in the sand fly biology and vector capacity for Leishmania parasites. In this study, we assessed the significance of the microbial community of rabbit feces in oviposition and larval development of Lutzomyia longipalpis as well as bacterial colonization of the gut of freshly emerged flies. Sterile (by autoclaving) and non-sterile (control) rabbit feces were used in the two-choice assay to determine their oviposition attractiveness to sand fly females. Bacteria were identified by amplification and sequencing of the 16S rRNA gene with universal eubacterial primers. Sterile, control (non-sterile), and sterilized and inoculated rabbit feces were used to assess the significance of bacteria in L. longipalpis development. Newly emerged adult flies were surface-sterilized and screened for the bacterial population size and diversity by the culturing approach. The digestive tract of L4 sterile and control larvae was incubated with Phalloidin to visualize muscle tissues and DAPI to visualize nuclei. Two-choice behavioural assays revealed a great preference of L. longipalpis to lay eggs on rabbit feces with an active complex bacterial community (control) (85.8 % of eggs) in comparison to that of sterile (autoclaved) rabbit feces (14.2 %). Bioassays demonstrated that L. longipalpis larvae can develop in sterile rabbit feces although development time to adult stage was greatly extended (47 days) and survival of larvae was significantly lower (77.8 %) compared to that of larvae developing in the control rabbit feces (32 days and 91.7 %). Larval survival on sterilized rabbit feces inoculated with the individual bacterial isolates originating from this substrate varied greatly depending on a bacterial strain. Rhizobium radiobacter supported larval development to adult stage into the greatest extent (39 days, 88.0 %) in contrast to that of Bacillus spp. (76 days, 36.0 %). From the complex natural bacterial community of rabbit feces, R. radiobacter survived pupation and colonized the newly emerged females most successfully (82.6 % of all bacteria cultured); however, only 25 % of females were positive for bacteria in the digestive tract upon emergence. Immunohistochemistry did not reveal any obvious differences in anatomy of the digestive tract between control and axenic larvae. The bacterial community in the sand fly larval habitat affects oviposition and larval development although bacteria are not essential for successful development of L. longipalpis. Different bacteria contribute to larval development to various degrees and some, e.g. Rhizobium radiobacter, survive pupation and colonize the digestive tract of newly emerged females. With the establishment of the axenic rearing system, this study opens new venues to study the effect of bacteria on the gut epithelial immunity and vector competence of sand flies for Leishmania parasites with a goal to develop paratransgenic approaches for Leishmania control.


Genetic diversity and differentiation among populations of the Indian eri silkworm, Samia cynthia ricini, revealed by ISSR markers.
Samia cynthia ricini (Lepidoptera: Saturniidae), the Indian eri silkworm, contributes significantly to the production of commercial silk and is widely distributed in the Brahmaputra river valley in North-Eastern India. Due to over exploitation coupled with rapid deforestation, most of the natural populations of S. cynthia ricini are dwindling rapidly and its preservation has become an important goal. Assessment of the genetic structure of each population is a prerequisite for a sustainable conservation program. DNA fingerprinting to detect genetic variation has been used in different insect species not only between populations, but also between individuals within a population. Since, information on the genetic basis of phenotypic variability and genetic diversity within the S. cynthia ricini populations is scanty, inter simple sequence repeat (ISSR) system was used to assess genetic diversity and differentiation among six commercially exploited S. cynthia ricini populations. Twenty ISSR primers produced 87% of inter population variability among the six populations. Genetic distance was lowest between the populations Khanapara (E5) and Mendipathar (E6) (0.0654) and highest between Dhanubhanga (E4) and Titabar (E3) (0.3811). Within population, heterozygosity was higher in Borduar (E2) (0.1093) and lowest in Titabar (E3) (0.0510). Highest gene flow (0.9035) was between E5 and E6 and the lowest (0.2172) was between E3 and E5. Regression analysis showed positive correlation between genetic distance and geographic distance among the populations. The high G(ST) value (0.657) among the populations combined with low gene flow contributes significantly to the genetic differentiation among the S. cynthia ricini populations. Based on genetic diversity, these populations can be considered as different ecotypes and in situ conservation of them is recommended.


Studies on the kinetics of killing and the proposed mechanism of action of microemulsions against fungi.
Microemulsions are physically stable oil/water clear dispersions, spontaneously formed and thermodynamically stable. They are composed in most cases of water, oil, surfactant and cosurfactant. Microemulsions are stable, self-preserving antimicrobial agents in their own right. The observed levels of antimicrobial activity associated with microemulsions may be due to the direct effect of the microemulsions themselves on the bacterial cytoplasmic membrane. The aim of this work is to study the growth behaviour of different microbes in presence of certain prepared physically stable microemulsion formulae over extended periods of time. An experiment was designed to study the kinetics of killing of a microemulsion preparation (17.3% Tween-80, 8.5% n-pentanol, 5% isopropyl myristate and 69.2% sterile distilled water) against selected test microorganisms (Candida albicans, Aspergillus niger, Schizosaccharomyces pombe and Rhodotorula spp.). Secondly, an experiment was designed to study the effects of the microemulsion preparation on the cytoplasmic membrane structure and function of selected fungal species by observation of 260 nm component leakage. Finally, the effects of the microemulsion on the fungal membrane structure and function using S. pombe were studied using transmission electron microscopy. The results showed that the prepared microemulsions are stable, effective antimicrobial systems with effective killing rates against C. albicans, A. niger, S. pombe and Rhodotorula spp. The results indicate a proposed mechanism of action of significant anti-membrane activity, resulting in the gross disturbance and dysfunction of the cytoplasmic membrane structure which is followed by cell wall modifications, cytoplasmic coagulation, disruption of intracellular metabolism and cell death.


Modern India and the vitamin D dilemma: evidence for the need of a national food fortification program.
India is located between 8.4 and 37.6 degrees N latitude with the majority of its population living in regions experiencing ample sunlight throughout the year. Historically, Indians obtained most of their vitamin D through adequate sun exposure; however, darker skin pigmentation and the changes which have accompanied India's modernization, including increased hours spent working indoors and pollution, limit sun exposure for many. Inadequate sun exposure results in reduced vitamin D synthesis and ultimately poor vitamin D status if not compensated by dietary intake. Dietary vitamin D intake is very low in India because of low consumption of vitamin D rich foods, absence of fortification and low use of supplements. All these factors contribute to poor vitamin D status as measured by low circulating levels of 25-hydroxy vitamin D. Our review searches the published literature specific to India for evidence that would confirm the need to fortify food staples with vitamin D or stimulate public health policies for vitamin D supplementation and dietary guidelines tailored to the Indian diet. This review documents findings of widespread vitamin D deficiency in Indian populations in higher and lower socioeconomic strata, in all age groups, in both genders and people in various professions. Moreover, poor vitamin D status in India is accompanied by increased bone disorders including osteoporosis, osteomalacia in adults and rickets and other bone deformities in children. Without a concerted national effort to screen for vitamin D status, to implement policies or guidelines for vitamin D fortification and/or supplementation and to re-assess recommended dietary intake guidelines, dramatic increase in the number of bone disorders and other diseases may lie ahead.


Effect of gastrin I and gastrin II on canine bile flow.
The role of gastrin in the hormonal control of canine hepatic bile flow was evaluated. Because of the importance of the presence of sulfation of the carboxyl terminal peptide in the function of other cholecystokinetic hormones and peptides in the biliary tract, the choleretic properties of sulfated gastrin II were compared to the choleretic properties of nonsulfated gastrin I. Exogenous administration of gastrin I and II to dogs with chronic bile fistulas demonstrated that gastrin II, but not I, significantly increased hepatic bile flow. Chemical stimulation of the release of endogenous gastrin in dogs with denervated antral pouches did not increase hepatic bile flow, whereas a choleresis resulted when the innervated antrum was stimulated. Serum gastrin values obtained during the infusion of gastrin II at doses that produced a choleresis resulted in serum gastrin values that were greater than those produced by a more physiological stimulus, such as chemical antral stimulation. The results of this study suggest that only the sulfated gastrin II, not gastrin I, is a choleretic agent in dogs and only at pharmacological, not physiological doses.


Malignant pericardial effusion in breast cancer: terminal event or treatable complication?
Few data are available on malignant pericardial effusion (MPCE) in breast cancer. We identify the patient prone to develop MPCE describe the result of surgical management, and try to identify a subgroup of patients who do not benefit from surgical management. We performed an audit of our policy of active search for MPCE in breast cancer patients and its treatment by subxiphoid pericardial fenestration. Nineteen patients with MPCE had a mean of 3.2 other sites of recurrence: 17 had pleural recurrence. Six patients had exertional dyspnea and 13 had dyspnea at rest; three needed emergency pericardiocentesis. An average of 740 ml of fluid was recovered; cytology was diagnostic in 11 cases and histopathology in 10 cases. At discharge, six patients had no dyspnea and six had exertional dyspnea. Of 10 patients who did not receive systemic treatment, eight died within 30 days. Nine patients who received systemic treatment had an average survival of 8.3 months. Patients with pleural recurrence presenting with dyspnea should be evaluated for the presence of a MPCE. Subxiphoid pericardial fenestration is the treatment of choice. Patients who will not receive systemic treatment should be managed conservatively.


PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer.
PSGR, a new prostate tissue-specific gene with homology to the G protein-coupled odorant receptor gene family, has been identified. Here we report the characteristics of the predicted protein sequence of PSGR and its prostate tissue specificity and expression profile in human prostate cancer and matched normal tissues. Using multiple tissue Northern blots from over 50 different tissues, PSGR expression was restricted to human prostate tissues. Paired normal and tumor specimens from 52 primary prostate cancers, obtained by laser capture microdissection or manual microdissection, were analyzed for PSGR expression by semiquantitative and real-time PCR assays. The differential expression of PSGR between normal and tumor tissues was highly significant (P < 0.001), and 32 of 52 (62%) matched prostate specimens exhibited tumor-associated overexpression of PSGR. Of note, there was very little or no expression of PSGR in many normal specimens in comparison with the generally high expression of PSGR seen in matched tumor specimens. In situ hybridization assays showed restricted PSGR expression in the epithelial cells of the normal and tumor tissue sections. Restricted expression of PSGR in prostatic epithelial cells, overexpression of the PSGR in a significant percentage of prostate cancers, and the predicted protein sequence of PSGR with seven transmembrane domains provide a foundation for future studies evaluating the potential of PSGR as a prostate cancer gene expression marker and the utility of PSGR protein as a novel target for developing immunotherapeutic strategies for prostate cancer.


Episodes of status epilepticus in young adults: etiologic factors, subtypes, and outcomes.
The aim of this study was to evaluate the type, duration, etiology, treatment, and outcome of status epilepticus (SE) episodes, among patients aged 16-50 years. A total of 101 SE episodes in 88 young adult patients fulfilled our criteria. The mean age was 32 years. Status epilepticus episodes were most frequently observed in patients 21-30 years of age. A total of 53% of the patients were male, and 57% had pre-existing epilepsy. Seventy of the 101 episodes were convulsive SE. The most common etiology was withdrawal of or change in antiepileptic drugs (AEDs), seen in 31% of the SE episodes. This study included treatment of SE with traditional AEDs. Sixty-six episodes were treated successfully with intravenous infusion of 18-mg/kg phenytoin, and six episodes were treated with 10-mg/kg phenytoin. A total of 28% of the SE episodes remained refractory to first-line treatment, which was related to the duration of SE and mortality. The outcome was death in 14% of the patients due to underlying etiologies in the hospital.