Gearing Up the Human Ankle-Foot System to Reduce Energy Cost of Fast Walking.
During locomotion, the human ankle-foot system dynamically alters its gearing, or leverage of the ankle joint on the ground. Shifting ankle-foot gearing regulates speed of plantarflexor (i.e., calf muscle) contraction, which influences economy of force production. Here, we tested the hypothesis that manipulating ankle-foot gearing via stiff-insoled shoes will change the force-velocity operation of plantarflexor muscles and influence whole-body energy cost differently across walking speeds. We used in vivo ultrasound imaging to analyze fascicle contraction mechanics and whole-body energy expenditure across three walking speeds (1.25, 1.75, and 2.0 m/s) and three levels of foot stiffness. Stiff insoles increased leverage of the foot upon the ground (p < 0.001), and increased dorsiflexion range-of-motion (p < 0.001). Furthermore, stiff insoles resulted in a 15.9% increase in average force output (p < 0.001) and 19.3% slower fascicle contraction speed (p = 0.002) of the major plantarflexor (Soleus) muscle, indicating a shift in its force-velocity operating region. Metabolically, the stiffest insoles increased energy cost by 9.6% at a typical walking speed (1.25 m/s, p = 0.026), but reduced energy cost by 7.1% at a fast speed (2.0 m/s, p = 0.040). Stiff insoles appear to add an extra gear unavailable to the human foot, which can enhance muscular performance in a specific locomotion task.


On the Relationship Between High-Order Linkage Disequilibrium and Epistasis.
A plausible explanation for statistical epistasis revealed in genome wide association analyses is the presence of high order linkage disequilibrium (LD) between the genotyped markers tested for interactions and unobserved functional polymorphisms. Based on findings in experimental data, it has been suggested that high order LD might be a common explanation for statistical epistasis inferred between local polymorphisms in the same genomic region. Here, we empirically evaluate how prevalent high order LD is between local, as well as distal, polymorphisms in the genome. This could provide insights into whether we should account for this when interpreting results from genome wide scans for statistical epistasis. An extensive and strong genome wide high order LD was revealed between pairs of markers on the high density 250k SNP-chip and individual markers revealed by whole genome sequencing in the Arabidopsis thaliana 1001-genomes collection. The high order LD was found to be more prevalent in smaller populations, but present also in samples including several hundred individuals. An empirical example illustrates that high order LD might be an even greater challenge in cases when the genetic architecture is more complex than the common assumption of bi-allelic loci. The example shows how significant statistical epistasis is detected for a pair of markers in high order LD with a complex multi allelic locus. Overall, our study illustrates the importance of considering also other explanations than functional genetic interactions when genome wide statistical epistasis is detected, in particular when the results are obtained in small populations of inbred individuals.


Central sleep apnoea syndrome in chronic heart failure: an underestimated and treatable comorbidity.
Chronic heart failure is a clinical syndrome with a high mortality and morbidity. Despite optimal therapy, five-year survival is still only 50%. Central sleep apnoea syndrome is seen in approximately 40% of patients with congestive heart failure. Sleep apnoea syndrome can be divided into two forms in these patients: obstructive sleep apnoea syndrome (OSAS) and central sleep apnoea syndrome (CSAS, Cheyne-Stokes respiration), of which CSAS is the most common. CSAS is a form of sleep apnoea in congestive heart failure which is driven by changes in pCO(2). As a consequence of apnoea-hypopnoea an imbalance in myocardial oxygen delivery/consumption ratio will develop, sympathetic and other neurohormonal systems will be activated and right and left ventricular afterload will be increased. Sleep apnoea is associated with an increased mortality in patients with systolic heart failure. Treatment of sleep apnoea increases left ventricular ejection fraction and transplant-free survival. Because of its high prevalence, poor quality of life, poor outcome, and the beneficial effects of treatment, physicians treating patients with heart failure should be aware of central sleep apnoea. There are different treatment options, but the exact effects and indications of each option have not yet been fully determined. Further studies should be done to further investigate its prevalence, and to establish the most adequate therapy for the individual patient. (Neth Heart J 2010;18:260-3.).


Historical Changes in Histological Diagnosis of Lung Cancer.
Histological classification of lung cancer is essential for investigations of carcinogenesis and treatment selection. We examined the temporal changes of lung cancer histological subtypes. Lung cancer cases diagnosed in the Life Span Study cohort between 1958 and 1999 were collected from tumor registries (TR), mainly consisting of population-based cancer registries. A total of 1,025 cases were histologically reviewed according to the World Health Organization 2004 Classification by a panel of pathologists (PP). Sensitivity and specificity of diagnoses in TR were calculated, assuming that the diagnosis by PP was the gold standard. Sensitivity and specificity were 0.91 and 0.92 for adenocarcinoma (AD), respectively, and 0.92 and 0.94, respectively, for squamous cell carcinoma (SQ). They were similar for AD and SQ throughout the observation period. For small cell carcinoma (SM), sensitivity was low until about 1980 (0.47 in 1958-1969, and 0.61 in 1970-1979) and then became higher thereafter (0.98 in 1980-1989, and 0.95 in 1990-1999), whereas specificity was high during the whole period (range 0.99 to 1.00). Among 45 cases that were not reported as SM in TR but diagnosed as SM by PP, 16 cases were recorded as undifferentiated carcinoma in TR. Diagnosis of AD and SQ of lung cancer were generally consistent between TR records and PP review, but SMs tended to be coded as other histological types until the 1970s.


Kidney-targeted triptolide-encapsulated mesoscale nanoparticles for high-efficiency treatment of kidney injury.
Bad water solubility and undesired toxicity of triptolide (TP) still restrict its clinical applications in renal diseases. In this work, well-defined, monodispersed, and uniform-sized TP-encapsulated mesoscale nanoparticles (TP-MNPs) were fabricated through a nanoprecipitation method, which possesses special kidney-targeting capacity, slow-release property, and high-efficiency treatment for renal ischaemia-reperfusion injury (IRI). The TP-MNPs had good cytocompatibility in wide TP concentration (0-500 ng ml-1) and time ranges (6-24 h). Ex vivo organ fluorescence imaging and pharmacokinetic analysis suggested that TP-MNPs possessed excellent kidney-targeting capability with long retention time (7 days). The TP-MNPs with a very low dose of TP (0.01 mg kg-1) could effectively protect the kidney against IRI, while 0.01 mg kg-1 TP was completely ineffective. After treatment with TP-MNPs, the serum creatine, blood urea nitrogen, expression of C3 complement, and phospho-extracellular signal-regulated kinase of renal IRI mice were estimated to be 5.9-, 2.0-, 5.4-, and 2.8-fold lower than those of the mice treated with TP, respectively. Compared with TP, the TP-MNPs exhibited ignorable hepatotoxicity, reproductive toxicity, and immunotoxicity, such as lower alanine aminotransferase (0.5 fold) and aspartate aminotransferase (0.2 fold), and a higher ratio of CD4+/CD8+ (2.2 fold). Thus, the monodispersed and uniform-sized TP-MNPs with special kidney-targeting and slow-release property may pave an avenue for designing a new therapeutic strategy for renal diseases.


Speaking one more language in early life has only minor effects on cognition in Taiwanese with low education level: the Taishan Project.
Increasing evidence shows that bilingualism or multilingualism may have beneficial effects on preventing dementia. We performed a cross-sectional, community-based study in Taiwan. Some elders (older than 70 years) in Taiwan can speak Japanese because of the formal Japanese education they received before World War II, when Taiwan was under Japanese rule. After the war, Mandarin Chinese was adopted as the official language of Taiwan. We assessed whether constantly using three languages had an effect on dementia prevalence and cognitive function. We defined multilingualism as the ability to fluently speak Taiwanese (T), Japanese (J), and Mandarin Chinese (C) in daily life. We evaluated the Mini-Mental State Examination and AD8 questionnaire results of 514 community-dwelling people older than 70 years in Taishan, Taiwan. Seventy-three of the subjects (14.2%) were multilingual (T, J, C) and 441 (85.8%) were bilingual (T, C). No difference was noted in dementia prevalence between multilingual (6.8%) and bilingual (7.4%) populations, but multilinguals were older than bilinguals (mean age: 79.9 vs 77.3 years). Multilinguals had higher Mini-Mental State Examination scores than bilinguals (mean: 24.6 vs. 22.7). However, after the subjects were stratified into low and high education level groups, the Mini-Mental State Examination difference was found to be significant in only the low education level group. Dementia prevalence did not significantly differ between the multilingual (T, J, C) and bilingual (T, C) groups. However, given that the average age of the multilingual group was approximately 2 years older than that of the bilingual group, there may have been minor effects in the multilingual group.


Investigating US medical students' motivation to respond to lapses in professionalism.
As unprofessional behaviour in physicians can compromise patient safety, all physicians should be willing and able to respond to lapses in professionalism. Although students endorse an obligation to respond to lapses, they experience difficulties in doing so. If medical educators knew how students respond and why they choose certain responses, they could support students in responding appropriately. The aim of this study was to describe medical students' responses to professionalism lapses in peers and faculty staff, and to understand students' motivation for responding or not responding. We conducted an explorative, qualitative study using template analysis, in which three researchers independently coded transcripts of semi-structured, face-to-face interviews. We purposefully sampled 18 student representatives convening at a medical education conference. Preliminary open coding of a data subset yielded an initial template, which was applied to further data and modified as necessary. All transcripts were coded using the final template. Finally, three sensitising concepts from the Expectancy-Value-Cost model were used to map participants' responses. Students mentioned having observed lapses in professionalism in both faculty staff and peers. Students' responses to these lapses were avoiding, addressing, reporting or initiating policy change. Generally, students were not motivated to respond if they did not know how to respond, if they believed responding was futile and if they feared retaliation. Students were motivated to respond if they were personally affected, if they perceived the individual as approachable and if they thought that the whole group of students could benefit from their actions. Expectancy of success, value and costs each appeared to be influenced by (inter)personal and system factors. The Expectancy-Value-Cost model effectively explains students' motivation for responding to lapses. The (inter)personal and system factors influencing students' motivation to respond are modifiable and can be used by medical educators to enhance students' motivation to respond to lapses in professionalism observed in medical school.


Best Practice Guidelines for Surgical Site Infection Prevention With Surgical Treatment of Early Onset Scoliosis.
Postoperative surgical site infection (SSI) is unfortunately a commonly encountered complication in the surgical treatment of children with Early Onset Scoliosis (EOS). There is documented variation in the treatment of this patient population. Previous work building consensus for the approach to high risk patients (eg, neuromuscular etiology) has been promising. The goal of the current study is to apply similar principles to develop consensus-based guidelines for the treatment of patients with EOS. A focus group from 2 multicenter pediatric spine deformity study groups developed a list of statements to be distributed to a larger group of EOS experts. Using the Delphi process, participants were presented with a systematic review of the literature as well as a review of current practices in growth friendly surgery. The first round was conducted using an electronic survey. Results of this survey were then discussed face-to-face and the statements were further refined. A final round was conducted using the Audience Response System, allowing participants to vote for each statement (strongly agree or agree). Agreement >80% or disagreement <20% was considered consensus. A total of 29 of 57 statements reached consensus. Negative statements (statements of disagreement) were excluded, so the final consensus guidelines included 22 statements. The number of statements from the previously published Best Practice Guidelines (BPG) approved for insertion and lengthening growth friendly procedures were 12 of 14 and 11 of 14, respectively. The high risk BPG therefore does not cover all of the issues specific to the EOS population, and explains why 22 statements reached consensus in the current guideline. Upon completion of the surveys, 100% of the participants agreed to support its publication. Using the Delphi process several "best practices" were developed for growth friendly surgical treatment of EOS. Level V.


α-N-Protected dipeptide acids: a simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide.
The importance of dipeptides both in medicinal and pharmacological fields is well documented and many efforts have been made to find simple and efficient methods for their synthesis. For this reason, we have investigated the synthesis of α-N-protected dipeptide acids by reacting the easily accessible mixed anhydride of α-N-protected amino acids with free amino acids under different reaction conditions. The combination of TBA-OH and DMSO has been found to be the best to overcome the low solubility of amino acids in organic solvents. Under these experimental conditions, the homogeneous phase condensation reaction occurs rapidly and without detectable epimerization. The present method is also applicable to side-chain unprotected Tyr, Trp, Glu, and Asp but not Lys. This latter residue is able to engage two molecules of mixed anhydride giving the corresponding isotripeptide. Moreover, the applicability of this protocol for the synthesis of tri- and tetrapeptides has been tested. This approach reduces the need for protecting groups, is cost effective, scalable, and yields dipeptide acids that can be used as building blocks in the synthesis of larger peptides.


Cystic artery and cystic duct assessment with 64-detector row CT before laparoscopic cholecystectomy.
To retrospectively assess 64-detector row computed tomography (CT) in the preoperative depiction of the cystic duct and cystic arteries in and around the Calot triangle. Institutional review board approval was obtained, with waiver of informed consent. A total of 245 consecutive patients (133 men, 112 women), including 48 patients who subsequently underwent cholecystectomy, were examined. Two independent observers evaluated the CT data set on the basis of axial sections, coronal and sagittal multiplanar reformations, and three-dimensional volume rendering. The relationship between the cystic arteries and the Calot triangle--which is bordered by the undersurface of the liver, common hepatic duct, and cystic duct--was also evaluated, and each patient was classified on the basis of the origin of the cystic arteries and the course to the Calot triangle. Statistical analysis was performed, and percentages and confidence intervals were calculated. The cystic arteries were delineated in 234 of the 245 patients. Both the Calot triangle and the cystic arteries were delineated in 223 patients. One cystic artery was seen in the Calot triangle in 173 patients, and two cystic arteries were seen in the Calot triangle in 12. One artery in the Calot triangle with accessory arteries from different origins outside the Calot triangle was seen in 18 patients, and no cystic artery was identified in 20. Cystic arteries were seen in 42 (92%; 95% confidence interval: 87%, 98%) of the 48 patients who subsequently underwent cholecystectomy. The relationship between the cystic arteries and the Calot triangle was in agreement with the surgical records for all patients. The configuration of the cystic duct and cystic arteries can be depicted preoperatively with 64-detector row CT in patients scheduled to undergo cholecystectomy.


Non-Anastomotic Complete ePTFE Axillobifemoral Bypass Disruption and Thrombosis Following Shoulder Dislocation.
Complete disruption of an expanded polytetrafluoroethylene (ePTFE) vascular graft is rare. This is a report of a case of a 70 year old man presenting with left shoulder dislocation, which was reduced immediately. Two weeks later, the patient presented with Rutherford 2b bilateral lower limb ischaemia related to the thrombosis of an ePTFE axillobifemoral bypass. The graft was implanted five years earlier for treatment of an aorto-enteric fistula secondary to an infected aortobifemoral bypass. A non-anastomotic pseudoaneurysm associated with complete disruption of the ePTFE graft was found. Systematic analysis of the explant showed that the rupture occurred at the level of a ringed external support and that ongoing tears also occurred on the posterior wall of the graft at the level of this external support. In conclusion, complete analysis of failure mechanisms even from an isolated report is mandatory.


Association of polymorphisms in mitofusin-2 gene with type 2 diabetes in Han Chinese.
MFN2 and ESRRA are candidate genes involved in the pathogenesis of T2D. Five tag-SNPs in MFN2 gene and three in ESRRA gene were selected and genotyped with TaqMan or PCR-RFLP method in stage 1 populations (555 patients with T2D and 649 control subjects) and stage 2 populations (546 patients with T2D versus 419 control subjects) in Han Chinese. And combining our published data, we estimated the interactions between genetic variants in the MFN2, ESRRA, and PGC-1α genes on the T2D risk using MDR. rs873458 (G > A) and rs2878677 (C > T) in MFN2 gene were significantly associated with T2D (P = 0.005 and 0.01) in stage 1 populations, and the association of other SNPs with T2D was not found. In stage 2 populations, we further confirmed the association between rs2878677 and T2D (P = 0.01). Combining the two stage populations, the data supported more significant effect of rs873458 and rs2878677 on T2D risk (P = 0.003 and 0.0001). A-C-G-T-C and G-T-C-T-C in MFN2 had significant association with T2D (P = 0.007 and 0.009). The present study also provided the evidence that MFN2 had interactions with PGC-1α (P < 0.0001) or ESRRA (P < 0.0001). This study suggested a role of MFN2 polymorphism in the risk of T2D; however, further studies are needed.


Induction of autophagy in axonal dystrophy and degeneration.
Autophagy is a highly regulated cellular mechanism for the bulk degradation of cytoplasmic contents. It has been implicated in a variety of physiological and pathological conditions relevant to neurological diseases. However, the regulation of autophagy in neurons and its role in neuronal and axonal pathology are not yet understood. Using transgenic mice producing green fluorescent protein-tagged autophagic marker microtubule-associated protein light chain 3 (GFP-LC3), we provide molecular evidence for the induction of autophagy in axonal dystrophy and degeneration in Purkinje cells of the Lurcher mice, a model for excitotoxic neurodegeneration. We show that the excitotoxic insult of Lurcher mutation triggers an early response of Purkinje cells involving accumulation of GFP-LC3-labeled autophagosomes in axonal dystrophic swellings (a hallmark of CNS axonopathy). In brain, LC3 interacts with high affinity with the microtubule-associated protein 1B (MAP1B). We show that MAP1B binds to LC3 of both cytosolic form (LC3I) and lipidated form (LC3II). Moreover, in cell culture, overexpression of MAP1B results in reduced LC3II levels and number of GFP-LC3-labeled autophagosomes; phosphorylated MAP1B is associated with GFP-LC3-labeled autophagosomes. Furthermore, in brain, phosphorylated MAP1B accumulates in axonal dystrophic swellings of degenerating Purkinje cells and binds to LC3 at increased level. Therefore, the MAP1B-LC3 interaction may participate in regulation of LC3-associated autophagosomes in neurons, in particular at axons, under normal and pathogenic conditions. We propose that induction of autophagy serves as an early stress response in axonal dystrophy and may participate in the remodeling of axon structures.


Control of phyllotaxy by the cytokinin-inducible response regulator homologue ABPHYL1.
Phyllotaxy describes the geometric pattern of leaves and flowers, and has intrigued botanists and mathematicians for centuries. How these patterns are initiated is poorly understood, and this is partly due to the paucity of mutants. Signalling by the plant hormone auxin appears to determine the site of leaf initiation; however, this observation does not explain how distinct patterns of phyllotaxy are initiated. abphyl1 (abph1) mutants of maize initiate leaves in a decussate pattern (that is, paired at 180 degrees), in contrast to the alternating or distichous phyllotaxy observed in wild-type maize and other grasses. Here we show that ABPH1 is homologous to two-component response regulators and is induced by the plant hormone cytokinin. ABPH1 is expressed in the embryonic shoot apical meristem, and its spatial expression pattern changes rapidly with cytokinin treatment. We propose that ABPH1 controls phyllotactic patterning by negatively regulating the cytokinin-induced expansion of the shoot meristem, thereby limiting the space available for primordium initiation at the apex.


The changing face of pulmonary hypertension diagnosis: a historical perspective on the influence of diagnostics and biomarkers.
Pulmonary hypertension is a complex, multifactorial disease that results in right heart failure and premature death. Since the initial reports of pulmonary hypertension in the late 1800s, the diagnosis of pulmonary hypertension has evolved with respect to its definition, screening tools, and diagnostic techniques. This historical perspective traces the earliest roots of pulmonary hypertension detection and diagnosis through to the current recommendations for classification. We highlight the diagnostic tools used in the past and present, and end with a focus on the future directions of early detection. Early detection of pulmonary hypertension and pulmonary arterial hypertension and the proper determination of etiology are vital for the early therapeutic intervention that can prolong life expectancy and improve quality of life. The search for a non-invasive screening tool for the identification and classification of pulmonary hypertension is ongoing, and we discuss the role of animal models of the disease in this search.


Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study.
To investigate the role of the brain dopaminergic system in cognitive impairment in patients with Parkinson disease (PD). We studied 28 patients with PD and 16 age-matched healthy control subjects using [18F] fluorodopa (fluorodopa F 18) positron emission tomography. Patients with PD showed a variable degree of cognitive impairment, which was assessed using the Mini-Mental State Examination and detailed neuropsychologic assessment, including tests sensitive for frontal lobe function. [18F] Fluorodopa uptake was reduced in the putamen (to 36% of the control mean; P<.001), the caudate nucleus (to 61% of the control mean; P<.001), and the frontal cortex (to 45% of the control mean; P<.001) in patients with PD compared with controls. There was no significant association between the degree of overall cognitive impairment of patients and [18F] fluorodopa uptake values. The influx constant (Ki(occ)) in the caudate nucleus had a negative association with performance in the attention-demanding Stroop interference task, especially with the interference time. The Ki(occ) in the frontal cortex had a positive correlation with performance in the digit span (backwards), verbal fluency, and verbal immediate recall tests. Thus, the better the patient performed in tasks demanding immediate and working memory and executive strategies, the better the [18F] fluorodopa uptake in the frontal cortex. In the putamen, no significant correlation was seen between the Ki(occ) value and any of the cognitive tests. The severity of the motor symptoms of PD and [18F]fluorodopa uptake showed a negative correlation in the putamen (r = -0.38; P = .04), and in the caudate nucleus a similar trend was seen (r = -0.36; P = .06). Reduced [18F]fluorodopa uptake in PD in the caudate nucleus (and frontal cortex) is related to impairment in neuropsychologic tests measuring verbal fluency, working memory, and attentional functioning reflecting frontal lobe function. This indicates that dysfunction of the dopamine system has an impact on the cognitive impairment of patients with PD. However, our results do not exclude the possibility of more generalized cognitive impairment in PD, the pathophysiology of which is probably different and more generalized.


Association and predatory capacity of fungi Pochonia chlamydosporia and Arthrobotrys cladodes in the biological control of parasitic helminths of bovines.
Nematophagous fungi are used in the biological control of the parasitic helminths of animals and plants. The association of ovicidal and predator nematophagous fungi may present a complementary and increased action on the biological control of helminths. Joint growth compatibility and predation tests were carried out on infective larvae of nematode parasites of bovines with the nematophagous fungus ovicide Pochonia chlamydosporia and the nematophagous fungus predator Arthrobotrys cladodes. The tests of antagonism in direct confrontation, antibiosis and the effect of volatile metabolites between the isolates of P. chlamydosporia and A. cladodes indicated the viability of joint growth of these fungi. The association of the fungi P. chlamydosporia and A. cladodes presented a higher predatory capacity of infective larvae of the parasitic nematodes of bovines when compared to the predation of the fungi used alone. Therefore, under laboratory conditions, the fungi studied presented growth compatibility and the association of these increased the nematicidal activity against parasitic helminths of cattle.


The Validity and Applicability of Using a Generic Exposure Assessment Model for Occupational Exposure to Nano-Objects and Their Aggregates and Agglomerates.
Control banding can be used as a first-tier assessment to control worker exposure to nano-objects and their aggregates and agglomerates (NOAA). In a second tier, more advanced modelling approaches are needed to produce quantitative exposure estimates. As currently no general quantitative nano-specific exposure models are available, this study evaluated the validity and applicability of using a generic exposure assessment model (the Advanced REACH Tool-ART) for occupational exposure to NOAA. The predictive capability of ART for occupational exposure to NOAA was tested by calculating the relative bias and correlations (Pearson) between the model estimates and measured concentrations using a dataset of 102 NOAA exposure measurements collected during experimental and workplace exposure studies. Moderate to (very) strong correlations between the ART estimates and measured concentrations were found. Estimates correlated better to measured concentration levels of dust (r = 0.76, P < 0.01) than liquid aerosols (r = 0.51, P = 0.19). However, ART overestimated the measured NOAA concentrations for both the experimental and field measurements (factor 2-127). Overestimation was highest at low concentrations and decreased with increasing concentration. Correlations seemed to be better when looking at the nanomaterials individually compared to combined scenarios, indicating that nanomaterial-specific characteristics are not well captured within the mechanistic model of the ART. Although ART in its current state is not capable to estimate occupational exposure to NOAA, the strong correlations for the individual nanomaterials indicate that the ART (and potentially other generic exposure models) have the potential to be extended or adapted for exposure to NOAA. In the future, studies investigating the potential to estimate exposure to NOAA should incorporate more explicitly nanomaterial-specific characteristics in their models.


Correlation between longitudinal bone growth, growth hormone, and insulin-like growth factor-I in prepubertal dogs.
To determine the association between longitudinal bone growth and concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in serum from prepubertal dogs. Animals-6 male 14-week-old German Shepherd Dogs. Blood was obtained every 30 minutes for 14 consecutive days. Concentrations of GH and IGF-I in serum were determined, using a canine-specific radioimmunoassay and conventional radioimmunoassay after acid-ethanol extraction, respectively. Simultaneous biplanar radiography was performed daily to measure bone growth. Spectral analysis was used to estimate specific features of GH secretion during an extended period. Multiple linear regression with different lag times between independent and dependent variables was used to determine the strongest predictors of bone growth. The power spectra of GH concentrations in serum had a primary peak at a frequency of 0.02 cycles/h or a periodicity of 50 h/cycle. A significant determinant of longitudinal bone growth was a lag time of 1 day in concentration of GH in serum. The relationship between IGF-I concentration in serum and bone growth was not significant. The primary frequency of GH secretion is outside the time frame of a single day and the concentration of GH in serum is a primary determinant of bone growth. A better understanding of the components of bone growth provide discernment to improved diagnosis and treatment of abnormal bone growth.


Trends in Health Disparities of Rural Latinos Pre- and Post-Accountable Care Organization Implementation.
We present findings from a longitudinal investigation, the purpose of which was to compare health disparities of rural Latino older adult patients diagnosed with diabetes to their non-Latino White counterparts. A pre-post design was implemented treating Medicare Accountable Care Organization (ACO) participation by Rural Health Clinics (RHCs) as an intervention, and using diabetes-related hospitalizations to measure disparities. Data for a nationwide panel of 2,683 RHCs were analyzed for a study period of eight years: 2008 - 2015. In addition, data were analyzed for a subset of 116 RHCs located in Florida, Texas, and California that participated in a Medicare ACO in one or more years of the study period. Two broad findings resulted from this investigation. First, for both the nationwide panel of RHCs and the three-state sample of "ACO RHCs," there was a decrease in the mean disparities in diabetes-related hospitalization rates over the eight-year study period. Second, in comparing a three-year time period after Medicare ACO implementation in 2012 to a four-year period before the implementation, a statistically significant difference in mean disparities was found for the nationwide panel. There are a number of factors that may contribute to the decrease in diabetes-related hospitalization rates for Latinos in more recent years. Future research will identify specific contributors to reducing diabetes-related hospitalization disparities between Latinos and the general population, including the possible influence of ACO participation by RHCs. This paper presents original research conducted using data related to rural Latino older adults. The data represent multiple states and an eight-year time period. The U.S. Latino population is growing at a rapid pace. As a group, they are at a high risk for developing diabetes, the complications of which are serious and costly to the patient and the U.S. healthcare system. With the continued growth of the Latino population, it is critical that their health disparities be monitored, and that factors that contribute to their health and well-being be identified and promoted.


The fidelity of mutans streptococci transmission and caries status correlate with breast-feeding experience among Chinese families.
Our previous study reported that the fidelity of mutans streptococci (MS) transmission from mother to infant was gender- and race-specific within a Birmingham, Ala., population. We hypothesized that fidelity might be a function of postnatal nurturing practices. The purpose of the present study was to investigate those factors that could be correlated with MS transmission among Chinese children whose nurturing histories were known. Forty-eight families with 2- to 3-year-old children were selected from two kindergartens of Beijing, China. A questionnaire concerning the childhood nursing practice was obtained from the parents. Dental caries status was examined, and bacterial samples were collected for all participants twice at 6-month intervals. An average of six isolates of MS was picked at random from selective medium from each individual at each visit. Chromosomal DNA fingerprints were performed for all MS isolates to determine the genomic similarity within each family and among individuals. The results showed that 66% of the children at 2-3 years of age harbored MS, and 46% were caries-active. Of those children, 70% were breast-fed. Among the children whose chromosomal DNA fingerprint genotypes of MS matched that of their mothers, 88% were breast-fed compared with only 12% who were not breast-fed (p = 0.03). We also found that children who were breast-fed for more than 9 months were likely to harbor strains of MS common to their mothers (p = 0.04) and experience more dental caries (dmft = 4.4) at 3 years of age compared with children who were breast-fed less than 9 months (dmft = 1.4, p = 0.04). The data suggest that breast-feeding, especially prolonged breast-feeding, may correlate with the fidelity of transmission and that prolonged breast-feeding may contribute to a higher caries rate.


Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.
Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1(cax/cax) (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1(cax/cax) mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1(cax/cax) SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7(+)/MYOD(-) progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice.


Unpacking vertical and horizontal integration: childhood overweight/obesity programs and planning, a Canadian perspective.
Increasingly, multiple intervention programming is being understood and implemented as a key approach to developing public health initiatives and strategies. Using socio-ecological and population health perspectives, multiple intervention programming approaches are aimed at providing coordinated and strategic comprehensive programs operating over system levels and across sectors, allowing practitioners and decision makers to take advantage of synergistic effects. These approaches also require vertical and horizontal (v/h) integration of policy and practice in order to be maximally effective. This paper examines v/h integration of interventions for childhood overweight/obesity prevention and reduction from a Canadian perspective. It describes the implications of v/h integration for childhood overweight and obesity prevention, with examples of interventions where v/h integration has been implemented. An application of a conceptual framework for structuring v/h integration of an overweight/obesity prevention initiative is presented. The paper concludes with a discussion of the implications of vertical/horizontal integration for policy, research, and practice related to childhood overweight and obesity prevention multiple intervention programs. Both v/h integration across sectors and over system levels are needed to fully support multiple intervention programs of the complexity and scope required by obesity issues. V/h integration requires attention to system structures and processes. A conceptual framework is needed to support policy alignment, multi-level evaluation, and ongoing coordination of people at the front lines of practice. Using such tools to achieve integration may enhance sustainability, increase effectiveness of prevention and reduction efforts, decrease stigmatization, and lead to new ways to relate the environment to people and people to the environment for better health for children.


A population-based study of ulnar neuropathy at the elbow in Washington State workers' compensation.
There are no population-based studies of return to work after ulnar neuropathy at the elbow (UNE). We examine the predictors of return to work following a diagnosis of work-related UNE. Workers diagnosed with work-related UNE between 1995 and 2000 were identified from the administrative records of the Washington State workers' compensation system (n = 2,863). The medical records of 250 randomly selected surgical cases were reviewed. The end of wage replacement, our primary outcome, is a surrogate marker of the potential ability to return to work. Cox proportional hazards regression analyses were used to model duration of wage replacement as a function of select sociodemographic, clinical, electrodiagnostic, and disability predictors. The mean wage replacement and medical benefits paid per case were $19,100 and $15,200, respectively. Older age, concomitant carpal tunnel syndrome, receipt of wage replacement benefits prior to diagnosis, and longer diagnostic delays were associated with lower return to work potential after injury. Type of treatment (surgical or conservative care) was not associated with return to work. Among surgically treated workers, receipt of wage replacement before establishing a diagnosis was inversely associated with return to work in multivariate models that included clinical severity and electrodiagnostic criteria. Work-related UNE is a common and costly occupational health challenge. Efforts to accurately diagnose UNE and maximize functional recovery should start in the first medical encounter. Older workers, those who have concomitant carpal tunnel syndrome, or who are already receiving wage replacement benefits at the time of diagnosis deserve special attention.


[Iron sources forming nitrosyl complexes in animal tissues].
Treatment of perfused mouse liver with nitric oxide does not change the intensities of ESR signals of iron-sulfur proteins characteristic of this tissue. Proceeding from this evidence and also from the ratio between the iron content in these proteins and dinitrosyl iron complexes (complexes 2.03) formed in the liver when it contacts with NO, it is concluded that iron-sulfur proteins are not involved in the formation of complexes 2.03. It seems that only the loosely bound form of non-heme iron-free iron is involved in this process.


Adsorption of polyelectrolyte-nanoparticle systems on silica: influence of ionic strength.
In this work the effect of ionic strength on the adsorption behavior of cationic polyelectrolyte (acrylamide-acrylamidopropyltrimethylammonium chloride) and negatively charged silica particles has been studied by means of ellipsometry. The adsorption of the polyelectrolyte was observed to increase with increasing salt concentration, a behavior typical for polyelectrolytes with a screening-reduced solvency and a nonelectrostatic affinity for the surface. A similar dependence on the ionic strength was observed when studying the electrolyte effect on the nanoparticle adsorption to the preadsorbed polyelectrolyte film, suggesting that the polyelectrolyte surface conformations largely govern the binding capacity of the particles to the surface.


What are the functional consequences of neurocognitive deficits in schizophrenia?
It has been well established that schizophrenic patients have neurocognitive deficits, but it is not known how these deficits influence the daily lives of patients. The goal of this review was to determine which, if any, neurocognitive deficits restrict the functioning of schizophrenic patients in the outside world. The author reviewed studies that have evaluated neurocognitive measures as predictors and correlates of functional outcome for schizophrenic patients. The review included 1) studies that have prospectively evaluated specific aspects of neurocognition and community (e.g., social and vocational) functioning (six studies), 2) all known studies of neurocognitive correlates of social problem solving (five studies), and 3) all known studies of neurocognitive correlates and predictors of psychosocial skill acquisition (six studies). Despite wide variation among studies in the selection of neurocognitive measures, some consistencies emerged. The most consistent finding was that verbal memory was associated with all types of functional outcome. Vigilance was related to social problem solving and skill acquisition. Card sorting predicted community functioning but not social problem solving. Negative symptoms were associated with social problem solving but not skill acquisition. Notably, psychotic symptoms were not significantly associated with outcome measures in any of the studies reviewed. Verbal memory and vigilance appear to be necessary for adequate functional outcome. Deficiencies in these areas may prevent patients from attaining optimal adaptation and hence act as "neurocognitive rate-limiting factors." On the basis of this review of the literature, a series of hypotheses are offered for follow-up studies.


Physiologic correlates of culture-bound dissociation: A comparative study of Brazilian spiritist mediums and controls.
Mediumship and spirit possession are cultural phenomena found in many societies worldwide. In Brazil, Spiritism (a tradition in which mediumship is emphasized) is the third largest religious denomination. The present study aimed to investigate physiologic correlates of nonpathological dissociative experiences by comparing 20 female spiritist mediums with several years of socially sanctioned practice to 20 female nonmedium control subjects from the same religious context. We measured plasma levels of hormones and neuroactive substances, as well as vital signs and heart rate variability (HRV) parameters, before and immediately after spirit communication. Although no between-group differences were noted in basal physiological parameters, in response to the possession experiences the groups differed in heart rate and in plasma concentrations of noradrenaline, thyroid-stimulating hormone (TSH), prolactin, and creatine phosphokinase (CPK). The changes in parameters indicated an arousal response in mediums and a relaxation response in control participants, and the same pattern of changes was observed in HRV parameters from each group during the possession experiences. However, the changes in physiologic parameters for mediums were mild and of short duration: 1 hour after the possession experiences, no difference in cardiac autonomic regulation was noted. No significant group effect was noted for melatonin. Cognitive control processes may explain the arousal associated with the dissociative state. Findings from this study suggest that pathological and nonpathological dissociation may have different physiological correlates.


Continuous culture of rat C6 glioma in serum-free medium.
In this communication we describe serum-free culture conditions for the serial propagation of the C6 glioma cell line. The growth rate, saturation density, and morphology of these cells are equivalent to those of their serum-grown counterparts when cultured in a 3:1 mixture of Dulbecco's modified Eagle's medium and Ham's medium F-12 supplemented with trace elements, insulin, transferrin, fibroblast growth factor, linoleic acid complexed to fatty acid-free bovine serum albumin, and a serum-spreading factor (SSF) partially purified from human plasma. The requirement for SSF in the medium can be satisfied by preincubating the tissue culture dishes with SSF. Tissue culture dishes sequentially pretreated with poly-D-lysine and purified cold insouluble globulin will also substitute for this requirement. The fatty acid-free bovine serum albumin/linoleic acid complex increases the growth rate of these cells but has no appreciable effect on their morphology, saturation density, or ability to grow with repeated subculture. The growth stimulation caused by this complex appears to be dependent on the fatty acid, as the fatty acid-free bovine serum albumin alone has no effect on the growth rate. Linoleic acid is cytotoxic in the absence of bovine serum albumin, and the fatty acid-free bovine serum albumin prevents this toxicity. Other fatty acids including oleic, arachidonic, and palmitic only partially substitute for the growth-promoting effect of linoleic acid.


In vitro Validation of Quantitative Light-Induced Fluorescence for the Diagnosis of Enamel Fluorosis in Permanent Teeth.
This study aimed to validate quantitative light-induced fluorescence (QLF) as a diagnostic tool for mild and moderate enamel fluorosis in permanent teeth, comparing it to visual diagnosis and histological assessment completed using polarized light microscopy (PLM). The buccal surfaces of 139 teeth were visually classified using the Thylstrup and Fejerskov Index (TFI) into sound (TFI 0; n = 17), mild (TFI 1-2; n = 69), and moderate (TFI 3-4; n = 43) fluorosis. Fluorosis was then assessed with QLF (variables ΔF, A, and ΔQ at 5-, 15-, and 30-radiance thresholds) using as reference areas the entire surface and a region of interest (ROI), identified as the most representative region of a fluorosis lesion. PLM images of longitudinal thin sections including the ROI were assessed for histological changes. Correlations among TFI, PLM, and QLF were determined. A receiver-operating characteristic curve was conducted to determine QLF's diagnostic accuracy when compared to the TFI and PLM assessments. This was used to assess the probability that the images were correctly ranked according to severity as determined by PLM and TFI. A positive correlation was found between QLF and PLM, and between QLF and TFI. QLF showed the highest sensitivity and specificity for the diagnosis of mild fluorosis. There was also a strong agreement between TFI and PLM. The selection of a ROI resulted in a stronger correlation with TFI and PLM than when the entire surface was used. The study results indicate that defining an ROI for QLF assessments is a valid method for the diagnosis of mild and moderate enamel fluorosis.


Isoimmunization in pregnancy to Gerbich antigen.
A case of hemolytic disease of the newborn due to Gerbich, a public antigen, is presented. The antibody which was IgG1 reacted in vitro with mononuclear phagocytes. Serial sonographic and amniotic fluid examinations were followed and a mildly jaundiced neonate was delivered. Further investigation may establish a relationship between severity of disease and IgG subclasses, a mononuclear phagocyte assay, and sonographic measurements. Sources of compatible blood for possible maternal, fetal, or neonatal transfusion include blood bank rare donor files, relatives, and autologous donation.


Synergistic Effects of Resveratrol and Temozolomide Against Glioblastoma Cells: Underlying Mechanism and Therapeutic Implications.
Temozolomide (TMZ) is a commonly used anti-glioblastoma (GBM) drug. However, glioblastoma cells frequently show primary and acquired resistance to TMZ. As a promising anti-GBM candidate, resveratrol (Res) faces the similar problem as TMZ. Although resveratrol combined with TMZ (Res/TMZ) has been reported to be used to treat GBMs, it remains unclear whether this combination is broad-spectrum for all glioma cells until now, especially for GBM cells/cases with dual drug resistance. The study aimed to evaluate the synergistic effects of resveratrol and TMZ against GBMs and identify the underlying mechanisms. Drug sensitivities of rat RG-2, human LN-18 and LN-428 cell lines and effectiveness of Res/TMZ combinations were investigated via multiple experimental methods. O6-methylguanine-DNA methyltransferase (MGMT) was observed by Western blotting and immunocytochemistry (ICC). Transducer and activator of transcription 3 (STAT3) signaling pathway and expression changes of STAT3-related gene were detected to explore the possible synergistic mechanism. One hundred micromolar resveratrol and 500 μM TMZ inhibited the growth of RG-2 cells and the low-dose combination (25 μM/250 μM) showed similar suppressive effects. LN-18 and, especially, LN-428 cells were neither sensitive to 100 μM resveratrol nor to 500 μM TMZ, while their growth was suppressed by combination of 75 μM Res/750 μM TMZ with the suppressive rates of 62.5% and 28.6% and apoptosis rates of 11.9% and 7.4%, respectively. Resveratrol had regulatory effect on the expression of MGMT and it could significantly down-regulate MGMT overexpression caused by TMZ. In addition, STAT3/Bcl-2/survivin signaling pathway was also remarkably inhibited in Res/TMZ-treated GBM cells. Our results demonstrated synergistic effects of Res/TMZ on RG-2 cells and their bilaterally sensitizing effects to LN-18 and LN-428 cells. Frequent upregulation of MGMT and activation of STAT3 are the unfavorable factors for the treatment of GBMs and they may be the potential targets of Res/TMZ therapy.


Exploiting features of adenovirus replication to support mammalian kinase production.
Faced with the current wealth of genomic data, it is essential to have robust and reliable methods of converting DNA sequences into their functional gene products. We demonstrate here that when conditions are established that take advantage of the replication-associated virus amplification, the virus-induced shutdown of host protein synthesis as well as the activation of signalling pathways that normally occur during virus replication, adenovirus biology can be exploited to generate a potent kinase expression system. Residual virus in the protein production has always been a limitation for adenovirus systems and we describe a DNA intercalator/ultraviolet light treatment that eliminates residual adenovirus in protein preparations that has no deleterious effect on enzyme activity. The use of mammalian cells in combination with adenovirus generated a variety of active enzymes which could not be produced in Escherichia coli or baculovirus-infected insect cells. Thus, the utility of adenovirus-mediated enzyme expression as a versatile alternative to established protein production technologies is demonstrated.


Determination of nutritional and bioactive properties of peptides in enzymatic pea, chickpea, and mung bean protein hydrolysates.
Within the primary structure of many pea and mung bean proteins are peptide sequences that can potentially be used in the formulation of therapeutic products for the treatment and prevention of human diseases. However, these peptide sequences need protease treatments before they can be released free of the parent proteins. Unlike chemical hydrolysis, enzymatic treatment enables more efficient tailoring of peptide products without formation of toxic by-products or destruction of amino acids. This review provides information on current methods that have been used to convert inactive pea and mung bean proteins into bioactive peptides. It focuses on 3 main bioactive properties, such as inhibitions of (1) angiotensin converting enzyme (ACE) activity; (2) calmodulin (CaM)-dependent enzymes; and (3) copper-chelating activity. ACE is an established marker for hypertension, high levels of some CaM-dependent enzymes are risk factors for various human diseases including cancer and Alzheimer's disease, and high vascular copper concentrations may potentiate atherosclerosis. Also reviewed are the production and evaluation of activity of hypoallergenic peptides that may offer protection against anaphylactic reactions. The 3 main proteins discussed are chickpea, mung bean, and field pea.


6K1, NIa-VPg, NIa-Pro, and CP of Wheat Streak Mosaic Virus Are Collective Determinants of Wheat Streak Mosaic Disease in Wheat.
Wheat streak mosaic virus (WSMV; genus Tritimovirus, family Potyviridae) is the causal agent of the most economically important wheat streak mosaic disease of wheat (Triticum aestivum) in the Great Plains region of the United States. WSMV determinants responsible for wheat streak mosaic disease in wheat are unknown. Triticum mosaic virus (TriMV), a wheat-infecting virus, was used as an expression vector for the transient expression of each of the WSMV-encoded cistrons in wheat. WSMV-encoded 6K1, NIa-VPg, NIa-Pro, and CP cistrons in TriMV elicited symptoms specific to different stages of wheat streak mosaic disease without significantly affecting the genomic RNA accumulation. WSMV 6K1 produced early wheat streak mosaic disease-like symptoms of severe chlorotic streaks and patches. NIa-VPg and CP caused severe chlorotic streaks, followed by moderate stunting (only with NIa-VPg) of wheat, mimicking early- and mid-stage symptoms of wheat streak mosaic disease. WSMV NIa-Pro caused mild chlorotic streaks, followed by dark green leaves with severe stunting, representing the late symptoms of wheat streak mosaic disease. Collectively, these data suggest that cumulative effects of WSMV-encoded 6K1, NIa-VPg, NIa-Pro, and CP are responsible for different stages of wheat streak mosaic disease symptoms in wheat. Furthermore, deletion analysis of wheat streak mosaic disease determinants revealed that complete 6K1 and NIa-Pro, amino acids 3 to 60 and 121 to 197 of NIa-VPg, and amino acids 101 to 294 of CP are responsible for wheat streak mosaic disease-like symptoms in wheat. This study suggests that management strategies for wheat streak mosaic disease in wheat should target WSMV determinants of the disease phenotype.


The relationships between stress, coping strategies, and quality of life among gynecologic cancer survivors.
Many studies have reported that gynecologic cancer diagnosis, surgery, adjuvant therapy, and survivorship can be extremely stressful for many people during their cancer journey, and most cancer survivors have experienced stress after cancer, which impacts their quality of life. Importantly, healthy stress management will assist patients in overcoming obstacles in their lives and enhance both the quality of life and the cancer adjustment process. This study aimed to investigate the relationships between stress, coping strategies, and quality of life among gynecologic cancer survivors and to assess the mediating effects of coping on the relationship between quality of life and stress. A series of regression models and Sobel test were conducted to investigate whether coping strategies mediated the relationship between stress and quality of life. Stress was a predictor of quality of life. Acceptance was the mediator between stress and quality of life. Tailored programs that foster coping strategies, such as the strategy of acceptance, to reduce stress and maintain quality of life in this vulnerable group need to be developed.


Differences in skin-prick and patch-test reactivity are related to the heterogeneity of atopic eczema in infants.
Current data indicate an obvious relation between food allergy and atopic eczema in infants. However, diagnostic methods for food allergy need to be supplemented. The objective was to study the relevance of food patch testing in the detection of food allergy in correlation with oral food challenge and skin prick tests in atopic infants. Infants with atopic eczema (n = 113) aged 2-24 months were studied. Each patient was subjected to double-blind, placebo-controlled, or open cow's milk challenge, and skin prick and patch tests. Polysensitization, as judged from skin test results, was common in patients with atopic eczema (79/113). Cow's milk challenge was positive in 54/113 infants; reactions were immediate in 36/54 and delayed in 18/54. Immediate-type reactions were associated with skin prick test positivity and delayed reactions with patch test positivity. Altogether 26% of the cow's milk-allergic infants were detected by patch testing only. Patch testing improved the accuracy of skin testing in the diagnosis of food allergy in infants with atopic eczema, but it needs to be standardized. Polysensitization appears to be more common than generally believed among infants with atopic eczema.


Nutrients and non-nutrients composition and bioactivity of wild and cultivated Coprinus comatus (O.F.Müll.) Pers.
Mushrooms have been reported as sources of biomolecules with various potential. Coprinus comatus was studied to obtain information about this species, comparing cultivated and wild samples. Free sugars, fatty acids, tocopherols, organic acids and phenolic acids were analyzed by chromatographic techniques coupled to different detectors. C. comatus methanolic extract was tested for its antioxidant potential (reducing power, radical scavenging activity and lipid peroxidation inhibition) and antimicrobial properties (tested towards Gram positive and negative bacteria, and microfungi). The toxicity for liver cells was tested in porcine liver primary cells. Both studied samples revealed similar nutritional value and energy contribution. The cultivated sample revealed the highest content in free sugars, monounsaturated fatty acids and tocopherols, while the wild mushroom was richer in saturated and polyunsaturated fatty acids, organic acids and phenolic compounds. The cultivated species also revealed the highest antioxidant potential and antimicrobial activity (with exception towards Gram negative bacteria and Aspergillus ochraceus). Both species revealed no toxicity towards porcine liver cells. The present study proved that cultivated and wild mushrooms from the same species could be excellent options as food and as sources of nutritional and bioactive compounds. Furthermore, differences in wild and cultivated samples were comparatively investigated for the first time.


Hydrogeology, chemical and microbial activity measurement through deep permafrost.
Little is known about hydrogeochemical conditions beneath thick permafrost, particularly in fractured crystalline rock, due to difficulty in accessing this environment. The purpose of this investigation was to develop methods to obtain physical, chemical, and microbial information about the subpermafrost environment from a surface-drilled borehole. Using a U-tube, gas and water samples were collected, along with temperature, pressure, and hydraulic conductivity measurements, 420 m below ground surface, within a 535 m long, angled borehole at High Lake, Nunavut, Canada, in an area with 460-m-thick permafrost. Piezometric head was well above the base of the permafrost, near land surface. Initial water samples were contaminated with drill fluid, with later samples <40% drill fluid. The salinity of the non-drill fluid component was <20,000 mg/L, had a Ca/Na ratio above 1, with δ(18) O values ∼5‰ lower than the local surface water. The fluid isotopic composition was affected by the permafrost-formation process. Nonbacteriogenic CH(4) was present and the sample location was within methane hydrate stability field. Sampling lines froze before uncontaminated samples from the subpermafrost environment could be obtained, yet the available time to obtain water samples was extended compared to previous studies. Temperature measurements collected from a distributed temperature sensor indicated that this issue can be overcome easily in the future. The lack of methanogenic CH(4) is consistent with the high sulfate concentrations observed in cores. The combined surface-drilled borehole/U-tube approach can provide a large amount of physical, chemical, and microbial data from the subpermafrost environment with few, controllable, sources of contamination.


New evidence of animal consciousness.
This paper reviews evidence that increases the probability that many animals experience at least simple levels of consciousness. First, the search for neural correlates of consciousness has not found any consciousness-producing structure or process that is limited to human brains. Second, appropriate responses to novel challenges for which the animal has not been prepared by genetic programming or previous experience provide suggestive evidence of animal consciousness because such versatility is most effectively organized by conscious thinking. For example, certain types of classical conditioning require awareness of the learned contingency in human subjects, suggesting comparable awareness in similarly conditioned animals. Other significant examples of versatile behavior suggestive of conscious thinking are scrub jays that exhibit all the objective attributes of episodic memory, evidence that monkeys sometimes know what they know, creative tool-making by crows, and recent interpretation of goal-directed behavior of rats as requiring simple nonreflexive consciousness. Third, animal communication often reports subjective experiences. Apes have demonstrated increased ability to use gestures or keyboard symbols to make requests and answer questions; and parrots have refined their ability to use the imitation of human words to ask for things they want and answer moderately complex questions. New data have demonstrated increased flexibility in the gestural communication of swarming honey bees that leads to vitally important group decisions as to which cavity a swarm should select as its new home. Although no single piece of evidence provides absolute proof of consciousness, this accumulation of strongly suggestive evidence increases significantly the likelihood that some animals experience at least simple conscious thoughts and feelings. The next challenge for cognitive ethologists is to investigate for particular animals the content of their awareness and what life is actually like, for them.


[Scarf pin: an intrabronchial foreign body who is not unusual].
Inhalation of foreign bodies is rare in adults. Inhalation of scarf pin is a phenomenon more frequent in the female population in Morocco. The aim of our study was to describe the characteristics of this particular foreign body and illustrate the circumstances and consequences of its inhalation. Twenty-six young patients, all veiled, were hospitalized in the service of Respiratory Diseases University Hospital Ibn Rushd of Casablanca between January 2005 and July 2011 for inhaled scarf pin. The mean age was 16 years. Inhalation was accidental in all cases, whereas patients initiated to wear the veil. The penetration syndrome was found in all cases. Clinical examination was normal in all patients. The chest X-ray showed the foreign body as a linear opacity, located right in 18 cases and left in eight cases. Flexible bronchoscopy was able to extract the pin in 21 cases. The pin was released spontaneously in three cases and two patients were operated on. The scarf pin is a foreign body especially more common in women who wear the Islamic veil. Flexible bronchoscopy is an essential means of therapy, but the best preventive treatment is avoiding to put in the mouth sharp objects.


Marijuana smoking and fungal sensitization.
The possible role of marijuana (MJ) in inducing sensitization to Aspergillus organisms was studied in 28 MJ smokers by evaluating their clinical status and immune responses to microorganisms isolated from MJ. The spectrum of illnesses included one patient with systemic aspergillosis and seven patients with a history of bronchospasm after the smoking of MJ. Twenty-one smokers were asymptomatic. Fungi were identified in 13 of 14 MJ samples and included Aspergillus fumigatus, A. flavus, A. niger, Mucor, Penicillium, and thermophilic actinomycetes. Precipitins to Aspergillus antigens were found in 13 of 23 smokers and in one of 10 controls, while significant blastogenesis to Aspergillus was demonstrated in only three of 23 MJ smokers. When samples were smoked into an Andersen air sampler, A. fumigatus passed easily through contaminated MJ cigarettes. Thus the use of MJ assumes the risks of both fungal exposure and infection, as well as the possible induction of a variety of immunologic lung disorders.


The Surface of Ionic Liquids in Water: From an Ionic Tug of War to a Quasi-Ordered Two-Dimensional Layer.
The sustainable development encompasses the search for new materials for energy storage, gas capture, separation, and solvents in industrial processes that can substitute conventional ones in an efficient and clean manner. Ionic liquids (ILs) emerged and have been advanced as alternative materials for such applications, but an obstacle is their hygroscopicity and the effects on their physical properties in the presence of humidity. Several industrial processes depend on the aqueous interfacial properties, and the main focus of this work is the water/IL interface. The behavior of the aqueous ionic liquids at the water-vacuum interface is representative for their water interfacial properties. Using X-ray photoelectron spectroscopy in combination with molecular dynamics simulations we investigate four aqueous IL systems, and provide molecular level insight on the interfacial behaviour of the ionic liquids, such as ion-pair formation, orientation and surface concentration. We find that ionic liquids containing a chloride anion have a lowered surface enrichment due to the low surface propensity of chloride. In contrast, the ionic liquids containing a bistriflimide anion are extremely surface-enriched due to cooperative surface propensity between the cations and anions, forming a two-dimensional ionic liquid on the water surface at low concentrations.


Role of CC chemokines in skeletal muscle functional restoration after injury.
The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradually returned to control (uninjured) levels by 14 days. Muscle function and histological characteristics were monitored in injured mice that were genetically deficient for the CCR5 receptor (a major receptor for MIP-1alpha and MIP-1beta) and also rendered MCP-1 deficient with neutralizing antibodies. To dissect the role of these chemokines, additional studies were conducted in CCR5- and CCR2-deficient mice. CCR5-/- mice injected with MCP-1 antiserum for the first 3 days after injury exhibited a twofold greater maximal isometric tetanic torque deficit at 14 days after injury than did controls (i.e., 33% vs. 17%; P = 0.002). The impaired functional recovery was accompanied with an increased fat infiltration within the regenerating muscle without a significant difference in the influx of inflammatory cells, including macrophages. Strength recovery was also impaired in mice deficient for the receptor of MCP-1, CCR2, but not in CCR5-/- mice that were not injected with MCP-1 antiserum. The data suggest that MCP-1/CCR2 plays a role in the regeneration and recovery of function after traumatic muscle injury.


Gene vectors for cytokine expression in vivo.
The understanding of cytokine networks and the exploitation of these networks for the treatment of immune and inflammatory diseases as well as cancer depend on in vivo delivery of cytokines. Due to instability of recombinant cytokine proteins, investigators have employed cytokine-encoding gene therapy vectors to induce high levels of cytokine expression in vivo. Numerous gene therapy vectors have been developed recently which are suitable for this purpose. Recent advances in the design of adenovirus, adeno-associated virus, poxvirus, retrovirus, lentivirus, and nonviral vectors are described here. Properties of the various vector systems which determine their usefulness for cytokine gene delivery are compared. The implementations of cytokine-encoding gene therapy vectors for analyzing immune responses and for the therapy of inflammatory disorders, immune disease, infections and cancer are reviewed.


Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice.
Glucagon-like peptide-1 (7-36)amide (GLP-1) is cleaved by dipeptidyl peptidase-4 (DPP-4) to GLP-1 (9-36)amide. We examined whether chemical inhibition or genetic elimination of DPP-4 activity affects cardiovascular function in normoglycemic and diabetic mice after experimental myocardial infarction. Cardiac structure and function was assessed by hemodynamic monitoring and echocardiography in DPP-4 knockout (Dpp4(-/-)) mice versus wild-type (Dpp4(+/+)) littermate controls and after left anterior descending (LAD) coronary artery ligation-induced myocardial infarction (MI). Effects of sustained DPP-4 inhibition with sitagliptin versus treatment with metformin were ascertained after experimental MI in a high-fat diet-streptozotocin model of murine diabetes. Functional recovery from ischemia-reperfusion (I/R) injury was measured in isolated hearts from Dpp4(-/-) versus Dpp4(+/+) littermates and from normoglycemic wild-type (WT) mice treated with sitagliptin or metformin. Cardioprotective signaling in the murine heart was examined by RT-PCR and Western blot analyses. Dpp4(-/-) mice exhibited normal indexes of cardiac structure and function. Survival post-MI was modestly improved in normoglycemic Dpp4(-/-) mice. Increased cardiac expression of phosphorylated AKT (pAKT), pGSK3beta, and atrial natriuretic peptide (ANP) was detected in the nonischemic Dpp4(-/-) heart, and HO-1, ANP, and pGSK3beta proteins were induced in nonischemic hearts from diabetic mice treated with sitagliptin or metformin. Sitagliptin and metformin treatment of wild-type diabetic mice reduced mortality after myocardial infarction. Sitagliptin improved functional recovery after I/R injury ex vivo in WT mice with similar protection from I/R injury also manifest in hearts from Dpp4(-/-) versus Dpp4(+/+) mice. Genetic disruption or chemical inhibition of DPP-4 does not impair cardiovascular function in the normoglycemic or diabetic mouse heart.


Parathyroid adenomas with pronounced lymphocytic infiltration: no evidence of autoimmune pathogenesis.
Pronounced lymphocytic infiltration in parathyroid adenoma is rare, with only six previously reported cases in the literature. The aims of this study are to review the features and investigate the pathogenesis of this rare entity. Two solitary parathyroid adenomas having this feature were reported, and the clinicopathologic features of all the documented cases were reviewed. The nature of the lymphoid infiltrate and the presence of Epstein-Barr virus (EBV) were analyzed to unveil the pathogenesis of this infiltrate. One adenoma was found in a 70-yr-old woman with primary hyperparathyroidism and valvular heart disease. The other was an autopsy finding in a 48-yr-old man who had presented with hypercalcemic crisis. The lymphoid cell population within the tumors was composed of B cells and different subsets of T cells. EBV was not detected in the infiltrates. The lymphocytic infiltrate in parathyroid adenoma is an unusual histologic entity. Its presence is unlikely to imply an autoimmune disorder. We hypothesize that the lesion may be a result of local tissue response to parathyroid adenoma.


Evaluating the implementation and effectiveness of a multi-component intervention to reduce post-surgical opioid prescribing: study protocol of a mixed-methods design.
Opioids prescribed after surgery accounted for 5% of the 191 million opioid prescriptions filled in 2017. Approximately 80% of the opioid pills prescribed by surgical care providers remain unused, leaving a substantial number of opioids available for non-medical use. We developed a multi-component intervention to address surgical providers' role in the overprescribing of opioids. Our study will determine effective strategies for reducing post-surgical prescribing while ensuring adequate post-surgery patient-reported pain-related outcomes, and will assess implementation of the strategies. The Minimising Opioid Prescribing in Surgery study will implement a multi-component intervention, in an Illinois network of six hospitals (one academical, two large community and three small community hospitals), to decrease opioid analgesics prescribed after surgery. The multi-component intervention involves four domains: (1) patient expectation setting, (2) baseline assessment of opioid use, (3) perioperative pain control optimisation and (4) post-surgical opioid minimisation. Four surgical specialities (general, orthopaedics, urology and gynaecology) at the six hospitals will implement the intervention. A mixed-methods approach will be used to assess the implementation and effectiveness of the intervention. Data from the network's enterprise data warehouse will be used to evaluate the intervention's effect on post-surgical prescriptions and a survey will collect pain-related patient-reported outcomes. Intervention effectiveness will be determined using a triangulation design, mixed-methods approach with staggered speciality-specific implementation for contemporaneous control of opioid prescribing changes over time. The Consolidated Framework for Implementation Research will be used to evaluate the site-specific contextual factors and adaptations to achieve implementation at each site. The study aims to identify the most effective hospital-type and speciality-specific intervention bundles for rapid dissemination into our 56-hospital learning collaborative and in hospitals throughout the USA. All study activities have been approved by the Northwestern University Institutional Review Board (ID STU00205053).


Ouabain-like and non-ouabain-like factors in plasma of patients with essential hypertension.
Circulating inhibitor of Na+,K+-ATPase and ouabain-like immunoreactivity were studied in patients with essential hypertension. In the plasma of patients, two types of Na+,K+-ATPase inhibitors (ouabain-like and non-ouabain-like inhibitors) and ouabain-like immunoreactivity were detected. Ouabain-like inhibitor was clearly detected at a low KCl concentration (0.1 mM) in the assay buffer, and non-ouabain-like inhibitor was detected at a high KCl concentration (10 mM). The plasma level of ouabain-like inhibitor correlated significantly with that of ouabain-like immunoreactivity (p less than 0.001) and with a mean blood pressure (p less than 0.01). The plasma level of non-ouabain-like inhibitor was not correlated with the levels of either ouabain-like immunoreactivity or mean blood pressure. The level of plasma ouabain-like inhibitor did not correlate with that of plasma non-ouabain like inhibitor. Both ouabain-like inhibitor and ouabain-like immunoreactivity in the plasma of patients with essential hypertension were significantly higher than those in normotensive subjects, but the plasma level of non-ouabain-like inhibitor in patients with essential hypertension was not higher than that in normotensive subjects. These results suggest that the plasma from patients with essential hypertension contains ouabain-like factor(s) which is important to maintain the high blood pressure.


Characterization of trapping force on metallic mie particles.
Transverse trapping force on three types of metallic Mie particles (gold, nickel, and silver) is measured for different values of the numerical aperture of an objective used for trapping. The experimental results are compared with those calculated with a modified ray-optics model. It is found that, unlike the situation for a trapped dielectric particle, the maximum transverse trapping efficiency for a trapped metallic particle is increased with the numerical aperture of the trapping objective. After consideration of radiometric force, which is caused by the heating effect, and spherical aberration, which is induced by the refractive-index mismatch, the measured results agree well with the theoretical prediction. The magnitude of the radiometric force is approximately ten times stronger than the maximum transverse trapping force.


Gene expression reveals evidence for EGFR-dependent proximal-distal limb patterning in a myriapod.
Evolution of segmented limbs is one of the key innovations of Arthropoda, allowing development of functionally specific specialized head and trunk appendages, a major factor behind their unmatched evolutionary success. Proximodistal limb patterning is controlled by two regulatory networks in the vinegar fly Drosophila melanogaster, and other insects. The first is represented by the function of the morphogens Wingless (Wg) and Decapentaplegic (Dpp); the second by the EGFR-signaling cascade. While the role of Wg and Dpp has been studied in a wide range of arthropods representing all main branches, that is, Pancrustacea (= Hexapoda + Crustacea), Myriapoda and Chelicerata, investigation of the potential role of EGFR-signaling is restricted to insects (Hexapoda). Gene expression analysis of Egfr, its potential ligands, and putative downstream factors in the pill millipede Glomeris marginata (Myriapoda: Diplopoda), reveals that-in at least mandibulate arthropods-EGFR-signaling is likely a conserved regulatory mechanism in proximodistal limb patterning.


Brain-Tumor-Regenerating 3D Scaffold-Based Primary Xenograft Models for Glioma Stem Cell Targeted Drug Screening.
Glioma stem cells (GSC) present a critical therapeutic challenge for glioblastoma multiforme (GBM). Drug screening against GSC demands development of novel in vitro and in vivo platforms that can mimic brain microenvironment and support GSC maintenance and tumorigenesis. Here, we report, a 3-dimensionel (3D) biomimetic macro-porous scaffold developed by incorporating hyaluronic acid, porcine brain extra cellular matrix (ECM) and growth factors that facilitates regeneration of GBM from primary GSCs, ex vivo and in vivo. After characterizing with human and rat GBM cell lines and neurospheres, human GSCs expressing Notch1, Sox-2, Nestin, and CD133 biomarkers were isolated from GBM patients, cultured in the 3D scaffold, and implanted subcutaneously in nude mice to develop patient derived xenograft (PDX) models. Aggressive growth pattern of PDX with formation of intratumoral vascularization was monitored by magnetic resonance imaging (MRI). Histopathological and phenotypial features of the original tumors were retained in the PDX models. We used this regenerated GBM platform to screen novel siRNA nanotherapeutics targeting Notch, Sox-2, FAK signaling for its ability to inhibit the tumorigenic potential of GSCs. Current clinical drug, Temozolomide and an anticancer phytochemical, nanocurcumin, were used as controls. The siRNA nanoparticles showed excellent efficacy in inhibiting tumorigenesis by GSCs in vivo. Our study suggests that the brain-ECM mimicking scaffold can regenerate primary gliomas from GSCs in vitro and in vivo, and the same can be used as an effective platform for screening drugs against glioma stem cells.


Electrostatic solitons and Alfvén waves generated by streaming instability in electron-positron plasmas.
Electron-positron plasmas may be present in laboratory experiments and certain astrophysical environments. Due to the inertia symmetry there have been some debates about whether the nonlinear electrostatic solitons generated easily in electron-proton plasmas may develop in electron-positron plasmas. In this study we show the formation of electrostatic solitons and electromagnetic Alfvén waves in extensive magnetized electron-positron plasma system generated by streaming instabilities based on electromagnetic particle simulations along with fluid theory analyses. In particular, the four-component beam-plasma system may lead to the formation of interlacing electron and positron solitons in the early evolution stage (say, t<20ω_{p}^{-1}, where ω_{p}^{} is the plasma frequency) and large-amplitude Alfvén waves in the later phase (say, t>150ω_{p}^{-1}). The magnetic-field perturbations are generated by the beam and firehose-type instabilities associated with temperature anisotropy of T_{∥}>T_{⊥} resulting from the parallel plasma heating by the electrostatic instability. It is shown that the growth rates and the dominant wavelengths of both electrostatic and electromagnetic instabilities are consistent with the fluid theory. The coexistence of electrostatic solitons and electromagnetic Alfvén waves with significant magnetic field fluctuations in the same system is a unique feature of electron-positron plasmas and the unified theory behind the formation mechanisms is well addressed in the paper.


Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes.
The relative functional maturity of neonatal mouse spleen T- and B-cell populations was assessed by comparing the ability to respond to the thymic-independent antigen, DNP-Ficoll, or thymic-dependent SRBC by producing antibody in vitro. Although mouse spleen cells responded to DNP-Ficoll at an earlier age than they responded to SRBC or TNP-SRBC, the reason for the lag in the T-dependent response was confounded by the finding of high numbers of suppressor T lymphocytes in the neonatal spleen. Thus, small numbers of neonatal spleen T cells or thymocytes significantly decreased the in vitro antibody response of adult spleen cells. Although B lymphocytes appear to be functionally mature soon after birth, their acitivity may be modulated by an excess of suppressor T cells; e.g., the reconstitution of helper cell function in the neonatal spleen required anti-theta treatment before addition of adult helper cells. Suppressive activity attributable to T cells seems to play a dominant role in determining the ability of the neonatal animal to react positively or negatively to antigenic stimulation.


Fibroblast growth factor receptor signaling in Xenopus retinal axon extension.
Fibroblast growth factor receptors (FGFRs) and N-cadherin both regulate axon extension in developing Xenopus retinal ganglion cells (RGCs). Cultured cerebellar neurons have been shown to require FGFR activity for N-cadherin-stimulated neurite outgrowth, raising the possibility that N-cadherin is a FGFR ligand. To investigate this possibility in the developing visual system, retinal neurons were transfected with a dominant-negative FGFR (XFD) and plated on purified N-cadherin substrates. XFD-expressing neurons extended markedly shorter processes than control GFP-expressing neurons, implicating a role for FGFRs in N-cadherin-stimulated neurite outgrowth. To examine whether N-cadherin and FGFRs share the same pathway or use distinct second messenger pathways, specific inhibitors of implicated signaling molecules were added to neurons stimulated by N-cadherin, basic fibroblast growth factor (bFGF), or brain-derived nerve factor (BDNF) (which stimulates RGC outgrowth by a FGFR-independent mechanism). Diacylglycerol (DAG) lipase and Ca2+/calmodulin kinase II inhibitors both significantly reduced outgrowth stimulated by N-cadherin or bFGF but not by BDNF. Furthermore, we show that inhibiting DAG lipase activity in RGC axons extending in vivo toward the optic tectum reversibly slows axon extension without collapsing their growth cones. Thus, a common second-messenger signaling pathway mediating both N-cadherin- and bFGF-stimulated neurite extension is consistent with a model in which N-cadherin directly modulates the FGFR or a model whereby both FGFR and N-cadherin regulate the same second-messenger system.


IFN-gamma and Fas ligand are required for graft-versus-tumor activity against renal cell carcinoma in the absence of lethal graft-versus-host disease.
To determine the mechanisms of graft-versus-tumor (GVT) activity in the absence of graft-versus-host disease (GVHD) against a solid tumor, we established two allogeneic bone marrow transplantation models with a murine renal cell carcinoma (RENCA). The addition of 0.3 x 10(6) donor CD8(+) T cells to the allograft increased the survival of tumor-bearing mice without causing GVHD. The analysis of CD8(+) T cells deficient in cytotoxic molecules demonstrated that anti-RENCA activity is dependent on IFN-gamma and Fas ligand (FasL), but does not require soluble or membrane-bound TNF-alpha, perforin, or TRAIL. Recipients of IFN-gamma(-/-) CD8(+) T cells are unable to reject RENCA compared with recipients of wild-type CD8(+) T cells and, importantly, neither group develops severe GVHD. IFN-gamma(-/-) CD8(+) T cells derived from transplanted mice are less able to kill RENCA cells in vitro, while pretreatment of RENCA cells with IFN-gamma enhances class I and FasL expression and rescues the lytic capacity of IFN-gamma(-/-) CD8(+) T cells. These results demonstrate that the addition of low numbers of selected donor CD8(+) T cells to the allograft can mediate GVT activity without lethal GVHD against murine renal cell carcinoma, and this GVT activity is dependent on IFN-gamma and FasL.


The role of serratiopeptidase in the resolution of inflammation.
Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase (COX-I and COX-II), a key enzyme associated with production of different inflammatory mediators including interleukins (IL), prostaglandins (PGs) and thromboxane (TXs) etc. Currently, arthritis, sinusitis, bronchitis, fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs (NSAIDs) alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs (anti-inflammatory) emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an anti-inflammatory drug. The study also illustrates a comparative analysis of conventional drugs and enzyme based therapeutic to combat inflammation.


Risk, Feasibility, and Cost Evaluation of a Prisoner Condom Access Pilot Program in One California State Prison.
This study evaluated the safety and security impact, feasibility, and cost of a program to provide condoms to inmates. A 1-year pilot study of wall-mounted condom dispensing machines in one California state prison compared pre- and post-intervention rates of penal code violations related to sexual misconduct, contraband, controlled substances, and violence. The rates of penal code violations were unchanged or decreased compared to the pre-pilot year. Discreetly located condom dispensers were vandalized less frequently than those in plain view (p < .05). Distributing condoms using the pilot model would cost less than $2 per inmate annually. Results suggest that the use of discreetly located dispensing machines is an acceptable, feasible, low-cost option to prevent the transmission of sexually transmitted diseases and poses no safety or security risk in a typical medium-security prison setting.


Squeezout phenomena and boundary layer formation of a model ionic liquid under confinement and charging.
Electrical charging of parallel plates confining a model ionic liquid down to nanoscale distances yields a variety of charge-induced changes in the structural features of the confined film. That includes even-odd switching of the structural layering and charging-induced solidification and melting, with important changes of local ordering between and within layers, and of squeezout behavior. By means of molecular dynamics simulations, we explore this variety of phenomena in the simplest charged Lennard-Jones coarse-grained model including or excluding the effect a neutral tail giving an anisotropic shape to one of the model ions. Using these models and open conditions permitting the flow of ions in and out of the interplate gap, we simulate the liquid squeezout to obtain the distance dependent structure and forces between the plates during their adiabatic approach under load. Simulations at fixed applied force illustrate an effective electrical pumping of the ionic liquid, from a thick nearly solid film that withstands the interplate pressure for high plate charge to complete squeezout following melting near zero charge. Effective enthalpy curves obtained by integration of interplate forces versus distance show the local minima that correspond to layering and predict the switching between one minimum and another under squeezing and charging.


An evaluation of the strategic approach to the rehabilitation of traumatic brain injury (TBI) patients.
The objective of our study was to evaluate a goal-driven strategic plan for the step-by-step rehabilitation of traumatic brain injury (TBI) patients, with effectiveness measured in terms of quality of life, as compared to patients treated according to a standard, progressive rehabilitation program. We studied 40 patients after TBI awakened from a long-term coma. The patients were divided into two equal groups: a control group (n=20) involving patients treated before the introduction of the strategic approach, and an experimental group (n=20) involving patients rehabilitated under the strategic approach. In evaluating the effectiveness of rehabilitation we used a structured interview with clinical observation and a scale for assessing the quality of life of patients after TBI. The deterioration in the quality of life of TBI patients is mainly related to difficulties in satisfying physiological needs, self-care, reduced mobility and disorders of cognitive, regulatory, and social functions. In both groups, the feature most susceptible to rehabilitation related change was movement, while the least susceptible functions were associated with the use of different means of transport. This change is significantly greater in persons in the experimental group, as compared to controls. We found that a rehabilitation program controlled by a strategic plan, with the cooperation of the patient, is more effective in improving the quality of life, as the patient is more self-motivated to individually designed objectives.


Quantitative evaluation of inflammatory and immune responses in the early stages of chronic Helicobacter pylori infection.
The early consequences of Helicobacter pylori infection and the role of bacterial virulence determinants in disease outcome remain to be established. The present study sought to measure the development of host inflammatory and immune responses and their relationship to the putative bacterial virulence factors cag pathogenicity island (cagPAI), vacA allele, and oipA in combination with bacterial colonization density in a feline model of the early stages of H. pylori infection. Gastric tissues obtained from infected and uninfected cats were evaluated for H. pylori ureB, cagPAI, vacA allele, and oipA and colonization density (urease, histology, and real-time PCR). Inflammation was assessed by measuring mRNA upregulation of gamma interferon (IFN-gamma), interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, and IL-12 p40 and histopathology. The mucosal immune response was characterized by morphometric analysis of lymphoid follicles and by differentiating lymphocyte populations with antibodies against surface markers. Infecting H. pylori strains were positive for vacAs1 but lacked cagPAI and an active oipA gene. Colonization density was uniform throughout the stomach. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and increased severity of inflammatory infiltrates and fibrosis were observed in infected cats. The median number and total area of lymphoid aggregates were 5 and 10 times greater, respectively, in the stomachs of infected than uninfected cats. Secondary lymphoid follicles in uninfected cats were rare and positive for BLA.36 and B220 but negative for CD3 and CD79 alpha, whereas in infected cats they were frequent and positive for BLA.36, CD79 alpha, and CD3 but negative for B220. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and marked hyperplasia of secondary lymphoid follicles are early consequences of H. pylori infection in cats. The response appears to be similar to that of infected people, particularly children, can develop independently of the pathogenicity factors cagPAI and oipA, and is not correlated with the degree of colonization density or urease activity.


Process and outcome indicators for infection control and prevention in European acute care hospitals in 2011 to 2012 - Results of the PROHIBIT study.
IntroductionHospitals from 24 European countries were asked for information on infection prevention and control (IPC) indicators as part of the Prevention of Hospital Infections by Intervention and Training (PROHIBIT) survey. Methods: Leading IPC personnel of 297 hospitals with established healthcare-associated infection (HCAI) surveillance provided information on local surveillance and feedback by using a questionnaire. Results: Most hospitals focused on bloodstream infection (BSI) (n = 251) and surgical site infection (SSI) (n = 254), with a SSI post-discharge surveillance in 148 hospitals. As part of the HCAI surveillance, meticillin-resistant Staphylococcus aureus (MRSA) was the leading multidrug-resistant organism (MDRO) under surveillance. Seventy-nine per cent of hospitals (n = 236) monitored alcohol-based hand rub (ABHR) consumption. Feedback to the local IPC committees mainly included outcome data on HCAI (n = 259; 87%) and MDRO among HCAI (n = 245; 83%); whereupon a feedback of MDRO data depended on hospital size (p = 0.012). Discussion/conclusion: Objectives and methods of surveillance vary across Europe, with BSI, SSI and MRSA receiving considerably more attention than indicators such as pneumonia and urinary tract infection, which may be equally important. In order to maximise prevention and control of HCAI and MDRO in Europe, surveillance should be further improved by targeting relevant HCAI. The role of feedback should be explored in more detail.