Melatonin reduces X-ray irradiation-induced oxidative damages in cultured human skin fibroblasts.
Melatonin is a hormone with multiple functions in humans, produced by the pineal gland and stimulated by beta-adrenergic receptors. Melatonin has been shown to have radioprotection properties, but there has been little progress toward identifying the specific mechanisms of its action. To clarify the role of melatonin as a radioprotective compound, in response to X-ray irradiation, we investigated the effects of X-ray irradiation and melatonin on cytotoxicity, lipid peroxidation and alteration of the cell cycle in cultured skin fibroblast. An 8 Gy dose of X radiation resulted in cell death in 63% of irradiated cells, i.e. the cell viability was 37%. The damage was associated with lipid peroxidation of the cell membrane, as shown by the accumulation of malondialdehyde (MDA). By pre-incubation with melatonin (10(-5) M), a significant preventive effect was noted on the increase in the absolute number of surviving cells (up to 68% of cells were survived), and the levels of MDA were markedly decreased. These findings suggest a close correlation between an increase of lipid peroxidation and a rate of cell death. Morphological changes associated with apoptotic cell death were demonstrated by TEM. DNA flow-cytometry analysis revealed that X radiation increased pre-G1 apoptotic population by 7.6% compared to a very low level (1.3%) of non-irradiated cells. However, in the presence of melatonin, this apoptotic population decreased up to 4.5% at 10(-5) M. The p53 and p21 protein levels of skin fibroblasts increased 4 h after 8 Gy irradiation, but melatonin pretreatment did not change those levels. This study suggests that melatonin pretreatment inhibits radiation-induced apoptosis, and melatonin exerts its radioprotective effect by inhibition of lipid peroxidation and without any involvement of the p53/p21 pathway.


Ambulatory microdose induction of buprenorphine-naloxone in two adolescent patients with sickle cell disease.
Sickle cell disease (SCD) is a hematologic disorder defined by presence of sickle-shaped red blood cells that can occlude blood vessels and cause tissue ischemia and pain. Treating SCD pain adequately and safely is difficult given today's opioid climate. Buprenorphine-naloxone has been described as an alternative option to treat chronic pain in the adult literature; however, it historically required discontinuation of full-agonist opioids before initiation, resulting in opioid withdrawal. Herein we present two adolescents with SCD who successfully weaned off large doses of full-agonist opioids by using microdose induction of buprenorphine-naloxone in clinic, without experiencing significant opioid withdrawal. Ambulatory microdose induction may remove hurdles that otherwise would discourage patients from trying this regimen while still controlling pain safely.


Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein.
Retinoblastoma is a childhood tumor that can arise because of mutant alleles acquired as somatic or germinal mutations. The mutant allele can be carried in the germ line. The mutations creating these alleles act by inactivating copies of a recessive oncogene located within band q14 of chromosome 13 and termed the RB1 locus. We have reported isolation of a cDNA fragment that recognizes chromosomal sequences possessing many of the attributes of the retinoblastoma gene associated with the RB1 locus. We now report that this segment is additionally the target of somatic mutations in mesenchymal tumors among patients having no apparent predisposition to retinoblastoma and no previous evidence of retinoblastoma. These tumors provide additional evidence that the cloned sequences are representative of a gene that is a frequent target of inactivation during tumorigenesis. Sequence analysis of this cDNA provides little insight into its normal functional role.


Leg stiffness and mechanical energetic processes during jumping on a sprung surface.
The purposes of this study were: a) to examine the effect of verbal instructions given to the subjects on the control of lower extremity stiffness and b) to determine the effect of leg stiffness on mechanical energetic processes during drop jumps on a sprung surface. A total of 10 female athletes performed a series of drop jumps on a sprung surface from heights of 20 and 40 cm. The instructions given to the subjects were a) "jump as high as you can" and b) "jump high a little faster than at your previous jump." The jumps were performed at each height until the athlete could not achieve a shorter ground contact time. Four jumps per subject per height were analyzed. The ground reaction forces were measured using a "Kistler" force plate (1000 Hz). The athletes' body positions were recorded using a high-speed (250 Hz) video camera. The deformation of the sprung surface was determined by another high-speed camera operating at 500 Hz. Surface EMG was used to measure muscle activity in five leg muscles. The contact time showed high correlation with leg stiffness as well as with ankle and knee stiffness. The change in leg stiffness was not due to the duration of the preactivation but rather to the level of activation during this phase. An increase in leg stiffness caused an increase in the energy stored and recovered in and by the sprung surface and a decrease of the energy produced by the subjects. By influencing contact time through verbal instructions, it is possible to control leg stiffness. Maximal vertical take-off velocity of the center of mass and maximal take-off body energy can be achieved having different levels of leg stiffness. The maximization of mechanical power is achieved by optimal leg stiffness values and leg muscle preactivation levels.


Effects of genistein on neuronal apoptosis, and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats.
Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression, downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovariectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.


[Case of primary leiomyosarcoma of the seminal vesicle].
A 72-year-old male visited our hospital with a complaint of perineal and voiding pain. An elastic hard mass was palpated by rectal examination in the cranial lesion of prostate. On CT scan and MRI it was located at the site of the right seminal vesicle. Trans-rectal needle biopsy specimen showed leiomyosarcoma. Radical cystoprostatectomy with pelvic lymph node dissection was performed at Hokkaido University Hospital. Microscopic examination of the resected specimen revealed the tumor arose from the right seminal vesicle without involvement of the bladder and the prostate gland. Three months after the operation the tumor recurred at lung and pelvic lymph node. He died 10 month postoperatively. Autopsy finding showed many visceral organs metastases without local recurrence. In the past, nine cases of leiomyosarcoma of seminal vesicle were published in the literature. Including our case, pathological diagnosis by core needle biopsy was attempted in five cases, though accurate diagnosis was made in only two cases. In our case, Immunohistological study by SMA and desmin was useful for histological diagnosis preoperatively.


Differential effects of acetylcholine and glutamate blockade on the spatiotemporal dynamics of retinal waves.
In the immature vertebrate retina, neighboring ganglion cells express spontaneous bursting activity (SBA), resulting in propagating waves. Previous studies suggest that the spontaneous bursting activity, asynchronous between the two eyes, controls the refinement of retinal ganglion cell projections to central visual targets. To understand how the patterns encoded within the waves contribute to the refinement of connections in the visual system, it is necessary to understand how wave propagation is regulated. We have used video-rate calcium imaging of spontaneous bursting activity in chick embryonic retinal ganglion cells to show how glutamatergic and cholinergic connections, two major excitatory synaptic drives involved in spontaneous bursting activity, contribute differentially to the spatiotemporal patterning of the waves. During partial blockade of cholinergic connections, cellular recruitment declines, leading to spatially more restricted waves. The velocity of wave propagation decreases during partial blockade of glutamatergic connections, but cellular recruitment remains substantially higher than during cholinergic blockade, thereby altering correlations in the activity of neighboring and distant ganglion cells. These findings show that cholinergic and glutamatergic connections exert different influences on the spatial and temporal properties of the waves, raising the possibility that they may play distinct roles during visual development.


Advances in critical care monitoring.
A critical evaluation of monitoring in critical illness must recognize first that there are many different types of monitoring that may take place, and that each type of monitor may be evaluated appropriately by different standards. Monitoring may occur with imaging devices, analyzers that require the permanent removal of tissue or fluid for analysis, or monitors that observe physiology with either invasive or noninvasive methods without requiring an ex vivo sample.


[Minimally invasive coronary bypass grafting; first clinical experience in Groningen University Hospital].
To evaluate the feasibility of minimally invasive coronary artery bypass grafting (mini-CABG) and the clinical results of the first 70 consecutive patients who underwent mini-CABG. Retrospective. Thorax centre of Groningen University Hospital, the Netherlands. Seventy patients with angina pectoris and electro-cardiographically objectivated ischaemia, due to proximal stenosis of the left anterior descending coronary artery (LAD) or of the right coronary artery (RCA) were included in the study. Inclusion criteria were characteristics of the stenosis implying increased risk for morbidity and mortality at PTCA and a second coronary operation in patients who had a stenosed vein graft to the LAD. Through a small anterolateral thoracotomy (8-10 cm) in the 4th or 5th intercostal space the left internal mammary artery (LIMA) was harvested. The LIMA-to-LAD anastomosis was performed on the beating heart without cardiopulmonary bypass, by means of devices which provided temporary stabilization and occlusion of the LAD. Data of the period of hospital stay were gathered by using a standard form and on the period thereafter by telephone interviews with the patients, their general practitioners or cardiologists. The in-hospital mortality was 2. In 4 patients perioperative myocardial infarction occurred. Conversion to conventional CABG was needed in 3 patients, and a temporary postoperative intra-aortic balloon pump in 1. Rethoracotomy for bleeding was done in 1 patient, who received blood transfusion. In the other patients mean postoperative bleeding was 310 ml (SD: 180). Complications were respiratory infection (n = 2) and atrial fibrillation (n = 10). The mean operation time was 95 min (SD: 26). The mean hospital stay was 4.5 days (SD: 1.9). The mini-CABG is a feasible treatment for patients with high-risk stenosis of the LAD or RCA or with a diseased vein graft to the LAD with an acceptable mortality and morbidity and a short hospital stay.


Assessment of sickness certification and concepts of musculoskeletal disease and illness in the general population.
To investigate how laymen assess the need for sickness certification and how they use the concepts "disease" and "illness" in relation to musculoskeletal disorders. Mail questionnaire with simulated case histories. A stratified, random sample of 600 Norwegians, aged 16-69 years. Scores that measured the respondents' use of the concept "illness", and their view on need for sickness certification were constructed and analysed. Response rate was 54%. The respondents perceived seven case histories describing musculoskeletal health problems more often as "illness" (61%) than as "disease" (46%). There was a close correlation between the use of "illness" and assessed need for sickness certification. However, sickness certification could be suggested for cases with neck pain, even if the patient was not perceived as ill. Women suggested sickness certification significantly more often than men. Age, length of education, and personal experience with serious musculoskeletal health problems influenced suggestions on certification among men. However, these variables could not explain any difference in use of the concept "illness".


Classification of Salivary Gland Neoplasms.
Presently, there is no universal 'working' classification system acceptable to all clinicians involved in the diagnosis and management of patients with salivary gland neoplasms. The most recent World Health Organization Classification of Tumours: Head and Neck Tumours (Salivary Glands) (2005) for benign and malignant neoplasms represents the consensus of current knowledge and is considered the standard pathological classification based on which series should be reported. The TNM classification of salivary gland malignancies has stood the test of time, and using the stage groupings remains the current standard for reporting treated patients' outcomes. Many developments in molecular and genetic methods in the meantime have identified a number of new entities, and new findings for several of the well-established salivary malignancies need to be considered for inclusion in any new classification system. All clinicians involved in the diagnosis, assessment and treatment of patients with salivary gland neoplasms must understand and respect the need for the various classification systems, enabling them to work within a multidisciplinary clinical team environment.


Analytical methodology for sulfonated lignins.
There is a significant need to characterize and classify lignins and sulfonated lignins. Lignins have so far received a good deal of attention, whereas this is not true for sulfonated lignins. There is a clear demand for a better understanding of sulfonated lignins on a chemical as well as physical level. Many of the analytical methods have been developed with different goals in mind, for example, detection of sulfonated lignins in pulp-mill effluents, elucidation of structural changes in lignosulfonates during a pulping process, or identification of properties that may affect a formulation when sulfonated lignins are used as a dispersant. When sulfonated lignins are used in industrial applications, analytical data obtained using different techniques may be necessary to enable prediction of their behavior in the target application. In the present review, a critical discussion of established and promising analytical techniques for the characterization of sulfonated lignins is presented.


[Digestive manifestations of periarteritis nodosa in a series of 120 cases].
In a series of 120 patients with periarteritis nodosa (PAN), 50 had gastrointestinal manifestations; 34 had transient abdominal pain which regressed spontaneously or in response to corticosteroid therapy and required no further investigation. Thirty one more serious episodes occurred in the remaining 26 patients. Eight of these were in fact the initial signs of PAN and 13 required laparotomy. There were 20 episodes of abdominal pain (peritonitis: 9, pancreatitis: 4, acute cholecystitis: 2, duodenal ulcer: 3, intestinal infarction: 1, unexplained pain without diagnosis at laparotomy: 1) and 11 of gastrointestinal hemorrhage (melaena or hematemesis: 4; hematochezia: 5). Clinical and biological features of patients with and without gastrointestinal manifestation were not significantly different except for cardiac involvement which was significantly more frequent (p less than 0.05) in the second group. Corrected survival rates were significantly lower (p less than 0.05) in patients with gastrointestinal manifestations. These results show that, in patients with PAN, digestive manifestations, particularly perforations, carried a poor prognosis. Nevertheless exploratory laparotomy and surgery unrelated to PAN (eg appendicectomy) were well tolerated.


The effect of mode of delivery on neonatal outcome of twins with birthweight under 1500 grams.
The purpose of this retrospective study was to evaluate the mode of delivery on neonatal outcome of twins weighing <1500 grams. We reviewed the effect of birth order, presentation, and method of delivery on neonatal outcome in twin gestation under 1500 grams at Princess Badeea' Teaching Hospital in North Jordan over the 6 years from 1994 to 1999. During the study period, there were 51 475 deliveries of which 695 were twin. One hundred and eight (108) sets of twins weighing <1500 grams were included in the study (15.5%), of which 41 were in vertex-vertex presentation, 40 in vertex-nonvertex, and 27 with first twin in nonvertex presentation. The second twin was characterised by a higher incidence of respiratory distress syndrome (82% vs. 70%; P = 0.02), more neonatal mortality (23% vs. 17.6%), and lower Apgar scores at 1 and 5 minutes. Cesarean delivery for vertex-vertex presentation did not improve the neonatal outcome. Rather, the incidence of RDS was significantly greater in this group delivered by caesarean section (65.6% vs. 42%; P = 0.012). For nonvertex presentation, those delivered by caesarean section had a lower incidence of neonatal mortality. We conclude that there was no advantage in caesarean delivery after multivariate analysis to correct for differences in birthweight between the groups. The differences in the neonatal outcome of nonvertex twin presentation was accounted for by the differences in birthweight, rather than in mode of delivery.


Methods of surgical treatment of bilateral vocal fold paralysis.
Bilateral vocal fold paralysis presents as their complete or partial immobilisation. The median or paramedian position of vocal folds contributes to the narrowing of the airway at the level of the glottis and manifests as inspiratory dyspnoea. For many years iatrogenic injury of recurrent laryngeal nerves during thyroidectomy has been viewed as the most common underlying reason. It is very often a lifethreatening condition requiring not only corticosteroid administration and intubation, which only constitute a short-term symptomatic therapy, but also surgical intervention, including tracheostomy. The most common surgical methods implemented in bilateral vocal fold paralysis include posterior cordectomy, arytenoidectomy, and, more and more commonly, re-innervation. Other techniques used in restoring airway patency include laterofixation, botulinum toxin injection, and laryngeal stimulation, which is still under research. Stem cell and gene therapy are also being researched. Notably, the main purpose of surgical treatment is the provision of airway patency with the preservation of the phonatory and protective functions of the larynx.


Cross-sectional survey: risk-averse French GPs use more rapid-antigen diagnostic tests in tonsillitis in children.
We tested the following hypotheses: (1) risk-averse general practitioners (GPs) might use more Rapid Antigen Diagnostic Tests (RADTs) in tonsillitis in children, probably to decrease their diagnostic uncertainty regarding the aetiology of the disease (viral vs due to group A Streptococcus); and (2) GPs not using RADT might prescribe more antibiotics when they are risk averse. We conducted a cross-sectional survey of a nationwide French representative sample of 1093 GPs in 2012. Multivariate analyses adjusted on the four stratification variables (age, gender, location and volume of activity, ie, the number of annual consultations) were performed to identify the risk domains associated with indicators of good or poor practice. 69.4% of GPs were aware of national guidelines regarding tonsillitis and declared that they had taken these guidelines into account for their last paediatric tonsillitis case. 59.1% declared they used RADT in their last patient aged between 3 and 16 years presenting with tonsillitis; 29.7% of these tests were positive. Among the GPs who used RADT, 30.7% prescribed an antibiotic; 98.3% did either prescribe an antibiotic because of a positive RADT result, or did not prescribe an antibiotic in view of a negative result. Among the GPs who did not use RADT, 50.7% prescribed an antibiotic. In multivariate analyses, risk-averse GPs declared being more aware of and compliant with guidelines (OR=1.56, p<0.01), and used RADTs more often for their last patient (OR=1.30, p<0.05). Among GPs not using RADT in their last patient, risk-averse GPs prescribed more antibiotics compared with risk-tolerant doctors (OR=1.18, p<0.05). Individual risk attitudes influenced GPs' practices in tonsillitis, particularly the use of RADTs and antibiotic prescriptions.


Using a "time machine" to test for local adaptation of aquatic microbes to temporal and spatial environmental variation.
Local adaptation occurs when different environments are dominated by different specialist genotypes, each of which is relatively fit in its local conditions and relatively unfit under other conditions. Analogously, ecological species sorting occurs when different environments are dominated by different competing species, each of which is relatively fit in its local conditions. The simplest theory predicts that spatial, but not temporal, environmental variation selects for local adaptation (or generates species sorting), but this prediction is difficult to test. Although organisms can be reciprocally transplanted among sites, doing so among times seems implausible. Here, we describe a reciprocal transplant experiment testing for local adaptation or species sorting of lake bacteria in response to both temporal and spatial variation in water chemistry. The experiment used a -80°C freezer as a "time machine." Bacterial isolates and water samples were frozen for later use, allowing transplantation of older isolates "forward in time" and newer isolates "backward in time." Surprisingly, local maladaptation predominated over local adaptation in both space and time. Such local maladaptation may indicate that adaptation, or the analogous species sorting process, fails to keep pace with temporal fluctuations in water chemistry. This hypothesis could be tested with more finely resolved temporal data.


[A comparative study on skin tests and allergen-specific IgE levels determined by enzyme allergo-sorbent testing (EAST)].
Ninety seven randomly selected subjects with bronchial asthma and allergic rhinitis were classified for the comparative studies. The level of allergen specific IgE determined by Enzyme Allergo-Sorbent Testing (EAST) was compared with skin tests. The statistically significant correlation was found for 9 selected allergens. However, the Spearman's rank correlation coefficient values varied largely, depending on a given allergen. They ranged from 0.74 (Dermatophagoides pteronyssinus) to 0.33 (Birch pollen) what might be, in the authors' opinion, a result of Bencard allergens use for skin tests and Kallestad allergens for EAST.


Synthesis of Spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]s via [4+1+1] Annulation of N-Aryl Amidines with Diazo Homophthalimides and O2.
Synthesis of spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]s through a unique [4+1+1] annulation of N-aryl amidines with diazo homophthalimides and O2 is presented. This unprecedented spirocyclization reaction features readily obtainable substrates, structurally and pharmaceutically attractive products, a cost-free and clean oxygen source, sustainable reaction medium, tolerance of a broad spectrum of functional groups, and an interesting reaction mechanism based on sequential C(sp2)-H/C(sp3)-H bond cleavage and oxygen insertion.


Increasing ethnic minority participation in Alzheimer disease research.
The Alzheimer's Association and National Institutes of Health have emphasized the need for participation of racial/ethnic populations in Alzheimer disease (AD) clinical research. Many articles have described strategies to enhance participation including establishing enduring ties to the community and tailoring the site to be more culturally welcoming or user-friendly to the community. Yet, most of these reports are not data driven. To get a better indication of the knowledge base, this review summarizes research across a broad range of domains (e.g., cancer, kidney disease, AD) that used systematic approaches to identify methods and factors that reduce barriers to recruitment, participation, and retention of a more racially and ethnically diverse population. Overall, 121 reports were found with 8 of these in AD. As a relatively new area of investigation, the literature was primarily descriptive; outcome data were seldom provided. While these studies help to identify areas of potential importance in racial/ethnic participation, hypothesis-driven research remains necessary to tease apart the key techniques that engender racial/ethnic participation in AD studies. This article suggests several recommendations, including the need for prospective research of specific recruitment methods. Fundamentally, researchers should consider that these strategies apply to all potential research participants, and not simply to traditionally underserved racial/ethnic populations.


[Clinical and prognostic value of monitoring the acute phase protein levels in patients with myocardial infarction].
The value of evaluating the protein levels at the acute stage was examined to define the clinical course and prognosis of myocardial infarction. The time course of hospital myocardial infarction was studied in 117 patients. The Manchini radial immunodiffusion with reference monospecific antisera was employed to determine individual proteins during the acute stage (orosomucoid, C-reactive protein, alpha 1-antitrypsin, C3 complement, ceruloplasmin). The level of circulating immune complexes was measured by polyethylene glycol precipitation. There was a close correlation between the circulating immune complex levels and some acute phase parameters, suggesting the relationship between immune and inflammatory processes. The changes in the magnitude of some acute phase parameters and circulating immune complexes were found to be significant in predicting the development of complications and the fatal outcome of the disease.


Equation of state for hard-sphere fluids offering accurate virial coefficients.
The asymptotic expansion method is extended by using currently available accurate values for the first ten virial coefficients for hard sphere fluids. It is then used to yield an equation of state for hard sphere fluids, which accurately represents the currently accepted values for the first sixteen virial coefficients and compressibility factor data in both the stable and the metastable regions of the phase diagram.


Indirect hydrogen analysis by gas chromatography coupled to mass spectrometry (GC-MS).
Gas chromatography (GC) is an analytical tool very useful to investigate the composition of gaseous mixtures. The different gases are separated by specific columns but, if hydrogen (H2 ) is present in the sample, its detection can be performed by a thermal conductivity detector or a helium ionization detector. Indeed, coupled to GC, no other detector can perform this detection except the expensive atomic emission detector. Based on the detection and analysis of H2 isotopes by low-pressure chemical ionization mass spectrometry (MS), a new method for H2 detection by GC coupled to MS with an electron ionization ion source and a quadrupole analyser is presented. The presence of H2 in a gaseous mixture could easily be put in evidence by the monitoring of the molecular ion of the protonated carrier gas.


Association of low job control with a decrease in memory (CD4+ CD45RO+) T lymphocytes in Japanese middle-aged male workers in an electric power plant.
To clarify the relationship between perceived job stress and lymphocyte subpopulations, a cross-sectional study was conducted in 231 male electric power plant workers (aged 40 to 60, mean 46 years). Job stress, i.e., job control, job demands, and social support at work, was assessed by means of the Japanese version of the Job Content Questionnaire. Blood samples were taken from all the workers, and numbers of CD4+ T lymphocyte subpopulations, total CD4+ T, T (CD3+) lymphocytes, CD16CD56+ natural killer (NK) cells, total lymphocytes, and white blood cells were determined. After controlling for age, number of cigarettes smoked per day, alcohol drinking, frequency of regular exercise, job demands, and social support at work by the partial correlation coefficients, numbers of memory (CD4+ CD45RO+) T, total CD4+ T, and total T (CD3+) lymphocytes were positively correlated with job control (p<0.05). Neither job demands nor social support at work showed significant correlations with lymphocyte subpopulations. It is suggested that lower job control is associated with a decrease in the number of CD4+ CD45RO+ T lymphocytes in male middle-aged workers.


[Total hip arthroplasty after avascular necrosis due to sickle cell disease in Senegal: series of 48 replacements].
The purpose of this study is to describe the outcome of total hip arthroplasty for management of aseptic osteonecrosis of the femoral head due to sickle cell disease. This consecutive series carried out over a 7-year period in 38 patients with a sickle-cell anaemia includes a total of 48 cemented prosthesis. The mean follow-up period was 5 years. Arthroplasty restored normal hip function (PMA score = 18) in 64% of cases. In 32% of cases the PMA score was more than 15. Pain was greatly reduced with total relief being achieved in 94% of cases. Walking ability also improved with 85% of patients having an unlimited walking distance. Radiological examination demonstrated edging on 36% of cupulas and 29% of the shafts. Complications were observed in 19% of cases. The main complications were loosening and dislocation of the prosthesis. Although the complication rate was high, functional outcomes in this series were good. These findings indicate that arthroplasty should be considered as the treatment of choice for aseptic osteonecrosis due to stage 3 and 4 sickle-cell disease in young patients. Use of uncemented implant and type of frictional torque are discussed.


Bacillus sp. probiotic supplementation diminish the Escherichia coli F4ac infection in susceptible weaned pigs by influencing the intestinal immune response, intestinal microbiota and blood metabolomics.
Probiosis is considered a potential strategy to reduce antibiotics use and prevent post-weaning diarrhea (PWD). This study investigated the effect of Bacillus amyloliquefaciens DSM25840 or Bacillus subtilis DSM25841 supplementation on growth, health, immunity, intestinal functionality and microbial profile of post-weaning pigs after enterotoxigenic E. coli (ETEC) F4 challenge. Sixty-four post-weaning piglets (7748 g ± 643 g) were randomly allocated to four groups: control basal diet (CO); CO + 1.28 × 106 CFU/g of B. amyloliquefaciens (BAA); CO + 1.28 × 106 CFU/g feed of B. subtilis (BAS); CO + 1 g colistin/kg of feed (AB). At day (d) 7, animals were challenged with 105 CFU/mL of ETEC F4ac O149 and then followed for fecal score and performance until d 21. Blood was collected at d 6, d 12 and d 21 for immunoglobulins, at d 8 for acute phase proteins, at d 8 and d 21 for metabolomics analysis. Jejunum was sampled for morphometry, quantification of apoptosis, cell proliferation, neutral and acid mucine and IgA secretory cells, and microarray analysis at d 21. Jejunum and cecum contents were collected for microbiota at d 21. AB and BAS reduced the fecal score impairment compared to CO (P < 0.05) at d 14. Body weight (BW), average daily weight gain (ADWG), average daily feed intake (ADFI) and gain to feed ratio (G:F) did not differ between Bacillus groups and CO. AB improved BW at d 7, d 14 and d 21, ADWG ADFI and G:F from d 0 to d 7 (P < 0.05). At d 8, CO had higher plasma arginine, lysine, ornithine, glycine, serine and threonine than other groups, and higher haptoglobin than AB (P < 0.05). At d 21, CO had lower blood glycine, glutamine and IgA than BAS. Morphology, cells apoptosis and mucins did not differ. BAS and AB increased the villus mitotic index. Transcriptome profile of BAS and AB were more similar than CO. Gene sets related to adaptive immune response were enriched in BAA, BAS and AB. CO had enriched gene set for nuclear structure and RNA processing. CO had a trend of higher Enterobacteriaceae in cecum than the other groups (P = 0.06). Bacillus subtilis DSM25841 treatment may reduce ETEC F4ac infection in weaned piglets, decreasing diarrhea and influencing mucosal transcriptomic profile.


Cardiovascular Mortality in Type 2 Diabetes Patients with Incident Exposure to Insulin Glargine.
The study investigated the impact of insulin glargine exposure on cardiovascular mortality in type 2 diabetes patients with incident insulin initiation. All consecutive diabetes patients aged >40 years were screened at their first diabetes outpatient visit between 01/01/2001 and 12/31/2008 (n = 79869). Exclusion criteria restricted the cohort to 4990 incident insulin users, aged 40-79 years, who were followed up for death until 12/31/2011. Baseline was defined 6 months after insulin initiation. Adjusted time-dependent competing risk regression analysis was performed. Mean baseline age was 62 ± 9 years, with mean follow-up of 4.7 ± 1.9 years. During 23179 person-years of exposure time, there were 887 deaths (521 cardiovascular). Glargine cumulative time exposure significantly lowered overall cardiovascular, subhazard ratio (SHR) 0.963 (CI 95% 0.944-0.981, p < 0.001), and myocardial infarction mortality, SHR 0.945 (CI 95% 0.899-0.994, p = 0.028), but not stroke mortality. Glargine cumulative dose exposure (10,000 IU increments) significantly lowered cardiovascular mortality, SHR 0.977 (CI 95% 0.960-0.993, p = 0.006), but not for myocardial infarction and stroke. Both cumulative dose and time exposure to insulin glargine were associated with lower cardiovascular mortality. The effect was mostly driven by myocardial infarction end point, supporting the concept of macrovascular benefit for basal analogue insulin use in type 2 diabetes.


Plasmonic induced triple-band absorber for sensor application.
We design and investigate a triple-band plasmonic metamaterial absorber (PMA) for sensor application. The underlying mechanism is investigated theoretically and numerically. Three characteristic absorption peaks are demonstrated to be induced by different plasmonic modes which lead to different responses for the plasmonic sensor. These modes show great improvement for the sensitivity and accuracy of the plasmonic sensors. This triple-band plasmonic metamaterial optical absorber has great potential to improve the performance in practical applications.


The Characteristics and Functionalities of Mobile Apps Aimed at Patients Diagnosed With Immune-Mediated Inflammatory Diseases: Systematic App Search.
Immune-mediated inflammatory diseases (IMIDs) are systemic conditions associated with a high social and health impact. New treatments have changed the prognosis of IMIDs and have increased patient autonomy in disease management. Mobile apps have enormous potential to improve health outcomes in patients with IMIDs. Although a large number of IMID apps are available, the app market is not regulated, and functionality and reliability remain uncertain. Our aims are to review available apps for patients with IMIDs or caregivers and to describe the main characteristics and functionalities of these apps. We performed an observational, cross-sectional, descriptive study of all apps for patients with IMIDs. Between April 5 and 14, 2021, we conducted a search of the App Store (iOS) and Play Store (Android) platforms. We used the names of the different IMIDs as search terms. The inclusion criteria were as follows: content related to IMIDs, English or Spanish language, and user population consisting of patients and health care consumers, including family and caregivers. The variables analyzed were as follows: app name, type of IMID, platform (Android or iOS), country of origin, language, category of the app, cost, date of the last update, size, downloads, author affiliation, and functionalities. We identified 713 apps in the initial search, and 243 apps met the criteria and were analyzed. Of these, 37% (n=90) were on Android, 27.2% (n=66) on iOS, and 35.8% (n=87) on both platforms. The most frequent categories were health and well-being/fitness apps (n=188, 48.5%) and medicine (n=82, 37.9%). A total of 211 (82.3%) apps were free. The mean time between the date of the analysis and the date of the most recent update was 18.5 (SD 19.3) months. Health care professionals were involved in the development of 100 (41.1%) apps. We found differences between Android and iOS in the mean time since the last update (16.2, SD 14.7 months vs 30.3, SD 25.7 months) and free apps (85.6% vs 75.8%; respectively). The functionalities were as follows: general information about lifestyles, nutrition, or exercises (n=135, 55.6%); specific information about the disease or treatment (n=102, 42%); recording of symptoms or adverse events (n=51, 21%); agenda/calendar (n=44, 18.1%); reminder medication (n=41, 16.9%); and recording of patient-reported outcomes (n=41, 16.9%). A total of 147 (60.5%) apps had more than one functionality. IMID-related apps are heterogeneous in terms of functionality and reliability. Apps may be a useful complement to IMID care, especially inpatient education (their most frequent functionality). However, more than half of the IMID apps had not been developed by health care professionals or updated in the last year.


Maternal Lactobacillus reuteri supplementation shifts the intestinal microbiome in mice and provides protection from experimental colitis in female offspring.
The purpose of our experiment was to explore how stochastic (inter-individual variation) gut microbiome composition may link to inflammatory bowel disease (IBD) susceptibility and guide the development of a perinatal preventative probiotic. Dextran sodium sulfate (DSS) was introduced to C57BL/BJ mice to induce acute colitis as a model of IBD. Potentially protective bacteria were identified using a discovery-validation cohort approach toward stochastic DSS susceptibility. Lactobacilli (two different cocktails of L. reuteri and L. johnsonii strains) or control media were supplemented by mouth to dams prior to delivery and during lactation (i.e., perinatal probiotic). The pups were evaluated for DSS susceptibility at young adulthood. Fecal Lactobacillus was increased in the DSS-resistant mice in both the discovery and validation cohorts. Maternal supplementation of female offspring with an L. reuteri cocktail (strains 6798-1, 6798-jm, and 6798-cm) induced progressive microbiome separation and protection against colitis by young adulthood. Maternal supplementation of L. reuteri could confer protection against DSS colitis in young adult female mice. This work is the first to exploit stochastic mammalian microbiome variation to guide microbial therapeutic identification. Our findings underscore neonatal microbiome plasticity and set the stage for the potential development of perinatally deliverable protective probiotics against human IBD.


Use of a T'LIFT transabdominal organ retraction device in two-portal laparoscopic ovariectomy in dogs.
To describe the use of the T'LIFT transabdominal organ retraction device to suspend ovaries during canine laparoscopic ovariectomy (LapOVE) and compare its use to a transabdominal suspension suture (TSS). Randomized clinical trial. Client-owned intact bitches (n = 30). Dogs were randomly assigned either to group T, in which LapOVE was performed with the T'LIFT, or to group S, in which a TSS was used. Laparoscopic ovariectomy was performed by using a standard two-portal protocol. Signalment (age, weight, body condition score [BCS], fat score of the ovarian pedicle [FSOP]), overall operative time, ovarian resection time, and perioperative complications were compared between groups. No significant differences were found between groups regarding age, weight, BCS, or FSOP. Surgical times were not significantly different between groups. No significant differences in major or minor complications were recorded. Overall operative time was significantly shorter for the last half of the cases compared with the first half, for the overall population, and within each group. Ovarian resection time for the last cases was significantly shorter compared with that for the first ones only in group T. The T'LIFT was used to suspend ovaries for two-portal LapOVE, with no major complications noted. There was no significant difference in surgical times or complications compared with transabdominal suturing. The T'LIFT can be considered as an alternative to transabdominal suture for ovarian suspension in dogs undergoing LapOVE.


Analysis of the demographic characteristics and medical conditions of the uninsured utilizing a free clinic.
The number of medically uninsured people in the United States rose from 46 million in 2008 to an astonishing 50.7 million in 2009. This population is unable to seek medical care due, in part, to the decrease in employment-based health insurance and the increase in the cost of health care. Free health clinics exist to ensure access to health care by providing a safety net for underserved populations, ultimately decreasing health disparities among people of different socioeconomic statuses. The purpose of this study was to determine the demographic characteristics of the uninsured people who utilized a free health clinic and the purpose for their visits. Investigators gathered information from over 2,000 hand-written medical records to determine whether the demographic characteristics and health conditions of the uninsured differed from the general population. While there was no predominate medical condition in this population, special attention is needed to the prevention of smoking and obesity among the uninsured. This uninsured population had a significantly higher rate of smoking (P < 0.01) and obesity (P < 0.05) than the general population. In addition to treatment for medical conditions, 1 in 4 patients came for a physical exam. This study adds to the literature by describing characteristics of a free clinic population and their medical conditions. This research can contribute to the improvement of a health care delivery system that is challenged in providing access to medical care by low-income and uninsured populations.


Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequences.
Previous studies have found that genes which are differentially expressed within the developing human brain disproportionately neighbor conserved noncoding sequences (CNSs) that have an elevated substitution rate in humans and in other species. One explanation for this general association of differential expression with accelerated CNSs is that genes with pre-existing patterns of differential expression have been preferentially targeted by species-specific regulatory changes. Here we provide support for an alternative explanation: genes that neighbor a greater number of CNSs have a higher probability of differential expression and a higher probability of neighboring a CNS with lineage-specific acceleration. Thus, neighboring an accelerated element from any species signals that a gene likely neighbors many CNSs. We extend the analyses beyond the prenatal time points considered in previous studies to demonstrate that this association persists across developmental and adult periods. Examining differential expression between non-neural tissues suggests that the relationship between the number of CNSs a gene neighbors and its differential expression status may be particularly strong for expression differences among brain regions. In addition, by considering this relationship, we highlight a recently defined set of putative human-specific gain-of-function sequences that, even after adjusting for the number of CNSs neighbored by genes, shows a positive relationship with upregulation in the brain compared with other tissues examined.


The economic burden of infections following intramedullary nailing for a tibial shaft fracture in England.
Determine the impact of infections on direct costs and healthcare resource use in England for patients undergoing intramedullary nailing (IMN) for tibial shaft fractures. Non-concurrent cohort based on retrospectively collected data with 2-year follow-up. England. The study population included adult patients (≥18 years) in England with a diagnosis of tibial shaft fracture (International Classification of Diseases-10, S822) in the inpatient setting between May 2003 and June 2017 followed by a procedure for IMN for tibial shaft fracture within 30 days. Patient data were derived from the Clinical Practice Research Datalink linked to National Health Service Hospital Episode Statistics datasets. Infection. The primary outcome was total inpatient costs from index stay admission through 1 year of follow-up. Secondary outcome included cumulative total healthcare costs, and resource utilisation at 30 days, 90 days, 1 year and 2 years. Overall, 805 patients met the inclusion criteria. At index inpatient stay, 3.7% had a post-IMN infection, rising to 11.7% at 1 year. One-year inpatient costs were 80% higher for patients with infection (p<0.001). Total costs were estimated to be £14 756 (95% CI £13 123 to £16 593) for patients with infection versus £8279 (95% CI £7946 to £8626). Length of stay (LOS), readmission and reoperation were the key drivers of healthcare costs (all p<0.001). After adjustment, LOS was higher by 109% (95% CI 62% to 169%), from 10.5 days to 21.9 days, for patients with infection. The odds of being readmitted or requiring reoperation were higher by 5.18 times (95% CI 3.01 to 9.13) and 2.47 times (95% CI 1.48 to 4.09), respectively, for patients with infection versus those without infection. Post-IMN infection significantly increases inpatient costs, LOS, readmissions and reoperations associated with tibial fracture fixation. Healthcare burden could be reduced through novel surgical site infection prevention strategies.


Glycolytic strategy as a tradeoff between energy yield and protein cost.
Contrary to the textbook portrayal of glycolysis as a single pathway conserved across all domains of life, not all sugar-consuming organisms use the canonical Embden-Meyerhoff-Parnass (EMP) glycolytic pathway. Prokaryotic glucose metabolism is particularly diverse, including several alternative glycolytic pathways, the most common of which is the Entner-Doudoroff (ED) pathway. The prevalence of the ED pathway is puzzling as it produces only one ATP per glucose--half as much as the EMP pathway. We argue that the diversity of prokaryotic glucose metabolism may reflect a tradeoff between a pathway's energy (ATP) yield and the amount of enzymatic protein required to catalyze pathway flux. We introduce methods for analyzing pathways in terms of thermodynamics and kinetics and show that the ED pathway is expected to require several-fold less enzymatic protein to achieve the same glucose conversion rate as the EMP pathway. Through genomic analysis, we further show that prokaryotes use different glycolytic pathways depending on their energy supply. Specifically, energy-deprived anaerobes overwhelmingly rely upon the higher ATP yield of the EMP pathway, whereas the ED pathway is common among facultative anaerobes and even more common among aerobes. In addition to demonstrating how protein costs can explain the use of alternative metabolic strategies, this study illustrates a direct connection between an organism's environment and the thermodynamic and biochemical properties of the metabolic pathways it employs.


Thoracoscopic Esophagojejunostomy in the Upper Mediastinum After Thoracoscopic Esophagectomy with Total Gastrectomy.
Esophagectomy and esophageal reconstruction with organs other than the gastric tube are complicated and difficult surgical procedures. We developed a new method of thoracoscopic esophagectomy with intrathoracic esophagojejunostomy in the upper mediastinum when the gastric tube cannot be used as an esophageal substitute for reconstruction. Total gastrectomy, preparation of pedicled jejunal conduit, and transhiatal lower mediastinal dissection were done under laparotomy. Upper and middle mediastinal dissection was performed thoracoscopically. After esophageal transection with a linear stapler above the arch of the azygos vein, an anvil was inserted transorally. A circular stapler-inserted jejunal conduit was introduced to the upper mediastinum via the transhiatal route with relaparotomy. Esophagojejunostomy was completed by double stapling technique. We completed this procedure for 10 consecutive cases without conversion to thoracotomy. The median operation time, amount of blood loss, duration of intrathoracic anastomosis, and number of dissected total and thoracic nodes was 741 (665-1019) minutes, 835 (380-2090) ml, 94.5 (70-211) minutes, and 59 (16-165) and 30 (10-54) nodes, respectively. There was no anastomotic leakage, conduit necrosis, or hospital mortality. Two cases showed delayed anastomotic stenosis. The median body weight loss 3 months after surgery was 13.9%. The overall 5-year survival rate was 90% (stage I, 100% and stage III, 83.3%). Thoracoscopic esophagectomy with intrathoracic esophagojejunostomy is safe and curative. This operation can be performed as a minimally invasive surgical procedure for esophageal cancer patients in whom the stomach cannot be used as a reconstruction conduit.


Demonstration of rectosigmoid fistula dynamic scintigraphic peritoneography.
Intraperitoneal installation of chemotherapy through a Mediport implanted subcutaneously in the abdominal wall is used currently for treatment of peritoneal metastases from ovarian, gastric and colonic carcinoma. There is a variable incidence of complications due to the procedure reported in the literature. The main predisposing factor for these complications is the inhomogeneous distribution of the chemotherapeutic drugs within the peritoneal cavity. We report an unusual case of a rectosigmoid fistula that developed 6 wk following the insertion of a Bardport subcutaneously in the abdominal wall for intraperitoneal therapy. The fistula was clearly demonstrated by dynamic scintigraphic peritoneography. This is a new modification of scintigraphic peritoneography as practiced routinely. We endorse the previous recommendation that scintigraphic peritoneography be performed before every intraperitoneal installation of a chemotherapeutic drug or radiopharmaceutical to ensure the homogeneous distribution of the drugs and to prevent complications.


The role of carbon ion radiotherapy for unresectable locally recurrent rectal cancer: a single institutional experience.
Treatment for locally recurrent rectal cancer after surgery is still a challenge. With the physical and biological advantages, carbon-ion radiotherapy (CIRT) could be a choice for these patients. The purpose of this study was to investigate the efficacy and safety of CIRT for unresectable locally recurrent rectal cancer in Chinese patients. Date from 25 patients with unresectable locally recurrent rectal cancer treated by CIRT from July 2015 to April 2019 were analyzed retrospectively. The endpoints of this study were overall survival (OS), local control (LC) and acute and late toxicity. With the median follow-up of 19.6 (range 5.1-52.5) months, data of all 25 patients were collected. Median prescribed dose for tumor was 72Gy (relative biologic efficacy (RBE)) (range 48-75.6Gy (RBE)). The LC rates at 1 and 2 years were 90.4 and 71.8%. Overall LC at 1- and 2-year were 76.2 and 30.5% for 9 patients whose prescribed tumor doses of CIRT< 66 Gy (RBE), 100 and 100% for 16 patients whose prescribed doses of CIRT≥66 Gy (RBE). Patients received ≥66 Gy (RBE) had obviously better LC rates than those received < 66 Gy (RBE) (P = 0.001). The OS rates at 1 and 2 years were 82.9 and 65.1%, respectively. No acute toxicity over grade 2 was observed, grade 3 late toxicity were observed in 3 patients: gastrointestinal toxicity (n = 1), neuropathy (n = 1), pelvic infection (n = 1). No Grade 4 or higher toxicity was observed. Our study shows that CIRT is effective for unresectable locally recurrent rectal cancer patients with acceptable toxicity.


Health, science and development: the emergence of American cutaneous leishmaniasis as a medical and public health challenge in Amazonas state, Brazil.
The history of the emergence of American cutaneous leishmaniasis in the Brazilian state of Amazonas since the 1970s is analyzed as an object of knowledge and a medical and public health challenge. An overview of the period is provided, including the public health measures and scientific studies undertaken in the context of the execution of large-scale regional developments pursued in the name of national integration by the federal government. The methodology uses documental analysis of laws, the scientific literature, research reports, epidemiological bulletins, and newspapers. The results show that American cutaneous leishmaniasis emerged as a major health problem in Amazonas in close association with the political, economic, and socioenvironmental changes seen in the period.


[Interaction and firing pattern of rabbit amygdalar neurons in the state of unconditioned fear manifested as freezing].
In order to reveal characteristics of functioning of amygdalar neuronal network during unconditioned fear, firing patterns of basal and central nuclear neurons and their interaction were studied during freezing (fear), active unconditioned motor reactions (in the absence of fear) to emotionally significant stimuli, and during quiet wakefulness. As compared to other states, specific changes in interaction of adjacent amygdalar neurons took place during freezing. Such changes were not revealed in firing of single neurons. During freezing, the number of short-latency (to 100 ms) excitatory connections increased and the number of long-latency (250-450 ms) inhibitory connections decreased. In freezing, more frequently than in other states, delta-2 range frequencies (from 2 to 4 Hz) were observed in the interneuronal interaction. During active locomotor reactions to stimuli, the number of interacting neurons decreased, the number of long-latency (200-250 ms) excitatory and short-latency (50-200 ms) inhibitory connections decreased, and theta 1-range frequencies were frequently observed in the interaction. It was concluded that, for the development of fear, the balance between excitatory and inhibitory links of amygdalar neuronal network is essential.


Archaeoparasitology at a 17th century colonial site in Newfoundland.
Excavations at the 17th century site of Ferryland during the past 2 summers have revealed thousands of artifacts and the remains of several structures. Of particular interest here was the discovery of the remains of a privy and associated stable. Examination of privy contents revealed the presence of eggs of 4 parasites: Ascaris, Trichuris, Taenia, and Dicrocoelium. Their identification represents the first reported discovery of parasite remains in an archeological context in Canada. Due to possible contamination by domestic animal feces, it was not possible to determine with certainty if the eggs are of human origin.


Systemic inflammatory response syndrome without systemic inflammation in acutely ill patients admitted to hospital in a medical emergency.
Criteria of the systemic inflammatory response syndrome (SIRS) are known to include patients without systemic inflammation. Our aim was to explore additional markers of inflammation that would distinguish SIRS patients with systemic inflammation from patients without inflammation. The study included 100 acutely ill patients with SIRS. Peripheral blood neutrophil and monocyte CD11b expression, serum interleukin-6, interleukin-1beta, tumour necrosis factor-alpha and C-reactive protein were determined, and severity of inflammation was evaluated by systemic inflammation composite score based on CD11b expression, C-reactive protein and cytokine levels. Levels of CD11b expression, C-reactive protein and interleukin-6 were higher in sepsis patients than in SIRS patients who met two criteria (SIRS2 group) or three criteria of SIRS (SIRS3 group). The systemic inflammation composite score of SIRS2 patients (median 1.5; range 0-8, n=56) was lower than that of SIRS3 patients (3.5; range 0-9, n=14, P=0.013) and that of sepsis patients (5.0; range 3-10, n=19, P<0.001). The systemic inflammation composite score was 0 in 13/94 patients. In 81 patients in whom systemic inflammation composite scores exceeded 1, interleukin-6 was increased in 64 (79.0%), C-reactive protein in 59 (72.8%) and CD11b in 50 (61.7%). None of these markers, when used alone, identified all patients but at least one marker was positive in each patient. Quantifying phagocyte CD11b expression and serum interleukin-6 and C-reactive protein concurrently provides a means to discriminate SIRS patients with systemic inflammation from patients without systemic inflammation.


Do Rubber Floor Mats Prevent Lameness in Gestating Sows Housed in Large Groups? A Field Experiment on Three Commercial Farms in France.
Lameness and foot disorders are major health and welfare issues in intensive swine production systems. They are exacerbated when sows are housed in large groups on slatted concrete floors during gestation. Our study aimed to assess the effect of rubber mats in the lying area of the gestation pen on lameness and leg health in gestating sows housed in large pens in commercial conditions. The study was conducted on three commercial farms over two successive gestations. A total of 582 Large White × Landrace sows, housed in 10 static groups, were enrolled: 5 groups in pens with rubber mats and 5 groups on slatted concrete floors. Lameness, bursitis, leg injuries, claw growth defects and claw lesions were measured at the beginning, middle and end of each gestation period. The rubber mats decreased the risk of suffering from bursitis, but had no effect on the risk of lameness, leg injuries, claw growth defects or claw lesions. Sows housed on rubber mats were heavily soiled compared with those on slatted concrete floors because the mats were not perforated for slurry evacuation. Locomotion disorders and foot lesions remained prevalent despite the rubber mats in the lying area of the gestation pens, but adding rubber mats in service rooms and farrowing crates may produce better results.


Effects of Various Levels of CO(2) on the Induction of Crassulacean Acid Metabolism in Portulacaria afra (L.) Jacq.
In response to water stress, Portulacaria afra (L.) Jacq. (Portulacaceae) shifts its photosynthetic carbon metabolism from the Calvin-Benson cycle for CO(2) fixation (C(3)) photosynthesis or Crassulacean acid metabolism (CAM)-cycling, during which organic acids fluctuate with a C(3)-type of gas exchange, to CAM. During the CAM induction, various attributes of CAM appear, such as stomatal closure during the day, increase in diurnal fluctuation of organic acids, and an increase in phosphoenolpyruvate carboxylase activity. It was hypothesized that stomatal closure due to water stress may induce changes in internal CO(2) concentration and that these changes in CO(2) could be a factor in CAM induction. Experiments were conducted to test this hypothesis. Well-watered plants and plants from which water was withheld starting at the beginning of the experiment were subjected to low (40 ppm), normal (ca. 330 ppm), and high (950 ppm) CO(2) during the day with normal concentrations of CO(2) during the night for 16 days. In water-stressed and in well-watered plants, CAM induction as ascertained by fluctuation of total titratable acidity, fluctuation of malic acid, stomatal conductance, CO(2) uptake, and phosphoenolpyruvate carboxylase activity, remained unaffected by low, normal, or high CO(2) treatments. In well-watered plants, however, both low and high ambient concentrations of CO(2) tended to reduce organic acid concentrations, low concentrations of CO(2) reducing the organic acids more than high CO(2). It was concluded that exposing the plants to the CO(2) concentrations mentioned had no effect on inducing or reducing the induction of CAM and that the effect of water stress on CAM induction is probably mediated by its effects on biochemical components of leaf metabolism.


MDM2-MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance.
Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2-MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2-MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD ) in the micromolar range for the MDM2-MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2-MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2-MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation.


Endothelin axis induces metalloproteinase activation and invasiveness in human lymphatic endothelial cells.
The molecular mechanisms involved in lymphangiogenesis were unknown until recently. We previously demonstrated that the endothelin-1 (ET-1) axis stimulates lymphatic endothelial cells (LEC) and lymphatic vessels to grow and invade. Here we further investigated the effect of ET-1 on lymphatic vessels and evaluated whether ET-1 actions result in the functional activation of lymphangiogenesis. Using highly purified human LEC, characterized for the expression of ET-1 axis members by quantitative real-time PCR, we found that the endothelin B receptor (ETB), upon activation by ET-1, induced matrix-metalloproteinase activation, demonstrating that ET-1 influenced the activity of the proteolytic enzymes required for LEC invasion. Functional assays performed by using intradermal lymphangiography demonstrated that ET-1 promoted the formation of lymphatic vessels and that these vessels were capable of lymphatic flow. ETB blockade with the specific antagonist BQ788 inhibited matrix-metalloproteinase activation and dye transport within the lymphatic vessels, demonstrating that ETB is involved in the regulation of the growth of and in the formation of functional vessels upon activation by ET-1. Our results suggest that ET-1 is a lymphangiogenic mediator and that targeting pharmacologically ETB may be therapeutically exploited in a variety of diseases, including cancer.


Immunohistochemical analysis of the endocrine cells in the pancreatic islets of cattle.
The distribution of endocrine cells and the areas of islets in the bovine pancreas were investigated by immunohistochemical methods. The islets in the A-region, which consisted of the left lobe, the ventral portion of the body, and the ventral and distal portions of the right lobe, contained a central core of insulin-containing (B-) cells surrounded by glucagon containing (A-) cells, a few somatostatin-containing (D-) cells and sporadic pancreatic polypeptide-containing (PP-) cells. The islets in the B-region, which consisted of the uncinate process, and the dorsal and proximal portions of the body and the right lobe, contained a central mass of B-cells, and peripheral cells which were predominantly PP-cells with a few D-cells but no A-cells. The areas of islets in the B-region were small as compared with those in the A-region. From these findings it is suggested that A- and PP-cells have a complementary relationship to one another. In view of this hypothesis, two types of islet, A-cell-rich and PP-cell-rich islets, were identified. The A-region contained A-cell-rich islets derived from the dorsal pancreatic primordium, while the B-region contained PP-cell-rich islets that originated from the ventral primordium. In the bovine pancreas, the areas containing PP-cell-rich islets are greater than those in previously examined species.


ParB Partition Proteins: Complex Formation and Spreading at Bacterial and Plasmid Centromeres.
In bacteria, active partition systems contribute to the faithful segregation of both chromosomes and low-copy-number plasmids. Each system depends on a site-specific DNA binding protein to recognize and assemble a partition complex at a centromere-like site, commonly called parS. Many plasmid, and all chromosomal centromere-binding proteins are dimeric helix-turn-helix DNA binding proteins, which are commonly named ParB. Although the overall sequence conservation among ParBs is not high, the proteins share similar domain and functional organization, and they assemble into similar higher-order complexes. In vivo, ParBs "spread," that is, DNA binding extends away from the parS site into the surrounding non-specific DNA, a feature that reflects higher-order complex assembly. ParBs bridge and pair DNA at parS and non-specific DNA sites. ParB dimers interact with each other via flexible conformations of an N-terminal region. This review will focus on the properties of the HTH centromere-binding protein, in light of recent experimental evidence and models that are adding to our understanding of how these proteins assemble into large and dynamic partition complexes at and around their specific DNA sites.


Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5.
The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB.


A rational approach to the diagnosis of arthritis.
The evaluation of patients with joint pain begins during the medical history and the physical examination, when the differential diagnosis can often be narrowed to a few likely possibilities. Many patients with joint pain have mild, self-limited symptoms that are best managed conservatively. Exceptions are patients with acute monoarthritis with effusion, in whom septic arthritis must often be excluded by diagnostic joint aspiration. Patients with evidence of active joint inflammation also require prompt evaluation. Laboratory tests for rheumatologic problems lack the sensitivity and specificity to allow their use as screening tools. Laboratory tests are most valuable when used selectively in patients with a clinically significant likelihood of disease. A single test used to rule in or rule out the most likely joint disease is more helpful than a panel of tests used for every patient with joint pain. Testing should aid in determining prognosis or planning treatment.


Culture and Self-Care: Practices in Jamaican Adults with Diabetes Mellitus Residing in South Florida.
Jamaican adults with diabetes mellitus (DM) living in South Florida often believe taking conventional medications can cause harm. In an effort to limit adverse effects of these medicines, they frequently engage in folk care. However, this practice could actually increase risks of DM-associated complications, such as chronic kidney disease. Little is known about what folk care Jamaican adults are integrating into everyday health care. This focused ethnography explored and described how Jamaican adults with DM who live in South Florida use folk care for managing their DM. Knowing what folk care is part of everyday health practices among ethnical and racially diverse populations, such as Jamaican adults in this study, can help inform nephrology nursing practice and support future research.


Orientation Tuning of Correlated Activity in the Developing Lateral Geniculate Nucleus.
Neural circuits and the cells that comprise them undergo developmental changes in the spatial organization of their connections and in their temporal response properties. Within the lateral geniculate nucleus (LGN) of the dorsal thalamus, these changes have pronounced effects on the spatiotemporal receptive fields (STRFs) of neurons. An open and unresolved question is how STRF maturation affects stimulus-evoked correlated activity between pairs of LGN neurons during development. This is an important question to answer because stimulus-evoked correlated activity likely plays a role in establishing the specificity of thalamocortical connectivity and the receptive fields (RFs) of postsynaptic cortical neurons. Using multielectrode recording methods and white noise stimuli, we recorded neural activity from ensembles of LGN neurons in cats across early development. As expected, there was a progressive maturation of the spatial and temporal properties of visual responses. Using drifting bar stimuli and cross-correlation analysis, we also determined the orientation-tuning bandwidth of correlated activity between pairs of LGN neurons at different stages of development (Sillito and Jones, 2002; Andolina et al., 2007; Stanley et al., 2012; Kelly et al., 2014). Despite the larger RFs and slower responses of immature LGN neurons compared with mature neurons, our results show that correlated activity in the LGN was as tightly tuned for orientation early in development as it was in the adult. Closer examination revealed this age-invariant orientation tuning of correlated activity likely involves cellular mechanisms related to spike fatigue in young animals and a progressive decrease in response latency with development.SIGNIFICANCE STATEMENT Orientation tuning is a fundamental property of neurons in primary visual cortex. An important and unresolved question is how orientation tuning emerges during brain development. This study explores a potential mechanism for the establishment of orientation tuning based on correlated activity patterns among ensembles of maturing neurons in the lateral geniculate nucleus (LGN) of the thalamus. Results show that correlated activity between pairs of LGN neurons is more tightly tuned than predictions based simply on receptive field size, indicating that correlated activity has the properties needed to play an important role in the development of geniculocortical circuits and the emergence of cortical orientation tuning.


Presenile dementia with motor neuron disease.
Seventy-one Japanese cases of presenile dementia with motor neuron disease were reviewed. The clinico-pathological features were: (1) progressive dementia with insidious onset, mostly in the presenile period: (2) neurogenic muscular wasting in the course of illness (ALS- or SPMA-like symptoms); (3) duration from the onset of the illness to death: 2-5 years (average 30.6 months); (4) extrapyramidal symptoms and definite sensory deficits are less commonly present; (5) no characteristic abnormalities in the CSF or EEG; (6) no known consanguinity or familial occurrence; (7) non-specific mild to moderate degenerative changes in the fronto-temporal cerebral cortex, hypoglossal nuclei and spinal cord, and frequently in the substantia nigra. The author was interested in discovering whether the frequency and topology of lesions in the brain of patients with presenile dementia and motor neuron disease differed characteristically from the distribution found in cases of Alzheimer's disease, Pick's disease, Creutzfeldt-Jakob disease or progressive subcortical gliosis. Presenile dementia with motor neuron disease might be a new disease entity.


The prevalence of prehypertension and hypertension among US adults according to the new joint national committee guidelines: new challenges of the old problem.
The recently released Seventh Report of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provides a new classification of blood pressure levels. Little is known about the current situation of elevated blood pressure in the United States, according to the new guidelines. Cross-sectional analysis of national representative data collected from 4805 adults 18 years and older surveyed in the 1999-2000 National Health and Nutrition Examination Survey. We examined the prevalence of prehypertension and hypertension according to the new JNC guidelines, people's awareness and management of hypertension, and the differences across sociodemographic and body weight groups. Elevated blood pressure is a serious problem in the United States. Approximately 60% of American adults have prehypertension or hypertension, and some population groups, such as African Americans, older people, low-socioeconomic-status groups, and overweight groups, are disproportionately affected. The prevalence of hypertension has increased by approximately 10 percentage points during the past decade. The awareness and appropriate management of hypertension among hypertensive patients remain low: 31% were not aware of their disease, only two thirds (66%) were told by health professionals to adopt lifestyle modifications or take drugs to control hypertension, and only 31% controlled their hypertension. With 60% of the population affected, the United States is facing a serious challenge in the prevention and management of prehypertension and hypertension. People's awareness and control of hypertension remain poor. This study highlights the seriousness of the problem and the importance of promoting lifestyle modifications.


Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials.
Recent systematic reviews and meta-analyses of randomized, double-blind, placebo-controlled trials (double-blind, placebo-controlled RCTs) have reported controversial findings regarding the associations between calcium supplements on the risk of cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between them. We searched PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles for double-blind, placebo-controlled RCTs in November, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) for the risk of cardiovascular disease were calculated using a random effects model. The main outcomes were CVD, coronary heart disease (CHD), and cerebrovascular disease. A total of 13 double-blind, placebo-controlled RCTs (n = 28,935 participants in an intervention group and 14,243 in a control group)) were included in the final analysis. Calcium supplements significantly increased the risk of CVD (RR 1.15, 95% CI 1.06-1.25], I2 = 0.0%, n = 14) and CHD (RR 1.16, 95% CI 1.05-1.28], I2 = 0.0%, n = 9) in double-blind, placebo-controlled RCTs, specifically in healthy postmenopausal women. In the subgroup meta-analysis, dietary calcium intake of 700-1000 mg per day or supplementary calcium intake of 1000 mg per day significantly increased the risk of CVD and CHD. The current meta-analysis found that calcium supplements increased a risk of CVD by about 15% in healthy postmenopausal women.


Probing the Near-Field of Second-Harmonic Light around Plasmonic Nanoantennas.
We introduce a new concept that enables subwavelength polarization-resolved probing of the second-harmonic near-field distribution of plasmonic nanostructures. As a local sensor, this method utilizes aluminum nanoantennas, which are resonant to the second-harmonic wavelength and which allow to efficiently scatter the local second-harmonic light to the far-field. We place these sensors into the second-harmonic near-field generated by plasmonic nanostructures and carefully vary their position and orientation. Observing the second-harmonic light resonantly scattered by the aluminum nanoantennas provides polarization-resolved information about the local second-harmonic near-field distribution. We then investigate the polarization-resolved second-harmonic near-field of inversion symmetric gold dipole nanoantennas. Interestingly, we find strong evidence that the second-harmonic dipole is predominantly oriented perpendicular to the gold nanoantenna long axis, although the excitation laser is polarized parallel to the nanoantennas. We believe that our investigations will help to disentangle the highly debated origin of the second-harmonic response of inversion symmetric plasmonic structures. Furthermore, we believe that our new method, which enables the measurement of local nonlinear electric fields, will find widespread implementation and applications in nonlinear near-field optical microscopy.


P53 and taurine upregulated gene 1 promotes the repair of the DeoxyriboNucleic Acid damage induced by bupivacaine in murine primary sensory neurons.
The research aimed to explore the biological role of p53 protein and long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in bupivacaine (bup)-induced neurotoxicity. Our work treated dorsal root ganglion (DRG) cells with bup, detected cell viability through CCK-8, apoptosis through TUNEL assays, DeoxyriboNucleic Acid (DNA) damage through γ-H2AX protein and comet assay, including p53 mRNA, protein and TUG1 expression through q-PCR and western blot, furthermore, cell viability and DNA damage were determined after the silencing of p53 and TUG1, biological information and TUG1 FISH combined with p53 protein immunofluorescence (IF) was performed to determine the cellular localization of these molecule. In vivo experiments, we explored the impact of intrathecal injection of bup on p53 mRNA and protein, TUG1, γ-H2AX protein expression. The results showed that bup was available to signally decreased cell viability, promoted apoptosis rate and DNA damage, additionally, bup increased p53 mRNA and protein and TUG1 expression. P53 siRNA and TUG1 siRNA significantly increased DNA damage. Furthermore, bioinformatics analysis and colocalization experiments revealed that the p53 protein is a transcription factor of TUG1, in vivo experiment, intrathecal injection of bup increased the p53 mRNA, p53 protein, TUG1 and γ-H2AX protein in the murine DRG. In this study, it was found p53 and TUG1 promote the repair of the DNA damage induced by bup in murine dorsal root ganglion cells, suggesting a new strategy for the amelioration of bup-induced neurotoxicity.


Specialized neuropeptide Y- and glucagon-like immunoreactive amacrine cells in the peripheral retina of the turtle.
There are many regional differences in cell morphology and neurochemistry in the retina. This study examined a specialized population of neuropeptide Y- and glucagon-like immunoreactive amacrine cells in the peripheral retina of the turtle. Some of the dendritic processes from these peptidergic amacrine cells formed a dense circumferentially oriented nerve fiber plexus which ran parallel to the ora serrata. Collaterals from this plexus projected into and innervated the nonpigmented ciliary epithelium in the pars plana region of the ciliary body. Electron microscopy revealed that the neuropeptide Y- and glucagon-like immunoreactive processes in the ciliary epithelium contained many labeled, large dense-cored vesicles. Small crystals of lipid-soluble fluorescent dye were implanted in the retina near the ora serrata in fixed retinal tissue to search for other peripheral retinal specializations. Numerous thick and thin cell processes oriented parallel to the ora serrata were labeled in the retina by the dye. In addition, many dye-labeled somata with circumferentially oriented dendritic arborizations were seen in the extreme periphery of the retina. Many of these dye-labeled cells and processes were clearly not associated with the neuropeptide Y- and glucagon-like immunoreactive cells described above. This study has shown that some peptidergic neurons in the peripheral retina have a unique morphology in comparison to more centrally located cells. The function of these specialized peripheral cells is not established, but the innervation of the ciliary epithelium by peptidergic amacrine cells suggests that they may be involved in control of aqueous inflow.


Intracranial hypertension and adult respiratory distress syndrome: usefulness of tracheal gas insufflation.
The management of increased intracranial pressure (ICP) in patients with an associated acute lung injury is difficult. High levels of PaCO2 as tolerated for permissive hypercapnia are deleterious for cerebral circulation. In such circumstances, tracheal gas insufflation (TGI), which was recently proposed to reduce PaCO2, may be of benefit. We report the cases of two patients with severe adult respiratory distress syndrome and head trauma complicated with elevated ICP. The introduction of TGI decreased PaCO2 by 17 and 26%, decreased ICP, and increased calculated cerebral perfusion pressure. We conclude that TGI could be added to a pressure-targeted strategy of ventilatory management when severe adult respiratory distress syndrome was associated to an intracranial hypertension.


[Current opinions in therapeutics of advanced laryngeal carcinoma].
The treatment of advanced laryngeal cancer constitutes a constant challenge to surgeons. Although various therapeutic modalities have been employed in the past century, the cure rate remains unsatisfactory. Current opinions in the therapeutics of this disease pay more attention to the preservation of larynx function and the improvement of quality of life. It is practical to improve the survival rate and quality of life by upgrading the conservative surgical techniques and radiotherapy tactics, neo-adjuvant therapies, and especially the combined treatment using concurrent chemoradiotherapy.


Structural organization of the human PON1 gene.
Serum paraoxonase/arylesterase (PON) is an "A" esterase found in the HDL2 fraction of mammalian sera closely associated with apolipoproteins A1 and J. This enzyme hydrolyzes the active metabolites (oxons) of several organophosphate (OP) insecticides as well as the P-F bond of the nerve agents soman and sarin. PON also destroys biologically active, multioxygenated phospholipids. Two factors result in large individual variations in PON serum levels, a substrate-dependent activity polymorphism and large individual differences in PON protein levels that are stable over time. Animal model studies indicate that PON activity levels are likely to play a major role in determining sensitivity to OPs. The arg192 PON isoform appears to be a risk factor in coronary artery disease. We report here the characterization of a 28-kb contig encompassing 300 bp of 5' sequence, the entire coding region, and 2 kb of 3'-flanking sequence of the PON gene. The structural portion of the paraoxonase protein is encoded by nine exons that form the primary transcript through the use of typical splice donor and acceptor sites. DNA sequences of the regions surrounding all the coding exons have been determined. A polymorphic CA repeat is located in intron 4.


Use of NTRIP for optimizing the decoding algorithm for real-time data streams.
As a network transmission protocol, Networked Transport of RTCM via Internet Protocol (NTRIP) is widely used in GPS and Global Orbiting Navigational Satellite System (GLONASS) Augmentation systems, such as Continuous Operational Reference System (CORS), Wide Area Augmentation System (WAAS) and Satellite Based Augmentation Systems (SBAS). With the deployment of BeiDou Navigation Satellite system(BDS) to serve the Asia-Pacific region, there are increasing needs for ground monitoring of the BeiDou Navigation Satellite system and the development of the high-precision real-time BeiDou products. This paper aims to optimize the decoding algorithm of NTRIP Client data streams and the user authentication strategies of the NTRIP Caster based on NTRIP. The proposed method greatly enhances the handling efficiency and significantly reduces the data transmission delay compared with the Federal Agency for Cartography and Geodesy (BKG) NTRIP. Meanwhile, a transcoding method is proposed to facilitate the data transformation from the BINary EXchange (BINEX) format to the RTCM format. The transformation scheme thus solves the problem of handing real-time data streams from Trimble receivers in the BeiDou Navigation Satellite System indigenously developed by China.


Classical management of refractory adult immune (idiopathic) thrombocytopenic purpura.
Treatment of chronic immune (idiopathic) thrombocytopenic purpura with corticosteroids and/or splenectomy results in safe platelet counts in over 70% of patients without additional treatment. Therapy of patients who are refractory to these two treatments may be difficult. The treatment approach to refractory ITP patients, described in this report, is arbitrarily divided into four levels: levels 1 through 3 represent treatments with increasing side effects; level 4 therapy may be tried when the others have failed. Patients undergoing these treatments may require concomitant intravenous gammaglobulin, high-dose corticosteroids or platelets, to maintain the platelet count in the setting of mucosal bleeding or severe thrombocytopenia.


Functional properties of metallomesogens modulated by molecular and supramolecular exotic arrangements.
New concepts for the synthesis of metallomesogens have been recently developed in order to use the metal centre as a scaffold for grafting different functionalities and inducing non-conventional shapes and properties in the resulting complexes. Our strategy was based on the synthesis of mesogenic coordination complexes whose molecular architectures are controlled by the modulation of different and tunable molecular motifs: the nature of the metal ion and the surrounding ligands as central unit, the number of flexible chains at the periphery, and the nature of counter-ions in ionic complexes. The appropriate choice of molecular construction motifs allows control at global architectures and induces pre-selected properties from the level of single molecule to supramolecular network, confirming that metal coordination provides a helpful tool for obtaining multifunctional soft materials.


A multidimensional measure of caregiving appraisal: validation of the Caregiver Appraisal Scale in traumatic brain injury.
To investigate the factor structure and concurrent validity of the Caregiver Appraisal Scale (CAS) in a sample of caregivers of adults with traumatic brain injury (TBI). Prospective cohort study. Two sites: (1) Outpatient clinics associated with a comprehensive inpatient brain injury rehabilitation program and (2) a comprehensive residential postacute rehabilitation program in the Southern United States. One hundred forty-nine caregivers of adults with TBI enrolled in the TBI Model Systems Project and 92 caregivers of adults with TBI admitted to a residential postacute rehabilitation program. Most caregivers were women and either parents or spouses of the injured person. Caregiver Appraisal Scale (CAS); Subjective Burden Scale (SBS); Objective Burden Scale (OBS); General Health Questionnaire (GHQ). Principal components analysis with varimax rotation yielded four factors: perceived burden (PB), caregiver relationship satisfaction (CRS), caregiving ideology (CI), and caregiving mastery (CM), which were found to be fairly stable across treatment settings. Adequate concurrent validity was demonstrated for the perceived burden factor, and adequate internal consistency was found for three of four scales. Preliminary support for the use of the CAS in caregivers of adults with TBI was obtained. However, further scale development, particularly for the CM factor, will likely improve the stability and usefulness of this instrument.


Higher muscle performance in adolescents compared with adults after a resistance training session with different rest intervals.
The aim of the present study was to compare the effect of 3 different rest intervals between sets on the total training volume, number of repetitions, ratings of perceived exertion (RPE), and resistance to fatigue in adolescents and adults during a resistance training session in the isoinertial chest press exercise. Fifteen male adolescents (15.2 ± 1.2 years; 20.7 ± 2.0 kg·m(-2); Tanner -4; 61.5 ± 8.9, 10 repetition maximum [RM]) and 15 adults (22.2 ± 2.7 years; 23.3 ± 2.0 kg·m(-2); Tanner -5; 84.3 ± 13.5, 10RM) without previous experience with resistance training participated in the study. After 10RM test-retest on 3 different occasions, participants were randomly assigned to a resistance training protocol with 30-, 60-, and 120-second rest interval between sets. The protocol consisted of 3 sets with 10RM. In all studied variables, with exception to total training volume and RPE, adolescents presented superior results as compared with adults (p < 0.001). On the other hand, both adults and adolescents exhibited a higher resistance to fatigue, total training volume, and number of repetitions with a longer rest interval (120 > 60 > 30 seconds) (p < 0.01). Thus, these results indicate that adolescents present a higher recovery capacity between sets in a resistance training session than adults and a longer rest interval results in a higher number of repetitions completed, total training volume, and resistance to fatigue.


Electronic states of a C70 monolayer on the surface of Ag(111).
We have investigated the electronic states of a C(70) monolayer on the surface of Ag(111) (1 ML C(70)/Ag(111)) using synchrotron radiation photoelectron spectroscopy and soft x-ray absorption spectroscopy techniques. The experimental data exhibit metallic properties and at least 2.6 e(-) charge transfer per C(70) molecule. The screening effect of Ag(111) on the electronic structure of C(70) is remarkable; it greatly reduces or even eliminates the on-site Hubbard energy. The work functions of the C(70) multilayer and monolayer are determined as 4.53 eV and 4.52 eV respectively. The energy levels of C(70) align with the Fermi level of the Ag(111) substrate, and the shift of the vacuum level caused by C(70) adsorption is negligible. Potassium doping indicates that 1 ML C(70)/Ag(111) can still accommodate about nine electrons and that the sample remains metallic at any doping level.


Precision intrauterine contraception may significantly increase continuation of use: a review of long-term clinical experience with frameless copper-releasing intrauterine contraception devices.
The purpose of this paper is to review the experience with the frameless, anchored, GyneFix copper-releasing intrauterine contraceptive devices (IUCDs/IUDs) (Contrel Europe, Belgium), and to demonstrate their high acceptability and low rate of discontinuation of use, which could contribute to current efforts that aim to reduce radically the high number of unintended pregnancies and induced abortions, particularly in young women. This paper is based on studies that examined the differences in uterine volume and cavity size, related to age and parity, and on original clinical research data and practical experience with frameless copper IUDs, as well as on literature data on the IUD-endometrial cavity relationship of conventional IUDs, with special reference to side effects and user discontinuation. The mean transverse diameter in nulliparous and parous women is significantly less than the length of the transverse arm of the TCu380A IUD (ParaGard, Duramed, NY, USA) or the levonorgestrel intrauterine system (Mirena, Bayer, Germany). Small, frameless, flexible, and unidimensional copper IUDs appear to be well tolerated, with less impact on menstrual bleeding, resulting in low discontinuation rates when compared with standard-size conventional IUDs, which often result in increased expulsion rates, complaints of pain and erratic or increased menstrual bleeding, and subsequent high rates of discontinuation, particularly in young women. The unidimensional GyneFix IUDs fit the majority of uterine cavities. An IUD that fits is likely to result in increased tolerance and continued use of the method. As this would appeal to women, the logical result should be greater use of the method and fewer unintended pregnancies and induced abortions. Recommending the standard TCu380A (ParaGard) IUD or the Mirena levonorgestrel intrauterine system, primarily developed for use in parous women, for general use in nulliparous and adolescent women should be done with caution in the light of current scientific evidence, except if 3-D sonography indicates that the uterine cavity is sufficiently large.


The impact of vitamin D supplementation on peripheral neuropathy in a sample of Egyptian prediabetic individuals.
Background: Vitamin D deficiency is seen more frequently in diabetic patients with distal symmetrical polyneuropathy. Unfortunately, there is a shortage of data concerning prediabetic individuals with peripheral neuropathy (PN). Therefore, we aimed to study the association of vitamin D deficiency with PN severity and to determine the effect of vitamin D supplementation on PN in prediabetics. Methods: A case-control study was conducted consisting of 89 prediabetic individuals with PN and a control group of prediabetics without PN, recruited from the outpatient department of the National Institute of Diabetes and Endocrinology, Cairo, Egypt. All patients were screened for PN using clinical examination and Douleur Neuropathique 4 diagnostic questionnaire (DN4). Group A (with PN) was assessed for neuropathic severity using the Short-Form McGill Pain Questionnaire (SF-MPQ). In addition, 25-hydroxyvitamin D, ionized calcium, phosphorus, parathyroid hormone (PTH), glycated hemoglobin (HbA1c), fasting blood glucose (FBG), 2-hour post 75g glucose (2h-PPBG) and lipid profile were measured for both groups. Prediabetic patients with PN were given vitamin D3 200.000 IU IM monthly for three months. After three months, clinical assessment, DN4, SF-MPQ and all laboratory measures were repeated. Results: Vitamin D was not associated with the severity of PN patients. However, supplementation of vitamin D resulted in a highly significant improvement in glycemic parameters , p≤0.001. Interestingly, neuropathy score and severity before vitamin D supplementation were (6.4±1.6 and 28.3±7.2) and after became (2.5±0.9 and 17±6.3, p≤0.001). Conclusion: Correction of vitamin D deficiency in prediabetics with PN as well as hypovitaminosis D, improves glycemic parameters, PN score and severity.


Combined modality therapy of resectable high risk rectal cancer.
Aim of this phase I-II study was to evaluate the efficacy of preoperative concomitant radiochemotherapy in resectable high risk (TNM stage: II and III) rectal tumors, 64 patients entered the study: 37 had low rectal cancer, 27 mid-rectal cancer. 50 patients were clinically staged as stage III (Dukes C) and 14 as stage II (Dukes B). Treatment protocol included bolus mitomycin C at the dose of 10 mg/m2 on day 1 and 5FU continuous infusion at the daily dose of 1000 mg/m2 on day 1, 2, 3, 4. Concomitant external radiotherapy up to a dose of 3780 cGy was delivered at the daily dose of 180 cGy. Surgery was performed 4 to 5 weeks after radiation therapy (RT). Before surgery all patients were clinically restaged to evaluate the response to concomitant radiochemotherapy. Treatment compliance was 97%. Toxicity was 27% prevalently shown as bone marrow depletion and radiodermatitis. In 37 patients (61%) there was 50% reduction (partial response) of neoplastic volume. In 5 patients (8%) no neoplastic cells were evidenced in the surgical specimen on histology (complete response). The distance between the lower margin of the tumor and the internal anal orifice increased in 72% of cases. Postoperative morbidity was 28%. The incidence of anastomotic dehiscences was 8.7% over 46 anterior resections. Postoperative mortality was nil. Definitive staging evidenced 24 patients (39%) stage I or with no evidence of tumor. The incidence of local recurrence was 5% and that of distant metastasis 8%.