Prioritizing limb loading improves symmetry during dual-tasking in individuals following anterior cruciate ligament reconstruction.
Understanding the extent to which attention prioritization interfere with limb loading in daily activities following anterior cruciate ligament reconstruction (ACLr) is important for reshaping loading behaviors. A dual-task paradigm, prioritizing limb loading symmetry (LLS) during standing or response time during an upper extremity task response time task was used to probe the effects of attention prioritization of loading. Individuals 115.6 ± 17.8 days post-ACLr (ACLr; n = 13) and matched healthy individuals (n = 13; CTRL) performed a simple response time (RT) task and 2 dual tasks prioritizing limb loading (LS-RT) and response time (RT-LS). 2 × 3 General Linear Model repeated measures analyses determined effects of group and focus condition on LLS error and response time. Significant interaction (P = 0.010) was noted in LLS error. ACLr group, exhibited greater LLS error in RT (P = 0.001) and RT-LS (P = 0.001) than LS-RT condition. ACLr group exhibited greater LLS error in the RT (P = 0.001) and RT-LS (P = 0.040) than CTRL, but not in LS-RT. A main effect of condition (P < 0.001) for response time indicated that times were slower in LS-RT compared to RT (P < 0.001) and to RT-LS (P < 0.001) for both groups. These data suggest that limb loading symmetry during standing is more automatic for controls than individuals following ACLr. Unlike controls, improving loading symmetry during standing requires additional attention in individuals in early recovery following ACLr.


N-methyl-D-aspartate receptor participates in neuronal transmission of photic information through the retinohypothalamic tract.
In order to assess the hypothesis that excitatory amino acids (EAA) are involved in the transmission of light information from retina to suprachiasmatic nucleus (SCN) and pineal via the retinohypothalamic tract (RHT), we have determined whether injections of EAA agonist into SCN could mimic the suppressive effects of light pulse on pineal melatonin production, and whether pretreatment with antagonists could block effects of light pulse in the intact rat. Injection of the EAA agonist N-methyl-D-aspartate (NMDA: 1.0 mM; 0.5 microliter) into the SCN suppressed plasma melatonin level and pineal N-acetyltransferase activity. The pretreatment with D-aminophosphonovalerate (D-APV: 2.5 or 10 mM; 2.0 microliters) or N-[1-(2-thienyl)-cyclohexyl]-piperidine (10 mM; 2.0 microliters) which are NMDA type receptor antagonists blocked the suppressive effect of the light pulse (3.0 Ix for 2 min), while the pretreatment with neither vehicle nor L-APV (optic isomer APV: 10 mM; 2.0 microliters) could block the effect of light. Alpha-D-glutamyl-amino-methylsulfonate (10 mM; 2.0 microliters or 25 mM; 2.0 microliters), which is a relative antagonist for non-NMDA type receptor, had no effect, either. These results suggest that EAA is involved in the transmission of light information through RHT and that in rat SCN EAA operates at the NMDA type receptor on the SCN.


The isolation of salmonellas from British pork sausages and sausage meat.
Between 1969 and 1974, 1467 packets (3309 samples) of pork sausages and sausage meat produced by two large and two medium sized manufacturers and several local butchers were examined for the presence of salmonellas. Of these, 435 packets (786 samples) were found to contain salmonellas, but there was a wide variation in the isolation rates according to the producer. The salmonella incidence in samples from several small and two medium sized producers was low (0-11%) while the results from the two large producers investigated showed a striking difference, the rate of salmonella contamination in the product of one was low (about 2%) and in that of the other consistently high (40-60%). A comparison of liquid enrichment media, incubation temperatures and selective agar media was also carried out to determine the most efficient combination for the isolation of salmonellas from minced meat products. The results showed that (a) incubation of enrichment cultures at 43 degrees C. yielded a consistently greater number of salmonella isolations that at 37 degrees C., regardless of plating medium, (b) tetrathionate broth A (Rolfe) was superior to selenite broth as en enrichment medium at both 37 and 43 degrees C. and (c) brilliant green agar gave better results than deoxycholate citrate sucrose agar and bismuth sulphite agar as a selective medium.


[Involvement of Wnt signaling in hippocampal plasticity].
Wnt signaling is a signal transduction pathway involving peptides of Wnt family as key molecules. In this review, the data on the role of canonical and non-canonical Wnt pathway in hippocampal structural and synaptic plasticity have been analyzed. Wnt-mediated signal transduction is involved in normal functional plasticity, and the disturbances in Wnt-mediated mechanisms form a basis for the development of cerebral pathologies. A special attention is devoted to glycogen synthase kinase 3beta (GSK-3beta), one of most important from both plasticity and pathology perspectives component of the canonical Wnt pathway. The studies in this area, besides their fundamental significance, are important for translation to the medicine, and the key components of the Wnt pathway are potential targets for the developmentn of pathogenetical therapeutics for a number of socially significant cerebral pathologies.


Responses of an Agricultural Soil Microbiome to Flooding with Seawater after Managed Coastal Realignment.
Coastal areas have become more prone to flooding with seawater due to climate-change-induced sea-level rise and intensified storm surges. One way to cope with this issue is by "managed coastal realignment", where low-lying coastal areas are no longer protected and instead flooded with seawater. How flooding with seawater impacts soil microbiomes and the biogeochemical cycling of elements is poorly understood. To address this, we conducted a microcosm experiment using soil cores collected at the nature restoration project site Gyldensteen Strand (Denmark), which were flooded with seawater and monitored over six months. Throughout the experiment, biogeochemical analyses, microbial community fingerprinting and the quantification of marker genes documented clear shifts in microbiome composition and activity. The flooding with seawater initially resulted in accelerated heterotrophic activity that entailed high ammonium production and net removal of nitrogen from the system, also demonstrated by a concurrent increase in the abundances of marker genes for ammonium oxidation and denitrification. Due to the depletion of labile soil organic matter, microbial activity decreased after approximately four months. The event of flooding caused the largest shifts in microbiome composition with the availability of labile organic matter subsequently being the most important driver for the succession in microbiome composition in soils flooded with seawater.


Averaged electrode voltages in users of the Clarion cochlear implant device.
Averaged electrode voltages (AEVs) are of secondary importance for integrity testing of cochlear implant devices featuring back-telemetry. However, AEVs are device-independent and may show intermittent failures and deviant stimulation patterns unnoticed by telemetry. We collected AEVs from 18 users of the Clarion 1.2 system and 6 users of the HiFocus system in order to establish norms for evaluating AEVs in difficult cases. The stimuli were presented with the standard clinical software. Monopolar stimulation at about 16 microA showed large AEVs (mean, 173 microV) suitable for integrity testing. No electrode failures were found. The AEV amplitudes from neighboring electrodes differed by less than 30% (2 SD). The AEVs from subjects with the Clarion HiFocus electrode and/or the Clarion electrode positioner were within the normal range. The AEV amplitudes from bipolar stimulation were much more variable. Inversion of phases between electrodes was found in patients with an altered state of the cochlea (otosclerosis and osteogenesis imperfecta) and in a patient with a curled electrode tip. There was no correlation across subjects between AEVs and electrode impedances. Therefore, impedances are dominated by the electrode-tissue interface, in contrast to AEVs, which are determined by the volume conduction in the body.


Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency.
To examine whether amniotic membrane transplantation (AMT), in preparing the perilimbal stroma, enhances the success of allograft limbal transplantation (ALT). Thirty-one eyes of 26 consecutive patients had cytologically proven limbal deficiency resulting from chemical burns (14 eyes); Stevens-Johnson syndrome, toxic epidermal necrolysis, or pseudopemphigoid (5 eyes); contact lens-induced keratopathy (3 eyes); aniridia (3 eyes); multiple surgical procedures (2 eyes); atopy (2 eyes); or an unknown cause (2 eyes). Based on the severity of limbal deficiency, group A (mild), comprising 10 eyes, received AMT alone; group B (moderate), comprising 7 eyes, received AMT and ALT; and group C (severe), comprising 14 eyes, received AMT, ALT, and penetrating keratoplasty. All patients except those in group A received continuous oral cyclosporine. Except for the 2 eyes with atopy, all amniotic membrane-covered surfaces showed rapid epithelialization (in 2 to 4 weeks) and reduced inflammation, vascularization, and scarring, and the surfaces became smooth and wettable. For the mean follow-up period of 15.4 months, 25 (83%) of 30 eyes showed visual improvement, consisting of 6 or more lines (13 eyes), 4 to 5 lines (6 eyes), or 1 to 3 lines (6 eyes). Visual improvement decreased with the severity of limbal deficiency from 8 (100%) of 8 eyes in group A to 5 (71%) of 7 eyes in group B and 11 (79%) of 14 eyes in group C. In group C, corneal graft rejection occurred in 9 (64%) of 14 eyes, and reversible early limbal allograft rejection was noted in 3 (14%) of 21 eyes of groups B and C. For partial limbal deficiency with superficial involvement, AMT alone is sufficient and hence superior to ALT because there is no need to administer cyclosporine. For total limbal deficiency, additional ALT is needed, and AMT helps reconstruct the perilimbal stroma, with reduced inflammation and vascularization, which collectively may enhance the success of ALT.


Renal transplantation in patients with IgA mesangial glomerulonephritis.
Most patients with IgA nephritis are suitable candidates for renal transplantation. In about 33% of patients the disease may recur after transplantation, although there are differences in the various series because of the different criteria for biopsy, the different length of follow-up and the different ethnicities. Living donation, genetic factors and time of progression of original disease have been found to be related with the risk of recurrence by some investigators, but these associations were not confirmed by other studies. The graft survival in patients with IgA nephritis is similar or even better than that observed with other renal diseases. The available data indicate that recurrence has a little impact on the 10-yr graft survival. However, a minority of patients may show a rapid progressive course after recurrence. Little information is available on the impact of recurrence in the very long term. There is no established treatment for preventing or treating the recurrence of IgA nephritis.


[Incorporation of phosphatidylcholine into Escherichia coli membrane affects secretion of penicillin beta-lactamase].
To study the biological function of phosphatidylcholine in bacteria, the borrelial pcs gene was inserted into ptac85 plasmid. Then E. coli Top10 pcs+ was constructed via the transformation of the recombinant plasmid. Phosphatidylcholine (30%) in total phospholipids was achieved when the bacterial cells were incubated in Luria-Bertani (LB) medium supplemented with 1% choline and induced by 0.5 mmol/L isopropy-beta-D-thiogalactoside (IPTG) for 4-8 hours at 37 degrees C. Ampicillin inhibitionof E. coli Top10 pcs+ was tested at first, and then beta-lactamase activity in periplasm was examined. Finally Western blot was used to detect the amount of beta-lactamase in both bacterial periplasm and cytoplasm. Antibiotic tests showed that high concentrations of ampicillin inhibited the growth of E. coli Top100 pcs+ with an IC50 of 70-800 microg/mL. Active assays revealed that the beta-lactamase activity in periplasm was only 1/5 of that for the control strain E. coli Top10/p(tac)85. Western blotting confirmed that the low activity of beta-lactamase in E. coli Top10 pcs+ resulted from a lower amount of beta-lactamase in its periplasm. Our results demonstrated that the phospatidylcholine incorporated into bacterial membrane retarded secretion of Escherichia coli penicillin beta-lactamase from cytoplasm into periplasm, which suggested that phosphatidylcholine might play a role in the regulation of protein secretion in those bacteria able to synthesize phosphatidylcholine.


Assessing high-impact spots of climate change: spatial yield simulations with Decision Support System for Agrotechnology Transfer (DSSAT) model.
Drybeans (Phaseolus vulgaris L.) are an important subsistence crop in Central America. Future climate change may threaten drybean production and jeopardize smallholder farmers' food security. We estimated yield changes in drybeans due to changing climate in these countries using downscaled data from global circulation models (GCMs) in El Salvador, Guatemala, Honduras, and Nicaragua. We generated daily weather data, which we used in the Decision Support System for Agrotechnology Transfer (DSSAT) drybean submodel. We compared different cultivars, soils, and fertilizer options in three planting seasons. We analyzed the simulated yields to spatially classify high-impact spots of climate change across the four countries. The results show a corridor of reduced yields from Lake Nicaragua to central Honduras (10-38 % decrease). Yields increased in the Guatemalan highlands, towards the Atlantic coast, and in southern Nicaragua (10-41 % increase). Some farmers will be able to adapt to climate change, but others will have to change crops, which will require external support. Research institutions will need to devise technologies that allow farmers to adapt and provide policy makers with feasible strategies to implement them.


What is normal blood pressure? Comparison of ambulatory pressure level and variability in patients with normal or abnormal left ventricular geometry.
To assess the level and pattern of normal ambulatory blood pressure (ABP) using a non-BP standard to identify normality, we examined the level and variability of ABP during the waking day, at work, at home, and during sleep and looked at physician and technician BP measurements in 191 adults whose left ventricular (LV) geometry was classified by echocardiography. Clinic BPs were similar in the 120 subjects with normal LV geometry and the 35 subjects with concentric LV remodeling. Pressures were only modestly higher in the 15 subjects with concentric LV hypertrophy than in the 21 with eccentric hypertrophy. In contrast, these subject groups differed with regard to their ABPs during the waking hours, at home, and especially at work. However, no difference in BP variability, as assessed by the standard deviation of awake systolic or diastolic BP, existed among the subject groups identified by LV geometric patterns. Comparison of patients with concentric LV hypertrophy, the LV pattern associated with the worst prognosis, with normotensive subjects with normal LV geometry suggests that awake ABPs in adults below 139/86 mm Hg might be considered normal, whereas values over 149/95 mm Hg might be considered pathologic. Verification of these conclusions is needed, however, in larger series and with the use of additional measures of preclinical hypertensive disease.


Treatment of venous malformations with tumescent-assisted sclero-embolic and ablative lasers (SEALs): Safe and effective long-term outcomes.
Perivascular infiltration of tumescent anaesthesia (TA) is an essential element of endovenous thermal ablative procedures employed to treat superficial venous disease. In addition to anaesthesia, TA is administered to achieve vessel wall approximation and to protect surrounding structures from thermal damage. However, its role in the treatment of venous malformations (VMs) has not been established. To assess the safety and efficacy of tumescent-assisted thermal and chemical ablative methods in the treatment of VMs. Adult and paediatric patients presenting with VMs were treated using a combination of endovenous laser ablation, foam embolo-sclerotherapy and liquid embolisation using n-BCA. All procedures were ultrasound-guided. Treatment outcomes were assessed in early and late follow-ups. To assess the efficacy of TA in achieving vessel wall approximation, cross-sectional lesional diameters were measured by ultrasound, before and after the administration of TA during endovenous procedures. In a 12 month period, 22 patients recruited in the study presented with 27 VMs which included 23 extra-truncular lesions (16 subcutaneous and seven intramuscular) and four truncular anomalies. On average the subcutaneous lesions measured 5.5 mm (1.9-24.5 mm) in diameter, intramuscular lesions measured 9.2 mm (5.9-15.1 mm) and truncular anomalies measured 4.9 mm (1.2-12 mm) in diameter. Perivascular infiltration of TA resulted in a significant reduction in vessel calibre (90% reduction on average). Intramuscular VMs were less compressible with TA (69.2% reduction) compared to subcutaneous lesions (98% reduction). Truncular anomalies such as the embryonic marginal vein achieved complete approximation (100% reduction). Procedures were safely tolerated with no major complications such as thromboembolism, stroke, nerve damage or tissue necrosis. Most patients had significant clinical as well as ultrasonographic improvement. Tumescent-assisted endovenous laser ablation and foam sclerotherapy provides safe and effective outcomes in patients with a variety of VMs.


Lycium barbarum polysaccharides extend the mean lifespan of Drosophila melanogaster.
The fruits of Lycium barbarum are considered medicinal foods with high nutritional value and bioactivity. In this study, we aimed to evaluate the effect of a crude L. barbarum polysaccharide (LBP) and two derived fractions, LBP-1 and LBP-2, on the lifespan of Drosophila melanogaster (fruit fly). The average lifespan of fruit flies was extended by supplementing their diet with either of the three LBP preparations. In vivo analysis of antioxidant activities detected increased superoxide dismutase (SOD) and catalase (CAT) activities and decreased malondialdehyde (MDA) levels. Dietary LBP supplements significantly reduced the mortality rate of fruit flies induced by paraquat and hydrogen peroxide. Importantly, the strongest anti-aging activity was exhibited by the LBP-2 fraction, containing arabinogalactan with a molecular weight of 9 × 104 Da. Further studies showed that the anti-aging activity of LBP was, at least in part, mediated by an age-related signaling pathway (MAPK, TOR, S6K) and the expression of longevity genes (Hep, MTH, and Rpn11).


Highly-substrate active isoenzyme acetylcholinesterase-II, in rosy eye mutant of Aedes aegypti mosquito.
Insecticide bioassays were carried out on larvae and adults of rosy eye mutant and wildtype strains of A. aegypti. Both the strains were equally susceptible to DDT, malathion and deltamethrin. Biochemical assays showed an increase in acetylcholinesterase enzyme (AChE) activity in all the stages of mutant strain with both the substrates i.e. acetylthiocholine iodide and S-butyrylthiocholine iodide. However, there was no difference in the percent inhibition of enzyme activity with propoxur in these two strains. Polyacrylamide gel electrophoresis performed in native conditions on the homogenates of adults of rosy eye mosquitoes showed that AChE-II allele was highly active with the substrate acetylthiocholine iodide as compared to wildtype strain. Frequency of the highly active AChE-II allele in the mutant strain was about 68%, whereas it was about 5% in the wildtype strain.


Dynamical scaling of surface growth in simple lattice models.
We present extensive simulations of the atomistic Edwards-Wilkinson (EW) and Restricted Edwards-Wilkinson (REW) models in 2+1 dimensions. Dynamic finite-size scaling analyses of the interfacial width and structure factor provide the estimates for the dynamic exponent z=1.65+/-0.05 for the EW model and z=2.0+/-0.1 for the REW model. The stochastic contribution to the interface velocity U due to the deposition and diffusion of particles is characterized for both the models using a blocking procedure. For the EW model the time-displaced temporal correlations in U show nonexponential decay, while the temporal correlations decay exponentially for the REW model. Dynamical scaling of the temporal correlation function for the EW model yields a value of z, which is consistent with the estimate obtained from finite-size scaling of the interfacial width and structure factor.


Peripheral blood mitochondrial DNA content in relation to circulating metabolites and inflammatory markers: A population study.
Mitochondrial DNA (mtDNA) content might undergo significant changes caused by metabolic derangements, oxidative stress and inflammation that lead to development and progression of cardiovascular diseases. We, therefore, investigated in a general population the association of peripheral blood mtDNA content with circulating metabolites and inflammatory markers. We examined 310 subjects (50.6% women; mean age, 53.3 years) randomly selected from a Flemish population. Relative mtDNA content was measured by quantitative real-time PCR in peripheral blood cells. Peak circulating metabolites were quantified using nuclear magnetic resonance spectroscopy. The level of inflammation was assessed via established inflammatory markers. Using Partial Least Squares analysis, we constructed 3 latent factors from the 44 measured metabolites that explained 62.5% and 8.5% of the variance in the contributing metabolites and the mtDNA content, respectively. With adjustments applied, mtDNA content was positively associated with the first latent factor (P = 0.002). We identified 6 metabolites with a major impact on the construction of this latent factor including HDL3 apolipoproteins, tyrosine, fatty acid with αCH2, creatinine, β-glucose and valine. We summarized them into a single composite metabolite score. We observed a negative association between the composite metabolic score and mtDNA content (P = 0.001). We also found that mtDNA content was inversely associated with inflammatory markers including hs-CRP, hs-IL6, white blood cell and neutrophil counts as well as neutrophil-to-lymphocyte ratio (P≤0.0024). We demonstrated that in a general population relative peripheral blood mtDNA content was associated with circulating metabolites indicative of perturbed lipid metabolism and with inflammatory biomarkers.


EVOLUTION OF A POLYMORPHISM FOR OUTCROSSING RATE IN SENECIO VULGARIS: INFLUENCE OF GERMINATION BEHAVIOR.
A difference in germination behavior between the highly selling, nonradiate variant of Senecio vulgaris and the more outcrossing, radiate form had a large effect on the relative female fitness of these two morphs raised in mixed stands under conditions similar to those experienced in the wild. Of particular significance was the finding that female fitness differences between morphs were reversed in early- and late-sown plots. This was because a greater proportion of nonradiate than radiate seed germinated directly after sowing, and in early-sown plots a relatively large proportion of early-germinated nonradiate seedlings survived winter to produce large, highly fecund plants the following summer, that contributed greatly to the total female fitness of the nonradiate morph. In contrast, in late-sown plots (i.e., sown two weeks later), survivorship of early germinated seedlings was much reduced, and the radiate morph had an advantage because most radiate seed delayed germination until spring, therefore avoiding seedling mortality during winter. The effect of the association between morph type and germination behavior on morph female fitness in S. vulgaris is clearly important in regard to the evolution of the polymorphism for outcrossing rate in the species. This, in turn, emphasizes the point that an understanding of factors responsible for the evolution and maintenance of polymorphisms for outcrossing rate in the wild should be based on a detailed examination of the ecological genetics of such polymorphisms that extend beyond traditional studies of pollen discounting and inbreeding depression.


A flagellar surface glycoprotein mediating cell-substrate interaction in Chlamydomonas.
The Chlamydomonas flagellar surface exhibits interesting adhesive properties that are associated with flagellar surface motility. This dynamic surface property can be exhibited as the binding and movement of small polystyrene microspheres or as the interaction of the flagellar surface with a solid substrate followed by whole cell locomotion, termed "gliding". In order to identify flagellar surface proteins that mediate substrate interaction during flagellar surface motility, two immobilized iodination systems were employed that mimic the conditions for flagellar surface motility: small polystyrene microspheres derivatized with lactoperoxidase, and large glass beads derivatized with Iodogen. Use of these iodination conditions resulted in preferential iodination of a high-molecular-weight glycoprotein with apparent molecular weight of 300,000-350,000. These results suggest this glycoprotein as a major candidate for the surface-exposed adhesive component that directly interacts with the substrate and couples the substrate to a system of force transduction presumed to be located within the flagellum.


Ultrasound-Guided Brachial Plexus Block by Costoclavicular Space Approach: A Narrative Review.
In recent years, ultrasound-guided costoclavicular brachial plexus block (CCB) has gained attention as a novel approach for brachial plexus nerve block. Human anatomy studies have identified the costoclavicular space as the area between the midpoint of the clavicle and the first rib. This space accommodates the brachial plexus, axillary arteries, and veins. Its superficial and fixed position makes it a promising option for infraclavicular brachial plexus blockage, providing a safe and reliable analgesic effect. CCB combines the benefits of real-time ultrasound visualization of the nerve block needle, avoidance of peripheral blood vessels, and targeted delivery of local anesthetics to the nerve. Consequently, it significantly reduces the associated complications of other classical approaches such as interscalene brachial plexus block (ISB), supraclavicular brachial plexus block (SCB), lateral sagittal infraclavicular brachial plexus block (LS-ICB), and axillary brachial plexus block. These complications include phrenic paralysis, incomplete brachial plexus block, and pneumothorax. This narrative review examines the literature on brachial plexus block in the costoclavicular space, discussing the anatomical position, the procedure, clinical indications, choice of local anesthetic concentration and volume, and continuous nerve block of CCB. The aim is to provide a basis for future clinical practice and enhanced safety.


Ketogenic-Mimicking Diet as a Therapeutic Modality for Bipolar Disorder: Biomechanistic Rationale and Protocol for a Pilot Clinical Trial.
There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a 'ketogenic-mimicking diet' (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research.


Effects of lipid peroxide formation in fowl semen on sperm motility, ATP content and fertilizing ability.
The ability of samples of semen from individual male fowl to form the products of lipid peroxidation during 5 h aerobic incubation at 40 degrees C varied between 0 and 8 nmol malonaldehyde/10(9) spermatozoa. Formation of higher concentrations of malonaldehyde was associated with a partial or complete loss of fertilizing ability whilst the fertilizing ability of samples producing low or negligible concentrations of malonaldehyde remained unimpaired. The semen of birds which showed a tendency to form high concentrations of malonaldehyde was not readily identifiable as abnormal by assessment of sperm motility, morphology or ATP content. Nor was the loss of fertilizing ability during aerobic incubation associated with an obvious change in these characteristics.


Does the aberrant expression of CD2 and CD25 by skin mast cells truly correlate with systemic involvement in patients presenting with mastocytosis in the skin?
Neoplastic mast cells involving the bone marrow (BMMCs) of patients with mastocytosis display an aberrant expression of CD25 and/or CD2 antigens. The aim of this study was to determine the frequency of CD2 and CD25 expression on skin mast cells (sMCs) of patients with mastocytosis in the skin at the early stage of the disease. Furthermore, the usefulness of the phenotypic profile of sMCs for the diagnosis of systemic mastocytosis (SM) was evaluated. The 52 adults included in the study were diagnosed with mastocytosis strictly according to the criteria of the World Health Organization. CD117, CD2 and CD25 antigen expression on sMCs was detected by immunohistochemistry. The presence of the KIT D816V mutation in the BM was analyzed using allele-specific PCR. The presence of CD2- or CD25-positive sMCs was detected in 57.1% of cutaneous mastocytosis (CM) and 90.3% of SM cases (p = 0.008). In all mastocytosis patients, CD2 expression on sMCs was more frequent than CD25 expression (67.3 and 38.5%, respectively). Moreover, CD2 expression on sMCs was more frequent in SM than in CM cases (p = 0.02). The presence of one of the aberrant sMC antigens was detected in 84.2% of patients with the KIT D816V mutation in the BM. A positive correlation between densities of CD25- and CD117-positive sMCs was found in SM patients (r = 0.46, p = 0.009). Although sMCs displayed immunoreactivity for one of the neoplastic antigens in the majority of SM patients, the aberrant CD2 and/or CD25 expression on sMCs is not as indicative of SM as the BMMC immunophenotype.


Effect of individual SCFA on the epithelial barrier of sheep rumen under physiological and acidotic luminal pH conditions.
The objective of this study was to investigate whether individual short-chain fatty acids (SCFA) have a different potential to either regulate the formation of the ruminal epithelial barrier (REB) at physiological pH or to damage the REB at acidotic ruminal pH. Ruminal epithelia of sheep were incubated in Ussing chambers on their mucosal side in buffered solutions (pH 6.1 or 5.1) containing no SCFA (control), 30 mM of either acetate, propionate or butyrate, or 100 mM acetate. Epithelial conductance (Gt), short-circuit current (Isc), and fluorescein flux rates were measured over 7 h. Thereafter, mRNA and protein abundance, as well as localization of the tight junction proteins claudin (Cldn)-1, -4, -7, and occludin were analyzed. At pH 6.1, butyrate increased Gt and decreased Isc, with additional decreases in claudin-7 mRNA and protein abundance (each P < 0.05) and disappearance of Cldn-7 immunosignals from the stratum corneum. By contrast, the mRNA abundance of Cldn-1 and/or Cldn-4 were upregulated by 30 mM propionate, 30 mM butyrate, or 100 mM acetate (P < 0.05), however, without coordinated changes in protein abundance. At luminal pH 5.1, neither Gt, Isc, nor TJ protein abundance was altered in the absence of SCFA; only fluorescein flux rates were slightly increased (P < 0.05) and fluorescein signals were no longer restricted to the stratum corneum. The presence of acetate, propionate, or butyrate at pH 5.1 increased fluorescein flux rates and Gt, and decreased Isc (each P < 0.05). Protein abundance of Cldn-1 was decreased in all SCFA treatments but 30 mM butyrate; abundance of Cldn -4 and -7 was decreased in all SCFA treatments but 30 mM acetate; and abundance of occludin was decreased in all SCFA treatments but 30 mM propionate (each P < 0.05). Immunofluorescence staining of SCFA-treated tissues at pH 5.1 showed disappearance of Cldn-7, discontinuous pattern for Cldn-4 and blurring of occludin and Cldn-1 signals in tight junction complexes. The fluorescein dye appeared to freely diffuse into deeper cell layers. The strongest increase in Gt and consistent decreases in the abundance and immunosignals of tight junction proteins were observed with 100 mM acetate at pH 5.1. We conclude that SCFA may contribute differently to the REB formation at luminal pH 6.1 with possible detrimental effects of butyrate at 30 mM concentration. At luminal pH 5.1, all SCFA elicited REB damage with concentration appearing more critical than SCFA species.


FastML: a web server for probabilistic reconstruction of ancestral sequences.
Ancestral sequence reconstruction is essential to a variety of evolutionary studies. Here, we present the FastML web server, a user-friendly tool for the reconstruction of ancestral sequences. FastML implements various novel features that differentiate it from existing tools: (i) FastML uses an indel-coding method, in which each gap, possibly spanning multiples sites, is coded as binary data. FastML then reconstructs ancestral indel states assuming a continuous time Markov process. FastML provides the most likely ancestral sequences, integrating both indels and characters; (ii) FastML accounts for uncertainty in ancestral states: it provides not only the posterior probabilities for each character and indel at each sequence position, but also a sample of ancestral sequences from this posterior distribution, and a list of the k-most likely ancestral sequences; (iii) FastML implements a large array of evolutionary models, which makes it generic and applicable for nucleotide, protein and codon sequences; and (iv) a graphical representation of the results is provided, including, for example, a graphical logo of the inferred ancestral sequences. The utility of FastML is demonstrated by reconstructing ancestral sequences of the Env protein from various HIV-1 subtypes. FastML is freely available for all academic users and is available online at http://fastml.tau.ac.il/.


Prevention of cancer cachexia by pyrrolidine dithiocarbamate (PDTC) in colon 26 tumor-bearing mice.
The precise mechanism of cancer cachexia is not fully elucidated. This study was aimed to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NFkappaB) on interleukin (IL)-6 synthesis and cachexia in colon 26 tumor-bearing mice. Murine colon 26 adenocarcinoma cells were inoculated subcutaneously in male BALB/c mice to induce cachexia. Saline and various doses of PDTC (10, 50, or 100 mg/kg/d) were given intraperitoneally daily from 7 days after tumor inoculation to killing. Body weight, food intake, and tumor volume were monitored daily. Serum and tumor tissue levels of IL-6, serum biochemical indicator, and activity of NFkappaB in tumor tissue were investigated in all mice. Significant tissue wasting was observed in all tumor-bearing mice. By day 16, carcass weights of untreated tumor-bearing mice were about 71.3% of healthy controls (p < .01), and the weights of gastrocnemius muscle and epididymal fat were lowered by 42.4% and 70.4% (p < .01), respectively. Furthermore, tumor-bearing caused a significant decrease of serum albumin, glucose, and triglyceride (p < .01) and increase of IL-6 (p < .01) in serum and tumor tissues. Administration of PDTC dose dependently inhibited the NFkappaB activation in tumor tissues, inhibited IL-6 synthesis of the tumor cells, and attenuated the wasting of carcass weight, gastrocnemius muscle, and epididymal fat. Tumor growth was inhibited by PDTC with 100 mg/kg (p < .05). No differences of food intake were found between groups (p > .05). These results suggest that PDTC, an inhibitor of NFkappaB, can attenuate the development of cachexia in colon 26 tumor-bearing mice through inhibition of IL-6 synthesis regulated by NFkappaB.


Activin-treated ectoderm has complete organizing center activity in Cynops embryos.
The differentiation and organizer activity of newt ectoderm treated with activin A was studied in explantation and transplantation experiments. In the explantation experiments, ectoderm dissected from late morulae-early gastrulae stage embryos treated with a high concentration of activin A (100 ng/mL) formed only yolk-rich endodermal cells. Mesodermal tissues, such as notochord and muscle, were seldom found in these explants. When they were transplanted into the blastocoele of other early gastrulae, they formed part of the endoderm of the host embryo and induced a secondary axis with only posterior characters (including axial mesoderm and neural tissues). In contrast, whole secondary axes were induced when activin-treated ectoderm was transplanted into the ventral marginal zone (VMZ) of early blastulae. The transplanted pieces invaginated by themselves and differentiated into foregut structures including pharynx, stomach, and liver. These phenomena were also observed in experiments in which presumptive foregut was used instead of activin-treated ectoderm. These findings show that activin-treated ectoderm can act as the complete organizing center in Cynops.


SPEER-SERVER: a web server for prediction of protein specificity determining sites.
Sites that show specific conservation patterns within subsets of proteins in a protein family are likely to be involved in the development of functional specificity. These sites, generally termed specificity determining sites (SDS), might play a crucial role in binding to a specific substrate or proteins. Identification of SDS through experimental techniques is a slow, difficult and tedious job. Hence, it is very important to develop efficient computational methods that can more expediently identify SDS. Herein, we present Specificity prediction using amino acids' Properties, Entropy and Evolution Rate (SPEER)-SERVER, a web server that predicts SDS by analyzing quantitative measures of the conservation patterns of protein sites based on their physico-chemical properties and the heterogeneity of evolutionary changes between and within the protein subfamilies. This web server provides an improved representation of results, adds useful input and output options and integrates a wide range of analysis and data visualization tools when compared with the original standalone version of the SPEER algorithm. Extensive benchmarking finds that SPEER-SERVER exhibits sensitivity and precision performance that, on average, meets or exceeds that of other currently available methods. SPEER-SERVER is available at http://www.hpppi.iicb.res.in/ss/.


Multipolar hollow-core electrode for brain recordings.
A multicontact macroelectrode for brain recordings is described. Its hollow-core structure and slightly recessed contacts allow the electrode to be guided with a central stylet for minimal tissue trauma. The helical design of the electrode is characterized by high fatigue resistance and high flexibility allowing movement with the brain and preventing slicing through tissue. Clinical results have been obtained on epileptic patients.


Differences in dementia services and settings across place types and regions.
People with dementia have complex and unique social, environmental, and communication needs arising from impaired cognition. One response to dissatisfaction with the medical model of care in nursing homes has been the creation of more homelike and social options for care in the community. These options include community-based residential facilities and a variety of more independent senior dwellings. Staying in residential settings longer may be associated with benefits, including decreased financial burden and improved quality of life. However, with the boundaries between these place types often less than clearly drawn, it has become increasingly difficult to anticipate the specific services and environmental features provided by each. It is also difficult to effectively match facilities to the specific needs of older persons with dementia. Even social workers responsible for placements, especially in urban areas, may not be able to visit all local residential options. To better understand these new venues for dementia care, this study explored the range of services and settings available to people with dementia in three different place types in five Wisconsin counties: nursing homes, community-based residential facilities, and independent senior housing.


[Experimental studies on the cancer chemoprevention of tea pigments].
A batch of short-term tests were used to examine the effects of tea pigments on three stages of carcinogenesis, i.e. initiation, promotion and progression. Forward gene mutation test and micronuclei test were used to study the initiation stage of carcinogenesis; metabolic cooperation test and mice ear test to study the promotion stage. Viability and growth ability of Hela cells in soft agar and S180 solid tumor test in mice were used to examine the effect of tea pigments on the third stage of carcinogenesis. The results showed that both tea pigments and tea polyphenols had significantly protective effects on initiation, promotion and progression stages in carcinogenesis. In vitro study showed that tea pigments and tea polyphenols could induce QR and GST activity in Hep G2 cells. Oral administration of 0.1% tea polyphenols and 0.1% tea pigments could increase GST activity in rat liver by 25% and 18% respectively, and this increase was accompanied by the significant increase of GST 1-1, 1-2 and 3-3 protein expression level in rat liver. Our results suggested that the anticancer effect of tea pigments was the same as that of tea polyphenols, and the anticancer properties of tea pigments might be mediated by activating the enzymes such as QR and GST, which play important roles in the detoxification and exclusion of carcinogen.


Analysis of a framework using material balances in metabolic pathways to elucidate cellular metabolism.
A framework using material balances in metabolic pathways to study cellular metabolism is examined and the results are discussed. Rate measurements on extracellular compounds alone were found to be not always sufficient to validate proposed unique intracellular mechanisms. The conditions to delineate among candidate mechanisms based solely on extracellular measurements are established. The number of half reactions comprising the reaction network is found to be an important parameter.


Osteointegration of a Novel Silk Fiber-Based ACL Scaffold by Formation of a Ligament-Bone Interface.
Given the unsatisfactory results and reported drawbacks of anterior cruciate ligament (ACL) reconstruction, such as donor site morbidity and the limited choice of grafts in revision surgery, new regenerative approaches based on tissue-engineering strategies are currently under investigation. To determine (1) if a novel silk fiber-based ACL scaffold is able to initiate osteointegration in the femoral and tibial bone tunnels under in vivo conditions and (2) if the osteointegration process will be improved by intraoperatively seeding the scaffolds with the autologous stromal vascular fraction, an adipose-derived, stem cell-rich isolate from knee fat pads. Controlled laboratory study. A total of 33 sheep underwent ACL resection and were then randomly assigned to 2 experimental groups: ACL reconstruction with a scaffold alone and ACL reconstruction with a cell-seeded scaffold. Half of the sheep in each group were randomly chosen and euthanized 6 months after surgery and the other half at 12 months. To analyze the integration of the silk-based scaffold in the femoral and tibial bone tunnels, hard tissue histology and micro-computed tomography measurements were performed. Hard tissue histological workup showed that in all treatment groups, with or without the application of the autologous stromal vascular fraction, an interzone of collagen fibers had formed between bone and silk-based graft. This collagen-fiber continuity partly consisted of Sharpey fibers, comparable with tendon-bone healing known for autografts and allografts. Insertion sites were more broad based at 6 months and more concentrated on the slightly protruding, bony knoblike structures at 12 months. Histologically, no differences between the treatment groups were detectable. Analysis of micro-computed tomography measurements revealed a significantly higher tissue density for the cell-seeded scaffold group as compared with the scaffold-alone group in the tibial but not femoral bone tunnel after 12 months of implantation. The novel silk fiber-based scaffold for ACL regeneration demonstrated integration into the bone tunnels via the formation of a fibrous interzone similar to allografts and autografts. Histologically, additional cell seeding did not enhance osteointegration. No significant differences between 6 and 12 months could be detected. After 12 months, there was still a considerable amount of silk present, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed. ACL regeneration with a silk fiber-based scaffold with and without additional cell seeding may provide an alternative treatment option to current techniques of surgical reconstruction.


Genotoxicity evaluation of pesticide formulations containing alachlor and atrazine in multiple mouse tissues (blood, kidney, liver, bone marrow, spleen) by comet assay.
Every year, in the European countries more than 2 million tons of pesticides are released into the environment. More than 60% of those substances appear to be herbicides. Due to extensive production and application of this chemical their putative detrimental effect on life should be known and minimized. In this study we applied the comet assay on blood and 4 mouse organs (kidney, liver, bone marrow, and spleen) to evaluate possible genome damage caused by two pesticide formulations (Bravo and Gesaprim) containing alachlor and atrazine as active ingredients. Five male CBA mice were assigned to each of 4 treatment groups and control group. Bravo and Gesaprim were injected intraperitoneally once. Two different doses of Bravo were used: 0.031 ml/kg and 0.021 microl/kg, so that doses of alachlor mice received within the pesticide formulation given were 15 mg/kg and 0.01 mg/kg. Also Gesaprim was given at two different doses: 1.08 ml/kg and 0.07 microl/kg so that the doses of atrazine contained within the pesticide formulation given were 540 mg/kg and 3.5 x 10(-2) mg/kg. Mice were sacrificed 24 hours after treatment. Alkaline comet assay on the blood samples, kidney, liver, bone marrow and spleen was performed. Statistically significant (p<0.01) increase of tail length for all 5 tissues examined in mice treated with both Bravo and Gesaprim compared to the control was found. For both pesticides DNA of kidney and liver showed largest increase in migration. Also, distribution of tail length values for Bravo and Gesaprim for all mouse tissues examined showed a shift to the right when compared to the controls.


Fibroblastic reticular cells initiate immune responses in visceral adipose tissues and secure peritoneal immunity.
Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in nonclassical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). Compared with classical secondary lymphoid organs such as lymph nodes and Peyer's patches, FALCs develop along distinct differentiation trajectories and display a reduced structural complexity. Although it is well established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of classical secondary lymphoid organs, the role of FRCs in FALC-dependent peritoneal immunity remains unclear. Using FRC-specific gene targeting, we found that FRCs play an essential role in FALC-driven immune responses. Specifically, we report that initiation of peritoneal immunity was governed through FRC activation in a myeloid differentiation primary response 88 (MYD88)-dependent manner. FRC-specific ablation of MYD88 blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation and IgG class switching. Moreover, containment of Salmonella infection was compromised in mice lacking MYD88 expression in FRCs, indicating that FRCs in FALCs function as an initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.


Dysregulated Expression of RPS4Y1 (Ribosomal Protein S4, Y-Linked 1) Impairs STAT3 (Signal Transducer and Activator of Transcription 3) Signaling to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia.
Normal placentation and a successful pregnancy depend on appropriate trophoblast cell migration and invasion. Inadequate trophoblast invasion and impaired spiral artery remodeling may lead to pregnancy-related disorders, such as preeclampsia. RPS4Y1 (ribosomal protein S4, Y-linked 1) is a member of the S4E family of ribosomal proteins. In this study, we found that RPS4Y1 levels were upregulated in placental samples collected from preeclamptic patients, when compared with the normotensive pregnant women. In vitro, inhibition of RPS4Y1 induced trophoblast cell invasion, promoted placental explant outgrowth, and increased STAT3 (signal transducer and activator of transcription 3) phosphorylation along with elevated expression of N-cadherin and vimentin. Conversely, overexpression of RPS4Y1 results in reduced trophoblast cell invasion and decreased STAT3 phosphorylation. In addition, the suppression of RPS4Y1 promotes trophoblast cell invasion, which could be abolished by the STAT3 knockdown. Meanwhile, we observed reductions of STAT3 phosphorylation expression in preeclampsia patients. Collectively, these results demonstrate that the level of RPS4Y1 expression may be associated with preeclampsia by affecting trophoblast cell migration and invasion via the STAT3/epithelial-mesenchymal transition pathway.


A randomized control trial of a behavioral intervention for older adults with subjective cognitive complaints that combines cognitive rehabilitation strategies and lifestyle modifications.
This study examined the effectiveness of a 10-week cognitive rehabilitation and lifestyle modifying intervention that integrated compensation strategies, engagement in brain activities, and improving everyday function. The trial was registered with ClinicalTrials.gov (NCT03549078). Older adults with subjective cognitive concerns and normal performance on a cognitive screener were randomized into the intervention (n = 28) or waitlist control (n = 29) groups. The total sample comprised 57 individuals (age, mean = 74.8, SD = 6.5), mostly female (80.4% of the total sample), and well educated (education years: mean = 15.9, SD = 2.1). Outcome measures were completed at baseline, and immediately and 3- and 6-months post-intervention. Intervention participants reported significant improvements in aspects of everyday functioning and select compensation strategies and brain health activities. Increased compensation strategy use was maintained at 6-month follow up. This intervention has benefits for improving everyday functioning and increasing engagement with compensation strategies and brain health activities.


Dermatan Sulfate-Free Mice Display Embryological Defects and Are Neonatal Lethal Despite Normal Lymphoid and Non-Lymphoid Organogenesis.
The epimerization of glucuronic acid into iduronic acid adds structural variability to chondroitin/dermatan sulfate polysaccharides. Iduronic acid-containing domains play essential roles in processes such as coagulation, chemokine and morphogen modulation, collagen maturation, and neurite sprouting. Therefore, we generated and characterized, for the first time, mice deficient in dermatan sulfate epimerase 1 and 2, two enzymes uniquely involved in dermatan sulfate biosynthesis. The resulting mice, termed DKO mice, were completely devoid of iduronic acid, and the resulting chondroitin sulfate chains were structurally different from the wild type chains, from which a different protein binding specificity can be expected. As a consequence, a vast majority of the DKO mice died perinatally, with greatly variable phenotypes at birth or late embryological stages such as umbilical hernia, exencephaly and a kinked tail. However, a minority of embryos were histologically unaffected, with apparently normal lung and bone/cartilage features. Interestingly, the binding of the chemokine CXCL13, an important modulator of lymphoid organogenesis, to mouse DKO embryonic fibroblasts was impaired. Nevertheless, the development of the secondary lymphoid organs, including the lymph nodes and spleen, was normal. Altogether, our results indicate an important role of dermatan sulfate in embryological development and perinatal survival.


Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases.
Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.


A close association of RyRs with highly dense clusters of Ca2+-activated Cl- channels underlies the activation of STICs by Ca2+ sparks in mouse airway smooth muscle.
Ca(2+) sparks are highly localized, transient releases of Ca(2+) from sarcoplasmic reticulum through ryanodine receptors (RyRs). In smooth muscle, Ca(2+) sparks trigger spontaneous transient outward currents (STOCs) by opening nearby clusters of large-conductance Ca(2+)-activated K(+) channels, and also gate Ca(2+)-activated Cl(-) (Cl((Ca))) channels to induce spontaneous transient inward currents (STICs). While the molecular mechanisms underlying the activation of STOCs by Ca(2+) sparks is well understood, little information is available on how Ca(2+) sparks activate STICs. In the present study, we investigated the spatial organization of RyRs and Cl((Ca)) channels in spark sites in airway myocytes from mouse. Ca(2+) sparks and STICs were simultaneously recorded, respectively, with high-speed, widefield digital microscopy and whole-cell patch-clamp. An image-based approach was applied to measure the Ca(2+) current underlying a Ca(2+) spark (I(Ca(spark))), with an appropriate correction for endogenous fixed Ca(2+) buffer, which was characterized by flash photolysis of NPEGTA. We found that I(Ca(spark)) rises to a peak in 9 ms and decays with a single exponential with a time constant of 12 ms, suggesting that Ca(2+) sparks result from the nonsimultaneous opening and closure of multiple RyRs. The onset of the STIC lags the onset of the I(Ca(spark)) by less than 3 ms, and its rising phase matches the duration of the I(Ca(spark)). We further determined that Cl((Ca)) channels on average are exposed to a [Ca(2+)] of 2.4 microM or greater during Ca(2+) sparks. The area of the plasma membrane reaching this level is <600 nm in radius, as revealed by the spatiotemporal profile of [Ca(2+)] produced by a reaction-diffusion simulation with measured I(Ca(spark)). Finally we estimated that the number of Cl((Ca)) channels localized in Ca(2+) spark sites could account for all the Cl((Ca)) channels in the entire cell. Taken together these results lead us to propose a model in which RyRs and Cl((Ca)) channels in Ca(2+) spark sites localize near to each other, and, moreover, Cl((Ca)) channels concentrate in an area with a radius of approximately 600 nm, where their density reaches as high as 300 channels/microm(2). This model reveals that Cl((Ca)) channels are tightly controlled by Ca(2+) sparks via local Ca(2+) signaling.


Pretransplant survival is shorter in HIV-positive than HIV-negative subjects with end-stage liver disease.
Despite improved survival after liver transplantation (OLTX) in HIV-positive individuals treated with highly active antiretroviral therapy (HAART), some transplant candidates do not survive to OLTX. To determine if pretransplant outcome is related to severity of liver disease and/or HIV infection, we prospectively evaluated 58 consecutive HIV-positive candidates seen at a single center from 1997-2002. Of the 58, 15 (25.9%) were transplanted, whereas 21 (36.2%) died before OLTX, a median one month of evaluation, with more than half of those (12 of 21, 57.1%) dying from infection. By contrast, of 1,359 HIV-negative candidates, 860 (63.3%) were transplanted, whereas 211 (15.5%) died before OLTX (P < 0.001). The cumulative survival following initial evaluation was significantly shorter among HIV-positive than HIV-negative candidates (880 vs. 1,427 days, P = 0.035, Breslow) but was not related to the initial pretransplant MELD score (16 vs. 15), INR (1.5 vs. 1.5), creatinine (1.3 vs. 1.3 mg/dL), or total bilirubin (6.6 vs. 5.7 mg/dL), respectively, all P > 0.05. Among untransplanted HIV-positive candidates, the 21 who died did not differ from the 22 surviving in initial MELD (15 vs. 13), CD4 (230 vs. 327/microL), HIV load (both < 400 copies/mL), HAART intolerance (10/21, 47.6% vs. 10/22, 45.4%), or HCV infection (16/21, 76.2% vs. 16/22, 72.3%), all P > 0.05. Further, the 21 did not differ from the 15 transplanted in pre-OLTX CD4, HIV load, or MELD score, all P > 0.05. In conclusion, pretransplant survival appears shorter in HIV-positive OLTX candidates and is unrelated to severity of liver or HIV disease. Further study is warranted to determine risk factors for poorer pretransplant outcomes.


Pericardial cyst due to tuberculosis in an adolescent.
Patient with a mediastinal mass may be diagnosed incidentally or following evaluation for the symptoms due to compressive effects on the adjoining structures. Pericardial cysts account to 6% of mediastinal masses. Echocardiography, computerised tomography and magnetic resonance imaging aid in accurate diagnosis and localization of these cysts. Anaesthesia for patients with these cysts may occasionally turn out to be catastrophic during induction or in postoperative period. Surgery is the preferred choice of treatment in these patients.


Arvibacter flaviflagrans gen. nov., sp. nov., isolated from forest soil.
During a study of the bacterial community in forest soil of Kyonggi University, Suwon, South Korea, a glistening yellow-pigmented, Gram-stain-negative, aerobic, motile and rod-shaped bacterium, designated strain C-1-16T, was isolated. This strain was non-sporulating, catalase-negative and oxidase-positive. It was able to grow at 20-42 °C, at pH 6.0-9.0 and with 0-0.5 % (w/v) NaCl. This strain was taxonomically characterized by a polyphasic approach. Based on the results of 16S rRNA gene sequence analysis, strain C-1-16T formed a lineage within the family Chitinophagaceae of the phylum Bacteroidetes and closely related to the genera Filimonas(93.53 % sequence similarity), Sediminibacterium(92.52-90.75 %), Lacibacter(91.99-91.19 %) and Parasegetibacter(91.88-91.78 %). Flexirubin-type pigment was present for strain C-1-16T. The only respiratory quinone was menaquinone-7 (MK-7) and the major polar lipid was phosphatidylethanolamine. The predominant fatty acids of strain C-1-16T were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1 G, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and C16 : 0. The genomic DNA G+C content of this novel strain was 45.5 mol%. On the basis of phenotypic, genotypic and phylogenetic analysis, strain C-1-16T represents a novel species of a new genus in the family Chitinophagaceae, for which the name Arvibacter flaviflagrans gen. nov., sp. nov. is proposed. The type strain of Arvibacter flaviflagrans is C-1-16T (=KEMB 900-374T=KACC 18717T=JCM 31293T).


[Study on the title of Chongbian Yijingxiaoxue].
Chongbian Yijingxiaoxue was compiled by Jitian Zongxun in 1590 - 1610. The existing editions included a carved edition and copied edition, then came the photocopy. There was a chapter entitled 'Loujing Xuefa' which recorded 29 extrameridian points. This chapter was compiled into a verse in Volume 3 of Chongbian Yijingxiaoxue. As the book had always been confused with Yijing Xiaoxue, written by Liu Chun in the Ming Dynasty, its literature value increased and became necessary in literature research on extrameridian points. This kind of error was related to people's credulity and blindness on the authority of classical books and 'momentum of literature error'.


Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature.
The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature. Boys and girls (n = 429, 0.7-16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis. All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups. Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.


[Tissue metabolism in ruminants as affected by ionophores].
Remarkably influencing the VFA formation processes and their ratio in the rumen, ionophore action involves the range of free amino acids and individual enzymatic reactions of subcellular fractions of the rumen mucosa, heart muscle and longissimus muscle, kidneys and liver. The discovered reverse relationship between changes of levels of aminoacylation of tRNA and the amount of the respective free amino acids possibly is one of the crucial links in the common regulatory mechanism aimed at the maintenance of the specific stability of tissue and organ metabolism (including protein biosynthesis) in ruminants. It seems to be responsible for different effects of the ionophore on the investigated processes in different tissues and organs.


Experimental study of tetrodotoxin, a long-acting topical anesthetic.
To determine the effectiveness and toxicity of tetrodotoxin for use as a long-acting topical anesthetic. Four groups of six rabbits each received a 40-microl aliquot of either tetrodotoxin in one of three concentrations (10 mM, 1 mM, or 0.1 mM) or proparacaine 0.5% into the inferior conjunctival cul-de-sac of one eye, with the fellow eye of each rabbit receiving 40 microl of a 60-mM, pH 4.3 sodium citrate vehicle as a control. Corneal sensation was tested for up to 8 hours after administration of drugs, and response was noted by no blink, partial blink without full eyelid closure, and full blink. Slit-lamp examination at 12 and 24 hours after administration and pachymetry before and 24 hours after administration were performed to detect corneal toxicity. Rabbits receiving all three concentrations of tetrodotoxin did not demonstrate any ocular irritation, corneal thickening, or signs of systemic toxicity. At a dose of 10 mM, tetrodotoxin produced an anesthetic effect lasting up to 8 hours. At 1 mM, tetrodotoxin was an effective but shorter-acting anesthetic. At 0.1 mM, tetrodotoxin had no significant anesthetic effect. Proparacaine-treated rabbits initially were anesthetic, but this effect was largely gone by 1 hour and completely gone by 3 hours. Tetrodotoxin is a long-acting topical anesthetic in the rabbit cornea. Although additional toxicity studies are required, tetrodotoxin may provide an effective, long-lasting topical anesthetic for use in pain control after corneal procedures such as photorefractive keratectomy.


On the role of interfacial hydrogen bonds in "on-water" catalysis.
Numerous experiments have demonstrated that many classes of organic reactions exhibit increased reaction rates when performed in heterogeneous water emulsions. Despite enormous practical importance of the observed "on-water" catalytic effect and several mechanistic studies, its microscopic origins remains unclear. In this work, the second generation Car-Parrinello molecular dynamics method is extended to self-consistent charge density-functional based tight-binding in order to study "on-water" catalysis of the Diels-Alder reaction between dimethyl azodicarboxylate and quadricyclane. We find that the stabilization of the transition state by dangling hydrogen bonds exposed at the aqueous interfaces plays a significantly smaller role in "on-water" catalysis than has been suggested previously.


Myocardial hypoperfusion/reperfusion tolerance with exercise training in hypertension.
The purpose of this study was to examine whether exercise training, superimposed on compensated-concentric hypertrophy, could increase myocardial hypoperfusion-reperfusion (H/R) tolerance. Female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (age: 4 mo; N = 40) were placed into a sedentary (SED) or exercise training (TRD) group (treadmill running; 25 m/min, 1 h/day, 5 days/wk for 16 wk). Four groups were studied: WKY-SED (n = 10), WKY-TRD (n = 10), SHR-SED (n = 10), and SHR-TRD (n = 10). Blood pressure and heart rate were determined, and in vitro isolated heart performance was measured with a retrogradely perfused, Langendorff isovolumic preparation. The H/R protocol consisted of a 75% reduction in coronary flow for 17 min followed by 30 min of reperfusion. Although the rate-pressure product was significantly elevated in SHR relative to WKY, training-induced bradycardia reduced the rate-pressure product in SHR-TRD (P < 0.05) without an attenuation in systolic blood pressure. Heart-to-body weight ratio was greater in both groups of SHR vs. WKY-SED (P < 0.001). Absolute and relative myocardial tolerance to H/R was greater in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05). Endurance training superimposed on hypertension-induced compensated hypertrophy conferred no further cardioprotection to H/R. Postreperfusion 72-kDa heat shock protein abundance was enhanced in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05) and was highly correlated with absolute left ventricular functional recovery during reperfusion (R2= 0.86, P < 0.0001). These data suggest that both compensated hypertrophy associated with short-term hypertension and endurance training individually improved H/R and that increased postreperfusion 72-kDa heat shock protein abundance was, in part, associated with the cardioprotective phenotype observed in this study.


Heterogeneity in meta-analyses of treatment of acute postoperative pain: a review.
Heterogeneity and its causes must be assessed using meta-analyses (meta-analysis). Especially in meta-analysis dealing with treatment of acute postoperative pain, the type of surgery is a source of heterogeneity. We aimed to assess whether the type of surgery is considered a source of heterogeneity in meta-analysis and how it is taken into account in meta-analysis evaluating the efficacy of treatment of acute postoperative pain. We further compared meta-analysis that pooled trials of surgeries with highly heterogeneous postoperative pain levels, the heterogeneous group, with meta-analysis that pooled trials involving surgeries with homogeneous pain levels, the homogenous group. The meta-analysis reports available in Issue 3, 2011 of the electronic database of the Cochrane library and pooling results of randomized or quasi-randomized controlled trials that assessed the efficacy of treatment of acute postoperative pain alone were considered. A survey of experts established a rating of the postoperative pain levels for the type of surgery. For each meta-analysis, the different pain level ratings associated with the trials included in the meta-analysis were considered and the standard deviation (sd) of these ratings calculated. From the distribution of sd values, we defined the heterogeneous and homogeneous groups. Sixty-one meta-analyses were included; all assessed heterogeneity. Twenty-six meta-analyses considered the type of surgery as a subgroup (50% vs 38% in the homogeneous group vs heterogeneous group). Forty-four reports discussed the type of surgery as a source of clinical heterogeneity (85% vs 62% for the homogeneous vs heterogeneous group). Twenty-nine meta-analyses compared 'postoperative pain from dental surgery' to 'other type of surgery'. Meta-analyses evaluating treatment of postoperative pain should explore clinical heterogeneity associated with the type of surgery for better implications for practice.


When phylogenetic analysis complements the epidemiological investigation: a case of HIV-2 infection, Italy.
Human immunodeficiency virus type 2 (HIV-2) infection is geographically restricted, affecting West African countries such as Guinea- Bissau and Cape Verde. We describe a recent case of HIV-2 infection in an Italian patient. Phylogenetic analysis of the V3 region of HIV-2 indicated that the Italian patient was infected by HIV-2 subtype A2. The sequence obtained from the Italian patient clustered significantly with a sequence isolated from Senegal. A phylogenetic doubt may arise from a Guinea Bissau sequence because it was in a major clade with the Italian and Senegal sequences, but was not statistically significant. The discovery of another Italian case over a short time frame stresses the importance of strengthening the surveillance system for HIV-2 because of the increase in migration from endemic areas to Italy.


Extra-phosphoric effects of superdoses of a novel microbial phytase.
An experiment was conducted to evaluate the influence of a novel microbial phytase on broiler performance from d 0 to 42 and tibia ash at d 21. Male Cobb 500 broilers (n = 2,016) were fed 1 of 7 experimental diets: positive control (PC) formulated to meet or exceed nutrient recommendations; PC plus dicalcium phosphate (PC+DCP) formulated to provide Ca and P at 0.10% above the PC; PC plus 500 U/kg of microbial phytase (PC+500); negative control (NC) with Ca and P reduced from the PC by 0.16 and 0.15%, respectively; and NC plus 500 (NC+500), 1,000 (NC+1,000), or 1,500 (NC+1,500) U/kg of microbial phytase. Diets were fed in 3 phases from d 0 to 21, d 22 to 42, and d 43 to 49 to 32 birds/pen and 9 replicate pens/diet. From d 0 to 21, broilers fed the NC diet had decreased (P ≤ 0.05) BW gain and tibia ash compared with broilers fed all other diets, except tibia ash in birds fed PC+500. Phytase supplementation at 500, 1,000, or 1,500 U/kg to the NC improved (P ≤ 0.05) BW gain and tibia ash comparable with the PC. Feed conversion ratio (FCR) was improved (P ≤ 0.05) in broilers fed NC+1,500 compared with broilers fed all other diets. From d 0 to 49, growth performance was not influenced (P > 0.05) by diet. However, FCR was improved (P ≤ 0.05) in broilers fed 1,500 U/kg of microbial phytase compared with broilers fed the PC, PC+DCP, and NC. There were no differences in performance or tibia ash between broilers fed the PC or PC+DCP, which would indicate the PC diet was sufficient in Ca and P. Therefore, the improvements in FCR in the NC+1500 may be associated with mitigation of the antinutrient effects of phytate rather than improved P utilization.


He hit me; but it's okay! Female submissiveness in marital abuse: A review in Indian context.
India, a country with manifold multicultural bonds and relationships often witnesses a gross number of conflicted marital relationships. The plight in the frequency of marital abuse reporting in India has called gross public health attention globally. Multiple factors contribute to this arena in which, when we analyse can find out females submissiveness to report and or react to such kind of abusive incidences. The objective of this article is to review recent literature on female submissiveness in marital abuse. This narrative review is carried out to depict various perspectives that initiate abusive relationships and certain factors that prevent women from being subjected to rapid response. Literature relevant to the topic which was published within twenty years in prominent journals, newspapers, and websites has been reviewed thoroughly while writing this paper. Keywords for literature search included terms such as domestic violence, intimate partner violence/abuse, spouse abuse, married woman/female submissiveness, abusive marital relationships, and marital abuse. There is a paucity of studies analysing psychological and socio-demographic determinants of this submissiveness within such relationships in India. Several factors such as cultural, psycho-social, environmental attributes may prompt submissiveness among females in abusive marital relationships, which often leads to psychopathology and physical ailments. It is important to understand the need for a multidisciplinary approach to preventing marital abuse as a public health issue. By preventing and modulating such factors public health and women's well-being can be preserved in various domains.


Comparison of Body Composition Variables between Post-Bariatric Surgery Patients and Non-Operative Controls.
Since bariatric surgery results in massive weight loss, it may be associated with a disproportionate decrease in lean body mass. To evaluate body composition in post-bariatric surgery patients who had a successful weight loss at 12 months (>50% excess weight loss) with comparisons to healthy controls who were matched for age, sex and BMI. This is an observational analytic study using data from post-bariatric surgery patients who had laparoscopic Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (SG) at King Chulalongkorn Memorial Hospital. Patients who had percentage excessive weight loss (%EWL) >50% and achieved a BMI of <30 kg/m2 within 12 months after the surgery were included. Non-operative healthy controls matched for sex, age, and BMI (1:1) were recruited. The 12-month post-bariatric surgery BMI was used to match the BMI of the control subjects. A single bioelectrical impedance analysis (BIA) (Inbody 770) machine was used for the entire study. Sixty participants were included in this study. There are 30 post-bariatric surgery patients (female n = 19, male n = 11) and 30 non-operative controls (female n = 19, male n = 11). The 12-month post-bariatric surgery patients had lower percentage of body fat (PBF) (30.6% vs 35.9%, P-value .001) and trunk fat mass (10.3 vs 12.4 kg, P-value .04) than non-operative controls. The 12-month post-bariatric surgery patients also were found to have more soft lean mass (SLM) (47.7 vs 39.9 kg, P-value .001), fat free mass (FFM) (51.1 vs 42.3 kg, P-value .001), skeletal muscle mass (SMM) (27.5 vs 23 kg, P-value .003), and trunk lean mass (21.2 vs 19 kg, P-value .02). Despite the significant reductions in all body composition variables in post-bariatric surgery patients at 12-month follow-up, both fat free mass and skeletal muscle mass were found to be higher in the surgical patients compared to the control group. Thai Clinical Trials Registry, https://thaiclinicaltrials.org/ID:TCTR20200223003.


Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systematic review.
Metformin is commonly used for treating type 2 diabetes, and may also reduce cancer risk. Previous studies have demonstrated the association between metformin use and a decreased risk of head and neck cancer. Therefore, the aim of the present systematic review was to summarize the available literature on the in vitro anti-tumor effects of metformin on head and neck squamous cell carcinoma (HNSCC). Research studies were obtained from Cochrane Library, Embase, LILACS, MEDLINE and PubMed databases, without time or language restrictions. Only in vitro studies analyzing the effects of metformin on HNSCC cell lines were included. The authors methodically appraised all the selected studies according to the Grading of Recommendations Assessment, Development and Evaluation method to make a judgment of the evidence quality. Of the 388 identified reports, 11 studies met the inclusion criteria and were used for qualitative analysis. These studies demonstrated that metformin is important in inhibiting cell proliferation, inducing G0/G1 cell cycle arrest and apoptosis, and in regulating proteins involved in carcinogenesis pathways, which corroborates its potential in vitro anti-tumor effects. The present systematic review highlights the biological mechanisms of metformin used alone or together with traditional therapies for cancer. Though very limited, currently available preclinical evidence shows that metformin exerts a potential effect on head and neck carcinoma.


Identification of a robust DNA methylation signature for Fanconi anemia.
Fanconi anemia (FA) is a clinically variable and genetically heterogeneous cancer-predisposing disorder representing the most common bone marrow failure syndrome. It is caused by inactivating predominantly biallelic mutations involving >20 genes encoding proteins with roles in the FA/BRCA DNA repair pathway. Molecular diagnosis of FA is challenging due to the wide spectrum of the contributing gene mutations and structural rearrangements. The assessment of chromosomal fragility after exposure to DNA cross-linking agents is generally required to definitively confirm diagnosis. We assessed peripheral blood genome-wide DNA methylation (DNAm) profiles in 25 subjects with molecularly confirmed clinical diagnosis of FA (FANCA complementation group) using Illumina's Infinium EPIC array. We identified 82 differentially methylated CpG sites that allow to distinguish subjects with FA from healthy individuals and subjects with other genetic disorders, defining an FA-specific DNAm signature. The episignature was validated using a second cohort of subjects with FA involving different complementation groups, documenting broader genetic sensitivity and demonstrating its specificity using the EpiSign Knowledge Database. The episignature properly classified DNA samples obtained from bone marrow aspirates, demonstrating robustness. Using the selected probes, we trained a machine-learning model able to classify EPIC DNAm profiles in molecularly unsolved cases. Finally, we show that the generated episignature includes CpG sites that do not undergo functional selective pressure, allowing diagnosis of FA in individuals with reverted phenotype due to gene conversion. These findings provide a tool to accelerate diagnostic testing in FA and broaden the clinical utility of DNAm profiling in the diagnostic setting.


Hyperlipidemia increases the risk of retear after arthroscopic rotator cuff repair.
Hyperlipidemia (HL) has been identified as a risk factor for rotator cuff tear, but no studies have evaluated its effects on healing. The purpose of this study was to evaluate the effect of HL and statin use on rotator cuff healing after arthroscopic repair. This was a retrospective review of 85 patients (86 shoulders) who underwent arthroscopic rotator cuff repair with postoperative ultrasound evaluation. Ultrasound findings were graded no retear, partial-thickness retear (PT), or full-thickness retear (FT). Average age was 62.1 years (45.3-74.3 years). On ultrasound evaluation, 65 shoulders (75.5%) had no retear, 14 (16.3%) had PT, and 7 (8.1%) had FT. There was no significant difference in retear rate by age, technique, or tissue quality. There were 33 patients (38.8%) who had the diagnosis of HL, and all were taking a statin medication. Compared with patients without HL, patients with HL had significantly higher rates of FT (18.1% vs. 1.9%; P < .001) and PT (27.2% vs. 9.4%; P < .001). The total retear rate (PT and FT) for HL patients was significantly higher at 45.5% (15/33) compared with the patients without HL at 11.3% (6/53), with an odds ratio of 6.5 (P < .001). There was no difference in retear rate by dosage or type of statin mediation. After arthroscopic rotator cuff repair, HL was a risk factor for retear. Further investigation is warranted on this topic, and these results may help in managing expectations after surgery.


Burden of Misconception in Sexual Health Care Setting: A Cross-Sectional Investigation among the Patients Attending a Psychiatric Sex Clinic of Bangladesh.
Bangladesh is a country in South Asia with about 160 million people and achieved health related Millennium Development Goals (MDG) significantly. But sexual health is still an untapped issue with predominant myths and misconception. We aimed to look into the proportions of patients attending sexual health care services due to misconceptions. The descriptive, cross-sectional study was conducted among 110 patients attending Psychiatric Sex Clinic (PSC) of Bangabandhu Sheikh Mujib Medical University. Respondents were included in the study with convenient sampling from November 2016 to March 2017. Data were collected through face-to-face interview with semistructured preformed, pretested questionnaire and analyzed by SPSS software 16.0 version. Most of the patients (93%) were male, 60% were married, 62% were urban habitant, 42% were under grade 10, and 33% were service holder. Total 55% of the patients had misconceptions and 29% visited only for misconception; 14% had Premature Ejaculation; and 12% had desire disorder. 32% of the patients had psychiatric disorders and among them depression was most common, 13%. Positive openness in sexual health and appropriate strategy should be taken to improve the quality of sexual life as well as reduce the misconception in the people of Bangladesh.


Consumers' reports on the health effects of direct-to-consumer drug advertising.
We conducted a national telephone survey about health care experiences associated with direct-to-consumer advertising (DTCA) of prescription drugs. Among the 35 percent of our sample who had a physician visit during which DTCA was discussed, 25 percent received a new diagnosis, of which 43 percent were considered high priority according to authoritative sources. More than half also reported actions taken by their physician other than prescribing the advertised drug. Despite concerns about DTCA's negative consequences, we found no differences in health effects between patients who took advertised drugs and those who took other prescription drugs.


Evidence-based medical nutrition therapy for diabetes.
The 2002 American Diabetes Association (ADA) nutrition principles and recommendations are classified according to the level of evidence available using the ADA evidence grading system. Research also supports medical nutrition therapy (MNT) as an effective therapy in reaching treatment goals for glycemia, lipids, and blood pressure. Recommendations for carbohydrate, protein, dietary fat, micronutrients, and alcohol are summarized. The first priority for persons requiring insulin therapy is to identify a food/meal plan that can be used to integrate an insulin regimen into the person's lifestyle. MNT for type 2 diabetes progresses from prevention of obesity or weight gain to improving insulin resistance to contributing to improved metabolic control. The progressive decline in beta-cell failure requires that MNT progress from MNT as monotherapy to MNT in combination with oral glucose-lowering agents to MNT with insulin therapy. Monitoring of outcomes is essential to assess the outcomes of lifestyle interventions or to determine if changes in medication(s) are necessary.


Erectile function and assessments of erection hardness correlate positively with measures of emotional well-being, sexual satisfaction, and treatment satisfaction in men with erectile dysfunction treated with sildenafil citrate (Viagra).
We aimed to determine whether erectile function (EF) and assessments of erection hardness correlate positively with measures of psychosocial outcomes (ie, emotional well-being, sexual satisfaction, and satisfaction with erectile dysfunction [ED] treatment) in men treated with sildenafil citrate (Viagra; Pfizer Inc, New York, NY). Data were collected from 33 worldwide phase 2, 3, and 4 sildenafil clinical trials, which included almost 10,000 men with ED. Most of these trials were randomized, double-blind, and placebo-controlled (n = 27) and were undertaken to assess doses of 50 mg adjustable to 25 mg or 100 mg, depending on efficacy and tolerability (n = 32). Doses were taken approximately 1 hour before anticipated sexual activity but not more often than once daily. EF was assessed with use of the EF domain of the International Index of Erectile Function (IIEF) and with assessments of erection hardness (Erection Hardness Grading Scale [EHGS] and IIEF Q2 [the frequency of erections hard enough for penetration]). Change (baseline to end point) in emotional well-being in men treated for ED was assessed with the Self-Esteem and Relationship (SEAR) questionnaire, which consisted of the Confidence domain (ie, the Self-Esteem subscale and Overall Relationship subscale) and the Sexual Relationship domain. End point treatment satisfaction (overall, speed of onset, and duration of action) was assessed with the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). The IIEF was used to assess change and end point sexual satisfaction by means of the Intercourse Satisfaction domain, Q7 (frequency of satisfactory sexual intercourse), and the Overall Satisfaction domain (ie, Q13, satisfaction with sex life, and Q14, satisfaction with sexual relationship). In men treated with sildenafil for ED, scores for measures of EF (IIEF EF domain, IIEF Q2) and the percentage of erections graded completely hard and fully rigid (EHGS grade 4) correlated positively with scores for measures of psychosocial outcomes (SEAR emotional well-being, IIEF sexual satisfaction, and EDITS ED treatment satisfaction), indicating that when EF improved and erection hardness increased, these measures of psychosocial function also improved.


Liver abscess as a rare complication of Crohn's disease: a case report.
Pyogenic liver abscess is a rarely seen extraintestinal complication of Crohn's disease. It has different features from other liver abscesses. Its clinical and laboratory findings are not specific and mimic the reactivation of Crohn's disease and diagnosis can be delayed. The radiological methods are very useful in diagnosis and treatment of liver abscess. In this paper, we present a patient with pyogenic liver abscess which developed in the course of Crohn's disease.


What face mask for what use in the context of COVID-19 pandemic? The French guidelines.
In the context of the COVID-19 pandemic, wearing a face mask has become usual and ubiquitous, in both hospitals and community. However, the general public is consuming surgical or filtering face piece (FFP) masks irrespective of their specificity, leading to global supply shortage for the most exposed persons, which are healthcare workers. This underlines the urgent need to clarify the indications of the different categories of mask, in order to rationalize their use. The study herein specifies the French position for the rational use of respiratory protective equipment for healthcare workers.


Takotsubo syndrome with several hypertensive crises: an unexpected diagnosis.
We present an unusual clinical case of a 39-year-old woman admitted to the Department of Cardiology due to stenocardial pain accompanied by hypertensive crisis. The patient presented with severe chest pain and high blood pressure, along with a history of type 2 diabetes, hyperlipidemia, smoking, and hypertension. Initial tests showed elevated troponin T, glucose, CRP, and D-dimer levels, and electrocardiography and transthoracic echocardiography showed abnormalities suggesting acute myocardial infarction, but angiography did not reveal any significant coronary artery blockages. Further tests and imaging led to a diagnosis of takotsubo syndrome (TTS) and suspicion of pheochromocytoma, which was confirmed later biopsy. The presented case is very rare because the coexistence of TTS and pheochromocytoma is not common due to the rarity of the tumor. It is very important to make a quick and accurate diagnosis, because improperly treated cases can lead to death.


Hormonal profiles in women with breast cancer (review).
The literature concerning endogenous hormonal profiles in women with breast cancer and breast-cancer risk has been critically reviewed. The many published reports have been divided into 11 groups, with each group centered on a particular hypothesis that has been either explicitly formulated by the authors of the reports or perceived by other workers as a unifying hypothesis in certain studies. The hypotheses reviewed are: the adrenal androgen insufficiency hypothesis, the anovulation/luteal inadequacy hypothesis, the estriol hypothesis, the ovarian androgen excess hypothesis, the thyroid dysfunction hypothesis, the prolactin hypothesis, the estrone hypothesis, the estrogen-window hypothesis, the estrogen-excess hypothesis, the melatonin hypothesis, and the estrogen hydroxylation hypothesis. It is concluded that there remain, at present, only four viable hypotheses: the hypotheses of increased risk with adrenal androgen deficiency, ovarian dysfunction (luteal inadequacy and excessive ovarian androgen secretion), increased 16 alpha-hydroxylation of estradiol, and the hypothesis of decreased risk with pregnancy-induced lowering of prolactin levels. Adrenal androgen deficiency seems to be pertinent only in premenopausal cancer patients, and may be a genetic defect. Ovarian dysfunction seems to be pertinent to both premenopausal and post-menopausal patients and may also have a strong genetic component. Increased estradiol hydroxylation likewise seems to have a genetic component. The prolactin effect differs from the others, in that it is clearly environmental, rather than genetic, and may represent a permissive effect rather than a true risk-promoting effect.


Endothelial function and chronic exposure to air pollution in normal male subjects.
Exposure to urban air pollution, ultrafine particles or gases, is associated with acute cardiovascular mortality and morbidity. We investigated the effect of ambient air pollution on endothelial function in 40 healthy white male nonsmokers spontaneously breathing ambient air in Paris, France. Air pollutant levels (nitrogen, sulfur and carbon oxides, and particulate matter) were averaged during the 5 days preceding arterial measurements. Brachial artery endothelium-dependent flow-mediated dilatation and reactive hyperemia induced by hand ischemia and endothelium-independent glyceryl trinitrate dilatation were measured using a radiofrequency-based echo-tracking device at 2-week intervals. Flow-mediated dilatation was independently and negatively correlated with the average levels of sulfur dioxide (P<0.001) and nitrogen monoxide (P<0.01). Sulfur dioxide levels explained 19% of the variance of flow-mediated dilatation. An increase in gaseous pollutants, 2 weeks apart, was significantly associated with a decreased in flow-mediated dilatation. No association was found between air pollutants and glyceryl trinitrate-induced vasodilatation. Reactive hyperemia was significantly and positively correlated with particulate matter with aerodynamic diameters <10 microm and <2.5 microm (P<0.0001 and P<0.001, respectively) and nitrogen dioxide (P<0.01). An increase in particulate matter, 2 weeks apart, was significantly correlated with an increase in reactive hyperemia. Endothelial function was impaired by ordinary levels of pollution in healthy young males, in an urban area, and may be reduced by 50% between the least and the most polluted day. Gaseous pollutants affect large artery endothelial function, whereas particulate matter exaggerates the dilatory response of small arteries to ischemia.


A laboratory for handling chemical toxicants safely.
The Centers for Disease Control has a special Chemical Toxicant Laboratory (CTL) for handling very hazardous chemicals. It is designed to protect the workers, prevent the release of the chemical toxicant into the surrounding environment, and provide for the scientific integrity of the experiments conducted. A discussion of laboratory ventilation and special containment devices is presented. The design of the CTL, coupled with a realistic set of safety guidelines, provides for the safe conduct of research involving highly toxic chemicals.


Ultrasound-guided fine needle aspiration biopsy in the diagnosis of pulmonary cryptococcosis.
The purpose of this study was to assess the safety and reliability of ultrasound-guided fine needle aspiration biopsy (US-guided FNAB) combined with modified Papanicolaou's staining in the diagnosis of pulmonary cryptococcosis. The study included 10 patients (9 men, 1 woman, 28-70 yr). Percutaneous US-guided FNAB was performed through a puncture probe with central channel guidance (n = 8) or in a 'free-hand' manner (2), depending on the size of the lesion and the experience of the operator. Sonography disclosed homogeneously hypoechoic lesions with air bronchograms over the peripheral or central portion in nine patients, and occasional heterogeneous echogenicity with necrotic tissue without air bronchogram in one. Thirteen lesions were found on the chest radiographs of the 10 patients; these could be divided into three patterns: infiltrates (2), nodules or masses (7), and consolidation (4). Using US-guided FNAB and immediate modified Papanicolaou's stain, a diagnosis of pulmonary cryptococcosis was confirmed in nine of the 10 patients. The remaining case was proven by surgical resection. No major complications developed after US-guided FNAB. We conclude that this technique, combined with modified Papanicolaou's staining, provides a safe, rapid, and reliable method for diagnosing pulmonary cryptococcosis.


Long-term effects of mild traumatic brain injuries to oculomotor tracking performances and reaction times to simple environmental stimuli.
Understanding the long-term effects of concussive events remains a challenge for the development of modern medical practices and the prevention of recurrent traumas. In this study, we utilized indices of oculomotor performance and the ability to react to simple environmental stimuli to assess the long-term motor effects of traumatic brain injury in its mildest form (mTBI). We performed analysis of eye movement accuracy, investigated the presence of abnormal eye movements, and quantified time to react to simple environmental stimuli on long-term mTBI survivors. Results indicated the presence of impairments to basic neural functions used to explore and respond to environmental demands long after the occurrence of mTBIs. Specifically, the result revealed the presence of abnormal saccadic eye movements while performing horizontal smooth pursuit, diminished accuracy of primary saccadic horizontal eye movement, and a widespread slower reaction to both visual and auditory stimuli. The methodology used in this study indicated to be potentially useful in aiding future investigations of neural circuitry impaired by mTBI and provide indices of recovery in future clinical trials testing mTBI-related clinical interventions.