Causes and consequences of a tropical forest gold rush in the Guiana Shield, South America.
Statistical and spatial analyses of both historical time series and remotely sensed data show a link between the spatial distribution and growth of gold production across the Guiana Shield in northeast Amazonia. Results indicate that an exponential rise in production across an expanding area is primarily a delayed response to the 1971-1978 market flotation of international gold prices. The subsequent 10-fold (2-fold) average nominal (real) price increase has provided a compelling economic incentive to mass exploitation of lower-grade gold deposits. The ground-based and remotely sensed distributions of mining activity are strongly attached to these deposits that dominate the region's gold geology. The presence of these gold-bearing formations in conservation and sustainable timber zones has sparked social conflict and environmental degradation across the region. Left unmanaged, more than a quarter-million square-kilometer area of tropical forest zoned for protection and sustainable management could ultimately be compromised by the price-driven boom in gold mining through poorly integrated resource use planning, lack of reclamation effort, and control of illegal operations. Serious public health issues propagated through the unregulated mining environment further erode the financial benefits achieved through gold extraction. This study demonstrates in part how international economic policies successfully stabilizing more conspicuous centers of the global economy can have unintended but profound environmental and social impacts on remote commodity frontiers.


The role of mast cells in inflammatory processes: evidence for nerve/mast cell interactions.
In the rat, there is considerable evidence of mast cell/nerve interaction both in the normal and infected intestine. Between 67 and 87% of all mast cells in the intestinal lamina propria of rats infected 22-35 days earlier with Nippostrongylus brasiliensis were touching nerves. These membrane contacts were between subepithelial mast cells and nonmyelinated nerves containing substance P, calcitonin gene-related peptide and neurone specific enolase. 2.5S nerve growth factor (NGF) has a significant enhancement effect on antigen-induced histamine release without addition of phosphatidylserine, and the in vivo administration of NGF to rats causes both connective tissue and mucosal mast cells to dramatically increase in number. All of these effects are both dose dependent and NGF specific, as evidenced by inhibition with anti-NGF. 2.5S NGF also causes in vitro increase of colonies in methylcellulose cultures of human peripheral blood. The effects of NGF in this system are synergistic with other T cell-derived growth factors and relatively specific for metachromatic cell growth. These observations support the conclusions that nerves and mast cells may constantly communicate and provide a structural and conceptual framework whereby the central nervous system may communicate with inflammatory events.


Network architecture of the long-distance pathways in the macaque brain.
Understanding the network structure of white matter communication pathways is essential for unraveling the mysteries of the brain's function, organization, and evolution. To this end, we derive a unique network incorporating 410 anatomical tracing studies of the macaque brain from the Collation of Connectivity data on the Macaque brain (CoCoMac) neuroinformatic database. Our network consists of 383 hierarchically organized regions spanning cortex, thalamus, and basal ganglia; models the presence of 6,602 directed long-distance connections; is three times larger than any previously derived brain network; and contains subnetworks corresponding to classic corticocortical, corticosubcortical, and subcortico-subcortical fiber systems. We found that the empirical degree distribution of the network is consistent with the hypothesis of the maximum entropy exponential distribution and discovered two remarkable bridges between the brain's structure and function via network-theoretical analysis. First, prefrontal cortex contains a disproportionate share of topologically central regions. Second, there exists a tightly integrated core circuit, spanning parts of premotor cortex, prefrontal cortex, temporal lobe, parietal lobe, thalamus, basal ganglia, cingulate cortex, insula, and visual cortex, that includes much of the task-positive and task-negative networks and might play a special role in higher cognition and consciousness.


Glucagon-stimulated and postprandial plasma C-peptide values as measures of insulin secretory capacity.
Basal, postprandial (2 h after breakfast), and glucagon-stimulated plasma C-peptide concentrations were determined in a group of 36 adult diabetic patients. Basal and postprandial C-peptide values were measured on consecutive days to estimate the degree of variation of C-peptide secretion. In a subgroup of 15 diabetic patients treated chronically with diet and oral hypoglycemic agents (sulfonylureas or a combination of sulfonylureas and metformin), we studied whether administration of sulfonylureas immediately before breakfast had any effect on postprandial C-peptide values. Absolute differences between two consecutive fasting C-peptide concentrations in insulin-requiring patients were less than 0.1 nM in all but 1 patient, in whom the difference was 0.18 nM. In subjects treated with oral hypoglycemic agents the median difference was 0.12 nM (range 0-0.38 nM). Absolute differences between two consecutive postprandial C-peptide concentrations were all less than 0.1 nM in insulin-requiring patients. No significant difference was found between postprandial C-peptide concentrations with or without preceding administration of oral hypoglycemic agents (medians 1.35 and 1.30 nM, respectively). Glucagon-stimulated C-peptide concentrations were somewhat higher than the postprandial values. However, equal discrimination between insulin-requiring and non-insulin-requiring diabetic patients was found by measuring postprandial or glucagon-stimulated C-peptide concentrations.


Different Cortical Activation of Facial Synkinesis Patients with Different Course of Disease: A Task fMRI Study.
Facial synkinesis is a disease characterized by unintentional activation of facial muscles, which causes that the patients cannot control their facial expressions independently. Previous studies have shown that its pathogenesis is related to the reorganization of cerebral cortex, but it remains unclear what brain changes the patients have at different stage of the disease. For this study, we recruited 30 patients with facial synkinesis and 19 healthy control subjects from Shanghai Huashan Hospital. All participants completed bilateral blinking and grinning tasks while functional magnetic resonance imaging (fMRI) data was collected. We measured the brain activation strength of each task and observed the activation similarity of the ipsilateral tasks. Then we explored the correlation between activation pattern and clinical scale. Results showed different activation pattern along the courses of disease for blinking and grinning task, which may be due to the inconsistent process of cortical reorganization. The late stage group activated more in blinking task, but the least in grinning tasks, especially on the affected side (p<0.001 at voxel level, p<0.05 at cluster level, FWE corrected). Compared with healthy controls, the activation of patients between tasks on the affected side is more similar(p<0.05). There was a negative correlation in right postcentral gyrus between activation similarity and scale scores (symmetry of voluntary movement scores: R = -0.469, p = 0.009). This could be attributed to the rearrangement of the nervous system following facial nerve injury, leading to incorrect connections between nerves and muscles. Our study may be helpful for understanding mechanism of facial synkinesis and provide basis for the stage-dependent diagnosis and treatment.


Reducing Racial Health Care Disparities: A Social Psychological Analysis.
Large health disparities persist between Black and White Americans. The social psychology of intergroup relations suggests some solutions to health care disparities due to racial bias. Three paths can lead from racial bias to poorer health among Black Americans. First is the already well-documented physical and psychological toll of being a target of persistent discrimination. Second, implicit bias can affect physicians' perceptions and decisions, creating racial disparities in medical treatments, although evidence is mixed. The third path describes a less direct route: Physicians' implicit racial bias negatively affects communication and the patient-provider relationship, resulting in racial disparities in the outcomes of medical interactions. Strong evidence shows that physician implicit bias negatively affects Black patients' reactions to medical interactions, and there is good circumstantial evidence that these reactions affect health outcomes of the interactions. Solutions focused on the physician, the patient, and the health care delivery system; all agree that trying to ignore patients' race or to change physicians' implicit racial attitudes will not be effective and may actually be counterproductive. Instead, solutions can minimize the impact of racial bias on medical decisions and on patient-provider relationships.


Treatment of substance abuse during pregnancy and infant outcome.
The objective of this study is to analyze the effects of residential substance abuse treatment on pregnancy outcome among gravidas in a gender-specific program. All clients (cases) who entered a residential substance abuse program for pregnant and postpartum women were eligible for inclusion in the study (n=95). Only those who were in treatment at the time of delivery were included in the present analysis (n=57). Two comparison groups were used: (1) substance abusers who received no treatment during pregnancy (positive control group) and (2) pregnant women who were not substance abusers (negative control group). Cases were matched to controls on ethnicity (negative and positive controls) and drug of choice (positive controls only). Medical records were reviewed and abstracted for cases and controls. The primary drug of choice was cocaine for 56% of clients in the study, heroin 15.8%, and alcohol 10.8%. Average length of time in treatment before delivery was 11.7 weeks. The frequency of pregnancy complications allowing treatment and position controls was significantly higher than the negative control group (p<0.0001). The frequency of perinatal infant complications was increased among treatment group infants (p<0.0001). Two infants in the treatment group were positive for a substance of abuse at birth. In the treatment versus positive control group, mean birth weight (BW) was 3227 versus 2800 g (p<0.01), estimated gestational age (EGA) was 38.9 versus 39 weeks, average head circumference (FOC) was 33.8 versus 32.5 cm (p<0.05), and mean birth length (BLT) was 48.7 cm versus 46.9 (p<0.05). No significant differences were found between treatment and negative control groups. Maternal syphilis was increased in frequency in the positive control group compared with the negative control group (p<0.07). Thirty-percent of mothers had sexually transmitted diseases (STDs) for which infants were at risk and treated prophylactically; no infant in the treatment group contracted a vertically transmitted STD. For every 10 weeks in treatment, BW was increased 340 g, EGA 1 week, FOC 0.8 cm, and BLT 1.8 cm. Thus, substance abuse treatment for pregnant women in the program increased fetal growth, which significantly decreased the risk for poor neonatal outcomes. Importantly, maternal and infant perinatal complications in the treatment group were increased in frequency compared with the two control groups. This may possibly have occurred because healthcare providers were not blinded to maternal treatment status.


Multi-focal dysplasia is associated with high recurrence rates after successful ablation of dysplastic Barrett's esophagus.
Barrett's esophagus (BE) might recur after complete eradication of intestinal metaplasia (CEIM). We investigated factors associated with recurrence of BE after successful Radiofrequency ablation (RFA). A longitudinal study of BE patients with dysplasia treated with RFA from 2014 to 2021 in two large referral centers. Recurrence was identified in histologic specimens. Factors associated with post-RFA recurrence were analyzed using Cox regression analysis. A total of 728 patients with BE were identified, 118 had underwent RFA, and 113 had sufficient follow up time. Mean age was 63.7 (±11.7) years, 73.5% were males, 59.3% had long segment of BE, and 30.1% had multifocal dysplasia. During 340.8 patient-years of follow-up, 15 patients (13.3%) had recurrence of BE, which represent an incidence rate of 4.41% per patient-year. Incidence rate of recurrence with dysplasia was 1.17% per patient-year. Multifocal dysplasia, number of RFA sessions, and endoscopic resection before RFA were associated with risk of recurrence in univariate analysis. However, in cox regression analysis only multifocal dysplasia (HR 10.99; 95% CI 2.83-22.62, p = 0.001) was associated with post-RFA recurrence. Total recurrence rates after CEIM are low, and multifocal dysplasia before the ablative therapy is significantly associated with BE recurrence after CEIM. Patients with multifocal dysplasia should be monitored rigorously after successful ablation.


Principles and pitfalls of free hormone measurements.
The free hormone hypothesis states that a hormone's physiological effects depend on the free hormone concentration, not the total hormone concentration. Although the in vivo relationship between free hormone and protein-bound hormone is complex, most experts have applied this view to the design of assays used to assess the free hormone concentration in the blood sampled for testing in vitro. The history of the measurement of free thyroxine, probably the most frequently requested free hormone determination, offers a good example of the approaches that have been taken. Methods that require physical separation of the free hormone from the protein-bound hormone must address both the potential disturbance in the equilibrium between the two, as well as the challenge of quantifying small levels of hormone accurately and precisely. The implementation of mass spectrometry in the clinical laboratory has helped to develop proposed reference measurement procedures. These must be utilized to standardize the variety of immunoassay approaches that currently represent options commercially available to the routine clinical laboratory. Practicing endocrinologists should discuss the details of the free hormone assays offered by the clinical laboratory they utilize for patient result reporting, and clinical laboratories should implement the recommendations of published guidelines to ensure that free hormone results using commercially available immunoassays are as accurate and precise as possible.


Efficacy of intraoperative epidural steroids in lumbar discectomy: a systematic review.
This study is a descriptive review of the literature aimed at examining the efficacy of the use of intraoperative epidural steroids in lumbar disc surgery, a matter that remains controversial. The relevant clinical trials were selected from databases and reviewed. The methodological quality of each included study was assessed and graded for perceived risk of bias. All the documented significant and non-significant findings were collected. Our outcome targets were reduction in postoperative pain scores, consumption of analgesia, duration of hospital stay and no increase in complication rates. The variation in the timing of postoperative pain assessments necessitated grouping the outcome into three postoperative stages; early: 0 to 2 weeks, intermediate: more than 2 weeks to 2 months and late: more than 2 months to 1 year. Sixteen trials that were published from 1990 to 2012 were eligible. At least one significant reduction in pain score was reported in nine of the eleven trials that examined pain in the early stage, in four of the seven trials that examined pain in the intermediate stage and in two of the eight trials that examined pain in the late stage. Seven of the nine trials that looked at consumption of postoperative analgesia reported significant reduction while six of the ten trails that examined the duration of hospital stay reported significant reduction. None of the trials reported a significant increase of steroid-related complications. There is relatively strong evidence that intraoperative epidural steroids are effective in reducing pain in the early stage and reducing consumption of analgesia. There is also relatively strong evidence that they are ineffective in reducing pain in the late stage and in reducing duration of hospital stay. The evidence for their effectiveness in reducing pain in the intermediate stage is considered relatively weak. The heterogeneity between the trials makes it difficult to make undisputed conclusions and it indicates the need for a large multicenter trial with validated outcome measures that are recorded at fixed time intervals.


Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance.
Adipose tissue contains a population of multipotent adipose stem cells (ASCs) that form tumor stroma and can promote tumor progression. Given the high rate of ovarian cancer metastasis to the omental adipose, we hypothesized that omental-derived ASC may contribute to ovarian cancer growth and dissemination. We isolated ASCs from the omentum of three patients with ovarian cancer, with (O-ASC4, O-ASC5) and without (O-ASC1) omental metastasis. BM-MSCs, SQ-ASCs, O-ASCs were characterized with gene expression arrays and metabolic analysis. Stromal cells effects on ovarian cancer cells proliferation, chemoresistance and radiation resistance was evaluated using co-culture assays with luciferase-labeled human ovarian cancer cell lines. Transwell migration assays were performed with conditioned media from O-ASCs and control cell lines. SKOV3 cells were intraperitionally injected with or without O-ASC1 to track in-vivo engraftment. O-ASCs significantly promoted in vitro proliferation, migration chemotherapy and radiation response of ovarian cancer cell lines. O-ASC4 had more marked effects on migration and chemotherapy response on OVCA 429 and OVCA 433 cells than O-ASC1. Analysis of microarray data revealed that O-ASC4 and O-ASC5 have similar gene expression profiles, in contrast to O-ASC1, which was more similar to BM-MSCs and subcutaneous ASCs in hierarchical clustering. Human O-ASCs were detected in the stroma of human ovarian cancer murine xenografts but not uninvolved ovaries. ASCs derived from the human omentum can promote ovarian cancer proliferation, migration, chemoresistance and radiation resistance in-vitro. Furthermore, clinical O-ASCs isolates demonstrate heterogenous effects on ovarian cancer in-vitro.


Comparing the calcium binding abilities of two soybean calmodulins: towards understanding the divergent nature of plant calmodulins.
The discovery that plants contain multiple calmodulin (CaM) isoforms of variable sequence identity to animal CaM suggested an additional level of sophistication in the intracellular role of calcium regulation in plants. Past research has focused on the ability of conserved or divergent plant CaM isoforms to activate both mammalian and plant protein targets. At present, however, not much is known about how these isoforms respond to the signal of an increased cytosolic calcium concentration. Here, using isothermal titration calorimetry and NMR spectroscopy, we investigated the calcium binding properties of a conserved (CaM1) and a divergent (CaM4) CaM isoform from soybean (Glycine max). Both isoforms bind calcium with a semisequential pathway that favors the calcium binding EF-hands of the C-terminal lobe over those of the N-terminal lobe. From the measured dissociation constants, CaM4 binds calcium with a threefold greater affinity than CaM1 (K(d,Ca,mean) of 5.0 versus 14.9 μM) but has a significantly reduced selectivity against the chemically similar magnesium cation that binds preferentially to EF-hand I of both isoforms. The implications of a potential magnesium/calcium competition on the activation of CaM1 and CaM4 are discussed in context with their ability to respond to stimulus-specific calcium signatures and their known physiological roles.


[The net for protection to the elderly of Rio de Janeiro: a right to be conquered].
This article is based on previous studies using triangulation of methods for investigating if violence is obstructing the rights of the elderly. A questionnaire with open and closed questions was applied to a convenience sample of 72 elderly (60 or more years of age) of both sexes. Twenty-two key-informants (elderly people, community leaders and representatives of public institutions) were interviewed. In this survey we investigate the net for protection to the elderly of the city of Rio de Janeiro (institutions, assistance flow, integration, denunciations and measures taken). We analyzed 763 records of occurrences of the Police Department for the Aged and 135 of the NEAPI (Nucleus for Special Assistance for the Aged), taken care of in 2004. We emphasize domestic violence committed by close relatives and point to the need of structuring the formal net through increasing the number of institutions for protection to the aged, professional qualification, communication and integration among the agencies composing the net. We also consider important stimulating the informal nets for support and protection to the elderly.


In silico simulation modeling reveals the importance of the Casparian strip for efficient silicon uptake in rice roots.
Silicon (Si) uptake by the roots is mediated by two different transporters, Lsi1 (passive) and Lsi2 (active), in rice (Oryza sativa). Both transporters are polarly localized in the plasma membranes of exodermal (outer) and endodermal (inner) cells with Casparian strips. However, it is unknown how rice is able to take up large amounts of Si compared with other plants, and why rice Si transporters have a characteristic cellular localization pattern. To answer these questions, we simulated Si uptake by rice roots by developing a mathematical model based on a simple diffusion equation that also accounts for active transport by Lsi2. In this model, we calibrated the model parameters using in vivo experimental data on the Si concentrations in the xylem sap and a Monte Carlo method. In our simulation experiments, we compared the Si uptake between roots with various transporter and Casparian strip locations and estimated the Si transport efficiency of roots with different localization patterns and quantities of the Lsi transporters. We found that the Si uptake by roots that lacked Casparian strips was lower than that of normal roots. This suggests that the double-layer structure of the Casparian strips is an important factor in the high Si uptake by rice. We also found that among various possible localization patterns, the most efficient one was that of the wild-type rice; this may explain the high Si uptake capacity of rice.


Extraversion is linked to volume of the orbitofrontal cortex and amygdala.
Neuroticism and extraversion are personality factors associated with the vulnerability for developing depression and anxiety disorders, and are possibly differentially related to brain structures implicated in the processing of emotional information and the generation of mood states. To date, studies on brain morphology mainly focused on neuroticism, a dimension primarily related to negative affect, yielding conflicting findings concerning the association with personality, partially due to methodological issues and variable population samples under study. Recently, extraversion, a dimension primarily related to positive affect, has been repeatedly inversely related to with symptoms of depression and anxiety disorders. In the present study, high resolution structural T1-weighted MR images of 65 healthy adults were processed using an optimized Voxel Based Morphometry (VBM) approach. Multiple regression analyses were performed to test for associations of neuroticism and extraversion with prefrontal and subcortical volumes. Orbitofrontal and right amygdala volume were both positively related to extraversion. Extraversion was differentially related to volume of the anterior cingulate cortex in males (positive) and females (negative). Neuroticism scores did not significantly correlate with these brain regions. As extraversion is regarded a protective factor for developing anxiety disorders and depression and has been related to the generation of positive affect, the present results indicate that the reduced likelihood of developing affective disorders in individuals high on extraversion is related to modulation of emotion processing through the orbitofrontal cortex and the amygdala.


Enhancement of the Photosensitizing Properties of 6-Carboxypterin through Covalent Binding to the pH-Responsive and Biocompatible Poly(allylamine Hydrochloride).
A polymeric photosensitizer was synthesized through covalent attachment of the natural photosensitizer 6-carboxypterin (Cap) to a poly(allylamine hydrochloride) (PAH) polymer. The optimization of the functionalization steps and purification procedure is described. The overall yield of the functionalization reaction was 67% to generate the modified polymer (PAH-Cap), featuring a Cap substitution degree of approximately 1% and advantageous spectroscopic properties. Photosensitizing properties of PAH-Cap were observed to occur via both photooxidation mechanisms, i.e., type I and type II. This feature was demonstrated using a biologically relevant target molecule, 2'-deoxyguanosine (dG). The spectroscopic, photophysical, and photochemical behaviors in aqueous environments were studied and compared to Cap. To explore possible further relevant biological applications, experiments with PAH-Cap and dG were carried out at physiological pH. PAH-Cap can generate singlet molecular oxygen and initiate an electron transfer process at pH 7 in air-saturated solutions upon UVA irradiation. Moreover, based on its spectroscopic features, visible light can be used to initiate the photooxidation of biological compounds in water, with many interesting advantages compared to free Cap and other related pteridines. These advantages include an enhancement of the photosensitizing effect at physiological pH and the potential of PAH-Cap for its use as a building block in supramolecular assemblies. The functionalization strategy hereby described can be employed for the preparation of robust photoactive polymers with great potential for its application in photodynamic therapy (PDT) and disinfection technologies.


[The platysma myocutaneous flap (PMF) for reconstruction of defects after extended parotidectomy].
In order to reestablish the facial symmetry after the tumor removal, we can use sternocleidomastoid muscle transposition, dermis-fat graft, superficial musculoaponeurotic system (SMAS) plication, temporoparietal fascia flaps, microvascular free flaps and the platysma muscle flap. The technic depends on the size of the defect. In this study we present our results of using a superiorly based platysma myocutaneous flap for reconstruction of defects after extended parotidectomy. The patients were treated for malign tumor of parotid gland which invaded the skin. All flaps were readily harvested at the time of tumor resection. Only two patients presented venous congestion. No flap was lost. There was no morbidity of donor site. The cosmetic outcome was satisfactory. The platysma myocutaneous flap is an alternative to more complex reconstructive technics, such as free flap transfer, and gives a satisfactory cosmetic result. The platysma myocutaneous flap is easy to harvest and has low donor site morbidity. The main disadvantage is represented by the vascularity problems.


Ultrafiltration for patients with acute decompensated heart failure: A systematic review and meta-analysis.
Ultrafiltration plays an indispensable role in relieving congestion and fluid retention in patients with acute decompensated heart failure (ADHF) in recent years. So far, there is no consistent agreement about whether early ultrafiltration (UF) is a first-line treatment for patients with ADHF. We, therefore, conducted a meta-analysis to assess the efficacy and safety of UF. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that compared UF with diuretics in patients with ADHF and included our interested outcomes. The primary outcomes are heart failure rehospitalization, all-cause rehospitalization, and mortality. The second outcomes are fluid loss, weight loss, and adverse events. RevMan Version 5.4.1 was used to analyze the data of included studies. A total of 12 studies with 1197 patients were included. Our results showed a reduction in heart failure rehospitalization (risk ratio [RR] 0.67, 95% confidence interval [CI]: 0.52-0.87, P = .003) and all-cause rehospitalization (RR 0.62, 95% CI: 0.42-0.92; P = .02), an increase in fluid loss (1.47 L, 95% CI: 0.95-1.99 L, P < .001) and weight loss (1.65 kg, 95% CI: 0.90-2.41 kg; P < .001). There was no difference in mortality (RR 1.09, 95% CI: 0.78-1.51; P = .62). There were inconsistent agreements about which group have more total adverse events. Subgroup analysis showed that UF with larger mean fluid-remove rate (≥200 mL/h) could significantly remove more fluid, lose more weight, and decrease heart failure rehospitalization. Less weight loss for patients with ADHF may correlated to higher percent of ischemic etiology (ischemic etiology ≥50%). Although UF is more effective in removing fluid than diuretics and decrease rehospitalization of heart failure and all causes, there is not enough evidence to prove that UF is superior because of adverse events and mortality in the UF group. The mean fluid-removal rates should be set to ≥200 mL/h. Patient with different etiology may have different effects when treated with UF and it is a weak conclusion.Trial registration: The systematic review was registered with the International Prospective Registry of Systematic Reviews. (https://www.crd.york.ac.uk/prospero/, registration number CRD42021245049).


Fracture resistance and microleakage of endocrowns utilizing three CAD-CAM blocks.
This study assessed marginal leakage and fracture resistance of computer-aided design/computer-aided manufacturing (CAD/CAM) fabricated ceramic crowns with intracoronal extensions into the pulp chambers of endodontically treated teeth (endocrowns) using either feldspathic porcelain (CEREC Blocks [CB], Sirona Dental Systems GmbH, Bensheim, Germany), lithium disilicate (e.max [EX], Ivoclar Vivadent, Schaan, Liechtenstein), or resin nanoceramic (Lava Ultimate [LU], 3M ESPE, St Paul, MN, USA).). Thirty extracted human permanent maxillary molars were endodontically treated. Standardized preparations were done with 2-mm intracoronal extensions of the endocrowns into the pulp chamber. Teeth were divided into three groups (n=10); each group was restored with standardized CAD/CAM fabricated endocrowns using one of the three tested materials. After cementation with resin cement, specimens were stored in distilled water at 37°C for one week, subjected to thermocycling, and immersed in a 5% methylene-blue dye solution for 24 hours. A compressive load was applied at 35 degrees to long axis of the teeth using a universal testing machine until failure. Failure load was recorded, and specimens were examined under a stereomicroscope for modes of failure and microleakage. Results were analyzed using one-way analysis of variance and Bonferroni post hoc multiple comparison tests (α=0.05). LU showed significantly (p<0.05) higher fracture resistance and more favorable fracture mode (ie, fracture of the endocrown without fracture of tooth) as well as higher dye penetration than CB and EX. In conclusion, although using resin nanoceramic blocks for fabrication of endocrowns may result in better fracture resistance and a more favorable fracture mode than other investigated ceramic blocks, more microleakage may be expected with this material.


Effects of dietary supplementation with two potassium formate sources on performance of 8- to 22-kg pigs.
Dietary inclusion of salts of organic acids may modulate intestinal microbiota and enhance performance of pigs. Published data on the effects of potassium formate (KF; pH 6.0-8.5) on pig performance are scarce compared with that of potassium diformate (KDF; pH 4.1-4.5). Therefore, the objective was to evaluate the effects of KDF or KF supplementation on performance of 8- to 22-kg pigs. A 35-d growth trial was conducted with 144 PIC pigs (initial BW of 7.9 ± 0.69 kg) with 6 pigs (3 gilts and 3 barrows) per pen and 8 pens per treatment. Pigs were assigned to 3 diets based on corn (Zea mays), wheat (Triticum aestivum), and soybean (Glycine max) meal for each of the prestarter (days 1-14) and starter phases (days 15-35). The basal diet was supplemented with KDF at 1.20% or KF at 1.56% replacing corn starch to create diets 2 and 3, respectively, to provide a constant formate content. The ADG and feed conversion ratio (FCR) were not affected by the addition of KDF or KF during the prestarter phase. Addition of KDF or KF to the basal diet increased (P < 0.01) ADG and final BW and improved FCR (P < 0.05) during the starter and the overall 35-d period. The ADFI was not affected by the treatments. Performance of pigs fed diets supplemented with KF and KDF were similar. Diarrhea incidences were observed during week 1 but no differences were observed (P > 0.05) among treatments in term of the number of antibiotic treatments or fecal consistency scores. Overall, the supplementation of 1.56% KF or 1.20% KF improved performance of weaned pigs.


[Axonal composition of the marginal and basal optic tracts of the grass frog].
An electron-microscopy study of the marginal optic tracts (the medial and lateral divisions) and basal optic tract was performed for the frog Rana temporaria. The resemblance between the ultrastructure and composition of the marginal tracts is revealed. The basal tract is characterized by a relatively loose structure and considerable content of the myelinated large diameter fibres. The corresponding tract contains 3900 (4.7%), 4700, (4.9%), 700 (28%) of myelinated fibres and 79 800 (95.3%), 91500 (95.1%) and 1800 (72%) of unmyelinated ones. The spectra of the myelinated fibre diameters of the marginal tract are from 0.4 to 2.6 mum with the main peak at 1.0 mum and additional peak at 1.6 mum; the spectrum of the myelinated fibre diameters of the basal tract is from 0.4 to 4.0 mum with the main peak at 1.8 mum and the small additional peak at 3.2 mum. The spectra of the unmyelinated fibre diameters of all tracts are from 0.1 to 0.5 mum; 60% of them have a diameter of about 0.2 mum. 85 days after enucleation undegenerated myelinated fibres were not found in the basal tract of the frog kept at a temperature 18-20 degrees C. The medial and lateral marginal tracts contained a significant number of the undegenerated myelinated fibres, 33% and 13%, the diameter spectra being 0.6-1.4 mum and 0.6-1.0 mum, respectively. It is possible that these fibres participate in the organization of the ipsilateral visual projection on the tectum. Unmyelinated fibres remain unchanged in all the studied tracts.


Exceptional thermoelectric properties of flexible organic-inorganic hybrids with monodispersed and periodic nanophase.
Flexible organic-inorganic hybrids are promising thermoelectric materials to recycle waste heat in versatile formats. However, current organic/inorganic hybrids suffer from inferior thermoelectric properties due to aggregate nanostructures. Here we demonstrate flexible organic-inorganic hybrids where size-tunable Bi2Te3 nanoparticles are discontinuously monodispersed in the continuous conductive polymer phase, completely distinct from traditional bi-continuous hybrids. Periodic nanofillers significantly scatter phonons while continuous conducting polymer phase provides favored electronic transport, resulting in ultrahigh power factor of ~1350 μW m-1 K-2 and ultralow in-plane thermal conductivity of ~0.7 W m-1 K-1. Consequently, figure-of-merit (ZT) of 0.58 is obtained at room temperature, outperforming all reported organic materials and organic-inorganic hybrids. Thermoelectric properties of as-fabricated hybrids show negligible change for bending 100 cycles, indicating superior mechanical flexibility. These findings provide significant scientific foundation for shaping flexible thermoelectric functionality via synergistic integration of organic and inorganic components.


Progressive laser treatment of hereditary hemorrhagic telangiectasia of the gingiva: case report.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular malformation commonly found in the oral region. The symptoms range from minor epistaxis to severe, life-threatening hemorrhage. Red spots on the skin and in the mouth could lead to a diagnosis of HHT. The telangiectases can be irritated by normal dental procedures, and prophylactic antibiotics should be administered. The gingival HHT in this case demonstrates its significance to the dental community. A knowledgeable practitioner could be the first to recognize the potential diagnosis of HHT. Lesion variables will determine treatment parameters. Sequential photocoagulation with an argon laser appears to be an appropriate treatment algorithm.


Effects on local emergency departments of large-scale urban chemical fire with hazardous materials spill.
On 18 July 2001, a train hauling hazardous materials, including hydrochloric acid, hydrofluoric acid, and acetic acid, derailed in the city of Baltimore, Maryland, resulting in a fire that burned under a downtown street for five days. Firefighters were stymied in their efforts to extinguish the fire, and the city was subjected to thick smoke for several days. To determine whether an urban chemical fire with a hazardous materials spill resulted in a detectable public health impact, and to demographically describe the at-risk population for potential smoke and chemical exposure. The United States Centers for Disease Control and Prevention (CDC) was consulted about possible side effects from chemical exposure. Total numbers of emergency department (ED) patients and admissions from 15:00 hours (h), 15 July 2001 to 15:00 h, 21 July 2001 were collected from five local hospitals. Patient encounters citing specified chief complaints from 15:00 h, 15 July to 15:00 h, 18 July (pre-accident) were compared with the period from 15:00 h, July 18 to 15:00 h, 21 July (post-accident). Data were analyzed using Fisher's exact test. The United States Census Bureau's Topologically Integrated Geographic Encoding and Referencing (TIGER) digital database of geographic features and ArcView Geographic Information Systems (GIS) were used to create maps of Baltimore and to identify populations at-risk using attribute census data. There were 62,808 people residing in the immediate, affected area. The mean of the values for age was 33.7 +/- 3.2 years (standard deviation; range = 16 yrs) with 49% (30,927) males and 51% (31,881) females. A total of 2,922 ED patient encounters were screened. Chief complaints included shortness of breath, pre-event = 109 vs. post-event = 148; chest complaints = 90 vs. 113; burns and/or skin irritation = 45 vs. 42; eye irritation 26 vs. 34; throat irritation = 33 vs. 27; and smoke exposure = 0 vs. 15. There was a statistically significant increase (p < 0.05) for shortness of breath and smoke exposure-related complaints. No statistically significant increase in numbers of admitted patients with these complaints was found. In the setting of a large-scale urban chemical fire, local EDs can expect a significant increase in the number of patients presenting to EDs with shortness of breath and/or smoke inhalation. Most do not require in-patient hospitalization. Careful assessment of impact on local EDs should be considered in future city-accident planning. Some official warnings were widely misinterpreted or ignored. Public education on potential hazards and disaster preparedness targeted to populations at-risk should receive a high priority. Geographic information systems (GIS) may serve as useful tools for identifying demographics of populations at-risk for disaster planning and responses.


Hemi-Intravascular Stenting for Supermicrosurgical Anastomosis.
Although supermicrosurgical anastomosis is a widely known reconstructive microsurgical technique, it is difficult to perform. To expand the clinical use of supermicrosurgery, we used hemi-intravascular stenting (hemi-IVaS), which is performed by inserting an intravascular stent into one side of the vessel. We conducted lymphaticovenular anastomosis, free perforator flap transfer, and fingertip replantation with supermicrosurgical anastomosis using hemi-IVaS technique and examined its usefulness. Between January 2013 and February 2015, 11 anastomoses in 11 cases of lymphaticovenular anastomosis for lymphedema patients, 14 anastomoses in 7 cases of free perforator flap transfer with supermicrosurgical perforator-to-perforator anastomosis, and 9 anastomoses in 5 cases of fingertip replantation were performed using hemi-IVaS. Time required for anastomosis and complications were examined. Flap survival rate was also examined in free perforator flap transfer cases and fingertip replantation cases. In all cases, anastomoses were performed without complications such as inadvertent catching of the back wall of the vessel during the procedure or the need for reanastomoses. The average time required to complete the anastomosis was 16.4 ± 3.20 minutes using the hemi IVaS technique. All flaps survived in the supermicrosurgical perforator-to-perforator anastomosis as well as fingertip replantation cases. Hemi-IVaS could be a useful alternative to conventional intravascular stenting techniques and is also effective for supermicrosurgical perforator-to-perforator anastomosis. Further studies are needed to improve the success rate and to explore its other possible utilizations in supermicrosurgery.


Estimating the distribution of probable age-at-death from dental remains of immature human fossils.
In two historic longitudinal growth studies, Moorrees et al. (Am J Phys Anthropol 21 (1963) 99-108; J Dent Res 42 (1963) 1490-1502) presented the "mean attainment age" for stages of tooth development for 10 permanent tooth types and three deciduous tooth types. These findings were presented graphically to assess the rate of tooth formation in living children and to age immature skeletal remains. Despite being widely cited, these graphical data are difficult to implement because there are no accompanying numerical values for the parameters underlying the growth data. This analysis generates numerical parameters from the data reported by Moorrees et al. by digitizing 358 points from these tooth formation graphs using DataThief III, version 1.5. Following the original methods, the digitized points for each age transition were conception-corrected and converted to the logarithmic scale to determine a median attainment age for each dental formation stage. These values are subsequently used to estimate age-at-death distributions for immature individuals using a single tooth or multiple teeth, including estimates for 41 immature early modern humans and 25 immature Neandertals. Within-tooth variance is calculated for each age estimate based on a single tooth, and a between-tooth component of variance is calculated for age estimates based on two or more teeth to account for the increase in precision that comes from using additional teeth. Finally, we calculate the relative probability of observing a particular dental formation sequence given known-age reference information and demonstrate its value in estimating age for immature fossil specimens.


[Interstitial radiotherapy for cancers of the tongue and mouth floor mucosa].
The report deals with new procedures of interstitial, complex and combined treatment of cancer of the tongue and mucosa of fundus of the oral cavity with time space-differentiated doses of radiation. If indicated, cervical lymph nodes undergo surgery at the final stage of therapy. Interstitial radiotherapy has proved a highly-effective radical component of said treatment for cancers of the tongue and oral cavity.


Homo cerevisiae-Leveraging Yeast for Investigating Protein-Protein Interactions and Their Role in Human Disease.
Understanding how genetic variation affects phenotypes represents a major challenge, particularly in the context of human disease. Although numerous disease-associated genes have been identified, the clinical significance of most human variants remains unknown. Despite unparalleled advances in genomics, functional assays often lack sufficient throughput, hindering efficient variant functionalization. There is a critical need for the development of more potent, high-throughput methods for characterizing human genetic variants. Here, we review how yeast helps tackle this challenge, both as a valuable model organism and as an experimental tool for investigating the molecular basis of phenotypic perturbation upon genetic variation. In systems biology, yeast has played a pivotal role as a highly scalable platform which has allowed us to gain extensive genetic and molecular knowledge, including the construction of comprehensive interactome maps at the proteome scale for various organisms. By leveraging interactome networks, one can view biology from a systems perspective, unravel the molecular mechanisms underlying genetic diseases, and identify therapeutic targets. The use of yeast to assess the molecular impacts of genetic variants, including those associated with viral interactions, cancer, and rare and complex diseases, has the potential to bridge the gap between genotype and phenotype, opening the door for precision medicine approaches and therapeutic development.


Out-of-school participation patterns in children with high-functioning autism spectrum disorders.
This study examined differences in out-of-school activity participation between typically developing children and those with high-functioning autism spectrum disorders (HFASD). Children with HFASD, ages 6 to 12 (N = 52), and a control group (N = 53) were assessed using the Children's Assessment of Participation and Enjoyment and the Social Responsiveness Scale. Significant differences were seen in participation between typical and HFASD groups in number of activities in which children participate, the numbers of individuals with whom they participate, and the variety of environments in which they participate. These findings indicate that out-of-school participation is significantly different for children with HFASD than for typically developing peers. Findings suggest that social impairment is related to some aspects of participation and that addressing social skills in intervention could contribute to increased participation in out-of-school activities by children with HFASD, which would contribute to their long-term mental and physical health.


Monitoring and quantifying dynamic physiological processes in live neurons using fluorescence recovery after photobleaching.
The direct visualization of subcellular dynamic processes is often hampered by limitations in the resolving power achievable with conventional microscopy techniques. Fluorescence recovery after photobleaching has emerged as a highly informative approach to address this challenge, permitting the quantitative measurement of the movement of small organelles and proteins in living functioning cells, and offering detailed insights into fundamental cellular phenomena of physiological importance. In recent years, its implementation has benefited from the increasing availability of confocal microscopy systems and of powerful labeling techniques based on genetically encoded fluorescent proteins or other chemical markers. In this review, we present fluorescence recovery after photobleaching and related techniques in the context of contemporary neurobiological research and discuss quantitative and semi-quantitative approaches to their interpretation.


Pesticidal and pest repellency activities of a plant derived triterpenoid 2α,3β,21β,23,28-penta hydroxyl 12-oleanene against Tribolium castaneum.
Tribolium castaneum (Herbst) is a major pest of stored grain-based products, and cause severe damage to cereal grains throughout the world. The present investigation was aimed to determine the pesticidal and pest repellent activities of 2α,3β,21β,23,28-penta hydroxyl 12-oleanene against T. castaneum. The compound 2α,3β,21β,23,28-penta hydroxyl 12-oleanene is a triterpenoid which was isolated from the roots of Laportea crenulata Gaud. Surface film technique was used for pesticidal screening, whereas, pest repellency property of the triterpenoid was determined by filter paper disc method. At 24 hours of exposure duration, significant mortality records (80% and 86%) were observed at doses 0.88 and 1.77 mg/cm(2). No significant change in mortality records was observed when duration of exposure was increased up to 48 hours. The triterpenoid showed significant repellency activity at doses 0.47 and 0.94 mg/cm(2). These data suggest that the triterpenoid 2α,3β,21β,23,28-penta hydroxyl 12-oleanene possess both pesticidal and pest repellency activities against T. castaneum and can be used in controlling the pest of grain-based products.


Survival regression analysis: a powerful tool for evaluating fighting and assessment.
Theoretical models of animal contests frequently generate predictions about how asymmetries (e.g. differences in size, residence status) between contestants affect fight duration. Linear regression and nonparametric correlation analyses are commonly used to test the fit of data to such models. We show how survival regression analysis (SRA) is a powerful technique for studying the effect of asymmetries on the duration of contests. SRA, which is under-utilized by students of animal behaviour, offers several advantages over more frequently used procedures. It provides unbiased parameter estimates even when including censored data (i.e. results of contests that have not ended at the time when observations are stopped). The analysis of hazard functions, which is a component of SRA, is an easy way to test for consistency with predictions of the sequential assessment game model. These and other advantages of SRA are illustrated by using SRA and more conventional methods to analyse the effect of asymmetries on contest duration for encounters between female Mediterranean tarantulas, Lycosa tarentula (L.). It is hoped that this example of the advantages of SRA will encourage more widespread use of this powerful technique. Copyright 2000 The Association for the Study of Animal Behaviour.


Hyperhomocysteinemia: a trigger for complement-mediated TMA?
A 34-year-old man of North African descent was referred to the emergency department because of malignant hypertension (220/113 mmHg), acute visual disturbances and acute kidney failure (serum creatinine 14.0 mg/dL). Blood analysis was compatible with thrombotic microangiopathy (TMA). Kidney biopsy confirmed this diagnosis with histological changes including intimal edema, arteriolar thrombi, and severe tubulointerstitial damage. Fundoscopy showed hypertensive retinopathy stage IV. Subsequent biochemical screening revealed normal complement testing and a marked elevation in homocysteine concentration (161 µmol/L; normal value 7-15 µmol/L). Other secondary causes of TMA were excluded. Further genetic testing for cobalamin C (cblC) deficiency showed no pathogenic mutations in the MMACHC gene. However, a homozygous c.665C>T polymorphism (NM_005957.4) in the methylenetetrahydrofolate reductase (MTHFR) gene was found explaining the severe hyperhomocysteinemia due to reduced activity of MTHFR. Additional genetic testing for alternative complement pathway proteins showed mutations in the genes encoding factor H and factor B, both categorized as possibly pathogenic using mutation prediction software. This is the first described case of TMA in a patient with severe hyperhomocysteinemia caused by a genetic defect other than cblC. We postulate that endothelial damage due to hyperhomocysteinemia and hypertension could have triggered the TMA episode in this patient with two possible predisposing pathogenic mutations in the alternative complement pathway. Furthermore, our case demonstrates the need for complete full diagnostic testing in patients with TMA.


[Dental occlusion and subjective temporomandibular joint symptoms in men and women. Results of the Study of Health in Pomerania (SHIP)].
Aim of the study was to determine whether associations exist in men as well as in women between occlusal factors like malocclusions or factors of functional occlusion and subjective temporomandibular joint (TMJ) symptoms, based on the population-based Study of Health in Pomerania (SHIP-0). A representative sample of 4310 men and women (response rate 68.8%) aged 20 to 81 years was examined for subjective temporomandibular joint symptoms, malocclusions (incl. normal occlusion), factors of functional occlusion and for sociodemographic parameters. Men and women were analyzed separately with multiple logistic regression analyses, adjusted for age. The results were compared to other population-based studies from an own systematic review on this subject. In men and women, none of the 48 occlusal factors under survey (malocclusions or functional occlusion) was significantly more frequently associated with the dependent variable "subjective temporomandibular joint symptoms". In contrast, the parafunction "frequent clenching" was associated more frequently and clinically relevant with TMJ symptoms in both sexes (for men, odds ratio = 4.2, prevalence 4.9%; for women OR = 2.9, prevalence 5.6%). Malocclusions and functional occlusion factors only explained a smaller part of the differences between the male and female population with and without subjective TMJ symptoms. Compared to other population-based studies only few and inconsistent associations between occlusal factors and subjective temporomandibular symptoms were ascertainable in both sexes.


QAPSA: post-marketing surveillance of capsaicin 8% patch for long-term use in patients with peripheral neuropathic pain in France.
To describe the characteristics of patients treated with the capsaicin 8% patch, prescribing conditions, long-term effects of repeat treatment on pain intensity and perception, quality of life, and impact on concomitant medication. A national, longitudinal, prospective, non-interventional, post-marketing open study was conducted in 50 French pain centers. Adult volunteer non-diabetic patients with peripheral neuropathic pain receiving capsaicin 8% patch treatment were consecutively enrolled. Treatment could be repeated over a 12-month period, with 6 months' follow-up after last application. A total of 684 patients (age: 53.0 ± 14.9 years, mean ± standard deviation; post-traumatic/surgical peripheral neuropathic pain: 76.3%; pain intensity: 6.2 ± 1.7; pain duration: 3.0 years, median) were treated with 1 to 5 patches at 3/4 month intervals; 70.3% were naive to capsaicin 8% patch treatment at inclusion. Six months after last application, treatment was considered as successful for 21.8% (95% confidence interval: 17.5%-26.7%) of patients by a stringent criterion combining improvement according to the patient's global impression of change (PGIC) and at least 30% improvement on a numerical pain rating scale (NPRS). Clinically relevant improvement in health-related quality of life was observed at end-of-study. No unexpected safety concerns were observed with capsaicin 8% patch repeat treatment. The data of this post-marketing study meets the request by the French authorities for additional data on conditions of use in everyday practice. They confirmed the tolerance and long-term effect of capsaicin 8% patch in patients with peripheral neuropathic pain in real-world conditions.


A meta-analysis of case-control and cohort studies with interval-censored exposure data: application to chorionic villus sampling.
Chorionic villus sampling (CVS) is a valued method of prenatal diagnosis that is often preferred over amniocentesis because it can be performed earlier, but which has also raised concern over a possible association with increased risk of terminal transverse limb deficiency (TTLD). We present and apply a meta-analytic method for estimating a combined dose-response effect from a series of case-control and cohort studies in which the exposure variable is interval-censored. Assuming coarsening at random for the interval-censoring, and calling upon the familiar result of Cornfield to pool case-control and cohort information on the association between a rare binary outcome and a multilevel exposure variable, we form a likelihood-based model to assess the effect of gestational age at the time of CVS on the presence or absence of a rare birth defect. Effect estimates are computed with a variant of the EM algorithm termed the method of weights, which enables the use of standard weighted regression software. Our findings suggest that CVS exposure at early gestational age leads to an increased risk of TTLD.


Histologic and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome.
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.


Game-Theoretic Decision Support for Cyber Forensic Investigations.
The use of anti-forensic techniques is a very common practice that stealthy adversaries may deploy to minimise their traces and make the investigation of an incident harder by evading detection and attribution. In this paper, we study the interaction between a cyber forensic Investigator and a strategic Attacker using a game-theoretic framework. This is based on a Bayesian game of incomplete information played on a multi-host cyber forensics investigation graph of actions traversed by both players. The edges of the graph represent players' actions across different hosts in a network. In alignment with the concept of Bayesian games, we define two Attacker types to represent their ability of deploying anti-forensic techniques to conceal their activities. In this way, our model allows the Investigator to identify the optimal investigating policy taking into consideration the cost and impact of the available actions, while coping with the uncertainty of the Attacker's type and strategic decisions. To evaluate our model, we construct a realistic case study based on threat reports and data extracted from the MITRE ATT&CK STIX repository, Common Vulnerability Scoring System (CVSS), and interviews with cyber-security practitioners. We use the case study to compare the performance of the proposed method against two other investigative methods and three different types of Attackers.


Enhancement of serum antibody production in mice by oral administration of lipophilic derivatives of muramylpeptides and bacterial lipopolysaccharides with bovine serum albumin.
Lipophilic derivatives of muramylpeptides, namely N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutaminyl)-N epsilon-stearoyl-L-lysine [MDP-Lys (L18)] and 6-O-(2-tetradecylhexadecanoyl)-MDP (B30-MDP), were demonstrated to significantly enhance anti-bovine serum albumin (BSA) antibody production when they were incorporated in liposomes with BSA and administered by gastric intubation to BALB/c mice on days 0 and 1 (the primary immunization) and on days 27 and 28 (booster). N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) itself showed negligible activity under the same experimental conditions. A stearoyl derivative of sodium beta-N-acetylglucosaminyl-(1-4)-N-acetylmuramyl- L-alanyl-D-isoglutaminyl-(L)-stearoyl(D)-meso-diaminopimelic acid-(D)-amide-D-alanine (GM-53) that was isolated by enzymatic degradation of L. plantarum cell wall peptidoglycans showed a powerful adjuvant effect by oral administration in liposomes with BSA. Similar or stronger adjuvant effects were observed by oral administration of LPS preparations, KO3 LPS isolated from K. pneumoniae (a noncapsulated mutant, LEN-1), Bacto lipopolysaccharide W derived from E. coli (O127:B8) and BIOSTIM F1 fraction derived from K. pneumoniae (O1:K2). Liposomes as a vehicle for oral administration were not always required for the manifestation of the adjuvant effects of MDP-Lys (L18) and BIOSTIM F1. These compounds, but not B30-MDP, showed a powerful adjuvant effect when orally administered with BSA in phosphate buffered saline.


Recent advances in treatment of acute mania.
Standard and more recent advances in treatment of acute mania are reviewed with special emphasis on controlled studies. Lithium is still the drug of choice and the most common treatment for mania, but some of its limitations have become more apparent, and specific indications for its use are defined. Alternatives to lithium are recommended for psychotic, rapid cycling, severely manic, and lithium-refractory patients. Neuroleptics are effective and used commonly but carry risks of long term side effects. Substantial reduction in neuroleptic dose and duration of exposure is probably feasible in many patients. Neuroleptic-lithium combinations are popular but do not have clear advantages over treatment with a single drug in the initial treatment of acute mania. These combinations have also been associated with increased neurotoxicity. Carbamazepine, both alone and in combination with lithium, has been used increasingly over recent years. Its efficacy is comparable to lithium, but clinical features predicting responsiveness may be different for these two drugs. Carbamazepine-neuroleptic combinations offer little advantage over neuroleptics alone. Valproic acid, verapamil, clonazepam, lorazepam, benzodiazepine-neuroleptic combinations, clonidine, tryptophan, propranolol, and electroconvulsive therapy are also popular, but their effectiveness has not yet been adequately confirmed by controlled studies.


Factors contributing to pre-treatment loss to follow-up in adults with pulmonary tuberculosis: a qualitative evidence synthesis of patient and healthcare worker perspectives.
Since 2018, over 14 million people have been treated for tuberculosis (TB) globally. However, pre-treatment loss to follow-up (PTLFU) has been shown to contribute substantially to patient losses in the TB care cascade with subsequent high community transmission and mortality rates. To identify, appraise, and synthesise evidence on the perspectives of patients and healthcare workers on factors contributing to PTLFU in adults with pulmonary TB. We registered the title with PROSPERO (CRD42021253212). We searched nine relevant databases up to 24 May 2021 for qualitative studies. Two review authors independently reviewed records for eligibility and extracted data. We assessed methodological quality with the Evidence for Policy and Practice Information Centre tool and synthesised data using the Supporting the Use of Research Evidence framework. We assessed confidence in our findings using Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual). We reviewed a total of 1239 records and included five studies, all from low- and middle-income countries. Key themes reported by patients and healthcare workers were communication challenges among healthcare workers and between healthcare workers and patients; knowledge, attitudes, and behaviours about TB and its management; accessibility and availability of facilities for TB care; and human resource and financial constraints, weakness in management and leadership in TB programmes. Patients' change of residence, long waiting times, and poor referral systems were additional factors that contributed to patients disengaging from care. We had moderate confidence in most of our findings. Findings from our qualitative evidence synthesis highlight multiple factors that contribute to PTLFU. Central to addressing these factors will be the need to strengthen health systems and offer people-centred care.


[Pneumothermometric estimation of conditioning function of the respiratory system in ischemic heart disease].
The research was carried out on 153 patients with ischemic heart disease at standard ambient temperature and humidity. The conditioning function of the respiratory system was examined by pneumothermometric method. Values of expired air temperature (EAT) have been compared with predicted values. Statistically significant increase of EAT was observed: in myocardial infarction - 0.49 degrees C, in atherosclerotic cardiosclerosis - 0.36 degrees C, in unstable angina pectoris - 0.12 degrees C. These data how respiratory heat exchange flux in patients with ischemic heart disease, possibly due to lung haemodynamics disturbances which are common among patients with this pathology. This measuring of expired air temperature is advisable for functional diagnostics of the respiratory system in routine and emergency cases.


Postmastectomy analgesia with subcutaneous infiltration of ketamine with lidocaine in surgical wound.
Ketamine is an analgesic adjuvant useful in acute pain preventive treatment. However, there are few studies evaluating its efficacy in local administration for postoperative pain management. To compare ketamine´s efficacy plus 2% lidocaine versus placebo plus 2% lidocaine infiltrated into surgical wound as postoperative analgesia in patients undergoing mastectomy. An experimental, randomized, single-blind study was carried out in 18 patients older than 18 years scheduled for mastectomy under general anesthetic technique. The surgical wound was infiltrated before to its closure with 0.5 mg/kg of ketamine plus 10 mL of simple 2% lidocaine volumetric to 20 mL with saline solution (group 1) or 10 mL saline solution + 10 mL of simple 2% lidocaine (group 2). Each patient was randomly assigned to one of the two intervention groups by draw (from which a piece of paper was drawn indicating the group to which they would belong). The pain intensity was assessed by Analog Numerical Scale (ANS) at 2, 8 and 12 hours after surgery and the need for analgesic rescue doses. The scores on the ANS scale in both groups were similar at leaving (p 0.26) and 2 hours later (p 0.05). The ENA value was lower with 2% ketamine/lidocaine infiltration at 8 hours (ketamine 2.5 [2-3]; placebo 4 [3-7], p 0.01) and 12 hours (ketamine 3 [1-5]; placebo 5 [4-6], p < 0.001). Ketamine infiltrated into the surgical wound provides superior analgesia and improves ENA scores in the post-surgical period.


[Outflow pathways of venous blood from the myocardium in the dog and structures participating in their regulation].
The intramural pathways of the venous blood outflow from the cardiac wall have been studied histologically, histochemically and micrometrically in 20 control and 84 experimental dogs with an artificially produced circulatory disturbances, peculiar for congenital heart disease (open arterial canal, coarctation of the aorta and stenosis of the pulmonary trunk). The experimental animals have been observed for 6-12 months. In the venous line of the coronary basin several morphologically differed parts, anatomically and functionally connected between themselves and ensuring blood outflow from the myocardium, are distinguished: coronary sinus, subepicardial veins, paired sinusoid veins, myocardial sinusoids and endocardial cushions. In each of them there are their own adaptive structures, participating in regulation of the venous blood stream. In the cardial sinus, in the subepicardial and paired sinusoid veins--these are valves of various complexity. In the myocardial sinusoids, the regulatory function, together with the valves, are performed by the intimal and muscle cushions, connective tissue and muscle bridges. In the endocardial cushions they are realized by the valves, muscle sphincters, bundles of obliquely and longitudinally oriented leiomyocytes. All the adaptive structures mentioned are also found in the hearts of the control animals. Under modelling various hemodynamic disturbances, the degree of their development increases sharply. The latter ensures the maintenance of an optimal regimen of blood circulation in the myocardium of a functionally loaded heart and prevents development of decompensation in the organ.


Hyperinsulinemia, sex, and risk of atherosclerotic cardiovascular disease.
The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies. In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids. Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.


Correlation between the type of bcr-abl transcripts and blood cell counts in chronic myeloid leukemia - a possible influence of mdr1 gene expression.
The impact of BCR-ABL mRNA type (b3a2 vs. b2a2) on chronic myeloid leukemia (CML) phenotype is still a subject of controversies. We searched for a correlation between the BCR-ABL transcripts type and CML patients' characteristics, including MDR1 gene expression. Ninety-eight untreated chronic phase CML patients were studied. The type of BCR-ABL fusion transcripts and MDR1 gene expression were determined by reverse transcriptase polymerase chain reaction. B3a2 and b2a2 transcripts were found in 53 [54%] and 44 [45%] patients, respectively. One patient co-expressed b3a2/b2a2 and was excluded from analysis. The only difference in the clinical characteristics between the two groups was the platelets count, that was higher in b3a2((+)) patients [791.3±441.3×10(9)/L vs. 440.4±283.4×10(9)/L in b2a2((+)); P=0.007]. MDR1 over-expression [MDR1((+))] was observed in 48 patients (49.5%), more frequently in older patients >60 years [71% (24/34) vs. 38% (24/63) in younger; P=0.008], and was associated with a lower white blood cells (WBC) count [105.5±79.8× 10(9)/L vs. 143.6±96.5×10(9)/L in MDR1((-)) cases; P=0.047]. On performing the analysis only within the MDR1((+)) group, the b(3)a(2) ((+)) cases were characterized with a significantly higher platelets count [908.7±470.1×10(9)/L vs. 472.9±356.1×10(9)/L; P=0.006] and a lower WBC count [85.4±61.2×10(9)/L vs. 130±93.9×10(9)/L; P=0.004) compared to b2a2((+)) patients. No similar differences were found between b3a2((+)) and b2a2((+)) groups with normal MDR1 levels. These results indicate that the type of BCR-ABL transcripts correlates with the hematological parameters of CML, however only in the subgroup of patients characterized by MDR1 over-expression.


Emergency medicine resident documentation: results of the 1999 american board of emergency medicine in-training examination survey.
To assess how emergency medicine (EM) residents perform medical record documentation, and how well they comply with Health Care Financing Administration (HCFA) Medicare charting guidelines. In addition, the study investigated their abilities and confidence with billing and coding of patient care visits and procedures performed in the emergency department (ED). Finally, the study assessed their exposure to both online faculty instruction and formal didactic experience with this component of their curriculum. A survey was conducted consisting of closed-ended questions investigating medical record documentation in the ED. The survey was distributed to all EM residents, EM-internal medicine, and EM-pediatrics residents taking the 1999 American Board of Emergency Medicine (ABEM) In-Training examination. Five EM residents and the Society for Academic Emergency Medicine (SAEM) board of directors prevalidated the survey. Summary statistics were calculated and resident levels were compared for each question using either chi-square or Fisher's exact test. Alpha was 0.05 for all comparisons. Completed surveys were returned from 88.5% of the respondents. A small minority of the residents code their own charts (6%). Patient encounters are most frequently documented on free-form handwritten charts (38%), and a total of 76% of the respondents reported using handwritten forms as a portion of the patient's final chart. Twenty-nine percent reported delays of more than 30 minutes to access medical record information for a patient evaluated in their ED within the previous 72 hours. Twenty-five percent "never" record their supervising faculty's involvement in patient care, and another 25% record that information "1-25%" of the time. Seventy-nine percent are "never" or "rarely" requested by their faculty to clarify or add to medical records for billing purposes. Only 4% of the EM residents were "extremely confident" in their ability to perform billing and coding, and more than 80% reported not knowing the physician charges for services or procedures performed in the ED. The handwritten chart is the most widely used method of patient care documentation, either entirely or as a component of a templated chart. Most EM residents do not document their faculty's participation in the care of patients. This could lead to overestimation of faculty noncompliance with HCFA billing guidelines. Emergency medicine residents are not confident in their knowledge of medical record documentation and coding procedures, nor of charges for services rendered in the ED.


[The modification of radiation-induced immune response].
In the overview it is shown that immune response to ionizing radiation exposure is determined not only by dose and dose rate, as was believed earlier, but also by a complex of factors (individual's age at exposure, genetic status, etc.). The emphasis in the overview is made on analyses of factors of endogenous (antioxidants, cytokines, peptides, etc.) and exogenous nature which are capable of modifying immune response following radiation exposure.


Family Planning in the Democratic Republic of the Congo: Encouraging Momentum, Formidable Challenges.
Momentum for family planning in the Democratic Republic of the Congo (DRC) is evident in multiple ways: strong political will, increasing donor support, a growing number of implementing organizations, innovative family planning programming, and a cohesive family planning stakeholder group. Between 2013 and 2017, the modern contraceptive prevalence rate (mCPR) in the capital city of Kinshasa increased from 18.5% to 26.7% among married women, but as of 2013-14, it was only 7.8% at the national level. The National Multisectoral Strategic Plan for Family Planning: 2014-2020 calls for achieving an mCPR of 19.0% by 2020, an ambitious goal in light of formidable challenges to family planning in the DRC. Of the 16,465 health facilities reporting to the national health information system in 2017, only 40% offer family planning services. Key challenges include uncertainty over the political situation, difficulties of ensuring access to family planning services in a vast country with a weak transportation infrastructure, funding shortfalls for procuring adequate quantities of contraceptives, weak contraceptive logistics and supply chain management, strong cultural norms that favor large families, and low capacity of the population to pay for contraceptive services. This article describes promising initiatives designed to address these barriers, consistent with the World Health Organization's framework for health systems strengthening. For example, the national family planning coordinating mechanism is being replicated at the provincial level to oversee the expansion of family planning service delivery. Promising initiatives are being implemented to improve the supply and quality of services and generate demand for family planning, including social marketing of subsidized contraceptives at both traditional and non-traditional channels and strengthening of services in military health facilities. To expand contraceptive access, family planning is being institutionalized in nursing schools, allowing students to operate as community-based distributors. While major challenges remain, significant progress in family planning has been made in the DRC, which should be judged not in comparison with sub-Saharan African countries with high mCPR and mature programs, but rather with those starting from much further behind.


Defining indoor heat thresholds for health in the UK.
It has been recognised that as outdoor ambient temperatures increase past a particular threshold, so do mortality/morbidity rates. However, similar thresholds for indoor temperatures have not yet been identified. Due to a warming climate, the non-sustainability of air conditioning as a solution, and the desire for more energy-efficient airtight homes, thresholds for indoor temperature should be defined as a public health issue. The aim of this paper is to outline the need for indoor heat thresholds and to establish if they can be identified. Our objectives include: describing how indoor temperature is measured; highlighting threshold measurements and indices; describing adaptation to heat; summary of the risk of susceptible groups to heat; reviewing the current evidence on the link between sleep, heat and health; exploring current heat and health warning systems and thresholds; exploring the built environment and the risk of overheating; and identifying the gaps in current knowledge and research. A global literature search of key databases was conducted using a pre-defined set of keywords to retrieve peer-reviewed and grey literature. The paper will apply the findings to the context of the UK. A summary of 96 articles, reports, government documents and textbooks were analysed and a gap analysis was conducted. Evidence on the effects of indoor heat on health implies that buildings are modifiers of the effect of climate on health outcomes. Personal exposure and place-based heat studies showed the most significant correlations between indoor heat and health outcomes. However, the data are sparse and inconclusive in terms of identifying evidence-based definitions for thresholds. Further research needs to be conducted in order to provide an evidence base for threshold determination. Indoor and outdoor heat are related but are different in terms of language and measurement. Future collaboration between the health and building sectors is needed to develop a common language and an index for indoor heat and health thresholds in a changing climate.


Recurrent Focal myositis: a rare inflammatory myopathy.
Focal myositis is an acute and localized muscle inflammation of unknown aetiology. The clinical diagnosis is often difficult to obtain, since it can be confused with infections, vascular thrombosis or muscle tumours such as sarcomas. This leads to a significant delay in the diagnosis, resulting in the administration of inappropriate and potentially harmful treatments. We report here a case of recurrent focal myositis in a woman where the diagnosis was only obtained after 6 years, despite multiple hospital admissions. This case reinforces the importance of clinical knowledge and experience to tackle challenging medical scenarios.


Batrachochytrium dendrobatidis detected in Kihansi spray toads at a captive breeding facility (Kihansi, Tanzania).
The chytrid fungus Batrachochytrium dendrobatidis (Bd) is the aetiological agent of amphibian chytridiomycosis, a disease associated with global amphibian population declines. In November 2012, mass mortalities of Kihansi spray toads Nectophrynoides asperginis were observed at the Kihansi captive breeding facility, located in the Udzungwa Mountains, Tanzania. Mortalities increased rapidly, and dead toads showed typical clinical signs of chytridiomycosis, including reddening of the skin that was especially evident on the toe pads. Treatment of toads with itraconazole rapidly reduced mortalities. Dead toads (n = 49) were collected and used to perform Bd-specific polymerase chain reaction and subsequent nucleotide sequencing. All toads collected at the facility were positive for Bd. The obtained Bd 5.8S rRNA gene and flanking internal transcribed spacer regions (ITS1 and ITS2) were not 100% identical to any other Bd sequences in GenBank, but closely resembled isolates from Ecuador, Japan, USA, Brazil, Korea, and South Africa. To our knowledge, this is the first study reporting molecular characteristics of Bd isolated from the Udzungwa Mountains. Strict biosecurity measures at the breeding facility and in Kihansi spray wetlands where toads have been reintroduced have been implemented. Further studies on Bd epidemiology in the Udzungwa Mountains are recommended in order to understand its origin, prevalence, and molecular characteristics in wild amphibian populations. This will be important for conservation of several endemic amphibian species in the Udzungwa Mountains, which are part of the Eastern Arc Mountains, a global biodiversity hotspot.


Raman spectroscopic analysis of gunshot residue offering great potential for caliber differentiation.
Near-infrared (NIR) Raman microspectroscopy combined with advanced statistics was used to differentiate gunshot residue (GSR) particles originating from different caliber ammunition. The firearm discharge process is analogous to a complex chemical reaction. The reagents of this process are represented by the chemical composition of the ammunition, firearm, and cartridge case. The specific firearm parameters determine the conditions of the reaction and thus the subsequent product, GSR. We found that Raman spectra collected from these products are characteristic for different caliber ammunition. GSR particles from 9 mm and 0.38 caliber ammunition, collected under identical discharge conditions, were used to demonstrate the capability of confocal Raman microspectroscopy for the discrimination and identification of GSR particles. The caliber differentiation algorithm is based on support vector machines (SVM) and partial least squares (PLS) discriminant analyses, validated by a leave-one-out cross-validation method. This study demonstrates for the first time that NIR Raman microspectroscopy has the potential for the reagentless differentiation of GSR based upon forensically relevant parameters, such as caliber size. When fully developed, this method should have a significant impact on the efficiency of crime scene investigations.


Linking existing instruments to develop a continuum of care measure: accuracy comparison using function-related group classification.
To compare measurement accuracy of test forms with varied number of items (13, 8, and 4 items) generated from the self-care physical function item bank composed of Functional Independence Measure (FIM™) and the Minimum Data Set (MDS). Retrospective data analysis of 2499 Veterans who completed both FIM and MDS within 6 days. We compared measurement accuracy between the converted FIM (FIMc) motor score generated from the MDS and the original FIM (FIMa) motor score (13 items) at: (a) individual-level using point differences, and (b) group-level using function-related group (FRG). The differences of mean FIMa and FIMc scores were between 0.05 and 1.07 points for all test forms. Over 81% of FIMc from MDS_13 were within 15 points of the FIMa. 81-90% of FRGs generated by the FIM short forms was identical to those generated by the FIMa for stroke, lower limb amputation, knee and hip replacement; and 59.9-90.5% by all MDS test forms. All MDS test forms had above 74% agreement with same or adjacent FMGs (ICC 0.65-0.91). The accuracy is dependent on the comparison level (i.e., individual or group), length of the test and which FRG is used. Our results partially support using existing instruments-without decreasing the number of the items-to generate a continuum of care measurement.


Cross-linked actin networks (CLANs) in bovine trabecular meshwork cells.
A cytoskeletal feature of human trabecular meshwork (HTM) cells in vitro and ex vivo is the presence of cross-linked actin networks (CLANs) that are abundant in a proportion of TM cells exposed to dexamethasone (DEX) and also in cells from glaucoma patients. We wished to determine whether CLANs were present in the bovine trabecular meshwork (BTM), whether they were similarly induced by dexamethasone and whether the structures were comparable to CLANs in HTM cells. Cultures of HTM and BTM cells and ex vivo dissections of BTM tissue were stained with phalloidin (F-actin) and propidium iodide (nuclei) and imaged by confocal microscopy, thereafter being subjected to image analysis. Some CLAN-like structures were identified in ex vivo BTM tissue cultured with and without DEX. However we found that BTM cells in culture produced abundant CLANs when exposed to DEX; comparable to the best response from HTM cells. The CLANs were of similar dimensions and morphology to those found in human cells and they had a similar half life of 2 or 3 days following the removal of DEX. This work demonstrates that BTM cells provide a suitable model for future investigations of CLAN formation and function. BTM cultures are sufficiently hardy to thrive in low serum and serum-free conditions so we were able to show that aqueous humor stimulates CLAN formation in the target cells. Future research is directed at identifying the aqueous component(s) responsible for CLAN production.


Efficient current-induced spin torques and field-free magnetization switching in a room-temperature van der Waals magnet.
The discovery of magnetism in van der Waals (vdW) materials has established unique building blocks for the research of emergent spintronic phenomena. In particular, owing to their intrinsically clean surface without dangling bonds, the vdW magnets hold the potential to construct a superior interface that allows for efficient electrical manipulation of magnetism. Despite several attempts in this direction, it usually requires a cryogenic condition and the assistance of external magnetic fields, which is detrimental to the real application. Here, we fabricate heterostructures based on Fe3GaTe2 flakes that have room-temperature ferromagnetism with excellent perpendicular magnetic anisotropy. The current-driven nonreciprocal modulation of coercive fields reveals a high spin-torque efficiency in the Fe3GaTe2/Pt heterostructures, which further leads to a full magnetization switching by current. Moreover, we demonstrate the field-free magnetization switching resulting from out-of-plane polarized spin currents by asymmetric geometry design. Our work could expedite the development of efficient vdW spintronic logic, memory, and neuromorphic computing devices.


Quantifying the Impact of Patient-Specific Factors and Disease Severity on Clinical Decision Making in Cuff Tear Arthropathy: A Case-Based Survey.
Rotator cuff tears are a common cause of disability. Some patients with massive and irreparable tears can develop cuff tear arthropathy (CTA), which makes management more challenging. We sought to examine how orthopedists determine treatment for patients with CTA. Specifically, we investigated (1) the effect of patient age, symptoms, activity level, range of motion, and radiographic findings on the decision making of shoulder specialists and (2) the observer reliability of the Seebauer and Hamada grading systems. Five shoulder surgeons were each sent 108 simulated patient cases. Each simulated patient had a different combination of factors, including patient age, symptoms, activity level, range of motion, and radiographs. Responders graded the radiographs and chose a treatment (non-operative, arthroscopic, hemiarthroplasty, or reverse total shoulder arthroplasty). Spearman's correlations and χ 2 tests were used to assess the relationship between factors and treatments. Sub-analysis was performed on surgical cases. An intra-class correlation (ICC) was used to assess observer agreement. The significant Spearman's correlations were symptoms (0.45), Hamada grade (0.38), patient age (0.34), and Seebauer type (0.29). In sub-analysis of operative cases, the significant correlations were Hamada grade (0.56), patient age (0.51), Seebauer type (0.46), activity level (-0.13). The χ 2 analysis was significant for all factors except activity level. The inter- and intraobserver reliabilities were, respectively, Seebauer type (0.59 and 0.63) and Hamada grade (0.58 and 0.65). Interobserver reliability for patient management was 0.44. When evaluating CTA, patient symptoms, radiographic grade, and patient age are the factors most strongly associated with the decision making of shoulder specialists. Additionally, the Seebauer and Hamada classifications had similar reliability and clinical utility. However, there was only fair agreement regarding treatment, which indicates that CTA management remains controversial.


Intragastric bile acid concentrations are unrelated to symptoms of flatulent dyspepsia in patients with and without gallbladder disease and postcholecystectomy.
It has been proposed that duodenogastric reflux may be the basic underlying mechanism which gives rise to symptoms of flatulent dyspepsia. Fasting and postprandial gastric juice bile acid concentrations were measured in patients with flatulent dyspepsia with and without gall bladder disease and postcholecystectomy. There were 13 patients with gall bladder disease, 12 with normal gall bladders and 13 postcholecystectomy. Gastric juice was obtained by intubation. Bile acid concentrations were compared with 21 controls and 15 asymptomatic subjects with gall bladder disease. For 21 patients with gall bladder disease who underwent cholecystectomy, levels were again assessed postoperatively to allow correlation with outcome. The occurrence of reflux and the resultant gastric juice bile acids did not correlate with symptoms. Concentrations postcholecystectomy, including asymptomatic subjects were significantly higher than controls (p less than 0.01). It is concluded that limited duodenogastric reflux is common and need not be associated with symptoms even when the resultant intra-gastric concentrations are higher than normal.


Long-Term Outcomes of Stereotactic Radiosurgery for Vestibular Schwannoma Associated with Neurofibromatosis Type 2 in Comparison to Sporadic Schwannoma.
The efficacy of radiosurgery for neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS) remains debatable. We retrospectively analyzed radiosurgical outcomes for NF2-associated VS compared to sporadic VS using our database of 422 consecutive VS patients. Twenty-five patients with 30 NF2-associated VSs with a mean follow-up of 121 months were identified. NF2-associated VSs exhibited excellent tumor control (10-year cumulative rate, 92% vs. 92% in sporadic VSs; p = 0.945) and worse overall survival (73% vs. 97%; p = 0.005), mainly due to tumor progression other than the treated VSs. The presence of NF2 was not associated with failed tumor control via multivariate Cox proportional hazard analyses. No difference in radiation-induced adverse events (RAEs) was confirmed between cohorts, and prescription dose (hazard ratio 8.30, 95% confidence interval 3.19-21.62, p < 0.001) was confirmed as a risk for cranial nerve injuries via multivariate analysis. Further analysis after propensity score matching using age, volume, and sex as covariates showed that NF2-associated VSs exhibited excellent local control (100% vs. 93%; p = 0.240) and worse overall survival (67% vs. 100%; p = 0.002) with no significant difference in RAEs. Excellent long-term tumor control and minimal invasiveness may make radiosurgery a favorable therapeutic option for NF2 patients with small to medium VS, preferably with non-functional hearing or deafness in combination with postoperative tumor growth or progressive non-operated tumors, or with functional hearing by patients' wish.


Inherent variability of CT lung nodule measurements in vivo using semiautomated volumetric measurements.
The objective of our study was to evaluate repeatability and reproducibility of lung nodule volume measurements using volumetric nodule-sizing software. Fifty nodules, less than 20 mm in diameter, in 29 patients were scanned with 1.25-mm collimation using MDCT (time 1 = T1). During the same session, two additional scans, using identical technique, were obtained through each nodule (T2, T3). Three observers working independently then obtained volumetric measurements using a semiautomated volumetric nodule-sizing software package. Qualitative nodule characterization was also performed. The Bland-Altman method for assessing measurement agreement was used to calculate the 95% limits for agreement for nodule volumes at T1, T2, and T3. Automated nodule segmentation was successful in 438 (97%) of 450 measurements. Forty-three nodules were available for final evaluation. Twenty-six nodules had well-defined edges, and 17 had irregular or spiculated margins. Seventeen were freestanding, 16 were juxtapleural, and 10 were juxtavascular in location. Average nodule volume was 345.5 mm(3) (range, 49.3-1,434 mm(3)). The mean interobserver variability (repeatability) was 0.018% (SD = 0.73%), and the SD of the mean for the three contemporaneous scans (reproducibility) was 13.1% (confidence limits, +/- 25.6%). SD and confidence limits narrowed as volumes increased. Volumetric measurements show minimal interobserver variability (0.018%) but an interscan SEM of 13.1% (confidence limits, +/- 25.6%). Repeatability and reproducibility of volumetric measurements are better than those of linear measurements reported in the literature.


Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells.
Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity.