Effect of steam explosion on biodegradation of lignin in wheat straw.
The effect of steam explosion pretreatment on biodegradation of lignin in wheat straw was studied in this paper. Through experiments and analysis, 0.8MPa operation pressure and 1:20 wheat straw to water ratio are optimum for destroying lignin and the maximum of lignin loss rate is 19.94%. After steam explosion pretreatment, the wheat straw was retted by Trametes versicolor for 40 days. Biodegradation rate of lignin was tested and the maximum of 55.40% lignin loss rate was found on day 30. During the whole process of both steam explosion pretreatment and biodegradation, 75.34% lignin was degraded, without steam explosion the biodegradation of raw material the degradation rate of lignin was 31.23% only. FT-IR spectroscopy, TGA and SEM were used for further validating the results of biodegradation.


Is faecal-immunochemical test useful in patients with iron deficiency anaemia and without overt bleeding?
Both upper and lower endoscopies are indicated in patients with iron deficiency anaemia. However, these examinations are negative in a high proportion of cases. To assess whether faecal-immunochemical test (FIT) may be useful in selecting patients at higher risk of bleeding lesions in iron deficiency anaemia patients. Iron deficiency anaemia patients without overt bleeding were prospectively enrolled. All patients performed FIT, and underwent both upper and lower endoscopy. Predictive factors of potential bleeding lesions were evaluated at multivariate analysis. FIT was positive in 48 (34.3%) out of 140 enrolled patients, and a potential bleeding lesion was present in 63 (45%) patients. An endoscopic lesion was detected more frequently in FIT-positive than -negative patients (79.2% vs 27.2%; p<0.0001), at both upper endoscopy (52.1% vs 18.5%; p=0.0002) and colonoscopy (33.3% vs 8.7%; p=0.001). At multivariate analysis, FIT was found to be an independent predictor of both bleeding lesions (OR=9.5; 95% CI: 4.1-22; p<0.001) and cancer (OR=4.0, CI: 1.1-15; p=0.029). FIT positive-iron deficiency anaemia patients without overt bleeding are at increased risk to present with a bleeding lesion at endoscopy, including cancer. FIT positivity in this setting could be useful to prioritize urgent endoscopy.


LISS--an effective way to increase blood utilization.
The low ionic strength solution (LISS) of Low and Messeter was compared with both the automated low ionic strength Polybrene and the manual IDAT techniques. A five minute incubation with the LISS was sufficient to detect all significant antibodies. By extending the incubation period to 15 minutes it was possible to increase the sensitivity of the reaction (as measured by titer) beyond that of either of the other methods. This LISS procedure has enabled us to greatly extend the applications of a "standby procedure" for elective surgery. In this procedure routine crossmatching is not done. Rather, the blood is placed on standby and if required, transfusion is provided by using the LISS. In one general hospital this resulted in the reduction by 1,600 units of unneccessary crossmatches and an increase of 10% in the total blood utilization rate over a nine-month period.


Otogenic cerebral venous infarction: a rare complication of acute otitis media.
A case of cerebral venous infarction (CVI) as a complication of acute otitis media (AOM) was presented in a 16-month-old male patient. The patient admitted with AOM in the right ear, ipsilateral facial paralysis and contralateral hemiplegia. Computerized tomography of the brain showed low density areas involving both the cortex and subcortical white matter in the right frontoparietal region, and there were patchy and multifocal enhancing areas with intravenous contrast enhancement. These findings disclosed the diagnosis of venous infarctions involving the superficial cortical veins on the right side. Complete recovery was achieved with 2 weeks of sulbactam-ampicilline, amikacin and prednisolone treatment. Although it is rather rare, CVI should also be remembered among the otogenic intracranial complications.


Synovial fluid lactate and the diagnosis of septic arthritis.
To assess the value of synovial fluid lactate estimation in the diagnosis of septic arthritis, 238 specimens received for routine culture and 75 reference samples were examined using a rapid enzyme technique. Samples were collected without special treatment and the effect of delay in transport to the laboratory investigated. Raised levels were found in all cases of untreated septic arthritis, in six out of ten partially treated patients and in 19 out of 219 non-septic fluids. Special treatment of the sample was unnecessary if it was examined within six hours of aspiration. The predictive value of a negative result was 98 per cent and the value of the test appeared to be in the rapid exclusion of sepsis in untreated patients.


Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation.
Hair follicle stem cells (HFSCs) are implicated in the formation of hair follicles and epidermis. This study aims to clarify the role of SMAD2 in regulating the differentiation of HFSCs, which is involved with Smurf2. Functional assays were carried out in human HFSCs to assess the effect of SMAD2 and Smurf2 with altered expression on growth dynamics of HFSCs. Ubiquitination of SMAD2 and its protein stability were assessed. The binding relationship between NANOG and DNMT1 was assessed. A mouse skin wound model was induced to verify the effects of Smurf2/SMAD2/NANOG/DNMT1 on wound healing. SMAD2 overexpression was observed in HFSCs during differentiation and its ectopic expression contributed to promotion of differentiation and apoptosis of HFSCs while arresting cell proliferation. Mechanistic investigations indicated that Smurf2 promoted the ubiquitination and degradation of SMAD2, thus causing downregulation of SMAD2 expression. By this mechanism, NANOG expression was reduced and the subsequent DNMT1 transcriptional expression was also diminished, leading to suppression of differentiation and apoptosis of HFSCs while stimulating cell proliferation. Moreover, in vivo data showed that Smurf2 upregulation limited epidermal wound healing in mice by inhibiting the SMAD2/NANOG/DNMT1 axis. Our work proposed a potential target regarding SMAD2 restoration in promoting HFSC differentiation and skin wound healing.


Effects of percutaneous mitral valvuloplasty on left atrial appendage flow velocity.
This study shows an increase in LAA flow after PTMV in both normal sinus rhythm and atrial fibrillation. These results suggest that relief of mitral stenosis may not only confer hemodynamic benefits for the improvement of symptoms but also have a favorable influence on future thromboembolism.


Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing.
Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine.


B cell tumor vaccine enhanced by covalent attachment of immunoglobulin to surface proteins on dendritic cells.
Protein antigens have been covalently linked randomly to surface proteins on immature dendritic cells (DC). This has been achieved under physiological conditions using a heterobifunctional reagent that couples antigens to free thiol groups expressed on DC surface proteins. This results in a significant increase in the amount of antigen that is bound to DC, and the antigen/membrane protein complexes that are formed are rapidly internalized. DC, loaded covalently with either beta-galactosidase (beta-gal) or a tumor-associated immunoglobulin (Ig) when injected into mice, induce a beta-gal- or Ig-specific T cell response, and a protective anti-tumor immunity for tumors expressing either beta-gal or the targeted Ig. This response is shown here to be significantly greater than that which is induced by DC that are loaded with these antigens via the conventional antigen pulse protocol. These results establish a novel, safe, and viable approach of enhancing the effectiveness of DC-based vaccination strategies for B cell lymphoma.


Depth of Invasion, Lymphovascular Invasion, and Perineural Invasion as Predictors of Neck Node Metastasis in Early Oral Cavity Cancers.
The present study examines the role of demographic and pathological features of primary tumours in predicting neck metastasis in early oral cavity cancers, which has been a matter of debate. A single-centre, retrospective, institution review was conducted of all the patients presented to our centre from January 2014 to December 2021. Patient characteristics were compared between the two lymph node groups (lymph node positive and lymph node negative) and significant prognostic factors were determined. A total of 462 oral squamous cell carcinoma (OSCC) patients were included, 407 male and 55 female. Tobacco chewing (59.2%) was a major habit with buccal mucosa (49.5%) and tongue (44.8%) as primary sites. The majority of the patient's histology was of SCC (96.8%) with grade II (moderately differentiated, 74.5%). Univariate logistic regression analysis to predict lymph node metastasis showed pT size (< 0.001), LVI (< 0.001), and PNI (< 0.001) as significant tumor characteristics. On multivariate, pT size (OR-1.58, P - 0.0001) and LVI (OR-19.70, P - 0.0001) were reported to be statistically significant to predict lymph node metastasis. Reporting and studying the clinico-pathological features of primary tumors can give vital information in predicting the neck node metastasis in OSCC patients.


Neighborhood language isolation and depressive symptoms among elderly U.S. Latinos.
Neighborhood segregation related to cultural factors, such as language use, may influence elderly Latino depression. We examined the association between neighborhood-level Spanish language segregation and individual depressive symptoms among elderly Latinos. We linked U.S. Census language use data with geocoded population-based data from 1789 elderly Latinos (mean age = 70.6 years) participating in the Sacramento Area Latino Study on Aging (1998-2008). Neighborhood language segregation was measured with the Index of Concentration at the Extremes, which demonstrates the extent to which residents are concentrated at extremes of deprivation and privilege. We fit two-level generalized linear-mixed models with random intercepts for census tracts to quantify the association between neighborhood-level language segregation and depressive symptoms, adjusting for identified confounders. After adjusting for age, sex, and nativity, residents of highly segregated Spanish-speaking neighborhoods had more depressive symptoms than those in highly segregated English-only-speaking neighborhoods (β = -4.410; 95% confidence interval [CI] = -6.851 to -1.970). This association was largely attenuated upon adjustment for individual-level education (β = -2.119; 95% CI = -4.650 to 0.413). Linguistically segregated communities may benefit from targeted outreach given the high depression prevalence in these neighborhoods. Furthermore, our findings suggest that limited access to fundamental social protections, such as education, may drive the segregation-depression association among U.S. Latinos.


Fate of injected interleukin 1 in rats: sequestration and degradation in the kidney.
The tissue distribution and route of clearance of human recombinant interleukin 1 alpha (IL 1 alpha) injected intravenously in rats was studied. The plasma half-life was approximately 2.5 min, and this was increased after nephrectomy, the kidney being the major organ through which the IL 1 alpha was excreted. Two iodinated fragments of IL 1 alpha, of approximately 5 and 9 kDa, were excreted by the kidneys whereas only intact, 17-kDa IL 1 alpha was detected in plasma, suggesting that the protein was being degraded after uptake by the kidney. The results of in vivo experiments in which surface endopeptidase-24.11 was inhibited with phosphoramidon and in vitro experiments in which rat kidney homogenates were incubated with radiolabeled IL 1 alpha suggest that the cytokine was endocytosed and then hydrolysed by lysosomal proteinases.


Reduction of EEG activity caused by a light flash.
Intertrial EP variance measured in response to a brief binocularly presented flash of light decreases with a time-course that overlaps the average EP. This decrease in variance is not exclusive to the alpha frequency band (8-12 c/sec) but it is selective for it. Subjects with large initial variance tend to show a large decrease in variance. There is no relationship between the magnitude of the decrease in variance and the consistency of the EP. The phenomenon reflected by the decrease in variance is probably identical with 'event-related desynchronization.' The results support the hypothesis that an EP may consist of two processes that overlap in time: a reduction in background EEG activity and an almost deterministic transient potential change.


Time-varying encounter angle trajectory tracking control of unmanned surface vehicle based on wave modeling.
In this note, a wave simulation method based on the wave spectrum is proposed, and the wave simulation is transformed into external interference to verify the necessity of using variable encounter angle real wave interference. Firstly, A wave simulation method based on wave spectrum and equidistant method is proposed and demonstrated. Secondly, wave modeling is transformed into interference force related to the encounter angle by fully considering the real marine environment. Furthermore, a trajectory tracking controller with variable encounter angles and the actual sea state is designed using the disturbance modeling method. Finally, the necessity and authenticity of considering varying encounter angles and real sea conditions in the motion control of unmanned surface vehicles (USVs) are proved by simulation.


Qualitative descriptions of patient perceptions about fall risks, prevention strategies and self-identity: Analysis of fall prevention Motivational Interviewing conversations.
Older adults are often reluctant to engage in fall prevention activities. To understand how older adults respond to fall prevention and identify attributes that affect their responses to fall prevention. Qualitative content analysis of Fall Prevention Motivational Interviewing conversations that were conducted as an intervention for a fall prevention study in the USA. We report the methods, results and discussions using the COnsolidated criteria for REporting Qualitative research checklist. Conversations from 30 participants were analysed. Participants showed various responses to fall prevention from acceptance and engagement to ambivalence to denial or giving up. Three attributes affecting how they responded to fall prevention were as follows: (a) their perception of fall risks, (b) their perception about fall prevention strategies and (c) self-identity. If participants perceived that their fall risks were temporary or modifiable, they were more likely to engage in fall prevention. If participants perceived that their fall risks were permanent or unmodifiable, they seemed to have difficulty accepting fall risks or gave up engaging in fall prevention strategies. Participants were more willing to adopt fall prevention strategies that involved minor adjustments but expressed more resistance to adopting strategies that required major adjustments. Further, their response to accepting or not accepting fall prevention was influenced by their perception of whether the fall risks and fall prevention strategies aligned with their self-identity. Findings underscore the importance of understanding older adults' self-identify and perceptions about fall prevention. Exploring older adults' self-identity and perceptions about fall prevention can be useful to support their engagement in fall prevention.


Elevated MHC class I and II antigens in cultured human embryonic myoblasts following stimulation with gamma-interferon.
The expression of major histocompatibility complex (MHC) antigens on the surface of cultured human embryonic myoblasts was studied by fluorescence microscopy. Class I or II MHC antigens were detected by monoclonal antibodies (MoAb) recognizing monomorphic determinants on HLA-A, B and C (class I), or HLA-DP, DQ and DR (class II) and a secondary fluorescein-labelled sheep anti-mouse immunoglobulin (Ig) antibody. Myoblasts were simultaneously identified using a MoAb directed against myosin light chains 1 and 2 (MLC1 and MLC2) and a combination of biotin-labelled sheep anti-mouse Ig antibody and Texas Red labelled streptavidin. We found that myoblasts demonstrated only very weak expression of either class of MHC but that, in the presence of more than 100 units of gamma-interferon (gamma-IFN) for 56-72 h, both class I and II MHC antigen expression increased significantly. During this time, class I antigen increased more than class II and at lower gamma-IFN concentrations. The implications of these findings for myoblast transfer therapy in Duchenne muscular dystrophy patients is discussed.


Capsule and mosaic pattern of hepatocellular carcinoma: correlation between CT and MR imaging.
Computed tomography (CT) was compared with magnetic resonance (MR) imaging in depicting the capsule and the mosaic pattern of hepatocellular carcinoma in 34 patients. The kappa statistic was used to compare results from both modalities. For the detection of the capsule, there was a substantial agreement beyond chance between late enhanced CT (more than 5 min after dynamic CT) and MR imaging (kappa = 0.76). Late enhanced CT and MR imaging had almost perfect agreement for the demonstration of the mosaic pattern (kappa = 0.85). These agreements were better than the agreements between unenhanced CT and MR imaging or between early enhanced CT and MR imaging. These results suggest that late enhanced CT compares favorably with MR imaging in depicting the capsule and the mosaic pattern of hepatocellular carcinoma.


Spectral absorption index in hyperspectral image analysis for predicting moisture contents in pork longissimus dorsi muscles.
Spectral absorption index was proposed to extract the morphological features of the spectral curves in pork meat samples (longissimus dorsi) under the conditions including fresh, frozen-thawed, heated-dehydrated and brined-dehydrated. Savitzky-Golay (SG) smoothing and multiplicative scatter correction (MSC) were used for calibrating both the spectral reflectance and absorbance values. The absorption values were better than the reflectance values and the calibrated spectra by MSC were better than the raw and SG smoothing corrected spectra in building moisture content predictive models. The optimized partial least square regression (PLSR) model attained good results with the MSC calibrated spectral absorption values based on the spectral absorption index features (R(2)P=0.952, RMSEP=1.396) and the optimal wavelengths selected by regression coefficients (R(2)P=0.966, RMSEP=0.855), respectively. The models proved spectral absorption index was promising in spectral analysis to predict moisture content in pork samples using HSI techniques for the first time.


Effects of electrode area on electrocardiographic voltages.
Effects of two different sizes of chest electrodes--100 and 750 mm2 area--on x and z Frank leads were determined using electrocardiographic data from 25 subjects. In most cases, differences in Rx and Rz were below 50 uV, but in nine cases (36%) differences exceeded this value for either Rx or Rz or both. In six cases, differences exceeded 100 uV. For an additional 20 subjects, standard precordial leads were recorded using the same two electrode sizes. QRS amplitudes were significantly affected for V4 but not for V1 or V6. Variability caused by electrode size is greater than that caused by beat-to-beat variation and is comparable to that found in day-to-day variation. Interchangeability of data among ECG recording laboratories can be significantly improved by standardizing electrode size for precordial electrodes.


Metagenomics unraveled the characteristics and microbial response to hypersaline stress in salt-tolerant aerobic granular sludge.
In this study, the salt-tolerant aerobic granular sludge (SAGS) was cultivated with the increased salinity (0-9% NaCl), showing oval shape, and clear outline. The related sludge characteristics in the formation process of SAGS as well as the effects of salinity on the performance (removal ability, sludge biomass and EPS component) of SAGS were evaluated. Increased salinity accelerated the formation of SAGS, and resulted in the excess secretion of EPS. Relationship between EPS and settling capacity of SAGS was determined, with the increase of salinity, SVI decreased linearly and the sedimentation performance of granular sludge was enhanced. Pearson correlation analysis showed that shorter settling time (3 min) and longer anaerobic influent time (30 min) were beneficial to the operation of SAGS reactor. Metagenomics results showed that the SAGS was dominated by Candida, Halomonas and other salt-tolerant bacteria, the enrichment of these salt-tolerant microbes played an important role in maintaining the stability of granular sludge system and improving the overall salt-tolerant performance. Compared with S9 samples, the proteome regulation in S0 sample was more active and the abundance of Cell motility related proteins was 5 times higher than that in S9 samples. Extracellular structure related proteins was more active in S9, and its abundance was 3.6 times that of S0.


Removal of T4 endonuclease V-sensitive sites from SV40 DNA after exposure to ultraviolet light.
The induction and removal of sites sensitive to T4 endonuclease V from ultraviolet-irradiated Simian Virus 40 (SV40) Form I (supercoiled) DNA during a lytic infection of monkey CV-1 cells was investigated by agarose tube gel electrophoresis. Endonuclease-sensitive sites were induced at a rate of 0.049 sites/SV40 genome per J/m2, or 1.4 sites/1 . 10(8) daltons of DNA per J/m2. This value is similar to the yield of endonuclease-sensitive sites and pyrimidine dimers in uninfected host CV-1 cell DNA. Removal of endonuclease-sensitive sites was dose dependent and non-linear for at least 24 h after irradiation. These results suggest that SV40 DNA is subject to the excision repair mechanisms of the host cell, and that the excision of pyrimidine dimers may be one of the biochemical events underlying host cell reactivation.


Neuroscience may supersede ethics and law.
Advances in technology now make it possible to monitor the activity of the human brain in action, however crudely. As this emerging science continues to offer correlations between neural activity and mental functions, mind and brain may eventually prove to be one. If so, such a full comprehension of the electrochemical bases of mind may render current concepts of ethics, law, and even free will irrelevant.


Comparative Trends in Percutaneous Coronary Intervention in Japan and the United States, 2013 to 2017.
Adoption of the results of large-scale randomized controlled trials in percutaneous coronary intervention (PCI) may differ internationally, yet few studies have described the potential variations in PCI practice patterns. Using representative national registries, we compared temporal trends in procedural volume, patient characteristics, pre-procedural testing, procedural characteristics, and quality metrics in the United States and Japan. The National Cardiovascular Data Registry CathPCI was used to describe care in the United States, and the J-PCI was used to assess practice patterns in Japan (numbers of participating hospitals: 1,752 in the United States and 1,108 in Japan). Both registries were summarized between 2013 and 2017. PCI volume increased by 15.8% in the United States from 550,872 in 2013 to 637,650 in 2017, primarily because of an increase in nonelective PCIs (p for trend <0.001). In Japan, the volume of PCIs increased by 36%, from 181,750 in 2013 to 247,274 in 2017, primarily because of an increase in elective PCIs (p for trend <0.001). The proportion of PCI cases for elective conditions was >2-fold greater in Japan (72.7%) than in the United States (33.8%; p < 0.001). Overall, the ratio of nonelective PCI (vs. elective PCI; 27.3% vs. 66.2%; p < 0.001) and the performance of noninvasive stress testing in patients with stable disease (15.2% vs. 55.3%; p < 0.001) was lower in Japan than in the United States. Computed tomography angiography was more commonly used in Japan (22.3% vs. 2.0%; p < 0.001). Elective PCI is more than twice as common in Japan as in the United States in contemporary practice. Computed tomography angiography is much more frequently used pre-procedurally in Japan than in the United States.


Elements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets.
In ER-associated degradation (ERAD), misfolded ER proteins are degraded by the proteasome after undergoing ubiquitylation. Yeast Doa10 (human MARCHF6/TEB4) is a membrane-embedded E3 ubiquitin ligase that functions with E2s Ubc6 and Ubc7. Ubc6 attaches a single ubiquitin to substrates, which is extended by Ubc7 to form a polyubiquitin chain. We show the conserved C-terminal element (CTE) of Doa10 promotes E3-mediated Ubc6 activity. Doa10 substrates undergoing an alternative ubiquitylation mechanism are still degraded in CTE-mutant cells. Structure prediction by AlphaFold2 suggests the CTE binds near the catalytic RING-CH domain, implying a direct role in substrate ubiquitylation, and we confirm this interaction using intragenic suppression. Truncation analysis defines a minimal E2-binding region of Doa10; structural predictions suggest that Doa10 forms a retrotranslocation channel and that E2s bind within the cofactor-binding region defined here. These results provide mechanistic insight into how Doa10, and potentially other ligases, interact with their cofactors and mediate ERAD.


Vacuum radio frequency drying: a novel method to improve the main qualities of chicken powders.
Vacuum radio frequency drying (VRFD) combining the advantages of RF heating with vacuum drying (VD) was applied to produce chicken powders. Drying time and some properties of VRFD the powders were compared with VD and microwave vacuum drying (MVD) (915 MHz and 2450 MHz). Results showed that the total drying time of VRFD chicken powders was the shortest (100 min) while that for VD powders was the longest (180 min). VRFD chicken powders exhibited the lowest hygroscopicity (2.17%), the highest water holding capacity (254.80%), and better color and taste. Besides, VRFD powders had maximum umami flavor among the obtained powders. Contrarily, the color and flavor of VD powders were the most undesirable. Additionally, VRFD had less effect on protein secondary structures compared with MVD. It was concluded that, VRFD possesses the necessary potential for use at industrial level in the production of chicken powders with high qualities.


Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome.
The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low-density lipoprotein (LDL) size, before and after sustained release metformin (Met-SR) therapy in women with polycystic ovarian syndrome (PCOS). Sixty women with PCOS and sixty age-matched controls in the age group 18-45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.


Prescription and non-prescription drug use: a longitudinal study.
This study examines changes in the lifetime prevalence of prescription and non-prescription drug use in a national longitudinal sample of young adults. Cohort data used in this study are from the National Longitudinal Survey, Youth Cohort (NLSY) who responded to questions on use of prescription drugs for the years 1984 and 1992 (N = 8,771). Results reveal increases in the lifetime prevalence of prescription use of sedatives, transquilizers, and stimulants. Prescription use was higher among women while non-prescription use was higher among men. Non-prescription drug use in 1984 was significantly related to prescription use in 1992.


[Diagnostic and clinical problems tick-borne meningitis based on personal observations].
The author presents 17 patients with tick-born neuroinfections. The correct diagnosis was established during serological examinations.


Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain.
The authors tested the hypotheses that subarachnoid hemorrhage (SAH) leads to delayed cell death with the participation of apoptotic-like mechanisms and is influenced by the degree of acute decrease in the cerebral blood flow (CBF) following hemorrhage. Subarachnoid hemorrhage was induced in rats by endovascular perforation of the internal carotid artery or injection of blood into the prechiasmatic cistern. Cerebral blood flow was measured using laser Doppler flowmetry for 60 minutes. Brain sections stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) showed DNA fragmentation at 2 and 7 days after both methods of inducing SAH in one third to two thirds of the surviving animals in the different experimental groups. More than 80% of the TUNEL-positive cells were neuron-specific nuclear protein-positive (neurons), but immunoreactivity to glial fibrillary acidic protein (astrocytes) and transferrin (oligodendrocytes) were markedly decreased in TUNEL-positive areas. Most of the TUNEL-positive cells displayed chromatin condensation and/or blebs and immunostained for increased Bax; approximately 50% of them were immunoreactive to cleaved caspase-3 and a few to Bcl-2. The duration of the acute CBF decrease below 30% of the baseline level was related to the degree of TUNEL staining. Subarachnoid hemorrhage resulted in delayed cell death in a large proportion, but not all, of the surviving animals. The acute CBF decrease was related to the degree of subsequent cell death. These findings indicated the relevance of apoptotic-like pathways. There appears to be a temporal therapeutic window during which adequate treatment might reduce the final damage following SAH.


Prdm1 overexpression causes a photoreceptor fate-shift in nascent, but not mature, bipolar cells.
The transcription factors Prdm1 (Blimp1) and Vsx2 (Chx10) work downstream of Otx2 to regulate photoreceptor and bipolar cell fates in the developing retina. Mice that lack Vsx2 fail to form bipolar cells while Prdm1 mutants form excess bipolars at the direct expense of photoreceptors. Excess bipolars in Prdm1 mutants appear to derive from rods, suggesting that photoreceptor fate remains mutable for some time after cells become specified. Here we tested whether bipolar cell fate is also plastic during development. To do this, we created a system to conditionally misexpress Prdm1 at different stages of bipolar cell development. We found that Prdm1 blocks bipolar cell formation if expressed before the fate choice decision occurred. When we misexpressed Prdm1 just after the decision to become a bipolar cell was made, some cells were reprogrammed into photoreceptors. In contrast, Prdm1 misexpression in mature bipolar cells did not affect cell fate. We also provide evidence that sustained misexpression of Prdm1 was selectively toxic to photoreceptors. Our data show that bipolar fate is malleable, but only for a short temporal window following fate specification. Prdm1 and Vsx2 act by stabilizing photoreceptor and bipolar fates in developing OTX2+ cells of the retina.


Decreased insulin-stimulated brown adipose tissue glucose uptake after short-term exercise training in healthy middle-aged men.
To test the hypothesis that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) improve brown adipose tissue (BAT) insulin sensitivity. Healthy middle-aged men (n = 18, age 47 years [95% confidence interval {CI} 49, 43], body mass index 25.3 kg/m2 [95% CI 24.1-26.3], peak oxygen uptake (VO2peak ) 34.8 mL/kg/min [95% CI 32.1, 37.4] ) were recruited and randomized into six HIIT or MICT sessions within 2 weeks. Insulin-stimulated glucose uptake was measured using 2-[18 F]flouro-2-deoxy-D-glucose positron-emission tomography in BAT, skeletal muscle, and abdominal and femoral subcutaneous and visceral white adipose tissue (WAT) depots before and after the training interventions. Training improved VO2peak (P = .0005), insulin-stimulated glucose uptake into the quadriceps femoris muscle (P = .0009) and femoral subcutaneous WAT (P = .02) but not into BAT, with no difference between the training modes. Using pre-intervention BAT glucose uptake, we next stratified subjects into high BAT (>2.9 µmol/100 g/min; n = 6) or low BAT (<2.9 µmol/100 g/min; n = 12) groups. Interestingly, training decreased insulin-stimulated BAT glucose uptake in the high BAT group (4.0 [2.8, 5.5] vs 2.5 [1.7, 3.6]; training*BAT, P = .02), whereas there was no effect of training in the low BAT group (1.5 [1.2, 1.9] vs 1.6 [1.2, 2.0] µmol/100 g/min). Participants in the high BAT group had lower levels of inflammatory markers compared with those in the low BAT group. Participants with functionally active BAT have an improved metabolic profile compared with those with low BAT activity. Short-term exercise training decreased insulin-stimulated BAT glucose uptake in participants with active BAT, suggesting that training does not work as a potent stimulus for BAT activation.


Association of Different Prescribing Patterns for Oral Corticosteroids With Fracture Preventive Care Among Older Adults in the UK and Ontario.
Identifying and mitigating modifiable gaps in fracture preventive care for people with relapsing-remitting conditions such as eczema, asthma, and chronic obstructive pulmonary disease who are prescribed high cumulative oral corticosteroid doses may decrease fracture-associated morbidity and mortality. To estimate the association between different oral corticosteroid prescribing patterns and appropriate fracture preventive care, including treatment with fracture preventive care medications, among older adults with high cumulative oral corticosteroid exposure. This cohort study included 65 195 participants with UK electronic medical record data from the Clinical Practice Research Datalink (January 2, 1998, to January 31, 2020) and 28 674 participants with Ontario, Canada, health administrative data from ICES (April 1, 2002, to September 30, 2020). Participants were adults 66 years or older with eczema, asthma, or chronic obstructive pulmonary disease receiving prescriptions for oral corticosteroids with cumulative prednisolone equivalent doses of 450 mg or higher within 6 months. Data were analyzed October 22, 2020, to September 6, 2022. Participants with prescriptions crossing the 450-mg cumulative oral corticosteroid threshold in less than 90 days were classified as having high-intensity prescriptions, and participants crossing the threshold in 90 days or more as having low-intensity prescriptions. Multiple alternative exposure definitions were used in sensitivity analyses. The primary outcome was prescribed fracture preventive care. A secondary outcome was major osteoporotic fracture. Individuals were followed up from the date they crossed the cumulative oral corticosteroid threshold until their outcome or the end of follow-up (up to 1 year after index date). Rates were calculated for fracture preventive care and fractures, and hazard ratios (HRs) were estimated from Cox proportional hazards regression models comparing high- vs low-intensity oral corticosteroid prescriptions. In both the UK cohort of 65 195 participants (mean [IQR] age, 75 [71-81] years; 32 981 [50.6%] male) and the Ontario cohort of 28 674 participants (mean [IQR] age, 73 [69-79] years; 17 071 [59.5%] male), individuals with high-intensity oral corticosteroid prescriptions had substantially higher rates of fracture preventive care than individuals with low-intensity prescriptions (UK: 134 vs 57 per 1000 person-years; crude HR, 2.34; 95% CI, 2.19-2.51, and Ontario: 73 vs 48 per 1000 person-years; crude HR, 1.49; 95% CI, 1.29-1.72). People with high- and low-intensity oral corticosteroid prescriptions had similar rates of major osteoporotic fractures (UK: crude rates, 14 vs 13 per 1000 person-years; crude HR, 1.07; 95% CI, 0.98-1.15 and Ontario: crude rates, 20 vs 23 per 1000 person-years; crude HR, 0.87; 95% CI, 0.79-0.96). Results from sensitivity analyses suggested that reaching a high cumulative oral corticosteroid dose within a shorter time, with fewer prescriptions, or with fewer or shorter gaps between prescriptions, increased fracture preventive care prescribing. The results of this cohort study suggest that older adults prescribed high cumulative oral corticosteroids across multiple prescriptions, or with many or long gaps between prescriptions, may be missing opportunities for fracture preventive care.


Impact of an aggressive coronary stenting strategy on the incidence of target lesion revascularization.
Coronary stenting has been shown to reduce the incidence of target lesion revascularization (TLR) compared with balloon angioplasty in highly selected patients. However, the impact of an aggressive coronary stenting strategy in unselected patients on the overall incidence of TLR is unclear. We assessed the effect of increased stenting by comparing long-term results in consecutive patients who underwent successful percutaneous revascularization (with or without stents) during June to December 1995 (n=347) with those in June to December 1996 (n=401). Stents were used in 22.5% of patients in 1995 versus 66.1% in 1996 (p <0.0001). Mean age of the patients was 62+/-11 years (71% men) in 1995 versus 63+/-10 in 1996 (76% men) (p=NS). The 2 groups were well matched with the exception that the 1996 cohort included more patients with unstable coronary syndromes (25% in 1995 vs 34% in 1996 (p=0.003). There was no significant difference in the incidence of in-hospital adverse events. After 12 months of follow-up (complete in 95% of patients in each group), the incidence of TLR was significantly lower in the 1996 cohort than in the 1995 cohort (8.5% vs 14.7%, p=0.0075). This was mainly due to reduced requirement for repeat angioplasty in 1996 patients compared with 1995 (6.5% vs 11.8%, p=0.011). It is concluded that in an unselected patient population, an aggressive coronary stenting strategy was associated with a marked overall reduction in requirement for TLR over a 12-month period.


Cloning and functional identification of pmKPI cDNA in Poecilobdella manillensis.
Kazal-type serine protease inhibitors play a role in physiological processes such as blood coagulation and fibrinolysis. The amino acid residues at the P1 site are different, and they inhibit different types of proteases. The inhibitory mechanism of the protease in the salivary glands of Poecilobdella manillensis is still unclear. Based on cloning, prokaryotic expression and bioinformatics analysis, we studied the role of Kazal-type serine protease inhibitors in P. manillensis and analyzed their expression by quantitative real-time PCR. The results suggested that the recombinant protein was successfully expressed in the supernatant when a prokaryotic expression vector was constructed and induced with 0.2 mmol/L IPTG at 37 °C for 4 h, and the enzymatic activity was determined. The mature protein encodes 91 amino acids and has a relative molecular weight of 9929.32 Da, and after removing the signal peptide, the theoretical isoelectric point was 8.79. It is an unstable protein without a transmembrane domain. The mature protein contains two Kazal-type domains, in which all P1 residues are Lys, consisting of an α helix and three antiparallel β sheets. The upregulated expression of the mRNA was induced after a meal was provided, and the results showed an increasing and then decreasing trend. Taken together, the results indicate that mature proteins from P. manillensis inhibit thrombin activity, laying the foundation for the subsequent in-depth study of the function of genes encoding Kazal-type serine protease inhibitors.


The biology of wound healing in the corneal stroma. Castroviejo lecture.
The healing and remodeling of a stromal incision in described at the gross, fibrillar, and cellular levels. The possibility that the healing of the wound and the clearing of the scar can be accelerated by biological interventions is discussed. Castroviejo Lecture was given on November 9, 1986.


[Surgery of the cervical spine in rheumatoid arthritis. Diagnostics and indication].
The cervical spine is often affected in rheumatoid arthritis. Beside destructive changes, instabilities can occur, mainly in the upper cervical spine. Typical symptoms are missing so that routine x-ray examinations are needed to prevent severe consequences up to death. AP/lateral cervical spine x-rays and lateral functional x-rays are the standard diagnostic tool. Depending on the findings, further neurological examination and MRI must be initiated. Aim is the early recognition, respectively prevention of myelopathy. Therapy includes stage dependent conservative and surgical measures.


Post-partum sacral fracture associated with heparin treatment.
We report the case of a 19-year-old woman who consulted for low-back pain 3 weeks after her first delivery. This young woman had a personal history of protein C deficiency and was treated daily during her pregnancy with low-molecular-weight heparin. Her body mass index was 34 and she only gained 10 kg during her pregnancy. Since the delivery - which occurred without any complication - she had suffered from a gradually increasing right-buttock pain and limp. Magnetic resonance imaging (MRI) revealed a fracture of the right sacral ala. After analgesia and 1 month of home relative bed rest, the patient recovered her functional capacities. Regarding our patient, who had no potential clinical risk factors for osteoporosis, the causal effect of heparin is thus possible but not certain. This case report illustrates the fact that clinicians should have a high suspicion of pelvic fracture in post-partum women, even in very young ones, presenting sudden onset of low back and pelvic pain, especially when they have received heparin during pregnancy. MRI seems to be the key exam because it is able to detect and stage fractures or microfractures.


Simple variant t(8;21) acute myeloid leukemias harbor insertions of the AML1 or ETO genes.
We report on the molecular characterization of two acute myeloid leukemias (AML), one AML-M1 (patient 1) and one AML-M2 (patient 2) with t(8;21)(p21;q22) and t(8;20)(q22;p13), respectively, at diagnosis. The locations of the breakpoints, 21q22 in patient 1 and 8q22 in patient 2, prompted us to search for a cryptic t(8;21)(q22;q22) and involvement of the AML1 and ETO genes. Dual-color fluorescence in situ hybridization (FISH) using whole chromosome painting probes for chromosomes 8, 20, and 21 confirmed the conventional cytogenetic karyotypes. However, dual-color FISH using appropriate ETO and AML1 probes disclosed an insertion of AML1 into 8q22 on the derivative chromosome 8 in patient 1 and of ETO into 21q22 on one chromosome 21 in patient 2, leading to AML1-ETO fusion signals. Both cases expressed an AML1-ETO transcript, shown by reverse transcriptase polymerase chain reaction and cDNA sequencing. Creation of functional AML1-ETO fusion genes in these two simple variant t(8;21) probably occurred through complex mechanisms, combining translocation and insertion of chromosomal segments.


Effects of fatty acids on the growth of Caco-2 cells.
Epidemiological studies suggest that polyunsaturated fatty acids may protect against colorectal neoplasia. In order to explore this observation, cell proliferation and viability, lipid composition, membrane fluidity, and lipid peroxidation were measured in Caco-2 cells after 48h incubation with various fatty acids. Saturated and monounsaturated fatty acids incorporated less well in the membranes than polyunsaturated fatty acids (PUFAs). All of the PUFAs tested had an inhibitory effect on cell proliferation/viability whereas the saturated and monounsaturated fatty acids did not. Addition of palmitic acid had no significant effect on membrane fluidity whereas unsaturated fatty acids increased membrane fluidity in a dose-dependent manner. PUFAs strongly increased tumor cell lipid peroxidation in a dose-dependent manner. Saturated and monounsaturated fatty acids increased lipid peroxidation in this cell line only at high concentration. Preincubation of Caco-2 cells with vitamin E prevented the inhibition of proliferation/viability, the elevation of the MDA concentration and the increased membrane fluidity induced by PUFAs. Our data indicate that PUFAs are potent inhibitors of the growth of colon cancer cells in vitro.


Flavonol glycosides from Elaeagnus lanceollata (Elaeagnaceae).
Two new flavonol glycosides were isolated together with two known glycosides and an ester from the leaves of E. lanceollata Warb. Their structures were characterized by spectroscopic methods.


Impact of deprivation on glycaemic control in youth with type 1 diabetes in the southwestern region of France.
The objective of this multicenter cross-sectional study was to determine predictors of poor glycaemic control in children with type 1 diabetes mellitus (T1DM), particularly with respect to socioeconomic status (SES). Our study population consisted of 1154 children who attended T1DM follow-up consultation with a pediatric diabetes specialist. Clinical and demographic data were retrieved retrospectively from patients' records. Individual deprivation was defined by an EPICES (Evaluation of the Deprivation and Inequalities of Health in Healthcare Centers) score ≥ 30. Patients were assigned to quintiles of the European Deprivation Index (EDI) based on their area deprivation scores. We used multivariable linear regression models to detect potential associations between glycaemic control and indicators of low SES. In total, 33% (n = 376) of patients had an EPICES score ≥ 30 and 23% (n = 268) were in the 5th EDI quintile. Multivariable linear regression analysis showed that poor glycaemic control was associated with both individual (β 0.38; 95%CI 0.26-0.5; p < 0.001) and area deprivation (β 0.26; 95%CI 0.08-0.43; p = 0.004). Demographic factors, body mass index (BMI) and insulin regimen were also independently associated with poor glycaemic control (p < 0.001). Interestingly, access to diabetes technologies was not related to SES or either glycaemic control. Low SES is associated with a higher risk of poor glycaemic control, independently of insulin regimen. BMI, age at the time of consultation, duration of diabetes, and insulin regimen. Also have an impact on HbA1c. These parameters need to be considered when developing novel treatment strategies for children with T1DM to better target at-risk patients.


Liquid biopsy in ovarian cancer: advantages and limitations for prognosis and diagnosis.
Ovarian cancer (OC) is a highly fatal gynecologic malignancy, often diagnosed at an advanced stage which presents significant challenges for disease management. The clinical application of conventional tissue biopsy methods and serological biomarkers has limitations for the diagnosis and prognosis of OC patients. Liquid biopsy is a novel sampling method that involves analyzing distinctive tumor elements secreted into the peripheral blood. Growing evidence suggests that liquid biopsy methods such as circulating tumor cells, cell-free RNA, circulating tumor DNA, exosomes, and tumor-educated platelets may improve early prognosis and diagnosis of OC, leading to enhanced therapeutic management of the disease. This study reviewed the evidence demonstrating the utility of liquid biopsy components in OC prognosis and diagnosis, and evaluated the current advantages and limitations of these methods. Additionally, the existing obstacles and crucial topics for future studies utilizing liquid biopsy in OC patients were discussed.


Implications of Immunotherapy for Pediatric Malignancies: A Summary from the APSA Cancer Committee.
Although survival for many pediatric cancers has improved with advances in conventional chemotherapeutic regimens and surgical techniques in the last several decades, it remains a leading cause of disease-related death in children. Outcomes in patients with recurrent, refractory, or metastatic disease are especially poor. Recently, the advent of alternative classes of therapies, including immunotherapies, have revolutionized systemic treatment for pediatric malignancies. Several classes of immunotherapies, including chimeric antigen receptor (CAR) T cell therapy, transgenic T-cell receptor (TCR)-T cell therapy, bispecific T-cell engagers, and monoclonal antibody checkpoint inhibitors have been FDA-approved or entered early-phase clinical trials in children and young adults. The pediatric surgeon is likely to encounter these therapies during the care of children with malignancies and should be familiar with the classes of therapy, indications, adverse events, and potential need for surgical intervention in these cases. This review from the APSA Cancer Committee offers a brief discussion of the three most encountered classes of immunotherapy in children and young adults and discusses surgical relevance. LEVEL OF EVIDENCE: IV.


Age at menarche and endometrial cancer risk: a dose-response meta-analysis of prospective studies.
Evidence between age at menarche and endometrial cancer risk have been controversial. Therefore, we conducted a meta-analysis of prospective studies to analyze the aforementioned association. Relevant studies were identified by searching PubMed and EMBASE databases until the end of June 2015. A random-effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between menarcheal age and endometrial cancer risk. Our meta-analysis included eight prospective studies involving 4553 subjects with endometrial cancer. The summarized RRs of endometrial cancer for menarcheal age were 0.68 (95%CI = 0.58-0.81, I(2) = 41.9%, P = 0.099, n = 8) when comparing women with oldest category of menarcheal age with women with youngest category of menarcheal age. Notably, there was an 4% reduction in risk for per 2 years delay in menarcheal age (summarized RR = 0.96; 95%CI = 0.94-0.98, I(2) = 45.7%, P = 0.101, n = 6). Additionally, significant inverse associations were consistent within all stratified analyses. There was no evidence of publication bias or significant heterogeneity between subgroups detected by meta-regression analyses. Our findings support the hypothesis that late menarcheal age is inversely associated with endometrial cancer risk. Further larger prospective or pooled studies are warranted to fully adjust for potential confounders and distinguish whether the associations differ by histological subtypes of endometrial cancer.


Green synthesis of multipurpose carbon quantum dots from red cabbage and estimation of their antioxidant potential and bio-labeling activity.
We present a green synthesis of fluorescent carbon quantum dots (CQDs) by using red cabbage (rc) and a one-step hydrothermal approach. The rcCQDs were characterized by various techniques such as UV-visible spectroscopy, transmission electron microscopy (TEM), high-resolution TEM, Fourier-transform infrared spectroscopy, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy. The synthesized rcCQDs exhibited an average size of 3 nm, measured by TEM, blue fluorescence, and a quantum yield of 8.3%. The highest emission band was observed at approximately 402 nm when excited at 330 nm. The rcCQDs exhibited strong antioxidant activities by scavenging 61, 56, and 91% against 2, 2-diphenyl-1-picrylhydrazyl, hydroxyl, and potassium permanganate radicals, respectively. The scavenging activity of rcCQDs was comparable with that of standard antioxidant L-ascorbic acid. Cell Counting Kit (CCK)-8 assay depicted superior bio-compatibility and negligible cytotoxicity of rcCQDs on SH-SY5Y neuroblastoma cells. They were used as a fluorescent probe for bio-labeling of Escherichia coli and Staphylococcus aureus. The viabilities of the labeled bacterial cells were analyzed by AFM and UV-visible spectroscopy. Furthermore, the rcCQDs were utilized as a fluorescent ink, an alternative to pens, and maybe suitable for paints and varnish agents. This study provides detailed mechanistic insights into the antioxidant activity of as-synthesized rcCQDs, which suggest the practical applicability of CQDs for bio-medical applications. Key points • Carbon quantum dots were prepared from red cabbage using the hydrothermal method. • The scavenging activity of rcCQDs was evaluated for DPPH, OH, and KMnO4radicals. • The rcCQDs were used for the labeling of foodborne bacteria. • The rcCQDs could be utilized as fluorescent ink. Graphical abstract Schematic representation of CQDs prepared from red cabbage (rc) with multifunctional applications.


Non-genotoxicity of acrylic acid and n-butyl acrylate in a mammalian cell system (SHE cells).
Acrylic acid (AA), ethyl acrylate (EA) and n-butyl acrylate (BA) are widely used in the production of plastics, coatings and acrylic fibres. Occupational exposure occurs primarily via inhalation and/or skin contact. In chronic inhalation experiments EA and BA did not induce neoplastic changes in rats and mice (Klimisch and Reininghaus 1984; Miller et al. 1985). Additional investigations showed that AA and BA were not carcinogenic in mice after chronic dermal application (De Pass et al. 1984). However, recently other authors reported a weak carcinogenic potential of AA and BA after chronic dermal administration to mice (Cote et al. 1986). The conditions of the latter study lead to the suggestion that the observed tumours had developed secondarily due to the local irritating and corrosive properties of AA and BA. This view is supported by the negative results of AA, EA and BA in the conventional Ames test (Waegemaekers and Bensink 1984). Mutagenicity data in mammalian cell systems of EA were equivocal (Henschler 1986) and were lacking for AA and BA. For this reason the mutagenic potential of AA and BA was investigated in Syrian hamster embryo fibroblasts (SHE cells). DNA repair (UDS assay), chromosomal changes (micronucleus assay) and morphological transformation were chosen as biological end-points.


Hot Air Balloon: An Unusual Cause of Multicasualty Trauma Incident.
Hot air balloon incidents are few and far between compared with the total number of flights. Nevertheless, hot air balloon incidents may produce severe trauma involving several patients and are linked to significant mortality. The prehospital management of injured patients starts after having secured potential surrounding dangers, such as fire or explosion. In the context of a rescue by helicopter, close attention must be paid to potential obstacles, like trees or electrical wires, and the risk of aspiration of the balloon envelope into the rotor. Patients involved in such incidents are often split up in a closed perimeter around the crash point. The severity of the trauma depends essentially on the height of the fall. The most frequent traumatic lesions involve fractures of the lower limbs, the spine, and the pelvis as well as severe burns caused by the balloon fire. Because of the number of patients present, an initial triage is usually required at the site. The use of rescue helicopters can be helpful. They can perform aerial reconnaissance, provide on-site high-level resources, enable access to the patients even in hostile environments, and quickly transport them to trauma center hospitals.


Validation and feasibility of intraoperative three-dimensional transesophageal echocardiographic cardiac output.
In this pilot study, we attempted to validate three-dimensional transesophageal echocardiography (3DTEE) cardiac output and assess its feasibility intraoperatively. Twenty patients undergoing cardiac surgery underwent simultaneous cardiac output determinations during the clinically stable prebypass period by 3DTEE and thermodilution. The correlation coefficient between cardiac output measured by the two methods was 0.86. The 3DTEE mean bias was 0.27 L/min, limits of agreement -1.64 to 2.17 L/min (approximately +/-35%). Three-dimensional data acquisition averaged 43 s; postprocessing took 7 min. Three-dimensional TEE can measure cardiac output and is feasible perioperatively. Measurements have good correlation with thermodilution, though with a significant bias and wide limits of agreement.


Use-dependent properties of flecainide acetate in accessory atrioventricular pathways.
Flecainide acetate has been shown to have use-dependent properties. The use-dependent properties of flecainide were evaluated in 20 patients (13 men and 7 women, mean age 32 +/- 11 years) with accessory atrioventricular connections. Twenty to 30 stimulus drive trains were introduced in either the atrium or ventricle at progressively faster rates. The range of cycle lengths over which anterograde and retrograde conduction block occurred in the accessory pathway was assessed in the drug-free state and after oral loading with flecainide acetate. The block cycle length index was defined as the shortest cycle length during which 1:1 conduction was maintained in the accessory pathway minus the longest cycle length during which block in the accessory pathway occurred on the second paced beat. In the drug-free state, the (mean +/- SD) anterograde and retrograde block cycle length indexes were 20 +/- 12 and 20 +/- 9 ms, respectively. After flecainide therapy, the anterograde and retrograde block cycle length indexes increased to 80 +/- 33 and 65 +/- 29 ms, respectively (p = 0.002 compared with the drug-free state). The block cycle length index did not correlate with serum flecainide levels, but did correlate with other electrophysiologic markers of drug effect on accessory pathway conduction. The change in the block cycle length index demonstrates that flecainide has a progressive effect on accessory pathway conduction at more rapid rates, consistent with its in vitro use-dependent properties. This index is an excellent marker of drug efficacy.


Configuration of the interferon-alpha/beta receptor complex determines the context of the biological response.
Constituents of the Type 1 interferon (IFN) receptor (IFNABR) identified to date include the alpha and beta transmembrane subunits and the associated intracellular kinases, Jak 1 and Tyk 2. In this report, we demonstrate that a human cell type that expresses both subunits of IFNABR, together with Jak 1 and Tyk 2, exhibits a limited binding capacity for and is only partially sensitive to the effects of IFN-alpha/beta, despite adequate levels of the cytoplasmic transcription factors Stat1, Stat2, and Stat3. Specifically, a low affinity interaction between IFN-alpha/beta and cell surface receptors results in ISGF3 (Stat1:2) activation and an antiviral response, yet no IFN-inducible growth inhibition. Using a panel of murine cells that are variably configured with respect to the human IFNABR-alpha/beta subunits, we provide evidence that an additional component(s) encoded on human chromosome 21 is required to confer high affinity binding and IFN-inducible growth inhibition to cells that express the alpha and beta subunits of the IFNABR. The data indicate that transcriptional activation that leads to an antiviral response is mediated by IFN-alpha/beta activation of IFNABR-alpha and IFNABR-beta in the context of a low affinity interaction, yet a high affinity interaction is necessary for signal transducing events that mediate growth inhibition. We provide evidence that the extent of ISGF3 activation correlates directly with the magnitude of an antiviral but not a growth inhibitory response.


Detection of spirochaetal microorganisms by focus floating microscopy in necrobiosis lipoidica in patients from central Europe.
Necrobiosis lipoidica (NL) is a chronic inflammatory skin disease with unknown aetiology. The aim was to determine the presence of spirochaetal microorganisms in NL. Focus-floating microscopy (FFM) is a modified immunohistochemical technique that was developed to detect borrelial spirochaetes within tissue sections. It has proven to be more sensitive for the detection of spirochaetes than polymerase chain reaction (PCR). Fifty-six cases of NL as well as 44 negative and 33 positive controls were investigated for the presence of Borrelia within tissue specimens. Using FFM, Borrelia could be detected in 42 cases (75.0%) and were seen significantly more often in histologically active inflammatory-rich (38/41, 92.7%) than in inflammatory-poor (4/15, 26.7%) cases of NL (P < 0.001). Seven cases investigated with a Borrelia-specific PCR (23s-RNA) remained negative. In contrast, FFM was positive in 30 of 33 (90.9%) positive controls of acrodermatitis chronica atrophicans and 15 of the positive controls (45.5%) were also positive with PCR, whereas no negative controls revealed any microorganisms. Detection of spirochaetes in NL points to a specific involvement of B. burgdorferi or other similar strains in the development of or trigger for this disease.


Possible mechanisms of improved radiation response by cytotoxic RNase, Onconase, on A549 human lung cancer xenografts of nude mice.
The cytotoxic RNase, Onconase (ONC), isolated from amphibian oocytes, was used to study its effect on the radiation response in A549 human NSCLC in vitro and in vivo. In cell culture studies, we found that ONC increased the radiation response by ONC-induced inhibition of O2 consumption (QO2). The occurrence of apoptosis was increased by ONC and was dependent on dosages and time exposure (measured by a Tunnel in situ cell death detection assay). Moreover, ONC inhibited sublethal damage repair (SLDR), confirmed by a split dose experiment. In animal studies, ONC significantly increased the radiation-induced tumor growth delay of A549 tumors in vivo. Using a non-invasive DCE-MRI technology, ONC-induced changes of perfusion were observed in A549 tumors. We concluded that the ONC-induced enhancement in tumor oxygenation was mainly due to the reduction in QO2 rather than an increase in tumor blood flow. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients.


Dipeptidyl peptidase 3 plasma levels predict cardiogenic shock and mortality in acute coronary syndromes.
Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS). Plasma cDPP3 levels were assessed at baseline and 12-24 h after presentation in patients with ACS prospectively enrolled into the multi-centre SPUM-ACS study (n = 4787). Circulating DPP3 levels were associated with in-hospital CS when accounting for established risk factors including the ORBI risk score [per log-2 increase, hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.05-1.82, P = .021]. High cDPP3 was an independent predictor of mortality at 30 days (HR 1.87, 95% CI 1.36-2.58, P < .001) and at one year (HR 1.61, 95% CI 1.28-2.02, P < .001) after adjustment for established risk factors and the GRACE 2.0 score. Compared to values within the normal range, persistently elevated cDPP3 levels at 12-24 h were associated with 13.4-fold increased 30-day mortality risk (HR 13.42, 95% CI 4.86-37.09, P < .001) and 5.8-fold increased 1-year mortality risk (HR 5.79, 95% CI 2.70-12.42, P < .001). Results were consistent across various patient subgroups. This study identifies cDPP3 as a novel marker of CS and increased mortality in patients with ACS. Circulating DPP3 offers prognostic information beyond established risk factors and improves early risk assessment.


Utility and validity of neurite orientation dispersion and density imaging with diffusion tensor imaging to quantify the severity of cervical spondylotic myelopathy and assess postoperative neurological recovery.
Predicting postoperative prognosis with preoperative diagnostic imaging has clinical importance. Recent studies have indicated the utility of diffusion tensor imaging (DTI) to quantify the severity of cervical spondylotic myelopathy (CSM) and assess the prognosis of surgical outcomes. However, how to apply DTI to evaluate CSM in a clinical setting is not fully elucidated. Neurite orientation dispersion and density imaging (NODDI) is a model-based practical diffusion-weighted magnetic resonance imaging analysis for estimating specific microstructural features related directly to neuronal morphology. In a prior study, we indicated preoperative NODDI parameters are a promising tool with which to predict neuronal recovery after decompression surgery in patients with CSM with 2 years follow-up. However, the correlation between NODDI parameters and postoperative long-term outcomes and change of parameters over time postoperatively has remained largely unknown. Retrospective cohort study. To determine the change of parameters of NODDI and conventional DTI over time, and the relationship between parameters and neurological recovery 2 years after surgery. We included 28 consecutive patients with nontraumatic cervical lesions from CSM who underwent laminoplasty and were followed up for >2 years. Patients underwent magnetic resonance imaging before and approximately 2 weeks, 6 months, and 1 year after surgery. In addition to conventional DTI metrics, we evaluated intracellular volume fraction (ICVF) and orientation dispersion index, which are metrics derived from NODDI. The Japanese Orthopedic Association (JOA) scoring system was used before and 2 years after surgery to assess neurological outcome (JOA recovery rate). NODDI and conventional DTI values were measured at the C2-C3 intervertebral level (control value) and the most compressed levels (C3-C7 intervertebral levels) were measured by 3 observers. The changes of these values from preoperatively, 2 weeks after surgery, 6 months after surgery, and 1 year after surgery, were determined. The correlations between preoperative neurological severity, postoperative neuronal recovery, and preoperative DTI or NODDI metrics were determined. No financial or material support was obtained for this study. There is no conflict of interest. The preoperative ICVF and fractional anisotropy at the most compressed level were significantly less than the preoperative values at the control C2-C3 intervertebral level and fractional anisotropy at the most compressed level was increased in the immediate postoperative period. By contrast, ICVF at the most compressed level was not increased in the immediate postoperative period and a significant increase was observed at 6 months after surgery. Preoperative ICVF was significantly correlated with JOA recovery rate at 2 years after surgery. NODDI is a reproducible and reliable method for evaluation of CSM. ICVF improved after surgery and recovery of physical findings accompanied this change. ICVF may be applied clinically to predict postoperative recovery.


Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation.
Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive amyloid formation. Here, we demonstrate the use of aggregation-modulating peptides to knock down CsgA protein into aggregates with low stability and altered morphology. Remarkably, these CsgA-peptides also modulate fibrillation of the unrelated functional amyloid protein FapC from Pseudomonas, possibly through recognition of FapC segments with structural and sequence similarity with CsgA. The peptides also reduce the level of biofilm formation in E. coli and P. aeruginosa, demonstrating the potential for selective amyloid targeting to combat bacterial biofilm.


Prognostic impact of left ventricular noncompaction in patients with Duchenne/Becker muscular dystrophy--prospective multicenter cohort study.
The reported prevalence of left ventricular noncompaction (LVNC) varies widely and its prognostic impact remains controversial. We sought to clarify the prevalence and prognostic impact of LVNC in patients with Duchenne/Becker muscular dystrophy (DMD/BMD). We evaluated the presence of LNVC in patients with DMD/BMD aged 4-64 years old at the study entry (from July 2007 to December 2008) and prospectively followed-up their subsequent courses (n=186). The study endpoint was all-cause death and the presence of LVNC was blinded until the end of the study (median follow-up: 46 months; interquartile range: 41-48 months). There were no significant differences in baseline characteristics between patients with LVNC (n=35) and control patients without LVNC (n=151), with the exception of LV function. Patients with LVNC showed, in comparison with patients without LVNC, a significant negative correlation between age and LVEF (R=-0.7 vs. R=-0.4) at baseline; and showed a significantly greater decrease in absolute LVEF (-8.6 ± 4.6 vs. -4.3 ± 4.5, p<0.001) during the follow-up. A worse prognosis was observed in patients with LVNC (13/35 died) than in patients without LVNC (22/151 died, Log-rank p<0.001). Multivariate Cox analysis revealed that LVNC is an independent prognostic factor (relative hazard 2.67 [95% CI: 1.19-5.96]). LVNC was prevalent in patients with DMD/BMD. The presence of LVNC is significantly associated with a rapid deterioration in LV function and higher mortality. Neurologists and cardiologists should pay more careful attention to the presence of LVNC.


In tandem analysis of CLCN1 and SCN4A greatly enhances mutation detection in families with non-dystrophic myotonia.
Non-dystrophic myotonias (NDMs) are caused by mutations in CLCN1 or SCN4A. The purpose of the present study was to optimize the genetic characterization of NDM in The Netherlands by analysing CLCN1 and SCN4A in tandem. All Dutch consultant neurologists and the Dutch Patient Association for Neuromuscular Diseases (Vereniging Spierziekten Nederland) were requested to refer patients with an initial diagnosis of NDM for clinical assessment and subsequent genetic analysis over a full year. Based on clinical criteria, sequencing of either CLCN1 or SCN4A was performed. When previously described mutations or novel mutations were identified in the first gene under study, the second gene was not sequenced. If no mutations were detected in the first gene, the second gene was subsequently also analysed. Underlying NDM mutations were explored in 54 families. In total, 20% (8 of 40) of our probands with suspected chloride channel myotonia showed no CLCN1 mutations but subsequent SCN4A screening revealed mutations in all of them. All 14 probands in whom SCN4A was primarily sequenced showed a mutation. In total, CLCN1 mutations were identified in 32 families (59%) and SCN4A in 22 (41%), resulting in a diagnostic yield of 100%. The yield of mutation detection was 93% with three recessive and three sporadic cases not yielding a second mutation. Among these mutations, 13 in CLCN1 and 3 in SCN4A were novel. In conclusion, the current results show that in tandem analysis of CLCN1 and SCN4A affords high-level mutation ascertainment in families with NDM.


Cytoreductive surgery in patients with oligometastatic prostate cancer. Systematic review of the scientific literature.
Interest in oligometastatic prostate cancer has spiked due to the emergence of new evidence regarding more specific and accurate imaging, and the wider use of minimally invasive techniques. Nevertheless, the optimal management of this pathology is yet to be determined. Assess the efficacy and safety of cytoreductive surgery in patients suffering from oligometastatic prostate cancer. Systematic review of the scientific literature (01/01/2010-31/12/2021) within the MedLine, Embase, Cochrane Library, Cinahl, Scopus, Spanish Healthcare Technology Assessment Agencies (AETS, Agencias de Evaluación de Tecnologías Sanitarias) and ClinicalTrials.gov databases. The keywords used were prostatectomy, prostatic neoplasm, radical prostatectomy; the free search terms were prostatectomy and oligometastatic prostate. The inclusion criteria comprised studies on patients with oligometastatic prostate cancer who had been operated on using radical cytoreductive prostatectomy. The systematic review included 4 observational studies, 2 clinical trials, and 2 case series, of moderate quality. The results observed suggest that oligometastatic prostate cancer patients who had undergone cytoreductive prostate surgery obtained a benefit in terms of efficacy. Conversely, the majority of these studies showed a reduction in the number of localized complications, when compared to the best systemic treatments. Cytoreductive surgery in this group of patients is a safe procedure that reduces the incidence of localized complications and that presents promising results with regard to survival rates. To date, the lack of prospective trials limits the use of this therapeutic option to experimental environments.


Biological rhythms in the inflammatory response and in the effects of non-steroidal anti-inflammatory drugs.
It is well known that some signs and symptoms of rheumatoid arthritis (RA) vary within a day and between days, and the morning stiffness observed in RA patients has become one of the diagnostic criteria of the disease. Research carried out in the last 10 years confirmed these clinical observations, and circadian, circaseptan or circannual variations were detected in experimental inflammation and in patients with arthritis diseases. The human data showed also that large interindividual differences can be found in the symptoms of RA. The chronopharmacological studies carried out with the non-steroidal anti-inflammatory drugs (NSAID) revealed circadian and circannual variations in the effectiveness, toxicity and pharmacokinetics of NSAID. A review of the available data suggests that peak and trough values found in different arthritic diseases do not occur at the same hour of the day and that the side effects produced by NSAID are more important after the morning than the evening administration. This information should be used by clinicians to determine when to administer drugs to arthritic patients, to optimize the effectiveness of NSAID and/or to reduce the side effects of these drugs. These new data could also be useful to physicians who would like to individualize NSAID use in patients with different arthritic diseases.


drawMD APP-aided preoperative anesthesia education reduce parents anxiety and improve satisfaction.
There is no existing standard format for preoperative anesthesia education. The drawMD APP is an visible preoperative education tool. The aim of this study was to evaluate the effects of drawMD APP on pre-operative anesthesia education. The parents were randomized to receive drawMD APP-aided pre-operative anesthesia education or standard verbal education. Parental anxiety was measured before education (T0) and immediately after education (T1), and after operation (T4). Children's anxiety was assessed before education (T0) and at the operation room (T2). Children's emergence behavior and Parents' satisfaction were assessed after operation (T4). The parents' anxiety levels at T1 and T4 were significantly lower than that of the control. The satisfaction scores in the drawMD group were significantly higher than that in the control group. There were no differences in children's anxiety and the incidence of emergence delirium between the two groups. The drawMD APP-aided pre-operative education is effective in the reduction of parental pre-operative anxiety and in improvement of parents' satisfaction, but has no influence on children. Anesthesiologists can consider using drawMD APP to conduct pre-operative education in parents whose children are scheduled for surgery.


Non-lesional treatments for tremor in Parkinson's disease: A systematic review and meta-analysis.
Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non-lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta-analysis assessing the efficacy/effectiveness and safety of non-lesional treatments for tremor in iPD. Three electronic databases were searched using a combination of title/abstract keywords complemented by hand-searching of reference lists. A random-effects meta-analysis of standardized mean change scores was conducted where appropriate. Some 114 studies met inclusion criteria involving 8045 patients. The meta-analysis revealed an overall reduction of standardized mean change scores by (-0.93 [CI: -1.42; -0.43], p < 0.001) by 14 different dopaminergic and non-dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non-pharmacological interventions for tremor, except for electrical stimulation. The results of this meta-analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high-quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non-lesional treatments in cases with refractory tremor is lacking.


ELISA analysis of beta-secretase cleavage of the Swedish amyloid precursor protein in the secretory and endocytic pathways.
Limiting beta amyloid (Abeta) production could become an important therapeutic target in Alzheimer's disease (AD). Abeta is derived by the sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. A double missense mutation in APP found in a Swedish pedigree (APPsw) elevates Abeta40 and Abeta42 production. Abeta production and, therefore, beta-secretase cleavage of APPsw reportedly occur in the endoplasmic reticulum (ER), Golgi and endocytic compartments. However, the relative contribution of beta-secretase cleavage occurring in each compartment has not been determined. Experiments described here use a novel ELISA to measure the beta-cleaved product, APPswbeta. Using this ELISA, we provide new information regarding the relative amount of beta-secretase cleavage of APPsw that occurs in secretory and endocytic pathways. Using a dilysine retrieval motif to retain APPsw in the ER, we discovered that less than 15% of the beta-secretase cleavage was still detected. Experiments utilizing endocytosis-impaired mutants of APPsw revealed that little or no beta-secretase cleavage of APPsw appears to take place through endocytosis. Surprisingly, deletion of the entire cytoplasmic tail increased both APPswbeta and Abeta secretion, suggesting that protein interactions with this region normally impede beta-secretase cleavage. These results suggest that APPsw is cleaved by beta-secretase late in the secretory pathway.


An expert review of the inverse problem in electrocardiographic imaging for the non-invasive identification of atrial fibrillation drivers.
Electrocardiographic imaging (ECGI) has emerged as a non-invasive approach to identify atrial fibrillation (AF) driver sources. This paper aims to collect and review the current research literature on the ECGI inverse problem, summarize the research progress, and propose potential research directions for the future. The effectiveness and feasibility of using ECGI to map AF driver sources may be influenced by several factors, such as inaccuracies in the atrial model due to heart movement or deformation, noise interference in high-density body surface potential (BSP), inconvenient and time-consuming BSP acquisition, errors in solving the inverse problem, and incomplete interpretation of the AF driving source information derived from the reconstructed epicardial potential. We review the current research progress on these factors and discuss possible improvement directions. Additionally, we highlight the limitations of ECGI itself, including the lack of a gold standard to validate the accuracy of ECGI technology in locating AF drivers and the challenges associated with guiding AF ablation based on post-processed epicardial potentials due to the intrinsic difference between epicardial and endocardial potentials. Before performing ablation, ECGI can provide operators with predictive information about the underlying locations of AF driver by non-invasively and globally mapping the biatrial electrical activity. In the future, endocardial catheter mapping technology may benefit from the use of ECGI to enhance the diagnosis and ablation of AF.


How do I best manage insomnia and other sleep disorders in older adults with cancer?
Insomnia is common in older adults with cancer, with a reported prevalence of 19-60% in prior studies. Cancer treatments are associated with increased risk of insomnia or aggravation of pre-existing insomnia symptoms, and patients who are receiving active cancer treatments are more likely to report insomnia. Insomnia can lead to significant physical and psychological consequences with increased mortality. We discuss physiological sleep changes in older adults, and illustrated the various sleep disorders. We present a literature review on the prevalence and the effects of insomnia on the quality of life in older adults with cancer. We discuss the risk factors and presented a theoretical framework of insomnia in older adults with cancer. We present a case study to illustrate the assessment and management of insomnia in older adults with cancer, comparing and contrasting a number of tools for sleep assessment. There are currently no guidelines on the treatment of sleep disorders in older adults with cancer. We present an algorithm developed at the City of Hope Comprehensive Cancer Center by a multidisciplinary team for managing insomnia, using evidence-based pharmacologic and non-pharmacologic interventions.


Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution.
Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs. To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research. Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design. Comparative effectiveness trial of antihypertensive medications. Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data. Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions. The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier. This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered. In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better-performing groups. National Heart, Lung, and Blood Institute.


Systematic Reviews and Meta-Analyses of Portal Vein Embolization, Associated Liver Partition and Portal Vein Ligation, and Radiation Lobectomy Outcomes in Hepatocellular Carcinoma Patients.
To understand portal vein embolization (PVE), associated liver partition and portal vein ligation (ALPPS) and radiation lobectomy (RL) outcomes in hepatocellular carcinoma (HCC) patients. Systematic reviews of future liver remnant (FLR) percent hypertrophy, proportion undergoing hepatectomy and proportion with major complications following PVE, ALPPS, and RL were performed by searching Ovid MEDLINE, Ovid EMBASE, The Cochrane Library, and Web of Science. Separate meta-analyses using random-effects models with assessment of study heterogeneity and publication bias were performed whenever allowable by available data. Of the 10,616 articles screened, 21 articles with 636 subjects, 4 articles with 65 subjects, and 4 articles with 195 subjects met the inclusion criteria for systematic reviews and meta-analyses for PVE, ALPPS, and RL, respectively. The pooled estimate of mean percent FLR hypertrophy was 30.9% (95%CI: 22-39%, Q = 4034.8, p < 0.0001) over 40.3 +/- 26.3 days for PVE, 54.9% (95%CI: 36-74%, Q = 73.8, p < 0.0001) over 11.1 +/- 3.1 days for ALPPS, and 29.0% (95%CI: 23-35%, Q = 56.2, p < 0.0001) over 138.5 +/- 56.5 days for RL. The pooled proportion undergoing hepatectomy was 91% (95%CI: 83-95%, Q = 43.9, p = 0.002) following PVE and 98% (95%CI: 50-100%, Q = 0.0, p = 1.0) following ALPPS. The pooled proportion with major complications was 5% (95%CI: 2-10%, Q = 7.3, p = 0.887) following PVE and 38% (95%CI: 18-63%, Q = 10.0, p = 0.019) following ALPPS. Though liver hypertrophy occurs following all three treatments in HCC patients, PVE balances effective hypertrophy with a short time frame and low major complication rate.


Penile reconstruction after total penectomy or urethra-sparing total penectomy.
A technique for 1-stage penile reconstruction is described in which several innovations were introduced to improve the functional results. Two flexible rod penile prostheses are wrapped in synthetic mesh, which serves as a scaffold for the growing collagen fibers to replace the tunica albuginea. The proximal portions of the prostheses are placed in the corporeal stumps to provide added stability and the mesh-wrapped prostheses are covered with a scrotal flap. In patients who previously underwent a urethra-sparing penectomy the urethra is included in the reconstructed penis to provide a meatal location at the tip of the penis without the added risks of standard urethral reconstruction.


Adaptation of jejunal to colonic mucosal autografts in experimentally induced short bowel syndrome.
The behavior of jejunal to colonic mucosal autografts was studied in an experimental animal model of short bowel syndrome (SBS). Histological appearances, enterocyte enzyme activities, and in vitro glucose transport were studied at the donor and recipient graft sites in control, short-bowel syndrome, and gastrocolic fistula 5-week-old Sprague-Dawley rats. Small intestinal function was maintained in the jejunocolonic graft after 80% small bowel resection; animals in which small bowel was not resected showed loss of graft function and enzyme activity. This effect is dependent on the presence of jejunal chyme: after gastrocolic fistulae, the jejunum to colon grafts lost jejunal functional activities. Total parenteral nutrition did not alter graft behavior but improved the postoperative mortality of the procedures. The results provide additional information on intestinal adaptation in SBS.


Comparison of high- and low-intensity exercise training early after acute myocardial infarction.
The effects of the intensity of exercise training on cardiorespiratory variables were investigated in a consecutive series of men with recent (median 8 weeks) acute myocardial infarction. Forty-five patients were randomly assigned either to a high- (65 to 75% maximum oxygen consumption rate [VO2max]) or to a low-intensity (less than 45% VO2max) exercise group. Patients engaged in medically supervised aerobic training 3 sessions a week for 12 weeks. With training, mean VO2max significantly increased by 11% (2.09 to 2.31 liters/min) within the high group and by 14% (1.93 to 2.21 liters/min) within the low group. Differences between groups were not statistically significant. Both groups also had comparable changes in heart rate, blood pressure and double-product at submaximal and maximal workloads. Analysis of blood lipids revealed that both groups experienced a significant increase in high density lipoprotein cholesterol. There were no significant changes in total serum cholesterol or triglycerides. These findings suggest that within an unselected population of patients after acute myocardial infarction referred for cardiac rehabilitation, low- and high-intensity exercise training produces relatively similar changes in cardiorespiratory variables during the initial 3 months of exercise training.


Genetic risk factors for Creutzfeldt-Jakob disease.
Prion diseases are a group of fatal neurodegenerative disorders of mammals that share a central role for prion protein (PrP, gene PRNP) in their pathogenesis. Prions are infectious agents that account for the observed transmission of prion diseases between humans and animals in certain circumstances. The prion mechanism invokes a misfolded and multimeric assembly of PrP (a prion) that grows by templating of the normal protein and propagates by fission. Aside from the medical and public health notoriety of acquired prion diseases, the conditions have attracted interest as it has been realized that common neurodegenerative disorders share so-called prion-like mechanisms. In this article we will expand on recent evidence for new genetic loci that alter the risk of human prion disease. The most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD), is characterized by the seemingly spontaneous appearance of prions in the brain. Genetic variation within PRNP is associated with all types of prion diseases, in particular, heterozygous genotypes at codons 129 and 219 have long been known to be strong protective factors against sCJD. A large number of rare mutations have been described in PRNP that cause autosomal dominant inherited prion diseases. Two loci recently identified by genome-wide association study increase sCJD risk, including variants in or near to STX6 and GAL3ST1. STX6 encodes syntaxin-6, a component of SNARE complexes with cellular roles that include the fusion of intracellular vesicles with target membranes. GAL3ST1 encodes cerebroside sulfotransferase, the only enzyme that sulfates sphingolipids to make sulfatides, a major lipid component of myelin. We discuss how these roles may modify the pathogenesis of prion diseases and their relevance for other neurodegenerative disorders.


Author Correction: A New Hadrosaurine (Dinosauria: Hadrosauridae) from the Marine Deposits of the Late Cretaceous Hakobuchi Formation, Yezo Group, Japan.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Who needs capacity?
The UK Law Commission's Discussion Paper, Criminal Liability: Insanity and Automatism, recommends introducing the concept of capacity to the insanity defence. The concept of capacity has an established role in those parts of the law that concern the validity of the decisions that people make, for instance in composing a will or entering into a contract. Making mental capacity a criterion for criminal responsibility in a mentally disordered defendant, however, is potentially problematic. First, the term capacity already has several different meanings in the literature on the jurisprudence of mental abnormality. Second, using the concept of capacity in the way that the Law Commission proposes poses difficulties that relate to the provision of testimony by expert witnesses.


Basic-level individuals.
In this experiment, 4-year-old children interpreted a novel count noun taught ostensively for an unfamiliar object as referring to a basic-level kind (such as PERSON or DOG) rather than to a kind that individuates its members by type of situation (such as PASSENGER or PUPPY). Because ostension does not distinguish a basic-level kind from a situation-restricted kind, this finding suggests that children assume, as a default, reference to a basic-level kind rather than to a situation-restricted kind when they hear a count noun applied to an unfamiliar object in an ostensive definition. The experiment shows that the assumption guides children's interpretation only if the object is unfamiliar, and if no specific information is available calling for a situation-restricted kind interpretation. The proposed word-learning assumption is critical to an understanding of the psychologically privileged manner of individuation, and therefore, of quantification (e.g., counting) involving objects.


Linear combination of multiecho data: short T2 component selection.
The myelin sheath, which is wrapped around the axons in the brain, can be affected by many diseases, resulting in cognitive and physical disability. Other work showed water in the myelin sheath has a T2 approximately 15 ms. The current standard technique to estimate the fraction of myelin water in vivo is to collect multiecho data and fit the decay curves using a nonnegative least-squares (NNLS) algorithm. A new algorithm was developed to calculate optimized coefficients which were used to linearly combine multiecho data to estimate the myelin water signal. A set of simulations showed the new technique was accurate over a broad range of myelin water signal. The myelin water fraction from brain regions in scans from five volunteers, estimated by the linear combination method, agreed with the myelin water fraction estimated by the standard technique. The strength of the new technique is that the linear combination does not assume an underlying T2 model and is 20,000 times faster than NNLS.


Start RA treatment - Biologics or JAK-inhibitors?
Janus Kinase inhibitors (JAKi) have been approved for the treatment of Rheumatoid Arthritis (RA) for several years. They are the first oral advanced treatment with efficacy similar to, if not greater than, biologic agents. Recently, concerns over their safety was raised by the results from Oral Surveillance trial suggesting that tofacitinib, one of the JAKi, was associated with higher cardiovascular adverse events and malignancies than TNF inhibitors (TNFi). Since then, regulatory authorities have added warnings to the labels of JAKi. On this purpose, whether rheumatologists should use JAKi as first line advance treatment has become a controversial topic. Some rheumatologists have argued that biologics should be first line advance treatment since there are extensive effectiveness and safety data. In addition, with the advent of biosimilar drugs, they are the most cost-effective treatment. On the other hand, JAKi are very efficacious and are generally safe apart from older and high-risk patients. When TNFi are contraindicated and in certain RA patients ,especially when an oral drug is preferable, JAKi have significant advantage providing patients are involved in the decision-making process.