Technetium-99m radiolabeling and biological study of epirubicin for in vivo imaging of multi-drug-resistant Staphylococcus aureus infections via single photon emission computed tomography.
The development of functional imaging is a promising strategy for diagnosis and treatment of infectious and cancerous diseases. In this study, epirubicin was developed as a [99m Tc]-labeled radiopharmaceutical for the imaging of multi-drug-resistant Staphylococcus aureus infections. The labeling was carried out using sodium pertechnetate (Na99m TcO4 ; ~370 MBq). The other parameters such as amount of ligand, reducing agent (SnCl2 .2H2 O), and pH were optimized. The highest labeling yield ≥96.98% was achieved when 0.3 mg epirubicin, 13 μg SnCl2 .2H2 O, and ~370 MBq Na99m TcO4 were incubated at pH 7 for 15 min in the presence of ascorbic acid at room temperature. Radiochemical purity, stability, charge, and glomerular filtration rate were studied to evaluate the biological compatibility for in vivo administration. Biodistribution investigations showed radiotracer uptake (13.89 ± 1.56% ID/gm organ) by liver and 7.79 ± 0.38% ID/gm organ by kidneys at 30 min post-injection which promisingly wash out at 24 hr post-injection. Scintigraphy study showed selective uptake in S. aureus-infected tissues in contrast to turpentine oil-induced inflamed tissues. Target-to-non-target ratio (6.7 ± 0.05) was calculated at 1 hr post-injection using SPECT gamma camera. The results of this study reveal that the [99m Tc]-epirubicin can be a choice of imaging and monitoring the treatment process of multi-drug resistant S. aureus bacterial infections.


Purification and characterization of Ca2+/calmodulin-dependent actin-binding proteins from squid retina.
Ca2+/calmodulin (CaM)-dependent actin-binding proteins (CABPs) of 92, 105, 120 and 135 kDa were purified from squid retina. These proteins were eluted from the CaM affinity column in a Ca2+-dependent manner, and binding of the CABPs to F-actin was regulated by Ca2+/CaM. Electron microscopic observations employing the low-angle rotary shadowing technique showed the CABP molecules to have granular shapes similar to the granular proteins associated with actin filaments in squid rhabdomeral microvilli. We have previously reported that these actin filaments are fragmented upon exposure to light [(1988) J. Cell Biol. 106, 1151-1160]. Since the intracellular Ca2+ concentrations of the invertebrate retina are elevated during the light illumination, these results indicate that the CABPs are directly associated with the actin filament in the microvilli of the squid photoreceptors. We therefore suggest that the CABPs may regulate the light-induced structural changes of the microvillar cytoskeleton.


miRNAs expressed differently in cancer stem cells and cancer cells of human gastric cancer cell line MKN-45.
Recent studies show that cancers may originate from special cells named cancer stem cells (CSCs). As miRNAs have a prominent role in regulating cell activities, a question arise, that is, if there is any difference in miRNA expression level between CSC and other cancer cells of human gastric cancer cell line MKN-45. In this study, CSCs were isolated by fluorescence-activated cell sorter based on the expression level of cell surface marker CD44. CSC characteristics were checked using spheroid formation assay and soft agar assay. Using reverse transcriptase polymerase chain reaction (RT-PCR), the expression level of some stemness genes was studied. Real-time q-PCR was used for analysis of the expression level of miRNAs. CSCs were able to make spheroids and colonies, whereas other cancer cells failed to show aforementioned features. In addition, RT-PCR resulted in a difference in the expression levels of Nanog, Sox2, Lin28 and Oct-4 between these two kinds of cells. Real-time RT-PCR analysis demonstrated an increase in mir-21 and mir-302 expression level in CSCs, relative to cancer cells, whereas let-7a expression level was decreased in CSC in comparison with cancer cells, which may be due to their different differentiation level. On the other hand, mir-372, mir-373 and mir-520c-5p were markedly increased in cancer cells in comparison with CSCs. This study shows that there is a difference in miRNA expression level between CSCs and other cancer cells, which reflects dissimilar molecular pathways in these cells. These miRNAs may be promising objects for targeting CSCs specifically and efficiently.


Greening for greater good: investigating the critical factors for customer satisfaction with sustainable e-banking.
This study investigated the impact of efficiency, reliability, responsiveness, safety, and security on customer satisfaction with sustainable e-banking. The study used a quantitative methodology, with data collected from customers of commercial banks in South Punjab, Pakistan. A Likert scale questionnaire was used to collect cross-sectional data. A sample of 350 was analyzed using the Statistical Package for the Social Sciences (SPSS) for testing descriptive statistics, correlation analysis, and regression results. The study's results revealed that efficiency, reliability, responsiveness, safety, and security significantly impacted customer satisfaction with e-banking services. Efficiency and reliability were the most crucial factors influencing customer satisfaction, followed by safety, security, and responsiveness. The research findings have important implications for commercial banks, as they highlight the critical role of these factors in the development of sustainable e-banking practices. Overall, the study provides valuable insights for commercial banks seeking to improve their e-banking services and ensure customer satisfaction. Commercial banks can enhance their competitiveness and achieve sustainable growth in the highly competitive e-banking sector by prioritizing efficiency, reliability, responsiveness, and safety and security.


Evaluation of endometrial thickness by transvaginal ultrasound and baseline risk factors as a predictor for endometrial abnormalities in postmenopausal women.
To evaluate the endometrial thickness (ET) as a predictor of endometrial abnormalities in postmenopausal women and whether consideration of baseline risk factors increases diagnostic accuracy. This is a retrospective observational study of postmenopausal women presenting with bleeding or thickened endometrium (≥4 mm) on ultrasound, between 2003 and 2012. Risk factors for endometrial abnormality were analysed using logistic regression. Of 301 women, 220 were symptomatic and 81 were asymptomatic. The median ET was 6 mm (IQR 4-9) for symptomatic women and 9 mm (IQR 6-12) for asymptomatic women. Abnormal pathology was found in 35 symptomatic (15.9%) and 6 asymptomatic women (7.4%). For each 1 mm increase in ET, the odds of an abnormal diagnosis increased by 16.3% (95% CI 9.6-23.5) for symptomatic and 19.9% (95% CI 3.1-39.3) for asymptomatic women. The Youden's index method identified an ET threshold of ≥7.1mm for symptomatic and ≥14.5mm for asymptomatic women. In symptomatic women the sensitivity was 88.6% (95% CI 72.3-96.3) and specificity 69.2% (95% CI 61.9-75.6), while in asymptomatic women the sensitivity was 50.0% (95% CI 13.9-86.1) and specificity was 89.3% (95% CI 79.5-95.0). The addition of age in the symptomatic women model reduced the sensitivity (82.9% (95% CI 65.7-92.8)) but increased the specificity (72.4% (95% CI 65.3-78.6)). ET is a significant predictor of abnormality. In the absence of risk factors, our study suggests that invasive procedures may be withheld until the ET is ≥7.1 mm with bleeding and ≥14.5 mm in asymptomatic women with no bleeding.


Markers of hepatitis viruses and human T-lymphotropic virus types I/II in patients who have undergone open-heart surgery: evidence of increased risk for exposure to HBV and HEV.
Open-heart procedure is characterized by a high-risk for contracting blood-borne infections. We evaluated the prevalence of several markers of hepatitis viruses (B-E) and human T-cell lymphotropic virus types I/II (HTLV-I/II) in a consecutive series of patients who had undergone open-heart surgery. 204 patients and 158 selected age- and sex-matched healthy volunteers were investigated. Samples were collected at least 6-12 months postoperatively. Commercial enzyme immunoassays and confirmatory immunoblot assays for HCV, HEV and HTLV-I/II were used. None of the subjects tested positive for antibodies to HTLV-I/II. Prevalence of markers of past HBV infection and antibodies to HEV (anti-HEV) were higher in patients than in healthy controls (anti-HBc: 45.1% vs. 31%, p=0.009; anti-HBs: 31.9% vs. 22.2%, p=0.02; anti-HBe: 32.4% vs. 10.1%, p=0.000; anti-HEV: 5.4% vs. 0%, p=0.008). HBsAg and antibodies to HCV did not differ between the groups. HTLV, HBsAg and HCV infection markers did not differ between patients and healthy controls. However, patients had significantly increased prevalence of markers of previous HBV infection suggesting that an intensive vaccination schedule against HBV preoperatively might be helpful in minimizing the risk. The increased prevalence of anti-HEV in cardiac patients requires further investigation. Prospective studies are needed in order to definitely address whether the high prevalence of exposure to HBV and HEV infections in patients who had undergone open-heart surgery is procedure-related or not and whether it has any impact on morbidity of these patients.


Ocular findings in I-cell disease (mucolipidosis type II).
The ultrastructural study of the eyes in seven patients affected with I-cell disease (mucolipidosis type II) revealed important changes in the corneal, scleral, and uveal fibroblasts, while other cells were rarely involved. This explains the inconstant corneal clouding and the absence of ophthalmoscopic abnormalities clinically. At any moment of a patient's life, conjunctival biopsy specimens show characteristic alterations and allow the rapid and secure diagnosis of I-cell disease. This examination should be widely used in the screening of lysosomal diseases.


Different types of cell death and their shift in shaping disease.
Cell death is the irreversible stop of life. It is also the basic physiological process of all organisms which involved in the embryonic development, organ maintenance and autoimmunity of the body. In recent years, we have gained more comprehension of the mechanism in cell death and have basically clarified the different types of "programmed cell death", such as apoptosis, necroptosis, autophagy, and pyroptosis, and identified some key genes in these processes. However, in these previous studies, the conversion between different cell death modes and their application in diseases are rarely explored. To sum up, although many valued discoveries have been discovered in the field of cell death in recent years, there are still many unknown problems to be solved in this field. Facts have proved that cell death is a very complex game, and a series of core players have the ability to destroy the delicate balance of the cell environment, from survival to death, from anti-inflammatory to pro-inflammatory. With the thorough research of the complex regulatory mechanism of cell death, there will certainly be exciting new research in this field in the next few years. The sake of this paper is to emphasize the complex mechanism of overturning the balance between different cell fates and provide relevant theoretical basis for the connection between cell death transformation and disease treatment in the future.


Role of prophylactic antibiotics in elective laparoscopic cholecystectomy: A systematic review and meta-analysis.
The role of prophylactic antibiotics for laparoscopic cholecystectomy in low-risk patients is still unclear. This study aimed to verify the conclusion of previous meta-analyses concerning the effectiveness of antibiotic prophylaxis for elective laparoscopic cholecystectomy in low-risk patients. Comprehensive literature searches were performed on electric databases and manual searches. Randomized controlled trials (RCTs), prospective studies, and retrospective studies comparing antibiotic prophylaxis to placebo or no antibiotics in low-risk elective laparoscopic cholecystectomy were included. This study included 28 RCTs, three prospective studies, and three retrospective studies. In RCTs, prophylactic antibiotics did not prevent deep surgical site infections (SSI) (RR 1.10, 95% confidence interval [CI] [0.45-2.69], p=0.84) but reduced SSI (RR 0.70, 95% CI [0.53-0.94], p=0.02), and superficial SSI (RR 0.58, 95% CI [0.42-0.82], p=0.01). Prospective studies showed prophylactic antibiotics did not reduce superficial SSI (RR 0.35, 95% CI [0.01-8.40], p=0.52) but reduced SSI (RR 0.12, 95% CI [0.04-0.35], p=0.0001). In retrospective studies, antibiotic prophylaxis did not reduce SSI (RR 1.59, 95% CI [0.30-8.32], p=0.58). The pooled data (12121 patients) including RCTs and prospective and retrospective studies showed that prophylactic antibiotics were not effective in preventing deep SSI (RR 1.01 95% CI [0.46-2.21], p=0.98) but effective in reducing SSI (RR 0.67, 95% CI [0.51-0.88], p=0.003) and superficial SSI (RR 0.61, 95% CI [0.45-0.83], p=0.002). The use of prophylactic antibiotics is effective for reducing the incidence of SSI and superficial SSI but is not effective for preventing deep SSI in low-risk patients who underwent elective laparoscopic cholecystectomy.


Coupled experimental and computational approach to stomach biomechanics: Towards a validated characterization of gastric tissues mechanical properties.
Gastric diseases are one of the most relevant healthcare problems worldwide. Interventions and therapies definition/design mainly derive from biomedical and clinical expertise. Computational biomechanics, with particular regard to the finite element method, provides hard-to-measure quantities during in-vivo tests, such as strain and stress distribution, leading to a more comprehensive and promising approach to improve the effectiveness of many different clinical activities. However, reliable finite element models of biological organs require appropriate constitutive formulations of building tissues, whose parameters identification needs an experimental campaign consisting in different tests on human tissues and organs. The aim of the reported here research activities was the identification of mechanical properties of human gastric tissues. Human gastric specimens were tested at tissue, sub-structural and structural levels, by tensile, membrane indentation and inflation tests, respectively. On the other hand, animal experimentations on tissue layers from literature pointed out the mechanical response at sub-tissue level during tensile loading conditions. In detail, the analysis of experimental results at sub-tissue and tissue levels led to a fibre-reinforced visco-hyperelastic constitutive formulation and to the identification of gastric layers mechanical behaviour. Results from experimentations on human samples were coupled with data derived from animal models. Data from sub-structural and structural experimentations were exploited to upgrade and validate the constitutive formulations and parameters. The developed investigations led to a reliable constitutive framework of human gastric tissues that both describe stomach mechanical functionality and allow computational investigations. Indeed, the comparisons among average computational data and experimental medians provided the following RMSEs (Root Mean Square Errors): 0.89 N, 0.15 N for corpus and fundus during membrane indentation test, respectively, and 0.44 kPa during inflation test. Accounting for the magnitude of experimental and computational data, the RMSEs can be considered low and acceptable because they concerned biological samples. In fact, biological tissues and structures are affected by a high inherent inter-samples' variability, which is detectable in both the geometrical configuration and the mechanical behaviour. The specific values of the here reported RMSEs ensured the reliability of the achieved parameters and the quality of the overall developed procedure. Reliable computational models of the gastric district could become efficient clinical tools to find out the main crucial aspects of bariatric procedures, such as the mechanical stimulation of gastric mechano-receptors. Moreover, the methods of computational biomechanics will permit to run the preliminary tests of new and innovative bariatric procedures, on one hand, predicting the successful rate and the effectiveness, and, on other hand, reducing the use of animal testing.


Mannose-binding lectin deficiency--revisited.
There is an emerging interest for mannose-binding lectin (MBL) due to its role in innate immunity. In this survey we present a mixture of old and new data describing the effect MBL polymorphisms may have on the level and function of the molecule. Three single nucleotide substitutions in exon 1 of the mbl2 gene cause a dominant decrease of functional MBL in the circulation. Additionally, promoter variants influence expression of MBL. It has been assumed that the structural variant alleles may disrupt the assembly of MBL trimers or accelerate the degradation of the protein, thereby causing the decrease in MBL serum concentrations. We have analysed 1183 different sera in a double sandwich antibody ELISA using the same antibody to capture and detect MBL and find the same results as have been presented previously showing that different MBL promoter alleles have profound effect of on the MBL serum concentration. The use of a new anti-MBL monoclonal antibody, however, has shown that the amount of MBL in the circulation is less dependent on the presence of structural variant alleles than previously anticipated. Molecular characterisation of MBL revealed that sera from donors homozygous for the normal MBL genotype predominantly contained high molecular weight MBL, while sera from individuals heterozygous for the variant alleles contained both high and low molecular weight MBL. The ratio between high and low molecular weight MBL was dependent on the MBL promoter type on the normal haplotype. Sera deriving from individuals homozygous for MBL variant alleles contained mainly low molecular weight MBL. Of the different oligomers of MBL only the high molecular weight forms bound mannan efficiently and activated complement. In contrast to a previous notion, we demonstrate that variant alleles give rise to relatively high levels of MBL in the circulation. However, the variant MBL has lower molecular weight and is dysfunctional compared to normal MBL. The physiological relevance of variant MBL remains to be established.


Dopamine d1 and d2 receptor antagonism in the preoptic area produces different effects on maternal behavior in lactating rats.
The preoptic area (POA) is critical for maternal behavior in rats but little is known about what neurotransmitters released here influence maternal responding. POA infusion of 10 microg (but not 2 microg) of the dopamine D1 receptor antagonist SCH-23390 greatly impaired retrieval and licking of pups but not other maternal or nonmaternal behaviors in lactating rats. In contrast, POA infusion of 10 microg (but not 2 microg) of the D2 receptor antagonist raclopride facilitated nursing but did not affect oral maternal behaviors. SCH-23390 in the medial hypothalamus tended to impair licking but not retrieval. Raclopride in the medial hypothalamus had no effects. Therefore, D1 and D2 receptor activity, particularly in the POA, is important for regulating different maternal behaviors.


The use of real-time image stabilization and augmented reality eyewear in the treatment of oscillopsia.
The symptom of oscillopsia in patients with bilateral vestibular loss (BVL) can be reduced as dynamic visual acuity (DVA), the reduction in visual acuity during head movement, is improved by using real-time image stabilization, delivered by augmented reality eyewear. Tertiary multidisciplinary neurotology clinic. Prospective experimental study. Immersive virtual reality glasses used in combination with a compact digital video camera were used. A software algorithm was developed that used a center-weighted Lucas-Kanade optical flow method to stabilize video in real time. Six patients with BVL were tested for changes in DVA using the eyewear. The ability to read a Snellen chart during a 2-Hz oscillating head rotation DVA test was measured. For combined scores of vertical and horizontal head rotations, the mean number of lines readable at rest was 7.86, which dropped to 2.77 with head movement (a combination of vertical and horizontal perturbations). This increased to a mean of 6.14 lines with the image stabilization software being activated. This difference was statistically significant (P < .001). This is the first successful attempt to improve dynamic visual acuity in patients with bilateral vestibular loss. Recent hardware upgrades are promising in improving these results even further.


Anisotropic conductance at improper ferroelectric domain walls.
Transition metal oxides hold great potential for the development of new device paradigms because of the field-tunable functionalities driven by their strong electronic correlations, combined with their earth abundance and environmental friendliness. Recently, the interfaces between transition-metal oxides have revealed striking phenomena, such as insulator-metal transitions, magnetism, magnetoresistance and superconductivity. Such oxide interfaces are usually produced by sophisticated layer-by-layer growth techniques, which can yield high-quality, epitaxial interfaces with almost monolayer control of atomic positions. The resulting interfaces, however, are fixed in space by the arrangement of the atoms. Here we demonstrate a route to overcoming this geometric limitation. We show that the electrical conductance at the interfacial ferroelectric domain walls in hexagonal ErMnO(3) is a continuous function of the domain wall orientation, with a range of an order of magnitude. We explain the observed behaviour using first-principles density functional and phenomenological theories, and relate it to the unexpected stability of head-to-head and tail-to-tail domain walls in ErMnO(3) and related hexagonal manganites. As the domain wall orientation in ferroelectrics is tunable using modest external electric fields, our finding opens a degree of freedom that is not accessible to spatially fixed interfaces.


The extremes of spinal motion: a kinematic study of a contortionist in an open-configuration magnetic resonance scanner: case report.
Observational case study on a female contortionist. To investigate how the human spine of a young athlete aligns during extreme body contortions. To our knowledge, there are no data available in the literature on the spinal kinematics under extreme body contortions. Conventional and kinematic magnetic resonance imaging was used to study a 22-year-old female Chinese contortionist. The images were analyzed with regard to abnormal segmental motion and degenerative alterations. No abnormal segmental motion was observed. The patient had a normal spine beside a mild anterior displacement of L1 relative to L2, with mild disc degeneration and small anterior spondylosis. In addition, a mild disc degeneration was observed at T4/5. No other abnormal findings were diagnosed. The kinematic magnetic resonance investigation of the presented case did not reveal any evidence for abnormal segmental motion or subluxation in extreme body contortions and indicates that this excessive motion results from extreme spinal flexibility.


Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases.
Despite indications for resection of colorectal liver metastases having expanded, debate continues about identifying patients that may benefit from surgery. Clinicopathologic data from a total of 700 patients was gathered between January 1993 and January 2006 from a prospectively maintained dataset. Of these, 687 patients underwent resection for colorectal liver metastases. The median age of patient was 64 years and 36.8% of patients had synchronous disease. The overall 5-year survival was 45%. The presence of an inflammatory response to tumor (IRT), defined by an elevated C-reactive protein (>10 mg/L) or a neutrophil/lymphocyte ratio of >5:1, was noted in 24.5% of cases. Only the number of metastases and the presence or absence of an IRT influenced both overall and disease-free survival on multivariable analysis. A preoperative prognostic score was derived: 0 = less than 8 metastases and absence of IRT; 1 = 8 or more metastases or IRT, and 2 = 8 or more metastases and IRT-from the results of the multivariable analysis. The 5-year survival of those scoring 0 was 49% compared with 34% for those scoring 1. None of the patients that scored 2 were alive at 5 years. The preoperative prognostic score is a simple and effective system allowing preoperative stratification.


Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer.
Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early metazoan phylostrata. The up-regulation of unicellular metabolic and drug-resistance pathways and the downregulation of pathways related to circadian clock were identified. This evolutionary shift was associated with the enrichment of ploidy with bivalent genes (p < 10-16). The protein interactome of activated bivalent genes revealed the increase of the connectivity of unicellulars and (early) multicellulars, while circadian regulators were depressed. The mutual polyploidy-c-MYC-bivalent genes-associated protein network was organized by gene-hubs engaged in both embryonic development and metastatic cancer including driver (proto)-oncogenes of viral origin. Our data suggest that, in cancer, the atavistic shift goes hand-in-hand with polyploidy and is driven by epigenetic mechanisms impinging on development-related bivalent genes.


Medium-Term Outcomes of COVID-19 Infection After Kidney Transplantation for Ongoing Living and Deceased Kidney Transplantations within the COVID-19 Pandemic.
To present the early to midterm experience of two referral kidney transplantation centers with living and deceased kidney transplantations that were performed within the COVID-19 pandemic. All cases performed in two referral centers in Iran within the COVID-19 pandemic were investigated. Transplantations were performed from May 2020 to February 2021. The protocol for screening included nasopharyngeal RT-PCR with chest CT scan for living and deceased transplantations in center A and RTPCR for living transplantations and chest CT scan for deceased transplantations in center B. Patients were followed for 14-26 months after transplantation regarding COVID-19 infection and its outcomes in case of infection. 103 kidney transplantations were performed during the study period including 54 (52.4%) living and 49 (47.6%) deceased kidney transplantations. Twenty-four recipients (23.3%) and a living donor (1%) were infected with COVID-19. The severity of COVID-19 infection was mild, moderate, severe, and critical in 16 (66.6%), 4 (16.6%), 2 (8.4%), and 2 patients (8.4%), respectively. Two mortalities were observed within transplantation recipients with COVID-19 infection (1.9%). 87.5% (7/8) COVID-19 infections in center B were observed in recipients of deceased transplantations who were screened only by chest CT scan. The results of this study indicate a low frequency of COVID-19 mortality (1.9% for the whole cohort and 8.3% within COVID-19 infected patients) for recipients of living and deceased kidney transplantation that were performed within the COVID-19 pandemic. The above findings highlight for the first time in a large study the probability of living kidney transplantation during the COVID-19 pandemic in case strict screening of donors and recipients and close supervision of operating rooms and wards are implemented. We further hypothesize the inadequacy of chest CT scan for screening of COVID-19 in kidney transplantation surgery candidates.


Parathyroid and ultimobranchial glands of the sand boa, eryx johnii Daudin.
Eryx johnii and E. conicus possess two pairs of parathyroid glands (PTG) and one pair of ultimobranchial glands (UBG). The PTG is composed of cell cords and follicles, and is well vascularized. The presence of large vesicles with ciliated and glandular epithelium is the most striking feature of the PTG in E. johnii. Accessory PTG tissues are present. The unique feature of equal sized UBGs in Eryx is their location, i.e., bilaterally parallel and rostrally away from the thyrothymic region. The UBG is composed of follicles and cell aggregates, which are interspersed in a vascularized connective tissue stroma; ciliated and goblet cells are frequently present. The UBG of Eryx shows aging variation, but not seasonal changes; seasonal histological variations are observed in the PTG.


Preliminary experience of a PDCA-cycle and quality management based training curriculum for rat liver transplantation.
As repeatedly operating rat liver transplantation (LTx) until animals survive is inefficient in respect to time and use of living animals, we developed a new training concept. METHODS AND CONCEPTS: Training was divided into four phases: pretraining-phase, basic-microsurgical-training phase, advanced-microsurgical-training phases, and expert-microsurgical-training phase. Two "productivity-phases" were introduced right after the basic- and advanced-microsurgical-training phases, respectively, to allow the trainee to accumulate experience and to be scientifically productive before proceeding to a more complex procedure. PDCA cycles and quality criteria were employed to control the learning-process and the surgical quality. Predefined quality criteria included survival rate, intraoperative, postoperative, and histologic parameters. Three trainees participated in the LTx training and achieved their first survival record within 4-10 operations. All of them completely mastered the LTx in fewer procedures (31, 60 and 26 procedures) as reported elsewhere, and the more complex arterialized or partial LTx were mastered by trainee A and B in additional 9 and 13 procedures, respectively. Fast progress was possible due to a high number of training in the 2 Productivity-phases. The stepwise and PDCA-based training program increased the efficiency of LTx training, whereas the constant application and development of predefined quality criteria guaranteed the quality of microsurgery.


Four-dimensional sonography with B-flow imaging and spatiotemporal image correlation for visualization of the fetal heart.
To use B-flow imaging with 4-dimensional (4D) sonography and spatiotemporal image correlation (STIC) in the evaluation of normal fetal heart and congenital heart disease during pregnancy. Volume data sets of the fetal heart were acquired with automated transverse and longitudinal sweeps of the anterior chest wall. We studied 13 normal fetuses and 2 fetuses with congenital heart disease (1 double-outlet right ventricle and 1 hypoplastic left heart syndrome) at gestation ages ranging from 13 to 39 weeks using transabdominal 4D B-flow sonography with STIC (4D BF-STIC). 4D BF-STIC demonstrated dynamic angiographic features in both normal and abnormal fetal hearts. 4D BF-STIC images could not be obtained in 2 normal fetuses at 18.1 and 33.1 weeks because of the high fetal heart rate and inappropriate fetal position. In normal fetal heart, characteristic hemodynamic changes in both atria and ventricles were clearly demonstrated in systole and diastole. 4D BF-STIC also allowed visualization of the relationship, size, and course of the outflow tracts, thus helping the examiner to better understand the relationships between the vessels. In a case of hypoplastic left heart syndrome, dramatic hemodynamic changes including the right atrium, right ventricle, and pulmonary artery were evident. In a case of double-outlet right ventricle with ventricular septal defect, left-to-right shunt flow through a ventricular septal defect was clearly shown, as were great arteries originating in parallel from the right ventricle. 4D BF-STIC provides a means of real-time 3-dimensional evaluation of fetal intracardiac and extracardiac hemodynamics in the second and third trimesters. This novel technique assists in the evaluation of fetal cardiac hemodynamics and may play an important role in future fetal cardiac research and in the evaluation of congenital heart disease in the fetus.


MTHFR C677T Polymorphism is Associated with Tumor Response to Preoperative Chemoradiotherapy: A Result Based on Previous Reports.
Preoperative chemoradiotherapy (pRCT) followed by surgery has been widely practiced in locally advanced rectal cancer, esophageal cancer, gastric cancer and other cancers. However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response. It is very important to develop biomarkers (e.g., gene polymorphisms) to identify patients who have a higher likelihood of responding to pRCT. Recently, a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and epidermal growth factor receptor (EGFR) genes with the tumor response to pRCT; however, the results were inconsistent and inconclusive. A systematic review and meta-analysis was performed by searching relevant studies about the association of MTHFR and EGFR polymorphisms with the tumor regression grade (TRG) in response to pRCT in databases of PubMed, EMBAS, Web of science, Chinese National Knowledge Infrastructure, and Wanfang database up to March 30, 2015. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the association under 5 genetic models. A total of 11 eligible articles were included in the present meta-analysis, of which 8 studies were performed in rectal cancer and 3 studies were performed in esophageal cancer. We finally included 8 included studies containing 839 cases for MTHFR C677T, 5 studies involving 634 cases for MTHFR A1298C, 3 studies containing 340 cases for EGFR G497A, and 4 studies containing 396 cases for EGFR CA repeat. The pooled analysis results indicated that MTHFR C677T might be correlated with the tumor response to pRCT under the recessive model (CC vs. CTTT) in overall analysis (OR=1.426(1.074-1.894), P=0.014), rectal cancer (OR=1.483(1.102-1.996), P=0.009), and TRG 1-2 vs. 3-5 group (OR=1.423(1.046-1.936), P=0.025), while other polymorphism including MTHFR A1298C, EGFR G497A, and EGFR CA repeat polymorphisms exerted significant association under all genetic models in overall analysis or subgroup analysis. MTHFR C677T might be correlated with the tumor response to pRCT. Further well-designed, larger-scale epidemiological studies are needed to validate our results.


1-naphthyl N-methyl carbamate effect on intra- and extracellular concentrations of arachidonic acid metabolites, and on the chemiluminescence generation by mouse peritoneal macrophages.
1-Naphthyl N-methyl carbamate (carbaryl), potent carbamate insecticide with anticholinesterase activity, was tested for its ability to affect mouse peritoneal macrophages in particular arachidonic acid (AA) metabolism and oxidative burst. Carbaryl inhibited in a dose-related manner the reactive oxygen intermediate dependent chemiluminescence (CL) induced by opsonized zymosan (OZ), 12-O-tetradecanoyl phorbol-13-acetate (TPA) and calcium ionophore (A23187); this carbamate did not affect CL-mediated by AA. The intracellular and extracellular concentrations of prostaglandins (PGs) and 5-hydroxyeicosatetraenoic (5-HETE) generated in macrophages stimulated with OZ has been investigated for various periods. Carbaryl effect displayed two successive phases on AA metabolism stimulation. In a first phase (up to 2-15 min), carbaryl did not alter the rapid AA metabolite synthesis (total amount of intra- and extracellular metabolites) but it increased intracellular concentration of PGE2, PGA2, PGF2 alpha and decreased 5-HETE intracellular concentration. In a second phase (after 2-15 min), carbaryl inhibited AA metabolite synthesis. The release of cyclooxygenase (CO) and lipoxygenase (LO) metabolites decreased, in particular PGF2 alpha and PGD2 which in addition seemed to be submit to a cellular retention; the inhibition of other metabolite release appeared essentially related to the inhibition of their synthesis since the intracellular amount did not augment. The inhibition by carbaryl of the NADPH-oxidase dependent CL induced by OZ may be related to the alteration of the intra- and extracellular concentrations of AA metabolites.


Single-trial ERP Quantification Using Neural Networks.
Traditional approaches to quantify components in event-related potentials (ERPs) are based on averaging EEG responses. However, this method ignores the trial-to-trial variability in the component's latency, resulting in a smeared version of the component and underestimates of its amplitude. Different techniques to quantify ERP components in single trials have therefore been described in literature. In this study, two approaches based on neural networks are proposed and their performance was compared with other techniques using simulated data and two experimental datasets. On the simulated dataset, the neural networks outperformed other techniques for most signal-to-noise ratios and resulted in better estimates of the topography and shape of the ERP component. In the first experimental dataset, the highest correlation values between the estimated latencies of the P300 component and the reaction times were obtained using the neural networks. In the second dataset, the single-trial latency estimation techniques showed an amplitude reduction of the N400 effect with age and ascertained this effect could not be attributed to differences in latency variability. These results illustrate the applicability and the added value of neural networks for the quantification of ERP components in individual trials. A limitation, however, is that simulated data is needed to train the neural networks, which can be difficult when the ERP components to be found are not known a priori. Nevertheless, the neural networks-based approaches offer more information on the variability of the timing of the component and result in better estimates of the shape and topography of ERP components.


Complement regulates conventional DC-mediated NK-cell activation by inducing TGF-β1 in Gr-1+ myeloid cells.
Complement activation modulates DC-mediated T-cell activation, but whether complement affects DC-mediated priming of NK cells is unknown. Here, we demonstrated that conventional DCs (cDCs) from C3(-/-) and C5aR(-/-) mice are hyperresponsive to polyI:C, a TLR3 ligand, leading to enhanced NK-cell activation. We found that cDCs lack C5a receptor (C5aR) and do not respond to C5a directly. Depletion of Gr-1(+) myeloid cells augments polyI:C-induced cDC activation in WT but not in C3(-/-) or C5aR(-/-) mice, indicating that the effect of complement activation on cDCs is indirectly mediated through C5aR-expressing Gr-1(+) myeloid cells. We further demonstrated that the mechanism by which Gr-1(+) myeloid cells regulate the activity of cDCs involves C5a-dependent TGF-β1 production in Gr-1(+) myeloid cells. C5a enhances and blocking C5aR decreases TGF-β1 production in cultured bone marrow Gr-1(+) CD11b(+) cells. C5aR deficiency is associated with reduced circulating TGF-β1 levels, while depleting Gr-1(+) myeloid cells abrogates this difference between WT and C5aR(-/-) mice. Lastly, we showed that enhanced cDC-NK-cell activity in C3(-/-) mice led to delayed melanoma tumor growth. Thus, complement activation indirectly regulates cDC-NK-cell activation in response to inflammatory stimuli such as TLR3 by promoting TGF-β1 production in Gr-1(+) myeloid cells at steady state.


Mitogenome evidence shows two radiation events and dispersals of matrilineal ancestry from northern coastal China to the Americas and Japan.
Although it is widely recognized that the ancestors of Native Americans (NAs) primarily came from Siberia, the link between mitochondrial DNA (mtDNA) lineage D4h3a (typical of NAs) and D4h3b (found so far only in East China and Thailand) raises the possibility that the ancestral sources for early NAs were more variegated than hypothesized. Here, we analyze 216 contemporary (including 106 newly sequenced) D4h mitogenomes and 39 previously reported ancient D4h data. The results reveal two radiation events of D4h in northern coastal China, one during the Last Glacial Maximum and the other within the last deglaciation, which facilitated the dispersals of D4h sub-branches to different areas including the Americas and the Japanese archipelago. The coastal distributions of the NA (D4h3a) and Japanese lineages (D4h1a and D4h2), in combination with the Paleolithic archaeological similarities among Northern China, the Americas, and Japan, lend support to the coastal dispersal scenario of early NAs.


Control of stem cell renewal and fate by YAP and TAZ.
Complex physiological processes control whether stem cells self-renew, differentiate or remain quiescent. Two decades of research have placed the Hippo pathway, a highly conserved kinase signalling cascade, and its downstream molecular effectors YAP and TAZ at the nexus of this decision. YAP and TAZ translate complex biological cues acting on stem cells - from mechanical forces to cellular metabolism - into genome-wide effects to mediate stem cell functions. While aberrant YAP/TAZ activity drives stem cell dysfunction in ageing, tumorigenesis and disease, therapeutic targeting of Hippo signalling and YAP/TAZ can boost stem cell activity to enhance regeneration. In this Review, we discuss how YAP/TAZ control the self-renewal, fate and plasticity of stem cells in different contexts, how dysregulation of YAP/TAZ in stem cells leads to disease, and how therapeutic modalities targeting YAP/TAZ may benefit regenerative medicine and cancer therapy.


Replication of an enteric bovine coronavirus in intestinal organ cultures.
A coronavirus isolated in tracheal organ cultures from the faeces of a calf with diarrhoaea readily multiplied on passage in intestinal organ cultures. Evidence for multiplication was obtained by the production of viral haemagglutinin in organ culture fluids and the presence of immunofluorescence and viral particles in the columnar epithelial cells of the villi. Thus virus multiplication was studied in vitro in the cell type in which it multiplies naturally.


Plasma proteomic approach in patients with heart failure: insights into pathogenesis of disease progression and potential novel treatment targets.
To provide insights into pathogenesis of disease progression and potential novel treatment targets for patients with heart failure by investigation of the plasma proteome using network analysis. The plasma proteome of 50 patients with heart failure who died or were rehospitalised were compared with 50 patients with heart failure, matched for age and sex, who did not have an event. Peptides were analysed on two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC ESI-MS/MS) in high definition mode (HDMSE). We identified and quantified 3001 proteins, of which 51 were significantly up-regulated and 46 down-regulated with more than two-fold expression changes in those who experienced death or rehospitalisation. Gene ontology enrichment analysis and protein-protein interaction networks of significant differentially expressed proteins discovered the central role of metabolic processes in clinical outcomes of patients with heart failure. The findings revealed that a cluster of proteins related to glutathione metabolism, arginine and proline metabolism, and pyruvate metabolism in the pathogenesis of poor outcome in patients with heart failure who died or were rehospitalised. Our findings show that in patients with heart failure who died or were rehospitalised, the glutathione, arginine and proline, and pyruvate pathways were activated. These pathways might be potential targets for therapies to improve poor outcomes in patients with heart failure.


A multimodal X-ray spectroscopy investigation of uranium speciation in ThTi2O6 compounds with the brannerite structure.
ThTi2O6 derived compounds with the brannerite structure were designed, synthesised, and characterised with the aim of stabilising incorporation of U5+ or U6+, at dilute concentration. Appropriate charge compensation was targeted by co-substitution of Gd3+, Ca2+, Al3+, or Cr3+, on the Th or Ti site. U L3 edge X-ray Absorption Near Edge Spectroscopy (XANES) and High Energy Resolution Fluorescence Detected U M4 edge XANES evidenced U5+ as the major oxidation state in all compounds, with a minor fraction of U6+ (2-13%). The balance of X-ray and Raman spectroscopy data support uranate, rather than uranyl, as the dominant U6+ speciation in the reported brannerites. It is considered that the U6+ concentration was limited by unfavourable electrostatic repulsion arising from substitution in the octahedral Th or Ti sites, which share two or three edges, respectively, with neighbouring polyhedra in the brannerite structure.


Cerebral gas embolism associated with central venous catheter: Systematic review.
Cerebral gas embolism (CGE) is a potentially catastrophic complication of central venous catheters (CVCs) manipulation or accidental disconnection, which is rarely reported in the literature. This systematic review aims to characterize the clinical manifestations, imaging features and outcome of CGE associated with CVCs. Systematic literature search of all published cases of CGE associated with CVCs, and identification of previously unreported local cases. Descriptive analysis of all cases, mortality analysis for cases with individualized data. Of the 158 patients with CGE associated with CVCs found, 71.8% were male and mean age was 56.4years. CGE symptoms frequently occurred while in the upright position. The most frequent neurological manifestation was sudden-onset focal neurological sign (67.7%), followed by coma (59.5%), epileptic seizures (24.7%) and encephalopathy (21.5%). Imaging revealed intracranial air bubbles in 69.1% and cerebral ischemia or edema was demonstrated in 66.7%. Overall mortality was 21.7%, and clinical predictors of mortality were increasing age (p<0.001), coma (p=0.001), cardiorespiratory arrest shortly after symptom onset (p<0.001) and male sex (p=0.035). CGE associated with CVCs may mimic ischemic stroke, but patients frequently present a severe vigilance disturbance and epileptic seizures. Mortality occurs in 1/5 of patients, which substantiates implementation of protocols and measures to prevent this severe complication of CVC use.


Naive Expectations to Resignation: A Comparison of Life Descriptions of Newly Diagnosed Versus Chronic Persons Living With Stage D HF.
This study examined life descriptions of persons with stage D heart failure (HF) comparing those newly diagnosed to those with chronic HF. A secondary analysis of interviews from 75 participants followed in a longitudinal study of persons with stage D HF was thematically analyzed. There were 24 participants who were recently diagnosed with stage D HF (less than 2 years) and 51 participants with HF longer than 2 years. Both groups shared life descriptions along a continuum, where recently diagnosed participants described naive expectations with hope for improvement, while the chronic group appeared resigned to their fate and the reality of the limitations of living with HF. Four themes illustrated differences between the groups: outlook on life, activity adjustments, understanding of HF, and mood. Although persons with stage D HF share the same life descriptions, they have differing perspectives of life with HF. Findings from this study can help health-care providers tailor interventions based on the length of time from diagnosis.


Trends in Intensive Care Admissions and Outcomes of Stroke Patients Over 10 Years in Brazil: Impact of the COVID-19 Pandemic.
The coronavirus 2019 (COVID-19) pandemic affected stroke care worldwide. Data from low- and middle-income countries are limited. What was the impact of the pandemic in ICU admissions and outcomes of patients with stroke, in comparison with trends over the last 10 years? Retrospective cohort study including prospectively collected data from 165 ICUs in Brazil between 2011 and 2020. We analyzed clinical characteristics and mortality over a period of 10 years and evaluated the impact of the pandemic on stroke outcomes, using the following approach: analyses of admissions for ischemic and hemorrhagic strokes and trends in in-hospital mortality over 10 years; analysis of variable life-adjusted display (VLAD) during 2020; and a mixed-effects multivariable logistic regression model. A total of 17,115 stroke admissions were analyzed, from which 13,634 were ischemic and 3,481 were hemorrhagic. In-hospital mortality was lower after ischemic stroke as compared with hemorrhagic (9% vs 24%, respectively). Changes in VLAD across epidemiological weeks of 2020 showed that the rise in COVID-19 cases was accompanied by increased mortality, mainly after ischemic stroke. In logistic regression mixed models, mortality was higher in 2020 compared with 2019, 2018, and 2017 in patients with ischemic stroke, namely, in those without altered mental status. In hemorrhagic stroke, the increased mortality in 2020 was observed in patients 50 years of age or younger, as compared with 2019. Hospital outcomes of stroke admissions worsened during the COVID-19 pandemic, interrupting a trend of improvements in survival rates over 10 years. This effect was more pronounced during the surge of COVID-19 ICU admissions affecting predominantly patients with ischemic stroke without coma, and young patients with hemorrhagic stroke.


Discrimination of Pericarpium Citri Reticulatae in different years using Terahertz Time-Domain spectroscopy combined with convolutional neural network.
Pericarpium Citri Reticulatae (PCR) in longer storage years possess higher medicinal values, but their differentiation is difficult due to similar morphological characteristics. Therefore, this study investigated the feasibility of using terahertz time-domain spectroscopy (THz-TDS) combined with a convolutional neural network (CNN) to identify PCR samples stored from 1 to 20 years. The absorption coefficient and refractive index spectra in the range of 0.2-1.5 THz were acquired. Partial least squares discriminant analysis, random forest, least squares support vector machines, and CNN were used to establish discriminant models, showing better performance of the CNN model than the others. In addition, the output data points of the CNN intermediate layer were visualized, illustrating gradual changes in these points from overlapping to clear separation. Overall, THz-TDS combined with CNN models could realize rapid identification of different year PCRs, thus providing an efficient alternative method for PCR quality inspection.


Utility of the response bias scale (RBS) and other MMPI-2 validity scales in predicting TOMM performance.
The present study represents a replication and extension of the original Response Bias Scale (RBS) validation study. In addition to examining the relationship between the Test of Memory Malingering (TOMM), RBS, and several other well-researched Minnesota Multiphasic Personality Inventory 2 (MMPI-2) validity scales (i.e., F, Fb, Fp, and the Fake Bad Scale), the present study also included the recently developed Infrequency Post-Traumatic Stress Disorder Scale and the Henry-Heilbronner Index (HHI) of the MMPI-2. Findings from this retrospective data analysis (N=46) demonstrated the superiority of the RBS, and to a certain extent the HHI, over other MMPI-2 validity scales in predicting TOMM failure within the outpatient Veterans Affairs population. Results of the current study confirm the clinical utility of the RBS and suggest that, particularly if the MMPI-2 is an existing part of the neuropsychological assessment, examination of RBS scores is an efficient means of detecting negative response bias.


Design and synthesis of dipeptidyl alpha',beta'-epoxy ketones, potent irreversible inhibitors of the cysteine protease cruzain.
The dipeptidyl epoxy ketone 4 is a potent, irreversible inhibitor of cruzain, a cysteine protease isolated from Trypanosoma cruzi, with an apparent second order inhibition rate constant of 330,000 sec-1M-1.


Calycosin ameliorates atherosclerosis by enhancing autophagy via regulating the interaction between KLF2 and MLKL in apolipoprotein E gene-deleted mice.
Atherosclerosis is one of the underlying causes of cardiovascular disease. Formation of foam cells and necrotic core in the plaque is a hallmark of atherosclerosis, which results from lipid deposition, apoptosis, and inflammation in macrophages. Macrophage autophagy is a critical anti-atherogenic process and defective autophagy aggravates atherosclerosis by enhancing foam cell formation, apoptosis, and inflammation. Hence, enhancing autophagy can be a strategy for atherosclerosis treatment. Calycosin, a flavonoid from Radix Astragali, displays anti-oxidant and anti-inflammatory activities and therefore is potential to reduce the risk of cardiovascular disease. However, the anti-atherogenic effect of calycosin and the involved mechanism remains unclear. In this study, we assessed the potential benefits of calycosin on autophagy and atherosclerosis, and revealed the underlying mechanism. In this study, apoE-/- mice were fed high-fat diet for 16 weeks in the presence of calycosin and/or autophagy inhibitor chloroquine, which was followed by determination of atherosclerosis development, autophagy activity, and involved mechanisms. Calycosin protected against atherosclerosis and enhanced plaque stability via promoting autophagy. Calycosin inhibited foam cell formation, inflammation, and apoptosis by enhancing autophagy. MLKL was demonstrated as a new autophagy regulator, which can be negatively regulated by KLF2. Mechanistically, inhibitory effects of calycosin on atherogenesis were via improved autophagy through KLF2-MLKL signalling pathway modulation. This study demonstrated the atheroprotective effect of calycosin was through upregulating KLF2-MLKL-mediated autophagy, which not only proposed novel mechanistic insights into t atherogenesis but also identified calycosin as a potential drug candidate for atherosclerosis treatment.


The ideal rotation flap: an experimental study.
Numerous modifications exist and opinions vary between surgeons with regard to the design of the ideal rotation flap. A literature review revealed inconsistencies as well as three different designs of rotation flap (standard rotation flap, Ahuja's modified rotation flap, divine rotation flap) based on entirely different concepts. It is not clear which of these designs serves its purpose best in wound reconstruction since they have not been previously examined experimentally and directly compared. The aim of this study is to determine the optimal rotation flap design in wound reconstruction. Several modifications of the standard rotation flap are examined and the three different rotation flap designs are directly compared. This study tests the ability of various rotation flaps to close triangulated defects on sheets of neoprene, a synthetic rubber compound. Section A examines four important features in the design of the standard rotation flap: triangulation of a lesion, rotation flap circumference, pivot point and the back cut. Section B compares the standard rotation flap, Ahuja's modified rotation flap and the divine rotation flap. Tension resulting from wound closure is measured and the length of scar calculated. The standard rotation flap remains superior in comparison to the modified rotation flap and the divine rotation flap. Triangulation of a lesion should be performed with care and, in particular, the apex of the triangle should coincide with the geometrical pivot point. A flap circumference more than five times the width of the defect is of minimal benefit. The back cut is an effective modification and should be used if necessary.


Dysplasia and carcinoma in the rectal stump of total colitics who have undergone colectomy and ileo-rectal anastomosis.
From a group of 374 patients with ulcerative colitis who underwent colectomy and ileo-rectal anastomosis between 1952 and 1976, 104 presented for follow-up rectal biopsies over a 5 year period to 1986. These patients have been followed for an average of 28 years since the onset of the disease (range 11-56) and provide a unique model for the study of the development of carcinoma in colitis. A total of 443 biopsies was examined and epithelial morphology assessed according to the classification of Riddell et al. (1983). Five patients developed carcinoma of whom two showed dysplasia in biopsies taken a year or more before the diagnosis; one showed dysplasia 2 months before the appearance of cancer, another synchronous with it, and in the fifth patient dysplasia was not detected. Of 20 biopsies classified as 'indefinite for dysplasia, probably negative', 80% were associated with subsequent resolution, while of nine 'indefinite for dysplasia, probably positive' biopsies, eight (89%) were subsequently associated with either carcinoma (six) or dysplasia (two). The results emphasize the danger of absolute reliance upon dysplasia in assessing individual cancer risk in colitics, appear to demonstrate the usefulness of Riddell's classification and provide additional information on the natural history of dysplasia.


Introduction of selectivity and specificity to graphene using an inimitable combination of molecular imprinting and nanotechnology.
Recently, the nanostructured modified molecularly imprinting polymer has created a great attention in research field due to its excellent properties such as high surface to volume ratio, low cost, and easy preparation/handling. Among the nanostructured materials, the carbonaceous material such as 'graphene' has attracted the tremendous attention of researchers owing to their fascinating electrical, thermal and physical properties. In this review article, we have tried to explore as well as compile the role of graphene-based nanomaterials in the fabrication of imprinted polymers. In other words, herein the recent efforts made to introduce selectivity in graphene-based nanomaterials were tried collected together. The major concern of this review article is focused on the sensing devices fabricated via a combination of graphene, graphene@nanoparticles, graphene@carbon nanotubes and molecularly imprinted polymers. Additionally, the combination of graphene and quantum dots was also included to explore the fluorescence properties of zero-band-gap graphene.


Comparative assessment of antioxidant and immunomodulatory properties of skimmed milk protein hydrolysates and their incorporation in beverage mix.
Milk-derived protein hydrolysates have generated a great deal of interest recently due to their numerous beneficial health effects. However, there are few comparative studies on protein hydrolysates from different dairy species, their production, characterization, and bioactivity. In the present study, skimmed milk from both major and minor dairy species was hydrolyzed with alcalase, and its protein profiles were studied using tricine polyacrylamide gel electrophoresis and reverse phase-high protein liquid chromatography. The antioxidant and in vitro immunostimulatory properties were determined. Iron chelation activity was highest in hydrolysates of whey (25.00 ± 0.32 mmol L-1 ), casein (25.14 ± 0.34 mmol L-1 ), colostrum (24.52 ± 0.28 mmol L-1 ), and skimmed cattle milk (24.21 ± 0.26 mmol L-1 ). α,α-Diphenyl-β-picrylhydrazyl scavenging and 2,2'-azobis(2-amidino-propane) dihydrochloride activity was lowest in skimmed donkey milk protein hydrolysates (MPHs) (IC50 : 5.37 ± 0.05 mg mL-1 and 151.59 ± 2.1 mg mL-1 ). Production of nitric oxide and phagocytosis activity in RAW 264.7 (murine macrophage cell line) was significantly higher among whey and buffalo skimmed milk protein hydrolysate-treated groups as compared with the untreated group. The incorporation of whey protein hydrolysate and skimmed buffalo milk protein hydrolysate were sensorially acceptable at 10% level in beverage mix. This study comparatively evaluates the antioxidative and immunomodulatory properties of different skimmed MPHs and their potential applications as ingredients in pediatric, geriatric, and other health-promoting foods. © 2022 Society of Chemical Industry.


Hydronephrosis secondary to ureteropelvic obstruction in children: a review of 14 years of experience.
The clinical presentation and surgical management of 88 children and infants with hydronephrosis secondary to ureteropelvic obstruction are reported. The importance of recognizing associated anomalies of the genitourinary tract is stressed and the advantages of an anterior transperitoneal surgical approach are discussed. The operative technique and drainage procedure varied according to the nature and severity of the abnormality but the dismembered pyeloplasty with extrarenal drainage is favored.


Cadavers found outdoor in whom fungal growth was observed on the body surface: Consideration of the role of mycology in forensic medicine.
In forensic case work, fungal growth is occasionally observed on decomposed cadavers, however, the isolation of these organisms is not always carried out routinely. The usefulness of investigating fungi isolated from corpses in forensic settings, has been reported, such as providing trace evidence, estimating the time since death, and ascertaining the time of deposition. A 32-year-old male missing for 4 months, was found in a car in a forest far from his home and had died from blood loss, having been stabbed with a kitchen knife in the left side of his chest. Whitish or white greenish colonies ranging 5 cm to 8 cm in size were observed over his whole body. Penicillium commune and Cladosporium cladosporioides were isolated from the colonies. A 49-year-old male missing for one month, and was found dead at 500 m elevation in the mountains. An autopsy was conducted, but the cause of death could not be determined. Dark greenish or whitish colonies were found on his face and neck, and Epicoccum nigrum, Mucor sp.. Cladosporium sp., and Pestalotiopsis sp. were isolated. Penicillium sp. and Cladosporium sp. are major indoor fungi, and Epicoccum sp. and Pestalotiopsis sp. are plant pathogens found in outdoor environments. There was no discrepancy between the police statement and findings of the corpse such as place discovered, types of isolated fungi, and estimated time since death. Identifying fungi on cadavers may aid in forensic casework, and further studies are needed to develop for the use of fungi as a forensic tool.


Is three-dimensional laparoscopic spleen preserving splenic hilar lymphadenectomy for gastric cancer better than that of two-dimensional? Analysis of a prospective clinical research study.
Three-dimensional (3D) systems for laparoscopy provide surgeons with additional information on spatial depth not found in two-dimensional (2D) systems. This study enrolled 156 spleen-preserving splenic hilar lymphadenectomy (LSPSHL) patients in a randomized controlled trial (ClinicalTrials.gov Identifier NCT02327481) at the department of gastric surgery at Fujian Medical University Union Hospital between January 2015 and April 2016. The short-term efficacies were compared between the treatment groups. The unedited videos of 80 LSPSHL (40 procedures each for 3D and 2D) were rated for technical performance using the Generic Error Rating Tool. The data for 156 LSPSHL patients indicate that the estimated blood loss (EBL) (3D vs 2D = 66.3 vs. 99.0, P = 0.046) was significantly less in the 3D group. The postoperative recovery and complication rates were similar (P > 0.05). And there were no deaths within 30 days of surgery. Two observers analyzed 80 videos of LSPSHL. The results showed that there were fewer grasping-errors made in the 3D group than in the 2D group when dissecting the inferior pole region of spleen (IPRS) (P = 0.016) and the superior pole region of spleen (SPRS) (P = 0.022). Additionally, the inter-rater reliability was high regarding grasping-errors in the IPRS (intraclass correlation coefficient (ICC) 0.92) and in the SPRS (ICC 0.83). The ICC for the total number of errors was 0.82. The mean of errors in the 3D group (3D vs. 2D = 20.7 vs. 23.5, P = 0.022) was less than the 2D group. Compared with 2D LSPSHL, 3D technology reduces EBL and technical errors during splenic hilar dissection.


Use of an autologous liver round ligament flap zeros postoperative bile leak after curative resection of hilar cholangiocarcinoma.
Postoperative bile leak is a major surgical morbidity after curative resection with hepaticojejunostomy for hilar cholangiocarcinoma, especially in Bismuth-Corlette types III and IV. This retrospective study assessed the effectiveness and safety of an autologous hepatic round ligament flap (AHRLF) for reducing bile leak after hilar hepaticojejunostomy. Nine type III and IV hilar cholangiocarcinoma patients were consecutively hospitalized for elective perihilar partial hepatectomy with hilar hepaticojejunostomy using an AHRLF between October 2009 and September 2013. The AHRLF was harvested to reinforce the perihilar hepaticojejunostomy. Main outcome measures included operative time, blood loss, postoperative recovery times, morbidity, bile leak, R0 resection rate, and overall survival. All patients underwent uneventful R0 resection with hilar hepaticojejunostomy. No patient experienced postoperative bile leak. The AHRLF was associated with lack of bile leak after curative perihilar hepatectomy with hepaticojejunostomy for hilar cholangiocarcinoma, without compromising oncologic safety, and is recommended in selected patients.


Digital infections in cattle. Their radiologic spectrum.
A series of radiographs are presented to illustrate the relevant anatomy and radiology of infections of the digital region. The typical reaction to infection of bones, joints, and other soft tissues are described as they relate specifically to cattle.


Effect of calcitonin gene-related peptide antagonist on the cardiovascular events, mortality, and prostaglandin E2 production by nitrate-induced tolerant rats with acute myocardial infarction.
Anti-ischemic effects of NO releasing by nitroglycerin (NTG) and the release of calcitonin gene-related peptide (CGRP) are involved in the decrease of vascular remodeling in different cardiovascular diseases. Using a nitrate-free period is still generally required to prevent nitrate tolerance and should be used as the first-line option to maintain adequate symptom control and on an individual basis. Personalized anti-ischemic concerns require the urgent change of paradigm from interventional measures to predictive, preventive, and personalized treatment with organic nitrates and its combination with drugs that may improve prognosis and drugs that can be added for patients who remain symptomatic despite therapy with the other classes of agents. The purpose of this study was to evaluate the influence of human calcitonin gene-related peptide antagonist (CGRP8-37) on cardiohemodynamic events, prostaglandin E2 (PGE2) plasma concentration, the severity of ventricular arrhythmias, and mortality occurring during acute myocardial infarction (AMI) in NTG-tolerant and nontolerant rats. In the pilot study of efficacy of calcitonin gene-related peptide antagonist (CGRP8-37), 58 male Wistar rats were included. All procedures were performed according to protocols approved by the General Animal Care and Use Committee. Adult male rats underwent surgery to induce AMI by ligating the left anterior descending coronary artery or SHAM. ECG was used to confirm myocardial ischemia. In each experiment, a rat was maintained under anesthesia for the duration of the experiment. At the end of the experiment, the rat was killed by an overdose of pentobarbital. All animals in accordance with the received pharmacological agent were randomized into three groups: I-received only NTG, 50 mg/kg daily, s.c. injections b.i.d. 3 days prior to AMI; II-received NTG by the same dose, route, and frequency of administration + CGRP antagonist (CGRP8-37), 10 μg/kg two times daily by a similar period of administration; and III-served as control (C) group without preliminary tolerance to NTG. Subcutaneous injections of NTG (50 mg/kg) 30 min prior to AMI in NTG-tolerant animals (group I) and in NTG-tolerant rats + CGRP antagonist (group II) caused minor changes in blood pressure and heart period that was accompanied before NTG s.c. administration with blunted baroreflex sensitivity in response to i.v. administration of sodium nitroprusside in these groups of rats (0.66 ± 0.05 and 0.56 ± 0.04 ms/mmHg, P < 0.05, respectively) in comparison to C (group III) animals (0.9 ± 0.1 ms/mmHg). AMI 1 h duration was associated with a high incidence of ventricular arrhythmia and significant mortality in group I (70 %) and especially in group II (90 %) animals at 72 h after reperfusion as compared with group III rats (56 %), that correlated to a decrease of PGE2 plasma content in group II (2.2 ± 0.4 ng/ml, P < 0.001) and group I (3.6 ± 0.2 ng/ml, P < 0.01) vs. control group of rats (4.8 ± 0.3 ng/ml). CGRP could be involved in the mechanism of nitrate tolerance via the inhibition of release of the potent vasodilator CGRP leading to exacerbation of acute myocardial ischemia. The influence of CGRP antagonist could enhance this condition.


A Nacre-Inspired Separator Coating for Impact-Tolerant Lithium Batteries.
The commercial ceramic nanoparticle coated microporous polyolefin separators used in lithium batteries are still vulnerable under external impact, which may cause short circuits and consequently severe safety threats, because the protective ceramic nanoparticle coating layers on the separators are intrinsically brittle. Here, a nacre-inspired coating on the separator to improve the impact tolerance of lithium batteries is reported. Instead of a random structured ceramic nanoparticle layer, ion-conductive porous multilayers consisting of highly oriented aragonite platelets are coated on the separator. The nacre-inspired coating can sustain external impact by turning the violent localized stress into lower and more uniform stress due to the platelet sliding. A lithium-metal pouch cell using the aragonite platelet coated separator exhibits good cycling stability under external shock, which is in sharp contrast to the fast short circuit of a lithium-metal pouch cell using a commercial ceramic nanoparticle coated separator.


[Cutaneous mesenchymal neoplasms versus mesenchymal neoplasms of subcutaneous and deep soft tissue. Similarities and differences].
As in subcutaneous and deep soft tissues, cutaneous mesenchymal neoplasms are also relatively rare and characterized by a clinicopathological heterogeneity. There are striking differences in regard to the occurrence of different lines of differentiation of mesenchymal neoplasms in superficial and deep locations, and some distinct entities arise exclusively in the dermis. Superficially located mesenchymal neoplasms are characterized by a number of specific morphological features in comparison to deeper located lesions. Clinically important, dermal sarcomas of some lines of differentiation are associated with a favorable clinical prognosis, independent of the histological grading, which is important to know for the correct treatment of patients. In the following review similarities and distinguishing clinicopathological features of superficially and deeply located mesenchymal tumors are discussed.


Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control.
The rapidly proliferating cells in plant meristems must be protected from genome damage. Here, we show that the regulatory role of the Arabidopsis RETINOBLASTOMA RELATED (RBR) in cell proliferation can be separated from a novel function in safeguarding genome integrity. Upon DNA damage, RBR and its binding partner E2FA are recruited to heterochromatic γH2AX-labelled DNA damage foci in an ATM- and ATR-dependent manner. These γH2AX-labelled DNA lesions are more dispersedly occupied by the conserved repair protein, AtBRCA1, which can also co-localise with RBR foci. RBR and AtBRCA1 physically interact in vitro and in planta Genetic interaction between the RBR-silenced amiRBR and Atbrca1 mutants suggests that RBR and AtBRCA1 may function together in maintaining genome integrity. Together with E2FA, RBR is directly involved in the transcriptional DNA damage response as well as in the cell death pathway that is independent of SOG1, the plant functional analogue of p53. Thus, plant homologs and analogues of major mammalian tumour suppressor proteins form a regulatory network that coordinates cell proliferation with cell and genome integrity.


Chronic resveratrol administration has beneficial effects in experimental model of type 2 diabetic rats.
The present study was designed to evaluate whether long-term resveratrol administration has beneficial effects on the metabolic control and oxidative stress in diabetic rats. Male Wistar rats were divided into four groups: normal control, diabetic control, normal treated with resveratrol, and diabetic treated with resveratrol. Diabetes was induced by injection of streptozotocin (50 mg/kg; i.p.), fifteen minutes after the administration of nicotinamide (110 mg/kg; i.p.) in 12 h fasted rats. Four-month oral resveratrol administration (5 mg/kg/day) significantly attenuated the elevated levels of the blood glucose, glycosylated hemoglobin, total protein, albumin, urea, creatinine, and 8-isoprostane in diabetic rats. Moreover, resveratrol administration to diabetic rats improved the reduced levels of glutathione, total antioxidant capacity, and the antioxidant enzymes activities (superoxide dismutase, glutathione peroxidase, and catalase). No significant differences were observed in the activities of plasma aminotransferases (ALT and AST) and insulin levels between diabetic rats treated with resveratrol and diabetic controls. The results suggest that chronic resveratrol administration is safe and effective, and may be considered as a beneficial therapeutic compound in diabetes.


Experimental evaluation of cobalt adsorption capacity of walnut shell by organic acid activation.
Cobalt, from industrial waste and nuclear laundry, possess health risk to human beings, animals and plants. Number of methods, other than adsorption, have been reported in literature for Co removal from waste water. In this research walnut shell powder after modification has been utilized for Co adsorption. First step of modification involved chemical treatment by four different organic acids for 72 h. Samples were collected at 24, 48 and 72 h. Second step involved thermal treatment of 72 h samples. Unmodified and modified particles have been analyzed by chemical methods and instruments i.e. UV spectrometer, FTIR, cyclic voltammetry (CV) and microscopic imaging. Thermally treated samples have shown augmented Co adsorption. CV analysis showed thermally treated samples with better capacitance. Particles modified by oxalic acid presented better Co adsorption. Oxalic acid treated particles activated for 72 h with thermal treatment provided maximum adsorption capacity 1327 ± 20.6 mg/g against Co(II) at pH 7, stirring 200 rpm, initial concentration 20 ml, adsorbent dosage (5 mg) and contact time 240 min at room temperature.


Women and Alcohol: Limitations in the Cardiovascular Guidelines.
Patients and physicians rely on evidence-based guidelines to guide alcohol consumption recommendations, but significant discrepancies in alcohol consumption limits are found between different international societies. Current American Heart Association (AHA) preventive management guidelines on hypertension, transient ischemic attack, stroke, and stable ischemic heart disease recommend sex-specific daily alcohol consumption limits which are inconsistent from other international society recommendations. In this focused review of current American Heart Association guidelines and their sources, we evaluate the evidence behind sex-specific alcohol consumption cut-offs. We found insufficient experimental and epidemiologic evidence to conclude that women should have a reduced daily alcohol consumption limit as compared to men; further studies are required to determine whether sex-specific differences exist in alcohol metabolism and its related cardiovascular impact.


Prevalence and predictive modeling of undiagnosed diabetes and impaired fasting glucose in Taiwan: a Taiwan Biobank study.
We investigated the prevalence of undiagnosed diabetes and impaired fasting glucose (IFG) in individuals without known diabetes in Taiwan and developed a risk prediction model for identifying undiagnosed diabetes and IFG. Using data from a large population-based Taiwan Biobank study linked with the National Health Insurance Research Database, we estimated the standardized prevalence of undiagnosed diabetes and IFG between 2012 and 2020. We used the forward continuation ratio model with the Lasso penalty, modeling undiagnosed diabetes, IFG, and healthy reference group (individuals without diabetes or IFG) as three ordinal outcomes, to identify the risk factors and construct the prediction model. Two models were created: Model 1 predicts undiagnosed diabetes, IFG_110 (ie, fasting glucose between 110 mg/dL and 125 mg/dL), and the healthy reference group, while Model 2 predicts undiagnosed diabetes, IFG_100 (ie, fasting glucose between 100 mg/dL and 125 mg/dL), and the healthy reference group. The standardized prevalence of undiagnosed diabetes for 2012-2014, 2015-2016, 2017-2018, and 2019-2020 was 1.11%, 0.99%, 1.16%, and 0.99%, respectively. For these periods, the standardized prevalence of IFG_110 and IFG_100 was 4.49%, 3.73%, 4.30%, and 4.66% and 21.0%, 18.26%, 20.16%, and 21.08%, respectively. Significant risk prediction factors were age, body mass index, waist to hip ratio, education level, personal monthly income, betel nut chewing, self-reported hypertension, and family history of diabetes. The area under the curve (AUC) for predicting undiagnosed diabetes in Models 1 and 2 was 80.39% and 77.87%, respectively. The AUC for predicting undiagnosed diabetes or IFG in Models 1 and 2 was 78.25% and 74.39%, respectively. Our results showed the changes in the prevalence of undiagnosed diabetes and IFG. The identified risk factors and the prediction models could be helpful in identifying individuals with undiagnosed diabetes or individuals with a high risk of developing diabetes in Taiwan.


Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: discovery of DS-8108b, an orally active renin inhibitor.
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h.


Angular subtense effects on perception of polar and parallel projections of cubes.
Many authors contend that the perception of 2-D drawings of a 3-D object is governed by polar projective geometry. A problem for this position is that observers accept parallel projections, which are not produced with polar projective geometry, as accurate representations of 3-D objects. In Experiments 1 and 2, we used two different standards of comparison to study the perceptions of three line drawings of cubes--correct polar projections of cubes with subtenses of 15 degrees and 35 degrees, and a parallel projection--at five different angular subtenses. In Experiment 1, 14 observers judged each drawing when it subtended about 35 degrees, 15 degrees, 5 degrees, 4 degrees, and 2 degrees in width. Subjects used an 8-point rating scale to compare each drawing with a correct polar projection of a cube subtending 35 degrees, viewed with the drawing subtending 15 degrees. As predicted, both polar projections had their highest ratings at their correct vantage points. Ratings for the parallel projection were highest at small angular subtenses and decreased when it subtended 35 degrees. These findings were supported by a second experiment in which the 15 degrees polar projection was set at a 5 degrees viewing angle as a standard. In Experiment 3, 15 observers compared the three drawings, viewed at a second set of angular subtenses (30 degrees, 35 degrees, 40 degrees, 45 degrees, and 50 degrees), with a standard, the 35 degrees polar set at 45 degrees. Ratings fell with increases in viewing angle, and the parallel projection was rated lowest. The results indicate that parallel projections are assessed as polar projections that are correct for objects at a small angular subtense. Furthermore, projections at a small angular subtense are robust; that is, they are acceptable over a wide range of angular subtenses. We suggest that robustness can be explained by the modest variability in the proportions of pictures of cubes subtending small angles.


Effect of speech rate manipulations on articulatory dynamics in severe traumatic brain injury: an EMA and EPG study.
Manipulation of speech rate forms an integral part of the treatment of dysarthria and the effects of changes in speech rate on articulatory dynamics in persons with traumatic brain injury (TBI) is poorly documented. To determine the effects of manipulations of speech rate (habitual vs fast) on lingual kinematics and tongue-to-palate contacts in adult speakers with severe TBI and matched normal controls. Six adults with severe TBI and five matched non-neurologically impaired controls underwent testing of their articulatory function using electromagnetic articulography (EMA) and electropalatography (EPG). The results demonstrated that the TBI and control groups selected different strategies for increasing speech rate, with the TBI group showing an increase in articulatory effort estimated from an increase in maximum velocity and maximum acceleration/deceleration of tongue movement when speaking at the fast rate. The control group demonstrated no effects of a fast speech rate on articulatory kinematics for sentence productions. When speaking at a fast rate, individuals with severe TBI appear to use greater articulatory effort, possibly to preserve the distinctiveness of phonetic segments in order to avoid articulatory undershoot. In contrast, control subjects show a greater economy of effort when speaking at a fast rate, possibly to preserve articulatory precision.


Targeting AMPK: a new therapeutic opportunity in breast cancer.
This paper reviews the mammalian Target Of Rapamycin (mTOR) pathway dysregulation in breast cancer, and the current evidence targeting this pathway directly or through activation of AMP-activated protein kinase (AMPK) as an additional therapeutic opportunity for intervention in breast cancer. Relevant articles were identified through computerised searches of Medline and Pubmed. Secondary articles were identified from the reference lists of key papers and by hand searching. The current consensus to target the AMPK/mTOR pathway in breast cancer is based on in vitro and epidemiological evidences. A low incidence of cancer in diabetic patients on metformin has been explained in vitro by the drug's anti-proliferative effect through activation of AMPK. There is a need to explore the anticancer effects of metformin and the potential to develop the therapeutic avenues offered by targeting the AMPK/mTOR pathway.


Metabolic and Nutritional Support.
Hypermetabolism is a hallmark of larger burn injuries. The hypermetabolic response is characterized by marked and sustained increases in catecholamines, glucocorticoids, and glucagon. There is an increasing body of literature for nutrition and metabolic treatment and supplementation to counter the hypermetabolic and catabolic response secondary to burn injury. Early and adequate nutrition is key in addition to adjunctive therapies, such as oxandrolone, insulin, metformin, and propranolol. The duration of administration of anabolic agents should be at minimum for the duration of hospitalization, and possibly up to 2 to 3 years postburn.


Double Minority Status and Neighborhoods: Examining the Primacy of Race in Black Immigrants' Racial and Socioeconomic Segregation.
Sociologists have long viewed spatial assimilation as a measure of minorities' socioeconomic progress. While assimilation increases as socioeconomic status (SES) improves, blacks remain more highly segregated than any other race/ethnic group. I use the locational attainment model to determine whether black immigrants-like their U.S.-born counterparts-are highly segregated. This paper broadens the segregation literature by determining: (1) black immigrant segregation patterns after controlling for individual-level characteristics, (2) the extent to which segregation varies by location, and (3) if racial segregation has the same socioeconomic consequences for U.S.- and foreign-born blacks. I find that black immigrants face high racial and socioeconomic segregation in mainly Caribbean settlement areas. However, black immigrants in all but two predominantly African settlement areas experience no segregation. Essentially, I find that there is a great deal of diversity in black immigrants' segregation patterns stemming from differential treatment in the housing market based on African immigrants' higher SES and/or African immigrants' residential choices. Results in the two outlier African settlement areas (Minneapolis and Washington, D.C.) suggest that entry visa may play an important role in black segregation.


Analysing medical predictors for the outcome of infertility treatment: a 5-year follow-up survey.
For many couples, bearing children is a common life goal; however it cannot always be fulfilled. Undergoing infertility treatment does not always guarantee pregnancies and live births. Couples experience miscarriages and even discontinue infertility treatment. Significant medical predictors for the outcome of infertility treatment have yet to be fully identified. To further our understanding, a cross-sectional 5-year follow-up survey was undertaken, in which 95 women and 82 men that have been treated at the Women's Hospital of Heidelberg University participated. Binary logistic regressions, parametric and non-parametric methods were used for our sample to determine the relevance of biological (infertility diagnoses, maternal and paternal age) and lifestyle factors (smoking, drinking, over- and underweight) on the outcome of infertility treatment (clinical pregnancy, live birth, miscarriage, dropout rate). In addition, chi-square tests were used to examine differences in the outcome depending on the number of risk factors being present. In the binary logistic regression models for clinical pregnancies, live births and drop outs were statistically significant only for the maternal age, whereas the maternal and paternal BMI, smoking, infertility diagnoses and infections showed no significant predicting effect on any of the outcome variables. A correlation between the number of risk factors and the outcome of infertility treatment could not be excluded. The results confirm that maternal age has an effect on infertility treatment, whereas the relevance of other possible medical predictors remains unclear. Further large-scale studies should be considered to increase our knowledge on their predictive power.


Alteration of gene expression in rat colon mucosa after exercise.
The development of colon cancer is highly influenced by lifestyle factors such as nutrition and physical inactivity. Detailed biological mechanisms are thus far unclear. The purpose of this study was to investigate the effects of regular treadmill exercise on gene expression in rat colon mucosa. For this purpose, 6-week-old male Wistar rats completed a stress-free voluntary treadmill exercise period of 12 weeks. Sedentary rats served as a control group. In the colon mucosa, steady-state mRNA expression levels of approximately 10,000 genes were compared between both groups by micro-array analysis (MWG rat 10K array). A total of 8846 mRNAs were detected above background level. Regular exercise led to a decreased expression of 47 genes at a threshold-factor of 2.0. Three genes were found to be up-regulated in the exercise group. The identified genes encode proteins involved in signal transduction (n=11), transport (n=8), immune system (n=7), cytoskeleton (n=6), protein targeting (n=6), metabolism (n=5), transcription (n=3) and vascularization (n=2). Among the genes regulated by regular exercise, the betaine-homocysteine methyltransferase 2 (BHMT2) seems to be of particular interest. Physical activity may protect against aberrant methylation by repressing the BHMT2 gene and thus contribute to a decreased risk of developing colon cancer. We have also identified vascular endothelial growth factor (VEGF), angiopoietin-2 (ANG-2) and calcium-independent phospholipase a2 (iPL-A2), all of them with markedly reduced transcript levels in the mucosa of active rats. In summary, our experiment presents the first gene expression pattern in rat colon mucosa following regular treadmill activity and represents an important step in understanding the molecular mechanisms responsible for the preventive effect of physical activity on the development of colon cancer.


Heart rate variability (HRV) in deep breathing tests and 5-min short-term recordings: agreement of ear photoplethysmography with ECG measurements, in 343 subjects.
We analyzed heart rate variability (HRV) taken by ECG and photoplethysmography (PPG) to assess their agreement. We also analyzed the sensitivity and specificity of PPG to identify subjects with low HRV as an example of its potential use for clinical applications. The HRV parameters: mean heart rate (HR), amplitude, and ratio of heart rate oscillation (E-I difference, E/I ratio), RMSSD, SDNN, and Power LF, were measured during 1-min deep breathing tests (DBT) in 343 individuals, followed by a 5-min short-term HRV (s-HRV), where the HRV parameters: HR, SD1, SD2, SDNN, Stress Index, Power HF, Power LF, Power VLF, and Total Power, were determined as well. Parameters were compared through correlation analysis and agreement analysis by Bland-Altman plots. PPG derived parameters HR and SD2 in s-HRV showed better agreement than SD1, Power HF, and stress index, whereas in DBT HR, E/I ratio and SDNN were superior to Power LF and RMSSD. DBT yielded stronger agreement than s-HRV. A slight overestimation of PPG HRV over HCG HRV was found. HR, Total Power, and SD2 in the s-HRV, HR, Power LF, and SDNN in the DBT showed high sensitivity and specificity to detect individuals with poor HRV. Cutoff percentiles are given for the future development of PPG-based devices. HRV measured by PPG shows good agreement with ECG HRV when appropriate parameters are used, and PPG-based devices can be employed as an easy screening tool to detect individuals with poor HRV, especially in the 1-min DBT test.


Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review.
There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa; however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (including acetazolamide and methazolamide) and topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide) are effective first-line treatments. In patients unresponsive to carbonic anhydrase inhibitor treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implants), oral corticosteroid (deflazacort), intravitreal antivascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to retinitis pigmentosa. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first-line treatment in CME secondary to retinitis pigmentosa. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME.


Executive function in adolescents with PKU and their siblings: Associations with biochemistry.
Previous research shows consistent and marked executive function impairment in children with early and continuously treated phenylketonuria. This between groups analysis (phenylketonuria group vs sibling controls) found no significant differences in executive function (although adolescents with phenylketonuria performed slightly worse than their siblings). Biochemical relationships with executive function were confined to long-term measures of high phenylalanine:tyrosine ratio exposure, as well as tyrosine exposure independent of phenylalanine. This study suggests that early and continuously treated PKU results in non-significant EF differences (compared to siblings), although the influence of long-term exposure to poorer metabolic control is still evident.


Laparoscopic gastro-jejunal anastomosis using novel r2 deflectable instruments in an ex vivo model.
A novel 5 mm steerable instrument system (r2-DRIVE) was developed with active tip deflection and tip and shaft rotation. The feasibility and training effect of the r2 instruments were determined in a phantom model. Experienced laparoscopic surgeons and untrained novices performed laparoscopic gastro-jejunal anastomoses using porcine tissue and r2 DRIVE-instruments. Mean anastomosis time, anastomosis width and burst pressure were measured. Number of stitches, skipped stitches and dropped needles were counted. Results of trained and untrained subjects were compared. Mean time for suturing decreased rapidly for all participants, but was more evident for untrained persons. After five anastomoses no relevant improvement in anastomotic time was seen for the skilled group. The ease of use, efficacy of manipulation and swift training effect with the novel r2 instruments for both experienced laparoscopic surgeons and untrained non-surgeons could be demonstrated and after few cases stable anastomosis times and a fast learning curve were obtained. This study demonstrates the ease of use, efficacy of manipulation and swift training effect with the novel r2 instruments for both experienced laparoscopic surgeons and untrained non-surgeons. After few cases stable anastomosis times and a fast learning curve were obtained.


Primary large B-cell lymphoma involving the cerebellopontine angle mimic acoustic schwannoma: Role of MR Spectroscopy in differential diagnosis. A case report.
Primary central nervous system (CNS) lymphoma is a very rare aggressive non-Hodgkin disease that originates in CNS (brain, leptomeninges, spinal cord, or eyes). It seems to have increased over the last two decades in both immunocompromised and immunocompetent patients. Primary large B-cell lymphoma involving the cerebellopontine angle (CPA) is extremely rare: only 15 cases of large B-cell lymphoma of the CPA have been reported worldwide; based on our knowledge, no cases studied with MR Spectroscopy. Primary large B-cell lymphoma of the CPA must be differentiated from other cerebellopontine angle diseases, such as acoustic neuroma and meningioma. An early and accurate diagnosis of this neoplasm is necessary for the best management because it is a radiosensitive and chemosensitive tumor. Herein, we report a rare case of B-cell lymphoma involving the left CPA in a 65-year-old man who presented with 3 months of hearing loss on the left, illustrated by MR and TC imaging, highlighting how the MR Spectroscopy, thanks to their greater specificity, is decisive in achieving the correct diagnosis of primary lymphoma and differentiating it from acoustic schwannoma or meningioma. Therefore, in the suspicion of a malignant heteroplastic lesion of the CPA, we suggest including Spectroscopy in the MR study protocol.