Effectiveness of online learning in improving optometry student's reflective abilities.
Optometry education strives to develop competencies required for reflective practice in its pupils. The forced changes in academia during COVID-19 pandemic, rapid switching to online methods imposed serious challenges on the training of reflective skills. We hypothesize that the synchronous online sessions of case-based reflections are effective in imparting training for reflective practice in optometry students. A prospective study was done with planned, synchronous, online, small group workshops for case-based reflections through the second year of optometry program during 'introduction to patient care' course. The reflective competencies were measured with a modified Groningen Reflection Ability Scale (GRAS) at the beginning and towards conclusion. Data was analysed with Mann-Whitney one tail test and qualitative thematic methods. Total of 104 students participated in the study. The aggregate score showed significant improvement (p<0.05) in students' reflective ability. A rising trend was seen in each component namely self-reflection, empathetic and communication reflections. The results demonstrate that the reflective skills can be developed using virtual patient experiences, case-based reflective practices conducted in synchronous small group workshops in online mode. Students perceived it as useful activity in developing themselves as healthcare professionals.


Mitozolomide (NSC 353451), a new active drug in the treatment of malignant melanoma. Phase II trial in patients with advanced disease.
A phase II trial with mitozolomide was carried out in patients with malignant melanoma, since in preclinical studies this new imidazotetrazine had shown promising effects against human melanoma xenografts. Twenty-one evaluable patients with advanced malignant melanoma were treated with 115 mg m-2 of mitozolomide, given orally every 6 weeks. None of the patients had received prior chemotherapy. Two partial responses (10 and 7+ months) were observed. The responding patients had lung metastases, and one of them had, in addition, a huge (17 X 14 cm) lymph node metastasis in the groin. Also, one patient had a 48% tumour volume reduction of lung metastases. The dose limiting side effect of the treatment was bone marrow depression, with delayed leukopenia and thrombocytopenia. The median white blood cell counts and platelet nadirs were 2.5 X 10(9) 1(-1) (range 1.1-3.8) and 59 X 10(9) 1(-1) (range 14-95), respectively. Non-haematological adverse reactions were limited to mild or moderate nausea. It is concluded that orally administered mitozolomide is active against malignant melanoma and seems to have a response rate comparable to those of the most active established drugs.


Virulence comparisons of Aspergillus nidulans mutants are confounded by the inflammatory response of p47phox-/- mice.
While investigating the requirement for phagosomal alkalinization in the host defense against pulmonary aspergillosis, we observed high morbidity of p47(phox)(-/-) mice infected with pH-insensitive Aspergillus nidulans mutants despite a paucity of fungal growth. Fatal infection also resulted from a normally avirulent p-aminobenzoate auxotroph. This demonstrates that p47(phox)(-/-) murine immunity contributes significantly to A. nidulans lethality. These data have wider implications for microbial virulence studies with p47(phox)(-/-) mice.


Intravascular ultrasound evidence of perivascular trauma during routine percutaneous coronary intervention.
We assessed whether intravascular ultrasound (IVUS) can detect evidence of coronary perforation that is not visible by coronary angiography. Approximately 15,000 consecutive percutaneous coronary interventions (PCI) performed with IVUS guidance were reviewed retrospectively, pre- and post-PCI IVUS images were compared, and IVUS findings were compared with coronary angiography and in-hospital outcomes. We detected three distinct patterns that were not present pre-PCI and that were suggestive of perforation or perivascular trauma: perivascular blood speckle in 67 % (51/76), perivascular hematoma in 17 % (13/76), and new echolucent perivascular layer in 16 % (12/76). Angiographic appearance included perforation in 24 % (18/76), dissection in 33 % (25/76), lumen irregularity in 17 % (13/76), new stenosis in 5 % (4/76), and no abnormalities in 21 % (16/76). The site of a break in arterial wall with communication between the lumen and perivascular space could be detected in 61 % (46/76). This extended proximally and distally with equal frequency, but was primarily located within the lesion in 80 % (61/76), although the lumen was rarely compromised. Within 24 h, there were four emergent coronary artery bypass grafting procedures, one repeat PCI, and six periprocedural myocardial infarctions (defined as CK-MB ≥10 times the upper limit of normal), but there were no episodes of cardiac tamponade. Although infrequent, IVUS detected three distinct patterns of post-PCI perivascular trauma suggestive of a perforation that was detected angiographically in only 24 % of cases.


Biochemical decomposition of coal-tar dyes. II. Acute toxicity of coal-tar dyes and their decomposed products.
Twenty kinds of coal-tar dyes were subjected to median tolerance limit (TLm) test by use of Himedaka (Oryzias latipes) for the comparision of their acute toxicities. It became clear that 4 kinds of halogens substituted xanthene compounds dyes showed strong acute toxicities. From the fact that uranine had the lower acute toxicity than halogens substituted compounds and the toxicities of these 4 dyes increased through irradiation, it was assumed that halogen atoms in dyes might be responsible for these strong acute toxicities to fish.


Intermountain chronic disease risk score (ICHRON) validation for prediction of incident chronic disease diagnoses in an australian primary prevention population.
The Intermountain Chronic Disease Risk Score (ICHRON) is a primary prevention risk prediction tool that uses commonly ordered blood tests and is designed to be calculated by the electronic health record. ICHRON was highly predictive of 3-year chronic disease (ChrD) diagnosis in an internal validation; however, external validation is needed. ICHRON was calculated among patients from a region of Australia using sex-specific weightings of age and components of the comprehensive metabolic panel and the complete blood count. Original ICHRON weightings and risk stratification thresholds from the US-based derivation at Intermountain Healthcare were used. ICHRON was evaluated as a predictor of an incident 3-year ChrD diagnosis (coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, stroke, dementia, diabetes, renal failure, chronic obstructive pulmonary disease, and peripheral vascular disease). A total 5,512 females (49.6 ± 19.2) and 3,461 males (53.0 ± 18.6) were studied. Among females, 50.3%, 33.7% and 16.0% were low, moderate, and high-risk, respectively; and for males, 39.6%, 35.0%, and 25.4%. Frequency of a 3-year ChrD diagnosis among females was 2.2%, 8.5%, and 15.9% for low, moderate, and high-risk groups, respectively, and 4.7%, 9.7%, and 20.0% among males. C-statistics were 0.726 (0.700, 0.752) for females and 0.694 (0.665, 0.724) for males. ICHRON predicted ChrD diagnosis at 3-years among an external, geographically distant validation cohort. These findings show the value of ICHRON for primary care patients in distinct locales. Additionally, electronic calculation of ICHRON empowers the clinical use of this tool to identify and differentially manage and treat high-risk patients.


Continuous renal replacement therapy versus intermittent hemodialysis as first modality for renal replacement therapy in severe acute kidney injury: a secondary analysis of AKIKI and IDEAL-ICU studies.
Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI. This is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient's modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting. A total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan-Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01-1·60). In a complementary analysis of less severely ill patients (SOFA score: 3-10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01-3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients. Compared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique.


Neuronal nitric oxide synthase is permanently decreased in the cerebellum of rats subjected to chronic neonatal blockade of N-methyl-D-aspartate receptors.
Pharmacological blockade of the (NMDA) receptor at critical stages of brain development may have long-lasting effects on brain chemistry and on animal behavior. We report here experiments in which the competitive NMDA receptor antagonist CGP 39551 was administered to rat pups from postnatal day 7 (P7) to P18. The stage of treatment was selected to primarily target the cerebellum, whose granule cells undergo post-mitotic migration and establishment of synaptic connections during this period. We focused our study on the long-term consequences of CGP 39551 treatment on the neuronal isoform of nitric oxide synthase (nNOS) since nNOS is highly expressed in the cerebellum and it is functionally linked to the NMDA receptor. Treated rats exhibited a long-lasting (up to P70) decrease in the intensity of nNOS immunocytochemical staining in the cerebellar cortex accompanied by a decrement of calcium-dependent NOS catalytic activity. A comparable decrease of enzyme activity was measured in the cerebral cortex, but not in the hippocampus, of adult rats. Other neurochemical markers (glutamatergic, gabaergic, purinergic) and glutamine synthetase were unchanged, while a cholinergic marker was slightly increased in the cerebellum of CGP 39551 treated animals. Taken together these data show that blockade of NMDA receptor during the critical period of formation and stabilization of neuronal circuits preferentially affects long-term nNOS expression and catalytic activity in the cerebellum.


Anti-hepatitis C virus and synergistic potential of Syzgium cumine a bioassay guided screening in liver-infected hepatocytes.
Hepatitis C virus is still a global challenge affecting millions of carriers worldwide with the more devastating situation in developing countries. Present-day clinical manifestations are insufficient to tackle the increasing disease burden unaffordable cost, viral resistance and adverse effects of treatment. In this research, indigenous medicinal plants from Pakistan tested in bioassay guided manner on Huh-7 cell lines for their antiviral effect, synergism of purified fraction with interferon FDA approved drug regime, as the receptor for developing transfection model. The methanol extract of Syzgium cumine was observed against HCV through serum titter reduction in Quantitative Real Time PCR assay and the gene expression system, NS3protease inhibition was 76% and 51% against genotype 1a and 3a, respectively. More precisely the most active fraction SC14 was assessed in dose response assay and synergistic potential resulted in 50% reduction (EC50 Value) in HCV titer of genotype 1a and 3a at a concentration of 71.96 ± 8.67 µg and 31.75 ± 3.28 µg, respectively, at a concentration of 100 µg. As per our research work, the S. cumine extract has shown a promising effect on HCV genotypes 1a and 3a. Moreover the purified fraction S. cumine SC14 has a potential synergistic effect and ability to suppress the gene effect of NS3 during transfection in Huh-7 cells and GC/MS analysis reports the presence of Di-n-octyl phthalate (C24H38O4) which can be future direct-acting antiviral therapy against Hepatitis C virus.


[Current surgical options and outcomes for newborns with hypoplastic left heart syndrome].
Since the first successful palliation was performed by Norwood et al. in 1983, there have been substantial changes in diagnosis, management, and outcomes of hypoplastic left heart syndrome, Survival for stage 1 palliation has increased to 90% in many centres, with patients potentially surviving into adulthood. However, the associated morbidity and mortality remain substantial. Although the principles of staged surgical palliation of hypoplastic left heart syndrome are well established, there is significant variability in surgical procedure and management between centres, and several controversial aspects remain unresolved. In this review, we summarize the current surgical and management options for newborns with hypoplastic left heart syndrome and their outcomes.


Evaluation of hepatocellular carcinoma using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation.
The appearance of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS) in the vascular phase is described and evaluated as to whether the enhancement pattern correlates with the degree of cellular differentiation. One hundred four HCCs were prospectively evaluated with CEUS using coherent-contrast imaging (CCI) and SonoVue with a low mechanical index (<0.2). The enhancement of HCCs in the vascular phase was analyzed according to the degree of pathological differentiation obtained by fine-needle biopsy. In the arterial phase, all HCCs except for four well differentiated ones (96.2%) showed enhancement ( P<0.05). Histological differentiation of hypoechoic lesions in the early portal phase (7 HCCs; 16%) significantly differed from hyperechoic (1 HCC; 1%) or isoechoic lesions (87 HCCs; 83.6%) ( P<0.05), with a significant probability of a worse differentiation in hypoechoic lesions. Histological differentiation of isoechoic lesions in the late phase (30 HCCs; 28.8%) significantly differed from hypoechoic lesions (74 HCCs; 71.2%) ( P<0.05), with a significant probability of a better differentiation in isoechoic lesions. CEUS using CCI and SonoVue revealed enhancement in the arterial phase in >95% of HCCs, with a few well-differentiated cases not being diagnosed due to the absence of enhancement. Echogenicity in the portal and late phases correlated with cellular differentiation.


A collaborative workflow between pathologists and deep learning for the evaluation of tumour cellularity in lung adenocarcinoma.
The reporting of tumour cellularity in cancer samples has become a mandatory task for pathologists. However, the estimation of tumour cellularity is often inaccurate. Therefore, we propose a collaborative workflow between pathologists and artificial intelligence (AI) models to evaluate tumour cellularity in lung cancer samples and propose a protocol to apply it to routine practice. We developed a quantitative model of lung adenocarcinoma that was validated and tested on 50 cases, and a collaborative workflow where pathologists could access the AI results and adjust their original tumour cellularity scores (adjusted-score) that we tested on 151 cases. The adjusted-score was validated by comparing them with a ground truth established by manual annotation of haematoxylin and eosin slides with reference to immunostains with thyroid transcription factor-1 and napsin A. For training, validation, testing the AI and testing the collaborative workflow, we used 40, 10, 50 and 151 whole slide images of lung adenocarcinoma, respectively. The sensitivity and specificity of tumour segmentation were 97 and 87%, respectively, and the accuracy of nuclei recognition was 99%. One pathologist's visually estimated scores were compared to the adjusted-score, and the pathologist's scores were altered in 87% of cases. Comparison with the ground truth revealed that the adjusted-score was more precise than the pathologists' scores (P < 0.05). We proposed a collaborative workflow between AI and pathologists as a model to improve daily practice and enhance the prediction of tumour cellularity for genetic tests.


Trichilemmoma: an immunohistochemical study of cytokeratins.
The histogenesis of trichilemmoma remains unclear. To clarify the histogenesis of trichilemmoma by evaluating its cytokeratin (CK) expression. In three cases of trichilemmoma, CK expression was studied immunohistochemically using seven antikeratin antibodies against CK1, 10, 14-17 and 19, respectively. CK1 and CK10 were present in keratinizing ductal epithelium. CK14 was present in the whole layer. CK15 was present in suprabasal layers in two cases. CK16 was present in the suprabasal layer, but was absent in keratinizing ductal epithelium. CK17 was present in suprabasal layers and the sebaceous duct-like structure. CK19 was totally absent. These results showed that trichilemmoma may differentiate mainly towards two directions: infundibular keratinization and proliferation of the outer root sheath with undifferentiated and pluripotent characteristics.


Clinical Characteristics Associated with Musculoskeletal Extracutaneous Manifestations in Pediatric and Adult Morphea: A Prospective, Cohort Study.
Morphea is an autoimmune condition of the skin associated with functional sequelae resulting from musculoskeletal involvement. Systematic investigation of risk for musculoskeletal involvement is limited, particularly in adults. This knowledge gap impairs patient care because practitioners are unable to risk stratify patients. To address this gap, we determined the frequency, distribution, and type of musculoskeletal (MSK) extracutaneous manifestations affecting joint and bone with overlying morphea lesions using cross-sectional analysis of 1,058 participants enrolled in two prospective cohort registries (Morphea in Children and Adults Cohort [n = 750] and National Registry for Childhood Onset Scleroderma [n = 308]). Additional analysis included the identification of clinical features associated with MSK extracutaneous manifestations. MSK extracutaneous manifestations occurred in 274 of 1,058 participants (26% overall, 32% pediatric, and 21% adults). Children had a limited range of motion of larger joints (i.e., knees/hips/shoulders), whereas the involvement of smaller joints (i.e., toes/temporomandibular joint) was more common in adults. Multivariable logistic regression showed that deep tissue involvement had the strongest association with musculoskeletal features, with a lack of deep tissue involvement having a negative predictive value of 90% for MSK extracutaneous manifestations. Our results underscore the need to evaluate MSK involvement in adult and pediatric patients and the utility of using depth of involvement in addition to anatomic distribution to risk stratify patients.


Removal of diethyl phthalate from water by ozone microbubbles in a pilot plant.
Ozone microbubbles (OMBs) were used to remove diethyl phthalate (DEP) from water in a pilot plant. The removal of DEP and the mineralization efficiency were investigated under various reaction conditions. The removal of DEP by OMBs was very effective at the high pH and high ozone generation rates. Almost complete mineralization of DEP could be achieved at the high pH. The contribution of OH was computed by using a hydroxyl radical scavenger (i.e. t-BuOH). In neutral and alkaline media, the reaction of DEP with OH dominated over its direct reaction with ozone. The overall oxidation reaction fitted a second-order kinetic model. The overall rate constant and the volumetric mass transfer coefficient of ozone slightly increased with increasing pH. The results indicate that the OMBs were efficient in terms of the reduction of concentration of DEP and its complete mineralization.


Key concepts in genetic epidemiology.
This article is the first in a series of seven that will provide an overview of central concepts and topical issues in modern genetic epidemiology. In this article, we provide an overall framework for investigating the role of familial factors, especially genetic determinants, in the causation of complex diseases such as diabetes. The discrete steps of the framework to be outlined integrate the biological science underlying modern genetics and the population science underpinning mainstream epidemiology. In keeping with the broad readership of The Lancet and the diverse background of today's genetic epidemiologists, we provide introductory sections to equip readers with basic concepts and vocabulary. We anticipate that, depending on their professional background and specialist knowledge, some readers will wish to skip some of this article.


Interactions between dissolved natural organic matter and adsorbed DNA and their effect on natural transformation of Azotobacter vinelandii.
To better understand gene transfer in the soil environment, the interactions between dissolved natural organic matter (NOM) and chromosomal or plasmid DNA adsorbed to silica surfaces were investigated. The rates of NOM adsorption onto silica surfaces coated with DNA were measured by quartz crystal microbalance (QCM) and showed a positive correlation with carboxylate group density for both soil and aquatic NOM in solutions containing either 1mM Ca(2+) or Mg(2+). Increasing total dissolved organic carbon (DOC) concentrations of the NOM solution also resulted in an increase in the adsorption rates, likely due to divalent cation complexation with NOM carboxylate groups and the phosphate backbones of the DNA. The results from Fourier transform infrared spectroscopy (FTIR) for dissolved DNA and DNA adsorbed on silica beads also suggest that adsorption may result from divalent cation complexation with the DNA's phosphate backbone. The interactions, between DNA and NOM, however, did not influence natural transformation of Azotobacter vinelandii by DNA. These results suggest that DNA adsorbed to NOM-coated silica or otherwise complexed with NOM remains available for natural transformation in the environment.


Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitäts Trial (BASKET).
No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice. The Basel stent cost-effectiveness trial (BASKET) included 826 consecutive patients treated with angioplasty and stenting for 1281 de-novo lesions, irrespective of indication for angioplasty. Patients were randomised to one of two DES (Cypher, n=264; Taxus, n=281) or to a cobalt-chromium-based BMS (Vision, n=281) and followed up for 6 months for occurrence of major adverse cardiac events and costs. Analysis was by intention-to-treat. The primary endpoint was cost-effectiveness after 6 months, with effectiveness defined as reduction of major adverse cardiac events. Cardiac death, myocardial infarction, or target vessel revascularisation occurred in 39 of 544 (7.2%) patients with DES and 34 of 280 (12.1%) with BMS (odds ratio 0.56, 95% CI 0.35-0.91; p=0.02), without significant differences between the two DES. Total costs at 6 months were higher with DES (mean 10,544, SD 6849) than with BMS (9639, 9067; p<0.0001); higher stent costs of DES were not compensated for by lower follow-up costs. Incremental cost-effectiveness ratio of DES compared with BMS to avoid one major event was 18,311, and costs per quality-adjusted life-year gained were more than 50 000. Subgroup analyses showed that DES were more cost-effective for elderly patients in specific high-risk groups. In a real-world setting, use of DES in all patients is less cost effective than in studies with selected patients. Use of these stents could be restricted to patients in high-risk groups.


Influence of unilateral motor behaviors on the judgment of valenced stimuli.
Two experiments were conducted so as to examine how different motor activations (unilateral contraction and extension-flexion paradigms) of the motivational systems of approach and avoidance influenced participants' evaluations of valenced stimuli (figurative expressions and everyday life pictures). The results of the first Study (Study 1) showed that a motor congruence model was operative when processing positive facial expressions, this phenomenon was reversed, however, when negative faces were processed. This occurrence disappeared when weaker negative or positive faces were evaluated. These results were replicated in Study 2 with the use of valenced pictures taken from the International Affective Picture System (IAPS). The overall results were analyzed as a combination of conceptual-motor compatibility and motor congruence models throwing new light on the influence of motor behaviors on judgments.


The use of antiseptics in wound care.
Three critiques review the classic paper cited below and discuss its influence on developments in wound care.


Age matters: variations in parasitoid diversity along a successional gradient in a dry semi-deciduous tropical forest.
Parasitoids are an important group of insects because their species number is among the highest. Multiple studies have addressed the relationships between forest successional age and insect diversity by focusing on herbivorous organisms, but changes in diversity of parasitoids are still poorly known. This work analyses the diversity of parasitoids in tropical forests representing three successional stages. A total of 30 traps were placed, ten in each forest successional stages. We estimated true diversity of Ichneumonidae species and guilds and explored the relationship between their diversity and the abundance of plant species using an Indicator Species Analysis; the relationship between parasitoid species and plant richness and abundance was tested using a Redundancy Analysis. A total of 1522 individuals and 168 morpho-species were captured in four months. Species richness showed no differences; however, parasitoid abundance was higher in young forest, while intermediate forest had the highest true diversity values (1D) with 71.6 effective species. According to insect guilds, richness, abundance, and diversity were similar in the three vegetation successional stages. This finding may be explained based on the intermediate disturbance hypothesis, which postulates that moderate disturbance levels favor the highest diversity. In conclusion, successional age matters, i.e., diversity is the highest in intermediate stages, while the old forests harbors guilds unique to that successional stage, such as parasitoids of melitophagous larvae of bees. Other successional stages were characterized by a single species of parasitoid, belonging to the genera Eiphosoma and Anomalon, which may indicate altered and preserved forests, respectively.


Comparison of pressure- and volume-controlled ventilation during laparoscopic colectomy in patients with colorectal cancer.
This study investigated the differences in airway mechanics and postoperative respiratory complications using two mechanical ventilation modalities and the relationship between biomarkers and postoperative respiratory complications in patients with colorectal cancer who underwent laparoscopic colectomy. Forty-six patients with colorectal cancer scheduled for laparoscopic colectomy were randomly allocated to receive mechanical ventilation using either volume-controlled ventilation (VCV) (n = 23) or pressure-controlled ventilation (PCV) (n = 23). Respiratory parameters were measured and plasma sRAGE and S100A12 were collected 20 minutes after the induction of anesthesia in the supine position without pneumoperitoneum (T1), 40 minutes after 30° Trendelenburg position with pneumoperitoneum (T2), at skin closure in the supine position (T3), and 24 hours after the operation (T4). The peak airway pressure (Ppeak) at T2 was lower in the PCV group than in the VCV group. The plateau airway pressures (Pplat) at T2 and T3 were higher in the VCV group than in the PCV group. Plasma levels of sRAGE at T2 and T3 were 1.6- and 1.4-fold higher in the VCV group than in the PCV group, while plasma S100A12 levels were 2.6- and 2.2-fold higher in the VCV group than in the PCV group, respectively. There were significant correlations between Ppeak and sRAGE, and between Ppeak and S100A12. There were also correlations between Pplat and sRAGE, and between Pplat and S100A12. sRAGE and S100A12 levels at T2 and T3 showed high sensitivity and specificity for postoperative respiratory complications. Postoperative respiratory complications were 3-fold higher in the VCV group than in the PCV group. In conclusion, during laparoscopic colectomy in patients with colorectal cancer, the peak airway pressure, the incidence of postoperative respiratory complications, and plasma sRAGE and S100A12 levels were lower in the PCV group than in the VCV group. Intra- and postoperative plasma sRAGE and S100A12 were useful for predicting the development of postoperative respiratory complications.


Elevated ammonium concentrations from wastewater discharge depress primary productivity in the Sacramento River and the Northern San Francisco Estuary.
Primary production in the Northern San Francisco Estuary (SFE) has been declining despite heavy loading of anthropogenic nutrients. The inorganic nitrogen (N) loading comes primarily from municipal wastewater treatment plant (WTP) discharge as ammonium (NH(4)). This study investigated the consequences for river and estuarine phytoplankton of the daily discharge of 15 metric tons NH(4)-N into the Sacramento River that feeds the SFE. Consistent patterns of nutrients and phytoplankton responses were observed during two 150-km transects made in spring 2009. Phytoplankton N productivity shifted from NO(3) use upstream of the WTP to productivity based entirely upon NH(4) downstream. Phytoplankton NH(4) uptake declined downstream of the WTP as NH(4) concentrations increased, suggesting NH(4) inhibition. The reduced total N uptake downstream of the WTP was accompanied by a 60% decline in primary production. These findings indicate that increased anthropogenic NH(4) may decrease estuarine primary production and increase export of NH(4) to the coastal ocean.


Tunable optical topological transitions of plasmon polaritons in WTe2 van der Waals films.
Naturally existing in-plane hyperbolic polaritons and the associated optical topological transitions, which avoid the nano-structuring to achieve hyperbolicity, can outperform their counterparts in artificial metasurfaces. Such plasmon polaritons are rare, but experimentally revealed recently in WTe2 van der Waals thin films. Different from phonon polaritons, hyperbolic plasmon polaritons originate from the interplay of free carrier Drude response and interband transitions, which promise good intrinsic tunability. However, tunable in-plane hyperbolic plasmon polariton and its optical topological transition of the isofrequency contours to the elliptic topology in a natural material have not been realized. Here we demonstrate the tuning of the optical topological transition through Mo doping and temperature. The optical topological transition energy is tuned over a wide range, with frequencies ranging from 429 cm-1 (23.3 microns) for pure WTe2 to 270 cm-1 (37.0 microns) at the 50% Mo-doping level at 10 K. Moreover, the temperature-induced blueshift of the optical topological transition energy is also revealed, enabling active and reversible tuning. Surprisingly, the localized surface plasmon resonance in skew ribbons shows unusual polarization dependence, accurately manifesting its topology, which renders a reliable means to track the topology with far-field techniques. Our results open an avenue for reconfigurable photonic devices capable of plasmon polariton steering, such as canaling, focusing, and routing, and pave the way for low-symmetry plasmonic nanophotonics based on anisotropic natural materials.


Clinical results with Omni-Orthocor, an implantable antitachycardia pacing system.
Omni-Orthocor 234A and 239A are implantable pacers capable of synchronization with an external overdriver. Synchronous or asynchronous burst pacing, synchronized extrastimuli, or a combination of both can be obtained. Upon recognition of a tachycardia, the patient or physician can initiate pace-termination. Omni-Orthocor was implanted in 69 patients (53 for ventricular tachycardia, 11 for supraventricular tachycardia, 2 each with AV nodal reentry and WPW, and 1 patient with concealed accessory pathway). Thirty-five patients performed out of hospital termination. More resistant tachycardias were terminated in the hospital with 76.3% success in VT and only 50% success for SVT. Burst pacing was used in 75% of patients. Noninvasive electrophysiologic study was performed on all patients, and was the sole use of Omni-Orthocor in 20 patients. The device was not implicated in the six sudden death patients in this series.


Correction: Correlation between cognition and plasma noradrenaline level in Alzheimer's disease: a potential new blood marker of disease evolution.
A Correction to this paper has been published: https://doi.org/10.1038/s41398-020-01102-y.


Successful management of iliac mycotic aneurysm secondary to Klebsiella endocarditis--report of a case.
A case of common iliac mycotic aneurysm that presumably developed secondary to Klebsiella endocarditis was described. Recently, reports on gram negative septicemia and endocarditis have been on the increase. However, mycotic aneurysms secondary to bacterial endocarditis and particularly to Klebsiella endocarditis are rare. Inadequately treated serious gram negative septicemias have a high mortality rate. Early diagnosis and adequate combination chemotherapy with prompt surgical intervention were proven to be important factors in the successful management of such a complication.


The tomato Mi-1 gene confers resistance to both root-knot nematodes and potato aphids.
Mi-1, a Lycopersicon peruvianum gene conferring resistance to the agricultural pests, root-knot nematodes, and introgressed into tomato, has been cloned using a selective restriction fragment amplification based strategy. Complementation analysis of a susceptible tomato line with a 100 kb cosmid array yielded a single cosmid clone capable of conferring resistance both to the root-knot nematode Meloidogyne incognita and to an unrelated pathogen, the potato aphid Macrosiphum euphorbiae. This resistance was stable. The Mi-1 gene encodes a protein sharing structural features with the nucleotide-binding site leucine-rich repeat-containing type of plant resistance genes.


Characterization of the γδ T-cell compartment during infancy reveals clear differences between the early neonatal period and 2 years of age.
γδ T cells are unconventional T cells that function on the border of innate and adaptive immunity. They are suggested to play important roles in neonatal and infant immunity, although their phenotype and function are not fully characterized in early childhood. We aimed to investigate γδ T cells in relation to age, prematurity and cytomegalovirus (CMV) infection. Therefore, we used flow cytometry to characterize the γδ T-cell compartment in cord blood and peripheral blood cells from 14-day-, 2-year- and 5-year-old children, as well as in peripheral blood samples collected at several time points during the first months of life from extremely premature neonates. γδ T cells were phenotypically similar at 2 and 5 years of age, whereas cord blood was divergent and showed close proximity to γδ T cells from 14-day-old neonates. Interestingly, 2-year-old children and adults showed comparable Vδ2+ γδ T-cell functionality toward both microbial and polyclonal stimulations. Importantly, extreme preterm birth compromised the frequencies of Vδ1+ cells and affected the functionality of Vδ2+ γδ T cells shortly after birth. In addition, CMV infection was associated with terminal differentiation of the Vδ1+ compartment at 2 years of age. Our results show an adult-like functionality of the γδ T-cell compartment already at 2 years of age. In addition, we demonstrate an altered γδ T-cell phenotype early after birth in extremely premature neonates, something which could possible contribute to the enhanced risk for infections in this vulnerable group of children.


In-memory mechanical computing.
Mechanical computing requires matter to adapt behavior according to retained knowledge, often through integrated sensing, actuation, and control of deformation. However, inefficient access to mechanical memory and signal propagation limit mechanical computing modules. To overcome this, we developed an in-memory mechanical computing architecture where computing occurs within the interaction network of mechanical memory units. Interactions embedded within data read-write interfaces provided function-complete and neuromorphic computing while reducing data traffic and simplifying data exchange. A reprogrammable mechanical binary neural network and a mechanical self-learning perceptron were demonstrated experimentally in 3D printed mechanical computers, as were all 16 logic gates and truth-table entries that are possible with two inputs and one output. The in-memory mechanical computing architecture enables the design and fabrication of intelligent mechanical systems.


Proteome analysis of aflatoxin B1-induced hepatocarcinogenesis in tree shrew (Tupaia belangeri chinensis) and functional identification of candidate protein peroxiredoxin II.
In order to explore the proteins responsible for hepatocellular carcinoma (HCC), aflatoxin B(1)-induced hepatocarcinogenesis in tree shrew (Tupaia belangeri chinensis) was analyzed with 2-DE and MS. By comparing HCC samples with their own precancerous biopsies and HCC-surrounding tissues, a group of candidate proteins that differentially expressed in HCC were obtained. Peroxiredoxin (Prx) II, one of the candidates with distinct alteration, was further investigated and validated. Western blot and RT-PCR assays confirmed the overexpression of Prx II in both tree shrew and human HCC tissues. RNA interference for silencing Prx II was employed subsequently to explore the function and underlying mechanism of Prx II on liver cancer cell line Hep3B. Results showed the cell proliferation and clone formation decreased obviously when Prx II expression was inhibited, while the flow cytometer analysis showed the percentage of cell apoptosis enhanced. Inhibition of Prx II expression also obviously increased the generation of ROS and malondialdehyde, both are the products from peroxidation. These results imply the important role of Prx II in hepatocarcinogenesis, possibly through its function in regulating peroxidation and hereby to provide a favorable microenvironment for cancer cell surviving and progressing.


Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants.
Although there is controversy about the absolute need for a reversal agent for the new direct oral anticoagulants (DOACs), the absence of such an agent is a barrier to more widespread use of these agents. For the management of major life-threatening bleeding with the DOACs, most authorities recommend the use of four factor prothrombin complex concentrates, although the evidence to support their use in terms of improving outcomes is meager. At the present time, there are three antidotes in development and poised to enter the market. Idarucizumab is a drug-specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran. Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Ciraparantag is a universal antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.


Aging--RNA in development and disease.
Given that RNA is involved in virtually all biological processes, it is perhaps not surprising that several RNA-binding proteins are associated with aging and with different age-related disorders. Other articles in this volume will discuss some specific examples of diseases where RNA plays a role that are also associated with aging, such as cancer and inflammation, so here I will discuss some general aspects of how RNA changes with the aging process. I will also discuss some specific examples of RNA-binding proteins that are associated with age-dependent neurological diseases as these provide an interesting framework to examine how lifetime mutations might lead to a late onset disease, although the answers to these questions are still not well understood.


Studies on the substrate specificity of purified human milk bile salt-activated lipase.
The fatty acid specificity of the bile salt-activated lipase purified from human milk was studied using C12 to C54 (total acyl carbon) saturated and the C54 unsaturated triacylglycerols. Kinetic studies indicated that the short chain triacylglycerols were hydrolyzed more readily than the long chain triacylglycerols, and that the long chain unsaturated triacylglycerols were attacked more readily than the long chain saturated triacylglycerols. This fatty acid specificity was also apparent intramolecularly, both short chain and unsaturated fatty acids being released at higher rates than the saturated long chain acids. The enzyme possessed neither positional specificity nor stereospecificity as indicated by the nearly simultaneous appearance of the sn-1,2-, sn-2,3-, and sn-1,3-dioleoylglycerols from trioleoylglycerol. The hydrolyses of these three ester bonds were approximately at their anticipated chemical reactivities. Synthetic rac-1-monooleoylglycerols were hydrolyzed about 2 times faster than the sn-2-monooleoylglycerols. It is concluded that the bile salt-activated lipase may possess a special potential for a rapid release of short chain and polyunsaturated fatty acids from dietary triacylglycerols in the intestinal lumen of infants.


Case 11: large, infected, necrotic mixed-aetiology leg ulcer.
This painful and malodorous ulcer was covered with 40% necrotic tissue. Combined use of octenilin Wound gel and Wound Irrigation Solution gently debrided the necrotic tissue, and helped reduce the pain and malodour. Within 6 weeks, the wound was covered with granulation tissue.


Placenta accreta and cesarean scar pregnancy: overlooked costs of the rising cesarean section rate.
An unintended consequence of the rising cesarean section rate is abnormal placentation in subsequent pregnancies, leading to the clinical complications of placenta accreta and cesarean scar pregnancies. Both of these clinical entities are associated with high rates of maternal morbidity and mortality. This article reviews the potential mechanisms by which uterine scarring may lead to abnormal trophoblast invasion, the association of cesarean section with placenta accreta and scar pregnancies, current management, and suggestions for future research to reduce the incidence of these potentially devastating complications of pregnancy.


Distress and demoralization of hospital nurses as a function of sources of stress and job seniority.
To explore job-related factors associated with distress and demoralization among hospital nurses, using a cross-sectional mixed-method design. Sources of job stress for nurses are mainly organizational or emotional care-related and can result in adverse outcomes such as distress or demoralization, but factors associated with demoralization in nurses still need to be thoroughly explored. A convenience sample of 150 nurses from three public hospitals completed an online survey on job stress, distress, demoralization, and feelings of entrapment in the caring profession. Emotional job stress was linked to higher distress and demoralization, compared to no job stress, and to higher feelings of entrapment, compared to both organizational and no job stress, among senior nurses. This pilot study points to the study of demoralization as a promising line of research in hospital nursing, but further longitudinal studies with larger samples are needed.


Mutual inhibition of the binding of Clq and protein A to rabbit IgG immune complexes.
A complex of rabbit IgG antibody with horseradish peroxidase covalently linked to Sepharose 4B was used as an insoluble immune complex for studying the binding of complement factor C1q protein A from Staphylococcus aureus, and its IgG-binding fragments AB and B, to rabbit IgG. It was shown that protein A (mol. wt approx. 42,000) and fragments AB and B (mol. wts approx. 14,000 and 7000, respectively) inhibited the binding of C1q to insoluble immune complex at 4 degrees C. However, at 37 degrees C fragment B did not inhibit this binding. On the other hand, C1q, when bound to an insoluble immune complex, almost completely blocked the binding of protein A and fragment B at both temps. The higher affinity of C1q for its CH2-binding site than of fragment B for its CH2-binding site may explain the displacement of the latter from the CH2 domain. The mutual inhibition of the binding of C1q and protein A (and its smaller fragments) indicates that the binding sites for C1q and protein A are closely located in the CH2 domain.


MicroRNAs and colorectal cancer chemoresistance: New solution for old problem.
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with a significant mortality rate. Despite the great advances in cancer treatment in the last few decades, effective treatment of CRC is still under challenge. One of the main problems associated with CRC treatment is the resistance of cancer cells to chemotherapy drugs. Many studies have been carried out to identify CRC chemoresistance mechanisms, and shed light on the role of ATP-binding cassette transporters (ABC transporters), enzymes as thymidylate synthase, some signaling pathways, and cancer stem cells (CSC) in chemoresistance and failed CRC chemotherapies. Other studies have also been recently carried out to find solutions to overcome chemoresistance. Some of these studies have identified the role of miRNAs in chemoresistance of the CRC cells and the effective use of these micro-molecules to CRC treatment. Considering the results of these studies, more focus on miRNAs likely leads to a proper solution to overcome CRC chemoresistance. The current study has reviewed the related literature while discussing the efficacy of miRNAs as potential clinical tools for overcoming CRC chemoresistance and reviewing the most important chemoresistance mechanisms in CRC cells.


Thoraco-pelvic orthosis: a portable and removable bassinet for secure patient immobilization after primary bladder exstrophy closure.
A portable and removable thoraco-pelvic orthosis for patient immobilization after neonatal primary bladder exstrophy closure is described. The device is made of a polyethylene shell, moulded at 170°C, coated inside with a 5 mm pad of plastazote and works applying a constant gentle pressure on the hips.


A case of solid variant type of pancreatic serous cystadenoma mimicking islet cell tumor.
We report a case of the solid variant type of pancreatic serous cystadenoma in which the very small size of the cyst on ultrasonography and computed tomography made distinguishing this tumor from other hypervascular solid tumors difficult. Recognizing the imaging features of high signal intensity on heavily T2-weighted image on MR may be helpful for correctly diagnosing the solid variant type of pancreatic serous cystadenoma.


Gastrointestinal enzyme production of bioactive peptides from royal jelly protein and their antihypertensive ability in SHR.
In order to clarify the potential physiological function of royal jelly (RJ), we report here the gastrointestinal enzyme production of antihypertensive peptides from RJ. Intact RJ and its protein fraction did not retard the action of angiotensin I-converting enzyme (ACE) activity at all. However, development of ACE inhibition power of RJ was newly observed by pepsin hydrolysis (IC(50)=0.358 mg protein/mL), and the subsequent trypsin and chymotrypsin hydrolyses (IC(50)=0.099 mg protein/mL). Single oral administration of this gastrointestinal RJ hydrolysate (1 g/kg dose) in 10-week spontaneously hypertensive rat resulted in a significant reduction of systolic blood pressure of 22.7 plus minus 3.6 mmHg at 2 hr (P<0.05 vs. 0 hr by one-way ANOVA, n=7). Then, the RJ hydrolysate was fractionated with gel permeation chromatography to obtain the di- and tri-peptides (DTP) fraction. As a result of isolation from the DTP fraction by reversed phase-high performance liquid chromatography, eleven ACE inhibitory peptides were isolated from the DTP-RJ hydrolysate. Some of the ACE inhibitors were derived from the RJ-glycoprotein; eight peptides with the IC(50) value of <10 &mgr;M were identified from natural resources for the first time. Consequently, RJ protein was thought to be a good resource of ACE inhibitory peptides produced by the gastrointestinal enzyme hydrolyses.


70 years of Landau-Teller theory for collisional energy transfer. Semiclassical three-dimensional generalizations of the classical collinear model.
This article, in historical retrospective, describes the development of the celebrated Landau-Teller (LT) model of 1936 for vibrational-translational energy exchange in collisions of an atom with a diatomic molecule. We discuss semiclassical generalizations of the classical LT model and generalizations of the collinear LT model to account for the effects of rotation of the diatom on the vibrational relaxation rate. The former is based on the recovery of the Landau semiclassical exponent from the classical LT encounter time, and the latter on the definition of a 1-D driving mode within the manifold of the translational and rotational degrees of freedom of the colliding partners. The utility of generalized LT models is illustrated by three case studies that exemplify weak and strong effects of the rotation as well as the efficiencies of different driving modes in the vibrational relaxation of highly asymmetric diatoms.


The Association of Certain Seminal Phthalate Metabolites on Spermatozoa Apoptosis: An Exploratory Mediation Analysis via Sperm Protamine.
Earlier studies have suggested that exposure to phthalates (PAEs) may induce spermatozoa apoptosis. Sperm protamine as a molecular biomarker during spermatozoa apoptotic processes may mediate the association between PAE exposure and spermatozoa apoptosis. This study aimed to explore whether sperm protamine mediates the association of PAE exposure with spermatozoa apoptosis. We determined sperm protamine levels, 8 PAE metabolite concentrations in seminal plasma, and 3 spermatozoa apoptosis parameters among 111 men from an infertility clinic. The associations of PAEs as individual chemicals and mixtures with sperm protamine were determined. The mediating roles of protamine in the associations between PAEs and spermatozoa apoptosis parameters were examined by mediation analysis. After adjusting for confounders, we observed positive correlations between seminal plasma concentrations of mono(2-ethylhexyl) phthalate (MEHP) and sperm protamine-1 and protamine ratio. Estimates comparing highest vs. lowest quartiles of MEHP concentration were 4.65% (95% CI: 1.47%, 7.82%) for protamine-1 and 25.86% (95% CI: 3.05%, 53.73%) for protamine ratio. The quantile g-computation models showed that the adjusted protamine-1 per quartile increase in PAE mixture was 9.42% (95% CI: 1.00, 20.92) with MEHP being the major contributor. Although the joint association between PAE mixture and protamine ratio was negligible, MEHP was still identified as the main contributor. Furthermore, we found that protamine-2 and protamine ratio levels in the highest quartiles exhibited a decrease of 43.45% (95% CI: 60.54%, -19.75%) and an increase of 122.55% (95% CI: 60.00%, 209.57%) in Annexin V+/PI- spermatozoa relative to the lowest quartiles, respectively. Mediation analysis revealed that protamine ratio significantly mediated 55.6% of the association between MEHP and Annexin V+/PI- spermatozoa elevation (5.13%; 95% CI: 0.04%, 10.52%). Our findings provided evidence that human exposure to PAEs was associated with increased protamine levels which may mediate the process of spermatozoa apoptosis.


Effects of sublingual nitroglycerin on working conditions of the heart and arterial system: analysis using wave intensity.
The effects of nitroglycerin (NTG) on the vascular system are well known. However, the effects of NTG on the heart are still obscure, because these effects are modified by those on the vascular system, and vice versa. Therefore, to evaluate the hemodynamic effects of NTG, it is important to understand the interaction between the heart and the vascular system. Wave intensity (WI) is a new hemodynamic index that provides information about working conditions of the heart interacting with the arterial system. The purpose of this study was to evaluate the interactive effects of NTG on the cardiovascular system in normal subjects using wave intensity. We simultaneously measured carotid arterial blood flow velocity and diameter change using a specially designed ultrasonic system, and calculated the WI and the stiffness parameter β. Measurements were made in 13 normal subjects (9 men and 4 women, aged 47 ± 10 years) in the supine position before and after sublingual NTG. The maximum value of WI (W 1) and the mid-systolic expansion wave (X) increased (W 1 from 9.1 ± 4.3 to 12.3 ± 5.5 × 10(3) mmHg m/s(3), P < 0.001; X from 105 ± 185 to 345 ± 370 mmHg m/s(3), P < 0.05). β increased (from 10.5 ± 3.8 to 14.1 ± 3.8, P < 0.001). The pressure contours changed considerably. NTG increased W 1 and the mid-systolic expansion wave, which suggests enhanced cardiac power during the initial ejection and mid-systolic unloading. These results are new findings about the effects of NTG that can be added to the widely known late systolic unloading and preload reduction. NTG also increased arterial stiffness, which reduces the Windkessel function. By using an echo-Doppler system, WI can be obtained noninvasively. WI has the clinical potential to provide quantitative and detailed information about working conditions of the heart interacting with the arterial system.


Temporalis Muscle Tendon Unit Transfer for Smile Restoration After Facial Paralysis.
Temporalis muscle tendon unit (MTU) transfer may be used as a single-stage procedure for dynamic reanimation of the paralyzed face. Principles and biomechanics of muscle function and tendon transposition are essential in optimizing outcome. Critical steps and pearls for success include minimizing scarring, maintaining glide plains, mobilizing adequate tendon length, insertion of MTU at ideal tension based on intraoperative dynamic tension-excursion relationship, and insertion of tendon as close to the lip margin as possible. Because muscles adapt to tension, load, and task changes by altering their sarcomere arrangement and muscle fiber composition, physiotherapy should be initiated to use the repurposed temporalis MTU for smile restoration.


Attenuation by habitual alcohol drinking of the associations of obesity with blood pressure and pulse pressure.
Obesity and alcohol drinking are known to be risk factors for hypertension. However, it remains to be determined whether alcohol affects the relationships of obesity with blood pressure and pulse pressure. The participants in this study were 29 171 men who had received annual health checkups. Relationships of BMI with blood pressure and pulse pressure were investigated in four subject groups divided by average daily alcohol consumption (grams of ethanol/day), non-, light (<22), moderate (≥22 and <44) and heavy (≥44) drinkers. BMI was significantly correlated with SBP and DBP levels both in nondrinkers and drinkers. The strength of the correlations was significantly weaker in drinkers than in nondrinkers. Odds ratios for hypertension in subjects with vs. subjects without obesity tended to be lower with an increase in alcohol intake (odds ratios with 95% confidence intervals: 4.09 (3.69-4.52) in nondrinkers; 3.11 (2.62-3.68) in light drinkers; 2.87 (2.61-3.16) in moderate drinkers; 2.81 (2.49-3.18) in heavy drinkers). Pulse pressure was weakly but significantly associated with BMI and obesity, and these associations were significantly weaker in heavy drinkers than in nondrinkers. There were significant odds ratios for hypertension and high pulse pressure of the interaction term between obesity and alcohol drinking. The associations of BMI with blood pressure and pulse pressure and the associations of obesity with hypertension and high pulse pressure were weaker in drinkers than in nondrinkers. Thus, alcohol drinking attenuates the associations of obesity with hypertension and high pulse pressure.


Transforming growth factor-β1 induces cholesterol synthesis by increasing HMG-CoA reductase mRNA expression in keratinocytes.
In this study, we investigated the effect of TGF-β1 on cholesterol synthesis in human keratinocytes. TGF-β1 increased the level of cholesterol and the mRNA level of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in human keratinocytes. These results show that TGF-β1 induces cholesterol synthesis by increasing HMG-CoA reductase mRNA expression in human keratinocytes.


Proteome approach for identification of schistosomiasis japonica vaccine candidate antigen.
Experimental vaccination with radiation-attenuated cercariae (RAC) confers possible practical levels of resistance to challenge infection by humoral and by cellular mechanism. Here, we aimed to identify possible vaccine antigens by using specific IgG antibody from RAC vaccinated miniature pig. Two milligrams of soluble egg antigen (SEA) or schistosomal worm antigen preparation (SWAP) was fractionated using two dimensional liquid chromatography (proteome PF 2D) consisted of high performance chromatofocusing (HPCF) and high resolution reversed phase chromatography (HPRP). Of the 42 HPCF fractions of SEA or SWAP, 26 (61.9%) or 15 (35.7%) showed positive dot blot reaction with RAC vaccinated serum respectively. The dot blot positive fractions were applied to the second HPRP column. One hundred and seven out of 26 x 96 of SEA fractions and 18 out of 15 x 96 SWAP fractions reacted with RAC vaccinated serum. From the positive fractions we chose 17 of SEA and 10 of SWAP that had no reactivity with normal cercariae infected (NCI) sera and had single peak of 214 nm; and automated N-terminal amino acid sequence based on in situ Edman Reaction was conducted. Four sequences were obtained and applied to the homology search in NCBI database. A total of eight candidate genes were listed up and their cDNA clones from schistosomula stage were obtained. Two of the recombinant proteins (AAW27472.1 and AXX25883.1) showed strong reactivity with the RAC vaccinated serum but marginal with NCI serum. This protocol using proteome PF 2D could be applicable in identifying immunoreactive proteins from crude extract for the development of vaccines or for diagnostics.


Activation of collagen synthesis in primary culture of rat liver parenchymal cells (hepatocytes).
An increase in collagen synthesis by hepatic parenchymal cells (hepatocytes) was observed during 8 days in primary culture by the quantification of total [3H]hydroxyproline as a marker of total collagen synthesis and the ratio of [3H]hydroxyproline in the high-molecular-weight fraction to total [3H]hydroxyproline as a marker of collagen degradation after incubation of the cells with [3H]proline for 24 h. Type analysis of the collagen produced by the cells after 8 days in culture showed the presence of type I and type III collagens in addition to the components corresponding to type IV and type V (alpha A and alpha B) collagens. Only the latter two types were found in the collagens produced by the cells after 2 days in primary culture. The purity of the hepatocytes inoculated was 97%, and the majority of the contaminating small cells were erythrocytes. The rate of serum albumin synthesis, which is a typical function of the hepatocytes, was constant or increased during the culture period. Immuno-electron microscopic observation indicated the production of type I collagen by the hepatocytes after 8 days in primary culture. These results are explained only by the activation of collagen synthesis in the day-8 hepatocytes in primary culture.


New insights into denitrification and phosphorus removal with degradation of polycyclic aromatic hydrocarbons in two-sludge system.
Polycyclic aromatic hydrocarbons (PAHs) have led to failure of waste water treatment plant operations. In this study, a two-sludge system was used to solve this problem of simultaneously removing phosphorus, nitrogen, and PAHs. The results showed that increasing the maximum PAHs concentration to 15 mg/L did not have any negative effect on the removal rates of total nitrogen (79.68%) and chemical oxygen demand (75.94%); however, the phosphorus removal efficiency decreased to 61.16%. The system exhibited a stronger degradation ability for phenanthrene. Thauera, Hydrogenophaga, and Hyphomicrobium were enriched, which resulted in good denitrification, and contributed to PAHs removal. PAHs mixture promoted PAHs functional genes but restrained denitrification functional genes. However, single naphthalene enhanced denitrification functional genes, which confirmed the feasibility of denitrification coupled with PAHs degradation. In conclusion, for the removal of pollutants from sewage treatment, nitrogen and phosphorus removal coupled with PAHs could be maintained by selecting a two-sludge system.


Imputation Procedures for Cognitive Variables in the Mexican Health and Aging Study: Evaluating the Bias from Excluding Participants with Missing Data.
Non-response of cognitive data in cohort studies is a barrier to cognitive aging research. We describe the procedures for the imputation of non-responses for cognitive data in the Mexican Health and Aging Study (MHAS). Data came from the 2001-2015 MHAS waves. We also describe the association of cognition with education, age, and other variables in 2015 with and without the imputed values. Between 12.3% and 37.9% of participants were missing data for at least one cognition variable. When we conducted the analysis with and without the imputed values, the relationships between education, age, and cognition were similar in direction and significance, but different in magnitude. Non-response of cognitive data is common and non-random in the MHAS. Investigators should use the data sets that include the imputed values, which are publicly available.


Effects of sodium arsenate exposure on liver fatty acid profiles and oxidative stress in rats.
The present study aimed to evaluate the effect of arsenic on liver fatty acids (FA) composition, hepatotoxicity and oxidative status markers in rats. Male rats were randomly devised to six groups (n=10 per group) and exposed to sodium arsenate at a dose of 1 and 10 mg/l for 45 and 90 days. Arsenate exposure is associated with significant changes in the FA composition in liver. A significant increase of saturated fatty acids (SFA) in all treated groups (p<0.01) and trans unsaturated fatty acids (trans UFA) in rats exposed both for short term for 10 mg/l (p<0.05) and long term for 1 and 10 mg/l (p<0.001) was observed. However, the cis UFA were significantly decreased in these groups (p<0.05). A markedly increase of indicator in cell membrane viscosity expressed as SFA/UFA was reported in the treated groups (p<0.001). A significant increase in the level of malondialdehyde by 38.3 % after 90 days of exposure at 10 mg/l was observed. Compared to control rats, significant liver damage was observed at 10 mg/l of arsenate by increasing plasma marker enzymes after 90 days. It is through the histological investigations in hepatic tissues of exposed rats that these damage effects of arsenate were confirmed. The antioxidant perturbations were observed to be more important at groups treated by the high dose (p<0.05). An increase in the level of protein carbonyls was observed in all treated groups (p<0.05). The present study provides evidence for a direct effect of arsenite on FA composition disturbance causing an increase of SFA and TFAs isomers, liver dysfunction and oxidative stress. Therefore, arsenate can lead to hepatic damage and propensity towards liver cancer.


A double-edged sword in tumor angiogenesis and progression. Dual roles of mast cells, macrophages, and neutrophils.
Inflammatory cells act in concert with tumor cells, stromal cells, and endothelial cells to create an environment that is critical for the survival, development, and diffusion of the tumor. Under a variety of conditions, inflammatory cells are capable of polarization under their tumoricidal (growth arresting) or tumorigenic (growth promoting) forms. In this context, two major subsets of mast cells, macrophages, and neutrophils, have been described. This article is focused on the description of these different sub-populations and to the analysis of arrays of common and specific mediators involved in their action in the context of tumor growth. Different databases, including PubMed/MEDLINE, Scopus, and Google Scholar, were searched to review and analyze relevant literature concerning the different sub-populations of mast cells, macrophages, and neutrophils, and arrays of common and specific mediators involved in their action in the context of tumor growth.The analysis of the literature data confirm that the microenvironment can inhibit tumor growth and suppress or revert the malignant phenotype. Incorrect signals from the microenvironment can lead to initiation and promotion of neoplastic transformation of normal cells, and once tumor is formed, it modifies the stroma and initiates an inflammatory reaction and an immune response.


Gastroesophageal reflux: update on pathogenesis and diagnosis.
The study of GER has been hindered by the lack of a good animal model and by the presence of some reflux in all normal individuals. By the painstaking process of studying normal infants, children, and adults, it is becoming evident that abnormalities of acid clearance, especially in the recumbent position (or during sleep), may be critical to an understanding of this disorder. As more is learned about the conditions surrounding "normal" reflux, it will be possible to refine the techniques of diagnosis and thereby identify the abnormal with more security.


Some observations on the ageing in vitro of reprecipitated collagen fibres.
The changes in solubility and amounts of reducible cross-links have been studied during "ageing" in vitro of reprecipitated rat skin collagen fibres by incubation at 37 degrees C. Fibres from pre-reduced collagen devoid of aldehyde precursors became insoluble at the same rate as that of normal fibres during "ageing". Insolubilization occurred at a much faster rate in the presence of oxygen than in air and was almost completely inhibited when oxygen was excluded. The rate of decline of the reducible cross-links was, however, unaffected by oxygen tension. The results indicate that, during "ageing" in vitro, conversion of the lysine-derived cross-links to a non-reducible form is not associated with solubility changes. The relationship of these in vitro changes to those ocurring in vivo is unknown.


An immunophenotypic and molecular diagnosis of composite hairy cell leukaemia and chronic lymphocytic leukaemia.
Hairy cell leukaemia (HCL) and chronic lymphocytic leukaemia (CLL) are distinct clinicopathological B cell chronic lymphoproliferative disorders (B-CLPD). Both diseases have characteristic immunophenotypic and molecular features. The co-existence of two B-CLPD is perhaps more common than previously thought but a composite HCL and CLL has been rarely documented. A case is reported in which the morphology, integrated with an extensive immunophenotyping panel, and incorporation of the recently described HCL-associated BRAF V600E mutation, enabled the prompt diagnosis of composite HCL and CLL thus allowing appropriate treatment selection. This case serves to highlight the benefit of a multidisciplinary approach to the diagnosis of bi-clonal B-CLPD.


Synergistic effects of immunoregulation and osteoinduction of ds-block elements on titanium surface.
Ds-block elements have been gaining increasing attention in the field of biomaterials modification, owing to their excellent biological properties, such as antibiosis, osteogenesis, etc. However, their function mechanisms are not well understood and conflicting conclusions were drawn by previous studies on this issue, which are mainly resulted from the inconsistent experimental conditions. In this work, three most widely used ds-block elements, copper, zinc, and silver were introduced on titanium substrate by plasma immersion ion implantation method to investigate the rule of ds-block elements in the immune responses. Results showed that the implanted samples could decrease the inflammatory responses compared with Ti sample. The trend of anti-inflammatory effects of macrophages on samples was in correlation with cellular ROS levels, which was induced by the implanted biomaterials and positively correlated with the number of valence electrons of ds-block elements. The co-culture experiments of macrophages and bone marrow mesenchymal stem cells showed that these two kinds of cells could enhance the anti-inflammation and osteogenesis of samples by the paracrine manner of PGE2. In general, in their steady states on titanium substrate (Cu2+, Zn2+, Ag), the ds-block elements with more valence electrons exhibit better anti-inflammatory and osteogenic effects. Moreover, molecular biology experiments indicate that the PGE2-related signaling pathway may contribute to the desired immunoregulation and osteoinduction capability of ds-block elements. These findings suggest a correlation between the number of valence electrons of ds-block elements and the relevant biological responses, which provides new insight into the selection of implanted ions and surface design of biomaterials.


A comparison of ciliary sulcus and capsular bag fixation of posterior chamber intraocular lenses.
We compare indications, advantages, and disadvantages of ciliary sulcus and lens capsular bag (lens capsular sac) fixation of posterior chamber intraocular lenses (IOLs). Our findings suggest that, whenever possible, it is efficacious to implant the loops of posterior chamber IOLs within the capsular bag. This positions the lens optic and the supporting loops in the natural anatomical position, sequestered from highly vascular uveal tissue and the blood aqueous barrier. This should minimize the potential for complications that may be associated with iris-ciliary body contact. Considering the rapid increase in the number of implantations of IOLs now being performed (approximately 700,000 per year in the United States alone), a possible reduction of even 1% in clinically significant complications would make this effort worthwhile. Widespread application of in-the-bag implantation is predicated on the assumption that the surgeon is proficient with this procedure and that careful follow-up of patients does not reveal any significantly increased incidence of lens dislocation due to zonular rupture.


Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder.
Duloxetine hydrochloride has recently been approved by the US Food and Drug Administration for the treatment of major depressive disorder (MDD). Duloxetine is a potent inhibitor of serotonin and norepinephrine reuptake, with weak effects on dopamine reuptake. This article reviews the literature on duloxetine with regard to its pharmacodynamics, pharmacokinetics, clinical efficacy, and tolerability. A comprehensive search of MEDLINE was performed using the terms duloxetine, Cymbalta, and major depressive disorder, with no restriction on year. The Eli Lilly and Company clinical trial registry, and abstracts and posters from recent American Psychiatric Association meetings were also reviewed. Duloxetine exhibits linear, dose-dependent pharmacokinetics across the approved oral dosage range of 40 to 60 mg/d. No dose adjustment appears to be needed based on age. Duloxetine has shown efficacy in reducing depressive symptoms compared with placebo, and duloxetine recipients have shown significant improvements in global functioning compared with placebo (both, P < 0.05). Response and remission rates have been comparable to or greater than those seen with fluoxetine or paroxetine. Duloxetine is generally well tolerated, with nausea, dry mouth, and fatigue being the most common treatment-emergent adverse effects. Cardiovascular adverse effects do not appear to result in sustained blood pressure elevations, QTc-interval prolongation, or other electrocardiographic changes. Based on the available evidence, duloxetine is a well-tolerated and effective treatment for MDD in adults. Randomized head-to-head comparisons against established antidepressants are needed to determine the relative safety and efficacy of duloxetine.


Polymorphisms of DNA repair genes in endometrial cancer.
Endometrial cancer belongs to the commonest malignancy in females. Its development may be associated with the high exposure of endometrium to exo- and endogenous estrogens. Estrogens produce DNA bulky adducts and oxidative base damages which are removed in nucleotide excision repair (NER) and base excision repair (BER) pathways. The reaction of endometrial cells to DNA damage may be crucial for their susceptibility to cancer transformation. This reaction is executed mainly by DNA repair, which can be modulated by the variability in the genes encoding DNA repair proteins. In this report we genotyped 4 polymorphisms of 3 DNA repair genes in 94 endometrial cancer patients and 114 age-matched cancer-free women using RFLP-PCR. The following polymorphisms were studied: p.Arg194Trp, p.Arg399Gln of the XRCC1 gene, p.Ser326Cys of the hOGG1 gene and p.Lys751Gln of the ERCC2 gene. We found an association between the ERCC2 751Gln variant and endometrial cancer occurrence (OR 3.95; 95 % CI 1.88-8.31). Gene-gene interaction between the ERCC2 751Gln and XRCC1 194Trp variants also increased the risk of endometrial cancer (OR 4.41; 95 % CI 2.01-9.67). The risk in the carriers of the ERCC2 751Gln variant was increased by a positive cancer history in first degree relatives (OR 4.97; 95 % CI 1.98-12.48). The risk of endometrial cancer was not alter by polymorphism p.Ser326Cys of the hOGG1 gene. The 751 Lys/Gln polymorphism of the ERCC2 gene may be linked with endometrial cancer occurrence and its effect can be potentiated by variants of the XRCC1 gene or first degree relatives positive cancer history.


Administration of TLR7 agonist, resiquimod, in different types of chicken induces a mixed Th1 and Th2 response in the peripheral blood mononuclear cells.
This study evaluated the variation in immune response in peripheral blood mononuclear cells (PBMCs) of broiler, White Leghorn (WL) and Kadaknath breeds of chicken following administration of TLR7 agonist, resiquimod (R-848). Expression of different immune related genes viz., interferon-β (IFN-β), IFN-γ, IL-1β, IL-4, TLR7 and iNOS was assessed by quantitative real time PCR over a period of 24 h. The results indicated that there was a significant up-regulation in the relative expression of immune response genes post R-848 administration (P < 0.01). In conclusion, the transcriptional expression of IFN-β, IFN-γ, IL-1β, IL-4, iNOS and TLR7 genes in the PBMCs was significantly up-regulated over 24 h in broiler, WL and Kadaknath breeds of birds after the administration of R-848. Overall, R-848 induced a mixed Th1 and Th2 response in PBMCs of chicken origin ex vivo.


Increased proportions of dendritic cells and recovery of IFNγ responses in HIV/HCV co-infected patients receiving ART.
Dendritic cell (DC) numbers and functions can be affected by HIV and HCV disease, but the effects of antiretroviral therapy (ART) on DC and the implications of these changes are unclear. We examined circulating DC in samples from Indonesian patients beginning ART with advanced HIV disease and documented mild/moderate HCV hepatitis. Frequencies of myeloid and plasmacytoid DC increased after 6 months on ART, but frequencies of DC producing IL-12 or IFNα following stimulation with TLR agonists (CL075, CpG) did not change. IFNγ responses to CL075, HCV and other antigens rose over this period. Hence increased IFNγ responses during ART may be associated with increased DC frequencies rather than changes in their functional capacity.


[Treatment of iatrogenic obstructions of the ureter following hysterectomy].
Ureteral injury after abdominal hysterectomy has been observed in 14 patients between 1988 and 1992. Open surgery, percutaneous nephrostomy, double pigtail stent insertion using antegrade and retrograde route, and balloon dilatation were used for treatment. The experience of the authors is reviewed.


Pancreatic Enzyme Replacement and Nutritional Support With nab-Paclitaxel-based First-Line Chemotherapy Regimens in Metastatic Pancreatic Cancer.
At diagnosis, more than 80% of patients with pancreatic cancer (PC) suffer from significant weight loss due to malnutrition which is a major concern for patient management, and this may negatively impact treatment outcomes and patient prognosis. We performed an observational, retrospective study on patients with metastatic PC (mPC) undergoing first-line chemotherapy with nab-Paclitaxel containing schedules and receiving or not receiving nutritional support (NS) and pancreatic enzyme replacement therapy (PERT) to investigate their relevance in this setting. We observed that PERT and ancillary dietary interventions are related to longer overall survival (OS; median: 16.5 vs. 7.5 months, P < .001) and have a significant, independent, prognostic impact for better outcomes (P = .013), independently from the therapeutic regimen. Furthermore, PERT and NS prevented weight loss during chemotherapy and obtained an improvement of nutritional parameters such as phase angle and free-fat mass index, after 3 months of anticancer treatment. Consistently, the positive impact on OS correlated also with the prevention of Karnofsky performance status deterioration and a lower incidence of maldigestion-related symptoms. Our data suggest that an early and well-conducted NS in patients with mPC may impact on survival and preserve performance status, thus improving quality of life.


Purification and proteomic analysis of potent fibrinolytic enzymes extracted from Lumbricus rubellus.
Lumbrokinase derived from earthworms, Lumbricus rubellus is known to have fibrinolytic enzymes that have potential as therapeutic drugs due to its ability to dissolve fibrin. The current study is aimed to purify the Lumbrokinase from L. rubellus and identify its protein component. Water extract of local earthworm Lumbricus rubellus revealed several proteins. Therefore, to identify its protein component, purification through HiPrep DEAE fast flow and proteomic analysis were conducted prior to identifications. A combination of two-dimension gel electrophoresis (2DE) and electrospray ionization mass spectrometry analysis was used to identify the purified fractions. The purified fractions contain five protein bands, namely F25-1, F25-2, F85-1, F85-2, and F85-3, which displayed strong fibrinogenolytic activity. F25 fractions showed fibrinogenolytic activity of 974.85 U/mg, while F85 fractions showed higher activity of 1,484.11 U/mg. Fractions F85-1, F85-2, and F85-3 showed molecular weights of 42.6 kDa, 27.03 kDa, and 14 kDa, respectively and were identified as Lumbrokinase iso-enzymes. This preliminary study indicates that the F25 and F85 fractions are similar to published fibrinolytic protease-1 and lumbrokinase, respectively, in terms of their amino acid sequence.


A temporary-sustainable team: A new multidisciplinary team model for severe trauma.
The treatment of severe trauma, especially multiple injuries, requires multidisciplinary collaboration. The current study aims to highlight the challenges of consultation mode for severe trauma in general hospitals and emphasizes the need to create a new temporary-sustainable team. It suggests developing an information consultation mode and enforcing the fine management to improve the quality and safety of the medical treatment. The management mode of a temporary-sustainable team will reduce the cost and improve the treatment efficiency. Overall, a temporary-sustainable team has significant advantages over a traditional multidisciplinary team for severe trauma treatment.


Association between body mass index and clinical characteristics, as well as with management, in Chinese patients with breast cancer.
Body mass index (BMI) is a risk factor associated with breast cancer in postmenopausal women. This study aimed to identify the associations of BMI with clinical characteristics and management of breast cancer in female Chinese patients. Clinicopathological information on 1296 women who were diagnosed with breast cancer was collected at our hospital. We recorded the clinicopathological characteristics, molecular phenotypes, manner of diagnosis, implementation rate of preoperative examinations, and surgical method used. Significant differences were found in the tumor size, disease stage, manner of diagnosis, implementation rate of preoperative examinations, and the surgical method among different BMI groups. In premenopausal patients, significant differences were found in the distribution of molecular phenotypes and surgical approach among different BMI groups. In postmenopausal patients, different BMI groups showed significant differences in the tumor size, disease stage, distribution of molecular phenotypes, manner of diagnosis, rate of implementation of preoperative mammography, and surgical method. Higher BMI is associated with a larger tumor size, more advanced disease stage, diagnosis by physical examination, higher implementation rate of preoperative examinations, and lower radical surgery rate in Chinese women with breast cancer. However, the relationship between BMI and molecular phenotypes differs between pre- and postmenopausal women.


Effect of self-administered auricular acupressure on smoking cessation--a pilot study.
Tobacco smoking is still a worldwide health risk. Current pharmacotherapies have at best, a success rate of no more than 50%. Auricular (ear) acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant. We hereby describe the protocol for a three-arm randomised controlled trial to examine the possible benefits of self-administered acupressure for smoking cessation. Sixty consenting participants with confirmed habit of tobacco smoking will be recruited and randomized into three arms to receive either auricular acupressure at five true acupoints (NADA protocol), auricular acupressure at five sham points, or no auricular acupressure at all. Participants having auricular acupressure will exert firm pressure to each acupoint bilaterally via the bead in the attached plasters whenever they feel the urge to smoke. The treatment phase will last for six weeks during which all participants will be assessed weekly to review their smoking log, state of abstinence, end-exhalation carbon monoxide levels and possible adverse effects including withdrawal reactions and stress levels. At any time, a successful quit date will be defined with continuous abstinence for the following consecutive 7 days. From then on, participants will be evaluated individually for continuous abstinence rate (CAR), end-exhalation carbon monoxide levels and adverse effects of stress and withdrawal at specified intervals up to 26 weeks. Expectancy of treatment will be assessed with a four-item Borkovec and Nau self-assessment credibility scale during and after intervention. We incorporate validated outcome measures of smoking cessation into our randomised controlled trial design with the objectives to evaluate the feasibility and possible benefits of self-administered auricular acupressure as a non-invasive alternative to pharmacotherapy for smoking cessation. ClinicalTrials.gov: NCT01389622 (registered Jul 7 2011).


[Contraception on YouTube, Instagram, and TikTok : A content and quality analysis].
Young people and adults increasingly obtain information about contraception via social media. Against this background, the aim of this study is to investigate for the first time the content and quality of German-language contraceptive posts on YouTube, Instagram, and TikTok. Research questions on providers (F1), content (F2), and quality of contraceptive posts (F3) as well as audience reactions (F4) will be answered. A sample of N = 1000 contraceptive posts from YouTube (500), Instagram (250), and TikTok (250) was drawn. A maximum of 20 contraception-related audience comments per post were included in the comment sample (N = 12,454). Posts and comments were analyzed using reliability-tested codebooks. SPSS was used for data analysis. The study is preregistered and all data, materials, and analysis scripts are publicly available. The majority of contraceptive posts were found to be from health laypersons (52%), followed by media professionals and health professionals (F1). In terms of content, contraceptive posts covered all available contraceptive methods, with the pill (69%) and condoms (40%) dominating (F2). According to common quality criteria, there were clear deficits, with YouTube videos scoring best in comparison (F3). TikTok videos, on the other hand, were top performers in terms of audience interaction, attracting the most views, likes, and comments. Comment columns were often used by the audience to share their own contraceptive experiences or ask follow-up questions (F4). Future research as well as practice interventions are needed to further assess the quality of contraceptive information in social media and improve it in a more targeted way.


Working From Home: Experiences of Home-Working, Health Behavior and Well-Being During the 2020 UK COVID-19 Lockdown.
The Spring 2020 UK COVID-19 lockdown required normally office-based workers to modify their work-related practices to work at home. This study explored workers' experiences of adapting to home working, health behaviors and well-being. Twenty-seven home working employees (19 women; aged 23-57 years), from various industry sectors, gave individual semi-structured interviews. Topics focused on home working experiences, routine adaptations, and changes in health behaviors and well-being. Four themes were extracted: changes to the work interface; adaptations to a new workspace; changes to work-life balance; and adjustments to a new social context. Notably, participants reported greater reliance on computer-based interactions, which they felt discouraged physical activity and increased sitting. Working in a domestic environment reportedly challenged work-home boundaries. Work practices can incidentally detrimentally impact health-related behaviors and well-being. Organizations should develop policies and procedures to promote health-conducive home working.


The value of skin temperature measurements in forecasting the healing of a below-knee amputation for end-stage ischaemia of the leg in peripheral vascular disease.
In order to forecast the healing of a Burgess type below-knee amputation the skin temperature of the leg has been studied before operation in 39 instances using infra-red thermography in a 26 degrees C environment. Healing bore no relation to the mean skin temperature of the calf or that of the skin at the site of the anterior incision. However, when the skin temperature at the site of the incision for the long posterior flap was greater than 30.4 degrees C or when the ratio of the temperatures at the posterior and anterior incision sites (P/A) was greater than 0.98 healing was significantly more likely to occur. It is proposed that the temperatures at these sites should be used to assess the prospect of such an amputation healing.


Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states.
Embryonic stem cells (ESCs) are apparently homogeneous self-renewing cells, but we observed heterogeneous expression of Stella in ESCs, which is a marker of pluripotency and germ cells. Here we show that, whereas Stella-positive ESCs were like the inner cell mass (ICM), Stella-negative cells were like the epiblast cells. These states were interchangeable, which reflects the metastability and plasticity of ESCs. The established equilibrium was skewed reversibly in the absence of signals from feeder cells, which caused a marked shift toward an epiblast-like state, while trichostatin A, an inhibitor of histone deactelylase, restored Stella-positive population. The two populations also showed different histone modifications and striking functional differences, as judged by their potential for differentiation. The Stella-negative ESCs were more like the postimplantation epiblast-derived stem cells (EpiSCs), albeit the stella locus was repressed by DNA methylation in the latter, which signifies a robust epigenetic boundary between ESCs and EpiSCs.


A polymorphism in the protein kinase C gene PRKCB is associated with α2-adrenoceptor-mediated vasoconstriction.
α2-Adrenoceptors (α2-AR) mediate both constriction and dilatation of blood vessels. There is considerable interindividual variability in dorsal hand vein (DHV) constriction responses to α2-AR agonist activation. Genetic factors appear to contribute significantly to this variation. The present study was designed to identify the genetic factors contributing toward the interindividual variability in α2-AR-mediated vascular constriction induced by the selective α2-AR agonist dexmedetomidine. DHV constriction responses to a local infusion of dexmedetomidine were assessed by measuring changes in vein diameter with a linear variable differential transformer. The outcome variable for constriction was log-transformed dexmedetomidine ED50. A genome-wide association study (GWAS) of 433 378 single-nucleotide polymorphisms (SNPs) was carried out for determining the sensitivity of DHV responses in 64 healthy Finnish individuals. Twenty SNPs were selected on the basis of the GWAS results and their associations with the ED50 of dexmedetomidine were tested in an independent North American study population of 68 healthy individuals. In both study populations (GWAS and replication samples), the SNP rs9922316 in the gene for protein kinase C type β was consistently associated with dexmedetomidine ED50 for DHV constriction (unadjusted P=0.00016 for the combined population). Genetic variation in protein kinase C type β may contribute toward the interindividual variation in DHV constriction responses to α2-AR activation by the agonist dexmedetomidine.


Quantitative structure-activity relationship studies on some nonbenzodiazepine series of compounds acting at the benzodiazepine receptor.
Quantitative structure-activity relationship (QSAR) studies have been made on a few non-benzodiazepine series of compounds such as 3-substituted imidazo[1,2-b]pyridazines, 2-phenylimidazo[1,2-alpha]pyridines, 2-(alkoxycarbonyl) imidazo[2,1-b]benzothiazoles, and 2-arylquinolines. For the first series of compounds a Fujita-Ban approach has been followed, which revealed the highest activity contribution for 3,4-OCH2O group of 2-phenyl moiety and for a methoxy group at 6-position. For the rest of the series, a Hansch approach has been adopted. The hydrophobic and electronic properties of the various substituents have been found to play major roles in the binding of these compounds with the receptor. Based on these studies, a hypothetical model for the drug-receptor interaction has been proposed.


Determination of the absolute configuration of compounds bearing chiral quaternary carbon centers using the crystalline sponge method.
Determination of the absolute configuration of chiral tetra-substituted carbon centers is one of the most taxing steps in the enantioselective construction of this structural motif in asymmetric synthesis. Here, we demonstrate that the crystalline sponge method provides an effective way to crystallographically determine the absolute configuration of organic compounds bearing chiral quaternary carbons (including tetra-substituted ones) that are synthesized by recently developed enantioselective catalytic reactions.


A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings.
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders mainly characterized by progressive spasticity of the lower limbs. Adult case series dominate the literature, and there have been only a few studies in children. The purpose of this study is to describe our experience with pediatric HSP in Greece. We report the clinical and genetic findings in our patients and aim to offer insights into the diagnostic difficulties of childhood-onset disease. A series of 15 Greek children affected by pure HSP underwent extensive diagnostic investigations. Molecular analysis included whole exome sequencing (WES) or consecutive screening of candidate genes ATL1, SPAST, REEP1, and CYP7B1. WES performed in three cases yielded previously reported mutations in ATL1 and CYP7B1, and a variant c.397C>T of unknown significance in SPG7. Candidate gene screening performed in the remaining patients identified previously reported mutations in ATL1 (2), SPAST (2), and REEP1 (1), and two novel mutations, c.1636G>A and c.1413+3_6delAAGT, in SPAST. In six cases, the mutations were inherited from their parents, while in three cases, the mutations were apparently de novo. Our data confirm the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms. De novo occurrence of HSP does not seem to be uncommon. Candidate gene studies guided by diagnostic algorithms and WES seem both to be reasonable genetic testing strategies.


Profiling of Protease Cleavage Sites by Proteome-Derived Peptide Libraries and Quantitative Proteomics.
Biochemical profiling of active site specificity is a crucial step to characterize proteases, which play key roles in health and disease. Here, we present a protocol using proteome-derived peptide libraries in combination with quantitative proteomics to simultaneously identify cleavage motifs N- and C-terminal to the scissile peptide bond. First, bacterial or eukaryotic cell lysate is used to generate peptide libraries. Without further chemical modification, peptide libraries are then split into control and treated (incubate with active protease) aliquots. Control and treated libraries are stable isotope-labeled, mixed, and analyzed by liquid chromatography-tandem mass spectrometry. Enriched, semi-specific peptides represent the cleavage products of the test protease and the entire peptide sequence that encompasses the scissile peptide bond is reconstructed bioinformatically. The method is fast, cost-effective, and suited for proteases with narrow or loose specificity.


Electric-field-induced colour switching in colloidal quantum dot molecules at room temperature.
Colloidal semiconductor quantum dots are robust emitters implemented in numerous prototype and commercial optoelectronic devices. However, active fluorescence colour tuning, achieved so far by electric-field-induced Stark effect, has been limited to a small spectral range, and accompanied by intensity reduction due to the electron-hole charge separation effect. Utilizing quantum dot molecules that manifest two coupled emission centres, we present a unique electric-field-induced instantaneous colour-switching effect. Reversible emission colour switching without intensity loss is achieved on a single-particle level, as corroborated by correlated electron microscopy imaging. Simulations establish that this is due to the electron wavefunction toggling between the two centres, induced by the electric field, and affected by the coupling strength. Quantum dot molecules manifesting two coupled emission centres may be tailored to emit distinct colours, opening the path for sensitive field sensing and colour-switchable devices such as a novel pixel design for displays or an electric-field-induced colour-tunable single-photon source.


Dispermic origin of a 69,XXY triploid.
Triploidy, 69XXY, was found in a newborn with multiple abnormalities. Conception had occurred shortly after the mother ceased taking an oral contraceptive. The infant carried a pair of 21s with giant satellites; of the parents, only the father carried a giant-satellited 21. This, together with the XXY constitution, suggested a dispermic origin of the triploidy.


Heterotopic epithelialization presenting as a non-healing scalp wound after surgery.
Patients undergoing cerebral revascularization surgery have a relatively high incidence of wound complications. We report a case of heterotopic epithelialization of the dura presenting as a non-healing scalp wound after an extracranial-intracranial (EC-IC) arterial bypass. The scalp wound was revised twice without healing. During the third revision, epithelial tissue was found growing on the dura and was removed. After the epithelial tissue was removed, the wound healed without further complications. This case illustrates the importance of thoroughly examining a non-healing wound to find the cause.