Loss of the ORF in the SSUrDNA group I intron of one Naegleria lineage.
We have found a Naegleria lineage in which the SSUrDNA contains a group I intron with a length of 375 nucleotides. This is a unique finding because all group I introns detected until now in Naegleria are 1.3 kilobases long and contain an open reading frame coding for 245 amino acids. Sequence data show that the 375 nucleotide-long intron is at the same place in the SSUrDNA as, and is descendant from, the 1.3 kilobase group I intron present in other species of Naegleria. Our data indicate that in one lineage of Naegleria the group I intron lost part of its DNA that is not contributing to the secondary structure but that carries the open reading frame. The amoeboflagellate genus Naegleria contains strains without the intron and strains with the intron, with or without an open reading frame. Therefore, this genus provides a unique opportunity to study the function and evolution of both the group I intron and the open reading frame.


Distinction Between Hepatocellular Carcinoma and Hypervascular Liver Metastases in Non-cirrhotic Patients Using Gadoxetate Disodium-Enhanced Magnetic Resonance Imaging.
Purpose: This study aims to identify the hallmarks of gadoxetate disodium-enhanced magnetic resonance imaging distinguishing hepatocellular carcinoma (HCC) from hypervascular liver metastases (HLMs). Methods: Between January 2008 and October 2020, among patients who underwent gadoxetate disodium-enhanced MRI, those who met the following criteria were retrospectively included: without chronic hepatitis or liver stiffness ≤ 2.5 kPa on magnetic resonance elastography or F0/F1 on pathological assessment. Two blinded radiologists reviewed the imaging findings to judge the presence or absence of the enhancing capsule, nonperipheral washout, corona enhancement, hypointensity in the transitional/hepatobiliary phase (HBP), hyperintensity on T2-weighted/diffusion-weighted imaging (DWI), mosaic architecture, and blood products/fat in mass. The lesion-to-liver signal intensity ratios in HBP and DWI were also calculated. Univariate and multivariate analyses were performed to identify the imaging hallmarks distinguishing HCC from HLM. Interobserver agreement was calculated using kappa values and intraclass correlation coefficients (ICCs). Results: The final study cohort comprised 72 lesions in 44 patients (mean age, 65.0±11.9 years). Univariate analysis revealed higher frequencies of the following features in HCC than in HLM (P < .10): nonperipheral washout, corona enhancement, transitional phase hypointensity, mosaic architecture, and fat in mass (P = .002-.073). Multivariate analysis revealed that nonperipheral washout and mosaic architecture favored the diagnosis of HCC over that of HLM with odds ratios of 7.66 and 14.6, respectively (P = .038 and .029, respectively). The interobserver agreement for each item was moderate or substantial (kappa or ICC = .447-.792). Conclusion: Peripheral washout and mosaic architecture may be reliable imaging hallmarks for distinguishing HCC from HLM.


Marketing trials, marketing tricks - how to spot them and how to stop them.
Last this year in this journal, Barbour and colleagues reported a study of "marketing trials" in leading medical journals (Trials 2016;17:31). In this commentary I discuss their research, describe new analyses of the study cohort and consider measures to address marketing within academic medical literature. Barbour et al. sought to identify a subgroup of "marketing trials" within leading medical journals, but in reality, nearly all industry-financed trials serve marketing functions, and many exhibit marketing-related features, including biases, in their framing, methodology or reporting. I conducted new analyses of the cohort of Barbour et al., showing that most trials funded exclusively by drug manufacturers had direct involvement of the manufacturer in design, analysis and reporting, and features supportive of product seeding. However, these commercial enterprises were without exception presented to journal readers as academic-led projects, using attributional spin, which should itself be considered an important form of marketing bias. Barbour et al. correctly conclude that commercial bias in industry clinical trials articles often requires expertise to recognize, and in many cases cannot be identified from the published journal report. Several potential remedies are discussed, including independent clinical research, data sharing, improved reporting guidance, improved tools for assessing research quality, reforms to article attribution, submission checklists and new editorial standards. Medicine's journals have a responsibility to uphold rigorous scientific and reporting standards, require ready trials data access and ensure the commercial dimensions of research are brought prominently to their readers' attention. Failure to meet these responsibilities constitutes an enduring threat to the integrity of biomedical literature.


Fasting with diabetes: a prospective observational study.
To determine the proportion of diabetic patients who develop adverse glycaemic events when fasting regularly. Prospective observational study conducted at a tertiary care hospital in South Asia. Five hundred and twenty-three patients were assessed for eligibility, and 150 were included in the final analysis. Diabetic patients over 18 years of age who were willing to fast regularly and make a chart of their daily blood sugar levels were included in the study. The main outcome measures were hypoglycaemic and hyperglycaemic events. Frequencies and percentages were calculated for quantitative variables, while mean±SD were documented for qualitative variables. Relative risk was calculated as a measure of association. Of a total of 150 individuals, 10% experienced hypoglycaemia, while 3.3% reported hyperglycaemic episodes. Only 8.7% of the participants discontinued one or more fasts; however, none of them required hospitalisation. There is a negative association between a visit to a physician by diabetic patients before they begin to fast regularly and the risk of developing hypoglycaemia (relative risk 0.73). Many diabetic patients who fast regularly are at high risk of adverse glycaemic events. Most diabetics do not consult their physicians before fasting to adjust medications and lifestyle. Various strategies should be planned and implemented for the awareness and education of such patients to avoid adverse glycaemic events and subsequent complications.


Short unligated sticky ends enable the observation of circularised DNA by atomic force and electron microscopies.
A comparative study of the stabilisation of DNA sticky ends by divalent cations was carried out by atomic force microscopy (AFM), electron microscopy and agarose gel electrophoresis. At room temperature, molecules bearing such extremities are immediately oligomerised or circularised by addition of Mg2+or Ca2+. This phenomenon, more clearly detected by AFM, requires the presence of uranyl salt, which stabilises the structures induced by Mg2+or Ca2+. DNA fragments were obtained by restriction enzymes producing sticky ends of 2 or 4 nucleotides (nt) in length with different guanine plus cytosine (GC) contents. The stability of the pairing is high when ends of 4 nt display a 100% GC-content. In that case, 95% of DNA fragments are maintained circular by the divalent cations, although 2 nt GC-sticky ends are sufficient for a stable pairing. DNA fragments with one blunt end and the other sticky appear as dimers in the presence of Mg2+. Dimerisation was analysed by varying the lengths and concentrations of DNA fragments, the base composition of the sticky ends, and also the temperature. Our observation provides a new powerful tool for construction of inverted dimers, and circularisation, ligation analysis or short bases sequence interaction studies.


Iron-deficient erythropoiesis in blood donors and red blood cell recovery after transfusion: initial studies with a mouse model.
Most frequent red cell (RBC) donors and many first-time donors are iron deficient, but meet haemoglobin standards. However, the effects of donation-induced iron deficiency on RBC storage quality are unknown. Thus, we used a mouse model to determine if donor iron deficiency reduced post-transfusion RBC recovery. Weanling mice received a control diet or an iron-deficient diet. A third group receiving the iron-deficient diet was also phlebotomised weekly. This provided 3 groups of mice with different iron status: (1) iron replete, (2) mild iron deficiency with iron-deficient erythropoiesis, and (3) iron-deficiency anaemia. At ten weeks of age, blood was collected, leucoreduced, and stored at 4 ºC. After 12 days of storage, 24-hour (h) post-transfusion RBC recovery was quantified in recipients by flow cytometry. Before blood collection, mean haemoglobin concentrations in the iron-replete, iron-deficient, and iron-deficiency anaemia donor mice were 16.5±0.4, 11.5±0.4, and 7.0±1.4 [g/dL± 1 standard deviation (SD)], respectively (p<0.01 for all comparisons between groups). The 24-h post-transfusion RBC recoveries in recipients receiving transfusions from these three cohorts were 77.1±13.2, 66.5±10.9, and 46.7±15.9 (% ±1 SD), respectively (p<0.05 for all comparisons between groups). In summary, donor iron deficiency significantly reduced 24-h post-transfusion RBC recovery in recipient mice. RBCs from mice with mild iron deficiency and iron-deficient erythropoiesis, with haemoglobin levels similar to those used for human autologous blood donation, had intermediate post-transfusion RBC recovery, as compared to iron-replete donors and those with iron-deficiency anaemia. This suggests that, in addition to the effects of iron deficiency on donor health, frequent blood donation, leading to iron-deficient erythropoiesis, may also have adverse effects for transfusion recipients.


[Correction of the functional state of the autonomous nervous system in the women presenting with the postmastectomy syndrome at the stationary stage of the rehabilitative treatment].
A frequent consequence of the treatment of breast cancer is the postmastectomy syndrome that combines psycho-emotional and functional disorders in various body systems. The objective of the present study was to evaluate the influence of the program of differential physical rehabilitation on the functional state of the autonomic nervous system in the women with the postmastectomy syndrome at the stationary stage of the rehabilitative treatment. The study included 50 presenting with the postmastectomy syndrome following radical mastectomy as described by J.L. Madden. The patients were randomly divided into two groups comprised of 25 patients each. The main group consisted of the women at the mean age of 55,44±1,06 years, the group of comparison (2) was composed of the women at the mean age of 55,60±1,14 years. The program of the rehabilitative treatment of the patients in group 1 envisaged the use of the physical therapeutic modalities chosen on an individual basis in agreement with the basic principles of medical gymnastics including the differential selection of static and dynamic respiratory maneuvers with due regard for the type of vegetative regulation in a given patient, post-isometric relaxation, Vodder's manual lymphatic drainage and autotraining as described by J.H. Suhultz. The patients comprising the group of comparison performed therapeutic physical exercises as described by T.I. Grushina. The analysis of the literature and empirical data was combined with that of the heart rate variability was measured twice: within days 2-3 after the surgical intervention and on days 19-20 of the hospital stay. The methods of mathematical statistics were employed to treat the data obtained. The study has demonstrated reduced reserves of vegetative support, the overall decrease of the heart rate variability, and enhanced tension of the adaptive mechanisms in this group of women. Moreover, it showed the positive outcome of the physical rehabilitation program designed to correct most of the time-related and spectral parameters of the heart rate variability and gave evidence of the significant improvement of the total activity of the regulatory systems due to the enhancement of the high-frequency, low-frequency and very low-frequency components of the spectrum. The values of the stress index and the mode amplitude were reduced whereas the adaptive capabilities of the autonomic nervous system in women of the main group were extended. The proposed program of differential physical rehabilitation can be employed in the practical work of the specialized healthcare facilities for the correction of the functional state of the autonomic nervous system in the women with the postmastectomy syndrome.


The antioxidant potential of the Mediterranean diet in patients at high cardiovascular risk: an in-depth review of the PREDIMED.
Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols.


The correlation between direction and amount of retrusive movement and condyle position and joint space.
The direction and amount of retrusive movement may be correlated with the amount of joint space and the maximum intercuspal position of the condyle. The aim of this study was to identify any such correlation using an ultrasonic jaw motion analyzer and digital volumetric tomographic (DVT) scans. Thirty-five dental students were selected as subjects. DVT scans were obtained using a next-generation i-CAT CBCT unit, and the direction and amount of retrusive movement were measured with a 3-D analyzer. Spearman Rho correlation tests showed no correlation between the amount of retrusive movement and the condyle position and joint space on either the right or left side. There is sufficient reason to suggest that retrusive movement of the condyle does not occur in isolation but is influenced by glenoid fossa bone morphology.


Drug-induced dyskinesia in primates rendered hemiparkinsonian by intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
The right common carotid artery was surgically exposed under general anaesthesia in 6 cynomolgus monkeys and MPTP (0.5-2.2 mg/kg) directly infused. This produced a hemiparkinsonian syndrome in the contralateral limbs which responded to treatment with both levodopa and apomorphine. These drugs also precipitated dose-dependent contralateral rotation which reached a peak 2 weeks after MPTP infusion. A massive depletion of large, presumably dopaminergic cells was found from the ipsilateral substantia nigra pars compacta. Three animals receiving chronic therapy with apomorphine developed choreoathetoid movements of the limbs and the face contralateral to the infusion 2 weeks after the commencement of treatment. The severity of the dyskinesia gradually increased and after 4 weeks peak-dose hemiballistic movements were seen. Levodopa and the selective D-2 and D-1 dopamine agonists LY-171555 and SKF 38393 also reversed parkinsonian features and produced contralateral rotation and peak-dose dyskinesia. This unilateral model of parkinsonism in the primate will be of value in the elucidation of the mechanisms by which chronic levodopa or dopamine agonist therapy enhance involuntary movements in parkinsonism.


Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Treatment of Metastatic Non-Small Cell Lung Cancer, with a Focus on Afatinib.
Somatic epidermal growth factor receptor (EGFR) mutations are present in around 50% of Asian patients and in 10-15% of Caucasian patients with metastatic non-small cell lung cancer (NSCLC) of adenocarcinoma histology. The first-generation EGFR-tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have demonstrated improved progression-free survival (PFS) and response rates but not overall survival (OS) benefit in randomized phase III trials when compared with platinum-doublet chemotherapy. All patients treated with EGFR-TKIs will eventually develop acquired resistance to these agents. Afatinib, an irreversible ErbB family blocker, has shown in two randomly controlled trials in patients with EGFR-activating mutations, a significant improvement in PFS and health-related quality of life when compared to platinum-based chemotherapy. Afatinib improved OS in patients with Del19 mutations. In patients having progressed on first-generation EGFR-TKIs, afatinib did lead to a clinical benefit. A randomly controlled trial showed that PFS was significantly superior with afatinib vs. erlotinib in patients with squamous NSCLC in the second-line setting. A phase IIb trial comparing afatinib and gefitinib in first-line EGFR positive NSCLC showed significantly improved PFS with afatinib but OS was not significantly improved.


[Cerebral edema following experimental subarachnoid hemorrhage (author's transl)].
Despite the fact that cerebral edema appears to be a common complication of subarachnoid hemorrhage (SAH) due to a ruptured cerebral aneurysm, measurements of brain tissue water content have not been carried out in this entity. For this reason, the development of cerebral edema has been analized in a newly developed experimental SAH model. SAH was induced in cats under controlled ventilation by withdrawing needles previously pierced into one or both infraclinoid internal carotid arteries through a unilateral transorbital approach. Intracranial pressure (ICP), blood pressure, cortical EEG and somatosensory evoked potentials (SEP) to sciatic nerve stimulation were monitored for 3 to 24 hours. Using labelled microspheres of 15 mu diameter, four serial determinations of regional cerebral blood flow (rCBF) were performed in one group of five animals before and immediately after SAH as well as 10 to 20 min, and 3 to 6 h post SAH. RCBF were obtained in 60 areas of the brain from tissue samples weighing about 150 mg. Brain tissue water content was determined by the vacuum freeze-drying weighing procedure in the same brain samples. In another group of five, brain tissue specific gravity (SG) was measured by microgravimetry in samples of brain tissue weighing 30 to 50 mg. Regional differences in SG as well as in water content were calculated from 21 untreated control animals.+2


Measurement of Plasmodium falciparum transmission intensity using serological cohort data from Indonesian schoolchildren.
As malaria transmission intensity approaches zero, measuring it becomes progressively more difficult and inefficient because parasite-positive individuals are hard to detect. This situation may arise shortly before achieving local elimination, or during surveillance post-elimination to prevent reintroduction. Antibody responses against the parasite last longer than the infections themselves. This "footprint" of infection may thus be used for assessing transmission intensity. A statistical approach is presented for measuring the seroconversion rate (SCR), a correlate of the force of infection, from individual-level longitudinal data on antibody titres in an area of low Plasmodium falciparum transmission. Blood samples were collected from 160 Indonesian schoolchildren every month for six months. Titres of antibodies against AMA-1 and MSP-1(19) antigens of P. falciparum were measured using ELISA. The distribution of antibody titres among seronegative and -positive individuals, respectively, was estimated by comparing the titres from the study data (a mixture of both seropositive and -negative individuals) with titres from a (unexposed) negative control group of Indonesian individuals. Two Markov-Chain models for the transition of individuals between serological states were fitted to individual anti-PfAMA-1 or anti-PfMSP-1 titre time series using Bayesian Markov-Chain-Monte-Carlo (MCMC). This yielded estimates of SCR as well as of the duration of seropositivity. A posterior median SCR of 0.02 (Pf AMA-1) and 0.09 (PfMSP-1) person(-1) year(-1) was estimated, with credible intervals ranging from 1E-4 to 0.2 person(-1) year(-1). This level of transmission intensity is at the lower range of what can reliably be measured with the present study size. A Bayesian test for seroconversion of an individual between two observations is presented and used to identify the subjects who have most likely experienced an infection. Furthermore, the theoretical limits of measuring transmission intensity, and how these depend on duration and size of a study as well as on transmission intensity itself, is illustrated. This analysis shows that it is possible to measure SCR's from individual-level longitudinal data on antibody titres. In addition, individual seroconversion events can be identified, which can be useful in assessing interruption of transmission. Analyses of further serological datasets using the present method are required to improve and validate it. This includes measurement of the duration of antibody responses, how it depends on host age or cumulative exposure, or on the particular antigen used.


Double-quantum filtered rotational-echo double resonance.
The homonuclear scalar coupling of a directly bonded 13C-13C pair has been used to create a double-quantum filter (DQF) to remove the natural-abundance 13C background in 13C{15N} rotational-echo double-resonance (REDOR) experiments. The DQF scalar and REDOR dipolar evolution periods are coincident which is important for sensitivity in the event of weak 13C-15N dipolar coupling. Calculated and observed 13C{15N} DQF-REDOR dephasings were in agreement for a test sample of mixed recrystallized labeled alanines. Glycine metabolism in a single uniform-15N soybean leaf labeled for 6 min by 13CO2 was measured quantitatively by 13C{15N} DQF-REDOR with no background interferences.


Genetic Encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic Diels-Alder reactions.
Rapid, site-specific labeling of proteins with diverse probes remains an outstanding challenge for chemical biologists. Enzyme-mediated labeling approaches may be rapid but use protein or peptide fusions that introduce perturbations into the protein under study and may limit the sites that can be labeled, while many "bioorthogonal" reactions for which a component can be genetically encoded are too slow to effect quantitative site-specific labeling of proteins on a time scale that is useful for studying many biological processes. We report a fluorogenic reaction between bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) and tetrazines that is 3-7 orders of magnitude faster than many bioorthogonal reactions. Unlike the reactions of strained alkenes, including trans-cyclooctenes and norbornenes, with tetrazines, the BCN-tetrazine reaction gives a single product of defined stereochemistry. We have discovered aminoacyl-tRNA synthetase/tRNA pairs for the efficient site-specific incorporation of a BCN-containing amino acid, 1, and a trans-cyclooctene-containing amino acid 2 (which also reacts extremely rapidly with tetrazines) into proteins expressed in Escherichia coli and mammalian cells. We demonstrate the rapid fluorogenic labeling of proteins containing 1 and 2 in vitro, in E. coli , and in live mammalian cells. These approaches may be extended to site-specific protein labeling in animals, and we anticipate that they will have a broad impact on labeling and imaging studies.


Carbon-Assisted Minimally Invasive Transtubular Approach for Intercostal Nerve Schwannoma.
The intraoperative localization of an intercostal nerve schwannoma (INS) is extremely difficult because the lesion is generally not palpable, and the fluoroscopic visualization of anatomic landmarks in the ribs is unsatisfactory. Using activated carbon suspension to mark the soft-tissue approach could improve INS localization. We present a novel, simple, reproducible carbon-assisted minimally invasive transtubular approach for an INS. The patient was a 57-year-old man with a painful 12th left INS arising below the floating rib. A computed tomography image-guided, tumor-to-skin marking with aqueous carbon suspension was performed 48 hours before surgery. A minimally invasive transtubular approach following the carbon path allowed a precise tumor location. The INS was completely removed. The patient's thoracic radicular pain was immediately relieved after surgery. He was discharged the following day with residual numbness on the left thoracic side. At the 5-year follow-up, no tumor recurrence was noted in the control MRI. This article presents an alternative novel technique for resecting an intercostal schwannoma. Using a transtubular approach with carbon-marking assistance allowed a tumor gross total resection with immediate pain relief and a successful outcome.


In Vivo Evaluation of Two-Piece Implants Placed Following One-Stage and Two-Stage Surgical Protocol in Posterior Mandibular Region. Assessment of Alterations in Crestal Bone Level.
Endosseous implants can be placed following either two-stage technique requiring second-stage surgery or one-stage technique, which does not involve a second surgical intervention. The present study was undertaken to evaluate and compare the changes in crestal bone level when two-piece implants were placed in posterior mandibular region following one-stage and two-stage surgical protocol. A parallel group randomized prospective study was designed in which 20 two-piece implants were placed in the posterior mandibular region of 16 partially edentulous healthy patients following either one-stage (Group I) or a two-stage surgical protocol (Group II). Alterations in crestal bone level were assessed with the help of DentaScan at baseline, that is, at the time of implant placement, third month and sixth month. Nonsignificant differences were seen in both groups in terms of changes in crestal bone level at the final evaluation. Hence, it could be concluded that two-piece implants can be placed following one-stage surgical protocol as predictably as when two-stage surgical technique is followed.


A rare case of pulmonary artery embolism with choriocarcinoma: A case report and literature review.
Pulmonary embolism (PE) caused by malignant tumor is not uncommon, but pulmonary artery with choriocarcinoma is rare and difficult to timely diagnose and effectively treat. To the best of our knowledge, there are only 15 cases reported at present in the literature that present variable clinical characteristics and prognosis. In the current study reports a 21-year-old female with a history of chest pain and slight fever for 4 months who was treated as a case of pneumonia. Owing to the recurrence of the symptoms, a contrast-enhanced chest computer tomography scan was performed on the patient, which revealed complete occlusion of the right pulmonary artery. The patient was diagnosed to have pulmonary embolism (PE). However, no abnormalities were observed in D-dimer value, tumor antigen testing or ultrasonography. Positron emission tomography/computed tomography (PET/CT) was performed, which revealed the abnormal hypermetabolic lesion of the right pulmonary artery. Following the laboratory report of a significantly elevated human chorionic gonadotropin β-subunit level combined with characteristic appearance of PET-CT, the diagnosis of primary pulmonary artery with choriocarcinoma was established based on guidelines of the European Society for Medical Oncology and the criteria formulated by the International Federation of Gynecology and Obstetrics. The patient underwent chemotherapy and responded well to the treatment. Although rare, choriocarcinoma should be considered for any fertile women who presents with a massive PE. These findings emphasize the importance of the early diagnosis and treatment of this disease.


Cutaneous alternariosis microscopically mimicking blastomycosis.
A 57-year-old man status post several myocardial infarcts and heart transplantation presented with a slowly growing violaceous plaque on his lateral left knee at the site of prior minor trauma. A biopsy revealed a suppurative dermatitis with associated pseudocarcinomatous epithelial hyperplasia. There were multiple non-pigmented eosinophilic organisms with clear cytoplasmic halos within the infiltrate. A methenamine silver stain showed round to ovoid organisms of slightly variable size. Rare uni-polar budding, some of which was broad based, was apparent. A few short hyphae with indeterminate septa were also noted. Fontana-Masson, mucicarmine, Alcian blue and Fite stains were all negative. These findings suggested a diagnosis of blastomycosis. However, a fungal culture grew colonies of Alternaria species. Alternariosis has been previously shown to possess morphologic characteristics that can simulate other fungal infections. To our knowledge, a striking similarity to blastomycosis, as seen in our case, has not been previously reported. Dermatopathologists should be aware that alternariosis may mimic blastomycosis, especially when hyphal forms are rare or absent in tissue specimens. Culture is necessary for definitive classification.


[Risk factors of kidney injury in patients with COVID-19].
To determine the incidence and risk factors of acute kidney injury (AKI) in Russian cohort of patients with COVID-19. We included 315 patients, who were hospitalized with COVID-19 from October 2020 till February 2021. The diagnosis was established on the basis of the positive SARS-CoV-2 swab test and/or typical radiologic findings on CT scans. AKI complicated the clinical course in 92 (29.21%) cases. The independent risk factors of AKI were female sex, underline chronic kidney disease and the highest level of C-reactive protein during hospitalization. In the general group of patients were 41 (13%) lethal cases, in the group with AKI 32 (34.8%). Compared with those without AKI, patients with AKI had 4.065 (95% confidence interval 2.154 to 7.671) times the odds of death. Respiratory support, the highest serum creatinine and glucose levels appeared to be the risk factors of death among patients with AKI in the multivariable Cox regression. The clinical course of COVID-19 was complicated by AKI in 29% cases. The independent risk factors of AKI in patients with COVID-19 are underline chronic kidney disease, circulatory disorder and the highest level of C-reactive protein during hospitalization.


The treatment of Uygur medicine Dracocephalum moldavica L on chronic mountain sickness rat model.
Dracocephalum moldavica L, a traditional Uygur medicine, possesses some key cardiac activities. However, till date, no reports are available on the use of D. moldavica against chronic mountain sickness (CMS), which is a medical condition that affects the residents of high altitude. The present study was designed to explore the treatment efficacy of D. moldavica on CMS. 80 of the 100 Sprague Dawley rats enrolled were bred in simulated high altitude environment and the remaining 20 rats were kept in the plains. Water and alcohol extracts of D. moldavica were prepared. CMS rat model was prepared, and the rat hearts were removed for histopathological analysis. Blood samples were taken for hematological and biochemical analyses. Rat pulmonary artery pressure was determined to study the treatment efficacy. In the CMS model group, the levels of interleukin-6 (IL-6), C-reactive protein (CRP), and malondialdehyde (MDA) were found to be significantly higher than the control group; while the concentrations of SOD and GSH-Px decreased. D. moldavica could improve these levels, decrease pulmonary artery pressure, and improve the cardiac pathological state. The study results show that IL-6, CRP, MDA, SOD and GSH-Px participate and mediate the formation of CMS and D. moldavica is found to possess noticeable effects on CMS. The present study explored the basics of high altitude sickness and laid the foundation for further progress of Uygur medicines on the treatment of altitude sickness. Further preclinical and clinical studies with more sample size are recommended.


Parent-child dyadic mutuality and child behavior problems: an investigation of gene-environment processes.
Parent-child mutuality is comprised of emotional reciprocity, co-responsiveness, and cooperation, which together represent aspects of co-regulation of emotion and behavior that may be important in the etiology of children's behavior problems. Furthermore, individual differences in children's mutuality and behavior problems involve transactions between genetic and environmental influences. Behavioral genetic designs are useful for elucidating these processes. The sample included 396 children in adoptive families (53% female, age M = 8.16 years), of whom 244 were siblings (122 pairs). All of the siblings were genetically unrelated. In some families, one child was adopted but the other child was a biological child of the adoptive parents. We observed mother-child dyadic mutuality (a composite score including responsiveness, interaction reciprocity, and cooperation) during videotaped in-home observations. In addition, child behavior problems were assessed and represented as a composite score including observers' ratings of noncompliance, and parents' ratings of aggression and conduct problems. Greater mutuality was associated with lower levels of child behavior problems, both between families and within families (i.e., sibling differences). The sibling intra-class correlation for mutuality with the same parent was near zero in this sample of genetically unrelated siblings. The correlation between child behavior problems and dyadic mutuality did not vary as a function of mother-child genetic similarity. Mother-child mutuality is child specific within families, a finding that is consistent with theories regarding bi-directional parent and child effects in socialization. In addition, there was no evidence of passive gene-environment correlation, suggesting that the link between lower levels of maternal mutuality and higher levels of child behavior problems is not only reflecting overlapping genetic influences on parent and child behavior.


Efficacy and Safety of Intravitreal Dexamethasone Implants for Treatment of Refractory Diabetic Macular Edema.
To evaluate the safety and efficacy of intravitreal dexamethasone (IVD) implants in eyes with diabetic macular edema that did not respond to previous treatment. We included 46 eyes of 46 patients in this retrospective study. Each month, we recorded patient visual acuity with logarithm of the minimum angle of resolution using the Early Treatment Diabetic Retinopathy Study chart, central macular thickness measurements with optical coherence tomography, intraocular pressure (IOP), and posttreatment complication occurrence. The mean follow-up time was 8.95 ± 1.33 months (range, 6 to 12). Best-corrected visual acuity improved significantly in the first 4 months after IVD, but no statistically significant change was observed over the following 2 months. Although a statistically significant decrease in central macular thickness was observed in the first 3 months, the change was not statistically significant in the following 3 months. There was a statistically significant increase in IOP in the first 2 months, but no statistically significant change was observed in the following months. IOP was controlled with medication in all patients with elevated IOP. Of the 26 phakic patients, two had cataracts requiring surgery. Cases of refractory diabetic macular edema that did not respond to previous treatment, such as anti-vascular endothelial growth factor injections and laser photocoagulation, exhibited improvements in visual acuity and decreases in retinal thickness after IVD implantation. Both functional and anatomical effects were observed in the first 3 months after injection. Repeat injections and frequent examination might be required for continued improvement. Side effects, such as cataracts and elevation of IOP, may require medical or surgical treatment.


Electrical and optical performance evaluation in solution-process-based optoelectronic devices: theoretical modeling.
This paper presents a computational and semi-analytical approach for theoretical evaluation of solution-process-based optoelectronic devices, such as quantum dot (QD) infrared photodetectors. The dark current and photocurrent for infrared photodetectors are extracted on the basis of the model presented here. In this model, two main mechanisms have been assumed to contribute to the current of the device: the electron tunneling in the confined states and the drift of electrons in the continuum states. For the former, the Landauer-Büttiker formalism, in which the transmission function was obtained through the Green's function method was used. However, the drift-diffusion model was applied for the latter while considering the trapping and detrapping roles of QDs. Furthermore, different geometrical effects have been analyzed, including the QDs' size distribution, the space between QDs, the system's length, and the system's width, on the device's parameters, such as the absorption coefficient, photoconductive gain, dark current, and detectivity. The results seem to point to a great dependency of the device's performance on these geometrical aspects. For example, the nonuniformity of the QDs' sizes have been shown to exert negative effects on the device's detectivity. In addition, it could noticeably influence the tunneling current, such as by decreasing the maximum value of the current.


Validation of Nomograms for Survival and Metastases after Hysterectomy and Adjuvant Therapy in Uterine Cervical Cancer with Risk Factors.
Background. Three nomogram models for early stage uterine cervical cancer have been developed (KROG 13-03 for overall survival [OS], SNUH/AMC for disease-free survival [DFS], and KROG 12-08 for distant metastases-free survival [DMFS]) after radical hysterectomy (RH) and pelvic lymph node dissection (PLND). This study aimed to validate these models using our cohort with adjuvant radiotherapy. Methods. According to the eligibility criteria of nomogram studies, patients were enrolled in Group A (N = 109) for the two KROG models (RH with PLND and whole pelvic irradiation) and Group B (N = 101) for the SNUH/AMC model (RH with PLND and squamous histology). Using Cox-regression hazard models, the prognostic factors of our cohorts were evaluated. The risk probabilities induced from published nomogram scores were calculated and the concordance indices were evaluated. Results. Group A had 88.1% 5-year OS and 86.0% 5-year DMFS. Group B had 83.0% 5-year DFS. In multivariate analyses, large tumor size for OS (HR 8.62, P < 0.001) and DMFS (HR 5.13, P = 0.003), young age (≤40 versus 41-64 years) for OS (HR 4.63, P = 0.097) and DFS (HR 3.44, P = 0.051), and multiple lymph node metastases (0 versus ≥3) for DMFS (HR 4.03, P = 0.031) and DFS (HR 3.90, P = 0.038) were significantly correlated. The concordance indices for OS, DMFS, and DFS were 0.612 (P = 0.002), 0.597 (P = 0.014), and 0.587 (P = 0.020), respectively. Conclusion. The developed nomogram models after RH and PLND are clinically useful in predicting various types of survival with significance.


Sequestration of Ni (II), Pb (II), and Zn (II) utilizing biogenic synthesized Fe3O4/CLPC NCs and modified Fe3O4/CLPC@CS NCs: Process optimization, simulation modeling, and feasibility study.
The present study reports low-cost novel biogenic magnetite Citrus limetta peels carbon (Fe3O4/CLPC) nanocomposites and modified Fe3O4/CLPC@CS nanocomposites cross-linked with glutaraldehyde and subsequently employed in batch mode sequestration of heavy metals ions. Diverse techniques fully characterized them, and the influence of operating variables on adsorption reactions from aqueous solutions was investigated. The Brunauer, Emmett, and Teller (BET) surface areas of synthesized Fe3O4/CLPC and Fe3O4/CLPC@CS NCs were 53.91 and 32.16 m2/g, while the mesoporous diameters were 7.69 and 7.57 nm, respectively. The Langmuir isotherm and Pseudo second order kinetic were well-fitting and capable of explaining the adsorption reaction. The Langmuir-based monolayer adsorption (qmax) for Fe3O4/CLPC@CS NCs was 82.65, 95.24, and 64.10 mg/g, higher than Fe3O4/CLPC NCs, which were 70.92, 84.75, and 59.17 mg/g for Ni (II), Pb (II), and Zn (II), respectively. Each metal's pseudo second order correlation coefficient (R2 ≥ 0.99) reveals that nanocomposites surface binding functional groups controlled the adsorption rate via chemisorption. Further, thermodynamic results confirm that each studied metal ions' adsorption was spontaneous, endothermic, and characterized by an increase in randomness. In addition to magnetic separability, three ad-desorption cycles yielded exceptional adsorption efficacy and > 93% regenerability. The present study also reveals the effective utilization of Fe3O4/CLPC and Fe3O4/CLPC@CS NCs as cost-effective magnetic separable green adsorbents for heavy metals sequestration from electroplating wastewater.


Scheme to estimate water-leaving albedo from remotely sensed chlorophyll-a concentration.
Water-leaving albedo (αw(λ)) is an important component of the ocean surface albedo and is conventionally estimated based on remotely sensed chlorophyll-a concentration (Chl) (termed Chl-αw). We show that estimated αw(λ) by Chl-αw could be significantly biased in global oceans, because there is no guarantee of closure between the modeled remote sensing reflectance (Rrs(λ)) from Chl-inferred inherent optical properties (IOPs) and the input Rrs(λ) that is used to derive Chl. We thus propose a simple and improved scheme, termed Chl-αw_new, and show that the step to infer IOPs from Chl is not necessary, where αw(λ) can be accurately estimated from satellite-measured Rrs(λ) and a Chl-based look-up-table (LUT) for the bidirectional relationships of angular Rrs(λ). Evaluations with both HydroLight simulations and satellite measurements show that Chl-αw_new is equivalent to the recently developed αw scheme based on IOPs (IOPs-αw, [Remote Sens. Environ. 269, 112807]), where both schemes could significantly improve the estimation of αw(λ) compared to Chl-αw. Comparisons among Chl-αw, Chl-αw_new, and IOPs-αw highlight that optical closure of Rrs(λ) is essential for accurate remote sensing of αw(λ), while the model for Rrs(λ) bidirectionality has rather minor impacts. The impact of improved αw(λ) estimations on the solar flux exchanges at the air-sea interface is preliminarily evaluated in this effort, where the use of Chl-αw_new could increase the estimation of reflected solar radiation by over 68.7% in turbid waters compared to that using Chl-αw, highlighting the necessity of incorporating accurate αw schemes into the coupled ocean-atmosphere models, especially for regional models in coastal oceans.


Compared Methods for Reducing Stress in ROP Exams; Stake-Holding Examiner Perspective.
To better understand the sensory impact of retinal exam components typically experienced by infants undergoing various retinopathy of prematurity staging examinations, adults concerned for infant welfare and exam quality underwent similar exams to compare their perceived stress. Adults directly involved with ROP exams and infant stress reduction had cardiac monitoring and concomitant ordinal self symptom-score (1-10 Likert) during 15 components of the exam including lid speculum, various scleral depressors, indirect ophthalmoscopy, goniolens and direct ophthalmoscopy and retinal photography (Phoenix ICON) with or without topical anesthesia. Nine adults provided impressions and cardiac rhythm gathered supine over 15 minutes. Pain score for topical anesthetic 2 was less than for tropicamide 4. Lid specula numb scored a median 2 level (from 1 to 10) pain but without anesthetic scored 6. The goniolens numb scored 3. Scleral depression numb scored 3-4 but increased to 7 without topical anesthesia. Direct ophthalmoscope scored 3 through the goniolens and the retinal camera scored 4 pain. Brightness with low 350 Lux indirect scored 6-8 numb and 9 brightness without anesthetic. Full bright indirect, direct ophthalmoscope and the retinal camera all had Lux of 3000-4000 and were scored brightness 9, 7 and 10, respectively. Adults had minimal oculocardiac reflex during on-globe retinal examination methods (range 98% to 102%). Topical anesthesia provided a moderate reduction in pain during on-globe lid-speculum, scleral depressed indirect examination. There was a synergistic augmented sensory response between pain and brightness. Adults did not show the bradycardia typically elicited by retinal examinations in premature infants.


On the actual EPR detection of thioacyl radicals.
The direct EPR detection of thioacyl radicals has been reported only once, while thioacyl nitroxides remain an elusive species. We failed to detect the thioacyl radicals from two thioaldehydes and from phosphoryldithioformates but have obtained EPR evidence that thioacyl radicals react with 2-methyl-2-nitrosopropane to give thiocarbonyloxyaminyls rather than thioacyl nitroxides. The results of DFT calculations support this unexpected reactivity of thioacyls, while making questionable their previous EPR identification.


Polarized Raman and Infrared Spectroscopy and ab Initio Calculation of Palmitic and Stearic Acids in the Bm and C Forms.
A complete experimental study on the vibrational properties of palmitic and stearic acids crystallized in the Bm and C forms, both belonging to the monoclinic system with the P21/a (C2h5) space group, through polarized Raman and infrared spectroscopy, is reported in this paper. Density functional theory calculations were also performed to assign the normal modes and to help in the interpretation of the experimental data. The different polarizations were compared and their influence on the spectral profiles, in both the lattice and the internal mode regions, was discussed. In general, the Raman and infrared spectra exhibit accentuated differences among the polymorphic forms, which are associated with the different molecular modifications, defined as gauche and all-trans conformations. Insights about interaction among different groups are also furnished.


Factor structure of the Agitated Behavior Scale.
The Agitated Behavior Scale (ABS; Corrigan, 1989) is a 14-item scale developed to monitor agitation during the acute phase of recovery from acquired brain injury. While previous studies have supported the reliability, internal consistency, and concurrent validity of the ABS, the current study was designed to investigate its underlying factor structure, as well as to determine systematic effects of time-of-day on the occurrence of agitation. Subjects were 212 patients with traumatic or other recently acquired brain injury who exhibited agitation during their treatment on a specialized brain-injury unit of an acute rehabilitation hospital. Confirmatory factor analysis revealed that agitation is best represented by one general construct with three underlying factors: Aggression, Disinhibition, and Lability. Analysis of agitation by nursing shift in which ratings were made confirmed that overall level was lowest during the night shift; however, the relationship between time-of-day and underlying factors deviated from this pattern. Results are discussed in terms of the necessity for objective measurement, definition of the construct of agitation, and time-of-day issues in sampling agitated behavior.


The anti-oxidative defence system in the isolated rat uterus during spontaneous rhythmic activity.
Possible interactions between nitric oxide donors, reactive oxygen species and anti-oxidative defence enzymes led us to determine the activities of anti-oxidative defence enzymes in isolated uterine smooth muscle before and after spontaneous rhythmic activity ex vivo. For our experiments we used isolated uteri from female Wistar rats. Our results showed an increase in total superoxide dismutase (SOD) and Mn SOD activities in uterine smooth muscle after spontaneous contractions when compared with nonexercised uterine smooth muscle. The activity of catalase (CAT) and glutathione preoxidase (GSH-Px) were also increased. No statistically significant changes in the activities of glutathione reductase (GR) and CuZn SOD were found. It is known that an organism's anti-oxidative defence system (guarding against excessive reactive oxygen species generation) requires balanced increments in its individual anti-oxidative enzyme activities rather than increases in the activity of only some enzymes without increases in others. Thus, we may conclude that some adaptive responses are found in exercised uterine smooth muscle but are not complete. Therefore, our results indicate that changes in anti-oxidative enzyme activities may influence the results of the examination of substances ex vivo.


Epidemiology of Cancers in Kashmir, India: An Analysis of Hospital Data.
Cancer is a leading cause of mortality and morbidity in the world. The aim of the present study was to measure the pattern of different cancers in Kashmir, India, a cancer belt with peculiar cancer profile. A hospital based cancer registry was started by the Department of Community Medicine, Government Medical College, Srinagar, in January 2006, wherein information was collected from cancer patients who were diagnosed and treated in the hospital. Data has been analysed for a period extending from January 2006 to December 2012. Descriptive analysis has been done by using statistical software. A total of 1598 cancer patients were admitted during this period. Overall male to female ratio was 1.33 : 1. Stomach cancer was the most commonly reported cancer (25.2%), followed by colorectal cancer (16.4%) and lung cancer (13.2%) among males. For females, colorectal cancer (16.8%), breast cancer (16.1%), and stomach cancer (10.4%) were the most frequently reported cancers in order of frequency. Tobacco related cancers contributed to more than three-fourths of cancers among men and more than half of cancers for women. There is an urgent need to set up a population based cancer registration system to understand the profile of cancers specific to this geographic region.


Angiotensin II type 1 receptor blocker telmisartan suppresses superoxide production and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice.
Angiotensin II is involved in the process of atherosclerosis and stimulates superoxide production from cardiovascular cells. We examined the effect of telmisartan, an angiotensin II type 1 receptor blocker, on atherosclerosis. We chronically treated apolipoprotein E-deficient mice with two different doses of telmisartan dissolved in drinking water (0.3 and 3 mg/kg) starting from 4 weeks of age for 12 weeks. Lipid contents were not different in both telmisartan-treated groups compared with control group. Systolic blood pressure was significantly reduced with 3 mg/kg, but unchanged with 0.3 mg/kg. The total atherosclerotic lesion size at the aortic sinus was reduced with 0.3 mg/kg compared with control, and additional reduction was proved with 3 mg/kg. The fibrotic change was not different among three groups, but MOMA-2-, malondialdehyde-, 4-hydroxy-2-nonenal-immunostained areas were reduced by telmisartan. As the mechanism, we revealed that both doses of telmisartan markedly reduced superoxide production from in situ vessels assessed by lucigenin-enhanced chemiluminescence and dihydroethidium staining. And NAD(P)H dependent oxidase activity in vessels was reduced by telmisartan. Further, 8-iso-prostaglandin F2alpha level, a systemic oxidative stress marker, obtained from urine and plasma samples were significantly reduced by telmisartan. Telmisartan reduced atherosclerosis in apolipoprotein E-deficient mice at least partly via the suppression of oxidative stress.


The Contribution of lincRNAs at the Interface between Cell Cycle Regulation and Cell State Maintenance.
Cell cycle progression is controlled by the interplay of established cell cycle regulators. Changes in these regulators' activity underpin differences in cell cycle kinetics between cell types. We investigated whether long intergenic noncoding RNAs (lincRNAs) contribute to embryonic stem cell cycle adaptations. Using single-cell RNA sequencing data for mouse embryonic stem cells (mESCs) staged as G1, S, or G2/M we found differentially expressed lincRNAs are enriched among cell cycle-regulated genes. These lincRNAs (CC-lincRNAs) are co-expressed with genes involved in cell cycle regulation. We tested the impact of two CC-lincRNA candidates and show using CRISPR activation that increasing their expression is associated with deregulated cell cycle progression. Interestingly, CC-lincRNAs are often differentially expressed between G1 and S, their promoters are enriched in pluripotency transcription factor (TF) binding sites, and their transcripts are frequently co-regulated with genes involved in the maintenance of pluripotency, suggesting a contribution of CC-lincRNAs to mESC cell cycle adaptations.


Laryngeal suspension and epiglottic flap in laryngopharyngeal trauma.
Physicans treating laryngeal trauma are still looking for ways to improve results. Severe disruption of the supporting structures between hyoid and trachea may allow stretching and narrowing of the laryngeal lumen during the healing period. This can easily be prevented by placing wires across the disrupted zone. In addition, loss of the epithelial lining of the larynx is a serious cause of stenosis. By dissecting out the epiglottic cartilage, one can create a sizeable, useful flap of mucous membrane based in the vallecula to use in relining of the anterior larynx.


Automatic diagnosis of abnormal macula in retinal optical coherence tomography images using wavelet-based convolutional neural network features and random forests classifier.
The present research intends to propose a fully automatic algorithm for the classification of three-dimensional (3-D) optical coherence tomography (OCT) scans of patients suffering from abnormal macula from normal candidates. The method proposed does not require any denoising, segmentation, retinal alignment processes to assess the intraretinal layers, as well as abnormalities or lesion structures. To classify abnormal cases from the control group, a two-stage scheme was utilized, which consists of automatic subsystems for adaptive feature learning and diagnostic scoring. In the first stage, a wavelet-based convolutional neural network (CNN) model was introduced and exploited to generate B-scan representative CNN codes in the spatial-frequency domain, and the cumulative features of 3-D volumes were extracted. In the second stage, the presence of abnormalities in 3-D OCTs was scored over the extracted features. Two different retinal SD-OCT datasets are used for evaluation of the algorithm based on the unbiased fivefold cross-validation (CV) approach. The first set constitutes 3-D OCT images of 30 normal subjects and 30 diabetic macular edema (DME) patients captured from the Topcon device. The second publicly available set consists of 45 subjects with a distribution of 15 patients in age-related macular degeneration, DME, and normal classes from the Heidelberg device. With the application of the algorithm on overall OCT volumes and 10 repetitions of the fivefold CV, the proposed scheme obtained an average precision of 99.33% on dataset1 as a two-class classification problem and 98.67% on dataset2 as a three-class classification task.


The effects of rainfall and vegetation on litterfall production in the semiarid region of northeastern Brazil.
Litterfall has a strong influence on biodiversity and on the chemical and physical characteristics of the soil. Its production can be quite variable over time and space, and can be influenced by both natural and anthropogenic factors. We evaluated litterfall production and its relationship with rainfall, species richness, and the densities of the arboreal vegetation. Thirty litter traps were constructed with 1.0 m2 nylon mesh (1.0 mm) and randomly installed within a 2000 m × 500 m area of arboreal/shrub Caatinga (dryland) vegetation. Litter samples were collected monthly from November/2010 to June/2012, and the collected material was classified, dried, and weighted. Species richness and tree densities were determined by conducting phytosociological surveys in 20 m × 20 m plots surrounding each of the litter traps. The litterfall accumulation rate was 3.673 Mgha-1yr-1, similar to values from other seasonally dry tropical forests. Litterfall production was continuous, and principally accompanied the rainfall rate, but with a time interval of 2 to 3 months, with the greatest accumulation at the beginning of the dry season and the least during the rainy season. The different fractions of materials demonstrated distinct accumulation rates, with leaves being the principal category. Litterfall production was found to be related to tree density, but no link was found to species richness. The observed temporal heterogeneity of litterfall production demonstrated a strong link between rainfall and the dynamics of nutrient cycling in the semiarid region of Brazil.


High-order framework nucleic acid for targeted-delivery of antisense peptide nucleic acids to overcome drug resistance.
A sophisticated high-order framework nucleic acid (FNA) was engineered for the targeted delivery and responsive release of environment tolerant antisense peptide nucleic acids (asPNAs). The dendritic FNA-asPNAs system was constructed via simple one-pot modular assembly and demonstrated a good synergistic effect with chemotherapy on drug resistant cancer cells.


An analysis of unscheduled return visits to an urban emergency department.
This study was undertaken to identify the reasons for unscheduled return visits to an urban emergency department, particularly those relating to physician errors in diagnosis and management, and, where possible, to identify strategies to reduce unscheduled return visits. All patients returning to the Emergency Department, Christchurch Hospital, within seven calendar days of initial visit were identified. These cases were reviewed to identify reasons for return visit. Unscheduled return visits accounted for 2% of patient encounters. Sixty one per cent were due to illness related factors, 27% to patient related factors, 11% to physician related factors and 1% to system related factors. Significant management errors occurred in nine patients (4.4% of unscheduled return visits), three of whom were admitted. There were no ICU or CCU admissions and no deaths. Significant physician errors were a minor reason for reattendance at the emergency department and no specific areas of deficiency were identified. These might be further reduced by increasing the seniority and experience of staff and by the introduction of regular audit, continuing medical education and vocational training programmes. Interventions to reduce patient related unscheduled return visits might include better explanation of the role of the emergency department and better communication with patients about their illness and treatment.


Comparison of Combined Intraarticular and Intravenous Administration of Tranexamic Acid with Intraarticular and Intravenous Alone in Patients Undergoing Total Knee Arthroplasty without Drainage Catheter: A Clinical Trial Study.
We aimed to assess the most effective route for Tranexamic acid (TXA) administration among Intraarticular (IA), Intravenous (IV), and combined IA/IV for Total Knee Arthroplasty (TKA) surgeries. A double-blinded clinical trial was run on 147 TKA candidates. Blood loss and hemoglobin (Hb) drop were evaluated using the Gross and Nadler formula in three matched case groups administered TXA during the TKA through IV, IA, or combined IA/IV route. Tourniquet was used on all operations for controlling intraoperative blood loss. No drainage catheter was used for the cases. The combined group showed an average blood loss of 630±252 ml, which was significantly lower than that in the IV group (878±268 ml, P<0.01) and the IA group (774±288 ml, P=0.03). Furthermore, the mean Hb and hematocrit drop were significantly lower in the combined group, compared to the other two groups, 48 and 72 h postoperatively (P<0.05). The combined IA/IV route had a 28% and 19% reduction of blood loss, compared to the IV or IA methods, respectively. Therefore, using TXA via the combined IA/IV route may be more effective for reducing perioperative blood loss following TKA surgery using a tourniquet without drain placement.


Retroperitoneal laparoendoscopic single-site adrenalectomy: our initial technical experience.
We performed retroperitoneal laparoendoscopic single-site (LESS) adrenalectomy using a homemade multi-access platform to evaluate the feasibility and safety of this technique and to share our initial experiences. Since March 2011, 40 patients underwent retroperitoneal LESS adrenalectomy. A single incision of 2.5-3 cm was made under the 12th rib on the midaxillary line on the affected side. Next, a homemade multi-access platform was inserted through that incision, and a combination of lengthened curved and conventional rigid instruments was used for handling. The procedure was performed mainly according to the procedure for conventional laparoscopic retroperitoneal adrenalectomy. For 1 patient with pheochromocytoma, one additional trocar was used because the peritoneum was damaged. Surgery was successfully completed in all other patients without conversion to conventional laparoscopic or open surgery. Retroperitoneal LESS adrenalectomy is feasible; although initial technical adjustments are inevitable, some useful techniques are effective in simplifying the procedure.


Neutrophil extracellular traps formation and clearance is enhanced in fever and attenuated in hypothermia.
Fever and hypothermia represent two opposite strategies for fighting systemic inflammation. Fever results in immune activation; hypothermia is associated with energy conservation. Systemic Inflammatory Response Syndrome (SIRS) remains a significant cause of mortality worldwide. SIRS can lead to a broad spectrum of clinical symptoms but importantly, patients can develop fever or hypothermia. During infection, polymorphonuclear cells (PMNs) such as neutrophils prevent pathogen dissemination through the formation of neutrophil extracellular traps (NETs) that ensnare and kill bacteria. However, when dysregulated, NETs also promote host tissue damage. Herein, we tested the hypothesis that temperature modulates NETs homeostasis in response to infection and inflammation. NETs formation was studied in response to infectious (Escherichia coli, Staphylococcus aureus) and sterile (mitochondria) agents. When compared to body temperature (37°C), NETs formation increased at 40°C; interestingly, the response was stunted at 35°C and 42°C. While CD16+ CD49d+ PMNs represent a small proportion of the neutrophil population, they formed ~45-85% of NETs irrespective of temperature. Temperature increased formyl peptide receptor 1 (FPR1) expression to a differential extent in CD16+ CD49d- vs. CD49d+ PMNSs, suggesting further complexity to neutrophil function in hypo/hyperthermic conditions. The capacity of NETs to induce Toll-like receptor 9 (TLR9)-mediated NF-κB activation was found to be temperature independent. Interestingly, NET degradation was enhanced at higher temperatures, which corresponded with greater plasma DNase activity in response to temperature increase. Collectively, our observations indicate that NETs formation and clearance are enhanced at 40°C whilst temperatures of 35°C and 42°C attenuate this response. Targeting PMN-driven immunity may represent new venues for intervention in pathological inflammation.


Botany, traditional use, phytochemistry, pharmacology, quality control, and authentication of Radix Gentianae Macrophyllae-A traditional medicine: A review.
Radix Gentianae Macrophyllae, commonly known as Qinjiao (in Chinese), is dried roots of medicinal plants that belong to Gentianaceae family and Gentiana genus. It has medically been used for the treatment of various diseases such as arthritis, stroke, facial paralysis, and scapulohumeral periarthritis in China since ancient times. The aim of this paper is to provide a comprehensive and constructive overview of Qinjiao mainly containing Gentiana macrophylla Pall., Gentiana straminea Maxim., Gentiana crasicaulis Duthie ex Burk., and Gentiana daurica Fisch. in botany, traditional use, phytochemicals, pharmacology (biological activities and pharmacokinetics), quality control, and authentication according to the up-to-date data of available scientific literatures. All information regarding these four plants was collected from various academic search engines for example Google, Google Scholar, Web of Science, SciFinder, Pubmed, CNKI, and Wanfang. Additional information was obtained from botanical books, Chinese classic texts, and medical monographs. So far 166 compounds have been isolated and identified from Qinjiao plants together with Gentiana tibetica King ex Hook. f., Gentiana siphonantha Maxim., Gentiana officinalis H. Smith, and Gentiana waltonii Burk. Their constituents are mainly classified into iridoid glycosides, triterpenes, flavones, sterols, benzene derivatives, etc. The pharmacological studies demonstrate that Qinjiao plants display a wide range of bioactivities e.g. anti-inflammatory, anti-oxidant, hepato-protective, cardio- and neuro-protective, insecticidal, and anti-influenza effects. The conventional quality control is performed by determination of the concentration of some compounds, e.g., gentiopicroside, or establishment of the fingerprint. In addition to seed propagation, tissue culture technology has been used to address the limited supplies and guarantee the sustainable development of Qinjiao in the experimental scale. Although the identification of compounds from Qinjiao and demonstration of medicinal uses in vitro and in vivo have been carried out, various other studies on these plants should deserve our more attention. More efforts should be concentrated on the underlying mechanisms of their beneficial bioactivities. The proper toxic evaluation is indispensable to guarantee the safety, efficacy, and eligibility for medical use. To sum up, the summarized achievements could highlight the importance of Qinjiao and provide a solid foundation for scientists not only to further exploit the therapeutic potentials, but also possibly develop novel drugs in the subsequent research.


[The current view of the diagnosis and management of amebiasis in the light of the authors own case reports].
This comprehensive review is focused on a serious protozoan disease, amebiasis. This disease is caused by the human parasite Entamoeba histolytica (E. histolytica), the second leading cause of mortality due to protozoan disease worldwide (the leading cause is malaria). The incidence of amebiasis in the Czech Republic is very low, but it may be underreported as the disease often escapes diagnosis. Intestinal colonisation by E. histolytica may be asymptomatic. The clinical picture ranges from diarrhea to colitis or fulminant colitis when the parasite progresses to the trophozoite stage. Secondary dissemination in the blood or lymph system may induce systemic signs of the disease. Liver abscess is the most common extraintestinal form of amebiasis. The diagnosis of intestinal amebiasis is based on the clinical picture and parasitological examination of the stool. To diagnose extraintestinal amebiasis, serology tests are used to detect antibodies in the blood. Recently, molecular methods have been increasingly used for the detection of the nucleic acids of the pathogen in biological specimens. The first line therapy for amebiasis are 5-nitroimidazole drugs, currently available in the Czech Republic. However, surgical intervention should also be considered in patients with a severe course of the disease. Included in the review are the case reports of patients with severe concomitant intestinal and extraintestinal amebiasis.


Gene sequences and comparison of the fimbrial subunits representative of Bacteroides nodosus serotypes A to I: class I and class II strains.
We have determined the nucleotide sequences of the genes encoding the fimbrial subunits representative of the known Bacteroides nodosus serogroups. All of the genes are preceded by a highly conserved region which includes the likely promoter and transcriptional regulator sites as well as the ribosome-biding site, and are followed within a short but variable distance by a sequence with the characteristics of a transcription termination or attenuation signal. Based on sequence and organization, the subunits can be divided into two major classes called I (serogroups A, B, C, E, F, G, and I) and II (serogroups D and H). All contain the same seven-amino-acid positively charged leader sequence and conserved hydrophobic amino-terminal sequence typical of type 4 fibriae. Beyond this point the class II subunits are quite different from class I and share features more in common with those from other type 4 fimbriate bacteria, such as Moraxella bovis and Pseudomonas aeruginosa. The larger class I may be further subdivided into two subsets: (i) [A, E, F)(B, I)) and (ii) (C, G). These proteins exhibit three major clusters of variation, at either end of the presumptive disulphide loop which spans the central third of the protein, and near the carboxy-terimus, with dispersed changes in between. The length of the mature subunits varies from 152-156 amino acids, and the variation includes small insertions or deletions in the variable clusters between more conserved domains. The class II subunits are 149 amino acids in length and contain two pairs of cysteine residues: one is at the end of the amino-terminal conserved region, and the other is at the end of the protein. The major variation occurs in the central region of the molecule, and again small insertions or deletions are required to align adjacent conserved domains. There is also a striking absence of silent codon changes in the 5' coding region of all of these genes, indicating that these sequences have a secondary genetic function, probably in recombinational exchange.


Antibodies to new beta cell antigen ICA12 in Latvian diabetes patients.
In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria, and assays for the detection of autoantibodies are not available. In consequence, slowly progressive autoimmune diabetes or LADA is likely to be missed. Antibodies to GAD65 and IA-2 are the major immunological markers in autoimmune diabetes. Recently, a new beta cell antigen, called ICA12, has been identified, which has a homology to the SOX family of transcription factors. The aim of the study was to analyze the prevalence of ICA12 antibodies in diabetes mellitus patients and controls from Latvia and to see whether this antigen is important in revealing autoimmunity when antibodies against major antigens are not present. We studied 88 IDDM patients and 100 NIDDM patients as well as controls for the prevalence of GAD65, IA-2, and ICA12 antibodies by radioligand binding assay (RIA) using (35)S-labeled islet antigens. We found ICA12Abs in 26 of 88 IDDM patients (30%) vs. 4% in healthy controls (4/100) and in 9 of 100 NIDDM patients (9%) vs. 2% controls (2/100). ICA12Abs alone are present in only 3% (3/88) of the patients with IDDM and 1% (1/100) of the NIDDM patients. We conclude that ICA12 represents the minor antigens in autoimmune diabetes and that, as a minor antigen, ICA12 alone does not contribute significantly in revealing new cases of autoimmunity.


Retaining the ability to work-associated factors at work.
Prevention of work-related sickness absence has traditionally dealt with reduction of exposures to known risk factors. However, there is reason to believe that there are also factors at work that act as health supportive. This study aimed to identify workplace factors predicting retained work ability. The present prospective cohort study included the follow-up of 6337 randomly chosen, gainfully employed Swedish women and men for 1 year. Uni- and multivariate logistic regression analyses odds ratios (ORs) together with 95% confidence interval were calculated in order to estimate the strength of the associations between different factors reported in a baseline questionnaire, and retained work ability was defined as not being on long-term sick leave (> 14 days) during the follow-up. Work-related factors significantly associated with retained work ability were as follows: reporting the work as physically non-strenuous (women: OR 1.6; men: OR 2.1), working at a workplace where there are no plans to close down (w: OR 2.3) and feeling recuperated and full of energy (w : = R1.5), and often being in the mood for work (m : 1.4). Significant associations with retained work ability were also found for age, socioeconomic level, household composition, employment sector, and previous sick leave patterns. The findings highlight some factors at work, but also some in the personal sphere that are influential for retained work ability, regardless of sick leave patterns prior to the study period. Identifying such factors can provide valuable knowledge for workplace health promotion.


The passage of Florida's Statute on Assisted Reproductive Technology.
Until 1993, there were no statutes in the United States covering gestational surrogacy contracts, disposition of stored embryos and gametes, parentage of children born from donated gametes and embryos, and the inheritance rights of cryopreserved embryos of deceased donors. In March 1993, the Florida Assisted Reproductive Technology Act was passed to address some of these issues and to minimize the expense and emotional cost of related courtroom proceedings. Authors of the bill believed that motherhood of a newborn in the eyes of the law should be determined by two factors: genetic inheritance and the original intent of the woman to become the parent of record. The bill included the assumption that, in the cases of children born of gestational surrogacy, the commissioning genetic parents would be the "natural parents" of the child. Some of the reasons for legislative success of the statute include: 1) clear need for statutory guidance in cases involving reproductive technology, 2) relevance of the issue to cost containment (ie, judicial costs) in an era of health care reform, 3) careful use of scientific terminology and the support of the medical community, 4) involvement of a skilled legislative team, 5) participation of physician specialists in the development of the bill (ie, practicing gynecologists in assisted reproductive technology programs), 6) participation of the State of Florida legislative staff, and 7) consultation with appropriate lobbying groups (eg, Florida Catholic Conference). The successful legislative process that was followed to achieve passage of this bill can serve as an example for other states to emulate.


The 2nd China Bioanalysis Forum Annual Conference: clinical bioanalysis and large molecule bioanalysis.
Beijing, China, 7-8 June 2014. The second China Bioanalysis Forum (CBF) conference was successfully held in Beijing, China, in June 2014 and covered the theme of clinical bioanalysis and large molecule bioanalysis. Compared with the first conference in 2013, this conference was attended by scientists from a greater number of scientific disciplines and geographic areas. This report summarizes the major topics in the conference as well as the future plan of the CBF.


Studies on insecticide-resistant anophelines. 2. Chromosome arrangements in laboratory-developed DDT-resistant strains of Anopheles atroparvus.
The development of several DDT-resistant strains of Anopheles atroparvus is described. They were selected by larval treatment only (RL), selection of larval and adult females (RLAF), and selection of adult females and males (RAFM). Their rate of DDT-resistance was measured in the larval and adult states (mainly in the 32nd generation). The results were compared with those of a dieldrin-selected strain (R/dieldrin) and several normal and semi-normal reference strains. In the larval assay DDT-resistance was of the following order: RL>RLAF>RAFM>R/dieldrin. Topical application to adults gave: RLAF>(RL?)>RAFM>R/dieldrin; while adult tarsal contact gave: RAFM>RLAF>RL>R/dieldrin These different orders of resistance are discussed.The strains were subjected to cytological examination by the method of Frizzi. The percentages of heterozygous inversions found were as follows: R/dieldrin, 77.4%; RL, 55.3%; RLAF, 54.0%; RAFM, 24.4%; all normal and semi-normal strains about 12%-21%.The rate of DDT-resistance could not be correlated with the percentages of heterozygous inversions found in the various strains.


Compendium of the Reactions of H3O+ With Selected Ketones of Relevance to Breath Analysis Using Proton Transfer Reaction Mass Spectrometry.
Soft chemical ionization mass spectrometric techniques, such as proton transfer reaction mass spectrometry (PTR-MS), are often used in breath analysis, being particularly powerful for real-time measurements. To ascertain the type and concentration of volatiles in exhaled breath clearly assignable product ions resulting from these volatiles need to be determined. This is difficult for compounds where isomers are common, and one important class of breath volatiles where this occurs are ketones. Here we present a series of extensive measurements on the reactions of H3O+ with a selection of ketones using PTR-MS. Of particular interest is to determine if ketone isomers can be distinguished without the need for pre-separation by manipulating the ion chemistry through changes in the reduced electric field. An additional issue for breath analysis is that the product ion distributions for these breath volatiles are usually determined from direct PTR-MS measurements of the compounds under the normal operating conditions of the instruments. Generally, no account is made for the effects on the ion-molecule reactions by the introduction of humid air samples or increased CO2 concentrations into the drift tubes of these analytical devices resulting from breath. Therefore, another motivation of this study is to determine the effects, if any, on the product ion distributions under the humid conditions associated with breath sampling. However, the ultimate objective for this study is to provide a valuable database of use to other researchers in the field of breath analysis to aid in analysis and quantification of trace amounts of ketones in human breath. Here we present a comprehensive compendium of the product ion distributions as a function of the reduced electric field for the reactions of H3O+. (H2O)n (n = 0 and 1) with nineteen ketones under normal and humid (100% relative humidity for 37 °C) PTR-MS conditions. The ketones selected for inclusion in this compendium are (in order of increasing molecular weight): 2-butanone; 2-pentanone; 3-pentanone; 2-hexanone; 3-hexanone; 2-heptanone; 3-heptanone; 4-heptanone; 3-octanone; 2-nonanone; 3-nonanone; 2-decanone; 3-decanone; cyclohexanone; 3-methyl-2-butanone; 3-methyl-2-pentanone; 2-methyl-3-pentanone; 2-methyl-3-hexanone; and 2-methyl-3-heptanone.


Immunotherapy for EBV-Associated Nasopharyngeal Carcinoma.
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies in southern China and Southeast Asia. Unfortunately, 70% of NPC patients have locally advanced disease at the first diagnosis. Radiotherapy alone and concurrent chemoradiotherapy are important treatment approaches for NPC, but they have a limited effect on patients with locally advanced or distantly metastatic disease. 1-5 Nevertheless, the unique immune environment of the EBV-associated NPC provides rational targets for immunotherapy. Diverse types of immunotherapies are actively being studied, including adoptive immunotherapy, therapeutic vaccines, immune checkpoint inhibitors, lytic-induction therapy, and viral immunotherapy. Specifically, adoptive immunotherapy with lymphocyte infusion was well tolerated and effective in 71.4% of patients combined with first-line chemotherapy. Several therapeutic vaccines and PD-1/PD-L1 pathway checkpoint inhibitors have shown promising clinic outcomes at phase I/II clinical trials. Moreover, EBV-lytic inducing therapy and viral immunotherapy for NPC are also being investigated. In this review, we summarized the current status, advantages, and disadvantages of each immunotherapy for EBV-associated NPC, which may shed light on developing safer and more effective treatment modalities in the future.


Changes of nucleic acid and protein synthesis in hypertrophied guinea-pig heart during intermittent hypoxia.
The effect of intermittent normobaric hypoxia on nucleic acid and protein synthesis of guinea-pig heart was studied. De novo synthesis of purine nucleotides, of RNA and DNA, as well as RNA polymerase activities and protein synthesis, increased in the heart right ventricles of hypoxic animals compared to the controls. These results suggest an activation of cellular genetic apparatus with an increase of nucleic acid and protein syntheses during the compensatory processes following hypoxia.


A Journey Through the Landscapes of Small Particles in Binary Colloidal Assemblies: Unveiling Structural Transitions from Isolated Particles to Clusters upon Variation in Composition.
Two-dimensional (2D) amorphous binary colloidal assemblies composed of particles of two different sizes are characterized by the loss of hexagonal close-packing for larger particles, occurring when the size ratio between small (S) and large (L) particles dSdL exceeds a certain threshold value. For moderately low particle number ratios NSNL large particles still retain a denser arrangement with transitions from hexagonal symmetry to the coexistence of different types of symmetries as NSNL progressively departs from 0 to higher values. On the other hand, small particles reveal sparser arrangements: shape identification and quantification of structural transitions in small particle arrangements appear particularly challenging. In this article, we investigate their shapes and transitions for amorphous binary colloidal particles assembled at the air/water interface. For the quantitative characterization of the evolution in particle arrangements for NSNL variable between 0.5 and 2, we develop an innovative procedure for morphological analysis, combining Minkowski functionals, Voronoi diagrams and ad hoc techniques to recognize and classify specific features. Such a powerful approach has revealed a wide variety of landscapes featuring isolated particles, dimers, chains, small clusters evolving with the colloidal suspension composition. Our method can be applied to the analysis of spatial configurations of sparse colloidal patterns obtained in different conditions.


A new immunosuppressive pregnane glycoside from aqueous fraction of Epigynum cochinchinensis.
Chemical investigation on the aqueous fraction of the stems of Epigynum cochinchinensis led to the isolation of a new pregnane glycoside named as epigycoside A (1) along with three known analogues (2-4). The structure of compound 1 was elucidated by means of spectroscopic techniques, including HRESIMS, and 1D and 2D NMR experiments. The immunosuppressive activity of 1 was evaluated by an in vitro model of concanavalin A-induced mice splenocytes proliferation. Compound 1 showed significant inhibitory activity in a dose-dependent manner, closer to the efficacy of positive control, dexamethasone, at a concentration of 50 μM.


Method for accurate measurement of infrared emissivity for opaque low-reflectance materials.
Accurate determination of infrared (IR) emissivity is important for non-contact temperature measurement and for energy balance evaluation in systems that exchange radiation. A method for accurate measurement is proposed based on active modulation of the background radiation. The hemispherical directional reflectance is measured as a proxy for directional emissivity using an IR camera and an integrating sphere, while the background radiation is modulated using an IR emitter and a mechanical shutter. Measurement of the apparent temperature observed by the camera under two different illumination conditions allows the extraction of reflectance and emissivity. The accuracy of the measurement and its sensitivity to surface properties are analyzed, showing uncertainty values as low as 0.004 in some cases. Example measurements of natural and artificial surfaces are presented.


Isolated soft tissue cleft lip: the influence on the nasal cavity and supernumerary laterals.
The purpose of this investigation was to estimate the vertical deviation of the nasal floor and to register dental disturbances (i.e., hypo- and hyperdontia) in patients with an isolated soft tissue cleft lip. Thirty patients with isolated cleft lips were randomly selected from the files of the Department of Maxillo-Facial Surgery and Jaw Orthopedics. As a matched control group, 30 patients were selected from the files of the Department of Orthodontics. Panoramic radiographs were analyzed and the lowest point of the floor of the left and right nasal cavity was measured to the nearest 0.5 mm. The presence of supernumerary (deciduous or permanent) or missing lateral incisors was recorded from the patient's journals. The vertical position of the nasal floor differed significantly between the cleft and the non-cleft side (p < 0.001). Supernumerary, deciduous, and permanent laterals were recorded in 73% of the subjects in the cleft lip group (22 patients). In the control group, no differences were found between the position of the nasal floor on the left and right side and no supernumerary laterals were recorded. Missing laterals were not noted in any of the individuals investigated. Isolated cleft lips were in most cases associated with: (1) lowering of the nasal floor on the cleft side and (2) supernumerary primary or permanent lateral incisors on the cleft side. Panoramic radiographs can be used to detect differences in the vertical position of the floor of the nasal cavity in patients with isolated cleft lips and to diagnose supernumerary laterals.


Optimizing conditions for labeling of mesenchymal stromal cells (MSCs) with gold nanoparticles: a prerequisite for in vivo tracking of MSCs.
Mesenchymal stromal cells (MSCs) have an inherent migratory capacity towards tumor tissue in vivo. With the future objective to quantify the tumor homing efficacy of MSCs, as first step in this direction we investigated the use of inorganic nanoparticles (NPs), in particular ca. 4 nm-sized Au NPs, for MSC labeling. Time dependent uptake efficiencies of NPs at different exposure concentrations and times were determined via inductively coupled plasma mass spectrometry (ICP-MS). The labeling efficiency of the MSCs was determined in terms of the amount of exocytosed NPs versus the amount of initially endocytosed NPs, demonstrating that at high concentrations the internalized Au NPs were exocytosed over time, leading to continuous exhaustion. While exposure to NPs did not significantly impair cell viability or expression of surface markers, even at high dose levels, MSCs were significantly affected in their proliferation and migration potential. These results demonstrate that proliferation or migration assays are more suitable to evaluate whether labeling of MSCs with certain amounts of NPs exerts distress on cells. However, despite optimized conditions the labeling efficiency varied considerably in MSC lots from different donors, indicating cell specific loading capacities for NPs. Finally, we determined the detection limits of Au NP-labeled MSCs within murine tissue employing ICP-MS and demonstrate the distribution and homing of NP labeled MSCs in vivo. Although large amounts of NPs improve contrast for imaging, duration and extend of labeling needs to be adjusted carefully to avoid functional deficits in MSCs. We established an optimized labeling strategy for human MSCs with Au NPs that preserves their migratory capacity in vivo.


Biofouling on polymeric heat exchanger surfaces with E. coli and native biofilms.
The biofouling affinity of different polymeric surfaces (polypropylene, polysulfone, polyethylene terephthalate, and polyether ether ketone) in comparison to stainless steel (SS) was studied for the model bacterium Escherichia coli K12 DSM 498 and native biofilms originating from Rhine water. The biofilm mass deposited on the polymer surfaces was minimized by several magnitudes compared to SS. The cell count and the accumulated biomass of E. coli on the polymer surfaces showed an opposing linear trend. The promising low biofilm formation on the polymers is attributed to the combination of inherent surface properties (roughness, surface energy and hydrophobicity) when compared to SS. The fouling characteristics of E. coli biofilms show good conformity with the more complex native biofilms investigated. The results can be utilized for the development of new polymer heat exchangers when using untreated river water as coolant or for other processes needing antifouling materials.


[Myocardial revascularization via a median sternotomy without cardiopulmonary bypass in 250 patients--midterm results and study of graft patency].
To evaluate mid-term results and one-year graft patency of less invasive coronary artery bypass grafting through a median sternotomy. From January 1, 1998, to December 31, 1999, 250 patients had coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) through a median sternotomy. The patient base of 188 men and 62 women averaged 61.7 years, mean ejection fraction (EF) was 55.1%. An average of 2.7 (range 1 to 5) distal anastomoses per patient was achieved. Results are compared with a CPB subgroup of patients operated on through a median sternotomy in the same time (N = 1126). In a random subgroup of 100 patients (50 per group) an angiographic control of graft patency was done. A non-CPB group showed lesser occurrence of postoperative acute myocardial infarction (p = 0.038), atrial fibrillation (p = 0.029) and lower incidence of renal (p = 0.033) complications. We observed lower operative mortality (p = 0.019), as well as the occurrence of low cardiac output syndrome (p < 0.001) in the off pump group. The follow-up is 36 +/- 12 months and the number of patients with recurrent angina (5.4%), late AMI (0%) and late death (0.4%) is acceptable. We did not find an inordinate number of vein grafts occlusions (2.2%) and stenoses (7.8%) at anastomotic sites. None of the arterial grafts in both groups were occluded. We detected lower incidence of postoperative complications and decreased operative mortality in a non-CPB group. Angiographic assessment displayed an excellent run-off in both groups of patients. Off-pump coronary bypass grafting is associated with sufficient short-term graft patency and mid-term clinical outcomes.


Xeno-organ donor pigs with multiple genetic modifications - the more the better?
The number of donated human organs and tissues for patients with terminal organ failure falls far short of the need. Alternative sources, such as organs and tissues from animals, are therefore urgently required. During the past few years, major progress has been made in the development of genetically multi-modified donor pigs, and their organs have been shown to be safe and efficacious in life-supporting transplantation models into non-human primates, paving the way to clinical xenotransplantation studies. Here, we summarize recent developments in pig genome engineering and discuss efforts to develop the optimum donor pig for xenotransplantation. In addition, we speculate on how many genetic modifications may be required for initial xenotransplantation clinical trials.


Three-Dimensional Macroporous rGO-Aerogel-Based Composite Phase-Change Materials with High Thermal Storage Capacity and Enhanced Thermal Conductivity.
Three-dimensional porous network encapsulation strategy is an effective means to obtain composite phase-change materials (PCMs) with high heat storage capacity and enhanced thermal conductivity. Herein, macroporous reduced graphene oxide (rGO) aerogels with adjustable pore size are prepared by the emulsion template method and hydrothermal reduction process. Further, the shape-stabilized rGO-aerogel-based composite PCMs are constructed after the combination of 3D porous rGO supports and paraffin wax (PW) through vacuum melting infiltration. By regulating the pore structure of the rGO aerogel network, the rGO-based composite PCMs achieve excellent energy storage properties with a phase-change enthalpy of 179.94 J/g for the loading amount of 95.61 wt% and an obvious enhancement in thermal conductivity of 0.412 W/m-1·K-1, which is 54.89% higher than pristine PW and enduring thermal cycling stability. The obtained macroporous rGO-aerogel-based composite PCMs with high thermal storage and heat transfer performance effectively broaden the application of PCMs in the field of thermal energy storage.


Effects of apple consumption on plasma and erythrocyte antioxidant parameters in elderly subjects.
The effects of apple consumption on plasma and erythrocyte antioxidant parameters of elderly subjects were investigated in this study. Fifteen elderly subjects (mean age 71.86 +/- 4.17) participated in the study. They consumed an apple a day for 1 month. Before and after this period, fasting blood samples were obtained, and oxidant (malondialdehyde [MDA]) and antioxidant (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and antioxidant potential [AOP]) parameters were studied. MDA and AOP levels were studied in plasma, and SOD, GSH-Px, and CAT activities and MDA levels were measured in the erythrocytes. In the erythrocytes, GSH-Px and SOD activities were found to be higher (p < .001 and p < .01), but MDA levels were lower in the second samples relative to the first ones. In the plasma, AOP value was found to be higher in the second samples relative to first ones (p < .001). No differences were found, however, between the routine blood parameters such as total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, high-density-lipoprotein cholesterol, and triglyceride levels. The results show that consumption of apple leads to significant increases in the activities of some antioxidant enzymes and in the antioxidant potential values of the blood, and that decreases oxidation reactions in the body in significant amount. It is quite possible that reduced peroxidation processes owing to consumption of this fruit may play a part in some of their beneficial effects in the elderly subjects.


Haven Health is About to Disrupt the U.S. Healthcare System.
Background: Healthcare costs are increasing in the U.S. Healthcare market is fragmented and opaque. The Amazon, JP Morgan Chase, and Berkshire Hathaway partnered to form an independent healthcare company 'Haven', designed to support cost-containment in health care and to forge a better patient experience. Limited information is available in the public domain about Haven's strategy to deliver cost-effective healthcare for their employees. Objective: To describe the impact of Haven Health of modern healthcare. Methods: We reviewed literature in Pubmed (MEDLINE database of references and abstracts on life sciences and biomedical topics from the USA National Library of Medicine at the National Institutes of Health) and the public domain. Results: Amazon's expertise and abilities in e-commerce such as logistics, supply, and big data management will support Haven's quest to resolve inefficiencies in health care. Haven may attempt to directly negotiate with providers, bypassing insurance companies, to establish themselves as an independent payor. Additionally, Haven to establish themselves as a provider by building new low-cost primary care clinics, focusing on chronic disease prevention. The new healthcare system may leverage machine learning, artificial intelligence and big data analysis to support its initiatives and other 'big data' analytics to drive it all. Conclusions: Heaven Health may use its expertise to disrupt everything from the pharmaceutical supply chain to primary care and telehealth. More research is needed to evaluate the impact of Haven Healthcare on disease outcomes and healthcare costs.


Novel bioengineered MBenes for the treatment of Alzheimer's disease: An in-Sillico study.
Alzheimer's disease is a neurodegenerative disease caused by the deposition and accumulation of amyloid-β (Aβ) peptides in the brain neurons. Current medications are not a definitive cure for this disease, but they can hamper the signs and symptoms of Alzheimer's disease. Therefore, prevention is the best way to deal with this disease. In this study, the novel structures based on MBenes (such as Cd2B, Mo2B, Cu2B, and Ta2B) are proposed to prevent amyloid-β accumulation in Alzheimer's disease. Regarding the remarkable MBene properties such as tunability, biocompatibility, and low manufacturing cost, the effect of these structures on amyloid-β deformation was explored using molecular dynamics simulation. To provide an atomic analysis of Beta-amyloid behavior in the presence of these structures, the compaction, contact area, and stability of Beta-amyloid were investigated. The results indicated the satisfactory performance of MBenes on the destabilization of amyloid-β structures. Moreover, given the higher interactions between Cd2B and amyloid-β, the instability, compaction, and the contact area of amyloid-β particles were investigated in this complex. The findings confirmed Cd2B as the best structure to prevent amyloid-β accumulation. The results of this investigation paved the way for the development of these structures as a medicinal agent to prevent Alzheimer's disease.