Characterization of mouth-formed mouthguards: thermal performance.
This study examined whether the thermo-modeling process suits the thermal properties of the material constituting mouth-formed mouthguards (MGs). Five mouth-formed MGs were compared: four commercially available MGs (SDI™, Gel Nano™, Opro Shield Gold™, and Kipsta R300™) and one prototype. Differential scanning calorimetry was used to determine melting (T(m)) and crystallization (T(c)) temperatures and specific fusion and crystallization enthalpies (∆H(f) and ∆H(c) (J/g)). MGs were modeled with recording of vestibular flange and occlusal cushion temperatures (Toccl). Tm ranged from 45.3°C to 53.0°C and Tc ranged from 40.9°C to 48.2°C. Specific heat of fusion ranged from 40.2 J/g to 62.0 J/g. Toccl was higher than Tm for all MGs except Kipsta R300™. Guidelines provided by manufacturers may not be adapted to thermal properties of the MG material. To ensure proper thermomodeling, heating and biting durations should be adjusted.


Comparison of the effects of an angiotensin converting enzyme inhibitor and a calcium antagonist in hypertensive, macroproteinuric diabetic patients: a randomised double-blind study.
The objective of this study was to compare the effects of an angiotensin converting enzyme inhibitor, lisinopril, with those of a calcium blocker, nifedipine, on BP control and renal function, in a prospective randomised double-blind, double-dummy trial lasting 19 weeks in patients with diabetic nephropathy. We enrolled 28 diabetic patients with hypertension and macroproteinuria from the out-patient diabetic-renal clinic. The antihypertensive treatment consisted of lisinopril or nifedipine, and their effect on arterial BP, urinary albumin excretion, glomerular filtration rate, and renal blood flow were measured. BPs at entry were 166/99 (SD 23/9) mmHg for the lisinopril group and 165/99(21/7) mmHg for the nifedipine group. BPs fell to 143/88 (17/13) mmHg for the lisinopril group and 148/85(25/10) mmHg for the nifedipine group at the end of the study. The albumin excretion rate fell in the lisinopril group from 738.7 (635.2) micrograms/min to 644.6 (965.2) micrograms/min and rose in the nifedipine group from 981.2 (1022.2) micrograms/min to 1072.5 (908.5) micrograms/min (P = NS). Glomerular filtration rates fell from 105.2 (57.5) ml/min per 1.73 m2 to 72.1 (39.4) ml/min per 1.73 m2 in the lisinopril group and from 109.9 (50.0) ml/min per 1.73 m2 to 82.9 (53.9) ml/min per 1.73 m2 in the nifedipine treated group. Renal blood flow fell from 446.8 (217.9) ml/min per 1.73 m2 to 435.1 (243.3) ml/min per 1.73 m2 for the lisinopril group and from 473.0 (216.4) ml/min per 1.73 m2 to 419.0 (278.6) ml/min per 1.73 m2 for the nifedipine group. Differences between the groups were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)


Emergency Use and Efficacy of an Asynchronous Teledermatology System as a Novel Tool for Early Diagnosis of Skin Cancer during the First Wave of COVID-19 Pandemic.
Background: After the outbreak of the corona virus disease-19 (COVID-19) pandemic, teledermatology was implemented in the Hungarian public healthcare system for the first time. Our objective was to assess aggregated diagnostic agreements and to determine the effectiveness of an asynchronous teledermatology system for skin cancer screening. Methods: This retrospective single-center study included cases submitted for teledermatology consultation during the first wave of the COVID-19 pandemic. Follow-up of the patients was performed to collect the results of any subsequent personal examination. Results: 749 patients with 779 lesions were involved. 15 malignant melanomas (9.9%), 78 basal cell carcinomas (51.3%), 21 squamous cell carcinomas (13.8%), 7 other malignancies (4.6%) and 31 actinic keratoses (20.4%) were confirmed. 87 malignancies were diagnosed in the high-urgency group (42.2%), 49 malignancies in the moderate-urgency group (21.6%) and 16 malignancies in the low-urgency group (4.6%) (p < 0.0001). Agreement of malignancies was substantial for primary (86.3%; κ = 0.647) and aggregated diagnoses (85.3%; κ = 0.644). Agreement of total lesions was also substantial for primary (81.2%; κ = 0.769) and aggregated diagnoses (87.9%; κ = 0.754). Conclusions: Our findings showed that asynchronous teledermatology using a mobile phone application served as an accurate skin cancer screening system during the first wave of the COVID-19 pandemic.


[The lipid lowering effect of a new guar-pectin fiber mixture in type II diabetic patients with hypercholesterolemia].
The lipid-lowering effect of a new mixture of fiber consisting in guar and apple-pectin in combination with apple-pomaces has been estimated in 15 female type 2-diabetics [age mean = 62 (52-70) yr] with hypercholesterolemia (total-chol > 240 mg/dl and LDL-chol > 130 mg/dl). After a dietetic run-in-phase of 3 weeks the patients received the fiber mixture (1 package of 17 g with about 5.9 g water-soluble fiber) dissolved in 250 ml water for the next 9 weeks: during the first 3 weeks 2 portions per day, the next 3 weeks twice 1/2 portion and the last 3 weeks one 1/2 portion daily. The fiber mixture had to been consumed 30 minutes before taking a main meal. Regular intake of the fiber product led to a significant decrement in blood lipids, and this improvement under 2 portions daily has been maintained for the most part with the reduced dosage. The total-chol levels decreased by 11.3% during the first 3 weeks of fiber intake (p < 0.05) and by -12.6% during the next 3 weeks (p < 0.05), the decrease during the last 3 weeks under the reduced fiber intake was -9.6% (ns). The HDL-chol levels remained approximately the same during the whole period of observation. The triglyceride concentrations in serum could be lowered by -15.5% during the first 3 weeks of fiber intake, and by -19.2% during the next 3 weeks (p < 0.05), finally the decrease was -12.3% (ns). The atherogenic index (Chol-/HDL-chol) could be reduced on an average of 14.3% in relation to the initial value.(ABSTRACT TRUNCATED AT 250 WORDS)


Neurotrophic factors modulate hair cells and their potassium currents in chick otocyst explants.
Neurotrophins, retinoids and their receptors are present in the sensory epithelia of the inner ear during development. We show that these factors modulate the proliferation of hair cells and their K+-currents when the embryonic day 3 (ED 3) presumptive inner ear (i.e. otocyst) is maintained in organ culture. All trans-retinoic acid (RA) increases hair cell differentiation and enhances the acquisition of outward currents, including a delayed rectifier and a fast activating, transient type, voltage-gated potassium current. In contrast, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) decrease ionic current activity, and the addition of RA with the neurotrophins enhances this inhibitory response in an age-dependent manner. We measured the total number of cells per explant over time to determine precisely when and how these factors inhibit explant growth. We found that high concentrations of BDNF and NT-3 administered together, and low concentrations of both neurotrophins combined and administered with RA suppress otocyst cell numbers after 24 h in vitro. This suppressive response is induced by RA and NT-3, not by RA and BDNF. The suppressive or inhibitory influence of NT-3 and RA is the result of NT-3 binding to the low affinity receptor, p75NTR, not the result of RA increasing mRNA levels for the high affinity receptor, trkC. However, trk may act with p75NTR, as disruption of trk signalling alleviates the inhibitory response induced by NT-3 and RA. Our data suggest that various combinations and/or concentration gradients of these factors can differentially regulate inner ear development and hair cell excitability.


Chronic Popliteus Tendon Avulsion Fracture with Chronic Knee Pain and Locking: A Case Report.
A 31-year-old man who had a chronic popliteus avulsion fracture 18 years earlier treated with physical therapy presented with new onset left knee locking after exercising at the gym. Magnetic resonance imaging demonstrated a chronic popliteus avulsion fracture of the lateral femoral condyle. Surgical excision of the nonunited bone fragment was performed. Isolated popliteus avulsion fractures are extremely rare injuries that occur primarily in a skeletally immature patient population and for which treatment options are not well understood. Treatment options include conservative management and early surgical intervention, both of which have inherent risks and benefits. We recommend prompt imaging with computed tomography (CT) to better characterize the degree of injury and follow-up CT imaging in patients who do not undergo early surgical intervention.


Anterior cruciate ligament reconstruction in patients with generalized joint laxity.
Generalized joint laxity is a genetically determined component of overall joint flexibility. The incidence of joint laxity in the overall population is approximately 5% to 20%, and its prevalence is higher in females. Recently it was noticed that individuals with generalized joint laxity are not only prone to anterior cruciate ligament injuries but also have inferior results after a reconstruction. Therefore, an anterior cruciate ligament reconstruction in patients with generalized laxity should be undertaken with caution due to the higher expected failure rate from the complexity of problems associated with this condition. It is also necessary to identify the risk factors for the injury as well as for the post operative outcome in this population. A criterion that includes all the associated components is necessary for the proper screening of individuals for generalized joint laxity. Graft selection for an anterior cruciate reconstruction in patients with ligament laxity is a challenge. According to the senior author, a hamstring autograft is an inferior choice and a double bundle reconstruction with a quadriceps tendon-bone autograft yields better results than a single bundle bone-patella tendon-bone autograft. Future studies comparing the different grafts available might be needed to determine the preferred graft for this subset of patients. Improved results after an anterior cruciate ligament reconstruction can be achieved by proper planning and careful attention to each step beginning from the clinical examination to the postoperative rehabilitation.


A case law review of the individuals with disabilities education act for children with hearing loss or auditory processing disorders.
In 1975, Congress passed the Education for All Handicapped Children Act (Public Law 94-142), and it has been revised and modified several times. At the time of this writing, this law was most recently amended by the Individuals with Disabilities Education Improvement Act (Pub. L. No. 108-446, 118 Stat. 2647, December 3, 2004), which took effect on July 1, 2005. Colloquially the law is still referred to as the Individuals with Disabilities Education Act (IDEA). Children with hearing loss or auditory processing disorder (APD) may qualify for services under IDEA. However, a review of the literature found no review of case law for such children. This article provides a comprehensive review of case law involving the IDEA and children with hearing loss or APD from the U.S. Supreme Court and U.S. courts of appeals. We conducted a systematic review of case law. A LexisNexis search for cases involving IDEA and children with hearing loss or APDs was conducted. For the purpose of the present case review, all appellate decisions (cases accepted by the U.S. courts of appeals or the U.S. Supreme Court) were included if they found that the child had hearing loss or APD, regardless of the reason for the appeal under IDEA. In the instance of multiple cases that involved the same two parties, these cases are summarized together to provide the legal context. Brief explanations of IDEA and the federal judicial process as it pertains to IDEA disputes are presented. Following these explanations, a chronological review of IDEA appellate cases concerning students with hearing loss or APD is provided. The IDEA cases reviewed focus on three main issues: placement of the child, methodology of teaching, and the provision of services. This case law review provides a helpful summary of higher court cases for educational audiologists and parents of children with hearing loss or APDs, as well as educators, individualized education program team members, school administrators, and legal representatives involved in IDEA cases.


Biochemical & histochemical changes relating to fibrosis following infection with Mycobacterium tuberculosis in the guinea pig.
Guinea pigs infected with M. tuberculosis were studied for parameters relating to fibrosis following infection. The infected animals were followed up to a period of 44 wk and the changes that occurred in the lung, liver and spleen were studied. Corresponding tissues from animals injected with bleomycin, an anti-mitotic drug which has the ability to produce pulmonary fibrosis, served as positive controls. Tissue collagen, elastin and hexosamines were estimated biochemically. The presence of granuloma and stainable collagen in paraffin sections of these tissues was also studied. Establishment of the infection was assessed bacteriologically by culturing the viable organisms from the spleen. It was observed that a self-limiting infection was established in the guinea pigs and none of the animals died of the infection. In the infected animals, collagen, elastin and hexosamines showed an initial decrease followed by an increase. While the elastin and the hexosamine levels returned to the basal levels in all the three organs, collagen levels increased in the lung and were comparable to those of the bleomycin control. Collagen stainable by Van Gieson's method was found to be increased in the lung from the 4th wk onwards. The present report indicates the potential of adopting this system for studying mechanisms of fibrogenesis in tuberculous infection.


Total synthesis of (-)-bafilomycin A(1).
A highly stereoselective total synthesis of (-)-bafilomycin A(1), the naturally occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The synthesis features the highly stereoselective aldol reaction of methyl ketone 8b and aldehyde 60c and a Suzuki cross-coupling reaction of the highly functionalized advanced intermediates 12 and 39. Vinyl iodide 12 was synthesized by a 14-step sequence starting from the readily available beta-alkoxy aldehyde 14, while the vinylboronic acid component 39 was synthesized by a nine-step sequence from beta-hydroxy-alpha-methyl butyrate 44 via a sequence involving the alpha-methoxypropargylation of chiral aldehyde 49 with the alpha-methoxypropargylstannane reagent 54. Syntheses of fragments 12 and 39 also feature diastereoselective double asymmetric crotylboration reactions to set several of the critical stereocenters. The Suzuki cross-coupling of 12 and 39 provided seco ester 40, which following conversion to the seco acid underwent smooth macrolactonization to give 41. The success of the macrocyclization required that C(7)-OH be unprotected. The Mukaiyama aldol reaction between aldehyde 60c and the TMS enol ether generated from 8b provided aldol 65 with high diastereoselectivity. Finally, all silicon protecting groups were removed by treatment of the penultimate intermediate 65 with TAS-F (tris(dimethylamino)sulfonium difluorotrimethylsilicate), thereby completing the total synthesis of (-)-bafilomycin A(1).


Caring for dementia sufferers in the community: the caregivers problems.
Twenty-four carers of dementia sufferers were screened for psychological well being and compared with 19 carers of non-demented elderly. Carers of demented relatives showed significantly raised levels of stress on the Relatives' Stress Scale (RSS), and also increased psychiatric morbidity on the 30 item General Health Questionnaire (GHQ-30), when compared with the carers on non-demented relatives. Scores in the behaviour and mood disturbance scale (BMD) were significantly raised in the dementia group of patients, when compared with the non-demented group. However, high scores on the behaviour and mood disturbance Scale for the dementia sufferer were not correlated with increased stress and psychiatric morbidity scores found in the relatives of the patients with dementia. The implications of these findings are discussed.


Natural history of incomplete retinal pigment epithelial and outer retinal atrophy in age-related macular degeneration.
To assess the time course and risk factors for conversion of incomplete retinal pigment epithelium and outer retina atrophy (iRORA) to complete retinal pigment epithelium and outer retina atrophy (cRORA) in eyes with non-neovascular intermediate age-related macular degeneration (iAMD), using optical coherence tomography (OCT) analysis. Retrospective survival study. Tracked structural Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) volume datasets from 2 retinal specialists at the University of California-Los Angeles were retrospectively screened to identify consecutive participants with non-neovascular iAMD without signs of atrophy or macular neovascularization in either eye at baseline. In the first stage of selection, 321 consecutive iAMD eyes were screened for onset of iRORA. Eyes that developed iRORA within the first 24 months were followed for an additional 24 months to assess the rate of conversion to cRORA. A Kaplan-Meier survival curve was formulated to illustrate the conversion from iRORA to cRORA. Among 321 baseline participants with iAMD, 87 incident iRORA lesions (50 eyes, 42 participants) were included in the conversion analysis. Eighty-one iRORA lesions (93.1%) converted to cRORA within 24 months (median 14 months). Multivariate binary logistic regression analysis indicated that intraretinal hyperreflective foci and extrafoveal iRORA location at baseline were associated with a faster rate of progression to cRORA (model R2 = 0.816, p < 0.05). The majority of incident iRORA lesions progress to cRORA within a 24-month period. These findings may be of value in the design of early intervention trials for risk stratification and prognostication but need to be validated with a prospective analysis.


The prevalence of ulcerated plaques in the aortic arch in patients with stroke.
The cause of cerebral infarction is obscure in up to 40 percent of patients with this disorder who are studied prospectively. In this investigation, we determined the frequency of ulcerated plaques in the aortic arch and explored the part they may play in the formation of cerebral emboli. Using an autopsy data bank, we studied the prevalence of ulcerated plaques in the aortic arch in 500 consecutive patients with cerebrovascular and other neurologic diseases who were studied at autopsy. Ulcerated plaques were present in 26 percent of the 239 patients with cerebrovascular disease but in only 5 percent of the 261 patients with other neurologic diseases (P less than 0.001). After we controlled for age and heart weight, the adjusted rates were 16.9 percent and 5.1 percent, respectively (adjusted odds ratio, 4.0; 95 percent confidence interval, 2.1 to 7.8; P less than 0.001). Among the patients with cerebrovascular disease, the prevalence of ulcerated plaques in the aortic arch was 28 percent in the 183 patients with cerebral infarcts and 20 percent in the 56 patients with brain hemorrhage. The prevalence of ulcerated plaques was 61 percent among the 28 patients with no known cause of cerebral infarction, as compared with 22 percent among the 155 patients with a known cause of cerebral infarction (P less than 0.001). After adjustment for covariates, the prevalence was 57.8 percent among patients with no known cause of cerebral infarction and 20.2 percent among those with a known cause (adjusted odds ratio, 5.7; 95 percent confidence interval, 2.4 to 13.6; P less than 0.001). The presence of ulcerated plaques in the aortic arch was not correlated with the presence of extracranial internal-carotid artery stenosis, suggesting that these were two independent risk factors for stroke. Ulcerated plaques in the aortic arch may play a part in causing cerebral infarction, especially in patients in whom cerebral infarction has no known cause.


Stereotactic radiosurgery for Rathke's cleft cysts: an international multicenter study.
Rathke's cleft cysts (RCCs) are sellar collections from an incompletely regressed Rathke's pouch. Common symptoms of RCCs can include headaches, visual loss, and endocrinopathy. Surgery is required in some cases of symptomatic or growing RCCs. Recurrence after surgery is common (range 10%-40%). Stereotactic radiosurgery (SRS) has been used in an attempt to control growth and symptoms, but outcomes are not well known. The authors sought to study the outcomes of RCCs following Gamma Knife surgery for both salvage and initial treatment. The outcomes of 25 patients with RCCs who underwent SRS between 2001 and 2020 were reviewed. Four patients received initial SRS and 21 were treated with salvage SRS. Diagnosis was based on imaging or histopathology. Cyst control was defined as stability or regression of the cyst. Kaplan-Meier analysis was used to determine time to recurrence and determine potential factors for recurrence. The respective median clinical follow-up and margin dose were 6.5 years and 12 Gy. Overall control was achieved in 19 (76%) of 25 patients, and 4 recurrences required further intervention. The average time to recurrence was 35.6 months in those RCCs that recurred. Visual recovery occurred in 14 (93.3%) of 15 patients and no new post-SRS visual deficits occurred. The presence of a pretreatment visual deficit was often an indicator of RCC regrowth. All 3 patients with pretreatment hyperprolactinemia experienced resolution after SRS. New endocrinopathy related to SRS was noted in 5 (20%) of 25 patients, all of which were thyroid and/or cortisol axis related. Upfront SRS was used in 4 patients. No new endocrinopathies or visual deficits developed after upfront SRS, and the 1 patient with a pretreatment visual deficit recovered. One of the 4 patients with upfront SRS experienced a recurrence after 7.5 years. SRS produced effective recovery of visual deficits and carries a low risk for new visual deficits. Cyst control was achieved in approximately three-fourths of the patients. Following SRS, patients without pretreatment visual deficits are less likely to have RCC regrowth. Endocrinopathy can occur after SRS, similar to other sellar mass lesions. Initial SRS shows the potential for long-term cyst control, with improvement of symptoms and a low risk for complications.


Rational design to block amino acid editing of a tRNA synthetase.
Investigations in chemical biology have focused on the synthesis of custom-designed proteins with site-specific incorporation of novel amino acids. Their success requires stable production of misacylated tRNAs. Utilization of aminoacyl-tRNA synthetases has been hindered because of enzyme molecular recognition mechanisms that ensure high fidelity of protein synthesis. Leucyl-tRNA synthetase naturally misaminoacylates chemically diverse standard and nonstandard amino acids, but contains a separate amino acid editing active site to hydrolyze incorrectly mischarged tRNAs. In this work, a rational mutagenesis design to block enzyme editing is described and involves substitution of bulky amino acids into the amino acid binding pocket of the hydrolytic active site. These engineered enzymes stably misacylated isoleucine to tRNALeu. The use of these mutant leucyl-tRNA synthetases has the potential to produce pools of mischarged tRNAs that are linked to nonstandard amino acids for in vitro translation. In addition, since many of the leucyl-tRNA synthetases do not interact with or rely upon the tRNA anticodon for identity, these enzymes may offer an excellent scaffold for the development of orthogonal tRNA synthetase/tRNA pairs that can potentially be used to customize protein synthesis.


[The Minor T Allele of the Single Nucleotide Polymorphism rs 13360222 Decreases the Activity of the HAVCR2 Gene Enhancer in a Cell Model of Human Macrophages].
The TIM-3 receptor, encoded by the Hepatitis A Virus Cellular Receptor 2 (HAVCR2) gene, is an immune checkpoint and plays an important role in preventing the development of autoimmune reactions. This receptor is expressed on the surface of various immunocytes and its functions in myeloid cells remain poorly understood, compared to the role of T cell specific TIM-3 that is actively studied in the context of the search for promising therapeutic targets in cancer immunotherapy. During this study, we performed deletion analysis of the promoter region of the HAVCR2 gene, as well as functional characterization of its enhancer, and studied the effect of a number of single nucleotide polymorphisms (SNPs) on the activity of these regulatory elements in the relevant model of human macrophage-like cells-U937 activated monocytes. We have shown that the SNPs rs10515746(A) and rs4704853(A) located in the HAVCR2 gene promoter and associated with the development of a number of pathologies, do not affect the activity of the promoter in activated monocytes. However, a minor T variant of SNP rs13360222 located in the enhancer in the third intron of the gene, significantly reduces the ability of the enhancer to activate the HAVCR2 promoter, presumably due to weakening of the binding of nuclear receptor ESR2 to the respective region.


Gene expression with prognostic implications in cytogenetically normal acute myeloid leukemia.
Acute myeloid leukemia (AML) represents a heterogeneous group of leukemia entities that differ with regard to biology, clinical course, and prognosis. Over the past decades, it has been shown that most AML cases exhibit chromosomal aberrations, gene mutations, and disordered gene expression that alter normal gene function, thereby contributing to leukemic transformation. Especially, in cytogenetically normal AML (CN-AML) molecular genetic and gene expression analyses are becoming of increasing importance. In addition to the impact of gene mutations, including the MLL, FLT3, CEBPA, or NPM1 genes in CN-AML, recent analyses have provided evidence that altered gene expression might not only be of biological but also of prognostic relevance in CN-AML patients. Quantitative reverse-transcriptase polymerase chain reaction (Q-RT-PCR) and recent advances in genome-wide DNA microarray-based gene expression profiling (GEP) represent powerful tools for the systematic exploration of the molecular variation underlying the biologic and clinical heterogeneity of CN-AML. Ultimately, a better understanding of gene expression alterations and hence the molecular basis of the disease will contribute to a refined leukemia classification, which will include both previously known CN-AML subgroups and novel classes defined by distinct gene expression clusters with prognostic significance.


[Learning in online education: analysis of concept].
This work aimed at clarifying the concept learning in online education, expressed by the literature in the area of health. It is a study of analysis of concept, based on the Evolutionary Model, being highlighted attributes, background, consequents and substitute terms. Learning in the context of online education is characterized by a dynamic and continuous process of active construction of knowledge and acquisition of skills, with physical separation between students and teachers. Among the background events discussed stood out: interest and motivation in learning; dedication and time self-management; and interaction and communication tools. The main evident consequents were: student's autonomy; independent and active study; and construction of own knowledge. The prevailing substitute terms were collaborative learning and self-learning. The understanding of the concept can contribute to its implementation in nursing teaching activities in virtual environments.


Analysis of the hormone receptor status of circulating tumor cell subpopulations based on epithelial-mesenchymal transition: a proof-of-principle study on the heterogeneity of circulating tumor cells.
Although the enumeration of circulating tumor cells (CTCs) has been demonstrated to be a prognostic indicator in metastatic breast cancer, the heterogeneous characteristics of CTCs, such as variations in the epithelial-mesenchymal transition (EMT), may limit its broad clinical application. To investigate an uncomplicated and practicable detection approach based on the potential utility of the heterogeneity of CTCs from the standpoint of the EMT phenotype and ER/PR status of CTCs, an analysis was conducted using peripheral blood samples obtained from 28 metastatic breast cancer patients. The CanPatrol CTC enrichment technique was used to identify different CTC subpopulations, including epithelial-dominated CTCs, biophenotypic epithelial/mesenchymal CTCs, and mesenchymal-dominated CTCs, according to epithelial and mesenchymal markers. Furthermore, the hormone receptor (HR) status of each CTC was determined based on the expression levels of three reference genes and was characterized by four levels, which ranged from high-level expression to non-expression. We subsequently concluded that based on EMT phenotypes, the order of different CTC subgroups differed according to the HR expression status of the primary tumor. With respect to the HR status between tissues and CTCs, the variation tendency from high-level expression to non-expression of HR in CTCs was significantly correlated with the HR status of the primary tumor. The findings could provide evidence for the potential application of this uncomplicated and practicable detection approach for prognostic analysis and individualized endocrine therapeutic direction in a real-time manner via confirmation in further large-scale trials.


A Document Analysis of Nationally Available Faculty Assessment Forms of Resident Performance.
Written feedback by faculty of resident performance is valuable when it includes components based on assessment for learning. However, it is not clear how often assessment forms include these components for summative and formative feedback. To analyze prompts used in forms for faculty assessment of resident performance, guided by best practices in survey research methodology, self-regulation theory, and competency-based assessment. A document analysis, which is a qualitative approach used to analyze content and structure of texts, was completed on assessment forms nationally available in MedHub. Due to the number of forms available, only internal medicine and surgery specialties were included. A document summary form was created to analyze the assessments. The summary form guided researchers through the analysis. Forty-eight forms were reviewed, each from a unique residency program. All forms provided a textbox for comments, and 54% made this textbox required for assessment completion. Eighty-three percent of assessments placed the open textbox at the end of the form. One-third of forms contained a simple prompt, "Comments," for the narrative section. Fifteen percent of forms included a box to check if the information on the form had been discussed with the resident. Fifty percent of the assessments were unclear if they were meant to be formative or summative in nature. Our document analysis of assessment forms revealed they do not always follow best practices in survey design for narrative sections, nor do they universally address elements deemed important for promotion of self-regulation and competency-based assessment.


Comparison of percutaneous electrical nerve stimulation and ultrasound imaging for nerve localization.
Percutaneous nerve stimulation (PNS) is a non-invasive technique to localize superficial nerves before performing peripheral nerve blocks, but its precision has never been evaluated by high-resolution ultrasound. This study compared stimulating points at the skin with the position of nerve structures determined by ultrasound. Correlations between distances and percutaneous stimulation thresholds were determined. PNS was performed in 20 healthy volunteers systematically with a stimulating pen at the neck after attaching a transparent film with 49 (7×7) perforations. Stimulation thresholds were measured and impedance was controlled. Thereafter, an independent observer measured the depth (D) of the most superficial nerve structure with ultrasound. Distances between stimulating points and the most superficial nerve structure (S) were measured. Correlations between associated stimulating thresholds and distances D and S were calculated. The stimulating point with the lowest current was identical to the point closest to the nerve in only 10% of measurements. Median S was 12.6 (3.4-32.0) mm and D 7.6 (0.3-28.6) mm. Distances did not correlate with percutaneous stimulation thresholds. PNS with a stimulating pen is not a reliable technique for nerve localization in the brachial plexus as verified by high-resolution ultrasound.


A population-based study of hospital length of stay and emergency readmission following surgery for non-small-cell lung cancer.
We conducted a population-based analysis of time trends in length of stay (LOS), predictors of prolonged LOS and emergency readmission following resection for non-small-cell lung cancer (NSCLC). Incident lung cancers (ICDO2:C34), diagnosed between 2002 and 2008, were identified from the National Cancer Registry (NCR) of Ireland, and linked to hospital in-patient episodes (HIPE). For those with NSCLC who underwent lung resection, the associated hospital episode was identified. Factors predicting longer LOS (upper quartile, >20 days), and emergency readmission within 28 days of the index procedure (IP) were investigated using Poisson regression. A total of 1284 patients underwent resection. Eighty-four (7%) subsequently died in hospital and 1200 (93%) were discharged. Hundred and nineteen of 1200 (10%) were readmitted as an emergency within 28 days of discharge. Median LOS after the IP was 13 days (inter-decile range: 7-35). Risk of prolonged LOS was significantly greater in patients >75 years, resident in an area of highest deprivation, with 2+ comorbidities, who had undergone surgery in a lower-volume hospital, and died in hospital subsequent to the IP. Emergency readmission was significantly more likely in patients who were resident in an area of highest deprivation, with 2+ comorbidities, and had Stage III disease or worse. The main reasons for emergency readmission were: pulmonary complications (29%), cardio/cerebrovascular events (21%) or infection (20%). Half of the patients had a LOS in excess of 13 days, which was longer than any other country with published data. Patient and health-service factors were associated with prolonged LOS, while patient and tumour characteristics were associated with risk of emergency readmission. Deprivation was a conspicuous determinant of both LOS and readmission.


Effect of Genetic and Laboratory Findings on Clinical Course of Antisynthetase Syndrome in a Hungarian Cohort.
The aim of this study was to determine the clinical, serological, and genetic features of anti-Jo-1 positive antisynthetase patients followed by a Hungarian single centre to identify prognostic markers, which can predict disease phenotypes and disease progression. It was a retrospective study using clinical database of 49 anti-Jo-1 positive patients. 100% of patients exhibited myositis, 73% interstitial lung disease, 88% arthritis, 65% Raynaud's phenomenon, 43% fever, 33% mechanic's hand, and 12% dysphagia. We could detect significant correlation between anti-Jo-1 titer and the CK and CRP levels at disease onset and during disease course. HLA DRB1⁎03 positivity was present in 68.96% of patients, where the CK level at diagnosis was significantly lower compared to the HLA DRB1⁎03 negative patients. HLA DQA1⁎0501-DQB1⁎0201 haplotype was found in 58.62% of patients, but no significant correlation was found regarding any clinical or laboratory features. Higher CRP, ESR level, RF positivity, and the presence of fever or vasculitic skin lesions at the time of diagnosis indicated a higher steroid demand and the administration of higher number of immunosuppressants during the follow-up within anti-Jo-1 positive patients. The organ involvement of the disease was not different in HLA-DRB1⁎0301 positive or negative patients who were positive to the anti-Jo-1 antibody; however, initial CK level was lower in HLA-DRB1⁎0301 positive patients. Distinct laboratory and clinical parameters at diagnosis could be considered as prognostic markers.


Neural decoding of attentional selection in multi-speaker environments without access to separated sources.
People who suffer from hearing impairments can find it difficult to follow a conversation in a multi-speaker environment. Modern hearing aids can suppress background noise; however, there is little that can be done to help a user attend to a single conversation without knowing which speaker is being attended to. Cognitively controlled hearing aids that use auditory attention decoding (AAD) methods are the next step in offering help. A number of challenges exist, including the lack of access to the clean sound sources in the environment with which to compare with the neural signals. We propose a novel framework that combines single-channel speech separation algorithms with AAD. We present an end-to-end system that 1) receives a single audio channel containing a mixture of speakers that is heard by a listener along with the listener's neural signals, 2) automatically separates the individual speakers in the mixture, 3) determines the attended speaker, and 4) amplifies the attended speaker's voice to assist the listener. Using invasive electrophysiology recordings, our system is able to decode the attention of a subject and detect switches in attention using only the mixed audio. We also identified the regions of the auditory cortex that contribute to AAD. Our quality assessment of the modified audio demonstrates a significant improvement in both subjective and objective speech quality measures. Our novel framework for AAD bridges the gap between the most recent advancements in speech processing technologies and speech prosthesis research and moves us closer to the development of cognitively controlled hearing aids.


Indications that the erythrocyte receptor involved in enterotoxigenic Escherichia coli attachment is a sialoglycoconjugate.
A reverse hemagglutination assay was used to study adherence to human erythrocytes by Escherichia coli H10407, which possesses colonization factor antigen I. Pretreatment of erythrocytes with trypsin, chymotrypsin, papain, protease, and neuraminidase completely abolished attachment reactivity. In addition, the hemagglutination reaction was prevented by the presence of urea and guanidine. In contrast, the lipases, nucleotide hydrolases, exoglycosidases, and reagents affecting disulfide or sulfhydryl moieties did not alter receptor reactivity. Glycoconjugates containing sialic acid inhibited the hemagglutination reaction. Furthermore, a sialoglycoprotein isolated from the erythrocyte membrane inhibited the hemagglutination reaction. Collectively, these data indicate that the erythrocyte receptor responsible for attachment by E. coli possessing colonization factor antigen I is a sialoglycoconjugate.


[Home parenteral nutrition in patients with advanced cancer: experience of a single centre over ten years].
The use of Home Parenteral Nutrition (HPN) in patients with advanced cancer without the possibility of curative treatment continues to be a controversial subject entailing a considerable emotional burden. Nonetheless, this group of patients constitutes the main indication for HPN in many programmes. To present the characteristics of a series of patients included on an HPN programme over the last ten years. Retrospective study of the case histories of the 11 patients who received HPN over this period. The demographic and clinical details were noted along with their complications and evolution for comparison with those of a control group of patients with benign disease receiving HPN over the same period. For the comparisons, Student's t test and the chi-squared test were used as and when indicated. Results were considered statistically significant if p < 0.05. Eleven patients received HPN, nine of them because of an irresoluble intestinal obstruction and two because of a high flow fistula. The mean age at the start of HPN was 50.8 +/- 12.7 years versus 37.3 +/- 17.2 years for the group with benign disease (p < 0.05). The mean duration of HPN was 71.05 +/- 217 days in the first group, notably less than the second (387.15 +/- 995.85; p < 0.05), with a range between 5 and 760 days. The patients received the infusion through a previously implanted subcutaneous reservoir (n = 9) and on two occasions, electively, through a tunnelled catheter. The infection rate was higher in the group with cancer (0.34 episodes per patient and 1,000 days on HPN) than in the group with benign disease (0.08 episodes; p < 0.05). HPN was suspended in only one of the patients more than 5 days prior to death due to clinical deterioration. Two patients required admission due to a complication associated with the technique. In both cases, a fungal infection of the blood made it necessary to withdraw the catheter. The quality of life, measured by means of an activity scale, was similar at the start of HPN in both groups. None of the patients included on the programme is still alive. HPN offers patients with advanced cancer and severe intestinal dysfunction the possibility of an at-home treatment with a low complication rate. If we take into account the short mean duration of HPN, inclusion on the programme must be assessed individually and regularly revised.


Peer sexual harassment and deliberate self-injury: longitudinal cross-lag investigations in Canada and Sweden.
Although the receipt of peer sexual harassment in schools has been linked to deliberate self-injury, the direction of association over time has not been tested. Two longitudinal studies examined whether receipt of peer sexual harassment within schools predicts engagement in deliberate self-injury or vice versa. Differences between boys and girls were also tested. Surveys were conducted in two countries, Canada and Sweden. Measures of sexual harassment and deliberate self-injury were administered yearly in classrooms. Two waves of data were collected in the Canadian study (N = 161, 59.6% girls, mean age = 13.82 years); three waves of data were collected in Sweden (N = 513, 47% girls, mean age = 13.23 years). In the Canadian study, deliberate self-injury predicted subsequent peer sexual harassment; the converse relationship was not significant. No significant gender differences were found. Across the three waves of the Swedish study, peer sexual harassment predicted self-injury from T1 to T2, and self-injury predicted peer sexual harassment from T2 to T3. However, self-injury did not mediate peer sexual harassment at T1 and T3. Tests of gender differences revealed self-injury predicted sexual harassment from T2 to T3 among Swedish girls but not boys. Adolescents who deliberately self-injure may be vulnerable to sexual harassment by peers at school. Cultural norms may have a role in whether this process applies primarily to girls or to both genders. Sexual harassment by peers may also increase self-injury, but this is not subsequently linked to increases in receipt of sexual harassment.


High-fidelity recognition of RNA: solution structure of a DNA:RNA hybrid duplex with a molecular cap.
Binding RNA targets, such as microRNAs, with high fidelity is challenging, particularly when the nucleobases to be bound are located at the terminus of the duplex between probe and target. Recently, a peptidyl chain terminating in a quinolone, called ogOA, was shown to act as a cap that enhances affinity and fidelity for RNAs, stabilizing duplexes with Watson-Crick pairing at their termini. Here we report the three-dimensional structure of an intramolecular complex between a DNA strand featuring the ogOA cap and an RNA segment, solved by NMR and restrained torsion angle molecular dynamics. The quinolone stacks on the terminal base pair of the hybrid duplex, positioned by the peptidyl chain, whose prolinol residue induces a sharp bend between the 5' terminus of the DNA chain and the glycine linked to the oxolinic acid residue. The structure explains why canonical base pairing is favored over hard-to-suppress mismatched base combinations, such as T:G and A:A, and helps to design improved high-fidelity probes for RNA.


Light Affects Flagellar Agglutinability in Chlamydomonas eugametos by Modification of the Agglutinin Molecules.
The effect of light on the sexual competence of a light-sensitive mating type minus strain (mt(-)) of Chlamydomonas eugametos obtained by crossing a light-sensitive mating type plus strain (mt(+)) with a light-insensitive mt(-) strain is described. As previously demonstrated for the mt(+) parent, this study of one of the mt(-) offspring shows that (a) a light-sensitive mechanism affects flagellar agglutinability in a rapid process that does not require protein synthesis; (b) only the activity of the flagellar agglutinins (glycoproteins responsible for agglutination) is susceptible to light while agglutinins on the cell body surface are not affected by light. We further demonstrate that (a) membrane vesicles naturally released from nonagglutinable dark gametes remain inactive. Extracts of these vesicles also remain inactive even though they contain agglutinin-like components; (b) inactive mt(-) agglutinin is present in extracts of flagella from nonagglutinable dark gametes by comparison of its chromatographic, electrophoretic, and immunogenic properties with those of active agglutinin. When purified of all other flagellar proteins, it remains inactive; (c) a monoclonal antibody directed against the sexual agglutination site of the mt(-) agglutintin discriminates between active and inactive agglutinins when present in a native state on the flagellar surface, but is unable to discriminate between them when they are denatured in sodium dodecyl sulfate-electrophoresis gels and blotted onto nitrocellulose. Taken collectively these observations suggest that light activation involves the chemical modification of the agglutinins in situ on the flagellar surface.


Direct comparison of performance characteristics of two immunoassays for bone isoform of alkaline phosphatase in serum.
A clinical need exists for a sensitive and specific assay for the quantitation of the bone isoform of alkaline phosphatase in serum. The majority of methods do not meet this requirement; however, the recent development of immunoassays for this isoform may provide a solution. In a detailed evaluation of two immunoassays, we found a degree of imprecision that enables the discrimination of changes within the reference range. The cross-reactivity of the liver isoform was found to be between 7.1% and 12.7% when two different methods of assessment were used. The comparison of results with an electrophoretic procedure showed that the immunocapture method recovered less of the bone isoform in samples from children than in samples from patients with Paget disease; no such difference was found with the immunometric method. This suggests that the immunocapture antibody may discriminate between different bone isoforms in children whereas the immunometric assay does not.


Rab8a localisation and activation by Toll-like receptors on macrophage macropinosomes.
Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions. Cell surface ruffles give rise to phagosomes and to macropinosomes as multi-functional compartments that contribute to environmental sampling, pathogen entry, plasma membrane turnover and receptor signalling. Rapid, high resolution, lattice light sheet imaging demonstrates the dynamic nature of macrophage ruffling. Pathogen-mediated activation of surface and endosomal Toll-like receptors (TLRs) in macrophages upregulates macropinocytosis. Here, using multiple forms of imaging and microscopy, we track membrane-associated, fluorescently-tagged Rab8a expressed in live macrophages, using a variety of cell markers to demonstrate Rab8a localization and its enrichment on early macropinosomes. Production of a novel biosensor and its use for quantitative FRET analysis in live cells, pinpoints macropinosomes as the site for TLR-induced activation of Rab8a. We have previously shown that TLR signalling, cytokine outputs and macrophage programming are regulated by the GTPase Rab8a with PI3 Kγ as its effector. Finally, we highlight another effector, the phosphatase OCRL, which is located on macropinosomes and interacts with Rab8a, suggesting that Rab8a may operate on multiple levels to modulate phosphoinositides in macropinosomes. These findings extend our understanding of macropinosomes as regulatory compartments for innate immune function in macrophages. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.


Ampicillin Dose for Early and Late-Onset Group B Streptococcal Disease in Neonates.
Ampicillin is frequently used in neonates for early- and late-onset group B streptococcal (GBS) disease. In 2019, the American Academy of Pediatrics (AAP) published guidelines for GBS which included updated dosing recommendations for ampicillin for bacteremia and provided specific dosing recommendations for meningitis. The dosing recommendations in the guidelines were based off the 2018 Report of the Committee on Infectious Diseases (i.e., Red Book), which differed from the 2015 Red Book. For bacteremia, no dosing changes were recommended for ampicillin dosing in neonates ≤ 7 days of postnatal age (PNA), but less frequent dosing intervals were recommended for neonates > 7 days PNA. For meningitis, increased dosing recommendations were provided in the update. However, the rationale and supporting evidence for these changes were not provided. A literature search was performed to review articles pertaining to the pharmacokinetics (PK), pharmacodynamics (PD) and safety of ampicillin in neonates. The ampicillin dosing recommendations in the AAP guidelines were mainly supported by a 2014 publication that evaluated the PK and PD of ampicillin in neonates with gestational age (GA) of 24 to 41 weeks and PNA of 0 to 25 days. The proposed dosing from this study for bacteremia is included in the 2018 Red Book and 2019 guidelines. For meningitis, no supporting evidence was identified for the dosing recommendations in the 2018 Red Book and 2019 guidelines. Only one study has evaluated ampicillin concentrations in cerebrospinal fluid, but proposed dosing from this study was much lower than that included in the guidelines. The high ampicillin doses for GBS meningitis should be used with caution, as high ampicillin concentrations have been associated with seizures and no studies have evaluated efficacy of this dosing strategy. The purpose of this review is to identify key pieces of literature regarding dosing recommendations and safety of ampicillin in neonates. KEY POINTS: · Recent guidelines provide dosing recommendations for ampicillin, but the supporting evidence is not included.. · Literature supporting evidence for ampicillin dosing for bacteremia is available, but not for dosing for meningitis.. · Recommended meningitis dose may result in supratherapeutic concentrations and increase seizure risk..


Human exposure by mobile phones in enclosed areas.
Human exposure by mobile phones in enclosed areas such as train carriages, elevators, and cars is considered. Equivalent power density and whole body specific absorption rate (SAR) are estimated by applying multimode resonant cavity theory and a straight forward worst case approach. The results show that exceeding the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines due to simultaneous use of several mobile phones in enclosed areas is highly improbable.


Chlamydia pneumoniae infection-associated erythema multiforme.
There is a well-known correlation between Herpes simplex (HSV) infection and erythema multiforme (EM). More recently, in Japan, it was found that Chlamydia pneumoniae (Cp) may promote the development of EM. All cases of Cp infection-associated EM that had been diagnosed in our clinic over the past two years (from 2011 to 2012) were analyzed. Cp infection was diagnosed on the basis of a significant increase (>2.00) in anti-Cp IgM titers, as measured by the HITAZYME-ELISA test. There were 7 cases of Cp-EM, one male and 6 females. Median age was 13 years (range 3-29 years). It is recommended that the possible involvement of Cp infection, besides HSV or Mycoplasma pneumoniae infections, should be considered in all cases of EM.


Correlations between arthroscopic findings and synovial membrane histology in patients with rheumatoid synovitis of the knee joint.
Correlation and agreement between the diagnostic results of arthroscopic and histological examinations of the synovial membrane in rheumatoid synovitis of the knee joint have been discussed in small number of studies with contradictory conclusions. The aim of the present study was to determine the correlation between the arthroscopic characteristics and histology of the synovial membrane in patients with rheumatoid arthritis and synovitis of the knee joint. Sixty-four arthroscopies of the knee joint with guided multiple synovial biopsies were performed in patients with rheumatoid synovitis. Biopsy samples were taken under visual control from the evidently inflamed synovia in four regions of the knee joint. Arthroscopic assessment of the rheumatoid synovitis was done according the standard system of ACR including 6 criteria. The histological assessment of the synovitis met the EULAR criteria including 6 morphological variables. High positive correlation (r = +0.76) was established between the arthroscopic and histological assessment of the rheumatoid synovitis in the examined patients. High values were also found for the k coefficient for agreement (k = 0.70). The mean value of synovitis extent according to VAS was 43.16 mm and the mean value of intensity of the inflammatory process according to VAS was 54.31 mm. The agreement between the arthroscopic and histological diagnosis of the synovitis is in the range of high but not absolute correlation. The two methods are not contradictory and should be used concurrently in patients with chronic rheumatoid synovitis.


Aspirin in primary and secondary prevention in elderly adults revisited.
Despite the frequency and long duration of aspirin use, its role in primary and secondary prevention in older adults is not well studied. This review takes a critical look at the available literature on aspirin efficacy in elderly adults, and some relevant guidelines for practicing physicians are suggested.


Evaluation of postoperative recovery in day surgery patients using a mobile phone application: a multicentre randomized trial.
Many patients undergoing anaesthesia and surgery experience postoperative complications. Our aim was to investigate whether a systematic follow-up smartphone-based assessment, using recovery assessment by phone points (RAPP) compared with standard care, had a positive effect on day surgery patients' postoperative recovery. We also investigated whether there were differences in women and men's recovery and recovery scores. The study was a single-blind, multicentre randomized controlled trial. A total of 997 patients were randomly allocated to either RAPP or standard care. The Swedish web version of a quality of recovery (SwQoR) questionnaire was used to evaluate the patients' postoperative recovery, either on paper or using an application (RAPP) on postoperative days seven and 14. On postoperative day seven the RAPP group reported significantly better values in seven out of 24 items of the SwQoR: sleeping difficulties; not having a general feeling of wellbeing; having difficulty feeling relaxed/comfortable; and dizziness; headache; pain in the surgical wound; and a swollen surgical wound compared with the control group, implying a good postoperative recovery. Both men and women in the RAPP group reported significantly better values (and, hence good postoperative recovery) compared with the control group in the items sleeping difficulties; not having a general feeling of wellbeing and pain in the surgical wound. Measurement of patient-reported outcomes using a smartphone-based application was associated with decreased discomfort from several postoperative symptoms. Systematic e-assessment can thereby increase patients' quality of recovery and identify key areas for improvement in perioperative care. NCT02492191.


The pyrH gene of Lactococcus lactis subsp. cremoris encoding UMP kinase is transcribed as part of an operon including the frr1 gene encoding ribosomal recycling factor 1.
The pyrH gene of Lactococcus lactis subsp. cremoris MG1363, encoding UMP kinase, has been sequenced and cloned. It encodes a polypeptide of 239 amino acid residues (deduced molecular weight of 25951), which was shown to complement a temperature sensitive pyrH mutation in Escherichia coli, thus establishing the ability of the encoded protein to synthesize UDP. The pyrH gene in L. lactis is flanked downstream by frr1 encoding ribosomal recycling factor 1 and upstream by an open reading frame, orfA, of unknown function. The three genes were shown to constitute an operon transcribed in the direction orfA-pyrH-frr1 from a promoter immediately in front of orfA. This operon belongs to an evolutionary highly conserved gene cluster, since the organization of pyrH on the chromosomal level in L. lactis shows a high resemblance to that found in Bacillus subtilis as well as in Escherichia coli and several other prokaryotes


Patient with rheumatoid arthritis on methotrexate with multiple infecting organisms causing gastritis.
A 70-year-old man with a medical history of rheumatoid arthritis on methotrexate 2.5 mg every other day was being followed for cytomegalovirus (CMV) gastritis and Helicobacter pylori infection, who was also found to have adrenal masses bilaterally. A CT showed a 1 cm left adrenal nodule along with a 2.5 cm right adrenal mass suspicious for malignancy. A positron emission tomography showed metabolic activity in his adrenals that was non-specific (could be seen in benign as well as malignant lesions). The patient was started on valganciclovir 900 mg daily for 30 days. Following treatment the patient showed marked clinical improvement with a weight gain of 9 lbs and a complete resolution of his epigastric pain. A repeat oesophagogastroduodenoscopy performed with biopsy returned negative for CMV. A repeat CT abdomen to assess the adrenals was performed 2 weeks after completion of valganciclovir. His adrenal nodules had decreased significantly in size, with his left adrenal gland nodules measuring 1 cm and now his right adrenal gland nodule measuring 1 cm.


Is it time to question the 10-day rule?
In the early 1970s the 10-day rule was introduced into all radiography departments in the UK in order to eliminate the possibility of irradiating a developing embryo during radiography. Until now that rule has been regarded as generally a sufficient measure for this purpose. Recent findings in gynaecological research, however, may indicate that a new rule should be considered in order to ensure more certainly the safety of early life in the womb.


A statistical clustering approach to discriminating perfusion from conduit vessel signal contributions in a pulmonary ASL MR image.
The measurement of pulmonary perfusion (blood delivered to the capillary bed within a voxel) using arterial spin labeling (ASL) magnetic resonance imaging is often complicated by signal artifacts from conduit vessels that carry blood destined for voxels at a distant location in the lung. One approach to dealing with conduit vessel contributions involves the application of an absolute threshold on the ASL signal. While useful for identifying a subset of the most dominant high signal conduit image features, signal thresholding cannot discriminate between perfusion and conduit vessel contributions at intermediate and low signal. As an alternative, this article discusses a data-driven statistical approach based on statistical clustering for characterizing and discriminating between capillary perfusion and conduit vessel contributions over the full signal spectrum. An ASL flow image is constructed from the difference between a pair of tagged magnetic resonance images. However, when viewed as a bivariate projection that treats the image pair as independent measures (rather than the univariate quantity that results from the subtraction of the two images), the signal associated with capillary perfusion contributions is observed to cluster independently of the signal associated with conduit vessel contributions. Analyzing the observed clusters using a Gaussian mixture model makes it possible to discriminate between conduit vessel and capillary-perfusion-dominated signal contributions over the full signal spectrum of the ASL image. As a demonstration of feasibility, this study compares the proposed clustering approach with the standard absolute signal threshold strategy in a small number of test images.


[Homology between the Lpm system of allotypes in the American mink and the Gp system of allotypes in the domestic pig].
The 5 alpha-macroglobulin allotypes alpha M1, alpha M2, alpha M3, alpha M4 and alpha M5 were identified in pig. The alpha M1 allotype was reported as a marker of pig alpha-macroglobulin, the latter being homologous to alpha 2-macroglobulins in human and in mink. The allotypes alpha M2-alpha M5 were specified as markers of the second isotypical variant of pig alpha-macroglobulins, which was homologous to mink Lpm macroglobulin (alpha 1M). As seen from data obtained by International Comparative Test ISABR 87-88, alpha M1 is a new allotype, while allotypes alpha M2--alpha M5 correspond to four allotypes in the Gp system (Janik et al.). Based on these data, a conclusion was made on the homology between the Lpm system in american mink and the Gp system in pig. Since the allotypes studied are the part of alpha-macroglobulins, a locus controlling them was designated the AM locus. We also find it more advantageous to apply the same name to the homologous locus in mink, instead of the Lpm used earlier. Genetic control of 5 allotypes was studied and the structure of the AM locus in pig analysed in detail. Comparative study of organization of the above locus and the homologous locus in mink was carried out.


Methodology of validation of criteria for SLE.
The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunological knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody (FANA) and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity. Development of criteria sets is inherently circular, since the standard of evaluation must consist of the clinical diagnosis. Validation of the diagnosis over time can reduce but not eliminate the circularity. Selection of controls also influences sensitivity and specificity and, ideally, criteria should be developed with controls who represent particularly difficult problems of discrimination. Because the low "prior probability" of the diagnosis in many populations will result in a large number of false positives, preference in general should be for specificity over sensitivity. The 1982 criteria were developed from 177 patients with SLE and 162 control patients from 18 institutions using the next age-, race- and sex-matched patient seen as the control whenever possible. Results of a training sample were validated against a test sample of patients and against 500 patients from other databanks.


Cleavage of the IPS-1/Cardif/MAVS/VISA does not inhibit T cell-mediated elimination of hepatitis C virus non-structural 3/4A-expressing hepatocytes.
Hepatitis C virus (HCV) effectively establishes persistent infection in human livers. The non-structural (NS) 3/4A complex participates in this process by cleavage of interferon beta (IFN beta) promoter stimulator-1 (IPS-1; also termed Cardif/MAVS/VISA), which inhibits responses to double stranded (ds) RNA. However, it is not known whether this effect extends beyond innate responses. To test if HCV NS3/4A affects innate and adaptive immune responses in vivo. NS3 levels were semi-quantified in human liver biopsies, transfected cells, and in transgenic (Tg) mouse livers by western blot. The effect of NS3/4A on dsRNA-mediated signalling and on the integrity of IPS-1 was analysed using in vitro translation, transfected cells and Tg mice. Cytotoxic T cell (CTL)-mediated clearance of transient firefly luciferase (FLuc)- and/or NS3/4A-Tg hepatocytes was determined using in vivo imaging and western blot. NS3 protein levels were in a comparable range (0.1-49 microg/g tissue) in infected human livers and Tg mouse livers. Importantly, these levels of NS3/4A reduced murine innate responses to synthetic dsRNA in vivo, supporting the possibility that this occurs also in infected humans. The likely explanation for this was the NS3/4A-mediated cleavage of mouse IPS-1, albeit less efficiently than human IPS-1. Despite this, FLuc- and/or NS3/4A-expressing murine hepatocytes were effectively eliminated by hepatic CTLs, utilising the classical molecules for virus-infected cell lysis, including CD8, IFN gamma, perforin and FasL. Although HCV NS3/4A inhibits the innate immunity, this does not prevent CTL-mediated clearance of NS3/4A-expressing hepatocytes in vivo. Thus, other HCV proteins are most likely responsible for interfering with the adaptive immunity.


Influence of enzyme-substrate contacts located outside the EcoRI recognition site on cleavage of duplex oligodeoxyribonucleotide substrates by EcoRI endonuclease.
A complete understanding of the sequence-specific interaction between the EcoRI restriction endonuclease and its DNA substrate requires identification of all contacts between the enzyme and substrate, and evaluation of their significance. We have searched for possible contacts adjacent to the recognition site, GAATTC, by using a series of substrates with differing lengths of flanking sequence. Each substrate is a duplex of non-self-complementary oligodeoxyribonucleotides in which the recognition site is flanked by six base pairs on one side and from zero to three base pairs on the other. Steady-state kinetic values were determined for the cleavage of each strand of these duplexes. A series of substrates in which the length of flanking sequence was varied on both sides of the hexamer was also examined. The enzyme cleaved both strands of each of the substrates. Decreasing the flanking sequence to fewer than three base pairs on one side of the recognition site induced an asymmetry in the rates of cleavage of the two strands. The scissile bond nearest the shortening sequence was hydrolyzed with increasing rapidity as base pairs were successively removed. Taken together, the KM and kcat values obtained may be interpreted to indicate the relative importance of several likely enzyme-substrate contacts located outside the canonical hexameric recognition site.


Bioactive metal oxide nanoparticles from some common fruit wastes and Euphorbia condylocarpa plant.
For the first time, the potential of orange and banana peels as fruit wastes was evaluated in contrast with Euphorbia condylocarpa as a widely distributed medicinal plant of Kurdistan, Iran, for biosynthesis of Fe3O4, CuO, ZnO, and TiO2 NPs. The extracts of the green sources were assessed to monitor the bioreducing phytochemicals inside them using the UV-Vis spectrophotometer. Moreover, the obtained green nanoparticles were identified using the micrograph and diffractogram techniques to show their size, shape, and morphology. Also, the antibacterial activities of the green NPs were investigated against common pathogenic bacteria of Pseudomonas aureus, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae.


Excitatory amino acid transmitters in epilepsy.
For the majority of human epilepsy syndromes, the molecular and cellular basis for the epileptic activity remains largely conjectural. The principal hypotheses currently concern: defects in membrane ionic conductances or transport mechanisms; defects in gamma-aminobutyric acid (GABA)-mediated inhibitory processes; and enhanced or abnormal excitatory synaptic action. Substantial evidence exists in humans and animals for acquired abnormalities in excitatory amino acid neurotransmission that may participate in the abnormal patterns of neuronal discharge, and this could provide the morphological basis for a recurrent excitatory pathway sustaining seizure discharges in temporal lobe epilepsy. In practice, two approaches appear significant in the suppression of seizures. One is to act postsynaptically on receptors to decrease the excitation induced by glutamate, and the other is to decrease synaptic release of glutamate and aspartate. Agents acting upon adenosine or GABAB receptors decrease glutamate release in vitro but do not have significant anticonvulsant activity, probably because of their predominant actions at other sites. Lamotrigine blocks stimulated release of glutamate and shows anticonvulsant activity in a wide range of animal models.


Lipoma with osteocartilaginous metaplasia: case report and literature review.
Osteocartilaginous metaplasia in lipomas is rare and mainly encountered in large-sized, long-standing lipomas. This entity can be found at almost any site of the body, particularly in the soft tissues of the skeletal system, breast, pharynx, and nasopharynx. We describe a case of lipoma with osteochondroid metaplasia in a 65-year-old woman with an indolent lesion, and discuss differential diagnoses.


The Application of Sequential Extraction in Phosphorus Fractionation in Environmental Samples.
Maintaining the balance of phosphorus in ecosystems is a priority activity in environmental protection. To achieve this successfully, it is necessary to know the physicochemical properties of phosphorus forms. Speciation analysis is used for this purpose. This process helps to assess the concentration of various physical and chemical forms of phosphorus. When there are very unstable chemical forms of the analyte hindering the determination in the environmental test, fractionation is performed, i.e., the process of classifying the analyte or a group of analytes from a given sample according to physical properties. The paper discusses the phosphorus fractionation methods in environmental samples. The authors critically analyzed over a dozen phosphorus fractionation procedures using sequential extraction of this element. Particular attention was paid to the possibility of sequential extraction when determining the phosphorus pool available to plants (bioavailable fraction) and labile phosphorus able to migrate in the environment. The paper discusses examples of phosphorus fractionation in various environmental matrices, such as river and lake sediments, sewage sludge, composts, and soils. The selection of an appropriate method for the studied environment was made. Adapting the proposed methodology to the environmental matrix being tested determines the most accurate results of the experiment. Attention was also paid to the possibilities of practical applications of fractionation results, particularly the possibility of isolating phosphorus available for plants from various environmental matrices.


Allergic contact dermatitis to plant extracts in cosmetics.
Topically applied cosmetics and medicaments containing botanical extracts are commonly used. Despite popular beliefs of their benignancy, some botanicals have been implicated in causing allergic contact dermatitis in susceptible patients. The offending allergen may be the botanical extract itself or another ingredient such as a fragrance, preservative, dye, or sunscreen found in the product. Specific botanicals implicated in causing cosmetic contact dermatitis include Compositae family plants, tea tree oil, peppermint, lavender, lichens, henna, and others.


Scaling the Low-Shear Pulsatile TORVAD for Pediatric Heart Failure.
This article provides an overview of the design challenges associated with scaling the low-shear pulsatile TORVAD ventricular assist device (VAD) for treating pediatric heart failure. A cardiovascular system model was used to determine that a 15 ml stroke volume device with a maximum flow rate of 4 L/min can provide full support to pediatric patients with body surface areas between 0.6 and 1.5 m. Low-shear stress in the blood is preserved as the device is scaled down and remains at least two orders of magnitude less than continuous flow VADs. A new magnetic linkage coupling the rotor and piston has been optimized using a finite element model (FEM) resulting in increased heat transfer to the blood while reducing the overall size of TORVAD. Motor FEM has also been used to reduce motor size and improve motor efficiency and heat transfer. FEM analysis predicts no more than 1°C temperature rise on any blood or tissue contacting surface of the device. The iterative computational approach established provides a methodology for developing a TORVAD platform technology with various device sizes for supporting the circulation of infants to adults.


A narrative review of the pathophysiology of COVID-19 infection among cancer patients: Current evidence and research perspectives.
The mechanism by which a suppressed immune system of a cancer patient makes them susceptible to COVID-19 is still unclear. Any delay or discontinuation of cancer care due to the pandemic is expected to have a detrimental impact on the outcome of cancer. A few studies have addressed the incidence of COVID-19 among cancer patients, but the small sample size of such studies makes it difficult to draw inference to the general population. For our review, 'Pubmed' database and Google search engines were used for searching the relevant articles. The criterion used for review includes their relevance to the defined review question, which is the pathophysiological mechanism of COVID-19 among cancer patients and the relevant therapeutic interventions therewith. This review includes 20 studies and other relevant literature which address the determinants of COVID-19 among Cancer patients. Delay in cancer diagnosis will increase the stage progression of cancer patients and increased mortality in the future. A short delay in administering cancer related treatment to aid the odds of patient surviving the acute SARS-CoV-2 infection, should be at the discretion of the treating Physician. Oncologists dilemma in the current situation includes titrating the density of drug doses and intensity of treatment regimen, for the optimal management of metastatic and adjuvant cancer patients. Patients are thus subjected to suboptimal treatment and undetected disease recurrence, To circumvent the immunosuppressive effects of chemotherapy, Providers need to consider staggered regimen or alternate therapies such as biological/immunotherapy, targeted therapy, anti-angiogenic drugs, hormone therapy and/or antibody-based therapeutics. This review provides insights on the pathogenesis of SARS-CoV-2, which could enable Physicians in formulating therapeutic strategies for the management of severe patients, more so in Oncology settings, thus reducing the mortality. The key is to balance the continuation of urgent cancer care, but rationing the elective treatment according to the circumstances.


A Novel Approach of Promoting Adhesion of Reinforcing Cord to Elastomers by Plasma Polymerization.
Adhesion of cords to elastomers is crucial for many elastomeric products, such as tires and V-belts. The best adhesion system so far is based on a combination of resorcinol, formaldehyde, and a latex (RFL). However, this cord treatment has serious disadvantages in terms of processing and toxicity. A promising alternative is a plasma treatment of the cords prior to be embedded in the elastomer. For rayon cords, a plasma polymerization of sulfur-containing precursors results in adhesion levels close to RFL treatment. However, for polyethylene terephthalate (PET) cords, this treatment is not satisfactory. For this type of cords, a water-plasma activation followed by a silane dip is more promising, as 72% of the adhesion level of RFL treatment could be achieved. For rayon, an even higher adhesion level was realized.


Nature of the rate-limiting step in the supply of inorganic carbon for photosynthesis in isolated asparagus mesophyll cells.
Accumulation of acid-stable and acid-labile C has been studied in cells isolated from cladophylls of Asparagus sprengeri regel, as a function of the concentrations of the various inorganic C (C(i)) species in the external medium.The rate of CO(2) fixation was higher when C(i) was supplied as CO(2) as opposed to HCO(3) (-), at the same concentration. Participation of HCO(3) (-) was indicated when the external CO(2) and HCO(3) (-) concentrations were chosen such that, owing to interconversion between C(i) species, the same CO(2) concentrations would be reached at a certain point in time, regardless of which species was supplied initially; at this point, a higher fixation rate was observed in the case of HCO(3) (-) supply.In the presence of carbonic anhydrase, the apparent affinity for C(i) was raised. This enzyme raised fixation rate even under steady-state conditions, but only at limiting external C(i) concentrations. The decrease in external CO(2) concentration was correlated with a decreasing internal C(i) level when CO(2) was the species supplied.When 10 mum CO(2) was supplied initially fixation rate was almost independent of pH. However, when HCO(3) (-) was supplied at concentrations calculated to yield 10 mum CO(2) at equilibrium, fixation rate rose with pH. Carbonic anhydrase raised the fixation rate over the entire pH range when HCO(3) (-) was the species supplied.It is concluded that CO(2) was the major C(i) species permeating from the medium to the carboxylating site. Further, our results bring clear evidence that formation of CO(2) from HCO(3) (-) in the unstirred layer, and the diffusion of both species in this layer, rate limit CO(2) fixation by these isolated cells.


F-18 FDG PET/CT in rectal carcinoma: where are we now?
This short review aims at summarizing the available data pertaining to the usefulness of F-18 FDG PET/CT in rectal cancer. It is specifically focused on the emerging role of F-18 FDG PET/CT in assessing the response to neoadjuvant combined radiochemotherapy in locally advanced rectal cancer. It also probes the possibility of finding standardized PET/CT parameters that are capable of differentiating responders from nonresponders in whom therapeutic approach could be modified.


Efficacy and safety of intraoperative radiotherapy in rectal cancer: A systematic review and meta-analysis.
In recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial. To evaluate the value of IORT for patients with rectal cancer. We searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software. In this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000). The advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.


Diffusion-equation method for crystallographic figure of merits.
Global optimization methods play a significant role in crystallography, particularly in structure solution from powder diffraction data. This paper presents the mathematical foundations for a diffusion-equation-based optimization method. The diffusion equation is best known for describing how heat propagates in matter. However, it has also attracted considerable attention as the basis for global optimization of a multimodal function [Piela et al. (1989). J. Phys. Chem. 93, 3339-3346]. The method relies heavily on available analytical solutions for the diffusion equation. Here it is shown that such solutions can be obtained for two important crystallographic figure-of-merit (FOM) functions that fully account for space-group symmetry and allow the diffusion-equation solution to vary depending on whether atomic coordinates are fixed or not. The resulting expression is computationally efficient, taking the same order of floating-point operations to evaluate as the starting FOM function measured in terms of the number of atoms in the asymmetric unit. This opens the possibility of implementing diffusion-equation methods for crystallographic global optimization algorithms such as structure determination from powder diffraction data.


Elective stenting of symptomatic basilar artery stenosis.
Percutaneous angioplasty of the intracranial arteries still carries the risk of dissection, with acute closure and embolization. Stenting has been shown to improve the safety and durability of angioplasty in every circulatory bed in which it has been applied. However, stenting of the intracranial arteries has been limited by the availability of stents that can be reliably deployed intracranially. Twelve patients underwent elective stenting of the basilar artery after episodes of vertebrobasilar ischemia. In all patients, either medical therapy had failed or the patient had a contraindication for long-term anticoagulation. Information from independent neurological examinations, quantitative angiography, and clinical follow-up was collected. Differences between pretreatment and posttreatment degree of stenoses were subjected to 1-way ANOVA for repeated measures. There were 10 men and 2 women, all white, aged 40 to 82 years (mean age, 62.6 years). Stent placement was successful in all patients, leading to statistically significant changes in the degree of stenosis, from 71. 4% (range, 53% to 90%) to 10.3% (range, 0% to 36%) (P<0.0001). There were no deaths, stent thromboses, perforations, ruptures, or myocardial infarctions. Clinical follow-up was available for 0.5 to 16 months (mean, 5.9 months). One patient had nonspecific symptoms, and another had a transient ischemic attack. All other patients remained asymptomatic. Elective stenting of the basilar artery is feasible, with minimal risk to the patient. Its impact on long-term stroke prevention and its durability are unknown and will require further study.


Evolution of corneal epithelial remodeling after myopic laser in situ keratomileusis surgery measured by anterior segment optical coherence tomography combined with Placido disk.
To investigate patterns of short- and long-term variations in corneal epithelial thickness (CET) after myopic laser in situ keratomileusis (LASIK) using anterior segment optical coherence tomography (AS-OCT) combined with Placido disk-based topography. In this retrospective study, 36 subjects (72 eyes) who underwent LASIK myopic surgery and 53 healthy subjects (106 eyes) who served as controls were enrolled. AS-OCT (MS-39) was performed in all patients before, 1 day, 1 month, and 6 months after surgery. Statistical analysis was performed to analyze CET changes over time after LASIK and to detect patterns of definitive CET remodeling compared to healthy subjects. Multivariate analysis was performed to look for possible predictors of final CET. There was no statistically significant difference between groups in terms of demographic and anterior segment parameters (all P > 0.05). After LASIK, all sectors and rings got thicker over time (1.62-8.32 μm; P < 0.01). Except for the central sector, all areas achieved the thickest CET value one day after surgery with a progressive epithelial thinning between 1 and 6 months of follow-up. Changes on CET occurred independently of the grade of myopia before LASIK or final refraction (P > 0.05). None of the clinical variables studied, including diopters corrected, were found to be correlated with final CET (P > 0.05). Independent of anterior segment parameters and diopters corrected, CET becomes thicker after LASIK surgery. Central and inner ring sectors thicken more than those more peripheral. CET remodeling after myopic LASIK should be taken into consideration when planning refractive surgery.


Criticality in the (2+1)-dimensional compact Higgs model and fractionalized insulators.
We use a novel method of computing the third moment M3 of the action of the (2+1)-dimensional compact Higgs model in the adjoint representation with q=2 to extract correlation length and specific heat exponents nu and alpha without invoking hyperscaling. Finite-size scaling analysis of M3 yields the ratios (1+alpha)/nu and 1/nu separately. We find that alpha and nu vary along the critical line of the theory, which however exhibits a remarkable resilience of Z2 criticality. We propose this novel universality class to be that of the quantum phase transition from a Mott-Hubbard insulator to a charge-fractionalized insulator in two spatial dimensions.


Influence of St. Jude medical valve in patients with aortic stenosis and small aortic annulus on cardiac function and late survival result.
This clinical study analyzes our experience of postoperative cardiac function and long-term survival rate in patients with aortic stenosis and small-size St. Jude Medical (SJM) valve. Sixty-eight patients who underwent aortic valve replacement by SJM valve were divided into two groups by preoperative aortic annulus diameter. Group 1 consisted of 44 patients with small aortic annulus and small-size SJM valve (19 mm or 21 mm). In Group 1, small SJM standard valves were implanted in 16 patients, and small SJM Hemodynamic Plus (HP) valves were implanted in 28 patients. Group 2 consisted of 24 patients with large-size SJM standard valve (23 mm or larger). Preoperative left ventricular mass index, left ventricular dimension, the dimension of ascending aorta, and body surface area were significantly smaller in Group 1 than in Group 2. Average age at surgery was older in Group 1 than in Group 2. Effective orifice area index of the SJM valve measured by the manufacturer's data was smaller in Group 1 than in Group 2. Postoperative left ventricular mass indexes of Group 1 (standard valve or HP valve) and Group 2 significantly decreased in comparison with the preoperative mass indexes. Postoperative left ventricular ejection fraction and the peak ejection rate of Group 1 were not different from those of Group 2. The 10 year survival rate of Group 1 was 79%, and the rate of Group 2 was 77%. At 10 years after surgery, freedom from valve-related complication of Group 1 was 80%, and freedom from complication of Group 2 was 81%. Our results demonstrated that small-size SJM valve afforded satisfactory long-term survival rate and valve-related event-free rate for elderly patients with small body surface area and small aortic annulus.


Management of pediatric clival chordoma with extension to the craniocervical junction and occipito-cervical fusion: illustrative case.
Chordomas are rare malignant neoplasms that develop from the primitive notochord with < 5% of the tumors occurring in pediatric patients younger than the age of 20. Of these pediatric chordomas, those affecting the craniocervical junction (C1-C2) are even more rare; therefore, parameters for surgical management of these pediatric tumors are not well characterized. In this case, a 3-year-old male was found to have a clival chordoma on imaging with extension to the craniocervical junction resulting in spinal cord compression. Endoscopic-assisted transoral transclival approach for clival tumor resection was performed first. As a second stage, the patient underwent a left-sided far lateral craniotomy and cervical laminectomy for resection of the skull base chordoma and instrumented fusion of the occiput to C3. He made excellent improvements in strength and dexterity during rehab and was discharged after 3 weeks. In pediatric patients with chordoma with extension to the craniocervical junction and spinal cord compression, decompression with additional occipito-cervical fusion appears to offer a good clinical outcome. Fusion performed as a separate surgery before or at the same time as the initial tumor resection surgery may lead to better outcomes.


Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives.
Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.


Stimulation of endogenous prostacyclin protects the reperfused pig myocardium from ischemic injury.
Several attempts have been undertaken to reduce the severity of ischemic myocardial injury by exogenous administration of eicosanoids and by modification of endogenous eicosanoid production. The present study investigates whether defibrotide, a compound that stimulates endogenous prostacyclin (PGI2), has a beneficial effect in experimental ischemic myocardial injury. Anesthetized, open-chest minipigs were subjected to 1 h of coronary artery occlusion, followed by 3 h of reperfusion. Defibrotide (32 mg/kg x h) or its vehicle were infused i.v. throughout the experiment. Defibrotide increased cardiac PGI2 formation 3- to 4-fold greater than control (P < .05). Thromboxane levels remained unchanged. Irreversible ischemic injury, as identified by negative tetrazolium staining, amounted to 44 +/- 6% of the area at risk in pigs receiving vehicle but was reduced to 23 +/- 4% by defibrotide (P < .05). This reduced tissue injury in defibrotide-treated pigs was associated with improved functional recovery (left ventricular pressure, + dP/dtmax), during early reperfusion. Recovery did not occur in vehicle-treated pigs. Collagen (2 micrograms/ml)-induced platelet aggregation ex vivo was increased in vehicle-treated pigs during ischemia and reperfusion, but not in animals treated with defibrotide. Polymorphonuclear neutrophil leukocyte accumulation in the ischemic border zone was reduced from 59 +/- 17 cells/mm2 in vehicle-treated pigs to 17 +/- 9 cells/mm2 by defibrotide (P < .05). Pretreatment of the animals with indomethacin (3 mg/kg) prevented the reduction of infarct size and polymorphonuclear neutrophil leukocyte infiltration by defibrotide. Indomethacin increased infarct size in vehicle- and defibrotide-treated pigs by 71 and 59%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Selective Methane Oxidation Catalyzed by Platinum Salts in Oleum at Turnover Frequencies of Large-Scale Industrial Processes.
Direct catalytic methane functionalization, a "dream reaction", is typically characterized by relatively low catalyst activities. This also holds for the η(2)-(2,2'-bipyrimidyl)dichloroplatinum(II) [(bpym)PtCl2, 1] catalyst which oxidizes methane to methyl bisulfate in sulfuric acid. Nevertheless, it is arguably still one of the best systems for the partial oxidation of methane reported so far. Detailed studies of the dependence of activity on the SO3 concentration and the interplay with the solubility of different platinum compounds revealed potassium tetrachloroplatinate (K2PtCl4) as an extremely active, selective, and stable catalyst, reaching turnover frequencies (TOFs) of more than 25,000 h(-1) in 20% oleum with selectivities above 98%. The TOFs are more than 3 orders of magnitude higher compared to the original report on (bpym)PtCl2 and easily reach or exceed those realized in commercial industrial processes, such as the Cativa process for the carbonylation of methanol. Also space-time-yields are on the order of large-scale commercialized processes.


Role of developmental overnutrition in pediatric obesity and type 2 diabetes.
Childhood obesity continues to be a significant public health burden. Empirical evidence has begun to identify intrauterine and postnatal pathways that increase the likelihood of excess adiposity and increased risk of type 2 diabetes among offspring. Reviewed here is the evidence supporting a transgenerational vicious cycle that increases obesity and diabetes in offspring and contributes substantially to the increases in obesity and type 2 diabetes observed over the past several decades. The public health impact of these findings is discussed and future research opportunities are outlined.


[Reactions to mirror in three species of lemurs (Lemur fulvus, L. macaco, L. catta)].
Reactions when confronted with their own reflection in a mirror were observed in three captive groups of lemurs: L. fulvus, L. macaco and L. catta. The ability of a mirror to induce social facilitation of drinking was also studied in one individual of each species. As previously observed in monkeys, the three groups of lemurs showed much more attention to the mirror than to a non-reflective surface, especially nasal contacts. Only L. fulvus showed habituation to the mirror with successive presentations. No social behaviours were directed towards the reflection, in contrast to descriptions of mirror-image reactions in monkeys, and the mirror did not produce an effect of social facilitation. The results suggest that the mirror elicits a diminished social reaction in lemurs compared to monkeys, perhaps due to the absence of relevant olfactory stimuli.


Localized Metastatic Recurrence of HCC following Distal Extremity Trauma: Bone Scintigraphy and Anatomicopathological Correlation.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with a poor median survival when left untreated. Extrahepatic metastases involving musculoskeletal tissues typically present with concomitant nonosseous metastases at the time of diagnosis. A 61-year-old male on 1-year remission, following transarterial chemoembolization of a 2.3-cm hepatic HCC 1 year before, presented with a 2-month history of left wrist pain and swelling after falling on an outstretched hand. Computed tomographic scan revealed diffuse osteolytic lesions localized in left hand and distal forearm, associated with equivocal diffuse activity on bone scan. Subsequent surgical debridement revealed metastatic hepatocellular carcinoma.


Vector-Focused Approaches to Curb Malaria Transmission in the Brazilian Amazon: An Overview of Current and Future Challenges and Strategies.
In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been made towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to control or eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put into research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the optimization of conventional and development of innovative vector-control tools.