Algae biorefinery: A promising approach to promote microalgae industry and waste utilization.
Microalgae have a number of intriguing characteristics that make them a viable raw material aimed at usage in a variety of applications when refined using a bio-refining process. They offer unique capabilities that allow them to be used in biotechnology-related applications. As a result, this review explores how to increase the extent to which microalgae may be integrated with various additional biorefinery uses in order to improve their maintainability. In this study, the use of microalgae as potential animal feed, manure, medicinal, cosmeceutical, ecological, and other biotechnological uses is examined in its entirety. It also includes information on the boundaries, openings, and improvements of microalgae and the possibilities of increasing the range of microalgae through techno-economic analysis. According to the findings of this review, financing supported research and shifting the focus of microalgal investigations from biofuels production to biorefinery co-products can help guarantee that they remain a viable resource. Furthermore, innovation collaboration is unavoidable if one wishes to avoid the high cost of microalgae biomass handling. This review is expected to be useful in identifying the possible role of microalgae in biorefinery applications in the future.


Anatomists provide the foundation for learning pathophysiology.
The need for interdisciplinary graduate training programs which prepare students to conceptualize the application of their research in clinical settings continues to grow. Though several programs have been cultivated to address this need, demand still outweighs supply. The following describes a curriculum developed with the intent of incorporating medical knowledge into a PhD graduate training program. Development of this Molecular Medicine program by the Cleveland Clinic Lerner College of Medicine in collaboration with Case Western Reserve University was funded by the Howard Hughes Medical Institute "Med into Grad" initiative. The core curriculum of this program begins with a foundation in Human Physiology and Disease course in which anatomy faculty introduce students to a basic overview of gross anatomy structure and function. This course is followed by five fundamental basic science courses, a composite course focusing on principles of clinical and translation research, a course on laboratory techniques and three, 12-week research rotations. In the second year of the program, students begin their dissertation research, complete their qualifying examination, and partake in an individually tailored Clinical Experience course. Interdisciplinary graduate programs like this provide another venue for faculty in anatomical sciences to help aspiring translational scientists relate basic science knowledge to human pathophysiology and health.


Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation.
Antibody-mediated rejection (AMR) is the leading cause of graft failure. While donor-specific antibodies (DSAs) are associated with a higher risk of AMR, not all patients with DSAs develop rejection, suggesting that the characteristics of alloantibodies determining their pathogenicity remain undefined. Using human leukocyte antigen (HLA)-A2-specific antibodies as a model, we apply systems serology tools to investigate qualitative features of immunoglobulin G (IgG) alloantibodies including Fc-glycosylation patterns and FcγR-binding properties. Levels of afucosylated anti-A2 antibodies are elevated in seropositive patients, especially those with AMR, suggesting potential cytotoxicity via FcγRIII-mediated mechanisms. Afucosylation of both glycoengineered monoclonal and naturally glycovariant polyclonal serum IgG specific to HLA-A2 drives potentiated binding to, slower dissociation from, and enhanced signaling through FcγRIII, a receptor widely expressed on innate effector cells, and greater cytotoxicity against HLA-A2+ cells mediated by natural killer (NK) cells. Collectively, these results suggest that afucosylated DSA may be a biomarker of AMR and contribute to pathogenesis.


Heterocyclic aromatic amine concentrations and quality characteristics of traditional smoked and roasted poultry products on the northern Chinese market.
This study evaluated the heterocyclic aromatic amine (HAA) contents and quality characteristics of seven kinds of traditional smoked and roasted poultry products on the northern Chinese market. Harbin smoked chicken had the most abundant total HAAs, followed by Haroulian roasted chicken and Yishou smoked chicken. The contents of Norharman and Harman were much higher than those of other kinds of HAAs (P < 0.05). The water content of samples varied from 59.01% to 69.98% and the water activity varied from 0.953 to 0.976. The carbonyl content and TBARS values of the Beijing roasted duck and the Duiqing roasted goose were much higher than those of the other samples (P < 0.05). The sensory evaluation result of the Beijing roasted chicken was higher than that of the other samples (P < 0.05). Overall, the levels of HAAs in the industrial smoked and roasted products were lower than those in non-industrial products, which may provide a theoretical basis for the industrial production of smoked and roasted poultry products.


Abnormal steroidogenesis and aromatase activity in preeclampsia.
Estrogens and progesterone play critical roles in angiogenesis and vasodilation. Moreover, placental aromatase deficiency is detected in women with preeclampsia (PE) at delivery. We hypothesized that abnormal steroidogenesis occurs much earlier than typical PE diagnosis. Thus, we investigated whether the circulating steroid profile was already disturbed at 24-29 weeks of gestation in women with subsequent PE, and compared the profile with that of women with "placental" small gestational age (SGA) without PE. We selected nulliparous women (n = 90) from the MOMA trial, including women with PE (n = 25), SGA (n = 25), and controls (NP; n = 40), for plasma steroid profiling by gas chromatography/mass spectrometry and to measure placental growth factor and soluble fms-like tyrosine kinase-1. Placental aromatase expression was evaluated in a new set of women. Compared with that of controls, the women with PE had a significantly lower estrone/androstenedione ratio, and exhibited a decreasing trend for estradiol and estrone levels. Lower estriol levels were observed in the SGA group compared to the NP group. Compared with that of controls, the women with PE and SGA had significantly higher levels of 20α-dihydroprogesterone (20α-DHP) and 20α-DHP/progesterone ratios. Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA groups. Decreased expression of aromatase was observed in the PE group compared to the control group. Preeclampsia appears to be characterized by specific steroidogenesis dysregulation long before PE diagnosis, highlighting potential new biomarkers of PE.


Dataset for genotyping validation of cytochrome P450 2A6 whole-gene deletion (CYP2A6*4) by real-time polymerase chain reaction platforms.
This data article contains a supplementary figure and validation data relating to the research article entitled "Genotyping of wild-type cytochrome P450 2A6 and whole-gene deletion using human blood samples and a multiplex real-time polymerase chain reaction method with dual-labeled probes" (Shimizu et al., Clinica Chimica Acta 441, 71-74, 2015), which presents a multiplex real-time polymerase chain reaction method with dual-labeled probes for human P450 2A6 wild-type and whole-gene deletion. Real-time methods have dramatically improved the speed of complex genetic diagnostics compared to conventional assays based on restriction enzyme digestion. Here, we show the basic assay validation data by single and multiplex determinations in comparison with commercial TaqMan copy number assays for P450 2A6.


Healthcare Professionals' Views of Working with Medical Interpreters in a Cancer Setting: an Exploratory Study.
Australia, like many other nations, continues to become more culturally and linguistically diverse. Medical interpreters play a key role in bridging the linguistic gap between healthcare professionals (HCPs) and patients. Little research exists from the HCP's perspective about working with interpreters. This study aimed to explore the views of HCPs regarding working with interpreters in a cancer setting. This exploratory study utilised a cross-sectional, qualitative design, involving focus groups and semi-structured interviews. HCPs from the Oncology and Palliative Care units were invited to participate and were asked about their experiences of working with interpreters in a cancer setting. Interviews were audio-recorded and transcribed. An inductive thematic analysis of qualitative data derived an understanding of attitudes and beliefs which may affect the way in which HCPs interact with interpreters and patients. Twenty-five participants were recruited. Five key themes emerged from the data: (1) communication practices and preferences, (2) training and supports, (3) alternative methods for translation, (4) challenges faced by HCPs and interpreters, and (5) limitations of translation. Communication with non-English-speaking patients using interpreters could be significantly improved with further training and support for both HCPs and interpreters, and a greater appreciation for the challenges each party faces.


Comparison of the pathologic features and DNA ploidy value of prostate cancers detectable by sonography and by palpation.
Ultrasonography of the prostate detects some cancers that are not palpable, but the pathologic features of such cancers have not been well described. Since screening trials consistently find sonography more sensitive (though less specific) than digital rectal examination, nonpalpable cancers that are visible as hypoechoic lesions on ultrasound have been postulated to be early cancers of limited malignant potential and may not require aggressive treatment. To test this hypothesis, we determined the pathologic features and DNA ploidy value of prostate cancers in 63 radical prostatectomy specimens taken from patients with clinical stage T1 (n = 28) and T2 (n = 35) prostate cancer. In 40 patients (63%), the cancer appeared hypoechoic on ultrasound. The median volume of these cancers was 4.19 cm3 (range 0.45-19.22); 80% exhibited extra-capsular extension (ECE); 30% had seminal vesicle invasion (SVI); and 95% were nondiploid by nuclear image analysis (CAS 200 system). In patients with isoechoic cancer, tumor volume was significantly less (median 0.38 cm3) and ECE and SVI occurred less frequently (13% and 0%, respectively). Only seven (30%) had nondiploid tumors. In 35 patients, the tumor was palpable, and the pathologic features and DNA ploidy values (94% nondiploid) of these cancers were similar to those of the tumors that were visible on ultrasound. In seven patients, the cancer was visible by ultrasound but not palpable by digital rectal examination. Median tumor volume was 1.72 cm3 (range 0.45-18.98); four patients (57%) had ECE; one (14%) had SVI, and six (86%) had nondiploid cancers. We conclude that most cancers that appear hypoechoic on ultrasound are clinically important and exhibit aggressive pathologic features. Palpable cancers and sonographically visible cancers are similar and should be staged and treated similarly.


Asymmetric synthesis of antimitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells.
The (S,S)-enantiomer of combretadioxolane (3), designed as a chirally preorganized derivative of combretastatin A-4, exhibited quite strong tubulin polymerization-inhibitory activity (IC50: 4-6 microM). (S,S)-3 is 20 times more potent than vincristine as an in vitro growth inhibitor (in terms of GI50) of the multi-drug-resistant (MDR) cell line PC-12, which produces P-glycoprotein.


The value of intraoperative ultrasonography in neurosurgery.
Intraoperative ultrasonography is widely used in neurosurgery today. Here we attempt to clarify and demonstrate its usefulness in the operating room. Of 113 lesions, 112 were detected during surgery. The undetected lesion was a spinal arachnoid hematoma that had been absorbed during an intraoperative maneuver. No infection or complication occurred after surgery. Ultrasound guidance ensures safe tumor removal by minimizing injury to cerebral tissue and shortening operation time. Intraoperative ultrasonography improves the safety and efficiency of neurosurgery.


Resonant X-ray emission with a standing wave excitation.
The Borrmann effect is the anomalous transmission of x-rays in perfect crystals under diffraction conditions. It arises from the interference of the incident and diffracted waves, which creates a standing wave with nodes at strongly absorbing atoms. Dipolar absorption of x-rays is thus diminished, which makes the crystal nearly transparent for certain x-ray wave vectors. Indeed, a relative enhancement of electric quadrupole absorption via the Borrmann effect has been demonstrated recently. Here we show that the Borrmann effect has a significantly larger impact on resonant x-ray emission than is observable in x-ray absorption. Emission from a dipole forbidden intermediate state may even dominate the corresponding x-ray spectra. Our work extends the domain of x-ray standing wave methods to resonant x-ray emission spectroscopy and provides means for novel spectroscopic experiments in d- and f-electron systems.


Effect of bacterial association on virulence of Entamoeba histolytica to baby hamster kidney cell monolayers.
Axenic E. histolytica trophozoite strain NIH:200 and HMI:IMSS when co-associated with aerobic bacteria Escherichia coli strain K12 and serotype 056 showed marked increase in virulence as observed by destruction of baby hamster kidney (BHK) monolayers. However, when incubated with anaerobic bacterial strains Clostridium perfringens and Bacteroides fragilis virulence remained unaltered. Further, adherence of E. histolytica to BHK monolayer was found to be mediated by N-acetyl-D-galactosamine.


Significance of prophylactic modified radical neck dissection for patients with low-risk papillary thyroid carcinoma measuring 1.1-3.0 cm: first report of a trial at Kuma Hospital.
Papillary thyroid carcinoma (PTC) frequently metastasizes to and recurs in regional lymph nodes. Of the two compartments, the central compartment can be dissected through the same wound as the thyroidectomy, and the central node dissection (CND) is routinely performed in most Japanese surgical departments. However, the indications for prophylactic lateral compartment dissection (modified radical neck dissection [MND]) for low-risk PTC remain unclear. In this study, we investigated the indications for prophylactic MND for PTC patients with tumor measuring 1.1-3.0 cm without significant extrathyroid extension or distant metastasis. We investigated the lymph node disease-free survival (LN-DFS) rates of 829 patients who underwent CND and of 414 patients who underwent MND and CND between 2005 and 2007 at Kuma Hospital. The LN-DFS of these two groups was not significantly different. In the subset of patients with CND only, clinical central node metastasis (N1a) significantly predicted a worse LN-DFS. All N1a patients recognized as showing recurrence developed such recurrence in the lateral compartment. Other conventional prognostic factors, such as sex and age, were not related to LN-DFS. Taken together, N1a patients with low-risk PTC measuring 1.1-3.0 cm can be considered as candidates for prophylactic MND.


Nasopharyngeal lymphoepithelioma. Histological diagnosis as aided by immunohistochemical demonstration of keratin.
Eight cases of primary and metastatic nasopharyngeal lymphoepithelioma and four cases of malignant lymphoma of the pharyngeal region were studied for the presence of keratin by indirect immunofluorescence microscopy. The results showed that all the cases of primary and metastatic lymphoepithelioma contained keratin-positive cells, whereas all the lymphomas were negative for keratin. Anti-keratin antibody thus seems to be a valuable aid in the differential diagnosis between lymphoepithelioma and lymphoma.


Topical sodium cromoglycate (Opticrom) relieves ongoing symptoms of allergic conjunctivitis within 2 minutes.
Twelve patients with seasonal allergic conjunctivitis caused by either birch or timothy grass pollen were challenged out of season in both eyes, with the relevant allergen. Itching, redness, swelling, and tearing were assessed on a 0-3 scale. When a positive reaction, i.e., at least 4 points, had occurred in both eyes, one drop of 2% sodium cromoglycate was administered to one eye and one drop of placebo to the other eye in each patient, in a double-blind, randomized fashion. Symptoms were then assessed after 2, 10, 30, and 60 min. Sodium cromoglycate was statistically better than placebo in reducing the symptoms at 2, 10, and 30 min after the treatment had been administered, showing that topical application of 2% sodium cromoglycate can quickly relieve ongoing symptoms of allergic inflammation in the eye.


Single nucleotide polymorphism array analysis uncovers a large, novel duplication in Xq13.1 in a floppy infant syndrome patient.
To identify candidate genes for the clinical diagnosis of floppy infant syndrome (FIS) using single nucleotide polymorphism (SNP) array in a specific FIS family. SNP array analysis of the whole chromosome copy number was performed in the proband (III1). Multiple polymerase chain reaction (PCR) combined with denaturing high-performance liquid chromatography (DHPLC) was used to validate the array data. A large 5.818182 Mb duplication (Xq13.1: 67987646-73805828), which encompasses 66 known genes, was found in III1. The start and end points of the duplication were confirmed with an SNP array. Duplicated genes with potential roles in central and/or peripheral nervous system development (HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1, and SLC16A2) were confirmed by multiple PCR-DHPLC in III1. The patient's mother and grandmother carry duplications in these eight genes, but only on one X chromosome, while the patient's aunt does not carry any of the duplications. Based on the location of the eight candidate genes in Xq13.1, the large duplication found by SNP array does indeed exist and is predicted to be both novel and pathogenic. Moreover, we recommend SNP array as the first option for genetic diagnosis of both large-scale and rare/complicated diseases, such as FIS.


Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis.
Sulfur mustard "bis (2-chlroethyl) sulphide" (SM) is a chemical warfare agent that remains a threat to human health. The aim of this study was to identify protein expression signature or biomarkers that reflect chronic lung damages induced by SM exposure. Prior to analysis, plasma was fractionated using ethanol precipitation. Using two dimensional SDS-PAGE; fractionated protein profiles of 20 healthy and 20 exposed patients with lung diseases were established. Selected protein spots were successfully identified with MALDI TOF MS/MS. The results show that α1 haptoglobin isoforms were detected in plasma of the all lung disease patients but none of the healthy controls. Amyloid A1 isoforms was also detected in plasma of the lung disease patients but none of the healthy controls. Moreover, low molecular weight proteins were enriched in ethanol supernatant compared to ethanol precipitate. Our present results and previous studies suggest that ongoing tissue remodeling is involved in SM exposed lung damage patients. These finding might improve patient care and suitable therapies.


[Target volumes in radiotherapy - head and neck tumors intensity - modulated radiation therapy (IMRT) of nasopharyngeal carcinoma: practical aspects in the delineation of target volumes and organs at risk].
The objective of this paper is to give some practical landmarks for the delineation of target volumes and organs at risk in Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma. This delineation, drawn from anatomo-clinical data, natural history of the disease and radiological pre-treatment evaluation, seems to be easier to define than the delineation of other head and neck cancer localisations (oropharynx and oral cavity for example). Experience inside national and international cooperative groups should tend to standardize this initial and fundamental step of Nasopharyngeal Conformal Radiotherapy.


Risk management actions following genetic testing in the Cancer Health Assessments Reaching Many (CHARM) Study: A prospective cohort study.
Genetic testing can identify cancer risk early, enabling prevention and early detection. We describe use of risk management interventions following genetic testing in the Cancer Health Assessment Reaching Many (CHARM) study. CHARM assessed risk and provided genetic testing to low income, low literacy, and other underserved populations that historically face barriers to accessing cancer genetic services. CHARM was implemented in Kaiser Permanente Northwest (KPNW) and Denver Health (DH) between 2018 and 2020. We identified post-testing screening (mammography, breast MRI, colonoscopy) and surgical (mastectomy, oophorectomy) procedures using electronic health records. We examined utilization in participants who did and did not receive actionable risk management recommendations from study genetic counselors following national guidelines. CHARM participants were followed for an average of 15.4 months (range: 0.4-27.8 months) after results disclosure. Less than 2% (11/680) received actionable risk management recommendations (i.e., could be completed in the initial years following testing) based on their test result. Among those who received actionable recommendations, risk management utilization was moderate (54.5%, 6/11 completed any procedure) and varied by procedure (mammogram: 0/3; MRI: 2/4; colonoscopy: 4/5; mastectomy: 1/5; oophorectomy: 0/3). Cancer screening and surgery procedures were rare in participants without actionable recommendations. Though the number of participants who received actionable risk management recommendations was small, our results suggest that implementing CHARM's risk assessment and testing model increased access to evidence-based genetic services and provided opportunities for patients to engage in recommended preventive care, without encouraging risk management overuse.


Headache. Diagnosing subarachnoid hemorrhage: are CT scans enough?
Subarachnoid hemorrhage is a rare but potentially fatal cause of headache. According to results from a recent study, CT scans enable clinicians to identify patients with subarachnoid hemorrhage, with a high sensitivity. Does CT imaging rule out the need for lumbar puncture in patients who present with headache?


Vagal neural crest provides inhibitory neurotransmission to the chick embryo cloaca.
The intrinsic innervation of the developing chick cloaca originates in the vagal and sacral regions of the neural tube. Its major inhibitory neurotransmitters are nitric oxide (NO) and vasoactive intestinal peptide (VIP). It has previously been shown that the majority of neurons in the chick embryo cloaca are derived from vagal neural crest cells. This study aimed to identify the phenotype of these vagal-derived neurons using quail-chick chimeras. Chicken embryos were incubated until the 10-12 somite stage. The vagal neural tube was then microsurgically ablated in ovo and replaced with the vagal neural tube from age-matched quail embryos. Quail-chick chimera embryos were harvested at E12, and E14, and fixed and embedded in paraffin wax, and serially sectioned. Immunohistochemistry was performed using human natural killer-1 (HNK-1), quail-cell-specific perinuclear (QCPN), NOS and VIP antibodies. Expression of NOS and VIP neurons in the developing chick embryo cloaca was also further analysed using immunohistochemistry. HNK-1 labelled all ganglia in the myenteric and submucosal plexuses of the cloaca, whilst the quail-specific QCPN antibody labelled all ganglia derived from the transplanted quail vagal neural tube. NOS- and VIP-immunoreactive neurons appeared to make up a large proportion of the quail-derived vagal neural crest cells. Both NOS and VIP expression was seen to increase throughout development. This data suggests for the first time that the inhibitory neurons in the chick cloaca primarily originate in the vagal neural crest, thus providing new insights into the developmental origin of the intrinsic innervation of the developing cloaca.


Have a little faith: measuring the impact of illness on positive and negative aspects of faith.
The importance of faith and its associations with health are well documented. As part of the Patient Reported Outcomes Measurement Information System, items tapping positive and negative impact of illness (PII and NII) were developed across four content domains: Coping/Stress Response, Self-Concept, Social Connection/Isolation, and Meaning and Spirituality. Faith items were included within the concept of meaning and spirituality. This measurement model was tested on a heterogeneous group of 509 cancer survivors. To evaluate dimensionality, we applied two bi-factor models, specifying a general factor (PII or NII) and four local factors: Coping/Stress Response, Self-Concept, Social Connection/Isolation, and Meaning and Spirituality. Bi-factor analysis supported sufficient unidimensionality within PII and NII item sets. The unidimensionality of both PII and NII item sets was enhanced by extraction of the faith items from the rest of the questions. Of the 10 faith items, nine demonstrated higher local than general factor loadings (range for local factor loadings = 0.402 to 0.876), suggesting utility as a separate but related 'faith' factor. The same was true for only two of the remaining 63 items across the PII and NII item sets. Although conceptually and to a degree empirically related to Meaning and Spirituality, Faith appears to be a distinct subdomain of PII and NII, better handled by distinct assessment. A 10-item measure of the impact of illness upon faith (II-Faith) was therefore assembled.


Effects of sympathectomy on experimentally induced pulpal inflammation and periapical lesions in rats.
The role of sympathetic nerves in bone physiology is largely unknown. Recent studies have shown a correlation between sympathectomy and bone remodeling. The present experiments were aimed to study the effects of unilateral sympathectomy on bilateral experimentally induced pulpitis and periapical lesions in the rat maxilla and mandible. Adult male Sprague-Dawley rats were used. Experimental rats (n=11) had the right superior cervical ganglion surgically removed (SCGx) and control rats (n=5) had sham surgery. Pulpal inflammation and periapical bone lesions in the maxilla and mandible were created 14 days later in both experimental and control rats by exposing the dental pulp in the first and second molars and leaving them open to the oral microflora. The rats were perfused 20 days thereafter and the jaws processed for immunohistochemistry with neuropeptide Y (NPY) and ED1 as primary antibodies. Sympathectomy resulted in an almost complete loss of NPY-immunoreactive (IR) fibers in the right SCGx jaws. In the non-sympathectomized (non-SCGx) left side and in the control rats, sprouting of NPY-IR fiber was observed in the inflamed pulp tissue adjacent to reparative dentin formation and in the apical periodontal ligament of the partially necrotic first molars. Significantly more ED1-IR osteoclasts were found in the resorptive lacunae lining the periphery of the periapical lesions on the SCGx side compared with the non-SCGx side (P<0.04) and the controls (P<0.03). The size of the periapical lesions were larger on the SCGx side compared with the non-SCGx side (P<0.03) in the mandible, but not in the maxilla. We conclude that inflammation causes sprouting of NPY-IR nerve fibers and that unilateral removal of the SCG increases both the area of the periapical lesions and the number of osteoclasts in the inflamed region.


A prospective clinical analysis of pain behavior and self-injurious behavior.
It is a widely assumed but rarely tested proposition that the experience and expression of pain is altered among individuals with self-injurious behavior and disabilities. As a preliminary test of this proposition, the purpose of this case study was to apply a validated pain measure to examine ratings of pain behavior in relation to ratings of self-injurious behavior (SIB). A prospective correlational design was used with maternal ratings completed three times/day for 9 days using two item independent rating scales specific to pain and SIB. The participant was a 6-year-old boy with severe SIB secondary to midbrain tumor (pilocytic astrocytoma) resection and post-operative sequelae. Measures were taken in the child's home. Pain behavior was measured using the Non-Communicating Children's Pain Checklist Revised (NCCPC-R). Self-injury was measured using the Self-Injury Trauma Scale (SITS). Time intervals associated with elevated ratings of SIB were associated with elevated pain ratings. There was a significant difference (P<0.05) for pain ratings between time intervals with and without self-injury. It is suggested that additional empirical work is needed to clarify the relation between pain and self-injury to improve assessment and treatment outcomes.


Gas chromatography-mass spectrometry and the measurement of vitamin D metabolites in human serum or plasma.
Although methods for the measurement of vitamin D metabolites continue to be developed, few have been properly validated by comparison with methods based on gas chromatography-mass spectrometry, widely accepted as being the definitive methodology. To the best of our knowledge, only three such comparisons have been carried out (14, 42, 83), all three examining HPLC assays for 25-OH-D. This lack of proper validation leads to lack of certainty as to the specificity of many assays widely used for clinical investigation. In our view there is an obvious need for the continuing development of mass fragmentographic assays for vitamin D and its metabolites, primarily for use as reference procedures for the evaluation of less rigorous methodologies. Provided standards, both labeled and unlabeled, become more widely available, development of specific mass fragmentographic assays for any metabolite of vitamin D should be possible. For metabolites where no specific binding protein or antiserum is available, mass fragmentography may be the only alternative.


Six cases of leprosy associated with allogeneic hematopoietic SCT.
We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases.


Oxygen dissociation after transfusion of blood stored in ACD or CPD solution.
In 20 patients undergoing open-heart surgery, 2,3-diphosphoglycerate (2,3-DPG) concentrations, oxygen affinity of hemoglobin (Po2 at half saturation of hemoglobin with oxygen [P50]), hemoglobin concentration, and pH were measured repeatedly. Measurements were made before and at various times after open-heart surgery and replacement of blood loss with blood stored in acid-citrate-dextrose (ACD) or citrate-phosphate-dextrose (CPD) solutions for less than 72 hours (10 cases per group). Infusion of ACD blood caused P50 and 2,3-DPG concentration to decrease significantly after the operation. The infusion of blood stored in CPD did not significantly increase the oxygen affinity. No significant changes in hemoglobin concentration or pH were observed immediately after the operation in either group. To compensate for the increased oxygen affinity, there must be a rise in cardiac output or more likely a decrease in venous Po2. The transfusion of CPD blood, therefore, is more favorable in terms of oxygen supply, particularly in patients who have had cardiac surgery.


Computer algebra and the study of unconventional electron lenses.
The calculation of aberration coefficients, and even the derivation of paraxial equations, can involve an immense volume of elementary algebraic manipulation; the use of a computer to lighten this task for some unconventional electron lens types is described.


[The Freiburg speech intelligibility test : A pillar of speech audiometry in German-speaking countries].
The Freiburg speech intelligibility test according to DIN 45621 was introduced around 60 years ago. For decades, and still today, the Freiburg test has been a standard whose relevance extends far beyond pure audiometry. It is used primarily to determine the speech perception threshold (based on two-digit numbers) and the ability to discriminate speech at suprathreshold presentation levels (based on monosyllabic nouns). Moreover, it is a measure of the degree of disability, the requirement for and success of technical hearing aids (auxiliaries directives), and the compensation for disability and handicap (Königstein recommendation). In differential audiological diagnostics, the Freiburg test contributes to the distinction between low- and high-frequency hearing loss, as well as to identification of conductive, sensory, neural, and central disorders. Currently, the phonemic and perceptual balance of the monosyllabic test lists is subject to critical discussions. Obvious deficiencies exist for testing speech recognition in noise. In this respect, alternatives such as sentence or rhyme tests in closed-answer inventories are discussed.


Germacrane sesquiterpenes from leaves of Eupatorium chinense inhibit protein tyrosine phosphatase.
Three new germacrane-type sesquiterpene lactones (1-3) were isolated alongside seven known related congeners (4-10) from the leaves of Eupatorium chinense L. (Compositae). The planar structures of 1-3 were elucidated by their spectroscopic data, including 1D and 2D NMR spectra. The relative and absolute configurations of 1-3 were determined using NOESY experiments and electronic circular dichroism analyses. Compounds 1, 4, 5, and 7 inhibited protein tyrosine phosphatase (PTP) 1B activity with IC50 values of 25, 11, 28, and 24 μM, respectively. Among these, compound 4 exhibited an inhibitory effect on T-cell PTP (TCPTP) with an IC50 value of 25 μM. To our knowledge, this is the first study demonstrating the PTP inhibitory activity of the germacrane sesquiterpenes. The results show that compound 4 acts as an inhibitor of both PTP1B and TCPTP.


In-source H/D exchange and ion-molecule reactions using matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry with pulsed collision and reaction gases.
Controlled in-source ion-molecule reactions are performed for the first time in an external matrix assisted laser desorption ionization (MALDI) source of a Fourier transform ion cyclotron resonance mass spectrometer. The MALDI source with a hexapole ion guide that was originally designed to incorporate pulsed gas to collisionally cool ions (Baykut, G.; Jertz, R.; Witt, M. Rapid Commun. Mass Spectrom. 2000, 14, 1238-1247) has been modified to allow the study of in-source ion-molecule reactions. Upon laser desorption, a reaction gas was introduced through a second inlet and allowed to interact with the MALDI-generated ions trapped in the hexapole ion guide. Performing ion-molecule reactions in the high pressure range of the ion source prior to analysis in the ion cyclotron resonance (ICR) cell allows to maintain the ultra high vacuum in the cell which is crucial for high mass resolution measurements. In addition, due to the reaction gas pressure in the hexapole product ion formation is much faster than would be otherwise possible in the ICR cell. H/D exchange reactions with different peptides are investigated, as are proton-bound complex formations. A typical experimental sequence would be ion accumulation in the hexapole ion guide from multiple laser shots, addition of cooling gas during ion formation, addition of reaction gas, varied time delays for the ion-molecule reactions, and transmission of the product ions into the ICR cell for mass analysis. In this MALDI source H/D exchange reactions for different protonated peptides are investigated, as well as proton-bound complex formations with the reaction gas triethylamine. Amino acid sequence, structural flexibility and folding state of the peptides can be seen to play a part in the reactivity of such ions.


The saphenous venous flap.
Eight cases, in which a new single-pedicled venous flap, based on the long saphenous vein, was used to close defects around the knee, are presented with the details of indications, size and survival. Of the eight cases, seven achieved their aim; five flaps survived completely, two had partial distal loss and one died completely. This clinical work is further confirmation that fasciocutaneous island flaps of fairly large dimensions, with a single cephalad vein, survive and can be used to cover defects in their adjacent areas.


A simple and practical assay for the antigen-specific detection of platelet antibodies.
The antigen-specific assays currently used for characterization of platelet (PLT)-reactive auto- and alloantibodies are too technically complex and impracticable for most routine laboratories. Here, a novel antigen-specific particle assay (ASPA) for PLTs similar to that of red blood cells is described. PLTs were solubilized and then incubated with red-dyed polystyrene particles coated with monoclonal antibodies (MoAbs) to various PLT glycoprotein complexes. These particles were directly tested for coating with autoantibodies (n = 8) or indirectly tested for serum autoantibodies (n = 33) or alloantibodies against HPA-1a (n = 4) or HPA-5b (n = 5). Serum samples from healthy blood donors (n = 100) served as negative controls. Negative reactions were clearly distinguishable from positive reactions, and the results of the particle assay were in concordance with those obtained by the standard MoAb-specific immobilization of PLT antigen assay (MAIPA) in all cases with alloanti-bodies. In three patients, only the ASPA was able to detect autoantibodies that were completely undetectable by the MAIPA. In contrast, in only one patient, the MAIPA detected autoantibodies that the ASPA failed to detect. In our opinion, the new ASPA is reliable, yet less complex and time-consuming than the currently available assays, and it can be implemented in any routine laboratory.


Evaluation of a clinical aberrometer for lower-order accuracy and repeatability, higher-order repeatability, and instrument myopia.
Refractive surgery has stimulated the development of aberrometers, which are instruments that measure higher-order aberrations. The purpose of this study was to test one clinical aberrometer, the Complete Ophthalmic Analysis System (COAS), for its accuracy, repeatability, and instrument myopia for measuring sphere and astigmatism and its repeatability for measuring higher-order aberrations. Aberrations of 56 normal eyes (28 subjects) were measured with and without cycloplegia using a COAS, a conventional autorefractor and by subjective refraction. We evaluated lower-order accuracy (sphere and astigmatism) of the COAS and autorefractor by comparing that data with that of subjective refraction. We also tested COAS lower- and higher-order repeatability for 5 measurements taken in less than 1 minute. We evaluated instrument myopia by comparing cycloplegic and noncycloplegic measurements of the same eye. Data were analyzed for a 5.0-mm-diameter pupil. Mean COAS spherical error was between -0.1 and +0.4 diopters (D), depending on cycloplegia and the kind of sphere power computation selected. Cylinder power errors were less than 0.1 D. COAS repeatability coefficients were better than 0.25 D, and instrument myopia was less than 0.4 D. These were comparable with those of autorefraction. Higher-order repeatability was sufficient to allow reliable measurement of normal third-order aberrations and spherical aberration. Accuracy, repeatability, and instrument myopia of the COAS are similar to those of a conventional autorefractor. Accuracy and repeatability are also similar to those of subjective refraction. Like an autorefractor, the COAS provides instantaneous, objective measurements of sphere and astigmatism, but it also measures higher-order aberrations. We found that it is capable of reliably measuring problematic higher-order aberrations and is therefore a valuable asset for modern clinical eye care.


Gestational diabetes mellitus induces placental vasculopathies.
Gestational diabetes mellitus (GDM) poses significant long- and short-term risks to both the developing fetus and the mother. GDM can lead to maternal complications during pregnancy and increase the mother's risk of developing type 2 diabetes mellitus and cardiovascular disease later. The present study aimed to evaluate the maternal and fetal vasculopathies in the placenta of Saudi women with GDM. This prospective study examined 84 placentas from full-term pregnant women with no complications other than GDM; 40 placentas were collected from healthy women (controls), and 44 were collected from women diagnosed with GDM. The sampling took place in King Saud University Medical City, Riyadh, between January and August 2019. All placentas were histologically examined according to the Amsterdam Placental Workshop Group (2014, 2015). The results showed that the most common placental changes on the maternal side of the placenta in the GDM group were significant syncytial knots (77%), calcification (70%), villous agglutination (57%), decidual vasculopathy (43%), and retroplacental hemorrhage (34%). Placental infarction was the least common placental change in both groups. On the fetal side, vasculopathies included significant villous fibrinoid necrosis (70.5%), chorangiosis (50%), fibromuscular sclerosis (50%), and villous edema (38.6%). Significant villous fibrinoid necrosis, villous edema, and significant fibromuscular sclerosis were more prevalent in the GDM group. The present study concluded that gestational diabetes mellitus induces histopathological phenotypes in the full-term placenta. Increased decidual vasculopathy, syncytial knots, retroplacental hemorrhage, classification, villous agglutination, chorangiosis, villous edema, villous fibroid necrosis, and fibromuscular sclerosis may indicate GDM in the mother. Such findings in the placenta of a woman who has not been diagnosed with GDM increase the need for GDM examination in future pregnancies.


Neutral losses: a type of important variables in prediction of branching degree for acyclic alkenes from mass spectra.
Neutral losses are a type of important variables in mass spectral interpretation. Since it is hard to calculate or extract neutral losses from mass spectra, they are usually discarded. In this study, dissimilarity analysis was employed to extract mass spectral characteristics for predicting branching degree of acyclic alkenes. The relationships between branching degree and neutral loss were constructed under direction of experimental observation and mass spectral fragmentations. A branching degree predictor of acyclic alkenes was subsequently built based on the above relationships. After tested by the experimental data in previous studies, the predictor could correctly provide the branching degree from abundant ions of mass spectra. More importantly, this predictor was able to point out which acyclic alkenes could be predicted correctly or not.


First detection of the Africa/Caribbean/Latin American subtype of Culex flavivirus in Asian country, Taiwan.
Culex flavivirus (CxFV), a member of the genus flavivirus, is a novel insect-specific flaviviruses that can be divided into two subtypes, the cytopathic Asia/U.S. and the noncytopathic Africa/Caribbean/Latin American subtypes. The CxFV circulates in several Asian countries, and here we conducted the first study investigating CxFV in Taiwan. A total of 14,016 mosquitoes were collected between 2010 and 2012 and 3.4% (6/179) of the pools were CxFV-positive. The phylogenetic analyses indicate that the Taiwan isolates are closely related to the Africa/Caribbean/Latin American subtype, but form an independent cluster. In the cytology experiments, the CxFV Taiwan isolate infected only mosquito cells and caused cell-cell fusion that might be associated with a unique glycine residue at position 117 within the envelope protein, which is shared with the cytopathic effect-causing Asia/US subtype. This study marks the first time the Africa/Caribbean/Latin American subtype of CxFV has been identified in an Asian country and grouped into a novel cluster.


Inhibition of AMPK through Lyn-Syk-Akt enhances FcεRI signal pathways for allergic response.
AMPK was shown to negatively regulate FcεRI activation, and FcεR-mediated Fyn activation can counteract the LKB1/AMPK axis in mast cells. However, the relationship between the major Src family kinase Lyn and AMPK remains poorly defined. Here, we investigate the molecular mechanism for AMPK inhibition by FcεRI-Lyn signaling in rat RBL-2H3 cells. We found that FcεRI activation could rapidly inhibit AMPK activation through increased AMPK phosphorylation at the inhibitory Ser485/491 residues without a change at the activating Th172 residue, and this was accompanied by a reduction of ACC phosphorylation. Using specific inhibitors and gene silencing, we found that such AMPK inhibition involved a signaling cascade through Lyn-Syk-Akt. When AMPK was activated by AICAR, A769662 and metformin, FcεRI-mediated Syk, ERK, JNK and p38 activation, and TNFα release were all inhibited. Consistently, AMPK inhibition by compound C increased FcεRI-mediated Lyn activation. Moreover, AMPK activation dominantly impaired IgE-induced recruitment of signal proteins to the FcεRI by blocking the formation of FcεRIβ-Lyn-Syk, FcεRIγ-Lyn-Syk, and AMPK-FcεRIβ complexes. In vitro kinase assay further revealed the ability of AMPKα2 to phosphorylate FcεRIβ in the complex. In vivo, AMPK activation by metformin could readily reduce vascular permeability and ear swelling in a mouse model of passive cutaneous anaphylaxis mediated by IgE. In summary, our findings demonstrate that IgE-mediated FcεRI activation results in AMPK inhibition through activation of Lyn-Syk-Akt pathway, and as such FcεRI receptor can efficiently propagate Lyn-mediated allergic signaling and response. These results provide important insights into the use of AMPK activators for the treatment of allergic diseases. AMPK is inhibited by FcεRI via Lyn-Syk-Akt signaling in RBL-2H3 cells. AMPK inhibition supports FcεRI-mediated Lyn signaling and allergic response. Metformin has inhibitory effect on passive cutaneous anaphylaxis.


Follow-up magnetic resonance imaging in Hallervorden-Spatz disease.
Bilateral high signal emitting areas in the globus pallidus surrounded by low signal emitting areas have been described as a typical MRI finding in Hallervorden-Spatz disease (HSD). We made a diagnosis of HSD in an 11-year-old girl with progressive dystonia of 4 years duration who showed these typical MRI abnormalities. An initial MRI at the age of 9 was normal. Pathological confirmation of these typical MRI findings has not yet been described, but earlier reports as well as our case suggest that MRI may be helpful in making a clinical diagnosis of HSD. This case further shows that MRI may be normal in an early stage of the disease.


Low-loss plasmonic metamaterial based on epitaxial gold monocrystal film.
We demonstrate high-finesse plasmonic metamaterial with strong resonant response in the near-IR spectral range fabricated using a thin low-loss film of gold monocrystal. The monocrystal was grown using specially formulated simplified crystal growth procedure based on epitaxial deposition, which makes it readily accessible to both plasmonics and metamaterials communities.


Cholangiocarcinoma.
Cholangiocarcinoma may arise in the small bile ducts within the liver or in the large ducts in the hilum or the extrahepatic biliary tree. Curative surgical excision is being increasingly attempted for tumours at all sites and the best results are achieved with cancer at the lower end of the common bile duct. Palliative bypass surgery to drain the biliary tree gives good symptomatic relief and may provide prolonged survival because these tumours are often slow growing. Radiotherapy deserves more extensive trials since about 50 per cent of patients derive benefit. The results of treatment with cytotoxic drugs are so far disappointing.


Clinical study of multifactorial diagnosis in prostate biopsy.
To study the feasibility of using an artificial intelligence (AI) algorithm for the diagnosis of clinically significant prostate cancer (csPCa) on multiparametric MRI (mpMRI) in combination with conventional clinical information. A retrospective study cohort with 505 patients was collected, with complete information on age (≤60, 60-80, and >80 years), PSA (≤4, 4-10, and >10 ng/dL), and pathology results. The patients with ISUP group >2 were classified as csPCa, and the patients with ISUP = 1 or no evidence of prostate cancer were classified as non-csPCa. The diagnosis of mpMRI was made by experienced radiologists following the prostate imaging reporting and data system (PIRADS ≤ 2, PIRADS = 3, and PIRADS > 3). The mpMRI images were processed by a homemade AI algorithm, and the AI results were obtained as positive or negative for csPCa. Two logistic regression models were fitted, with pathological findings as the dependent variable, that is, a conventional model and an AI model. The conventional model used age, PSA, and PIRADS as the independent variables. The AI model took the AI result and the abovementioned clinical information as the independent variables. The predicted probability of the patients from the conventional model and the AI model were used to test the prediction efficacy of the models. The DeLong test was performed to compare differences in the area under the receiver operating characteristic (ROC) area under the curve (AUC) between the conventional model and the AI model. In total, 505 patients were included in the study; 280 were diagnosed with csPCa, and 225 were non-csPCa. The median age was 72.0 (67.0, 76.0) years, with a median PSA value of 13.0 (7.46, 27.5) ng/dL. Statically significant differences were found in age, PSA, PIRADS score and AI results between the csPCa and non-csPCa groups (all p < 0.001). In the multivariable regression models, all the variables were independently associated with csPCa. The conventional model (R2 = 0.361) and the AI model (R2 = 0.474) were compared with analysis of variance (ANOVA) and showed statistically significant differences (χ2 = 63.695, p < 0.001). The AUC of the ROC curve for the conventional model was 0.782 (95% confidence interval [CI]: 0.742-0.823), which was less than the AUC of the AI model with statistical significance (0.849 [95% CI: 0.815-0.883], p < 0.001). In combination with routine clinical information, such as age, PSA, and PIRADS category, adding information from the AI algorithm based on mpMRI could improve the diagnosis of csPCa.


A case report: special needs of hospitalized elders.
A case report is used to discuss common problems and complications of hospitalized elders. The report also illustrates the need for proactive hospital staff who are knowledgeable about the special needs of the aging population if this group is to be cared for successfully. The geriatric resource nurse model involves informal unit-based education aimed at expanding staff nurses' geriatric knowledge and is one of several models sponsored by the Hartford Foundation to improve care of the hospitalized elderly. Teaching rounds between geriatric resource nurses and advanced practice nurses are a primary feature of this model.


[Estrogen receptor gene polymorphism and its association with clinicopathological manifestation of lupus nephritis].
To investigate the distribution of estrogen receptor (ER) in patients with lupus nephritis (LN), and the association between ER gene polymorphism and the clinical and pathological features of the disease. The Pvu II and Xba I restriction fragment length polymorphism (RFLP) of estrogen receptor gene were analyzed in 245 biopsy proven LN patients (58 males and 187 females) and 172 normal controls(101 males and 71 females) by PCR-RFLP. The clinical and pathological features of 49 male and 152 female LN patients with genotype PpXx or Ppxx, ppxx were then analyzed respectively. It was found that genotype PpXx and ppxx, Ppxx were three major genotypes of ER gene in both lupus patients group and control group. The distribution of ER gene polymorphism was quite different in lupus patients of different genders. The frequency of the PpXx genotype was significantly higher in male LN patients than in both the gender matched normal controls (P<0.05) and the female LN patients (P<0.05), while no difference was shown in the frequency of PpXx genotype between female LN patients and female controls. Interestingly, varied clinical and renal pathological features were also demonstrated in female patients with different genotypes of ER gene. The distribution of ER gene polymorphism in LN patients varies with gender. The PpXx genotype of ER gene may be associated with the susceptibility of LN in male. ER gene polymorphism is probably one of the genetic factors contributing to the development of clinical heterogeneity and sexually dimorphic manifestations of LN.


A conductive self healing polymeric binder using hydrogen bonding for Si anodes in lithium ion batteries.
A ureido-pyrimidinone (UPy)-functionalized poly(acrylic acid) grafted with poly(ethylene glycol)(PEG), designated PAU-g-PEG, was developed as a high performance polymer binder for Si anodes in lithium-ion batteries. By introducing both a ureido-pyrimidinone (UPy) unit, which is capable of self-healing through dynamic hydrogen bonding within molecules as well as with Si, and an ion-conducting PEG onto the side chain of the poly(acrylic acid), this water-based self-healable and conductive polymer binder can effectively accommodate the volume changes of Si, while maintaining electronic integrity, in an electrode during repeated charge/discharge cycles. The Si@PAU-g-PEG electrode retained a high capacity of 1,450.2 mAh g-1 and a Coulombic efficiency of 99.4% even after 350 cycles under a C-rate of 0.5 C. Under a high C-rate of 3 C, an outstanding capacity of 2,500 mAh g-1 was also achieved, thus demonstrating its potential for improving the electrochemical performance of Si anodes.


Electrochemically promoted C-N bond formation from acetylenic amines and CO2. Synthesis of 5-methylene-1,3-oxazolidin-2-ones.
[reaction: see text] An efficient electrochemical synthesis of 5-methylene-1,3-oxazolidin-2-ones (2a-h) from acetylenic amines (1a-h) and carbon dioxide has been achieved by direct electrolysis of solution of MeCN and Et4NPF6 containing the amine, with subsequent CO2 bubbling and heating. The yields vary from good to excellent, the conditions are mild, and the use of toxic and harmful chemicals and catalysts is avoided.


Predictive factors of recurrence for patients with intrahepatic cholangiocarcinoma after hepatectomy.
To identify risk factors related to postoperative recurrence for intrahepatic cholangiocarcinoma (ICC) patients with negative resection margin. A total of 64 ICC patients who underwent resection with negative margin at our center from 2002 to 2010 were recruited in the present study. All clinicopathological characteristics were assessed using univariate analyses. Independent risk factors were identified by Cox regression. Factors significant at a p<0.10 in the univariate analyses were involved in the multivariate analyses. The diagnostic accuracy of the identified risk factors was evaluated using receiver operating curve (ROC). The overall 1-, 3- and 5-year recurrence-free survival rates for patients with ICC were 63%, 32% and 27%, respectively. The most common site of postoperative recurrence was the liver. Lymph node metastasis, perineural invasion and total tumor size greater than 5 cm showed prognostic power in multivariate analysis. The recurrence-free survival rates reduced with the increasing of the number of risk factor for patients with ICC. This study suggested liver was the most common recurrence site and confirmed lymph node metastasis, perineural invasion and total tumor size greater than 5 cm may be associated with poor outcome for ICC patients with negative resection margin.


Emerging models and trends in mental health crisis care in England: a national investigation of crisis care systems.
Inpatient psychiatric care is unpopular and expensive, and development and evaluation of alternatives is a long-standing policy and research priority around the world. In England, the three main models documented over the past fifty years (teams offering crisis assessment and treatment at home; acute day units; and residential crisis services in the community) have recently been augmented by several new service models. These are intended to enhance choice and flexibility within catchment area acute care systems, but remain largely undocumented in the research literature. We therefore aimed to describe the types and distribution of crisis care models across England through a national survey. We carried out comprehensive mapping of crisis resolution teams (CRTs) using previous surveys, websites and multiple official data sources. Managers of CRTs were invited to participate as key informants who were familiar with the provision and organisation of crisis care services within their catchment area. The survey could be completed online or via telephone interview with a researcher, and elicited details about types of crisis care delivered in the local catchment area. We mapped a total of 200 adult CRTs and completed the survey with 184 (92%). Of the 200 mapped adult CRTs, there was a local (i.e., within the adult CRT catchment area) children and young persons CRT for 84 (42%), and an older adults CRT for 73 (37%). While all but one health region in England provided CRTs for working age adults, there was high variability regarding provision of all other community crisis service models and system configurations. Crisis cafes, street triage teams and separate crisis assessment services have all proliferated since a similar survey in 2016, while provision of acute day units has reduced. The composition of catchment area crisis systems varies greatly across England and popularity of models seems unrelated to strength of evidence. A group of emerging crisis care models with varying functions within service systems are increasingly prevalent: they have potential to offer greater choice and flexibility in managing crises, but an evidence base regarding impact on service user experiences and outcomes is yet to be established.


Pardaxin produces postjunctional muscle contraction in guinea-pig intestinal smooth muscle.
The action of pardaxin (PX), a toxin isolated from the secretion of the Red Sea flatfish, Pardachirus marmoratus, was studied on longitudinal muscle of guinea-pig ileum. Pardaxin contracted the ileum and subsequently abolished muscle contraction to 5-hydroxytryptamine (5-HT), but did not affect the responses to acetylcholine (ACh) and substance P(SP). Pardaxin-induced contraction was only partially suppressed by atropine and not affected by tetrodotoxin or morphine. Preparations desensitized to 5-HT or SP responded normally to pardaxin. Pardaxin-induced contractions were normal in K+-depolarizing Krebs Ringer solution and not affected by black widow spider venom. It is concluded that the pardaxin-induced muscle contractions are not mediated through the release of neurotransmitters and do not involve 5-HT, SP or ACh receptors, but are due to a direct action on the muscle contractile mechanism.


Serologic evidence of avian influenza H9N2 and paramyxovirus type 1 infection in emus (Dromaius novaehollandiae) in India.
An avian influenza (AI) surveillance was undertaken in Maharashtra state, India during the period 2010-2011. There are no reports of AI surveillance in emus from India. A total of 202 blood samples and 467 tracheal and cloacal swabs were collected from eight emu farms. A hemagglutination inhibition (HI) assay was performed for detection of antibodies against AI H5N1, H7N1, H9N2, and avian paramyxovirus type 1 (APMV-1) viruses. A microneutralization (MN) assay was performed to confirm the presence of neutralizing antibodies against AI H9N2 and to compare with HI assays. A total of 28.2% and 28.7% of samples were positive for antibodies against AI H9N2 by HI and MN assays, respectively, using > or = 1:40 as a cut-off titer; 15.3% samples were positive for APMV-1 by HI assay using a > or = 1:10 cut-off titer. Seropositivity of AI H9N2 was nil in the grower (<1 yr) age group and highest (78%) in the breeder (2-3 yr) age group, whereas seropositivity against APMV-1 was observed in all age groups. Performance of both HI and MN assays was similar, suggesting the utility of using the MN assay along with HI assay for surveillance studies. This is the first report of the seroprevalence of AI H9N2 and APMV-1 in emus in India.


Inhibition by cocaine of noradrenaline release from sympathetic nerves in the rabbit ear artery.
1. Effects of cocaine on release of noradrenaline (NA) from sympathetic nerves were studied in the isolated perfused central artery of the rabbit ear. Indices of release were the vasoconstrictor response to nerve stimulation and stimulation-induced overflow of radioactivity after the nerves had been loaded with [3H]-NA. The overflow studies were carried out on phenoxybenzamine-treated arteries to eliminate the effect of cocaine on neuronal uptake. 2. Cocaine enhanced the constrictor responses of the artery to stimulation in concentrations of 3 and 30 mumols/l, but in higher concentrations (tested up to 300 mumols/l) the enhancement declined and was replaced by inhibition. Responses to extraluminal NA remained enhanced throughout the concentration range (tested up to 150 mumols/l). 3. In contrast, cocaine depressed the overflow of radioactivity, the effect being detectable in a concentration of 3 mumols/l (a decrease of 15%); the decrease was 40% at the highest concentration tested (90 mumols/l). 4. It is suggested that when assessed in terms of the vasoconstrictor response, inhibition of transmitter release by cocaine is masked by inhibition of neuronal uptake except in high concentrations of cocaine.


Predicting Spray Dried Dispersion Particle Size Via Machine Learning Regression Methods.
Spray dried dispersion particle size is a critical quality attribute that impacts bioavailability and manufacturability of the spray drying process and final dosage form. Substantial experimentation has been required to relate formulation and process parameters to particle size with the results limited to a single active pharmaceutical ingredient (API). This is the first study that demonstrates prediction of particle size independent of API for a wide range of formulation and process parameters at pilot and commercial scale. Additionally we developed a strategy with formulation and target particle size as inputs to define a set of "first to try" process parameters. An ensemble machine learning model was created to predict dried particle size across pilot and production scale spray dryers, with prediction errors between -7.7% and 18.6% (25th/75th percentiles) for a hold-out evaluation set. Shapley additive explanations identified how changes in formulation and process parameters drove variations in model predictions of dried particle size and were found to be consistent with mechanistic understanding of the particle formation process. Additionally, an optimization strategy used the predictive model to determine initial estimates for process parameter values that best achieve a target particle size for a provided formulation. The optimization strategy was employed to estimate process parameters in the hold-out evaluation set and to illustrate selection of process parameters during scale-up. The results of this study illustrate how trained regression models can reduce the experimental effort required to create an in-silico design space for new molecules during early-stage process development and subsequent scale-up.


Adeno-associated virus-based Alzheimer's disease mouse models and potential new therapeutic avenues.
Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that presents with cognitive decline. The current understanding of underlying disease mechanisms remains incomplete. Genetically modified mouse models have been instrumental in deciphering pathomechanisms in AD. While these models were typically generated by classical transgenesis and genome editing, the use of adeno-associated viruses (AAVs) to model and investigate AD in mice, as well as to develop novel gene-therapy approaches, is emerging. Here, we reviewed literature that used AAVs to study and model AD and discuss potential gene therapy strategies. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.


Structural elements of the 50 S subunit of E. coli ribosomes.
The large (50 S) subunit from E. coli ribosomes consists of 32 different proteins and two RNA molecules of different length. In an attempt to determine the three-dimensional arrangement of the proteins in the subunit, we are also interested in obtaining direct information on the shape of the proteins within the subunit. This is possible only with ribosomal subunits which, unlike natural protonated subunits, are homogeneous for neutrons. These homogeneous particles are produced by reconstituting 50 S particles from RNA and proteins isolated from bacteria grown at different levels of D2O in the culture medium, 76% D2O for RNA and 84% D2O for proteins. Model calculations and test experiments reveal that the pursued strategy allows direct determination of radii of gyration of 50 S components within the particle with reasonable precision. Data evaluation and interpretation are significantly facilitated by contrast variation of the reconstituted particles. The determination of protein shape parameters is only one aspect of the new strategy. The pair distance measurements are completely independent of its success. Data on radii of gyration of five ribosomal proteins in situ are reported: L1 (26 +/- 2 A), L2 (22 +/- 2 A), L3 (22 +/- 2 A), L4 (20 +/- 2 A), and L23 (13 +/- 2 A).


Next-generation narrow band imaging system for colonic polyp detection: a prospective multicenter randomized trial.
Previous studies have yielded conflicting results on the colonic polyp detection rate with narrow-band imaging (NBI) compared with white-light imaging (WLI). We compared the mean number of colonic polyps detected per patient for NBI versus WLI using a next-generation NBI system (EVIS LUCERA ELITE; Olympus Medical Systems) used with standard-definition (SD) colonoscopy and wide-angle (WA) colonoscopy. this study is a 2 × 2 factorial, prospective, multicenter randomized controlled trial. this study was conducted at five academic centers in Japan. patients were allocated to one of four groups: (1) WLI with SD colonoscopy (H260AZI), (2) NBI with SD colonoscopy (H260AZI), (3) WLI with WA colonoscopy (CF-HQ290), and (4) NBI with WA colonoscopy (CF-HQ290). the mean numbers of polyps detected per patient were compared between the four groups: WLI with/without WA colonoscopy and NBI with/without WA colonoscopy. Of the 454 patients recruited, 431 patients were enrolled. The total numbers of polyps detected by WLI with SD, NBI with SD, WLI with WA, and NBI with WA were 164, 176, 188, and 241, respectively. The mean number of polyps detected per patient was significantly higher in the NBI group than in the WLI group (2.01 vs 1.56; P = 0.032). The rate was not higher in the WA group than in the SD group (1.97 vs 1.61; P = 0.089). Although WA colonoscopy did not improve the polyp detection, next-generation NBI colonoscopy represents a significant improvement in the detection of colonic polyps.


An ovarian leiomyoma: a case report.
We present a rare case of a 61-year-old Japanese woman with an ovarian leiomyoma. That was detected during a mass screening. To our knowledge, this is the first report of an ovarian leiomyoma found during a mass screening. We performed a total abdominal hysterectomy and a bilateral salpingo-oophorectomy. The tumor originated in the right ovary, and it did not connect with the uterus. The smooth muscle origin of the tumor was detected by immunohistochemical staining with antibodies to vimentin, desmin, and smooth-muscle actin (SMA).


The role of in-person focus groups in the management of urinary incontinence in women from a mixed-methods, randomized pilot study.
To assess the quantitative and qualitative components of in-person focus groups as a potential intervention for female patients with urinary incontinence. Women over the age of 18 seeking treatment for UI were randomized to standard care with focus group participation or to standard care alone. All participants completed validated questionnaires: MESA, UDI-6, OAB-SAT-q, PGI-S, PGI-I, SQoL-F, PHQ-9, IPAQ at the beginning and conclusion of the study. Questionnaires were analyzed with repeated measures of ANOVA models in an intention-to-treat manner. Three moderated focus group sessions were held and audio recorded. Recordings were transcribed and categorized by frequency into themes using grounded theory methodology. A total of ten control and eight intervention participants agreed to participate. Seven women attended all three focus group sessions and were included in the final analysis. Transcripts from focus group sessions observed women identified most with (1) urinary incontinence (UI) as a chronic disease, (2) shame managing UI, and (3) social constraints of toileting. Participants self-reported appreciation of focus group participation and desire for on-going sessions. Analysis of the questionnaires did not demonstrate statistically significant differences. Data ascertained from questionnaires were unable to demonstrate a meaningful effect in improved treatment outcomes for control and intervention participants. Grounded theory analysis of transcripts identified four primary themes: (1) appreciation of the focus group, (2) UI as a gendered issue, (3) lack of public awareness, and (4) history of negative provider interactions. All focus group participants self-reported interest in attending future focus group sessions.


Diarrhoea, malnutrition, and dehydration associated with school water, sanitation, and hygiene in Metro Manila, Philippines: A cross-sectional study.
Diarrhoea, malnutrition, and dehydration threaten the lives of millions of children globally due to inadequate water, sanitation, and hygiene (WaSH). Our study aimed to identify environmental and behavioural risk factors of these health outcomes among schoolchildren in Metro Manila, Philippines. We analysed data from a multistage cluster sample of schoolchildren in grades 5, 6, 7, 9, and 10 (ages ~10-15 years old) to investigate WaSH facilities and hygiene practices. Outcomes were: self-reported diarrhoea, measured via questionnaire; observed malnutrition (stunting, undernutrition [underweight/thin and wasted/severely thin], over-nutrition [overweight and obese]), measured via anthropometry; dehydration, measured via urine specific gravity/urine test strips. We used multiple logistic regression to explore correlates. We included 1558 students from 15 schools in three cities. Over 28% (421) of students had diarrhoea and 68% (956) were dehydrated. Over 15% (227) of students were stunted, ~9% (127) were undernourished, and >21% (321) were over-nourished. Diarrhoea was associated with poor handwashing, while dehydration was associated with the lack of water in school restrooms. Stunting was linked with not using the school restroom, the lack of water in school restrooms, and the lack of hygiene lessons in school. Undernutrition was associated with the lack of a school restroom cleaning policy. Risks of diarrhoea, stunting, and undernutrition decreased as the number of school restrooms increased. Risks of stunting and overnutrition decreased as the numbers of school toilets increased. Having more than seven handwashing basins was associated with decreased risk of dehydration. Findings from our cross-sectional study cannot describe causation. We have found associations that suggest that school restroom cleaning policies, adequate water supply, improved handwashing, and hygiene education are needed to prevent disease. School-based WaSH interventions are recommended to provide water in school WaSH facilities, promote handwashing, and improve hygiene-related knowledge.


Effects of imidazoline I₂ receptor ligands on morphine- and tramadol-induced antinociception in rats.
Currently available analgesics cannot meet the increasing clinical needs and new analgesics with better therapeutic profiles are in great demand. The imidazoline I₂ receptor is an emerging drug target for analgesics. However, few studies have examined the effects of selective I₂ receptor ligands on the antinociceptive activity of opioids. This study examined the antinociceptive effects of the opioids morphine (0.1-10 mg/kg) and tramadol (3.2-56 mg/kg), the nonselective I₂ receptor ligand agmatine (10-100 mg/kg), and the selective I₂ receptor ligands 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI; 1-10 mg/kg) and 2-(4, 5-dihydroimidazol-2-yl) quinoline hydrochloride (BU224; 1-10mg/kg), alone and in combination, in a warm water tail withdrawal procedure in rats. Morphine and tramadol but not agmatine, 2-BFI or BU224 increased tail withdrawal latency in a dose-related manner at 48°C water. Agmatine and 2-BFI but not BU224 dose-dependently enhanced the antinociceptive effects of morphine and tramadol, shifting the dose-effect curves of morphine and tramadol leftward. The enhancement of agmatine and 2-BFI on morphine and tramadol antinociception was prevented by BU224. These results, combined with the fact that BU224 and 2-BFI share similar behavioral effects under other conditions, suggest that BU224 has lower efficacy than 2-BFI at I₂ receptors, and that the enhancement of opioid antinociception by I₂ receptor ligands depends on their efficacies.


Real-time multiplex PCR assay for detection of Brucella spp., B. abortus, and B. melitensis.
The identification of Brucella can be a time-consuming and labor-intensive process that places personnel at risk for laboratory-acquired infection. Here, we describe a real-time PCR assay for confirmation of presumptive Brucella isolates. The assay was designed in a multiplex format that will allow the rapid identification of Brucella spp., B. abortus, and B. melitensis in a single test.


Continent urinary diversion and bladder augmentation in children: the Mainz pouch procedure.
The formation of a bowel reservoir of large capacity at low pressure by using small and large bowel (ileocaecal segment) has proved reliable for achieving continent urinary diversion (n = 80), for bladder augmentation (n = 42) as well as for total bladder replacement (n = 24). Encouraged by the results we obtained in our adult patients, we have used this technique during the last 3.5 years in 29 children. Indications for urinary diversions in children have been: neurogenic bladder with diplegia (n = 8), bladder exstrophy (n = 2), traumatic loss of the bladder (n = 1), urogenital sinus (n = 1) and rhabdomyosarcoma of the prostate or bladder (n = 2). Bladder augmentation was indicated in 6 children with iatrogenic bladder loss, in 5 children with neurogenic bladder without diplegia and in 4 boys with incontinent epispadias or exstrophy. In children with bladder exstrophy or incontinent epispadias, continence was achieved using a modified Young-Dees technique with formation of a long intra-abdominal muscular tube made out of the bladder plate or the low-capacity bladder. The capacity of the urinary reservoir was guaranteed by bladder augmentation or bladder replacement with an ileocaecal pouch. During a mean follow-up period of 26 months (bladder augmentation) and 21 months (continent diversion) there was only one postoperative complication (intussusception ileus) which required operative revision. Two children had to undergo reoperation because of nipple problems. Follow-up, with monitoring of biochemical and metabolic parameters, is necessary to show whether this technique will provide a long-term successful solution for these problems.


Impact of clinical complete response on treatment outcomes in patients with locally advanced HPV-negative oropharyngeal squamous cell carcinoma.
To evaluate treatment outcomes after definitive chemoradiotherapy (CRT) for human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC). We analyzed data concerning HPV-negative OPSCC patients treated with curative intent. All patients received concomitant high-dose cisplatin-based chemotherapy. Two different RT techniques were used: (1) sequential boost IMRT (S-IMRT) to a total dose of 70 Gy (2 Gy/fraction); (2) simultaneously integrated boost (SIB-IMRT) to a total dose of 67.5 Gy (2.25 Gy/fraction). Survival outcomes were estimated. In total, 69 HPV-negative OPSCC patients were included (n = 40 S-IMRT; n = 29 SIB-IMRT). The median follow-up time was 40 months. The 3-year overall survival, disease-free survival, distant metastasis-free survival and locoregional-free survival were 67.1%, 63.3%, 64.5% and 66.0%, respectively. Alcohol abuse and advanced stage disease at presentation were the main risk factors for worse survival outcomes. Complete clinical response (cCR) at 3 months after CRT improved overall survival (86.3% versus 42.5%, p < 0.01). The cCR events were greater but not statistically significant in SIB-IMRT group compared to S-IMRT patients (69% versus 47.5%, p = 0.09). The positive impact of cCR at 3 months on survival needs to be confirmed in randomized clinical trials, as well as its close correlation with SIB-IMRT technique. A proper stratification of HPV-negative OPSCC patients should be paramount to tailor treatment strategy in the near future.


Selective translational repression of HIV-1 RNA by Sam68DeltaC occurs by altering PABP1 binding to unspliced viral RNA.
HIV-1 structural proteins are translated from incompletely spliced 9 kb and 4 kb mRNAs, which are transported to the cytoplasm by Crm1. It has been assumed that once in the cytoplasm, translation of incompletely spliced HIV-1 mRNAs occurs in the same manner as host mRNAs. Previous analyses have demonstrated that Sam68 and a mutant thereof, Sam68DeltaC, have dramatic effects on HIV gene expression, strongly enhancing and inhibiting viral structural protein synthesis, respectively. While investigating the inhibition of incompletely spliced HIV-1 mRNAs by Sam68DeltaC, we determined that the effect was independent of the perinuclear bundling of the viral RNA. Inhibition was dependent upon the nuclear export pathway used, as translation of viral RNA exported via the Tap/CTE export pathway was not blocked by Sam68DeltaC. We demonstrate that inhibition of HIV expression by Sam68DeltaC is correlated with a loss of PABP1 binding with no attendant change in polyadenosine tail length of the affected RNAs. The capacity of Sam68DeltaC to selectively inhibit translation of HIV-1 RNAs exported by Crm1 suggests that it is able to recognize unique characteristics of these viral RNPs, a property that could lead to new therapeutic approaches to controlling HIV-1 replication.


Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.
Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.


Computational Analysis of DNA Modifications in Confocal Images.
Computational analysis of digital images provides a robust and unbiased way to compare and investigate the amount (pixel intensity) and spatial distribution of DNA modifications. The DNA modifications in the cells are visualized by fluorescence labeling and the images are captured by confocal microscopy. The key advantage of the confocal over conventional microscope is that it images only a thin optical section around the focal plane of the microscope therefore it can precisely record signals only from the focal plane inside the nucleus. In this chapter, we will describe in detail several analysis methods to visualize and quantify the DNA modification signals including how to investigate codistribution of such signals when using dual labeling.


Handsearching still a valuable element of the systematic review.
The Cochrane Methodology Register, Medline, Embase, AMED, Biosis, Cinahl, LISA, and Psycinfo were consulted along with researchers who may have carried out relevant studies. Studies were considered eligible if they compared searching by hand with searching one or more electronic databases to identify reports of randomised trials. The main outcome measure was the number of reports of randomised trials identified from searches made by hand compared with electronic searching. Data were extracted regarding the electronic database searched, the complexity of electronic search strategy used, the characteristics of the journal reports identified, and the type of trial report identified. Thirty-four studies were included. Handsearching identified between 92 and 100% of the total number of reports of randomised trials found in the various comparisons in this review. Searching Medline retrieved 55%, Embase 49% and Psycinfo 67%. The retrieval rate of the electronic database varied depending on the complexity of the search. The Cochrane highly sensitive search strategy (HSSS) identified 80% of the total number of reports of randomised trials found; searches categorised as 'complex' (including the Cochrane HSSS) found 65% and 'simple' searches found 42%. The retrieval rate for an electronic search was higher when the search was restricted to English-language journals, at 62% versus 39% for journals published in languages other than English. When the search was restricted to full reports of randomised trials, the retrieval rate for an electronic search improved: a complex search strategy retrieved 82% of the total number of such reports of randomised trials. Hand searching is still valuable in identifying randomised trials for inclusion in systematic reviews of healthcare, particularly trials reported as abstracts or letters, those published in languages other than English, along with all reports published in journals not indexed in electronic databases. Where time and resources are limited, however, searching an electronic database using a complex search (or the Cochrane HSSS) will identify the majority of trials published as full reports in English language journals, provided, of course, that the relevant journals have been indexed in the database.


Monoclonal antibody detects monosialogangliosides having a sialic acid alpha 2----3-galactosyl residue.
A murine monoclonal antibody (mAb), designated mAb 202, was generated using a human melanoma cell line, UCLASO-M14 as the immunogen. mAb 202 reacted with two (GM2 and GM3) of the four (GM2, GM3, GD2, and GD3) gangliosides expressed by M14. Several authentic monosialogangliosides, including GM4, GM3, GM2, GM1, GM1b, and sialylparagloboside were then tested for their binding to 202 mAb by the immune adherence inhibition assay, TLC-enzyme immunostaining, and enzyme-linked immunosorbent assay. All showed positive binding but in varying degrees. GM4 showed the strongest affinity. No significant differences of reactivity were observed between the sialic acid derivatives, N-acetyl and N-glycolyl, in these gangliosides. Disialogangliosides such as GD3, GD2, GD1a, and GD1b, trisialoganglioside GT1b, and neutral glycolipids including GlcCer, GalCer, LacCer, GbOs3Cer, GbOs4Cer, GgOs3Cer, GgOs4Cer, and nLcOs4Cer were all negative. These results indicate that the 202 mAb detects sialyl alpha 2----3Gal residue in the monosialoganglioside, irrespective of the internal structure. Since GM4 is not expressed by M14 cells, the terminal disaccharide (sialyl alpha 2----3Gal) in GM3 and/or GM2 must have been the epitope responsible for the generation of the antibody.


Elastic dosage compensation by X-chromosome upregulation.
X-chromosome inactivation and X-upregulation are the fundamental modes of chromosome-wide gene regulation that collectively achieve dosage compensation in mammals, but the regulatory link between the two remains elusive and the X-upregulation dynamics are unknown. Here, we use allele-resolved single-cell RNA-seq combined with chromatin accessibility profiling and finely dissect their separate effects on RNA levels during mouse development. Surprisingly, we uncover that X-upregulation elastically tunes expression dosage in a sex- and lineage-specific manner, and moreover along varying degrees of X-inactivation progression. Male blastomeres achieve X-upregulation upon zygotic genome activation while females experience two distinct waves of upregulation, upon imprinted and random X-inactivation; and ablation of Xist impedes female X-upregulation. Female cells carrying two active X chromosomes lack upregulation, yet their collective RNA output exceeds that of a single hyperactive allele. Importantly, this conflicts the conventional dosage compensation model in which naïve female cells are initially subject to biallelic X-upregulation followed by X-inactivation of one allele to correct the X dosage. Together, our study provides key insights to the chain of events of dosage compensation, explaining how transcript copy numbers can remain remarkably stable across developmental windows wherein severe dose imbalance would otherwise be experienced by the cell.


Effect of heparin on bone formation in cultured fetal rat calvaria.
To assess the effects of heparin on bone formation we measured [3H]proline incorporation into collagenase-digestible (CDP) and noncollagen protein (NCP), [3H]thymidine (TdR) incorporation into DNA, and DNA content in 21-day-old fetal rat calvaria cultured in BGJ medium with bovine serum albumin for 24-96 hours. Heparin at 5-125 micrograms/ml decreased TdR incorporation by 26-51% at 24 and 96 hours. At 96 hours, heparin 5, 25, and 125 micrograms/ml decreased [3H]proline incorporation into CDP by 41, 48, and 32%, respectively, with no significant change in NCP. To evaluate the possible role of PGE2 in these inhibitory responses, media PGE2 concentration was measured and the effects of heparin on CDP labeling and DNA synthesis were tested in the presence of indomethacin, piroxicam, and flurbiprofen to inhibit endogenous prostaglandin E2 (PGE2) production and in the presence of a high concentration (10(-7) M) of exogenous PGE2. Heparin did not alter PGE2 production at 24 hours but at 48 hours there was a significant reduction. At 96 hours, indomethacin (10(-6) M) inhibited [3H]-proline incorporation into CDP by 38% but had no effect on the labeling of NCP. Heparin had no further significant inhibitory effect in the presence of indomethacin. Piroxicam and flurbiprofen did not alter DNA content and had a smaller inhibitory effect than indomethacin on the labeling of CDP. Moreover, addition of heparin produced a further inhibition of CDP and DNA content and finally, heparin decreased CDP labeling by 71% in the presence of PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment of reflex sympathetic dystrophy of the hand with an active "stress loading" program.
Reflex sympathetic dystrophy (RSD) is a syndrome characterized by pain out of proportion to injury, vasomotor and trophic changes, stiffness, and decreased function. It is important to separate the active disease process of RSD from its resultant state of contracture and fibrosis. Our treatment program is based on active "stress loading," which consists of active traction and compression exercises that provide stressful stimuli to the extremity without joint motion. Fifty-two patients with RSD were treated during a 3-year period. Their results and long-term follow-up on 41 patients are presented. The "stress loading" program has been used consistently during the past 20 years. The advantages of the program are its effectiveness, simplicity, safety, and noninvasiveness.


Demonstration and Mitigation of Aerosol and Particle Dispersion During Mastoidectomy Relevant to the COVID-19 Era.
COVID-19 has become a global pandemic with a dramatic impact on healthcare systems. Concern for viral transmission necessitates the investigation of otologic procedures that use high-speed drilling instruments, including mastoidectomy, which we hypothesized to be an aerosol-generating procedure. Mastoidectomy with a high-speed drill was simulated using fresh-frozen cadaveric heads with fluorescein solution injected into the mastoid air cells. Specimens were drilled for 1-minute durations in test conditions with and without a microscope. A barrier drape was fashioned from a commercially available drape (the OtoTent). Dispersed particulate matter was quantified in segments of an octagonal test grid measuring 60 cm in radius. Drilling without a microscope dispersed fluorescent particles 360 degrees, with the areas of highest density in quadrants near the surgeon and close to the surgical site. Using a microscope or varying irrigation rates did not significantly reduce particle density or percent surface area with particulate. Using the OtoTent significantly reduced particle density and percent surface area with particulate across the segments of the test grid beyond 30 cm (which marked the boundary of the OtoTent) compared with the microscope only and no microscope test conditions (Kruskall-Wallis test, p = 0.0066). Mastoidectomy with a high-speed drill is an aerosol-generating procedure, a designation that connotes the potential high risk of viral transmission and need for higher levels of personal protective equipment. A simple barrier drape significantly reduced particulate dispersion in this study and could be an effective mitigation strategy in addition to appropriate personal protective equipment.


Advances in prevention of mother-to-child HIV transmission.
Advances have been made in the understanding of the pathogenesis of mother-to-child transmission of human immunodeficiency virus (HIV). Most transmission occurs during delivery and after birth throught breastfeeding. For this reason, efforts to interrupt transmission have focused on peripartum period and infant feeding. This includes the use of antiretroviral therapy, elective cesarean section and avoidance of breastfeeding. This review summarizes recent major studies and new development on the prevention of mother-to-child HIV transmission. The application and the impact of such interventions in developing world is discussed. Prevention of mother-to-child transmission of HIV should now be integrated as part of basic maternal and child health services in developing countries.


T cell-mediated immunotherapy of metastases: state of the art in 2005.
Advances in cellular and molecular immunology have led to the development of strategies for effective augmentation of antitumour immune responses in cancer patients. This review focuses on the manipulation of T cell immunity either by active specific immunotherapy (ASI) using tumour vaccines, or by adoptive immunotherapy (ADI) with immune T cells. Such therapies offer exquisite specificity of tumour recognition based on the ability of the T cell to distinguish single amino acid differences in any protein from any compartment of the tumour cell. Examples are presented of clinical survival benefits for cancer patients by postoperative ASI with a modified autologous tumour vaccine of high quality. Furthermore, clinical studies employing ADI with T cells activated and expanded ex vivo have demonstrated 'proof of principle' that tumour-specific T cells are capable of mediating anticancer activity in vivo, as measured by regression of metastatic tumours. Translation of these findings into a standardised immunotherapy is, however, not easy and will require coordination and cooperation among academic, private and federal sectors.


Thoracic metastasectomy for germ cell tumours: long term survival and prognostic factors.
This study evaluated the results of thoracic metastasectomy for germ cell tumours to assess long term survival and identify prognostic factors. A series of 141 consecutive patients who underwent resection of thoracic metastases at Royal Brompton Hospital were retrospectively reviewed. Kaplan-Meier estimates of survival were calculated for clinical variables related to primary tumour and thoracic metastases, using the Cox model for multivariate analysis. Complete resection was achieved in 123 cases (87%); pathology showed viable malignant elements in 46 (32%), necrosis or fibrosis in 32, differentiated teratoma in 63. The overall survival was 77% at five years and 65% at 15 years, being significantly shorter in patients with malignant teratomatous elements (51% at five years, P = 0.0001) or incomplete resection (64% at five years, P = 0.019). At multivariate analysis these factors retained their prognostic value, with a relative risk of death of 5.7 for malignant teratomatous elements and 4.0 for incomplete resection. In addition, the Cox model revealed a 3.2 times higher risk of relapse in patients with malignant teratomatuos elements at the time of thoracic metastasectomy. These data confirm the value of thoracic metastasectomy to asses pathological response and achieve permanent cure of chemoresistant disease.


[Management of COVID-19 in Brazil: a humanitarian catastrophe.]
Letter to the editor about the current situation of the COVID-19 pandemic in Brazil.


Effects of eye color and sex on accuracy in archery.
126 subjects were 47 children in Grade 7, 49 students in Grade 8, and 30 adults, who shot arrows at bull's-eye targets from varying distances. Analysis of variance of accuracy scores indicated that there was no difference for eye color, but boys scored more points than did girls.


An Optimized Decision Method for Smart Teaching Effect Based on Cloud Computing and Deep Learning.
In order to improve the effect of intelligent teaching and give full play to the role of intelligent technology in modern physical education, in this paper, cloud computing and deep learning methods are used to comprehensively evaluate the teaching effect of colleges and universities, and calculate the evaluation effect and accuracy. Cloud computing and deep learning algorithm combine the teaching evaluation scale, teaching content, and characteristics to formulate teaching plans for different students and realize targeted teaching evaluation. The results show that the teaching evaluation method proposed in this paper can improve students' learning interest by about 30%, enhance learning initiative by about 20%, and the matching rate between the actual teaching effect and the expected requirements is 98%. Therefore, cloud computing and deep learning model can improve the accuracy of teaching effect evaluation in colleges and universities, provide support for the formulation of teaching evaluation schemes, and promote the development of intelligent teaching in colleges and universities.


A magnetic levitation based low-gravity simulator with an unprecedented large functional volume.
Low-gravity environment can have a profound impact on the behaviors of biological systems, the dynamics of fluids, and the growth of materials. Systematic research on the effects of gravity is crucial for advancing our knowledge and for the success of space missions. Due to the high cost and the limitations in the payload size and mass in typical spaceflight missions, ground-based low-gravity simulators have become indispensable for preparing spaceflight experiments and for serving as stand-alone research platforms. Among various simulator systems, the magnetic levitation-based simulator (MLS) has received long-lasting interest due to its easily adjustable gravity and practically unlimited operation time. However, a recognized issue with MLSs is their highly non-uniform force field. For a solenoid MLS, the functional volume V1%, where the net force results in an acceleration <1% of the Earth's gravity g, is typically a few microliters (μL) or less. In this work, we report an innovative MLS design that integrates a superconducting magnet with a gradient-field Maxwell coil. Through an optimization analysis, we show that an unprecedented V1% of over 4000 μL can be achieved in a compact coil with a diameter of 8 cm. We also discuss how such an MLS can be made using existing high-Tc-superconducting materials. When the current in this MLS is reduced to emulate the gravity on Mars (gM = 0.38g), a functional volume where the gravity varies within a few percent of gM can exceed 20,000 μL. Our design may break new ground for future low-gravity research.