E3 ubiquitin ligase Nedd4 is a key negative regulator for non-canonical inflammasome activation.
The non-canonical inflammasome plays important roles in endotoxic shock and pyroptosis. Murine caspase-11, corresponding to human caspase-4, is centrally located in the non-canonical inflammasome pathway, which is directly activated by cytosolic lipopolysaccharide. It has been reported that ubiquitination strictly regulates inflammatory responses. However, the role of ubiquitination in regulating the non-canonical inflammasome is little known. In this study, we show that the E3 ubiquitin ligase, Nedd4 is an important negative regulatory component of the non-canonical inflammasome pathway. Nedd4 deficiency promoted mouse death from sepsis and cell pyroptosis, resulting from non-canonical inflammasome activation. Furthermore, Nedd4 induced the K48-linked polyubiquitination and subsequent degradation of caspase-11 through the 26S proteasome. Meanwhile, caspase-11 (or caspase-4) reciprocally regulated the level of Nedd4 protein by cleavage. Thus, Nedd4 appears to have a key role in balancing the level of non-canonical inflammasome activation in response to gram-negative bacterial infection.


[Prevention of Obesity and Promotion of Healthy Nutrition in Children by a Kindergarten-Based Intervention: An Evaluation Study].
This outcome evaluation study has investigated different diet concepts in day-care centres and their effects on health-related dietary behaviour of children and their families. No advantage of a certain approach to manage food and diet-related activities in day-care centres could be shown.


Biological nutrient removal with limited organic matter using a novel anaerobic-anoxic/oxic multi-phased activated sludge process.
An anaerobic-anoxic/oxic (A2/O) multi-phased biological process called "phased isolation tank step feed technology (PITSF)" was developed to force the oscillation of organic and nutrient concentrations in process reactors. PITSF can be operated safely with a limited carbon source in terms of low carbon requirements and aeration costs whereas NAR was achieved over 95% in the last aerobic zone through a combination of short HRT and low DO levels. PCR assay was used for XAB quantification to correlate XAB numbers with nutrient removal. PCR assays showed, high NAR was achieved at XAB population 5.2 × 10(8) cells/g MLVSS in response to complete and partial nitrification process. It was exhibited that low DO with short HRT promoted XAB growth. Simultaneous nitrification and denitrification (SND) via nitrate were observed obviously, SND rate was between 69-72%, at a low DO level of 0.5 mg/l in the first aerobic tank during main phases and the removal efficiency of TN, [Formula: see text], COD, TP was 84.7 .97, 88.3 and 96% respectively. The removal efficiencies of TN, [Formula: see text], and TP at low C/N ratio and DO level were 84.2, 98.5 and 96.9% respectively which were approximately equal to the complete nitrification-denitrification with the addition of external carbon sources at a normal DO level of (1.5-2.5 mg/l).


Slowing Down Time: An Exploration of Personal Life Extension Desirability as it Relates to Religiosity and Specific Religious Beliefs.
As medical technology continues increasing the possibility of living a longer life, the public's valuing of these developments must be considered. This study examines attitudes toward extending the human life span within a student population at a Christian university. Religious factors were hypothesized to affect life extension desirability. Scores on measures of willingness to defer to God's will, meaning derived from religion, positive afterlife beliefs, and intrinsic religiosity were significantly and inversely related to life extension desirability. Implications of these findings are discussed, including encouraging medical practitioners to respect decision-making processes of religious persons who may find life extension interventions undesirable.


Spi6 protects alloreactive CD4(+) but not CD8 (+) memory T cell from granzyme B attack by double-negative T regulatory cell.
Memory T (Tm) cells pose a major barrier to long-term transplant survival. Whether regulatory T cells (Tregs)can control them remains poorly defined. Previously,we established that double-negative (DN) Tregs suppress effector T (Teff) cells. Here, we demonstrate that DNTregs effectively suppress CD4+/CD8+Teff and CD8+Tm but not CD4+Tm cells, whereas the suppression on CD8+Tm is abrogated by perforin (PFN) deficiency in DNTregs. Consistently, in a BALB/c to B6-Rag1-/-skin transplantation, transfer of DN Tregs suppressed the rejection mediated by CD4þ/CD8+Teff and CD8+Tmcells (76.0±4.9, 87.5±5.0 and 63.0±4.7 days, respectively)but not CD4þTmcells (25.3±1.4 days). Both CD8þ effector memory T and central memory T compartments significantly reduced after DN Treg transfer. CD4+Tm highly expresses granzyme B (GzmB) inhibitor serine protease inhibitor-6 (Spi6). Spi6 deficiency renders CD4þTm susceptible to DN Treg suppression. In addition,transfer of WT DN Tregs, but not PFN-/-DN Tregs,inhibited the skin allograft rejection mediated by Spi6-/-CD4þTm(75.5±7.9 days). In conclusion, CD4+ and CD8+Tm cells differentially respond toDNTregs' suppression.The GzmB resistance conferred by Spi6 in CD4þTm cells might hint at the physiological significance of Tmpersistence


Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies.
Neither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines. We collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated. Among 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes. Vaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.


Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input.
We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. To study the contribution of Aδ- and C-fibres in pain perception, we measured thresholds and response times to selective C- and Aδ-fibre activation in congenitally blind, late blind and normally sighted participants. Ultrafast constant-temperature heat pulses were delivered to the hand with a CO2 laser using an interleaved adaptive double staircase procedure. Participants were instructed to respond as quickly as possible when detecting a laser-induced sensation. We used a 650 ms cut-off criterion to distinguish fast Aδ- from slow C-fibre-mediated sensations. Congenitally blind participants showed significantly faster reaction times to C- but not to Aδ-fibre-mediated sensations. In contrast, thresholds for Aδ- and C-fibre stimulation did not differ between groups. Late blind individuals did not differ from sighted controls in any aspect. A follow-up experiment using only suprathreshold stimuli for Aδ- and C-fibre activation confirmed these findings and further showed that congenitally blind individuals detected significantly more C-fibre-mediated stimuli than sighted controls. A decomposition analysis of the reaction times indicated that the faster response times in the congenitally blind are due to more efficient central processing of C-fibre-mediated sensations. The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre-mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity. WHAT DOES THIS STUDY ADD?: Hypersensitivity to heat pain in congenital blindness is associated with faster responses to C-fibre activation, likely caused by more efficient central processing of C-fibre-mediated input.


Prevention of anthracycline-induced cardiotoxicity: a systematic review and network meta-analysis.
Background Anthracycline based chemotherapy is commonly used in many malignancies. While life expectancy increases with the use of this medication, cardiac toxicity causes a risk for patients' health due to anthracyclines. Objective This systematic review and meta-analysis emphasizes on prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Methods We conducted a systematic review of electronic databases including PubMed, Medline, EMBASE, ClinicalTrials.gov, Web of Science, and the Cochrane Library from inception to June 2019 collecting published articles on primary prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. We conducted a network meta-analysis and a pairwise meta-analysis in order to compare direct and indirect cardiac agents group with control group calculate left ventricular ejection fraction change. Primary studies results were pooled using random effects model, frequent network meta-analyses, and performed pairwise meta-analysis using netmeta and meta packages respectively in R software version 3.5.1. Results Twelve studies reported left ventricular ejection fraction outcome among 526 patients in the cardiac agent group and 508 in the control group. Based on Surface Under the Cumulative Ranking cure result, spironolactone was the best in left ventricular ejection fraction change and based on meta-analysis, cardiac group had 1.98 unit left ventricular ejection fraction more than the control group (MD = 1.98, 95% CI 0.15-3.81, p value = 0.03). Conclusions The amount of left ventricular ejection fraction used by cardiac agents in anthracycline-based chemotherapy was reduced to a lesser extent. The effective and ineffective drugs were spironolactone and metoprolol, respectively.


A retrospective study of the stability of midface osteotomies in cleft lip and palate patients.
Relapse following midface osteotomies in cleft lip and palate patients was investigated in a retrospective study. The amount of surgical movement and subsequent relapse was measured using a computer aided digitisation programme with reference to the cranial base. The mean maxillary surgical advance was 5.09 mm horizontally and 5.70 mm vertically. After a mean follow up period of 22 months the mean relapse of the anterior maxilla was 0.90 mm (17%) horizontally and 1.55 mm (27.2%) vertically. Preliminary indications are that direct skeletal fixation of the maxilla by bone plates results in less relapse than when cranio-maxillary fixation is employed.


Isolation of cDNA clones coding for peroxisomal proteins of Candida tropicalis: identification and sequence of a clone for catalase.
A cDNA library, complementary to mRNAs of alkane-grown Candida tropicalis, was screened by differential DNA dot-blot hybridization with [32P]cDNA reverse-transcribed from mRNA of alkane-grown cells or from cells in which peroxisome formation was repressed by growth on glucose. 9% of the library encodes alkane-induced sequences. The cell-free translation products of eight hybrid-selected mRNAs were characterized by SDS-polyacrylamide gel electrophoresis and fluorography: most of them are probably peroxisomal proteins. Among these, a catalase clone was identified by immunoprecipitation of the translation product with anti-catalase. The clone was sequenced: the inferred amino acid sequence is homologous to the carboxytermini of mammalian and Saccharomyces cerevisiae catalases. C. tropicalis catalase mRNA is 1.7-1.8 kb long by Northern analysis, of which 1.5-1.6 kb is required to code for the 57 kDa polypeptide. Catalase mRNA (assayed by dot-blot hybridization) is strikingly induced in C. tropicalis by growth on alkanes, suggesting that peroxisome induction is transcriptionally regulated. This sublibrary of alkane-induced, mostly peroxisomal clones, together with a recently developed cell-free peroxisome protein import assay, will permit investigation of the targeting of proteins to peroxisomes.


Restoration of missing or misplaced canines.
Restorative treatments for canines were discussed to correct three clinical abnormalities: (1) fully erupted permanent canine in the lateral incisor position, (2) missing permanent canines, and (3) partially exposed canines in normal arch position. The primary concerns are the development of esthetics, anterior guidance, and adequate support for fixed restorations.


Controlled, double-blind, randomized trial of amitriptyline in relieving articular pain and tenderness in patients with rheumatoid arthritis.
Thirty-six patients with definite or classical rheumatoid arthritis participated in a double-blind, randomized, placebo-controlled trial to assess the effectiveness of adding amitriptyline to the treatment regimen for the relief of pain not adequately controlled by non-steroidal anti-inflammatory drugs. Dosage of amitriptyline was increased gradually up to 25 mg 3-times daily and patients were followed up for 12 weeks. Assessments were made of joint pain and tenderness every 4 weeks. The results showed no difference between the amitriptyline and placebo-treated patients for either parameter.


The 5A/6A polymorphism of the stromelysin-1 gene and restenosis after percutaneous coronary interventions.
Matrix metalloproteinase stromelysin-1 has been implicated in the process of exaggerated lumen re-narrowing after primarily successful interventions in coronary arteries. We examined the possibility that the 5A/6A promoter polymorphism of the stromelysin-1 gene is associated with restenosis after stenting or percutaneous transluminal coronary angioplasty (PTCA). The study included 3333 consecutive patients with symptomatic coronary artery disease who were treated with stent implantation (n=2857) or PTCA (n=476). Primary end-point was angiographic restenosis, defined as >/=50% diameter stenosis at 6-month follow-up angiography. Restenosis rates were 28.1%, 27.8%, and 29.5% in carriers of the stromelysin-1 genotypes 5A5A, 5A6A, and 6A6A, respectively (P=0.71). The incidence of death or myocardial infarction and the need for revascularization at the site of the intervention due to symptoms or signs of ischaemia in the presence of angiographic restenosis were not significantly different between the genotype groups at 1 year. Separate analysis of the patients who underwent stenting and the patients who were treated with PTCA did not indicate the existence of a treatment type-related association between the 5A/6A polymorphism and restenosis. Our data strongly suggest that the 5A/6A polymorphism of the stromelysin-1 gene is not related to angiographic restenosis or the 1-year clinical outcome after interventions in coronary arteries.


The occurrence of capillary endothelial mitoses in the mesenchyme of the scala tympani during fetal development of the guinea pig.
Mitotic figures were found in the capillary endothelial cells of the cochleae of guinea pig fetuses, indicating a cellular proliferation. The significance of capillary sprouting in the mesenchyme beneath the basilar membrane a few days before opening of the scala tympani is discussed.


Statistics for clinical nursing practice: an introduction.
Difficulty in understanding statistics is one of the most frequently reported barriers to nurses applying research results in their practice. Yet the amount of nursing research published each year continues to grow, as does the expectation that nurses will undertake practice based on this evidence. Critical care nurses do not need to be statisticians, but they do need to develop a working knowledge of statistics so they can be informed consumers of research and so practice can evolve and improve. For those undertaking a research project, statistical literacy is required to interact with other researchers and statisticians, so as to best design and undertake the project. This article is the first in a series that guides critical care nurses through statistical terms and concepts relevant to their practice.


Novel synonymous substitution in POMGNT1 promotes exon skipping in a patient with congenital muscular dystrophy.
Walker-Warburg syndrome, muscle-eye-brain disease, Fukuyama congenital muscular dystrophy, congenital muscular dystrophy type 1C, and congenital muscular dystrophy type 1D are overlapping clinical entities belonging to a subgroup of the congenital muscular dystrophies (CMD), collectively designated dystroglycanopathies, in which the common underlying defect is hypoglycosylation of alfa-dystroglycan. Currently, six different genes are known to be implicated in these diseases: POMT1, POMT2, POMGNT1, FCMD, FKRP, and LARGE. We report the molecular characterization of a patient presenting clinical features of CMD and reduced immunostaining for alfa-dystroglycan in muscle. Three candidate genes (FCMD, POMT1 and POMGNT1) were analyzed, and a total of 18 sequence variants were detected: 15 polymorphisms in POMT1 [including three unreported single nucleotide polymorphisms (SNPs)], two polymorphisms in FCMD, and the exonic silent mutation c.636C > T in POMGNT1. Expression analysis revealed that this apparently silent mutation compromises correct premessenger RNA (mRNA) splicing, promoting skipping of the entire exon 7, with a consequent frameshift. In silico analysis of this mutation did not predict alterations in the canonical splice sequences, but rather the creation of a new exonic splice silencer. The recognition of such disease-causing elements may contribute to the further understanding of RNA processing and assist mutation screening in routine diagnosis, where such changes may be underestimated. To aid clinical diagnosis, we generated publicly available LOVD-powered Locus Specific Databases for these three genes and recorded all known sequence variants ( http://www.dmd.nl ).


Generalized granuloma annulare in a case of breast cancer: A case report and review of the literature.
Generalized granuloma annulare can be associated with breast cancer. Atypical granuloma annulare especially in older patients should alert physicians to the possibility of an occult malignancy.


Improvement by trapidil of cardiac function of the dog heart-lung preparation depressed by pentobarbital.
The effect of trapidil on depressed cardiac function was investigated in 5 dog heart-lung preparations. Trapidil at a dose of 60 mg improved cardiac function which had been severely depressed by 70 +/- 32 (S.D.) mg of sodium pentobarbital. This dose of trapidil, however, produced no significant increase in heart rate. The results suggest that trapidil would be useful in the treatment of heart failure.


Evidence-based use of prokinetic drugs for abomasal disorders in cattle.
Abomasal hypomotility is a prerequisite for abomasal displacement in cattle and is present immediately after surgical correction of left displaced abomasum or abomasal volvulus. Hypocalcemia, hypokalemia, and hyperinsulinemia should be corrected in cattle suspected to have abomasal hypomotility. The most effective prokinetic for calves and adult cattle suspected to have abomasal hypomotility is erythromycin.


Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients.
The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500μg/L), moderate (<500 and ≥100μg/L) or severe (<100μg/L). SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis.


Acute lipase-induced panniculitis in rats with ligated veins of the hindlimb: a contribution to the role of acute panniculitis as a precursor of lipodermatosclerosis of venous disease.
The authors studied the effect of ligation of the femoral and saphenous veins on the evolution of lipase injection-induced subcutaneous fibrosis and inflammation in the rats' hindlimbs. The superficial muscular fascia was thickened and the number of veins was increased 3 days and 3 weeks after vein ligation; both abnormalities disappeared 6 weeks postoperatively. Vein ligation did not quantitatively affect fascial thickening or fibrosing panniculitis in hindlimbs injected with lipase 6 weeks prior to sacrifice. The results contradict the proposition that lipase-induced injury of rats' subcutaneous tissues compromised by venous stasis may lead to a persistent chronic inflammation and fibrosis of the subcutaneous-fascial complex duplicating lipodermatosclerosis in man.


Formation of vinculin plaques precedes other cytoskeletal changes during retinoic acid-induced teratocarcinoma cell differentiation.
Immunofluorescence and immunoblotting techniques were used to study the presence and distribution of vimentin and keratin type intermediate filaments, actin, and vinculin (130 kD protein) during retinoic acid (RA)-induced differentiation of F9 embryonal carcinoma (EC) cells. The undifferentiated F9 cells regularly expressed vimentin, usually concentrated close to the nucleus, but not keratin. Actin appeared as short intracellular filaments and as spikes at the edges of the colonies, together with some diffuse cytoplasmic staining. F9 cells also showed a weak, diffuse cytoplasmic vinculin-specific fluorescence in addition to occasional small focal vinculin patches at the edges of the cell colonies. RA treatment led into a series of changes in the cytoskeletal organization of F9 cells. These changes were initiated by the appearance of distinct vinculin plaques and followed by formation of actin stress fibers and by profound changes in the organization of vimentin in the flattening cells. RA treatment finally led to the appearance and co-expression of keratin fibrils in many of the vimentin-containing F9 cells. This sequence of changes suggests that the vinculin-containing adhesion plaques may be important in the mechanism of RA-induced differentiation of EC cells.


Intra- and inter-speaker variations of formant pattern for lateral syllables in Standard Chinese.
Speech variation of speakers is a crucial issue for speaker recognition and identification, especially for forensic practice. Greater intra-speaker variation is one main reason for incorrect speaker identification in real forensic situations. Understanding the stability of acoustic parameters and their variation in speech is therefore significant for the evaluation of effective parameters for speaker identification. In this paper, all vowels in Standard Chinese including five monophthongs, eight diphthongs and four triphthongs were combined with lateral /l/. Finally, 15 lateral syllables with different tones for 10 speakers were selected and acoustically analyzed. Central frequencies of the first four formants for each syllable were measured for quantitative comparison of intra- and inter-speaker variation in order to provide a general idea of speaker variation in Standard Chinese, and finally serving for forensic application. Results show that the overall intra-speaker variation is less than the inter-speaker variation in great extent under laboratory condition though occasionally they are contrary. This supports the basis for forensic speaker identification, that is, intra-speaker variation should be less than inter-speaker variation in many acoustic features, and further validates the probability and reliability of forensic speaker identification.


Rare case of bronchoscopic debulking of endobronchial leiomyoma.
An endobronchial leiomyoma is a rare benign tumour of lung. It occurs from the smooth muscle of tracheobronchial tree or within lung parenchyma. It presents less than 2% of all benign lung tumours. We present a case report of a 39-year-old male, ex-smoker, with no family history of malignancies, presenting with cough and dyspnoea for 7 months with no symptomatic relief. CAT scan thorax showed well-defined oblong soft tissue mass lesion 24.2 mm × 15.4 mm in right major bronchus compromising central lumen. Flexible bronchoscopy revealed an endobronchial mass at right major bronchus. Patient underwent rigid bronchoscopy with endobronchial mass excision with an electrocautery snare and cryoprobe in the same seating. Complete debulking of tumour was achieved and histopathology report was suggestive of leiomyoma. Prompt investigations and intervention can give favourable outcomes in cases of endobronchial tumours.


Transcriptomic and metabolomic analyses reveal molecular mechanisms associated with the natural abscission of blue honeysuckle (Lonicera caerulea L.) ripe fruits.
Blue honeysuckle (Lonicera caerulea L.) is rich in phenolic compounds and has an extremely high nutritional value. Fruit abscission in the ripe period significantly impacts production and economic benefits. However, the mechanism associated with the abscission of blue honeysuckle fruit remains largely unknown. The easy-abscission cultivar 'HSY' and the hard-abscission cultivar 'Berel' were selected as plant materials. Anatomical changes of the 'HSY' fruit abscission zone (FAZ) during the abscission mainly included cell expansion, detachment, and collapse. Active changes in cell wall-degrading enzyme activity between 39 days postanthesis (DPA) and 55 DPA in 'HSY' FAZ, but not in 'Berel', suggest a critical role for cell-wall-degrading enzymes in regulating abscission. Transcriptome and metabolome analyses revealed that the genes and metabolites responding to abscission mainly act on pathways such as plant hormone signal transduction, starch and sucrose metabolism, pentose and glucuronate interconversions, and phenylpropanoid biosynthesis. The regulatory pathways of fruit abscission are mainly summarized into two parts: phytohormone synthesis and signal transduction, FAZ cell wall metabolism. In this study, 46 key genes related to plant hormone response, 45 key genes involved in FAZ cell wall metabolism, and 73 transcription factors were screened. Quantitative real-time PCR (qRT-PCR) assessed the expression pattern of 12 selected candidate genes, demonstrating the accuracy of the transcriptome data and elucidating the expression patterns of key candidate genes during growth and development. This study will provide an essential resource for understanding the molecular regulatory mechanism of fruit abscission in the blue honeysuckle.


Occipital condyle screw fixation viability according to age and gender anatomy: A computed tomography-based analysis.
To assess the Occipital condyle morphology in an all-age population of Northeastern Mexico, and determine age and gender related changes for surgical viability. A total of 175 consecutive HRCT scans were included and divided into 5 age groups. The condylar length, width, height, sagittal angle, anterior, posterior and medial intercondylar distances, and intercondylar angle of the OC were measured. Mean condylar length, width, and height in total population were 20.58 mm, 9.42 mm, and 9.02 mm, respectively. Differences were observed in most morphometric parameters when comparing age groups. Significant intergender differences in total population were observed in most parameters, when individualizing each age group the height remained significant in all. The group with the least height measurement was aged 5-9 years, this however, could allow the OC screw (≥6.5 mm) placement. Differences in most morphometric parameters of OC were observed between age groups and gender, particularly patients with 5-9 years. However, all groups presented a minimum height that allows the placement of a standard screw. A preoperative imaging study is always recommended due to the variability and complexity of the region.


Size Exclusion Chromatography Strategies and MASH Explorer for Large Proteoform Characterization.
Top-down mass spectrometry (MS)-based analysis of larger proteoforms (>50 kDa) is typically challenging due to an exponential decay in the signal-to-noise ratio with increasing protein molecular weight (MW) and coelution with low-MW proteoforms. Size exclusion chromatography (SEC) fractionates proteins based on their size, separating larger proteoforms from those of smaller size in the proteome. In this protocol, we initially describe the use of SEC to fractionate high-MW proteoforms from low-MW proteoforms. Subsequently, the SEC fractions containing the proteoforms of interest are subjected to reverse-phase liquid chromatography (RPLC) coupled online with high-resolution MS. Finally, proteoforms are characterized using MASH Explorer, a user-friendly software environment for in-depth proteoform characterization.


The Magenstrasse and Mill procedure can be combined with a Roux-en-Y gastric bypass to produce greater and sustained weight loss.
The Magenstrasse and Mill operation (M&M) is effective in producing sustained weight loss and reducing obesity-related co-morbidity. It avoids the implantation of foreign material and is a more physiological procedure by maintaining normal gastric emptying. Side-effects are minimal and operative mortality is low. Satisfactory weight loss is seen at 1 year with 60% of excess weight lost. The present study compared weight loss produced by the combination of a Roux-en-Y gastric bypass (RYGBP) with the standard M&M procedure. Between 1993 and 2001, 118 patients underwent surgery for the treatment of morbid obesity. 70 patients between 1993 and 1998 underwent only a M&M vertical gastric stapling, and 48 patients from 1998 underwent the M&M combined with a RYGBP. Median follow-up for the M&M procedure was 36 months (range 1 to 72) and for the combined M & M and RYGBP was 30 months (range 1 to 48). At all time points following surgery, patients having a RYGBP performed in addition to the standard M&M procedure demonstrated a significantly greater amount of weight lost (P<0.0001, Mann-Whitney U-test) and overall percentage of excess weight lost (P<0.0001, Mann-Whitney U-test). Both groups had a significant reduction in BMI, although this was greater in the group that underwent the combined procedure at 3 years (P<0.001, sample t-test). A more rapid and prolonged weight loss was found when the M&M procedure was performed in combination with a RYGBP. This suggests that this combined procedure may be more beneficial when greater amounts of weight loss are needed in the super-obese.


Take action now to prevent medication errors: lessons from a fatal error involving an automated dispensing cabinet.
An error in the administration of an anaesthetic medication related to an automated dispensing cabinet resulted in a patient fatality and a highly publicised criminal prosecution of a healthcare worker, which concluded in 2022. Urgent action is required to re-engineer systems and workflows to prevent such errors. Exhortation, blame, and criminal prosecution are unlikely to advance the cause of patient safety.


Lactate carriers in the artificially perfused human term placenta.
Thirty-two isolated cotyledons from human term placentae were perfused artificially with a tissue culture medium on the maternal and the fetal side. The transfer and uptake of labelled L-lactate and D-lactate (test substance) relative to L-glucose (reference substance, extracellular marker) were investigated in steady-state experiments (n = 9) and in a single passage paired tracer dilution technique (n = 23). The L-lactate transfer exceeded the L-glucose transfer two to three times. The L-lactate uptake into the trophoblast--both from the maternal and the fetal side--was more than three times that of D-lactate. L-lactate transfer and uptake were inhibited by phloretin. The L-lactate transfer showed a saturation kinetic at increasing chemical concentrations of lactate. It is concluded that lactate carriers exist both in the maternal and fetal side of the trophoblast.


TNF-α stimulation enhances the neuroprotective effects of gingival MSCs derived exosomes in retinal ischemia-reperfusion injury via the MEG3/miR-21a-5p axis.
Retinal ischemia-reperfusion injury (IRI) is one of the main pathogenic mechanisms of glaucoma, which are largely unknown, including neuroinflammation and neuronal death in the pathological process. In our previous studies, mesenchymal stem cells (MSCs) have been reported to play anti-inflammatory and neuroprotective roles. Additionally, conditioned culture medium (CM) of MSCs stimulated by TNF-α have achieved better antiallergic effects in an experimental allergic conjunctivitis mouse model. However, there is an urgent need for cell-free therapy approaches, like exosomes, to reduce the side effects of autoimmunity. The present study aimed to elucidate the pathways involving TNF-α-stimulated gingival MSC (GMSC)-exosomes (TG-exos), in modulating inflammatory microglia and alleviating apoptosis. In this study, exosomes from the CM of GMSCs were isolated by ultracentrifugation and were injected into the vitreous of mice. The results showed that intraocular injection of TG-exos into mice with IRI notably reduced inflammation and cell loss than that with G-exos (GMSC-exosomes). Similar results were observed in vitro. Additionally, with the microRNA (miR) arrays, it was found that miR-21-5p acted as a crucial factor in TG-exos for neuroprotection and anti-inflammation. Following target prediction and dual-luciferase assay suggested that miR-21-5p played a role by combining with programmed cell death 4 (PDCD4), which was regulated by the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) as a competing endogenous RNA (ceRNA). This study demonstrates a new therapeutic pathway for neuroprotection against IRI by delivering miR-21-5p-enriched exosomes through MEG3/miR-21-5p/PDCD4 axis and paves the way for the establishment of a cell-free therapeutic approach for glaucoma.


[Bromine concentration in urine following uptake of therapeutic and suicidal doses of carbromal].
The bromine concentration in urine after ingestion of therapeutic and suicidal doses of bromodiethylacetylcarbamide (carbromal) is described. Connections with the renal elimination of sodium and chlorine are described and discussed.


Clinical factors associated with decision to recommend methylphenidate treatment for children with ADHD in France.
European guidelines advise on best practices for the diagnosis and non-pharmacological and pharmacological treatment of attention-deficit hyperactivity disorder (ADHD). This study aimed to (1) assess whether clinician's decisions to initiate methylphenidate treatment in children diagnosed with ADHD are in accordance with European guidelines and (2) identify clinical factors associated with the decision to recommend methylphenidate prescription. 5 to 13-year-old patients with an ADHD diagnosis were consecutively evaluated in an outpatient child and adolescent psychiatry clinic in France. Patients underwent a multidisciplinary evaluation including a diagnostic interview, symptom severity assessments with parent questionnaires, and IQ testing. We compared children with (n = 105) and without (n = 55) recommended methylphenidate treatment using Student's t test or Wilcoxon Mann-Whitney test and Chi-square or Fisher's test. Multivariate logistic regression was implemented to determine the respective influence of each variable on treatment recommendation. Recommendation to initiate methylphenidate treatment was associated with (1) ADHD combined presentation, (2) co-occurring Oppositional Defiant Disorder/Conduct Disorder (ODD/CD), Developmental Coordination Disorder (DCD) and Learning Disorder (LD), (3) clinical severity and impairment indicated on parent questionnaires, and (4) reduced perceptual reasoning. Using a multivariate regression model, ADHD combined presentation [combined versus predominantly hyperactive/impulsive and unspecified OR 4.52 (1.23-16.55), p = 0.023], age [OR 1.46 (1.14-1.88), p = 0.003], ODD/CD [OR 5.53 (2.19-14.01), p < 0.001], DCD [OR 4.22 (1.70-10.48), p = 0.002], PRI [OR 0.97 (0.94-0.99), p = 0.01] were significantly associated with recommendation of methylphenidate treatment. Our results indicate that clinicians' treatment decision-making complies with European guidelines and is furthermore associated with the type and severity of ADHD symptoms but also with co-occurring disorders.


Initial biophysical characterization of Amynthas gracilis giant extracellular hemoglobin (HbAg).
The aim of the present work was the biophysical characterization of the Amynthas gracilis hemoglobin (HbAg). The oxy-HbAg optical absorption data, with Soret and Q bands centered at 415, 540 and 575 nm, were stable and unchanged at pH 7.0. An increase in pH promotes decrease in the intensity in the optical absorption bands, suggesting an oligomeric dissociation and partial oxidation. Identical stability at pH 7.0 was observed in DLS results that presented a hydrodynamic diameter of 28 nm, characteristic of the whole oligomer. DLS shows that HbAg undergoes oligomeric dissociation and an aggregation/denaturation process that corroborates spectroscopic data. Our results showed that the monomer d presents four isoforms with molecular mass (MM) ranging from 16,244 to 16,855 Da; the trimer subunit presents two isoforms, (abc)1 and (abc)2, with MM of 51,415 ± 20 Da and 51,610 ± 14 Da, respectively, and a less intense species, at 67,793 Da, assigned to the tetramer abcd. Monomeric chains a, obtained from reduction of the disulfide-bonded trimer abc, present four isoforms with MM 17,015 Da, 17,061 Da, 17,138 Da and 17,259 Da. DLS and LSI revealed an isoeletric point (pI) of oxy-HbAg of 6.0 ± 0.3 and 5.5, respectively. Data analysis by IEF-SDS-PAGE revealed that the pI of oxy-HbAg is 6.11, correlating with DLS and LSI data. These studies indicate that oxy-HbAg is very stable, at pH 7.0, and has differing properties from orthologous giant hemoglobins.


NMOSD with anti-MOG antibodies following anti-TNFα therapy: A case report.
Tumor necrosis factor α (TNFα) inhibitors are highly effective and a therapeutic choice for several inflammatory diseases. Their broad and long-term use is associated with a growing number of paradoxical autoimmune events including demyelinating lesions of the central nervous system (CNS). We report and discuss a case of neuromyelitis optica spectrum disorder (NMOSD) with positive myelin oligodendrocyte glycoprotein antibodies (MOG-IgG1) following anti-TNFα therapy for a pustular psoriasis.


Lifestyle-Related Factors and Atopy in Seven Danish Population-Based Studies from Different Time Periods.
The prevalence of allergic respiratory disease tends to increase in populations that adopt the so-called Westernized lifestyle. We investigated the association between atopy and several possible lifestyle-related factors in seven Danish population-based studies. A total of 20048 persons participated in the seven studies. We used logistic regression to analyse the associations between possible determinants and atopy defined as serum specific IgE or skin prick test positivity against inhalant allergens. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). In addition, individual participant data meta-analyses were performed. Atopy was significantly associated with younger age (OR per 1 year increase in age: 0.97; 95% CI: 0.97, 0.98); male sex (OR for males versus females: 1.34; 95% CI: 1.24, 1.45), heavy drinking (OR for heavy drinkers versus light drinkers: 1.15; 95% CI: 1.04, 1.27), never smoking (OR for current versus never smokers: 0.73; 95% CI: 0.67, 0.80), and higher educational level (OR for educated versus uneducated: 1.27; 95% CI: 1.15, 1.41). Atopy was not associated with blood pressure, serum total cholesterol, physical activity or body mass except in women only, where we found a positive association (OR for obese vs. normal weight: 1.18; 95% CI: 1.00, 1.39) with ptrend = 0.032. Of interest for preventive purposes, we found that atopy was associated with some of the reversible lifestyle-related factors that characterize a Westernized lifestyle.


Utilization of light energy in phototrophic Gemmatimonadetes.
Gemmatimonas phototrophica is, so far, the only described phototrophic species of the bacterial phylum Gemmatimonadetes. Its cells contain a unique type of photosynthetic complex with the reaction center surrounded by a double ring antenna, however they can also grow in the dark using organic carbon substrates. Its photosynthesis genes were received via horizontal gene transfer from Proteobacteria. This raises two questions; how the horizontally transferred photosynthesis apparatus has integrated into the cellular machinery, and how much light-derived energy actually contributes to the cellular metabolism? To address these points, the photosynthetic reactions were studied on several levels, from photophysics of the reaction center to cellular growth. Flash photolysis measurements and bacteriochlorophyll fluorescence kinetic measurements documented the presence of fully functional type-2 reaction centers with a large light harvesting antenna. When illuminated, the bacterial cells reduced their respiration rate by 58 ± 5%, revealing that oxidative phosphorylation was replaced by photophosphorylation. Moreover, illumination also more than doubled the assimilation rates of glucose, a sugar that is mostly used for respiration. Finally, light increased the growth rates of Gemmatimonas phototrophica colonies on agar plates. All the presented data provide evidence that photosynthetic complexes are fully integrated into cellular metabolism of Gemmatimonas phototrophica, and are able to provide a substantial amount of energy for its metabolism and growth.


Toxicity of Piper aduncum (Piperaceae) Essential Oil Against Euschistus heros (F.) (Hemiptera: Pentatomidae) and Non-Effect on Egg Parasitoids.
Plant essential oils have been recognized as significant natural resources for insecticides. Herein, we have assessed the toxicity of the essential oil of Piper aduncum (Piperaceae) against Euschistus heros (F.) (Hemiptera: Pentatomidae), a key soybean pest in Neotropical America. In addition, we have assessed its effect on the performance of egg parasitoids. The essential oil was obtained from the leaves of P. aduncum via hydrodistillation. Subsequently, bioassays of the concentration response to eggs (contact and immersion methods), nymphs, and adults (topical application) were conducted, to assess the lethal effects on the stink bug. We also evaluated the performance of parasitism and adult emergence of egg parasitoids, when the host eggs were treated with essential oil. In the egg bioassay, both exposure methods were efficient for unviable eggs (immersion LC50 = 15.64 mg mL-1; contact LC50 = 21.29 mg mL-1), with the highlight on the immersion method. The bioassay with nymphs indicated a higher toxicity of essential oil, with lower concentrations (LC50 = 11.37 mg mL-1) being required to cause the death of insects. For adults, a reduction in survival of insects was observed, and consequently, there was a reduction in the number of individuals in the next generation. Although the essential oil was toxic to E. heros, it exhibited lower toxicity for egg parasitoids, as there was no effect on parasitism and the emergence of wasps. We discuss likely explanations for such selectivity. In summary, we found that the essential oil was promising for the control of E. heros, because it caused deleterious effects at all development stages of the stink bug and had no effect on parasitism and emergence of the egg parasitoids, which suggested compatibility with biological control.


Rejuvenation of the lithosphere by the Hawaiian plume.
The volcanism responsible for creating the chain of the Hawaiian islands and seamounts is believed to mark the passage of the oceanic lithosphere over a mantle plume. In this picture hot material rises from great depth within a fixed narrow conduit to the surface, penetrating the moving lithosphere. Although a number of models describe possible plume-lithosphere interactions, seismic imaging techniques have not had sufficient resolution to distinguish between them. Here we apply the S-wave 'receiver function' technique to data of three permanent seismic broadband stations on the Hawaiian islands, to map the thickness of the underlying lithosphere. We find that under Big Island the lithosphere is 100-110 km thick, as expected for an oceanic plate 90-100 million years old that is not modified by a plume. But the lithosphere thins gradually along the island chain to about 50-60 km below Kauai. The width of the thinning is about 300 km. In this zone, well within the larger-scale topographic swell, we infer that the rejuvenation model (where the plume thins the lithosphere) is operative; however, the larger-scale topographic swell is probably supported dynamically.


NF-KappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissues.
Clear cell renal cell carcinoma (ccRCC) is the most frequently encountered tumor in the adult kidney. Many factors are known to take part in the development and progression of this tumor. Nuclear factor kappa B (NF-kappaB) is a family of the genes that includes five members acting in events such as inflammation and apoptosis. In this study, the role of NF-kappaB (p50 subunit) in ccRCC and its relation to angiogenesis and apoptosis were investigated. Formalin-fixed and paraffin embedded tissue blocks from 40 patients with ccRCC were studied. Expressions of NF-kappaB (p50), VEGF, EGFR, bc1-2 and p53 were detected immunohistochemically. The relationship of NF-kappaB with these markers and clinicopathological findings were evaluated. The expression of NF-kappaB was detected in 35 (85%), VEGF in 37 (92.5%), EGFR in 38 (95%), bc1-2 in 33 (82.5%) and p53 in 13 (32.5%) of 40 ccRCC patients. Statistical analyses revealed a significant relation between NF-kappaB expression and VEGF (p = 0.001), EGFR (p = 0.004), bc1-2 (p = 0.010) and p53 (p = 0.037). There was no significant correlation between NF-kappaB and such parameters as tumor grade, stage, age and sex. The results of this study indicated that in ccRCC cases NF-kappaB was associated with markers of angiogenesis and apoptosis such as VEGF, EGFR, bc1-2 and p53. In addition, the results did not only suggest a close relationship between NF-kappaB and VEGF, EGFR, bc1-2 and p53 in ccRCC, but also indicate that NF-kappaB was a potential therapeutic target in the treatment of ccRCC resistant to chemotherapy.


Ethnobotanical study of medicinal plants used against human ailments in Gubalafto District, Northern Ethiopia.
Traditional medicinal plant species documentation is very crucial in Ethiopia for biodiversity conservation, bioactive chemical extractions and indigenous knowledge retention. Having first observed the inhabitants of Gubalafto District (Northern Ethiopia), the author gathered, recorded, and documented the human traditional medicinal plant species and the associated indigenous knowledge. The study was conducted from February 2013 to January 2015 and used descriptive field survey design. Eighty-four informants were selected from seven study kebeles (sub-districts) in the District through purposive, snowball, and random sampling techniques. Both quantitative and qualitative data were collected through semi-structured interviews, guided field walks, demonstrations, and focus group discussions with the help of guided questions. Data were organized and analyzed by descriptive statistics with SPSS version 20 and Microsoft Office Excel 2007. A total of 135 medicinal plant species within 120 genera and 64 families were documented. Among the species, Ocimum lamiifolium and Rhamnus prinoides scored the highest informant citations and fidelity level value, respectively. In the study area, Asteraceae with 8.1% and herbs with 50.4% plant species were the most used sources for their medicinal uses. A total of 65 ailments were identified as being treated by traditional medicinal plants, among which stomachache (abdominal health problems) was frequently reported. Solanum incanum was reported for the treatment of many of the reported diseases. The leaf, fresh parts, and crushed forms of the medicinal plants were the most preferred in remedy preparations. Oral application was the highest reported administration for 110 preparations. A majority of medicinal plant species existed in the wild without any particular conservation effort. Few informants (about 5%) had only brief notes about the traditional medicinal plants. Ninety percent of the respondents have learned indigenous medicinal plants knowledge from their family members and friends secretly. Orthodox Church schools were found the main place for 65% of healer's indigenous knowledge origin and experiences. Elders, aged between 40 and 84 years, gave detailed descriptions about traditional medicinal plants. Traditional medicinal plants and associated indigenous knowledge are the main systems to maintain human health in Gubalafto District. But minimal conservation measures were recorded in the community. Thus, in-situ and ex-situ conservation practices and sustainable utilization are required in the District.


Glomerular hyperfiltration is a predictor of adverse outcomes following major urologic oncology surgery.
Glomerular hyperfiltration (GHF) has been associated with cardiovascular disease and all-cause mortality. We aimed to evaluate whether preoperative GHF is associated with 30-day complications following major urologic oncology procedures. We conducted a retrospective cohort study using subjects from the 2006 to 2019 American College of Surgeons National Surgical Quality Improvement Program database who underwent prostatectomy, cystectomy, or nephrectomy. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Patients were classified as having either low, normal, or high eGFR based on the 5th and 95th percentiles of age- and sex-specific quintiles for eGFR. Using multivariable logistic regression, we evaluated GHF as an independent predictor of postoperative complications. A total of 120,013 patients were eligible for analysis, of which 1706 (1.4%) were identified as having GHF, with a median eGFR of 105.37 ml/min per 1.73 m2 (IQR 94.84-116.77). Compared to patients with normal eGFR, patients with GHF were older (68 years, [IQR 60-71], p < 0.001), had a lower BMI (27.52 kg/m2 [IQR 23.71-31.95], p < 0.001), and greater 5-item modified frailty index scores (≥ 1, 70.6%, p < 0.001). Multivariable logistic regression demonstrated that GHF was associated with greater odds of any complication (OR 1.23, 95% CI 1.08-1.40, p = 0.002), non-home discharge (OR 1.86, 95% CI 1.50-2.30, p < 0.001), and prolonged LOS (OR 1.33, 95% CI 1.18-1.51, p < 0.001). GHF is associated with greater odds of 30-day complications following major urologic oncology surgery.


Isolated T wave alternans progressing to QRS-T alternation after ventricular defibrillation.
A 54-year-old woman underwent replacement of a thrombosed Björk-Shiley aortic valve prosthesis. Post operative electrical defibrillation resulted in isolated T wave alternation which progressed to total QRS-T electrical alternans. This report represents the first description of such a phenomenon.


Intraspecific interactions between adults and juveniles of the subtidal limpet, Patelloida mufria.
Regular monitoring of populations of the subtidal limpet Patelloida mufria (Hedley), which were at naturally large densities (>1000/m2), showed that at the times when there were peaks in juvenile recruitment, the mortality of adults increased greatly. This produced a cyclical pattern in the density of adults, suggesting the juveniles play a partial regulatory role. Experimental manipulations were done to test the influence of overall density and the density of juveniles on the growth and survival of adults. These indicated that an increase in overall density reduced the rate of growth of individuals and increased the rate of adult mortality during the peaks in juvenile recruitment. Similarly, removing these juveniles as they recruited averted this decline in adult abundance. The proposed mechanism to explain these results is that the juveniles have a competitive advantage over adults as they are much smaller and therefore require less energy to survive. It is hypothesisied, therefore, that there will be a threshold of adult size below which the recruits will lose their competitive advantage. Furthermore, if their density became too great, the cover of crustose algae (which is the main food of this species) would be removed resulting in a rapid decline in the numbers of P. mufria. Such an occurrence could be the ultimate regulatory agent for this species.


Multislice continuous arterial spin-labeled perfusion MRI in patients with chronic occlusive cerebrovascular disease: a correlative study with CO2 PET validation.
To compare the use of multislice continuous arterial spin labeling (CASL) and CO(2) positron emission tomography (PET) to assess CBF in patients with chronic occlusive cerebrovascular disease for the validation of quantitative CASL perfusion in an altered hemodynamic state. Eleven patients with occlusive carotid artery disease were studied with CASL and conventional MRI. Cerebral blood flow (CBF) was also measured with O(15)-labeled CO(2) gas using a whole-body PET scanner. The average values within region of interests (ROIs) drawn on coregistered CASL and PET images were used for the linear regression analysis and to assess the effect of transit time on the quantification using CASL. In all patients there was a significant correlation between the CBF values from CASL and PET (r = 0.71 +/- 0.07, P < 0.001). The slope of regression lines varied widely among patients (0.54-1.77). Longer transit times were estimated in four of 11 patients in the hypoperfusion region. Quantification of CBF using CASL is feasible and reasonable, even when employed in a routine clinical setting. However, the long transit time may lead to underestimation of the affected side in occlusive cerebrovascular disease.


Quantitative evaluation of blinking in blepharospasm using electrooculogram-integrated smart eyeglasses.
Smart eyeglasses with an integrated electrooculogram (EOG) device (JINS MEME ES_R®, JINS Inc.) were evaluated as a quantitative diagnostic tool for blepharospasm. Participants without blepharospasm (n = 21) and patients with blepharospasm (n = 19) undertook two voluntary blinking tests (light and fast) while wearing the smart eyeglasses. Vertical (Vv) and horizontal (Vh) components were extracted from time-series voltage waveforms recorded during 30 s of the blinking tests. Two parameters, the ratio between the maximum and minimum values in the power spectrum (peak-bottom ratio, Fourier transform analysis) and the mean amplitude of the EOG waveform (peak amplitude analysis) were calculated. The mean amplitude of Vh from light and fast blinking was significantly higher in the blepharospasm group than in the control group (P < 0.05 and P < 0.05). Similarly, the peak-bottom ratio of Vv from light and fast blinking was significantly lower in the blepharospasm group than in the control group (P < 0.05 and P < 0.05). The mean amplitude of Vh and peak-bottom ratio of Vv correlated with the scores determined using the Jankovic rating scale (P < 0.05 and P < 0.01). Therefore, these parameters are sufficiently accurate for objective blepharospasm classification and diagnosis.


Genotyping and the Future of Transfusion in Sickle Cell Disease.
Patients with sickle cell disease (SCD) have a high rate of red cell alloimmunization, which increases morbidity and mortality. Reasons for this susceptibility are multifactorial, but differences in antigen frequency between donors and recipients are one of the modifiable risk factors. Here, we evaluate the benefits of red cell molecular antigen-typing for both patients with SCD and their donors and describe how results from these critical tests could be used to enhance patient safety.


The ultrastructure of preimplantation hamster blastocysts developed in vivo and in vitro.
Scanning electron microscopy of zona-free blastocysts showed bulging trophoblast cells possessing slender microvilli and many small projections of various lengths. The trophoblast cells contained mitochondria in two shapes. One type consisted of spheroids with a few mitochondrial inner membranes. The other type had a more conventional appearance. Fibrous material varied in amount. The trophoblast cells from blastocysts cultured for 1 day had an appearance similar to that of trophoblast tissue fixed in vivo. However, the large, dense mitochondria with few cristae had diminished in number, and globular mitochondria occurred more frequently. Furthermore, the fibrous material was more sparsely distributed after culture. The experiments demonstrated that cultured hamster blastocysts have ultrastructural characteristics similar to those of in vivo blastocysts. Experiments are in progress to test whether the in vitro technique can determine the growth requirements of the hamster blastocyst.


Approach to gastroesophageal reflux disease in primary care: Putting the Montreal definition into practice.
To apply the recently published Montreal definition of gastroesophageal reflux disease (GERD) in primary care. The Montreal definition of GERD was developed by an international consensus group of experts in GERD and primary care physicians using rigorous evidence-based methods along with modern consensus development techniques and a patient-centred approach. Gastroesophageal reflux disease can be diagnosed in primarycare based on symptoms alone without additional diagnostic testing. Symptoms reach a threshold where they constitute disease when they are troublesome (cause difficulty) to patients. In addition to the cardinal symptoms of heartburn and regurgitation, people with GERD can also have sleep disturbances, chest pains, or respiratory symptoms. Monitoring patients' response to proton pump inhibitor therapy can confirm the success of management. Treatment for symptoms of GERD can also heal underlying reflux esophagitis if it is present. Primary care physicians can diagnose and manage GERD confidently in most patients by investigating and treating troublesome symptoms without the need for additional investigations or referral to specialists.


Lipoblastoma presenting as a mesenteric mass in an infant.
This article describes an infant with a large abdominal mass and hypertension. A 5-month-old infant girl with diarrhea of 1 week's duration and a large right-sided abdominal mass was brought for treatment. Computed tomography of the abdomen revealed a large, generally homogeneous, hypodense mass, which compressed the right kidney, resulting in dilatation of the right renal collecting system. At surgery, the mass was adherent anteriorly to the transverse colon and attached by a stalk to the mesentery near the origin of the right colic artery. Examination of the mass showed an encapsulated lipoblastoma. Cytogenetic analysis revealed a 46,XX karyotype with a reciprocal translocation between chromosome 2 and chromosome 8 with breakpoints at q23 and q11.2, respectively. Lipoblastoma is a rapidly growing but benign tumor, which can cause severe medical problems by compressing major organs. Cytogenetic analysis can reveal translocations involving chromosome 8 band q11.2, which appears to be a specific chromosome marker for lipoblastoma.


Adaptive changes in translation initiation activities for rat pancreatic protein synthesis with feeding of a high-protein diet.
We have previously demonstrated that dietary protein induced pancreatic hypergrowth in pancreaticobiliary diverted (PBD) rats. Dietary protein and dietary amino acids stimulate protein synthesis by regulating translation initiation in the rat skeletal muscle and liver. The aim of the present study was to determine whether feeding a high-protein diet induces activation of translation initiation for protein synthesis in the rat pancreas. In PBD rats in which the bile-pancreatic juice was surgically diverted to the upper ileum for 11-13 days, pancreatic dry weight and protein content were doubled compared with those in sham rats and further increased with feeding of a high-protein diet (60% casein diet) for 2 days. These pancreatic growth parameters were maintained at high levels for the next 5 days and were much higher than those of sham rats fed a high-protein diet. In both sham and PBD rats, feeding of a high-protein diet for 2 days induced phosphorylation of eukaryotic initiation factor 4E-binding protein 1 and 70-kDa ribosomal protein S6 kinase, indicating the activation of the initiation phase of translation for pancreatic protein synthesis. However, this increased phosphorylation returned to normal levels on Day 7 in PBD but not in sham rats. We concluded that feeding a high-protein diet induced pancreatic growth with increases in the translation initiation activities for pancreatic protein synthesis within 2 days and that prolonged feeding of a high-protein diet changed the initiation activities differently in sham and PBD rats.


Rather than interleukin-27, interleukin-6 expresses positive correlation with liver severity in naïve hepatitis B infection patients.
Effective cytokines can drive the commitment of naive T cells to regulate immune response after antigen-mediated activation. Aims are to elucidate the clinical role of serum IL-27 and IL-6 in the different stages of naïve hepatitis B virus (HBV)-infected patients. Samples with well-characterized clinical profiles were assessed from 395 HBV-infected patients including chronic hepatitis B (CHB) group in 291 patients, liver cirrhosis (LC) group in 57 patients, hepatocellular carcinoma (HCC) group in 47 patients. Another 139 non-HBV infected individuals were enrolled as control group (CG) including 104 with normal liver function (NF) and 35 with liver dysfunction (LD). The HBV-infected group and separated groups presented significantly higher IL-27 and IL-6 expression than the CG or subgroups of CG. In contrast to IL-27, IL-6 showed significant differences with deteriorating liver condition compared with LC or HCC with CHB groups. Furthermore, IL-6, rather than IL-27, showed significant statistical differences in patients with advanced liver disease compared with those of mild or moderate to severe liver disease and in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. The data associated with liver function, including Albumin, Bilirubin, INR, Platelet and AFP levels, were significantly correlated to IL-6 expression, but had weak correlation to IL-27 expression in HBV patients. Serum IL-27 can trigger immune response to prevent hepatic injury in different clinical-pathologic stages of HBV-infected patients earlier, but IL-6 may play an extremely important role to determine the liver progression.


Pathogenic viruses: smart manipulators of the interferon system.
Vertebrate cells are equipped with specialized receptors that sense the presence of viral nucleic acids and other conserved molecular signatures of infecting viruses. These sensing receptors are collectively called pattern recognition receptors (PRRs) and trigger the production of type I (alpha/beta) interferons (IFNs). IFNs are secreted and establish a local and systemic antiviral state in responsive cells. Viruses, in turn, have evolved multiple strategies to escape the IFN system. They try to avoid PRR activation, inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Here, we summarize current knowledge in light of most recent findings on the intricate interactions of viruses with the IFN system.


GnRH agonist trigger does not always cause luteolysis: a case report.
This study reports an IVF patient with excessive ovarian response, who received gonadotrophin-releasing hormone agonist (GnRHa) triggering. Fourteen oocytes were retrieved, and one embryo transferred 2 days later. Although no further luteal support was given, close follow-up showed consistently high oestradiol and progesterone concentrations, so no exogenous luteal support was given. A clinical pregnancy was achieved without signs or symptoms of ovarian hyperstimulation syndrome. This case report highlights the importance of individual follow-up post agonist trigger.


Direct and indirect competitive monoclonal antibody-based ELISA of Aflatoxin B1 in groundnut.
Direct and indirect competitive enzyme-linked immunosorbent assays were optimized for the determination of aflatoxin B1 in groundnut utilizing a specific monoclonal antibody developed at the University of Strathclyde, UK. The monoclonal antibody was conjugated to horseradish peroxidase (HRP) for direct competitive assay, while a commercially available goat-antimouse IgG-HRP conjugate was employed for indirect competitive ELISA. Both ELISAs detected aflatoxin B1 as low as 20 pg/well. Methanol-water-KCl (70 + 30 v/v, 0.5 %) extracts of groundnut were assayed by ELISA after diluting 1: 10 with PBS-Tween buffer or subjected to simple cleanup for 5:1 concentration prior to assay. The mean recoveries from groundnut spiked with 10 to 200/ig/kg of pure aflatoxin B1 were >90% in either ELISA, but the toxin recoveries at concentrations of 1-5μg/kg were only 65-67 % when subjected to cleanup and concentration before assay. The mean within-assay, inter-assay, and sub-sample coefficients of variation by ELISA of aflatoxin B1 in naturally contaminated groundnuts were, respectively, 8.9%, 11.1%, and 7.9% for direct competitive assay and 4.6%, 11.2%, and 8% for indirect competitive assay. Both ELISA methods are useful for routine analysis of aflatoxin B1 in groundnuts.


Successful repair of graft failure and abdominal aortic aneurysm following thoraco-abdominal bypass for atypical aortic coarctation.
A 54-year-old woman, who underwent descendo-abdominal aortic bypass grafting for atypical aortic coarctation complicated with Takayasu's arteritis 37 years previously, was referred to our hospital for treatment of a pseudoaneurysm due to rupture of the graft. Preoperative computed tomography scan also demonstrated an abdominal aortic aneurysm. First, an endovascular stent-graft repair of the pseudoaneurysm was performed, then the abdominal aortic aneurysm was repaired with the aid of cardiopulmonary bypass. Proper surgical planning was important to treat this rare development accompanied by aberrant circulation.


Epithelioid angiosarcoma of the thyroid: report of a case from an italian non-alpine area and review of the literature.
Epithelioid angiosarcoma of the thyroid is a rare mesenchymal neoplasm, mainly described in the Alpine area. This lesion was initially considered an anaplastic carcinoma, but immunohistochemical and ultrastructural features have proven the endothelial differentiation of tumor cells. In fact, the peculiarity of this tumor concerns the expression of low-molecular weight cytokeratins by neoplastic cells of endothelial origin. We describe a case of epithelioid angiosarcoma of the thyroid occurred in a 73-year-old woman from an Italian non-Alpine area, and a review of non-Alpine primary thyroid epitheliod angiosarcoma is presented.


Anticoagulant blood factor deficiencies (protein C).
Anti-coagulant proteins are essential to maintain blood hemostatis for the supply of oxygen and nutrients to tissue cells and for the removal of toxic by-products from metabolism. Hereditary or acquired deficiencies of Protein C, Protein S, or Antithrombin III can lead to disease states such as deep vein thrombosis (DVT) with the possibility of producing lung emboli. Phenomena named Factor V Lieden can produce a similar pathologic condition. Anti-coagulant deficiencies, including Factor V Lieden, are HIDDEN blood conditions that can allow blood clot development, especially with trauma to the tissue and circulatory system. It is proposed that all children between ages twelve to fourteen be checked hereditary deficiencies and Factor V Lieden complications. This would require the development of inexpensive assay equipment12. The present research focuses on the low cost production of Zymogen Protein C via purification from blood plasma Cohn Fraction IV-1. This process is difficult due to the several Homologous Vitamin K dependent proteins in the blood coagulation cascade. Traditional chromatography (ion exchange) cannot achieve the desired separation. Some more exotic technologies are very expensive so our work proposes to use Immobilized Metal Affinity Chromatography (IMAC). It is hoped to produce a lower cost product that can be used prophylactic ally to treat Protein C deficiencies and possibly other coagulation problems.


Selectively desulfated heparin inhibits P-selectin-mediated adhesion of human melanoma cells.
Accumulating evidence has suggested that one of the mechanisms by which heparin inhibits metastasis is by blocking the P-selectin-based interaction of platelets with tumor cells. Here we demonstrate that the sulfate groups at C6/N and especially C6, but not C2 and C3, of heparin play a critical role in P-selectin recognition and that 2-O,3-O-desulfated heparin can block P-selectin-mediated A375 human melanoma cell adhesion. Our findings show that chemical modification of heparin, especially 2-O,3-O-desulfation, may result in a therapeutic agent that is anti-metastatic because it blocks unwanted P-selectin-dependent adhesion but that lacks dose-limiting anticoagulant effects.


QTLs position of some important ornamental traits in recently developed OO lily population.
Lilium L. is a perennial ornamental bulbous species, belonging to Liliaceae family, which consists of about 100 species. One of the most important hybrids in Lilium L. is the Oriental hybrid lily. Different cross combinations have been done in the lily family such as AA (Asiatic × Asiatic), AL (Asiatic × Longiflorum), and OT (Oriental × Trumpet). The OO (Oriental × Oriental) combination is a new one. SSR and AFLP markers were used to overlap each other and the genetic linkage groups were created according to the haploid number of lily chromosomes (12 linkage groups). In this experiment, the final F1 population, which creates a genetic linkage group, was 100 individuals. For map construction, JOINMAP 4.0 software by treating segregation data of markers as a CP (out breeder full-sib family) model was used. After evaluation of ornamental traits, MapQTL 4.0 software was also used to find possible QTLs on these linkage maps. A total of 940 primers were tested and the best ones, which were 172 primer pairs (96 AFLP and 76 SSR markers), were used for map construction and the total of 616 loci (465 loci for AFLP marker and 151 loci for SSR marker) were scored. The entire mapped length was 2144.2 cM. 8 QTLs were obtained for flower number which is an important trait in lily. Each QTL locus explained the phenotypic variation of 2.4-89.5%. The highest amount of LOD (35.21) was found in LG-F1P2 for FN4 QTL. For leaf number, one-QTL was mapped with LOD of 7.08 between 2 markers on the LG-M10 of maternal maps. The QTL for petal length was placed on the LG-F1P2 of the F1 hybrid maps on the E-CGC/M-CGC-4 primer combination. The petal width QTLs also were mapped on the E-CGC/M-CGC-4. Qualitative locus named LN was mapped on the LG-M10 of the maternal maps. PW2 QTL was also localized on the LG-F4 of the paternal maps. In this experiment, 5 QTLs also were mapped for spot number in all F1 hybrids and paternal and maternal maps, and spot size. Moreover, one QTL with the length of 51 cM was measured on the LG-M8 of the maternal maps. Plant height QTL with the LOD of 12.54 was mapped on the primer combination of E-CGC/M-CGC-4 on the LG-F1P2 of the F1 hybrid maps.


Non-binary gender/sex identities.
An increasing number of individuals openly identify as non-binary (i.e., not exclusively female or male). Accordingly, psychological research on non-binary identities has expanded rapidly. We review key insights from this growing literature, first examining work that has demonstrated links between beliefs about the true nature of gender and/or sex (gender/sex) and feelings toward non-binary people. We also review research on non-binary people's self-concepts, which has shown the inadequacy of binary-focused gender/sex measurement practices for effectively studying non-binary people's lives and has suggested treating gender/sex as multidimensional. Then, we consider scholarship on non-binary people's wellbeing, including work exploring sources of joy and pleasure in non-binary people's lives (e.g., gender euphoria). Finally, we discuss recent advances in gender-inclusive theories and methods.


Effects of methylglyoxal bis(guanylhydrazone) and two phenylated analogues on S-adenosylmethionine decarboxylase activity from Eimeria stiedai (Apicomplexa).
1. Activity of S-adenosylmethionine decarboxylase, one of the rate-limiting enzymes of polyamine biosynthesis, was determined in oocysts of Eimeria stiedai, a coccidian parasite of the rabbit. 2. Several properties of the enzyme were compared to the mammalian enzyme. It showed considerably less substrate affinity than the analog enzyme from the rabbit. 3. The E. stiedai enzyme showed a low sensitivity to methylglyoxal bis(guanylhydrazone), a frequently used inhibitor of the enzyme in mammals, and two phenylated derivatives. 4. Results with the inhibitors are discussed in view of their potential use in chemotherapy.


Aortic root dilatation in young patients with cryptogenic stroke and patent foramen ovale.
No previous study has looked for an association between aortic dilatation and the clinical sequelae of patent foramen ovale (PFO), although a possible relationship has been identified in case reports. To compare aortic dimensions in patients with symptomatic PFO and healthy controls. Forty-seven patients were identified who presented with cryptogenic cerebrovascular accident (CVA) assessed as most likely secondary to PFO (confirmed by contrast study), were aged less than 50 years and underwent percutaneous PFO closure. Forty-seven age-, sex- and body surface area-matched healthy controls were also identified. Aortic root diameters were greater in PFO patients. The difference was more marked at the levels of the sinuses of Valsalva (34±4 vs 31±3 mm, P<0.01) and the proximal ascending aorta (32±4 vs 29±3, P<0.01) and more modest at the level of the aortic annulus (23±3 vs 22±2 mm, P=0.20). In addition, patients with massive right-to-left shunting tended to have larger aortic diameters. In contrast, left ventricular end-systolic and end-diastolic diameters were not larger than in controls (30±4 vs 32±5 mm, P=0.10 and 48±5 vs 50±4 mm, P=0.04, respectively). The present study shows that aortic diameter is increased in young patients with cryptogenic CVA and PFO compared with in healthy subjects. Our results suggest that aortic dilatation may potentiate the risk of CVA in PFO patients and support further research in this area.


Plastome Diversity and Phylogenomic Relationships in Asteraceae.
Plastid genomes are in general highly conserved given their slow evolutionary rate, and thus large changes in their structure are unusual. However, when specific rearrangements are present, they are often phylogenetically informative. Asteraceae is a highly diverse family whose evolution is long driven by polyploidy (up to 48x) and hybridization, both processes usually complicating systematic inferences. In this study, we generated one of the most comprehensive plastome-based phylogenies of family Asteraceae, providing information about the structure, genetic diversity and repeat composition of these sequences. By comparing the whole-plastome sequences obtained, we confirmed the double inversion located in the long single-copy region, for most of the species analyzed (with the exception of basal tribes), a well-known feature for Asteraceae plastomes. We also showed that genome size, gene order and gene content are highly conserved along the family. However, species representative of the basal subfamily Barnadesioideae-as well as in the sister family Calyceraceae-lack the pseudogene rps19 located in one inverted repeat. The phylogenomic analysis conducted here, based on 63 protein-coding genes, 30 transfer RNA genes and 21 ribosomal RNA genes from 36 species of Asteraceae, were overall consistent with the general consensus for the family's phylogeny while resolving the position of tribe Senecioneae and revealing some incongruences at tribe level between reconstructions based on nuclear and plastid DNA data.


Optimizing medications in older adults with cognitive impairment: Considerations for primary care clinicians.
To provide primary care physicians with an approach to medication optimization in older adults with cognitive impairment. The approach is based on an accredited memory clinic training program developed by the Centre for Family Medicine Primary Care Collaborative Memory Clinic. Dementia increases the risk of medication-related adverse events and adds to the complexity and challenge of providing optimal care for these older adults. Considerations include medication adherence, appropriate therapeutic targets for comorbid conditions, minimized use of medications with potentially adverse cognitive effects, and rational use and monitoring of cognition-enhancing drugs. Medication management plans must be individualized and based on goals of care. Primary care physicians must consider many factors in optimizing medications for those with cognitive impairment.


Barriers to effective care: Specialty drug treatment in Philadelphia.
In Philadelphia, the poorest big city in the United States, an estimated 60,000 people misuse opioids and more than 3500 have died of overdose in the past three years. In 2019, fentanyl was detected in 76% of drug-related deaths and 94% of opioid-involved deaths. While much attention has been directed at the public face of the city's drug problem, more than 75% of drug deaths in 2017 took place in a private residence. Based on qualitative research to understand the vulnerabilities of this hidden population of drug users, we interviewed kin of 35 people who had died of opioid overdose in 2017 to learn whether their loved one had interacted with any social services or harm-reduction interventions. In our demographically and geographically representative sample of decedents, we found that while most had received treatment at least once, many faced barriers to getting treatment when they needed it, including barriers related to stigma, structural racism, gender inequities, bureaucracy, insurance requirements, and cost. We argue that these barriers place an undue burden on people with substance use disorder and their kin during particularly fraught moments of heightened vulnerability. The failure of state and federal policies, practices, and infrastructure to address these barriers, and the failure to require that evidence-based care be provided during treatment have deleterious effects on people affected by the opioid epidemic in the United States.


Circular intermediates with missing nucleotides in the conversion of supercoiled or nicked circular to linear duplex DNA catalyzed by two species of BAL 31 nuclease.
The extracellular nucleases from Alteromonas espejiana BAL 31 can catalyze the endonucleolytic and/or exonucleolytic hydrolysis of duplex DNA in response to a variety of alterations, either covalent or noncovalent, in DNA structure. The nuclease can exist as at least two kinetically and molecularly distinct protein species. The two species that have been studied, called the 'fast' (F) and 'slow' (S) nucleases, both readily convert negatively supercoiled DNAs to linear duplex molecules and accomplish this conversion through the formation of a circular duplex intermediate containing usually a single interruption in one strand. It is further shown that most of these intermediates contain gaps arising from the removal in a processive manner of one or more nucleotide residues after the introduction of the initial strand break (nick). Considering only the intermediates with gaps, the average number of missing residues is 6.3 +/- 0.5 and 2.8 +/- 0.3, respectively, for DNA acted upon by the F and S enzymes independently of the extent of conversion of supercoiled DNA. The nicks and gaps are bounded by 3'-hydroxyl and 5'-phosphoryl termini. When singly nicked circular DNA is used as the substrate, conversion to the linear duplex form occurs predominantly through a gapped circular intermediate with the same average numbers, within experimental error, of missing nucleotides for the respective nuclease species as found when supercoiled DNA is the substrate. The conversion to linear duplex DNA is much slower when nicked circular DNA is the substrate compared to that found when supercoiled DNA is the starting material.


Scoring Systems of Peritoneal Dissemination for the Prediction of Operative Completeness in Advanced Ovarian Cancer.
We investigated the predictive value of scoring systems of peritoneal disseminations for complete surgery (CS) at primary debulking surgery (PDS) in advanced ovarian cancer. We retrospectively enrolled eligible patients with clinical stages III or IVA selected for PDS from January 2015 to December 2019. Concern variables were predictive index value (PIV) and peritoneal cancer index (PCI) from operative and pathological reports. Primary endpoints were cutoffs to predict operative completeness using the receiver operating characteristic curve. Among 111 patients, PIV ≥8 and PCI ≥13 were the best predictors of incomplete PDS, including optimal and suboptimal surgeries (AUC=0.821 and 0.855, respectively). CS rates in PIV ≤6 and PCI ≤12 were significantly higher than in PIV ≥8 (89.3% vs. 47.2%; p<0.05) and PCI ≥13 (90.9% vs. 41.2%: p<0.05). PIV and PCI are potential predictors for CS at PDS.


Phase behavior and morphology of equimolar mixed cationic-anionic surfactant monolayers at the air/water interface: isotherm and Brewster angle microscopy analysis.
The phase behavior and morphological characteristics of monolayers composed of equimolar mixed cationic-anionic surfactants at the air/water interface were investigated by measurements of surface pressure-area per alkyl chain (pi-A) and surface potential-area per alkyl chain (DeltaV-A) isotherms with Brewster angle microscope (BAM) observations. Cationic single-alkyl ammonium bromides and anionic sodium single-alkyl sulfates with alkyl chain length ranging from C(12) to C(16) were used to form mixed surfactant monolayers on the water subphase at 21 degrees C by a co-spreading approach. The results demonstrated that when the monolayers were at states with larger areas per alkyl chain during the monolayer compression process, the DeltaV-A isotherms were generally more sensitive than the pi-A isotherms to the molecular orientation variations. For the mixed monolayer components with longer alkyl chains, a close-packed monolayer with condensed monolayer characteristics resulted apparently due to the stronger dispersion interaction between the molecules. BAM images also revealed that with the increase in the alkyl chain length of the surfactants in the mixed monolayers, the condensed/collapse phase formation of the monolayers during the interface compression stage became pronounced. In addition, the variations in the condensed monolayer morphology of the equimolar mixed cationic-anionic surfactants were closely related to the alkyl chain lengths of the components.


Identification and analysis of genes associated with the severity and prognosis of sepsis.
With rapid progression, severe illness and high fatality rate, sepsis has become an acute and critical condition that seriously threatens human life and health. To detect miR-210 and miR-494 expression in patients with sepsis and their relationship with severity and prognosis. A total of 165 sepsis patients participated, including 105 patients with septic non-shock and 60 patients with septic shock. 53 sepsis patients died in 28 days, and 112 patients survived. The clinical information of all sepsis patients was retrospectively searched and reviewed. Based on the status of 28-day survival, they were categorized into survival group and death group. The expression levels in each group were compared on the first, third and seventh day. The ROC curve was applied to know the expression level of plasma miR-210 and miR-494 to predict the death. The two miRNAs expression of the septic shock group were significantly higher than that in sepsis non-shock group on the first, third and seventh day (all were P< 0.05). The ROC curve found that the AUC combined to predict the death on the third day was the largest, which was 0.925 (95%CI: 0.864-0.983). The sensitivity and specificity were 94.6% and 86.3%, respectively. The increased expression levels of plasma miR-210 and miR-494 are closely relevant to the severity and prognosis of sepsis patients. Combining the two items on the third day can predict the death of sepsis patients.


Blood flow restriction training activates the muscle metaboreflex during low-intensity sustained exercise.
Blood flow restriction training (BFRT) employs partial vascular occlusion of exercising muscle and has been shown to increase muscle performance while using reduced workload and training time. Numerous studies have demonstrated that BFRT increases muscle hypertrophy, mitochondrial function, and beneficial vascular adaptations. However, changes in cardiovascular hemodynamics during the exercise protocol remain unknown, as most studies measured blood pressure before the onset and after the cessation of exercise. With reduced perfusion to the exercising muscle during BFRT, the resultant accumulation of metabolites within the ischemic muscle could potentially trigger a large reflex increase in blood pressure, termed the muscle metaboreflex. At low workloads, this pressor response occurs primarily via increases in cardiac output. However, when increases in cardiac output are limited (e.g., heart failure or during severe exercise), the reflex shifts to peripheral vasoconstriction as the primary mechanism to increase blood pressure, potentially increasing the risk of a cardiovascular event. Using our chronically instrumented conscious canine model, we utilized a 60% reduction in femoral blood pressure applied to the hindlimbs during steady-state treadmill exercise (3.2 km/h) to reproduce the ischemic environment observed during BFRT. We observed significant increases in heart rate (+19 ± 3 beats/min), stroke volume (+2.52 ± 1.2 mL), cardiac output (+1.21 ± 0.2 L/min), mean arterial pressure (+18.2 ± 2.4 mmHg), stroke work (+1.93 ± 0.2 L/mmHg), and nonischemic vascular conductance (+3.62 ± 1.7 mL/mmHg), indicating activation of the muscle metaboreflex.NEW & NOTEWORTHY Blood flow restriction training (BFRT) increases muscle mass, strength, and endurance. There has been minimal consideration of the reflex cardiovascular responses that could be elicited during BFRT sessions. We showed that during low-intensity exercise BFRT may trigger large reflex increases in blood pressure and sympathetic activity due to muscle metaboreflex activation. Thus, we urge caution when employing BFRT, especially in patients in whom exaggerated cardiovascular responses may occur that could cause sudden, adverse cardiovascular events.


Terminology used by pathologists in reporting on sudden infant deaths.
To determine whether the terms used by pathologists in reporting on sudden infant deaths are applied consistently. Postal survey. Replies were received from 63 pathologists who carry out necropsies after sudden infant deaths. There was a pronounced variation in their use of the terms "sudden infant death syndrome" and "unascertained", with the last term being applied not only when there were apparently suspicious features but also in various other circumstances. Opinions were divided as to whether the term "sudden infant death syndrome" still serves a useful purpose. Deaths that had occurred while bed sharing were categorised in several different ways. Many pathologists commented on the inadequacy of the history available to them at the time of their report. There is a serious need for greater consistency in the way pathologists report on sudden death in infants. Pathologists should be provided with a full history before they carry out the necropsy.


SARS-CoV-2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID-19 model.
The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.


Uptake of GABA and putrescine by UGA4 on the vacuolar membrane in Saccharomyces cerevisiae.
The product of the UGA4 gene in Saccharomyces cerevisiae, which catalyzes the transport of 4-aminobutyric acid (GABA), also catalyzed the transport of putrescine. The Km values for GABA and putrescine were 0.11 and 0.69 mM, respectively. The UGA4 protein was located on the vacuolar membrane as determined by the effects of bafilomycin A1 and by indirect immunofluorescence microscopy. Uptake of both GABA and putrescine was inhibited by spermidine and spermine, although these polyamines are not substrates of UGA4. The UGA4 mRNA was induced by exposure to GABA, but not putrescine over 12h. The growth of an ornithine decarboxylase-deficient strain was enhanced by putrescine, and both putrescine and spermidine contents increased, when the cells were expressing UGA4. The results suggest that a substantial conversion of putrescine to spermidine occurs in the cytoplasm even though UGA4 transporter exists on vacuolar membranes.


Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndromes.
• Population pharmacokinetics and pharmacodynamics of rivaroxaban have been characterized in healthy subjects and in patients with total venous thromboembolism, deep vein thrombosis or atrial fibrillation. • This article is the first description of the population pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in patients with acute coronary syndrome (ACS). It is the largest population pharmacokinetic and pharmacodynamic study on rivaroxaban conducted to date (n= 2290). The PK and PK-PD relationship of rivaroxaban in patients with ACS were similar to those in other patient populations. In addition, model-based simulations showed that the influence of renal function and age on the exposure to rivaroxaban in the ACS population were similar to the findings from Phase 1 special population studies. These findings suggest that rivaroxaban has highly predictable PK-PD and may provide a consistent anticoagulant effect across the studied patient populations, which allows an accurate prediction of the dose to control anticoagulation optimally. The aim of this analysis was to use a population approach to facilitate the understanding of the pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndrome (ACS) and to evaluate the influence of patient covariates on the exposure of rivaroxaban in patients with ACS. METHODS A population pharmacokinetic model was developed using pharmacokinetic samples from 2290 patients in Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 46. The relationship between pharmacokinetics and the primary pharmacodynamic end point, prothrombin time, was evaluated. The pharmacokinetics of rivaroxaban in patients with ACS was adequately described by an oral one-compartment model. The estimated absorption rate, apparent clearance and volume of distribution were 1.24 h(-1) (interindividual variability, 139%), 6.48 l h(-1) (31%) and 57.9 l (10%), respectively. Simulations indicate that the influences of renal function, age and bodyweight on exposure in ACS patients are consistent with the findings in previous Phase 1 studies. Rivaroxaban plasma concentrations exhibit a close-to-linear relationship with prothrombin time in the ACS population, with little interindividual variability. The estimated pharmacokinetic and pharmacodynamic parameters for the ACS patients were comparable to those for venous thromboembolism prevention, deep vein thrombosis and atrial fibrillation patients. The similarity in pharmacokinetics/pharmacodynamics of rivaroxaban among different patient populations and the low interindividual variability in the exposure-prothrombin time relationship indicate that the anticoagulant effect of rivaroxaban is highly predictable and consistent across all the patient populations studied.


The Philosophical Basis of Bioethics.
In this article, I consider in what sense bioethics is philosophical. Philosophy includes both analysis and synthesis. Analysis focuses on central concepts in a domain, for example, informed consent, death, medical futility, and health. It is argued that analysis should avoid oversimplification. The synthesis or synoptic dimension prompts people to explain how their views have logical assumptions and implications. In addition to the conceptual elements are the evaluative and empirical dimensions. Among its functions, philosophy can be a form of prophylaxis--helping people avoid some commonly accepted questionable theories. Generally, recent philosophy has steered away from algorithms and deductivist approaches to ethical justification. In bioethics, philosophy works in partnership with a range of other disciplines, including pediatrics and neurology.


How to select patients for high-energy transurethral microwave thermotherapy.
To assist urologists in selecting patients for high-energy transurethral microwave thermotherapy (TUMT) on the basis of baseline characteristics. Two hundred forty-seven patients with lower urinary tract symptoms and benign prostatic hyperplasia were treated with high-energy TUMT using the Prostatron device, software version 2.5. To evaluate outcome at 26 weeks, the World Health Organization response evaluation criteria were used. Multiple logistic regression models were created to identify the predictive value of baseline parameters and total amount of energy used. In addition, receiver operating characteristic curve and the best cutoff point for the prediction of a good response of each criterion under the condition of equal "costs" of misclassification to cases and noncases were calculated. For each of the three response evaluation criteria, graphs are presented to determine whether high-energy TUMT using the Prostatron can be justified. Only the total amount of energy delivered by the device has a major impact in all three criteria used. Graphs have been constructed from our analysis to assist urologists in making clinical recommendations for treatment on the basis of the expected outcome when using high-energy TUMT.