Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds.
A series of 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes 2a-c and 4 and a related acyclic analogue 6a were synthesised and converted to the corresponding Mannich bases 3a-c, 5 and 6b. Evaluation of these compounds against murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed that the Mannich bases were more cytotoxic than the corresponding unsaturated ketones. 1,4-bis(3-Dimethylaminomethyl-2-oxo-1-cyclohexylmethylene)benzene dihydrochloride (3a) had lower IC(50) values than melphalan against the four cell lines and was 15 times more potent than this drug when examined against a panel of human tumours.


Validation of autism spectrum disorder diagnoses recorded in the Clinical Practice Research Datalink, 1990-2014.
Prior studies have reported that the validity of autism spectrum disorder (ASD) diagnoses recorded in the Clinical Practice Research Datalink (CPRD) was high; however, diagnostic criteria and screening practices have changed since the last study was published in 2004. 1) To calculate the positive predictive value (PPV) of ASD diagnoses recorded in the CPRD compared to original medical records and 2) to describe characteristics of cases and use of clinical codes that support the ASD diagnosis as recorded in the electronic data by general practitioners over time. We identified children with a code for ASD (autism spectrum disorder, autism, Asperger's, or pervasive developmental disorder) in the CPRD from 1990 to 2014. We evaluated presence of codes in the electronic medical record indicating the presence of developmental delay, speech delay, behavioral problems, and other supporting clinical codes (e.g., therapy, referrals, etc.). We also evaluated changes in recording of these clinical codes over time. We compared the information present in the electronic medical record to original medical records for a sample of cases and calculated PPVs of ASD diagnoses recorded in the CPRD. We identified 2154 children with a code for ASD. The mean age at diagnosis was 5.8 years, and 84% of cases were male. The majority (78.4%) had 1 ASD diagnosis code in their electronic medical record. Approximately half of the cases had a code indicating behavioral problem, developmental delay, or speech delay, and 24.7% had a code indicating specialist referral or visit. After review of original medical records, the PPV of ASD diagnoses recorded in the CPRD was 91.9%. The results of this study suggest that ASD diagnoses recorded in the CPRD are reliable and can be used with confidence to study ASD.


Pattern Recognition to Prognosticate Endometrial Cancer: The Science Behind the Art of Office Hysteroscopy-A Retrospective Study.
This study aimed to evaluate a specific glomerular pattern for prognostication of endometrial cancer (EC). The office hysteroscopy's picture and video of 4197 women were reviewed, 48 women who were suspected of type I EC were analyzed: 26 have glomerular pattern (group 1) and 22 without it (group 2). The histopathological grading after hysterectomy with glomerular pattern had grade 2 or grade 3 disease on final histology (n = 25; 96%). The sensitivity and specificity of this test were 84.6% and 81.8%, respectively, with a likelihood ratio of 4:6 in predicting and prognosticating those women who have high-grade tumor or invasive disease. This hysteroscopic picture might be used as a novel marker for risk stratification of EC.


Safety and Efficacy of High-Dose Tranexamic Acid in Spine Surgery: A Retrospective Single-Institution Series.
Currently, tranexamic acid (TXA) is the most widely used antifibrinolytic agent in spine surgery and has been proven to reduce perioperative blood loss. However, the safety of high-dose regimens remains in established. A retrospective chart review was performed to identify all adult patients who underwent spine surgery with high-dose TXA (50 mg/kg loading dose, mg/kg/h maintenance dose) between September 2019 and March 2020. Thirty-six patients were treated with intraoperative high-dose TXA during the study period. The mean age was 56.6 (range: 22-82). Average body mass index was 27.2 (5.1) kg/m2. Average preoperative Charlson Comorbidity Index was 3.0 (2.7). The mean number of spinal levels operated on was 6.9 (4.3). Seven cases (19.4%) were revision surgeries. The mean intraoperative blood loss was 587.1 (900.0) mL, and total blood loss was 623.8 (991.9) mL. Postoperatively, time to ambulation was on average 1.7 (1.7) days. The mean total length of stay was 9.8 days (7.9, range 2-41). The most common indication for surgery was tumor (n = 9, 25%), followed by fracture (n = 8, 22.2%), deformity (n = 7, 19.4%), pseudarthrosis (n = 6, 16.7%), and symptomatic lumbar disc herniation (n = 2, 5.6%). There were no thromboembolic or other significant complications among the 36 patients. This retrospective case series demonstrates that the use of high-dose TXA provides is potentially safe and efficacious in adult patients undergoing complex spine surgeries. However, further investigations are required before the true safety and optimal dosing can be determined for high-dose TXA.


Lipid composition of sputum from patients with asthma and patients with cystic fibrosis.
Lipids from the sputum of patients with asthma and with cystic fibrosis were isolated and characterized. In both cases, lipids constituted approximately 30% of the dry material. Phosphatidlycholine was the most abundant lipid, Significant amounts of phosphatidylethanolamine and phosphatidylglycerol were present. Hexosyl ceramides, sphingomyelin, phosphatidylinositol, lysophosphatidylcholine, and lysophosphatidylethanolamine were present as minor lipid components. Apperciable quantities of neutral lipids were present, of which triglycerides and cholesterol were the main constituents. Phosphatidylcholine, sphingomyelin, and phosphatidylgycerol were highly saturated. Large amounts of phosphatidylcholine containing mostly palmitic acid, particularly in the asthmatic sputum, suggest htat this highly saturated. Large amounts of phosphatidylcholine containing mostly palmitic acid, particularly in the asthmatic sputum, suggests that this highly saturated phospholipid is synthesized in the upper airways for reasons other than its beneficial surface-active properties in the alveoli.


Use of Lavandula angustifolia essential oil as a complementary therapy in adult health care: A scoping review.
In addition to its low toxicity risk, Lavender (Lavandula angustifolia Mill.) essential oil is recognised worldwide for its sedative, antidepressant, antiseptic, antifungal, relaxing, and antiemetic properties. Thus, the action mechanism of lavender oil has attracted significant attention from researchers interested in improving the physical, emotional, and spiritual well-being of patients. To investigate the scope of knowledge regarding the use of L. angustifolia essential oil as a complementary therapy in adult health care. A scoping review was carried out using a PRISMA-ScR checklist followed by a critical assessment being performed using the Joanna Briggs Institute level of evidence. The following databases were used: SCOPUS, MEDLINE/PubMed, Web of Science, Science Direct, SCIELO, Cochrane Library, LILACS, Wiley Online Library, CAPES, and FIOCRUZ Dissertations. Eighty-three articles published between 2002 and 2022 were selected for the analysis; More articles came from Iran than from any other country and most articles reported clinical trials. The applicability of lavender essential oil and its route of administration in different clinical situations were the main topics addressed in the articles. Most studies demonstrate the efficacy of L. angustifolia Mill. essential oil in relieving pain and decreasing anxiety. Few studies evaluated the anti-psoriatic, anti-toxoplasmotic, and wound healing properties and the protective actions against cerebral ischemia. One study reported on its safety, specifically the allergenic potential of linalool, the main chemical component of L. angustifolia essential oil. However, most studies did not involve the extensive investigations on this topic or report the safe quantities of this oil for human treatment, meaning further research into the safety of this treatment is required.


Observations concerning the limited mobilisation cast after anterior cruciate ligament surgery.
A limited mobilisation cast (LMC) with hinges locked at 20 and 60 degrees has been advocated for the care after anterior cruciate ligament (ACL) surgery. The brace presumably limits motion to 20 and 60 degrees and prevents straining of the ACL. Extension of more than 20 degrees as well as anterior drawer forces are known to strain the ACL. We have therefore tested whether the LMC reliably limits the desired range of motion: Extension of more than 20 degrees was found in 11 of 12 patients and averaged 12 degrees. The long leg cast reduced a 30 degree anterior drawer in unstable knees by 70%, a Lenox-Hill-Derotation Brace by 53% and the LMC by only 14%. It was concluded that a modified Lenox-Hill Brace locked at 30 and 60 degrees of flexion provides better stress-protection of the ACL than a LMC and that the safety of the conventional long leg cast should be remembered in legs with unfavourable soft tissue configurations. If a LMC is used, it should be fixed to the trunk with a waist- or shoulder-strap and the hinges must be freely adjustable.


Transposition Complex with Aortic Arch Obstruction: Outcomes of One-Stage Repair Over 10 Years.
The surgical management of transposition complex with aortic arch obstruction remains technically demanding due to anatomic complexity. Even in the recent surgical era, there are centers that address this anomaly with a staged strategy. This report presents our experiences with a one-stage repair of transposition complexes with aortic arch obstructions more than the last 10 years. Since 2003, 19 patients with a transposition of the great arteries (TGA, 2 patients) or a double outlet of the right ventricle (DORV, 17 patients) and aortic arch obstruction have undergone one-stage repair of their anomalies. The mean age was 6.7 ± 2.3 days, and the mean body weight was 3.4 ± 0.3 kg. The 2 patients with TGA exhibited coarctation of the aorta. The 17 patients with DORV all exhibited the Taussig-Bing type. The great artery relationships were anteroposterior in 4 patients (21.1%). The coronary artery anatomies were usual (1LCx; 2R) in 8 patients (42.1%). There were 2 early deaths (10.5%). Seven patients (36.8%) required percutaneous interventions. One patient required re-operation for pulmonary valvar stenosis and left pulmonary artery patch angioplasty. The overall survival was 84.2%. The freedom from mortality was 83.5% at 5 years, and the freedom from intervention was 54.4% at 5 years. The one-stage repair of transposition complexes with aortic arch obstructions resulted in an acceptable survival rate and a relatively high incidence of postoperative catheter interventions. Postoperative catheter interventions are highly effective. Transposition complexes combined with aortic arch obstructions can be managed by one-stage repair with good early and midterm results.


Help! I Need Somebody: Help-Seeking Among Workers with Self-Reported Work-Related Mental Disorders.
Worker mental health has emerged as one of the most significant challenges in contemporary workplaces. Knowing what intervention is effective is important to help workers adapt to mental health disorders but connecting workers to helpful resources is just as important and perhaps more of a challenge. With the multiple stakeholders involved, mental health disorders arising in the workplace pose specific challenges to help-seeking. The present study sought to explore the lived experience of workers and the personal and contextual influences on help-seeking among workers with work-related mental health disorders. A qualitative methodology was employed utilizing purposive sampling to conduct semi-structured interviews with individuals (n = 12) from various occupational backgrounds who had experienced a work-related (self-declared) mental health disorder. A Critical Theory approach was used to inform study design and analysis. Interpretative phenomenological analysis and thematic content analysis were combined to analyze the data. Three main themes emerged including: (1) self-preservation through injury concealment and distancing themselves from workplace stressors to minimize/avoid internal and external stigma; (2) fatigue relating to complex help-seeking pathways, accumulation of stressors, eroding the worker's ability to make independent decisions regarding supports; and (3) (mis)trust contributed to resources accessed by participants. Along with internalized stigma, findings point to the important role of social identity and trust and how these are influenced by relationships and organizational contexts. Findings indicate the need to educate workplace parties such as supervisors on mental health and pathways to help, simplifying pathways to service and removing barriers to help seeking including stigmatizing behaviours. Future quantitative research and intervention development directed at workplace mental health should integrate models and frameworks emphasizing relational and organizational dimensions in help-seeking.


Development of wire localization for occult breast lesions: Boston remembrances.
In the 1970s, the four authors of this article each set up mammographic screening programs and independently developed preoperative needle-wire localization techniques at different Boston-area hospitals. These innovations, which facilitated surgical biopsy of nonpalpable abnormalities, helped establish and popularize mammography and have only minimally changed over the ensuing decades. This historical perspective shares personal anecdotes of the early development of mammography and mammographic wire localizations.


Fluorescent imaging to provide visualized evidences for mercury induced hypoxia stress.
As one typical toxic and dangerous heavy metal, mercury brings incalculable hazards to the environment and human, the mechanism at the molecular level is unclear. There is no visualized evidence to support directly that mercury ions (Hg2+) exposure may induce secondary stress, which is associated with the risk of hypoxia microenvironment in biological systems. Hypoxia occurs in many physiological and pathophysiological processes in the living system, accompanying overexpression of various biomarkers, such as nitroreductase (NTR). Hence, we had successfully developed two NTR-selective fluorescent probes with excellent performance for evaluating the hypoxia degree in vivo and in vitro. We visualized and qualitatively monitored the fluctuations of the endogenous NTR levels in living cells and zebrafish. The imaging results exhibited that different doses of Hg2+ exposure elevated the NTR levels and the same trend in changes of NTR as extrinsic hypoxia exposure, suggesting that Hg2+ exposure induced microenvironmental changes resulting in the hypoxia stress. This is the first time to provide visual evidence to support that Hg2+ stress may involve in the intracellular hypoxia microenvironment through monitoring the dynamic of NTR levels in the living systems. Our results may provide a novel insight into the molecular mechanisms of typical heavy metal element induced toxicity.


[Ultrasound-guided regional anesthesia: best practice upper extremities].
Regional anesthesia of the upper extremities is now part of the standard repertoire of a clinical anesthesiologist. Assigning the correct procedure to the individual needs of the patient is becoming increasingly more difficult due to the wide variety of options. The principle use of regional anesthesiological procedures is hardly ever questioned anymore but it needs to be carefully considered and must be adapted exactly to the case at hand.


Smoking history, instructions and the effects of nicotine: two pilot studies.
In Study 1, ten never-smokers, ten ex-smokers and nine current smokers received nicotine (2 mg) and placebo gum hourly for 4 hours on 2 consecutive days in a randomized, double-blind, cross-over protocol. Dysphoria from nicotine was greatest in never-smokers, intermediate in ex-smokers, and least in current smokers (p less than 0.05). On the third day, subjects were given concurrent access to the same gums and told to chew ad lib. Across all subjects, nicotine was an aversive stimulus (i.e., self-administered less than placebo). Nicotine was avoided most in never-smokers, intermediate in ex-smokers and least in current smokers (p less than 0.05). Study 2 used a similar protocol and compared the nine current smokers in Study 1 who were not told they would receive nicotine with eight informed smokers, i.e., smokers told they would receive nicotine. Although nicotine appeared to be a reinforcer more often in the informed smokers than in the uniformed smokers (63% vs. 22%), this result was not statistically significant. Our results suggest 1) past drug history can influence the stimulus effects of nicotine and 2) the effects of instructions on the response to nicotine may be less in experimental settings than in therapeutic settings.


Diagnostic value and cost-effectiveness of FNA-CT versus FNAC for medullary thyroid carcinoma.
To evaluate the diagnostic performance and cost-effectiveness of calcitonin assays in fine-needle aspiration washout fluid (FNA-CT) compared to fine-needle aspiration cytology (FNAC) for medullary thyroid carcinoma (MTC). A total of 27,404 patients from three medical centres between January 2020 and May 2022 were screened for serum calcitonin (sCT). Of whom, 223 patients met endpoints and were enroled for analyses. Based on sCT levels, patients were divided into two groups (group 1: 10 pg/ml< sCT ≤100 pg/ml and group 2: sCT > 100 pg/ml). The diagnostic performance and cost-effectiveness of FNA-CT and FNAC were compared. Most patients (N = 25,228; 92.1%) with thyroid nodules had normal sCT levels. In group 1, 24 and 167 nodules were diagnosed as MTC and non-MTC lesions, respectively. FNA-CT showed better performance in diagnosing MTC than FNAC in terms of sensitivity (100.0% vs. 58.3%), negative predictive value (100.0% vs. 94.3%), and overall accuracy (100.0% vs. 94.7%). In group 2, 67 and 7 nodules were diagnosed as MTC and non-MTC lesions, respectively. The diagnostic performance of FNA-CT was superior to FNAC in terms of sensitivity (100.0% vs. 64.2%), negative predictive value (100.0% vs. 22.6%), and overall accuracy (100.0% vs. 67.6%). Furthermore, analysis from the decision tree model showed that FNA-CT was a cost-effective tool for diagnosing MTC lesions. FNA-CT can serve as an auxiliary and cost-effective approach for patients with indeterminate sCT levels to detect occult MTC lesions. FNA-CT can be recommended for patients with sCT >100 pg/ml to overcome the high false-negative rate of FNAC.


Antimicrobial resistance of urinary tract isolates in acute uncomplicated cystitis among college-aged women: choosing a first-line therapy.
The authors of this retrospective case study focused on antimicrobial susceptibility of urinary tract isolates in cases of acute uncomplicated cystitis in college-aged women, aged 18 to 24 years, diagnosed at a major south-central university student health center. The authors obtained pertinent data from patient medical and laboratory records, including, diagnoses, urine culture, and susceptibility results. Of 179 isolates, 161 (90%) were Escherichia coli (E. Coli) isolates, of which 23% were resistant to trimethoprimsulfamethoxazole, <1% were resistant to Ciprofloxacin, and <1% were resistant to nitrofurantoin. Sixty-eight (42%) E. Coli isolates were multidrug resistant. There were 18 isolates cultured in the study group that were significant organisms other than E. coli. For all organisms in the study group, there was a combined resistance rate of 22% to trimethoprim-sulfamethoxazole, <1.0% for Ciprofloxacin, and 7% for nitrofurantoin. The findings suggest that both Ciprofloxacin and Nitrofurantoin are acceptable choices for empiric therapy of acute uncomplicated urinary tract infection in this study population, keeping in mind the potential for rising resistance rates to Ciprofloxacin in the community setting.


Localization and characterization of transport-related elements in the plasma membrane of turtle bladder epithelial cells.
A mixed membrane preparation obtained from turtle bladder epithelial cells contains (Na+ + K+)-ATPase, adenylate cyclase and protein kinase, which interact with ouabain, norepinephrine and cyclic AMP, respectively. When such a preparation is obtained from bladders which had been preexposed to serosal fluids containing the tritiated form of 4,4'-diisothiocyano-2,2'-disulfonic stilbene, the subsequently isolated membrane proteins are enriched in tritium as well as in the afore-mentioned enzymes, none of which is inhibited. Free-flow electrophoresis separates the mixed membrane preparation into two distinguishable groups: one, construed as apical membranes, is enriched in norepinephrine-sensitive adenylate cyclase and cyclic AMP-sensitive protein kinase; the other, construed as basal-lateral membranes, is enriched in ouabain-sensitive ATPase and 4,4'-diisothiocyano-2,2'-disulfonic stilbene-binding proteins. The physiological counterparts of these enzymatically defined membrane markers are the mucosal sidedness of the transport effects of norepinephrine and cyclic AMP derivatives and the serosal sidedness of the transport effects of ouabain and disulfonic stilbenes in the intact turtle bladder. The discreteness and ion selectivity of each membrane-bound, transport-related element are discussed in relation to the corresponding characteristics of each transport process in vivo; the possibility of regulation of anion transport by adenylate cyclase-protein kinase system is also discussed.


Microbial production of propanol.
Both, n-propanol and isopropanol are industrially attractive value-added molecules that can be produced by microbes from renewable resources. The development of cost-effective fermentation processes may allow using these alcohols as a biofuel component, or as a precursor for the chemical synthesis of propylene. This review reports and discusses the recent progress which has been made in the biochemical production of propanol. Several synthetic propanol-producing pathways were developed that vary with respect to stoichiometry and metabolic entry point. These pathways were expressed in different host organisms and enabled propanol production from various renewable feedstocks. Furthermore, it was shown that the optimization of fermentation conditions greatly improved process performance, in particular, when continuous product removal prevented accumulation of toxic propanol levels. Although these advanced metabolic engineering and fermentation strategies have facilitated significant progress in the biochemical production of propanol, the currently achieved propanol yields and productivities appear to be insufficient to compete with chemical propanol synthesis. The development of biosynthetic pathways with improved propanol yields, the breeding or identification of microorganisms with higher propanol tolerance, and the engineering of propanol producer strains that efficiently utilize low-cost feedstocks are the major challenges on the way to industrially relevant microbial propanol production processes.


Diagnostics, surveillance and management of sexually transmitted infections in Europe have to be improved: lessons from the European Conference of National Strategies for Chlamydia Trachomatis and Human Papillomavirus (NSCP conference) in Latvia, 2011.
There is an urgent need for the recognition of sexually transmitted infections (STIs) as a serious public health problem in Europe. The lack of standardization in testing, along with poor reporting and surveillance mechanisms, have resulted in low reported rates of STIs in many European Union (EU) countries, reinforcing the erroneous assumption that STIs are not a major problem. Testing and diagnosis of STIs must therefore be improved and enhanced. Reporting of Chlamydia trachomatis infection, gonorrhoea and syphilis should be mandatory, and an integrated surveillance system for C. trachomatis implemented in all European countries. Implementation of the European Centre for Disease Prevention and Control (ECDC) surveillance mechanisms for STIs in all EU countries is highly recommended. A necessary component for successful introduction of the HPV vaccine, as with any vaccination programme is a well-planned and organized information campaign.


Staging in childhood non-Hodgkin's lymphoma. What are its benefits? How extensive should it be?
A review of published reports of the management of childhood non-Hodgkin's lymphoma was undertaken to determine the extent to which a staging procedure should be implemented and the benefits which could be derived. A variety of clinical, radiographic, surgical, and laboratory investigations were performed by different investigators. Overall, similar results were obtained for the different stages. The utility of the individual studies was not defined in any single review. However, it appeared that bone marrow biopsy was superior to bone marrow aspirates, staging laparotomy was generally not required, and lymphangiography did not constitute a routine staging procedure. Staging permitted identification of patients with primary sites at high risk for the development of central nervous system disease or failure. The reviews did not specify the minimum number of procedures to be performed. It is concluded that each patient should receive individual consideration, and diagnostic evaluation should consist of a series of tests sequentially performed and interrupted whenever sufficient information has been assembled for institution of therapy.


Retracted: Intelligent Question Answering System by Deep Convolutional Neural Network in Finance and Economics Teaching.
[This retracts the article DOI: 10.1155/2022/5755327.].


Top-down auditory attention modulates neural responses more strongly in neurotypical than ADHD young adults.
Human cognitive abilities naturally vary along a spectrum, even among those we call "neurotypical". Individuals differ in their ability to selectively attend to goal-relevant auditory stimuli. We sought to characterize this variability in a cohort of people with diverse attentional functioning. We recruited both neurotypical (N = 20) and ADHD (N = 25) young adults, all with normal hearing. Participants listened to one of three concurrent, spatially separated speech streams and reported the order of the syllables in that stream while we recorded electroencephalography (EEG). We tested both the ability to sustain attentional focus on a single "Target" stream and the ability to monitor the Target but flexibly either ignore or switch attention to an unpredictable "Interrupter" stream from another direction that sometimes appeared. Although differences in both stimulus structure and task demands affected behavioral performance, ADHD status did not. In both groups, the Interrupter evoked larger neural responses when it was to be attended compared to when it was irrelevant, including for the P3a "reorienting" response previously described as involuntary. This attentional modulation was weaker in ADHD listeners, even though their behavioral performance was the same. Across the entire cohort, individual performance correlated with the degree of top-down modulation of neural responses. These results demonstrate that listeners differ in their ability to modulate neural representations of sound based on task goals, while suggesting that adults with ADHD may have weaker volitional control of attentional processes than their neurotypical counterparts.


Kinetics for the distribution of acrylamide in French fries, fried oil and vapour during frying of potatoes.
Kinetic analysis for the formation of acrylamide in heated foods has been typically performed using only measured data of acrylamide in foods; however, its possible loss caused by release from heated foods into fried oil and air has seldom been considered. The results obtained from the monitoring of acrylamide by frying French fries indicated that acrylamide is distributed in three phases: French fries, frying oil, and air. From the evolved gas analysis of acrylamide and the measured concentration profile of the total acrylamide amount present in these phases, the kinetic behaviour for acrylamide formation does not obey the commonly used model of two-step consecutive reactions during frying, while a lumped kinetic model was proposed for the total acrylamide amount. Moreover, a high acrylamide level in air was observed, implying that, apart from consumers of French fries, fast-food restaurant workers are potentially subject to occupational hazards from acrylamide inhalation.


Construction and validation of a metabolism-related prognostic model for thyroid cancer.
Metabolic reprogramming is a common pathological process of cancer. Expression of metabolism-related genes differs in thyroid cancer (TC) patients with different prognoses. This work committed to constructing a prognostic model for TC through identifying metabolism-related signatures. Expression profiles of mRNAs and clinical data of TC, were acquired from The Cancer Genome Atlas. Differential analysis was performed on mRNA expression profiles. The obtained differentially expressed genes (DEGs) were overlapped with metabolism-related genes from MSigDB database to acquire metabolism-related DEGs. Cox regression and Least Absolute Shrinkage and Selection Operator analyses were performed to ascertain feature genes and to build a prognostic model for TC. The model was evaluated comprehensively through survival curve, time-dependent receiver operating characteristic (ROC) curve, gene set enrichment analysis (GSEA), and Cox regression analyses combining varying clinical information. 7 key genes related to metabolism, including AWAT2, GGT6, ENTPD1, PAPSS2, CYP26A, ACY3 and PLA2G10, were identified, based on which a prognostic model was constructed. The survival analysis indicated that high-risk group presented shorter survival time than low-risk group. ROC curve results exhibited that AUC values of 3-year and 5-year survival of TC patients were both >0.70. Besides, GSEA on high/low-risk groups revealed that DEGs were mainly gathered in biological functions and signaling pathways linked with keratan sulfate catabolism and triglyceride catabolism. Combined with clinical information, Cox regression analyses unveiled that the 7-gene prognostic model can be an independent predictor. In conclusion, this model can effectively predict prognoses of TC patients, and also offer guidance for clinical treatment of TC.


Pharmacological treatment of wounds.
Systemic treatment of patients with wounds can be directed at several physiological aspects of healing during the consecutive phases of tissue repair. Many approaches to pharmacological treatment have been tested in vitro, in animal experiments, or in clinical studies. Investigators and clinicians focus on treating underlying metabolic, infectious, inflammatory, or hemorrheological diseases and their complications. Drug treatment is often adjuvant or complementary to other measures such as compression, surgical intervention, reconstruction, or reopening procedures. This compounding fact can render interpretation of the results more difficult. As systemic treatment is not always without side-effects; local wound management is an option to consider. Topically applied growth factors certainly have the potential to influence the healing process. An indirect way of providing growth factors to wounds and chronic ulcers can be achieved by the application of grafts, cultured keratinocytes, and skin substitutes. Modulation of angiogenesis during wound healing is a recent target for research and treatment. Future reviews probably also will include genetic engineering methods for influencing wound healing.


Vesicourethral anastomosis after radical prostatectomy: experience with the Jewett modification.
The author's experience with the Jewett method of vesicourethral anastomosis after radical prostatectomy is described. Only 1 instance of stress incontinence has been encountered in more than 200 personal cases. The technique is described in detail.


Galectin-3 is Associated with Heart Failure Incidence: A Meta-Analysis.
Heart failure (HF) is a leading cause of death worldwide. The global prevalence of heart failure is projected to increase rapidly in the coming decades, and significant attention has turned to improving biomarker-based risk prediction of incident HF. This paper aimed to qualitatively and quantitatively evaluate the evidence associating levels of galectin-3 with the risk of incident HF. A review of PUBMED-indexed peer-reviewed literature was performed. Nine studies met the inclusion criteria, and all nine had data eligible for conversion and pooling. A randomeffects meta-analysis was performed using hazard ratios and 95% confidence intervals from a minimally adjusted model, a further adjusted model, and from subgroups within the further-adjusted model. The minimally-adjusted model provided an HR of 1.97 (95% CI 1.74-2.23) when comparing the top quartile of log-gal-3 to the bottom quartile. The further-adjusted model provided an HR of 1.32 (95% CI 1.21-1.44) for the same comparison. The positive, significant association was conserved during sensitivity analysis. There is a significant positive association between circulating galectin-3 and the risk of incident heart failure. Given the complex mechanistic relationship between galectin-3 and cardiovascular pathophysiology, further investigation is recommended for the possible implementation of galectin-3 into clinical risk prediction models.


Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date.
The longest survival of a non-human primate with a life-supporting kidney graft to date has been 90 days, although graft survival > 30 days has been unusual. A baboon received a kidney graft from an α-1,3-galactosyltransferase gene-knockout pig transgenic for two human complement-regulatory proteins and three human coagulation-regulatory proteins (although only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6 to 1.6 mg/dl) until termination. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136, the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory agents prevented immune injury and a protein-losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality.


Relation of cooked rice texture to starch structure and physicochemical properties under different nitrogen managements.
Nitrogen management, especially panicle nitrogen fertilization (PNF), can affect cooked rice textures by altering starch quality, but the details are unclear. In this study, the starch multi-level structures, physicochemical properties and cooked rice textures of indica under different nitrogen managements were analysed and their internal relations were investigated. With an increase in PNF, large granules, amylopectin short chains, amylose content, thermal temperatures, setback, and hardness first exhibited decreasing trends and then increasing trends, which were relatively lower under moderate PNF (N3), whereas α-1,6 linkage, relative crystallinity, protein content, enthalpy of gelatinization (△Hgel), peak viscosity, breakdown and stickiness exhibited the opposite trends. N3 treatment significantly increased △Hgel and breakdown and decreased setback, hardness and chewiness, suggesting that it might contribute to better starch thermal stability and pasting properties, ultimately improving cooked rice texture. Nitrogen management affected the texture of cooked rice mainly by improving starch multi-level structures, thermal and pasting viscosities.


New insights into the immunoultrastructural organization of cutaneous basement membrane zone molecules.
The epidermal basement membrane zone (BMZ) is composed of various molecules, each of which plays an important role in dermo-epidermal adhesion. Genetic abnormality of certain BMZ molecules leads to an inherited group of skin diseases collectively referred to as epidermolysis bullosa, whose hallmark is skin fragility of varying degrees. Furthermore, development of autoantibodies to certain BMZ molecules leads to the onset of a number of acquired autoimmune blistering diseases in which dermo epidermal separation occurs, including bullous pemphigoid and epidermolysis bullosa acquisita. The ultrastructural location of each BMZ molecule has been studied using a range of immunoelectron microscopy (immuno-EM) techniques. Recent technical advances in immuno-EM and in molecular engineering for production of epitope-specific antibodies have enabled a more correct and precise elucidation of the native ultrastructural molecular organization of the respective molecules and their relationship to each other. These recent studies have also revealed several misinterpretations in the previously established model of the immunoultrastructural organization of BMZ molecules. In response to these findings, this review focuses on three major BMZ-related molecules, type VII collagen, BPAG2 and laminin 5, for which recent immuno-EM studies have produced a revision in the accepted dogma on their ultrastructural distribution at the BMZ.


Differentiation between acute macular neuroretinopathy and paracentral acute middle maculopathy in elderly persons: two case reports.
We report one case of rare acute macular neuroretinopathy (AMN) in an elderly patient with hypertension and one case of common paracentral acute middle maculopathy (PAMM) in a patient with diabetes mellitus to illustrate the difference between the two diseases. This report describes two cases, one involving AMN and the other PAMM. The first patient was a 70-year-old man complaining of blurred vision for 3 days. He was examined with fundus photography, optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT); a diagnosis of AMN was established. The second patient was a 50-year-old woman who complained of decreased vision during the past month. She had had diabetes mellitus for 6 years. From the ophthalmic imaging examination, the patient was diagnosed with PAMM and non-proliferative diabetic retinopathy (NPDR). Both patients were treated with drugs for improving microcirculation and neurotrophic drugs; however, there was no significant improvement in visual acuity. AMN is more common in young patients and is rarely observed in elderly patients with systemic diseases. The OCTA examination has an auxiliary diagnostic value for deep retinal capillary network ischaemia. Meanwhile, OCT examination has important imaging value in differentiating AMN from PAMM and can help avoid missed diagnoses.


"Some things are even worse than telling a child he is going to die": Pediatric oncology healthcare professionals perspectives on communicating with children about cancer and end of life.
This study explored pediatric oncology healthcare professionals' (HCPs) perspectives on direct communication with children with advanced disease about their disease, palliative care, and end-of-life (EOL) communication. Forty-six pediatric oncologists, nurses, psychosocial team members, and other HCPs from six hospital centers in Israel participated in semi-structured interviews. The Grounded Theory method was used. Data were analyzed line-by-line with codes and categories developed inductively from participants' narratives. HCPs viewed communication about disease progression and EOL as vital because children were often aware of their prognosis, because lack of communication could lead to emotional distress, and because communication is a prerequisite for shared decision-making. HCPs identified several barriers for communication including HCP barriers (such as emotional strains, lack of training), parental barriers, guardianship law, and language and culture. HCPs also described strategies to promote EOL communication. Direct strategies include tailoring communication, allowing for silence, echoing children's questions, giving information gradually, and answering direct questions honestly. Indirect strategies included encouraging parents to talk to their children and teamwork with colleagues. Open communication with children who have cancer is essential. Nevertheless, multiple barriers persist. The rising accessibility of online information calls for urgent training of HCPs in communication so that children will not turn to unmediated and potentially misleading information online in the absence of HCP communication. Evidence-based effective communication training modules and emotional support should be offered to HCPs. Knowledge about children's development, age-appropriate communication, and cultural sensitivity should be included in this training.


Phase advance of sleep and temperature circadian rhythms in the middle years of life in humans.
Age-related changes in sleep may be linked to modifications in the circadian timing system. This study compared sleep patterns and unmasked circadian temperature parameters between a group of young subjects and a group of middle-aged subjects. Habitual bedtime and waketime were earlier in the middle-aged than in the young. In addition, middle-aged subjects reported a greater orientation toward morningness and they showed an earlier phase of temperature rhythm. No differences were found in amplitude of temperature rhythm or in habitual phase angle between sleep and the temperature rhythm. In conclusion, a phase advance of sleep and temperature circadian rhythm is already apparent in people in their forties and fifties. These changes precede modifications in amplitude or in habitual phase angle.


Caring behaviours of culturally diverse personal care attendants from the perspective of older people living in residential aged care settings.
This study aimed to determine whether older residents perceive differences in the care they receive from personal care attendants (PCAs) of similar cultural backgrounds versus those from other cultural backgrounds. The challenges encountered when receiving care from culturally diverse PCAs were also explored. A directed qualitative content analysis approach was utilised. Results showed that PCAs' personalities were perceived to have a greater impact on all aspects of care delivery than their cultural backgrounds. PCAs from other cultural backgrounds were also perceived to be more observant, pleasant, and sociable than their local counterparts, despite the communication challenges due to their limited English proficiency. This study indicates that migrant PCAs can significantly contribute to addressing workforce shortages in the aged care industry without compromising care quality, but it also highlights the need for long-term strategies to improve meaningful interaction between culturally diverse PCAs and residents and foster a positive work environment.


Neuropsychology of self-awareness in young adults.
Disorders of self-awareness are common following cortical damage, particularly to the frontal lobes, but there have been few studies of individual differences in self-awareness in the normal population. In the current study, we explored patterns of metacognitive awareness among healthy young adults, based on discrepancies of self- and other-ratings on the Frontal Systems Behavior Scale (FrSBe; Grace and Malloy, 2002). Those who showed poor metacognitive awareness showed more frequent lapses of attention, and higher levels of everyday absentmindedness, than those who accurately appraised their own behavior or those who overestimated their own FrSBe scores. Furthermore, among those with poor metacognitive awareness, online emergent awareness correlated positively with prospective memory performance, and negatively with anxiety scores. Our results suggest that accurate self-awareness in non-neurological participants relies on efficient sustained attention functioning, supporting the role of frontal control systems in neuroanatomical models of self-awareness.


Maternal effect on micronucleus induction in MS/Ae mice.
MS/Ae mice, which are mutagen-sensitive in both the dominant lethal test and micronucleus test, and CD-1 mice, which are the parental strain of MS/Ae, were mated in all four possible combinations. Both male and female offspring were subjected to the micronucleus test using mitomycin C (MMC), colchicine (Col), and 6-mercaptopurine (6-MP). Col showed equivocal results. However, MMC and 6-MP showed differential responses in that both male and female offspring from CD-1 dams had lower incidences of micronucleated polychromatic erythrocytes than those from MS/Ae dams regardless of sire strain. In addition, body weights of offspring from MS/Ae dams were lower than those from CD-1 dams regardless of sire strain. Numbers of offspring from MS/Ae dams tended to be smaller than those from CD dams. These results suggest that the traits of MS/Ae mice are associated more with maternal factors than with paternal ones.


Aggressive Renal Angiomyolipoma of the Lipomatous Variant With Inferior Vena Cava Thrombus: A Case Report and Review of the Literature.
Two variants of renal angiomyolipoma (AML)-classic and epithelioid-have been described. Although the epithelioid variant has been reported to demonstrate an aggressive clinical behavior, classic AML is usually benign. Herein, we report a case of a 42-year-old asymptomatic woman with a lipomatous variant of renal AML associated with an inferior vena cava thrombus managed with radical nephrectomy and caval thrombectomy.


Characterisation of the essential oil from different aerial parts of Lindera chunii Merr. (Lauraceae).
The essential oils from three organs (i.e. flowers, leaves and stems) of wild Lindera chunii Merr. in Dinghu Mountain (China) were obtained by microwave-assisted hydrodistillation. The essential oils were analysed by gas chromatography with flame ionisation detection and gas chromatography with mass spectrometry. The yields of essential oil varied from 0.06% to 0.59% and showed a remarkable variation among the plant organs. A total of 43 compounds accounting for 95.4-96.3% of the total essential oil were identified, and the major compounds were germacrene B (0.7-43.2%), viridiflorene (trace to 14.6%), globulol (6.3-11.6%), α-cadinol (1.7-8.6%) and τ-cadinol (0.5-7.3%). This study shows that the chemical compositions of the essential oils from the different organs of L. chunii are very variable.


Long-term fracture risk following adult-onset asthma: a population-based study.
There are few data on skeletal outcomes in the growing population of patients with adult-onset asthma. We conducted a population-based retrospective (historical) cohort study among 226 residents of Rochester, Minnesota, USA, who were 35 years of age or older when first diagnosed with asthma. Fractures were ascertained by review of comprehensive community medical records, and observed fractures were compared with expected numbers based on incidence rates in the local population (standardized incidence ratios, SIR). During 4,022 person-years of follow-up, 100 patients experienced 211 fractures, for an actuarially estimated cumulative incidence of 63% after 30 years compared with 59% expected ( p=0.004). Statistically significant increases were seen for moderate trauma fractures of the vertebrae (SIR, 2.9; 95% CI, 2.1 to 3.8) and ribs (SIR, 2.0; 95% CI, 1.2 to 3.2), as well as the proximal femur (SIR, 1.8; 95% CI, 1.02 to 2.8). As assessed by proportional hazards models, the only independent predictors of any subsequent moderate trauma fracture were age (hazard ratio [HR] per 10-year increase, 1.7; 95% CI, 1.5 to 2.1) and cumulative corticosteroid dose greater than the median of 1,775 mg (HR, 1.8; 95% CI, 1.1 to 3.0). In another multivariate analysis, the predictors of a moderate trauma vertebral fracture were older age (HR, 1.6; 95% CI, 1.3 to 2.1), concomitant chronic obstructive pulmonary disease (HR, 2.4; 95% CI, 1.2 to 4.9), cigarette smoking (HR, 2.3; 95% CI, 1.2 to 4.8), and cumulative corticosteroid dose greater than the median (HR, 2.6; 95% CI, 1.4 to 5.0). Other asthma therapies did not contribute significantly to these models. Thus, a 70% increase in overall fracture risk among unselected community patients with adult onset asthma was mainly confined to the subset who also had chronic obstructive pulmonary disease and was influenced by substantial corticosteroid use.


Plasma membrane from Candida tropicalis grown on glucose or hexadecane. II. Biochemical properties and substrate-induced alterations.
Isolated plasma membranes from the yeast Candida tropicalis grown on two different carbon sources (glucose or hexadecane), had similar contents of protein (60% of total dry weight), lipid (21-24%) and carbohydrates (16-21%). Sodium dodecyl sulphate gel electrophoresis of the membrane proteins revealed 17 and 19 protein bands, respectively, for glucose and hexadecane grown cells. There were marked differences in RF values and relative peak heights between the two gels. Sterols and free fatty acids were the major components of the plasma membrane lipids. Phospholipid content was less than 2% of total plasma membrane lipids. Membrane microviscosity, as determined by fluorescence polarization, was very high (16.6 P). Fatty acid determination of membrane lipids by gas chromatography showed a significant increase of C16 fatty acids in plasma membranes of cells grown on hexadecane. Reduced-oxidized difference spectra demonstrated the presence of a b-type cytochrome in both Saccharomyces cerevisiae and C. tropicalis plasma membranes. Its concentration in C. tropicalis plasma membranes was three-fold greater in cells grown on hexadecane than in glucose grown cells.


Dependence on RAD52 and RAD1 for anticancer drug resistance mediated by inactivation of mismatch repair genes.
Mismatch repair (MMR) proteins repair mispaired DNA bases and have an important role in maintaining the integrity of the genome [1]. Loss of MMR has been correlated with resistance to a variety of DNA-damaging agents, including many anticancer drugs [2]. How loss of MMR leads to resistance is not understood, but is proposed to be due to loss of futile MMR activity and/or replication stalling [3] [4]. We report that inactivation of MMR genes (MLH1, MLH2, MSH2, MSH3, MSH6, but not PMS1) in isogenic strains of Saccharomyces cerevisiae led to increased resistance to the anticancer drugs cisplatin, carboplatin and doxorubicin, but had no effect on sensitivity to ultraviolet C (UVC) radiation. Sensitivity to cisplatin and doxorubicin was increased in mlh1 mutant strains when the MLH1 gene was reintroduced, demonstrating a direct involvement of MMR proteins in sensitivity to these DNA-damaging agents. Inactivation of MLH1, MLH2 or MSH2 had no significant effect, however, on drug sensitivities in the rad52 or rad1 mutant strains that are defective in mitotic recombination and removing unpaired DNA single strands. We propose a model whereby MMR proteins - in addition to their role in DNA-damage recognition - decrease adduct tolerance during DNA replication by modulating the levels of recombination-dependent bypass. This hypothesis is supported by the finding that, in human ovarian tumour cells, loss of hMLH1 correlated with acquisition of cisplatin resistance and increased cisplatin-induced sister chromatid exchange, both of which were reversed by restoration of hMLH1 expression.


Children's misunderstandings of hazard warning signs in the new globally harmonized system for classification and labeling.
Accidental chemical poisoning causes more than 35 000 child deaths every year across the world, and it leads to disease, disability, and suffering for many more children. Children's ignorance of dangers and their failure to interpret hazard warning signs as intended contribute significantly to this problem. A new Globally Harmonized System for Classification and Labeling is being implemented internationally with a view to unifying the current multiple and disparate national systems. This study was designed to establish a productive, effective means of teaching the new GHS warning signs to primary school children (aged 7-11 years). A pre-test, post-test, follow-up test design was employed, with a teaching intervention informed by a Delphi survey of expert opinion. Children from one school formed the experimental group (n = 49) and a second school provided a control group (n = 23). Both groups showed a gain in knowledge from pre-test to post-test, the experimental group with a larger gain but which was not statistically significant. However, longer-term retention of knowledge, as shown by the follow-up test, was statistically significantly greater in the experimental group (p = 0.001). The employment of teaching to match children's preferred learning styles, and the use of active learning were found to be related to improved retention of knowledge. Part of the study involved eliciting children's interpretation of standard hazard warning symbols, and this provoked considerable concern over the potential for dangerous misinterpretation with disastrous consequences. This article focuses on the reasons for such misconception and the action required to address this successfully in testing the intervention.


The beta subunit of human chorionic gonadotropin lacks specificity for malignant cells in serous effusions.
The cytologic diagnosis of malignancy is frequently straightforward. For difficult cases, multiple immunostains and immunostain panels have been investigated without consensus. beta-human chorionic gonadotropin (hCG) has been reportedly expressed in malignancies, but not in normal tissue. HCG also has been reported as a specific marker of metastases in serous fluids when detected with laboratory assays. We investigated the clinical utility of hCG in this cytologic setting. A total of 97 cases of benign and malignant effusions were studied. Each case was immunostained with monoclonal hCG using the avidin-biotin technique and diaminobenzidine as a chromogen. Additionally, a mucicarmine stain was performed on most cases. Cases were evaluated for hCG expression and mucin in a blinded fashion. After the cases were reviewed, the diagnoses were unblinded and staining patterns were evaluated. Of the 47 benign cases studied, 23 (49%) exhibited immunoreactivity to hCG in at least 5% of mesothelial cells present. In contrast, 28 of 44 (64%) adenocarcionomas exhibited a similar degree of immunostaining. In all, 21 (48%) of the adenocarcinomas were also positive for mucin; five of these mucin-positive cases were negative for hCG. The combination of mucin and hCG detected 33 of 44 (75%) adenocarcinomas. We conclude that hCG lacks the specificity for malignant cells to be of clinical use in effusion cytology.


Digital subtraction angiography in the diagnosis of retinal vascular disease.
Digital subtraction angiography is a safe, inexpensive method of investigating systemic vascular disease in patients for whom conventional carotid angiography is too risky. We used this technique in five patients with a variety of retinal vascular conditions--a 55-year-old woman with occlusion of the right internal carotid artery, a 63-year-old man with bilateral occlusion of the internal carotid arteries, a 72-year-old man with occlusion of the stem of the left subclavian artery and an irregularity of the proximal portion of the innominate artery, a 77-year-old man with optic nerve head neovascularization and stenosis of the left internal and external and right internal carotid arteries, and a 74-year-old man with recurrent stenosis of the left internal carotid artery. In all five cases, digital subtraction angiography was helpful in determining the diagnosis and course of treatment.


A comparative study of sediment-bound trace elements and iron-bearing minerals in S. alterniflora and mudflat regions.
Elevated sediment-bound trace elements and iron-bearing minerals in intertidal habitats have been drawing more attention, but there is rarely a comparative study assessing these features between halophyte plants habitat and mudflats. In this paper, sediment samples were collected in S. alterniflora and the corresponding mudflat at 7 typical intertidal habitats (Chongming, Xiapu, Yueqing, Yunxiao, Zhanjiang, Beihai, and Zhuhai) from north to south of China, respectively. Trace element concentrations, including arsenic (As), mercury (Hg), cadmium (Cd), antimony (Sb) and scandium (Sc), and magnetic characteristics were determined. Variations in sediment-bound As, Hg, Cd, Sb were associated with S. alterniflora. Accumulations of sediment-bound As, Hg, Sb, Cd and Sc in S. alterniflora in Beihai were much higher than those in the mudflat. Concentration of sediment-bound As, Hg, Sb, Cd and Sc in S. alterniflora and mudflat were comparable in Yueqing, Xiapu, Yunxiao and Zhanjiang, respectively. Variations in low-frequency susceptibility, susceptibility of anhysteretic remanence magnetization, saturation isothermal remanence magnetization and frequency dependent susceptibility can explain the site-dependent accumulation of magnetic minerals in intertidal habitats. S. alterniflora tend to deplete sediment magnetic concentration and enhance sediment-bound As, Hg, and Sb concentration. The results of our study further revealed the coexistence of trace elements and magnetic minerals between the sampling sites and vegetative in intertidal habitats.


How much preoperative flexion contracture is a predictor for residual flexion contracture after total knee arthroplasty in hemophilic arthropathy and rheumatoid arthritis?
Although total knee arthroplasty (TKA) in hemophilic arthropathy (HA) or rheumatoid arthritis (RA) can improve functional ability, the postoperative range of motion (ROM) and prosthesis durability are reduced compared with those in osteoarthritic patients. We aimed to compare (1) the pre- and postoperative flexion contracture after TKA in HA and RA, (2) the threshold of preoperative flexion contracture as a predictor of residual contracture > 15° after TKA, and (3) the survival rate. Data from a consecutive cohort comprising 48 TKAs in HA and 92 TKAs in RA were retrospectively reviewed. The degree of flexion contracture was analyzed. Through receiver operating characteristics analysis, we aimed to determine the cutoff value of preoperative flexion contracture that increases the risk of residual contracture > 15° after TKA and compare the cutoff value in HA and RA. The survival rate was evaluated based on life table analysis and the Kaplan-Meier method. The degree of preoperative flexion contracture was not significantly different. The degree of postoperative residual flexion contracture was 5.6° in the HA group and 1.4° in the RA group, respectively (p < 0.001). The cutoff value of preoperative flexion contracture for residual contracture of > 15° at last-follow up was 25.0° in the HA group and 32.5° in the RA group. The 5- and 12-year survival rates were 96% and 87% in the HA and 99% and 95% in the RA group, respectively (n.s.). The postoperative residual flexion contracture was greater and the cutoff value of preoperative flexion contracture for residual contracture was smaller in the HA group than the RA group. Appropriate intra- and postoperative care to avoid postoperative residual contracture is required in HA patients. III.


Development and validation of a prognostic model for adult patients with acute myeloid leukaemia.
The high heterogeneity of acute myeloid leukaemia (AML) reflected in the patient- and disease-related factors accounts for the unsatisfactory prognosis despite the introduction of novel therapeutic approaches and drugs in recent years. In the development set (n = 412), parameters including age, hematopoietic cell transplantation-comorbidity index, white blood cell count, hemoglobin, biallelic CEBPA mutations, DNMT3A mutations, FLT3-ITD/NPM1 status, and ELN cytogenetic risk status were identified as independent prognostic factors for overall survival (OS) in the multivariable Cox regression analysis. A nomogram combining these predictors for individual risk estimation was established thereby. The prognostic model demonstrated promising performance in the development cohort. The calibration plot, C-index (0.74), along with the 1-, 2- and 3-year area under the receiver operating characteristic curve (AUC, 0.76, 0.79, and 0.74, respectively) in the validation set (n = 238) substantiated the robustness of the model. In addition to stratifying young (age ≤ 60 years) and elderly patients (age > 60 years) into three and two risk groups with significant distinct outcomes, the prognostic model succeeded in distinguishing eligible candidates for hematopoietic stem cell transplantation. The prognostic model is capable of survival prediction, risk stratification and helping with therapeutic decision-making with the use of easily acquired variables in daily clinical routine. This work was supported in part by grants from the National Natural Science Foundation of China (81770141), the National Key R&D Program of China (2016YFE0202800), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161406).


Geometric graph neural networks on multi-omics data to predict cancer survival outcomes.
The advance of sequencing technologies has enabled a thorough molecular characterization of the genome in human cancers. To improve patient prognosis predictions and subsequent treatment strategies, it is imperative to develop advanced computational methods to analyze large-scale, high-dimensional genomic data. However, traditional machine learning methods face a challenge in handling the high-dimensional, low-sample size problem that is shown in most genomic data sets. To address this, our group has developed geometric network analysis techniques on multi-omics data in connection with prior biological knowledge derived from protein-protein interactions (PPIs) or pathways. Geometric features obtained from the genomic network, such as Ollivier-Ricci curvature and the invariant measure of the associated Markov chain, have been shown to be predictive of survival outcomes in various cancers. In this study, we propose a novel supervised deep learning method called geometric graph neural network (GGNN) that incorporates such geometric features into deep learning for enhanced predictive power and interpretability. More specifically, we utilize a state-of-the-art graph neural network with sparse connections between the hidden layers based on known biology of the PPI network and pathway information. Geometric features along with multi-omics data are then incorporated into the corresponding layers. The proposed approach utilizes a local-global principle in such a manner that highly predictive features are selected at the front layers and fed directly to the last layer for multivariable Cox proportional-hazards regression modeling. The method was applied to multi-omics data from the CoMMpass study of multiple myeloma and ten major cancers in The Cancer Genome Atlas (TCGA). In most experiments, our method showed superior predictive performance compared to other alternative methods.


Moringa supplementation improves immunological indices and hematological abnormalities in seropositive patients receiving HAARTs.
Moringa oleifera Lam. is known to be of high nutritional and medicinal importance and has been demonstrated to possess a variety of biological activities. This study investigated the beneficial role of M. oleifera (moringa) supplementation in HIV positive subjects receiving antiretroviral drugs. Adult HIV positive individuals (104) attending the medical outpatient clinic in a tertiary health institution in Nigeria receiving highly active anti-retroviral therapies (HAARTs) were recruited in a randomized fashion for the study. Half of the subjects received moringa supplement (20 mg daily) additionally, while the others received only HAART and represented the control group. All subjects were monitored for 3 months during which their immunological status (CD4 counts and TNF-α), and hematological abnormalities at pre (baseline) and post study periods were determined. Baseline levels of CD4 increased while TNF-α decreased significantly in control and moringa supplemented groups (p < 0.01). However, the post study CD4 values in the moringa group were higher and TNF-α values were lower compared to the control group (p < 0.01). In addition, baseline hematological abnormalities (anemia, thrombocytopenia, leucopenia, lymphopenia, and neutropenia) were improved but most significantly in the moringa supplemented subjects. The results suggest that moringa has immune-beneficial properties and improved hematological abnormalities in HIV positive individuals receiving antiretroviral therapy.


Why do we help a micropreemie to live?
Helping a "micropreemie" to live by aggressive interventions may sometimes seem unnatural. However, utilitarian assessment of benefits derived from lifesaving efforts for a micropreemie is considered inappropriate. The goal in treating premature infants has advanced from fetal salvage to achieving "intact survival", which represents a new therapeutic target. In this way, the record for lifesaving in extremely low-birthweight infants is continually being broken. Why do we help a micropreemie to live? Moral and ethical emotions are the underlying reasons for the aggressive care devoted to premature infants, including micropreemies. Such human feelings might even be considered the purpose of life. Human emotion is the impetus for aggressive efforts to improve the survival prospects of premature infants. The beautiful and delicate nature of a newborn is compelling. The high-order emotion of empathy for another's misfortune is also important. Most human emotions are related to an awareness of death, and micropreemies are near death. In Oriental thought, a human being is a growing product of nature. Forces of nature and changes in a living being follow nature's rules. First and foremost, an individual life is part of the long chain of existence beginning before the self and continuing beyond it. An immature human being, even a newborn, is simultaneously a complete entity and part of nature's long chain of being, which has a wholeness of its own that affirms a micropreemie's right to life. A fetus is a member of human society in the sense that there is an overall reverence for life as a quality that lives on. The limit that bioethics must not exceed is the sanctity of life. We believe that the birth of a micropreemie is an important and serious event. We profoundly wish that a micropreemie might live and thrive, because we on earth must live with the continual presence and imminence of death.


Effects of varying media, temperature, and growth rates on the intracellular concentrations of yeast amino acids.
Variations of the yeast free amino acid pool under different culture conditions were studied in two Saccharomyces strains, the laboratory haploid strain S288C and the industrial fermentative yeast IFI256. The internal amino acid pool of both strains was measured when grown in laboratory (minimal and complete) versus semiindustrial (molasses with or without added biotin and/or diammonium phosphate) media, in fermentable (glucose, fructose, sucrose) versus respirable (glycerol) carbon sources, in different temperatures (22, 30, and 37 degrees C), pHs (2.0-4.75), and growth rates (0.018-0.24 h-1) in continuous culture, and at different phases of the growth curve in batch culture (lag, exponential, early and late stationary). Results indicated that environmental conditions, particularly the presence of amino acids in the media, enormously influenced the intracellular amino acid concentration. Higher values were detected in molasses than in laboratory media and in fermentable carbon sources (glucose, fructose, sucrose) than in glycerol. Variations in the amino acid pool along the growth curve were greater at 37 degrees C than at other temperatures; in all cases, the highest values were measured at the beginning of the exponential phase. In continuous culture and at different growth rates, intracellular free amino acid concentrations increased by 3-10-fold when the growth rate was lower than 0.05 h-1, representing 20-35% of the total (free plus protein) amino acid content and indicating that amino acid yield was a partly growth-linked parameter.


A right eye amaurosis patient with congenital absence of the internal carotid artery: A care compliant case report.
Absence or hypoplasia of the internal carotid artery (ICA) are rare developmental anomalies. Usually, patients with ICA agenesis are asymptomatic due to collateral circulation, but they may present with seizures, headache, or transient ischemic attack. We report a patient with right ICA absence in whom "paroxysmal right eye amaurosis" was the main symptom. A 76-year-old male patient suffered from "paroxysmal right eye amaurosis for 3 years". Three years prior, the patient had suffered sudden one-minute right eye amaurosis without any obvious cause. The attack reoccurred 1-2 times/year until one week before admission when he experienced two sudden right eye amaurosis. Congenital absence of the right ICA was diagnosed. In this patient with congenital absence of the right ICA, the ipsilateral anterior cerebral artery (ACA) was compensated by the anterior communicating artery (ACOM), and the ipsilateral middle cerebral artery (MCA) emerged from the carotid siphon of the contralateral ICA. The patient was given antiplatelet treatment consisting of aspirin and atorvastatin after admission and instructed to maintain the treatment after discharge. No symptom onset was observed during follow-up. Here, we report the patient's clinical manifestations and imaging findings and analyze the cause of the condition to provide a clinical reference for the study of congenital absence of the ICA.


The accuracy of artificial intelligence in predicting COVID-19 patient mortality: a systematic review and meta-analysis.
The purpose of this paper was to systematically evaluate the application value of artificial intelligence in predicting mortality among COVID-19 patients. The PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature, and VIP databases were systematically searched from inception to October 2022 to identify studies that evaluated the predictive effects of artificial intelligence on mortality among COVID-19 patients. The retrieved literature was screened according to the inclusion and exclusion criteria. The quality of the included studies was assessed using the QUADAS-2 tools. Statistical analysis of the included studies was performed using Review Manager 5.3, Stata 16.0, and Meta-DiSc 1.4 statistical software. This meta-analysis was registered in PROSPERO (CRD42022315158). Of 2193 studies, 23 studies involving a total of 25 AI models met the inclusion criteria. Among them, 18 studies explicitly mentioned training and test sets, and 5 studies did not explicitly mention grouping. In the training set, the pooled sensitivity was 0.93 [0.87, 0.96], the pooled specificity was 0.94 [0.87, 0.97], and the area under the ROC curve was 0.98 [0.96, 0.99]. In the validation set, the pooled sensitivity was 0.84 [0.78, 0.88], the pooled specificity was 0.89 [0.85, 0.92], and the area under the ROC curve was 0.93 [1.00, 0.00]. In the subgroup analysis, the areas under the summary receiver operating characteristic (SROC) curves of the artificial intelligence models KNN, SVM, ANN, RF and XGBoost were 0.98, 0.98, 0.94, 0.92, and 0.91, respectively. The Deeks funnel plot indicated that there was no significant publication bias in this study (P > 0.05). Artificial intelligence models have high accuracy in predicting mortality among COVID-19 patients and have high prognostic value. Among them, the KNN, SVM, ANN, RF, XGBoost, and other models have the highest levels of accuracy.


Motion preservation surgery for scoliosis with a vertebral body tethering system: a biomechanical study.
There is a paucity of studies on new vertebral body tethering (VBT) surgical constructs especially regarding their potentially motion-preserving ability. This study analyses their effects on the ROM of the spine. Human spines (T10-L3) were tested under pure moment in four different conditions: (1) native, (2) instrumented with one tether continuously connected in all vertebrae from T10 to L3, (3) additional instrumented with a second tether continuously connected in all vertebrae from T11 to L3, and (4) instrumented with one tether and one titanium rod (hybrid) attached to T12, L1 and L2. The instrumentation was inserted in the left lateral side. The intersegmental ROM was evaluated using a magnetic tracking system, and the medians were analysed. Please check and confirm the author names and initials are correct. Also, kindly confirm the details in the metadata are correct. The mentioned information is correct RESULTS: Compared to the native spine, the instrumented spine presented a reduction of less than 13% in global ROM considering flexion-extension and axial rotation. For left lateral bending, the median global ROM of the native spine (100%) significantly reduced to 74.6%, 66.4%, and 68.1% after testing one tether, two tethers and the hybrid construction, respectively. In these cases, the L1-L2 ROM was reduced to 68.3%, 58.5%, and 38.3%, respectively. In right lateral bending, the normalized global ROM of the spine with one tether, two tethers and the hybrid construction was 58.9%, 54.0%, and 56.6%, respectively. Considering the same order, the normalized L1-L2 ROM was 64.3%, 49.9%, and 35.3%, respectively. The investigated VBT techniques preserved global ROM of the spine in flexion-extension and axial rotation while reduced the ROM in lateral bending.


Reactivity of acetoacetate with alkaline picrate: an interference of the Jaffé reaction.
Spectrophotometric, kinetic, and polarographic studies of the interaction of acetoacetate with alkaline picrate have been undertaken in the presence of aqueous NaOH concentrations ranging between 0.50 mol/L and 2.50 mol/L. Spectrophotometric data has substantiated formation of the following acetoacetate-picrate complexes: 1:1 red, 490 nm; 2:1 orange, 390 nm; and 3:1 colorless, 265 nm. Depending upon the time of measurement, the composition of alkaline picrate, and the acetoacetate level in the test samples, acetoacetate may be either a positive or negative interference in kinetic Jaffé methods for the determination of creatinine. Polarograms of alkaline picrate in 0.50 mol/L NaOH showed three well-defined nitro group reduction waves and a more diffuse fourth reduction wave with approximate half-wave potentials of -0.62 V, -0.79 V, -0.94 V, and -1.32 V, respectively. Increasing the concentration of hydroxide and/or acetoacetate resulted in the disappearance of reduction waves 1 to 3 with only reduction wave 4 remaining. Based upon the polarographic results, a trinitro anion structure has been assigned for the 2:1 acetoacetate-picrate complex.


[Effect of the endolymphatic administration of protease inhibitors on pancreatic morphofunctional activity in acute experimental pancreatitis].
Experimental acute pancreatitis was induced in 16 dogs by administering infected bile under pressure. Functional and electron microscopic changes in the pancreas were studied before and after endolymphatic infusions of contrykal in a dose of 10 000 ATpE. It was established that endolymphatic administration of contrykal leads to an appreciable decrease in proteolytic activity of the pancreas and to inactivation of the kallikrein-kinin system. Electron microscopy studies of the exocrine apparatus of the pancreas after the dogs' death have demonstrated that endolymphatic administration of contrykal reduces intracellular processes of the synthesis of pancreatic enzymes.


Severe respiratory disease and its relationship with respiratory viruses in Colombia.
There are important gaps in our understanding of the epidemiology of respiratory virus infections in tropical countries. In September 2003, the Colombian epidemiological surveillance system was notified of several deaths from an acute respiratory disease (ARD). In order to identify the agents associated with ARD cases, a clinical and laboratory-based surveillance system was implemented throughout the country. Between September 19 and December 31, 2003, 64 suspected cases of ARD were reported; of these reported cases, 21 (33%) died. Among 25 patients who underwent virus studies, influenza A (H3N2) (n=7) was the most frequently identified agent. Other viruses included parainfluenza (4), influenza B (1), and respiratory syncytial virus (3). The peak occurrence of cases and deaths coincided with the replacement of the influenza A (H3N2) Panama strain, which had been circulating in Colombia since 1999, by three new influenza A (H3N2) strains (Korea, Fujian, and Wyoming). This outbreak led to the strengthening of surveillance for respiratory viruses and to new national recommendations for influenza vaccination in Colombia.


Application of comprehensive score of risk factors to determine the best time for surgical intervention in neonatal necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is a severe digestive systemic disease. Surgery is critical treatment for NEC patients. However, it is still hard to predict the optimal timing of surgery. Our study aimed to explore the indicative effect of comprehensive risk factors method in surgical intervention in NEC patients. Retrospective analysis was made on newborns with NEC, who were divided into group I (patients with NEC conservative therapeutic approach or no necrosis or perforation found in NEC operation) and group II (patients with necrosis or perforation found in NEC operation or failure of NEC conservative approach). Clinical manifestations and complications were recorded and the risk factors scores were calculated. The receiver operating characteristic curve and Youden index were calculated. One hundred and six NEC patients in Huizhou Central People's hospital were analysed. Significant difference was observed in the comprehensive scores of the two groups to judge the indications of NEC surgery. Among the risk factors of NEC surgery, the incidence specificity of abdominal induration, abdominal tenderness, hypotension and pneumoperitoneum was 100% in group II. The area under the curve of the comprehensive score of risk factors was 0.981 (95% confidence interval 0.958-1.000). The best cutoff value obtained by the maximum Youden index is 3.5 (sensitivity 97.2%; specificity 52.8%). When the specificity is 100%, the best interception value is 7.5 (sensitivity 91.4%; specificity 100%). Complications such as surgical intervention, mortality, stenosis after conservative treatment, perforation or necrosis during surgery were significantly different in different comprehensive scores. Abdominal induration, abdominal tenderness, hypotension and pneumoperitoneum are independent predictors of NEC surgery. Comprehensive risk factors score may be a potentially useful clinical decision-making tool for NEC surgery.


The impact of a high fidelity simulation-based debriefing course on the Debriefing Assessment for Simulation in Healthcare (DASH)© score of novice instructors.
Experiential learning, followed by debriefing, is at the heart of Simulation-Based Medical Education (SBME) and has been proven effective to help master several medical skills. We investigated the impact of an educational intervention, based on high-fidelity SBME, on the debriefing competence of novice simulation instructors. This is a prospective, randomized, quasi-experimental, pre- and post-test study. Sixty physicians without prior formal debriefing expertise attended a 5-day SBME seminar targeted on debriefing. Prior to the start of the seminar, 15 randomly chosen participants had to debrief a spaghetti and tape team exercise. Thereafter, the members of each team assessed their debriefer's performance using the Debriefing Assessment for Simulation in Healthcare (DASH)© score. The debriefing seminar that followed (intervention) consisted of 5 days of teaching that included theoretical and simulation training. Each scenario was followed by a Debriefing of the Debriefing (DOD) session conducted by the expert instructor. At the end of the course, 15 randomly chosen debriefers had to debrief a second tower building exercise and were re-evaluated with the DASH score by their respective team members. The Wilcoxon signed-rank test was used to compare pre- and post-test scores. Statistical tests were performed using GraphPad Prism 6.0c for Mac. A significant improvement in all items of the DASH score was noted following the seminar. The debriefers significantly improved their performance with regard to "maintaining an engaging learning environment" (Median [IQR]) (4[3-5] after the pre-test vs. 5.5[5-6] after the post-test, p<0.001); "structuring the debriefing in an organized way" (5[4-5] after the pre-test vs. 5[5-6] after the post-test, p=0.002); "provoking engaging discussion" (4[3-5.75] after the pre-test vs. 6[5-6] after the post-test, p<0.001); "identifying and exploring performance gaps" (5[4-6] after the pre-test vs. 6[5-6] after the post-test, p=0.014); and "helping trainees to achieve and sustain good future performance" (4[3-5] after the pre-test vs. 6[5-6] after the post-test, p<0.001). A simulation-based debriefing course, based mainly on DOD sessions, allowed novice simulation instructors to improve their overall debriefing skills including, more specifically, the ability to foster engagement in discussions and maintain an engaging learning environment.


Buckle muscle tension transducer: what does it measure?
The question is considered whether the strain of a buckle transducer attached to a muscle tendon provides a proportional measure of the force of the muscle acting directly on that tendon. It is shown that if muscle contains elastic and/or viscous elements in parallel with the force generator, the transducer strain may, under certain conditions, reflect other applied forces acting on the load (limb) in addition to the muscle force.


Determinants of survival in sinonasal and skull base chondrosarcoma: An analysis of the National Cancer Database.
Chondrosarcomas are rare, malignant chondroid tumors that can occur in the sinonasal and skull base regions. Surgery is a mainstay of treatment, but complete resection can be challenging because of the close proximity of critical neurovascular structures. Because of their rarity and relatively indolent nature, optimal treatment regimens are not established. Our objective was to assess determinants of survival for sinonasal and skull base chondrosarcomas utilizing the National Cancer Database (NCDB). The NCDB (2004-2017) was queried for cases of sinonasal and skull base chondrosarcoma. Multivariate hazard regression modeling was used to identify significant predictors of 60-month and 120-month overall survival (OS). Seven hundred thirty-six cases met inclusion criteria. OS for all treatment types was 84.7% [SE±0.02] at 60 months and 75.6% [SE±0.02] at 120 months. Surgery with or without adjuvant treatment was found to associate with highest OS at 60 and 120 months. For patients receiving adjuvant radiation during treatment, proton therapy had significantly better OS at 60 months (95.4% [SE±0.03] vs 82.3% [SE±0.03], -2 = 5.27; p = 0.02) and 120 months (85.1% [SE±0.08] vs 72.8% [SE±0.05], -2 = 4.11; p = 0.04) compared with conventional external beam. After adjustment for primary site, multivariate Cox regression modeling (n = 561) identified cofactors significantly associated with variation in mortality risk at 60 and 120 months, including age, Charlson-Deyo total score ≥ 3, insurance provision status, and tumor grade. Sinonasal and skull base chondrosarcoma are primarily treated with surgery with favorable OS. Adjuvant treatment may be required and proton radiation was associated with improved 60-month and 120-month survival compared with conventional radiation.


Viscosity as an inseparable partner of muscle contraction.
A simple model is presented where, by an iterative procedure, the forces delivered by the power strokes are summed up to overcome the load. The system is moderated by the viscous hindrance. The model reproduces the features of muscle contraction as defined by the data of He et al. [1997. ATPase kinetics on activation of permeabilized isometric fibres from rabbit and frog muscle: a real time phosphate assay. J. Physiol. 501, 125-148] on rabbit psoas muscle fibres. According to the model power strokes are random. Energy summation take place if the subsequent power stroke occurs before the energy delivered by the previous power stroke is completely used. In order the sarcomere to be competent to contract initial driving force must reach a threshold whose value increases with the load. The step size of the power stroke decreases with the increase of the load. The viscous regime is simulated by the equation, where 1/k measures the viscous hindrance of the system. The relationship between water activity, viscosity and stiffness is discussed. It is concluded that the three parameters vary cyclically and that when water activity decreases (sarcomere shortening, cross-bridge attachment) viscosity and stiffness increase.


Clinical outcomes of titanium-zirconium alloy narrow-diameter implants for single-crown restorations: a systematic review and meta-analysis.
Evidence is limited on whether titanium-zirconium alloy, narrow-diameter implants (Ti-Zr NDIs) have promising clinical outcomes when used to support single crowns. The purpose of this systematic review and meta-analysis was to evaluate clinical evidence, including survival rates, success rates, and marginal bone loss (MBL) on Ti-Zr NDIs that support single crowns. An extensive search was performed in the databases of PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library for studies published in English up to April 2022. Only peer-reviewed clinical studies with at least 10 patients and a follow-up time of at least 12 months were included. Risk of bias in each study was assessed and data extraction was carried out independently by two reviewers. The outcome variables were survival rates, success rates, and MBL. The search returned 779 results. Eight studies were identified for qualitative analysis and seven for quantitative synthesis. Overall, a total of 256 Ti-Zr NDIs were included. Cumulative implant survival rates and success rates were 97.5% (95% confidence interval (CI): 94.5% to 98.9%) and 97.2% (95% CI: 94.2% to 98.7%), respectively, over a maximum follow-up period of 36 months, with no difference between Ti-Zr NDIs and commercial pure titanium (cpTi) implants. Cumulative mean (SD) MBL was 0.44 (0.04) mm (95% CI: 0.36 to 0.52) after one year. Meta-analysis of MBL indicated a mean difference of 0.02 mm (95% CI: -0.23 to 0.10), with no differences between Ti-Zr NDIs and cpTi implants. Short-term results of Ti-Zr NDIs for single-crown restorations are quite promising, although the number of published studies and follow-up periods are insufficient to determine the real benefit for single crowns. Long-term, follow-up clinical studies are needed to verify the excellent clinical performance of Ti-Zr NDIs.


Antifungal susceptibility of the clinical and environmental strains of Cryptococcus gattii sensu lato in Taiwan.
The rare occurrence of human cryptococcosis caused by Cryptococcus gattii sensu lato leads to difficulties in establishing the antifungal susceptibility profile between species of this potentially lethal pathogen, which may be crucial for treating cryptococcosis. To establish an antifungal susceptibility profile of C. gattii s.l. in Taiwan. A total of 104 environmental C. gattii s.l. strains (including multilocal sequence typing ST7, ST106, ST274, ST328, ST546, ST548 and ST630) and 21 previously collected clinical strains (including ST7, ST44, ST06, ST274, ST328 and ST329) were included in this study. We determined the minimum inhibitory concentrations (MICs) of six antifungal agents (itraconazole, fluconazole, voriconazole, posaconazole, flucytosine and amphotericin B) against environmental C. gattii s.l. strains and compared the antifungal susceptibility profiles of environmental strains with those of clinical strains. The antifungal susceptibility data demonstrated that the MICs of antifungal agents against environmental strains were comparable to those against clinical strains. Compared with strains of Cryptococcus deuterogattii, those of C. gattii sensu stricto were more susceptible to azoles and flucytosine. The differences in antifungal susceptibility between the strains of each sequence type (ST) were significant. Correlation analysis of MICs revealed cross-resistance between azoles in environmental strains of C. gattii s.l. Geographic differences in the antifungal susceptibility of C. gattii s.l. isolated from different cities in Taiwan were observed in this study. Clinical and environmental strains were indistinguishable in antifungal susceptibility. The antifungal susceptibility of C. gattii s.l. is associated with STs. Therefore, establishing an ST-oriented domestic antifungal susceptibility database may help treat C. gattii s.l.-induced cryptococcosis.


Location of School Lunch Salad Bars and Fruit and Vegetable Consumption in Middle Schools: A Cross-Sectional Plate Waste Study.
The school lunch environment is a prime target for increasing a child's consumption of fresh fruits and vegetables (F/V). Salad bars are heavily encouraged in schools; however, more research is needed to examine the contexts in which salad bars promote consumption of F/V among students. To compare the amount of fresh F/V self-served, consumed, and wasted by students during lunch at schools with differing salad bar placement: inside or outside of the serving line. Cross-sectional plate waste study in which salad bar placement differed between schools. A random sample of middle school students (N=533) from six schools (three schools per district). Amount of fresh F/V taken, consumed, and wasted. Negative binomial multivariable regression examined placement of salad bars, adjusting for sex, grade, race/ethnicity, free/reduced status, day of the week, and nesting of students within schools. Almost all students (98.6%) in the schools with salad bars inside serving lines self-served F/V compared with only 22.6% of students in the schools with salad bars outside lines (adjusted prevalence ratio=5.38; 95% CI 4.04 to 7.17). Similarly, students at schools with salad bars inside the line had greater prevalence of consuming any F/V compared with students in schools with salad bars outside the line (adjusted prevalence ratio=4.83; 95% CI 3.40 to 6.81). On average, students with the salad bar outside the line wasted less F/V compared with those with salad bars inside the line (30% vs 48%, respectively). Few students visited salad bars located outside the lunch line. Salad bars inside the lunch line resulted in significantly greater fresh F/V taken, consumed, and wasted. When possible, schools should try to include salad bars inside the line to increase students' exposure to F/V.


Biological effects of off-pump vs. on-pump coronary artery surgery: focus on inflammation, hemostasis and oxidative stress.
Cardiopulmonary bypass (CPB) has been recognized as a cause of complex systemic inflammatory response, which significantly contributes to several adverse postoperative complications. In the last few years, off-pump coronary artery bypass grafting has gained widespread diffusion as an alternative technique to conventional on-pump coronary artery bypass grafting. Surgeons supporting off-pump surgery state that the avoidance of the CPB and myocardial ischemia-reperfusion significantly reduces the postoperative systemic inflammatory response and other biological derangements and, possibly, may improve the clinical outcomes. We review, here, the available evidence concerning possible differences between off-pump and on-pump procedures in terms of inflammation, hemostasis and oxidative stress. Consistent differences in the involvement of these systems are observed, but they are limited to the final steps of the surgical procedures and the early hours after. These findings suggest that the global surgical trauma may be as important, or even more, as the CPB in terms of systemic inflammatory and coagulation-fibrinolytic pathway activation. Further studies are needed in order to confirm this hypothesis.


COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review of critically unwell children and the association with underlying comorbidities.
Data show that children are less severely affected with SARS-Covid-19 than adults; however, there have been a small proportion of children who have been critically unwell. In this systematic review, we aimed to identify and describe which underlying comorbidities may be associated with severe SARS-CoV-2 disease and death. The study protocol was in keeping with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A total of 1726 articles were identified of which 28 studies fulfilled the inclusion criteria. The 28 studies included 5686 participants with confirmed SARS-CoV-2 infection ranging from mild to severe disease. We focused on the 108 patients who suffered from severe/critical illness requiring ventilation, which included 17 deaths. Of the 108 children who were ventilated, the medical history was available for 48 patients. Thirty-six of the 48 patients (75%) had documented comorbidities of which 11/48 (23%) had pre-existing cardiac disease. Of the 17 patients who died, the past medical history was reported in 12 cases. Of those, 8/12 (75%) had comorbidities.Conclusion: Whilst only a small number of children suffer from COVID-19 disease compared to adults, children with comorbidities, particularly pre-existing cardiac conditions, represent a large proportion of those that became critically unwell. What is Known: • Children are less severely affected by SARS-CoV-2 than adults. • There are reports of children becoming critically unwell with SARS-CoV-2 and requiring intensive care. What is New: • The majority of children who required ventilation for SARS-CoV-2 infection had underlying comorbidities. • The commonest category of comorbidity in these patients was underlying cardiac disease.


A multiunit CO2 anesthetizing system for use in transferring mosquitoes during field cage insectcide efficacy tests.
A multiunit CO2 delivery and anesthetizing system that supports expanded cage testing of mosquitoes is described. This system has proven more efficient than pipetting for conducting multiple tests and has facilitated the tripling of cage testing capabilities.


IVA cloning: A single-tube universal cloning system exploiting bacterial In Vivo Assembly.
In vivo homologous recombination holds the potential for optimal molecular cloning, however, current strategies require specialised bacterial strains or laborious protocols. Here, we exploit a recA-independent recombination pathway, present in widespread laboratory E.coli strains, to develop IVA (In Vivo Assembly) cloning. This system eliminates the need for enzymatic assembly and reduces all molecular cloning procedures to a single-tube, single-step PCR, performed in <2 hours from setup to transformation. Unlike other methods, IVA is a complete system, and offers significant advantages over alternative methods for all cloning procedures (insertions, deletions, site-directed mutagenesis and sub-cloning). Significantly, IVA allows unprecedented simplification of complex cloning procedures: five simultaneous modifications of any kind, multi-fragment assembly and library construction are performed in approximately half the time of current protocols, still in a single-step fashion. This system is efficient, seamless and sequence-independent, and requires no special kits, enzymes or proprietary bacteria, which will allow its immediate adoption by the academic and industrial molecular biology community.


Comparative efficacy and safety of antiviral traditional Chinese medicine injections for viral pneumonia: a systematic review and network meta-analysis.
Viral pneumonia (VP) is becoming a persistent and pervasive burden of disease. Traditional Chinese medicine Injections (TCMIs) have been proved effective in the treatment of patients with VP, which are now widely used in China. The evidence of TCMIs for VP is evolving rapidly. This study aims to assess the comparative efficacy and safety of TCMIs to provide more evidence and sights for the treatment selection of VP. Seven databases were searched from their inception up to 16 March 2022. Only randomized controlled trials (RCTs) are included to compare the efficacy and safety of antiviral TCMIs for the treatment of viral pneumonia. Clinical efficacy and rate of adverse events were considered as primary outcomes. A total of 76 RCTs with eight TCMIs comprising 7925 patients were included in the NMA. According to NMA, Reduning Injection combined with conventional antiviral drugs (CAD) produced superior effects in the effective outcomes and reduced the adverse event incidence rate of VP. This study indicated that TCMIs combined with CAD was more effective and safer than CAD monotherapy and compared different TCMIs therapies, which provided guidance and reference for the selection of clinical treatment medication.