Performance of phalangeal quantitative ultrasound parameters in the evaluation of reduced bone mineral density assessed by DX in patients with 21 hydroxylase deficiency.
The purpose of this study was to verify the performance of quantitative ultrasound (QUS) parameters of proximal phalanges in the evaluation of reduced bone mineral density (BMD) in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21 OHD). Seventy patients with 21 OHD (41 females and 29 males), aged between 6-27 y were assessed. The QUS measurements, amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), and ultrasound bone profile index (UBPI) were obtained using the BMD Sonic device (IGEA, Carpi, Italy) on the last four proximal phalanges in the non-dominant hand. BMD was determined by dual energy X-ray (DXA) across the total body and lumbar spine (LS). Total body and LS BMD were positively correlated to UBPI, BTT and AD-SoS (correlation coefficients ranged from 0.59-0.72, p < 0.001). In contrast, when comparing patients with normal and low (Z-score < -2) BMD, no differences were found in the QUS parameters. Furthermore, UBPI, BTT and AD-SoS measurements were not effective for diagnosing patients with reduced BMD by receiver operator characteristic curve parameters. Although the AD-SoS, BTT and UBPI showed significant correlations with the data obtained by DXA, they were not effective for diagnosing reduced bone mass in patients with 21 OHD.


Epitope mapping of BP230 leading to a novel enzyme-linked immunosorbent assay for autoantibodies in bullous pemphigoid.
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by circulating autoantibodies against BP180 and BP230. For BP180, the NC16A domain has previously been identified as the main antigenic target in BP, while data about the diagnostic value of epitopes on BP230 were inconclusive. To identify the most appropriate epitopes on BP230 to be applied in a simple, sensitive, and highly specific enzyme-linked immunosorbent assay (ELISA) for routine detection of serum autoantibodies. Ten overlapping linear fragments covering the whole length of BP230 were expressed in Escherichia coli. Based on Western blot analysis with sera from patients with BP (n = 49) and healthy controls (n = 94), the diagnostic performance of the fragments was compared by receiver operating characteristics curve analysis. The BP230-C3 fragment comprising the C-terminal portion (amino acids 2326-2649) was subsequently applied in a novel ELISA. The operating characteristics of this ELISA were analysed by probing sera from patients with BP (n = 118), pemphigus vulgaris (n = 50), rheumatoid arthritis and other inflammatory arthritides (n = 170), and systemic lupus erythematosus (n = 56), and from healthy blood donors (n = 483). Among all the fragments, BP230-C3 provided the best efficiency in serologically diagnosing BP by Western blot. An ELISA employing BP230-C3 revealed a diagnostic sensitivity of 56·8% and specificity of 97·6%. Its diagnostic added value amounted to 4·2% compared with the anti-BP180-NC16A-4X ELISA alone. Recombinant BP230-C3 is a suitable target antigen for the detection of serum autoantibodies against BP230.


Intensified association between waist circumference and hypertension in abdominally overweight children.
Abdominal adiposity is an important risk factor for childhood hypertension. The present study aimed to compare the strength of the association between waist circumference (WC) and hypertension in children with different WC levels. A total of 82,413 Chinese children aged 9-17 years were selected. An abdominally overweight child was defined as a child with WC ≥75th sex- and age-specific percentile. Hypertension was categorised as ≥95th sex-, age- and height-specific percentile. Logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of WC for hypertension after WC was transformed into sex- and age-specific z-score. Abdominally overweight children presented a higher risk of hypertension (OR: 2.39; 95% CI: 2.26, 2.54) than children with normal WC. In children with normal WC, one sex- and age-specific standard deviation increase in WC was associated with a 42% increase in odds of hypertension (OR: 1.42; 95% CI: 1.30, 1.55). That increase was elevated to 74% in abdominally overweight children (OR: 1.74; 95% CI: 1.66, 1.82). A similar pattern was also observed in different sex and area groups, and in children 9-14 years old. An intensified association between WC and hypertension was observed in abdominally overweight Chinese children. The gain in WC was associated with greater increase in hypertensive risk in abdominally overweight children than that of children with normal WC. These findings could improve intervention strategies for hypertension risk reduction in children.


Unplanned admission after ambulatory anaesthesia in France: analysis of a database of 36,584 patients.
Unplanned admission (UA) after ambulatory procedures is an unexpected event that has organisational and financial impacts. This study was undertaken to determine the current rate of UA in France and to evaluate the factors associated with the occurrence of this event. This is a retrospective analysis of a database of 36,584 patients issued from a private hospital in France. This study received an IRB approval. All of the patients that received ambulatory anaesthesia between April 2015 and June 2017 were included in this database. The overall rate of UA was 1.8% (95%CI: 1.3-2.3]. Hospitalisation after endoscopic procedures (gastrointestinal endoscopy and bronchial fibroscopy) was 1.1% (95%CI: 0.3-1.9), whereas it was 2.5% (95%CI: 1.8-3.2) after surgical procedures (p < 0.01). Organisational concerns, medical reason and surgical complications accounted respectively for one third of the hospitalisations. Pain was liable in 13% of cases, whereas PONV, residual sedation and urinary retention accounted respectively for 6.9%, 2.8% and 2.6% of cases. In a multivariate analysis, age > 60 years, ASA status > 2, general anaesthesia and the type of the procedures were identified risk factors. In this large cohort of ambulatory patients, the rate of UA remains significant. This is probably related, at least partly, to more invasive procedures scheduled in ambulatory setting. However, organisational problems occurred still frequently. Some factors appear to be easily improvable by appropriate preoperative information, better operating theatre scheduling and better analgesic strategy.


Case Report: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing.
T cell lymphomas (TCL) are a group of heterogeneous diseases with over 40 subtypes. In this study, we identified a novel TCL subtype which was featured by a unique T cell receptor (TCR) presentation, α, β and γ chains were co-existing in a single malignant T cell. A 45-year-old male patient was diagnosed T cell lymphoma after 2-month of abdominal distension and liver enlargement. Combining histology review, PET-CT scanning and immunophenotyes, the patient was not classified to any existing TCL subtypes. To better understand this unclassified TCL case, we performed single cell RNA sequencing paired with TCR sequencing on the patient's PBMC and bone marrow samples. To our surprise, we identified that the malignant T cells had a very rare TCR combination, by expressing two α chains, one β chain and one γ chain simultaneously. We further studied the molecular pathogenesis and tumor cell heterogeneity of this rare TCL subtype. A set of potential therapeutic targets were identified from the transcriptome data, such as CCL5, KLRG1 and CD38. We identified the first TCL case co-expressing α, β and γ chains and dissected its molecular pathogenesis, providing valuable information for precision medicine options for this novel TCL subtype.


Educating ethics codes by lecture or role-play; which one improves nursing students' ethical sensitivity and ethical performance more? A quasi-experimental study.
Promoting ethical and professional principles through education is the major way to build and maintain people's trust in the nursing. However, despite remarkable efforts in this area, sensitivity to these principles and their application in clinical practice remain low. This study aimed to compare the effect of educating codes of nursing ethics through methods of role-playing and lecture on the Ethical Sensitivity and Ethical Performance of nursing students. A single-blinded quasi-experimental study conducted on 114 nursing students of Urmia University of medical sciences, which recruited using convenience sampling and assigned to two groups of intervention (role-paly and lecture) and one group of control, so that the sixth-, seventh- and eighth-semester nursing students were allocated to the control, role-play and lecture groups, respectively. Data were collected using the Nurses' Ethical Performance Questionnaire (EPQ) and the Lutzen's Moral Sensitivity Questionnaire (MSQ) at three time-points of before, immediately after, and two months after the intervention. The same educational content was provided for both intervention groups, so that the role-play group received the intervention over an eight-day period and the lecture group received it in five sessions. The results showed there was a significant difference in the mean scores of ethical sensitivity and ethical performance between the three groups immediately (p < .001) and two months after the intervention (p < .001), so the mean scores were significantly higher in the role-play and lecture groups compared to the control group after the intervention (p < .001). In addition, after the intervention, the mean scores of ethical sensitivity and ethical performance in the role-play group were higher than the lecture group (p < .001). Educating codes of ethics by role-playing method had a greater positive effect on the promotion of the ethical sensitivity and ethical performance compared to the lecture.


Nationwide survey of surgically assisted rapid maxillary expansion.
We aimed to gather data on the current practice of surgically assisted rapid maxillary expansion (SARME) in the UK. Surveys were posted in the mail to all members of the British Association of Oral and Maxillofacial Surgeons (n=379) and 166 (44%) responded. In the previous year 69 responders (42%) had done at least one SARME operation. The technique used by individual surgeons may be more experience-based than evidence-based, which leads to considerable variation.


Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy.
Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.


A three-step method for analysing bacterial biofilm formation under continuous medium flow.
For the investigation and comparison of microbial biofilms, a variety of analytical methods have been established, all focusing on different growth stages and application areas of biofilms. In this study, a novel quantitative assay for analysing biofilm maturation under the influence of continuous flow conditions was developed using the interesting biocatalyst Pseudomonas taiwanensis VLB120. In contrast to other tubular-based assay systems, this novel assay format delivers three readouts using a single setup in a total assay time of 40 h. It combines morphotype analysis of biofilm colonies with the direct quantification of biofilm biomass and pellicle formation on an air/liquid interphase. Applying the Tube-Assay, the impact of the second messenger cyclic diguanylate on biofilm formation of P. taiwanensis VLB120 was investigated. To this end, 41 deletions of genes encoding for protein homologues to diguanylate cyclase and phosphodiesterase were generated in the genome of P. taiwanensis VLB120. Subsequently, the biofilm formation of the resulting mutants was analysed using the Tube-Assay. In more than 60 % of the mutants, a significantly altered biofilm formation as compared to the parent strain was detected. Furthermore, the potential of the proposed Tube-Assay was validated by investigating the biofilms of several other bacterial species.


Formation of ascochitine by plant pathogens of the genus Ascochyta.
Strains of fungi isolated from pulse crops: pea (Pisum sativum) and faba beans (Vicia faba) plants with symptoms of Ascochyta blight, footrot and stems lesions have been examined under laboratory conditions for their ability to produce ascochitine and metabolites toxic toArtemia salina. BothAscochyta pisi Lib and Ascochyta fabae LK Jones isolates formed ascochitine in yields of 20-480mg/kg. The highest yield of ascochitine was produced on rice and the lowest on maize grain.Ascochyta pinodes andPhoma medicaginis varpinodella (LK Jones) Boerema (formerlyAscochyta pinodella LK Jones) did not produce ascochitine.Crystalline ascochitine was found to be of moderate toxicity toArtemia salina larvae (LC50 = 85μg/cm(3)BSM*). Extracts ofPhoma medicaginis var,pinodella cultures were found to be highly toxic toArtemia salina.


'Tipping the Balance': Karl Friedrich Meyer, Latent Infections, and the Birth of Modern Ideas of Disease Ecology.
The Swiss-born medical researcher Karl Friedrich Meyer (1884-1974) is best known as a 'microbe hunter' who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer's 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a 'reservoir of disease' as a forerunner of 'one medicine' approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer's other intellectual contributions. Developed in a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer-like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet-can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet's and Smith's contributions to this scientific field have been widely acknowledged, Meyer's have been largely ignored. Drawing on Meyer's published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer's intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague-exchanges that not only showed how environmental and ecological conditions could 'tip the balance' in favor of parasites but which transformed Meyer thinking about resistance to infection and disease.


Anatomical evaluation of the vertebral artery (V2) and its influence in cervical spine surgery.
The aim of this study was to quantitatively evaluate the surgical anatomy of the vertebral artery and the sub-axial spine to assess their influence on cervical spine surgery. Retrospective data was evaluated from a total of 275 three-dimensional head and neck CT-angiograms. Vertebral artery diameter (VAD) and the distance between the uncinate process superior ridge and vertebral artery (UPVD) were measured. The minimum pedicle transverse angles (miPTAs), maximum PTA (MxPTAs), pedicle width (PW) and range of PTA (rPTA) were also measured. The mean value of the right UPVD was larger than that on the left: 4.5 vs. 3.6 mm (C3), 3.4 vs. 2.8 mm (C4), 3.0 vs. 2.5 mm (C5) and 3.1 vs. 2.4 mm (C6), respectively. The mean value of miPTA (32.2 vs. 31.7°: C3, 36.9 vs. 35.2°: C4, 35.3 vs. 33.9°: C5 and 29.9 vs. 29.2°: C6) and MxPTA (56 vs. 55.6°: C3, 61.7 vs. 60°: C4, 60.3 vs. 58.5°: C5 and 54.9 vs. 55°: C6) showed no statistical significance of laterality. The mean value of PW and rPTA ranged between 5.0-5.8 mm and 23.8-25.8° on both sides. Generally, right and mid- cervical segment decompression was found to be more secure than that on the left and in the lower cervical segment during an anterior cervical approach, considering the values of VAD and UPVD. Results of this study indicate that more attention should be paid to the mid-cervical pedicle screw fixation regarding the miPTA value, and rPTA (23.9-25.8°) should be maintained constantly regardless of cervical segment.


Assessment of Canadian policies regarding liver transplant candidacy of people who use alcohol, tobacco, cannabis, and opiates.
When last assessed in 2013, all Canadian liver transplant programs required 6 months of abstinence from alcohol. New studies have questioned the validity of this policy. Moreover, with recreational cannabis now legal in Canada, more transplant candidates may use cannabis. Given these changes, our objective was to obtain an understanding of current Canadian practices regarding liver transplantation and candidates with addiction or alcohol, tobacco, cannabis, or opiate use. Electronic surveys were distributed to the medical directors of all seven adult liver transplant programs in Canada. Questions were based on either a Likert-scale ranking or free response. The complete data set was aggregated to provide a national perspective on this topic and ensure each individual program remained anonymous. All seven programs responded to the survey. Of these programs, 43% always require 6-month abstinence from alcohol, 29% usually require it, and 14% sometimes require it. Formal alcohol rehabilitation is mandatory in two programs. The majority (57%) of programs never or rarely consider transplant for patients with acute alcoholic hepatitis; 29% require smoking cessation before consideration for transplant; and 71% felt that cannabis use is rarely or never a contraindication to liver transplantation. Significantly more Canadian programs now perform liver transplant for patients who have less than 6 months abstinence from alcohol, and alcoholic hepatitis is no longer an absolute contraindication in Canada. Policies on smoking and opiates are quite variable. Further study and discussion are critical for development of national policies to obtain equitable access to liver transplant for all.


Different blood acetaldehyde concentration following ethanol administration in a newly developed high alcohol preference and low alcohol preference rat model system.
A significant difference in blood-acetaldehyde concentration was observed between high alcohol-preference (HAP) rats and low alcohol-preference (LAP) rats, newly developed different alcohol preference lines. This difference of acetaldehyde accumulation may be due to cytosolic aldehyde dehydrogenase (ALDH1) polymorphism, which has been reported previously. As the doses of ethanol we employed are higher than that of voluntary drinking, there may be little direct relationship between acetaldehyde accumulation and alcohol preference. We suggest therefore that the ALDH1 polymorphism is associated with alcohol preference in HAP/LAP lines through some other unidentified mechanism.


Insulin like growth factor-1 works synergistically with dopamine to attenuate diabetic retinopathy by downregulating vascular endothelial growth factor.
Levels of Insulin-like growth factor-1 (IGF-1), a proangiogenic growth factor is elevated and dopamine downregulated in proliferative diabetic retinopathy (PDR). This study aims to investigate whether IGF-1 with dopamine can together modulate vascular endothelial growth factor (VEGF) to prevent proliferative diabetic retinopathy while also attenuating angiogenic effects of IGF-1. Effect of combination of levodopa L-Dopa with IGF-1 was tested on normal retinal pigment epithelium cells (ARPE-19) and human umbilical vein endothelial cells (HUVEC), followed by tube formation. Invivo analysis of anti-angiogenic potential assessed by chick chorioallantoic membrane (CAM) assay. Diabetes induction in wistar rats at two time points, 12 and 16 weeks, treated with L-Dopa+IGF-1 and analysed for morphological variations, serum and tissue dopamine levels, gene expression by real-time PCR and western blot assay. L-Dopa+IGF-1 on ARPE-19 cells caused no toxicity and worked synergistically. Reduced number of vessels observed. Significant improvement in inner retina thickness (*p < 0.05) was observed when L-Dopa was given alone and/or with IGF-1. Dopamine levels improved significantly in both serum and tissue (*p < 0.05). Levels of VEGF and IGF-1 receptors reduced significantly in 12 weeks. Western studies suggest that L-Dopa+IGF-1 modulates its effects via Akt/ERK dependent pathway. First ever report on synergistic effect of L-Dopa+IGF-1 in a rat model of diabetic retinopathy. Even though the effect of L-Dopa in combination with IGF-1 is comparable to levels of L-Dopa alone, this study presents an interesting finding of neuroprotective function of IGF-1, which has been studied in disease models of Parkinson's but not diabetes.


Computer analysis of amino acid chromatograms.
A procedure is described for the automatic off-line analysis of amino acid chromatograms of protein hydrolysates, using a small computer. The data requirements are basic, and, unlike previous programs, the present system allows the separation and identification of bands, as well as the quantitative determination of composition. With minor modification, the program could be extended for use with most types of chromatographic data. The validity of the application of the program to experimental data is discussed.


Does local irradiation affect gastric emptying in humans?
The authors measured gastric emptying in 13 patients undergoing radiation therapy to the chest, abdomen, or pelvis for nongastrointestinal cancer to investigate whether gastric emptying (GE) was altered by this therapy. Symptoms and weight were monitored at regular intervals. Patients served as their own controls and were compared to a group of healthy subjects. When studied prior to radiation therapy (baseline), cancer patients had a gastric emptying rate that was similar to a healthy control group (t1/2 mean+/-SEM 92.0+/-15.3 vs. 80.4+/-8.2 min). Irradiation did not change the emptying rate, either after the first dose (early) of 180 cGy (t1/2 99.5+/-17.9) or after 2 weeks of therapy (late) with 3000 cGy (t1/2 75.5+/-7.3). There was no correlation of radiation field or tumor type with gastric emptying rate. Two of the 13 patients experienced nausea and vomiting during their course of radiation, but their gastric emptying was unchanged from baseline.


Occupational exposures and mitigation strategies among homeless shelter workers at risk of COVID-19.
To describe the work environment and COVID-19 mitigation measures for homeless shelter workers and assess occupational risk factors for COVID-19. Between June 9-August 10, 2020, we conducted a self-administered survey among homeless shelter workers in Washington, Massachusetts, Utah, Maryland, and Georgia. We calculated frequencies for work environment, personal protective equipment use, and SARS-CoV-2 testing history. We used generalized linear models to produce unadjusted prevalence ratios (PR) to assess risk factors for SARS-CoV-2 infection. Of the 106 respondents, 43.4% reported frequent close contact with clients; 75% were worried about work-related SARS-CoV-2 infections; 15% reported testing positive. Close contact with clients was associated with testing positive for SARS-CoV-2 (PR 3.97, 95%CI 1.06, 14.93). Homeless shelter workers may be at risk of being exposed to individuals with COVID-19 during the course of their work. Frequent close contact with clients was associated with SARS-CoV-2 infection. Protecting these critical essential workers by implementing mitigation measures and prioritizing for COVID-19 vaccination is imperative during the pandemic.


Small bowel neuroendocrine tumours - casting the net wide.
Our aim is to provide an overview of small bowel neuroendocrine tumours (NETs), clinical presentation, diagnosis algorithm and management options. We also highlight the latest evidence on management and suggest areas for future research. Dodecanetetraacetic acid (DOTATATE) scan can detect NETs with an improved sensitivity than when compared with an Octreotide scan. It is complimentary to small bowel endoscopy that provides mucosal views and allows the delineation of small lesions undetectable on imaging. Surgical resection is the best management modality even in metastatic disease. Prognosis can be improved with the administration of somatostatin analogues and Evarolimus as second-line therapies. NETs are heterogenous tumours affecting most commonly the distal small bowel as single or multiple lesions. Their secretary behaviour can lead to symptoms, most commonly diarrhoea and weight loss. Metastases to the liver are associated with carcinoid syndrome.


Application of biomedical materials in the diagnosis and treatment of myocardial infarction.
Myocardial infarction (MI) is a cardiovascular emergency and the leading cause of death worldwide. Inflammatory and immune responses are initiated immediately after MI, leading to myocardial death, scarring, and ventricular remodeling. Current therapeutic approaches emphasize early restoration of ischemic myocardial reperfusion, but there is no effective treatment for the pathological changes of infarction. Biomedical materials development has brought new hope for MI diagnosis and treatment. Biomedical materials, such as cardiac patches, hydrogels, nano biomaterials, and artificial blood vessels, have played an irreplaceable role in MI diagnosis and treatment. They improve the accuracy and efficacy of MI diagnosis and offer further possibilities for reducing inflammation, immunomodulation, inhibiting fibrosis, and cardiac regeneration. This review focuses on the advances in biomedical materials applications in MI diagnosis and treatment. The current studies are outlined in terms of mechanisms of action and effects. It is addressed how biomedical materials application can lessen myocardial damage, encourage angiogenesis, and enhance heart function. Their clinical transformation value and application prospect are discussed.


Multiple strategies for the treatment of invasive breast carcinoma: A comprehensive prospective.
In this review, we emphasize on evolving therapeutic strategies and advances in the treatment of breast cancer (BC). This includes small-molecule inhibitors under preclinical and clinical investigation, phytoconstituents with antiproliferative potential, targeted therapies as antibodies and antibody-drug conjugates (ADCs), vaccines as immunotherapeutic agents and peptides as a novel approach inhibiting the interaction of oncogenic proteins. We provide an update of molecules under different phases of clinical investigation which aid in the identification of loopholes or shortcomings that can be overcomed with future breast cancer research.


Light propagation in high-spin organic microtubes self-assembled from shape persistent macrocycles carrying oxo-verdazyl biradicals.
A 1D paramagnetic organic tube self-assembled from a "clicked" shape-persistent macrocycle carrying high-spin oxoverdazyl biradicals shows optical wave guiding behavior.


Exome sequencing of individuals with Huntington's disease implicates FAN1 nuclease activity in slowing CAG expansion and disease onset.
The age at onset of motor symptoms in Huntington's disease (HD) is driven by HTT CAG repeat length but modified by other genes. In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We discovered damaging coding variants in candidate modifier genes identified in previous genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier-onset HD. Nuclease activities of purified variants in vitro correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion similar to those observed with complete FAN1 knockout. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD.


Lipid and apoprotein modifications in body builders during and after self-administration of anabolic steroids.
To determine the effects of anabolic steroids on serum lipid and apoprotein levels, 14 white male body builders who self-administered steroids for 2 to 3 months (steroid users) were studied; 10 agreed to screening while they were taking the drugs (ON treatment) and also at about 3 months following their suspension (OFF treatment). Controls consisted of 17 body builders who had never taken steroids (nonusers), and a group of 18 healthy sedentary subjects (controls). During the period of steroid administration, there was a slight reduction in total serum cholesterol, with a marked cholesterol decrease in the high-density lipoprotein (HDL) subfractions HDL2 and HDL3, and a significant reduction in the HDL2 cholesterol/HDL3 cholesterol ratio; the percentage of serum cholesterol transported by low-density lipoproteins (LDL) increased significantly. In addition, a marked apoprotein (apo) A-I reduction in the HDL2 and HDL3 subfractions was observed, as well as an apo A-II decrease that was significant only in the HDL3 subfraction, with an A-I/A-II ratio significantly reduced in both subfractions. Serum apo B was only slightly increased, with a very high B/A-I ratio. Apolipoprotein C-II and E levels showed no modifications, while apo C-III reduced significantly. Lipid and apoprotein values returned to almost normal levels in the OFF treatment period. Findings in the group of nonusers were similar to those in sedentary subjects. These results indicate that anabolic steroids profoundly alter the serum lipid-protein profile, and the changes may be caused in part by the significant differences observed in apoprotein levels.


Facile synthesis, characterization, and antimicrobial activity of cellulose-chitosan-hydroxyapatite composite material: a potential material for bone tissue engineering.
Hydroxyapatite (HAp) is often used as a bone-implant material because it is biocompatible and osteoconductive. However, HAp possesses poor rheological properties and it is inactive against disease-causing microbes. To improve these properties, we developed a green method to synthesize multifunctional composites containing: (1) cellulose (CEL) to impart mechanical strength; (2) chitosan (CS) to induce antibacterial activity thereby maintaining a microbe-free wound site; and (3) HAp. In this method, CS and CEL were co-dissolved in an ionic liquid (IL) and then regenerated from water. HAp was subsequently formed in situ by alternately soaking [CEL+CS] composites in aqueous solutions of CaCl2 and Na2 HPO4 . At least 88% of IL used was recovered for reuse by distilling the aqueous washings of [CEL+CS]. The composites were characterized using FTIR, XRD, and SEM. These composites retained the desirable properties of their constituents. For example, the tensile strength of the composites was enhanced 1.9 times by increasing CEL loading from 20% to 80%. Incorporating CS in the composites resulted in composites which inhibited the growth of both Gram positive (MRSA, S. aureus and VRE) and Gram negative (E. coli and P. aeruginosa) bacteria. These findings highlight the potential use of [CEL+CS+HAp] composites as scaffolds in bone tissue engineering.


Schizophrenia in real life: courses, symptoms and functioning in an Italian population.
In the general belief, schizophrenia is associated with the concepts of seriousness, incurability, dangerousness: this is incorrect. In recent decades, the interest in course studies increased and different trends emerged, not necessarily chronic, with the possibility of remission.The plan of this research was to draw a picture of the schizophrenia syndrome in a specific geographic area, in the past and at present time: this allows to detect needs, weaknesses and strengths, for a better planning of future interventions. The course of all cases diagnosed as schizophrenia (N = 1,759) in the period 1978-2008, was retrospectively studied in the entire population of an Italian province by observing, for a mean period of 12 years per person, age at first psychiatric consultation, number and length of admissions for both acute symptoms and residential-rehabilitation programs, number of interventions in outpatients. The cases under treatment (N = 842), were evaluated in terms of symptoms, using the Brief Psychiatric Rating Scale, and in terms of functioning, using the Personal and Social Functioning Scale. The disease course differs significantly between genders: males have an earlier age at first consultation (about 7 years earlier), higher admission rates, greater number of outpatient interventions and personal and social functioning significantly worse.Hospitalization resulted often unnecessary: 23.1% of cases were never hospitalized and 67.2% spent less than one week per year in hospital.A quarter of the cases meets the international criteria for remission and more than 75% are asymptomatic or mildly symptomatic; only 5.3% of cases shows severe symptoms. However, Personal and Social Functioning highlights, in about 1/3 of cases, relevant or serious problems mainly in Work and Relationships areas, whilst Aggressiveness is a serious problem only in 9%. In this population, schizophrenia in real life shows great individual variability in course, symptoms and functioning: in most cases nowadays it appears a less severe and chronic disease than in the past, but further improvements are needed on disability prevention and social inclusion.


Parents reported higher satisfaction rates when children recognised hospital staff from photographs placed in prominent locations.
Improved communication with staff during a child's hospitalisation is an important determinant of family satisfaction. We examined whether displaying staff photographs in prominent locations would help children and their parents or guardians to recognise staff and whether this enhanced identification would improve parental satisfaction with their child's hospitalisation. No photographs were displayed during the first part of the study. During the second part of the study, staff photographs were placed in prominent locations throughout the paediatric ward. Parents filled in a satisfaction questionnaire on discharge, and the children and their parents were asked how many staff members they could name. The children named a significantly larger number of staff members in phase two than phase one, while the parents' score was unchanged. Overall parental satisfaction was significantly higher in phase two. The parent's age, the duration of the child's hospitalisation and taking part in phase two of the study were significant predictors of parental satisfaction. When children were more able to recognise and name hospital staff, this indirectly improved parental satisfaction, even if the number that parents could identify remained unchanged. Displaying staff photographs is a simple way of increasing parental satisfaction during a child's hospitalisation.


Concentrations of gonadotropins, estradiol and progesterone in sows selected on an index of ovulation rate and embryo survival.
The objective of this study was to determine concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P4) and 17beta-estradiol (E2) in sows from a line selected on an index which emphasized ovulation rate (Select) and from a control line. A further classification of the sows in each line was made according to the estimated number of ovulations during an estrous cycle. Sows in the Select line were ranked into a high (HI) or low group (LI) when their estimated number of ovulations were 25 or more and 14 to 15, respectively. Sows of the control line were classified into groups as high (HC) or low (LC) when the estimated values for ovulation rate were 14-15 and 8-9 ovulations, respectively. Blood samples were collected every 12 h during a complete estrous cycle and samples were analyzed for concentrations of FSH and LH. Samples collected every 24 h were assayed for P4 and E2. Mean concentrations of FSH, LH, P4 and E2 did not differ (P > 0.10) between lines or between HI and LI or HC and LC groups. Selection of pigs for ovulation rate and embryonal survival did not affect concentrations of FSH, LH, P4 and E2 in sows during the estrous cycle.


Conservative surgery in patients with multifocal/multicentric breast cancer.
Many physicians recommend mastectomy in case of multifocal (MF) or multicentric (MC) breast cancer due to a theoretical risk of poor local control with less extensive surgery. We retrospectively evaluate outcome of patients with MF/MC cancers who had breast conservation with specific attention on local control and predictive factors of recurrence. Four hundred and seventy six patients with either MF (n = 421) or MC (n = 55) breast cancer, underwent breast-conserving surgery between 1997 and 2002 in a single institution. Median follow up was 73 months (range 11-118). Median age was 53 years (range 23-86). Invasive lobular carcinoma was found in 88 patients (18.5%) and mixed ductal-lobular cancer in 27 (5.7%) patients. Two hundred and sixty-seven patients (76.7%) had two identified tumor foci, 55 patients (15.3%) had three and 29 patients (8.0%) had four or more. Two hundred and sixty-one patients (55.3%) had nodal involvement. The 5-year cumulative incidence of local relapse was 5.1%. At the multivariate analysis, over-expression of HER2/neu and lack of both estrogen and progesterone receptors (HR: 3.2, 95% C.I. 1.01-10.0, and HR: 2.7, 95% C.I. 1.06-7.7, respectively) were associated with a higher ipsilateral breast cancer reappearance rate. Involvement of four or more lymph nodes and lack of estrogen and progesterone receptors (HR: 2.7, 95% C.I. 1.06-6.7, and HR: 4.7, 95% C.I. 2.1-10.4, respectively) were associated with poorer overall survival. In selected patients with MF/MC breast cancer, wide conservative surgery is not associated with poor local disease control and can be considered whenever acceptable cosmetic results can be achieved.


MicroRNAs in Testicular Cancer Diagnosis and Prognosis.
Testicular cancer processes a unique and clear miRNA expression signature. This differentiates testicular cancer from most other cancer types, which are usually more ambiguous when assigning miRNA patterns. As such, testicular cancer may represent a unique cancer type in which miRNAs find their use as biomarkers for cancer diagnosis and prognosis, with a potential to surpass the current available markers usually with low sensitivity. In this review, we present literature findings on miRNAs associated with testicular cancer, and discuss their potential diagnostic and prognostic values, as well as their potential as indicators of drug response in patients with testicular cancer.


Pre-hospital prediction of adverse outcomes in patients with suspected COVID-19: Development, application and comparison of machine learning and deep learning methods.
COVID-19 infected millions of people and increased mortality worldwide. Patients with suspected COVID-19 utilised emergency medical services (EMS) and attended emergency departments, resulting in increased pressures and waiting times. Rapid and accurate decision-making is required to identify patients at high-risk of clinical deterioration following COVID-19 infection, whilst also avoiding unnecessary hospital admissions. Our study aimed to develop artificial intelligence models to predict adverse outcomes in suspected COVID-19 patients attended by EMS clinicians. Linked ambulance service data were obtained for 7,549 adult patients with suspected COVID-19 infection attended by EMS clinicians in the Yorkshire and Humber region (England) from 18-03-2020 to 29-06-2020. We used support vector machines (SVM), extreme gradient boosting, artificial neural network (ANN) models, ensemble learning methods and logistic regression to predict the primary outcome (death or need for organ support within 30 days). Models were compared with two baselines: the decision made by EMS clinicians to convey patients to hospital, and the PRIEST clinical severity score. Of the 7,549 patients attended by EMS clinicians, 1,330 (17.6%) experienced the primary outcome. Machine Learning methods showed slight improvements in sensitivity over baseline results. Further improvements were obtained using stacking ensemble methods, the best geometric mean (GM) results were obtained using SVM and ANN as base learners when maximising sensitivity and specificity. These methods could potentially reduce the numbers of patients conveyed to hospital without a concomitant increase in adverse outcomes. Further work is required to test the models externally and develop an automated system for use in clinical settings.


Injection Adipocytolysis for Body and Jawline Contouring: Real-World Experience and Treatment Considerations.
The role of ATX-101 in submental fat reduction has been well documented; however, its applicability across multiple anatomic areas is to be explored. The authors sought to describe the experience with ATX-101 subcutaneous injections for body and jawline contouring and evaluate its safety. This single-arm, single-center observational study included 201 patients who underwent injection adipocytolysis with ATX-101 (area-adjusted dose of 2 mg/cm2) in the jowl, abdomen (upper/lower), thigh (inner/outer/banana roll), arm, anterior periaxillary fat, back (lower/upper/nape/lipoma), knee (anterior/medial), chest, and/or neck. The number of treatment sessions, treatment volumes, doses, injections required for each anatomic area, and associated adverse events were recorded. The mean number of treatment sessions conducted was 1.8. Multiple sessions were common for the jowl (mean: 2.0 and mean volume administered varied significantly between persons receiving 1 or multiple sessions [P = 0.005]). The mean volume and mean number of injections per session were highest in the chest (84.7 mL and 423.5, respectively) and lowest in the jowl (0.8 mL and 4.6, respectively). The chest (0.2 mL) and nape (0.2 mL) received the highest mean ATX-101 dose per injection site per session, whereas the inner thigh (0.11 mL) and upper back (0.11 mL) received the least. Adverse events observed were localized to the injection site. All patients experienced edema after each session, whereas numbness, tenderness, bruising, and paresis were experienced by 99.6%, 94.2%, 33.1%, and 2.6% of patients, respectively. Alopecia was not observed. ATX-101 was well tolerated for body and jawline contouring.


The response of bone to mechanical loading and disuse: fundamental principles and influences on osteoblast/osteocyte homeostasis.
Bone's response to increased or reduced loading/disuse is a feature of many clinical circumstances, and our daily life, as habitual activities change. However, there are several misconceptions regarding what constitutes loading or disuse and why the skeleton gains or loses bone. The main purpose of this article is to discuss the fundamentals of the need for bone to experience the effects of loading and disuse, why bone loss due to disuse occurs, and how it is the target of skeletal physiology which drives pathological bone loss in conditions that may not be seen as being primarily due to disuse. Fundamentally, if we accept that hypertrophy of bone in response to increased loading is a desirable occurrence, then disuse is not a pathological process, but simply the corollary of adaptation to increased loads. If adaptive processes occur to increase bone mass in response to increased load, then the loss of bone in disuse is the only way that adaptation can fully tune the skeleton to prevailing functional demands when loading is reduced. The mechanisms by which loading and disuse cause bone formation or resorption are the same, although the direction of any changes is different. The osteocyte and osteoblast are the key cells involved in sensing and communicating the need for changes in mass or architecture as a result of changes in experienced loading. However, as those cells are affected by numerous other influences, the responses of bone to loading or disuse are not simple, and alter under different circumstances. Understanding the principles of disuse and loading and the mechanisms underlying them therefore represents an important feature of bone physiology and the search for targets for anabolic therapies for skeletal pathology.


The role of phosphorus speciation of biochar in reducing available Cd and phytoavailability in mining area soil: Effect and mechanism.
The effect of phosphorus (P) speciation in biochar on soil available Cd and its mechanism to alleviate plant Cd stress remain largely unknown. Here, ammonium polyphosphate (PABC)-, phosphoric acid (PHBC)-, potassium dihydrogen phosphate (PKBC)-, and ammonium dihydrogen phosphate (PNBC)-modified biochar were used to investigate P speciation. The Cd immobilization mechanism of biochar was analyzed by XPS and 31P NMR, and the soil quality and the mechanism for the biochar to alleviate Cd stress were also determined. The results demonstrated that PBC (pristine biochar), PABC, PHBC, PKBC, and PNBC reduced the content of soil DTPA-Cd by 14.96 % - 32.19 %, 40.44 % - 47.26 %, 17.52 % - 41.78 %, and 21.90 % - 36.64 %, respectively. The XPS and 31P NMR results demonstrated that the orthophosphate on the surface of PABC, PHBC, PKBC, and PNBC accounted for 82.06 %, 62.77 %, 33.1 %, and 54.46 %, respectively, indicating that PABC has the highest passivation efficiency on soil Cd, which was ascribed to the highest orthophosphate content on the biochar surface. Pot experiments revealed that PABC could reduce the Cd content by 4.18, 4.41, 4.43, 2.94, and 2.57 folds in roots, stems, leaves, pods, and grains, respectively, and at the same time increase the dry and fresh weight of soybean and decrease Cd toxicity to soybean by improving the antioxidant system. In addition, application of the P-modified biochars improved the enzyme activity and physicochemical properties of the soil. This study provides a new perspective for studying the effect of P-modified biochars on soil Cd immobilization.


Global temperature change potential of nitrogen use in agriculture: A 50-year assessment.
Nitrogen (N) use in agriculture substantially alters global N cycle with the short- and long-term effects on global warming and climate change. It increases emission of nitrous oxide, which contributes 6.2%, while carbon dioxide and methane contribute 76% and 16%, respectively of the global warming. However, N causes cooling due to emission of NOx, which alters concentrations of tropospheric ozone and methane. NOx and NH3 also form aerosols with considerable cooling effects. We studied global temperature change potential (GTP) of N use in agriculture. The GTP due to N2O was 396.67 and 1168.32 Tg CO2e on a 20-year (GTP20) and 439.94 and 1295.78 Tg CO2e on 100-year scale (GTP100) during years 1961 and 2010, respectively. Cooling effects due to N use were 92.14 and 271.39 Tg CO2e (GTP20) and 15.21 and 44.80 Tg CO2e (GTP100) during 1961 and 2010, respectively. Net GTP20 was 369.44 and 1088.15 Tg CO2e and net GTP100 was 429.17 and 1264.06 Tg CO2e during 1961 and 2010, respectively. Thus net GTP20 is lower by 6.9% and GTP100 by 2.4% compared to the GTP considering N2O emission alone. The study shows that both warming and cooling effects should be considered to estimate the GTP of N use.


Indirect Calorimetry Overestimates Oxygen Consumption in Young Children: Caution is Advised Using Direct Fick Method as a Reference Method in Cardiac Output Comparison Studies.
Direct Fick method is considered a standard reference method for estimation of cardiac output. It relies on indirect calorimetry to measure oxygen consumption. This is important as only a minor measurement error in oxygen consumption can result in false estimation of cardiac output. A number of studies have shown that indirect calorimetry overestimates oxygen consumption in adults. The aim of this prospective single center observational method comparison study was to compare the determination of oxygen consumption by indirect calorimetry and reverse Fick method in pediatric patients. Forty-two children mean age 352 days (range 30 to 1303 days) and mean weight 7.1 kg (range 2.7-13.6 kg) undergoing corrective cardiac surgery were included in the study. The mean (standard deviation) oxygen consumption by reverse Fick method was 43.5 (16.2) ml/min and by indirect calorimetry 49.9 (18.8) ml/min (p < 0.001). Indirect calorimetry overestimated the reverse Fick oxygen consumption by 14.7%. Bias between methods was 6.5 (11.3) ml/min, limits of agreement (LOA) - 15.7 and 28.7 ml/min and percentage error of 47.7%. A significant bias and large percentage error indicates that the methods are not interchangeable. Indirect calorimetry and the direct Fick method should be used with caution as a reference method in cardiac output comparison studies in young children.


Localization of mGluR5, GABAB, GABAA, and cannabinoid receptors on the vago-vagal reflex pathway responsible for transient lower esophageal sphincter relaxation in humans: an immunohistochemical study.
Transient lower esophageal sphincter relaxations (TLESRs) are the predominant mechanisms underlying gastro-esophageal reflux. TLESRs are mediated by a vago-vagal reflex, which can be blocked by interaction with metabotropic Glutamate Receptor 5 (mGluR5), γ-aminobutyric acid type B (GABA(B)), γ-aminobutyric acid type A (GABA(A)), and cannabinoid (CB) receptors. However, the distribution of these receptors in the neural pathway underlying the triggering of TLESRs has not been evaluated in humans. Using immunohistochemistry, we investigated the distribution of mGluR5, GABA(A), GABA(B), CB1, and CB2 receptors in the human nodose ganglion, the brain stem, and the myenteric plexus of the esophagus. MGluR5, GABA(B), CB1, and CB2 receptors are abundantly expressed in neurons of the myenteric plexus of the LES, nodose ganglion cell bodies and nerve fibers, the dorsal motor nucleus, and nucleus of the solitary tract in the brain stem. GABA(A) receptors are expressed in the same regions except in the nodose ganglion and myenteric plexus of the LES. Human mGluR5, GABA(A,B), and CB(1,2) receptors are abundantly expressed along the vago-vagal neural pathway and involved in the triggering of TLESRs. These findings are not only in line with the central side effects observed during treatment with reflux inhibitors such as GABA(B) receptor agonists and mGluR5 antagonists, but also suggest that peripherally acting compounds may be effective.


Pregnancy following eclampsia: a longitudinal study at korle-bu teaching hospital.
To find out the reproductive performance of patients in the immediate pregnancy following an eclampsia. Longitudinal survey. Obstetrics Unit of Department of Obstetrics and Gynaecology in a teaching hospital. Three hundred and ninety seven women whose previous pregnancies were complicated by eclampsia were followed up based on a schedule of antenatal care from 14-16 weeks gestation till delivery. The occurrence of hypertensive complications, timing of delivery, fetal outcome and birth weight were noted. There were no cases of recurrent eclampsia and no maternal death. Pregnancy-induced hypertension and pre-eclampia recurred in 15.8% of the women. These recurrencies were more significant among those who had changed their male partners (p = 0.0005). The caesarean section rate was 65.9%. The mean ponderal indices in those who developed hypertensive complications were significantly lower than the normotensives (P<0.03 However, the overall perinatal mortality rate of 23.3 per 1000 deliveries was lower than the 62.8 per 1000 in the general obstetric population. Previous episode of eclampsia does not necessarily affect perinatal and maternal outcome adversely in subsequent pregnancy, provided adequate antenatal surveillance and timely delivery are offered to the patients.


Acute fatal pulmonary embolism during cyanoacrylate injection in gastric varices.
We report a case of massive pulmonary embolism during cyanoacrylate glue endoscopic injection in a patient with gastric varices from portal hypertension. A review of the literature and results in an animal model show the physiopathology and risk factors associated with this endoscopic procedure.


Demyelination Occurred as the Secondary Damage Following Diffuse Axonal Loss in a Rat Model of Radiation Myelopathy.
The main purpose of the present study was to examine the time and dose-dependent course of demyelination in the rat radiation myelopathy model in the first 180 days after irradiation of the spinal cord. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 50 Gy and 100 Gy, respectively. The behavioral dysfunction was observed by the forelimb paralysis scoring system. The histological damage in the irradiated spinal cord was examined by hematoxylin/eosin staining, luxol fast blue staining, immunohistochemical analysis, methylene blue/Azure II staining, and uranyl/lead salts staining. The gene expression of oligodendrocyte-related markers were also determined by quantitative real-time PCR. The complete loss of forelimb motor function in all animals was observed at 180 days 50 Gy post-irradiation and at 120 days 100 Gy post-irradiation. We demonstrated that a 50 and 100-Gy single-dose irradiation of the C2-T2 spinal cord segment resulted in diffuse axonal loss and elicited secondary demyelination damage in the spinal cord. We further observed that 100-Gy irradiation reduced the gene expression of myelin oligodendrocyte glycoprotein in irradiated spinal cord. Taken together, our data not only define diffuse axonal loss as the main histological damage but also provide the first evidence that demyelination occurred as the secondary damage in irradiated spinal cord.


Reduced immunogenicity of β-lactoglobulin by single amino acid substitution.
To reduce the immunogenicity of β-lactoglobulin (BLG), we prepared single amino acid substituted recombinant BLG mutants (BLG/P126A, BLG/V128D and BLG/D129A) in the methylotrophic yeast Pichia Pastris by fusion of the cDNA to the sequence coding for the α-factor signal peptide from Saccharomyces cerevisiae. Isoelectric points of single amino acid substituted BLGs were lower than that of native BLG. CD spectra indicated that the secondary structure of BLG had maintained native structure in single amino acid substituted BLGs. Fluorescence studies indicated that the conformation around Trp had not changed in single amino acid substituted BLGs. Anti-BLG antibody response was evaluated after immunization to C57BL/6 mice. Antibody response was reduced after immunization with BLG/P126A, BLG/V128D and BLG/D129A. And novel immunogenicity was not observed in the experiments. T cell proliferative response was evaluated in C57BL/6 mice, and it was clarified that BLG mutants also showed low response. Methods employed in this study was considered to be very effective to reduce immunogenicity of BLG.


Effects of diclofenac on experimental streptococcal necrotizing fasciitis (NF) in rabbit.
Aggravation of necrotizing fasciitis (NF) by the administration of non-steroidal antiinflammatory drugs (NSAIDs) has recently been suggested. A rabbit model of streptococcal NF was used to study the effects of parenteral administration of an NSAID on NF evolution and outcome. Of 16 rabbits inoculated with a Streptococcus pyogenes suspension together with staphylococcal alpha toxin, 8 were treated with two doses of 4 mg/kg diclofenac on day 1 after inoculation. Clinical, bacteriological and histological studies were performed until day 10. Under our experimental conditions, NSAID treatment significantly limited NF extension. A specific inverse relationship between the extent of inflammation and bacterial density in NF lesions was observed on day 1 after inoculation in the treated group suggesting that the greater severity of NF in humans treated with an NSAID could be due to the therapeutic delay induced by the misleading clinical effects of the NSAID, and not to inhibition of antibacterial defence.


Synthesis, characterization and metal ion-sensing properties of two Schiff base derivatives.
Two new Schiff base derivatives {2,2'-diphenyl-N,N'-bis(2-pyridylmethylene)biphenyl-4,4'-diamine} (1) and {2,2'-diphenyl-N,N'-bis(salicylidene)biphenyl-4,4'-diamine} (2) were synthesized and characterized by means of elemental analysis, (1)H NMR, FT-IR, and standard spectroscopy techniques. The molecular structure of 2 has been determined by X-ray single crystal analysis. The analyses of fluorescence properties of the compounds revealed that 1 and 2 are both poorly fluorescent and display sensitive fluorescence responses to a panel of 24 monovalent, divalent, and trivalent metal ions in CH(3)CN-DMSO (9:1, v/v). Results with imine 1 showed that Fe(3+), Cu(2+), Zn(2+), Cd(2+), Mn(2+), Zr(4+), Hg(2+), Cr(2+), Pb(2+), Sn(2+), Bi(2+), Al(3+), Ce(3+), La(3+), Sm(3+), Gd(3+), Nd(3+), Eu(3+) and Dy(3+) yields red shifts in emission and increases in intensity. And the greatest spectral changes for imine 2 include enhancements in emission intensity coupled with red shifts (Zr(4+), Sn(2+), Al(3+) and Zn(2+)) and strong quenching (Fe(3+)). The fluorescence enhancement mechanism of 1 and 2 for metal ions is based on: (i) CN isomerization; (ii) chelation-enhanced fluorescence (CHEF) effect; and (iii) excited-state intra/intermolecular proton transfer (ESPT).


A Clinical Model of Bone Angiosarcoma Patients: A Population-based Analysis of Epidemiology, Prognosis, and Treatment.
To investigate the epidemiological data, prognostic factors, and treatment outcomes of bone angiosarcoma (BA). This retrospective study was based on the Surveillance, Epidemiology, and End Results (SEER) database. The medical records of BA patients were selected from the SEER database from 1975 to 2016. Variables including patients' baseline demographics (age, sex, marital status, and year of diagnosis), tumor characteristics (tumor size, grade, and SEER Historic Stage A), and treatment (surgery and radiotherapy) were selected for further analysis. The research endpoints were overall survival (OS) and cancer-specific survival (CSS). The optimal cutoff values of continuous variables including age, year of diagnosis, and tumor size were identified using the X-tail program. Univariate Cox regression was used to identify potential prognostic factors and multivariate Cox regression was used to identify independent prognostic factors. All prognostic factors were included to predict the survival time compared to the median OS and CSS times via the novel nomograms. To validate the internal validation of nomograms, we analyzed the concordance indices (C-index). This study enrolled a total of 271 patients with malignant vascular bone tumors among residents of the United States between 1975 and 2016. After applying the exclusion criteria (one case without active follow-up), this study included 152 patients with BA. The median survival time of BA was significantly shorter than that of malignant vascular bone tumors for OS (9 months vs 27 months, P < 0.001). Age, year of diagnosis, tumor size, grade, stage, and surgery were identified as potential prognostic factors for OS or CSS in univariate Cox regression. However, only age (P < 0.001, P < 0.001), stage (P = 0.002, P < 0.001), and surgery (P = 0.001, P = 0.002) were independent prognostic factors for CSS and OS, respectively, in the multivariate analysis. Younger patients less than 54 years have significantly better prognosis for CSS/OS than patients between 54 and 67 years (Hazard ratios [HRs]: 1.651 [1.763-3.575], 2.557 [1.395-4.687]) and more than 67 years (HRs: 4.404 [2.237-8.670], 5.113 [2.923-8.942]). For CSS/OS, the survival time of patients with localized stage was significantly longer than that of patients with regional stage (HRs: 1.530 [0.725-3.228], 1.548 [0.834-2.873]) and that of patients with distant stage (HRs: 1.706 [0.899-3.237], 2.101 [1.254-3.520]). Patients with surgery had more survival time than patients without surgery for CSS/OS (HRs: 2.861 [1.542-5.310], 2.103 [1.308-3.379]). All factors were further included to generate nomograms for CSS and OS. The C-indexes for the internal validation of OS and CSS prediction were 0.787 (95% confidence interval [CI]: 0.738-0.836) and 0.768 (95% CI: 0.717-0.819), respectively. Age, stage, and surgery were closely associated with prognosis in patients with BA, and this clinical model was a favorable tool to evaluate survival possibilities.


Functional reconstitution of a crenarchaeal splicing endonuclease in vitro.
Sulfolobus tokodaii strain 7 is one of Crenarchaea whose entire genome has been sequenced. The genome sequence revealed that it possesses two open reading frames (ORFs) that are homologous to EndA, a protein responsible for splicing endonuclease activity in Archaea. Interestingly, one of the two ORFs lacks a putative catalytic amino acid residue for the nuclease activity. To investigate their functions, the two ORF products were individually expressed in Escherichia coli, partially purified, and tested for their nuclease activities in vitro. Using in vitro transcribed tRNA precursor as a substrate, we found that the two ORF products are concurrently required to cleave exon-intron junctions. Our finding implies that the splicing endonuclease for the organism is a multi-subunit complex composed of the two endA gene products.


Distribution of vasoactive intestinal polypeptide-like immunoreactivity in the mammalian heart. Interrelation with neurotensin- and substance P-like immunoreactive nerves.
The distribution of vasoactive intestinal polypeptide (VIP) immunoreactivity has been studied in the mammalian heart and compared with that of neurotensin and substance P by use of light-microscopic peroxidase-antiperoxidase immunohistochemistry. VIP-immunoreactive cell bodies are present in intracardiac ganglia in various locations. VIP-immunoreactive nerve fibers predominate in the atria and the conduction system but are rare in the ventricles and occur in cardiac ganglia, endocardium, and epicardium. VIP-ergic nerves supply the coronary vasculature having a preference for the microvasculature and the nodal cells of the sinuatrial node. The large vessels of the heart and periarterial cardiac glomera also receive a VIP-immunoreactive nerve supply. There is partial co-distribution with neurotensin- and substance P-immunoreactive nerve fibers but no co-location in identical nerve fibers is detectable. The VIP-ergic cardiac innervation, which is probably predominantly intrinsic, may stem from postganglionic parasympathetic neurons and is less substantial than the more homogeneous neurotensin-ergic and substance P-ergic nervous supply which is probably extrinsic. The occurrence of an extrinsic VIP-ergic cardiac innervation cannot be excluded however. The differential histotopography of the multitarget cardiac nerves containing the cardiovascular active peptides VIP, neurotensin and substance P may suggest multiple and complex peptide-peptide and peptide-classical transmitter interactions. These may contribute to the regulation of various cardiac functions.


Oxidative Stress Initiates Receptor-Interacting Protein Kinase-3/Mixed Lineage Kinase Domain-Like-Mediated Corneal Epithelial Necroptosis and Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3 Inflammasome Signaling during Fungal Keratitis.
Fungal keratitis remains a major cause of severe visual loss in developing countries because of limited choices of therapy. The progression of fungal keratitis is a race between the innate immune system and the outgrowth of fungal conidia. Programmed necrosis (necroptosis), a type of proinflammatory cell death, has been recognized as a critical pathologic change in several diseases. However, the role and potential regulatory mechanisms of necroptosis have not been investigated in corneal diseases. The current study showed, for the first time, that fungal infection triggered significant corneal epithelial necroptosis in human/mouse/in vitro models. Moreover, a reduction in excessive reactive oxygen species release effectively prevented necroptosis. NLRP3 knockout did not affect necroptosis in vivo. In contrast, ablation of necroptosis via RIPK3 knockout significantly delayed migration and inhibited the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in macrophages, which enhanced the progression of fungal keratitis. Taking these findings together, the study indicated that overproduction of reactive oxygen species in fungal keratitis leads to significant necroptosis in the corneal epithelium. Furthermore, the necroptotic stimuli-mediated NLRP3 inflammasome serves as a driving force in host defense against fungal infection.


Resolving thermoelectric "paradox" in superconductors.
For almost a century, thermoelectricity in superconductors has been one of the most intriguing topics in physics. During its early stages in the 1920s, the mere existence of thermoelectric effects in superconductors was questioned. In 1944, it was demonstrated that the effects may occur in inhomogeneous superconductors. Theoretical breakthrough followed in the 1970s, when the generation of a measurable thermoelectric magnetic flux in superconducting loops was predicted; however, a major crisis developed when experiments showed puzzling discrepancies with the theory. Moreover, different experiments were inconsistent with each other. This led to a stalemate in bringing theory and experiment into agreement. With this work, we resolve this stalemate, thus solving this long-standing "paradox," and open prospects for exploration of novel thermoelectric phenomena predicted recently.


Gas chromatography/multiphoton ionization/time-of-flight mass spectrometry using a femtosecond laser.
A laser can be used for the selective excitation and subsequent ionization of a molecule with an absorption band at the laser wavelength. This technique of multiphoton ionization (MPI), when combined with time-of-flight mass spectrometry (TOF-MS), permits the efficient detection of induced ions in mass analysis. This combination of MPI/TOF-MS can be coupled with gas chromatography (GC) to achieve even more enhanced selectivity. Thus, GC/MPI/TOF-MS can be employed for trace analysis of samples containing numerous chemical species. A variety of laser sources have been used for this purpose. Since molecules that are classified as environmental pollutants frequently contain chlorine and bromine atoms, the lifetime of the excited state can be decreased by energy transfer from the singlet to triplet levels by spin-orbit interaction. A high-power femtosecond laser with a pulse width shorter than the lifetime of the analyte molecule provides femtogram or even subfemtogram detection limits, which have not yet been achieved using the most sensitive high-resolution double-focus sector-type mass spectrometers. Numerous environmental pollutants such as dioxins in soils and pesticides in foods have been successfully quantified using GC/MPI/TOF-MS, and this technique has proven itself to be a useful and practical method for trace analysis.


Concurrent chemo-radiotherapy in elderly patients: tolerance and compliance in a series of 137 patients.
Aggressive cancer treatment is a challenge in elderly patients. The present study aims to assess tolerance in terms of acute toxicity and compliance of concurrent chemo-radiotherapy (cCRT) in a series of patients aged ≥70 years. Clinical records of patients aged ≥70 years who underwent cCRT between January 2005 and December 2013 were reviewed. Concurrent CRT had curative intent in 134 patients (97.8 %) and palliative intent in 3 patients (2.2 %). Chemotherapy (CT) drugs and schedule were selected according to tumor histology. Radiotherapy median dose was 45.0 Gy (range 11-70 Gy) for curative purposes and 54 Gy (range 40-56 Gy) for palliative purposes. Incidence of acute toxicity and compliance to cCRT were analyzed and correlated with age, Karnofsky Performance Status (KPS), and Charlson Comorbidity Index (CCI). Overall, 137 patients, 82 males (60 %) and 55 females (40 %), median age 74 years (range 70-90 years) were analyzed. Concurrent CRT schedule was completed by 132 patients (96.4 %). Thirty-one of these patients (23.5 %) temporarily interrupted treatment. Hematological toxicity with grade ≥1 was observed in 25 patients (18.2 %), gastrointestinal toxicity in 55 (40.1 %), and genitourinary in 13 (9.5 %). Mucositis with grade ≥1 was recorded in 19 patients (13.9 %). No statistical significant correlation between KPS, CCI, and toxicity was found. A correlation trend between mucositis and patient age (p = 0.05) was observed. Concurrent CRT for elderly was feasible and quite well tolerated. Great attention in prescribing CT dose should be paid to limit acute toxicity.


Comprehensive Transcriptome Analysis of Gonadal and Somatic Tissues for Identification of Sex-Related Genes in the Largemouth Bass Micropterus salmoides.
Largemouth bass (Micropterus salmoides) is an economically important fish. It can spawn many times during a breeding season, and there are no obvious morphological characteristics to distinguish male and female juvenile fish. So far, little is known about the genes regulating their sexual development in this species. Here, we performed RNA sequencing (RNA-Seq) analysis of the testis, ovary, and somatic tissue to identify sex-related genes in the largemouth bass. A total of 51,672 unigenes were obtained via the transcriptome analysis, and 5900 differential expression genes (DEGs), including 3028 up-regulated and 2872 down-regulated DEGs, were obtained in the somatic tissue, testis, and ovary. DEGs were retrieved by making comparisons: somatic tissue vs testis (1733-up and 1382-down), testis vs ovary (841-up and 807-down), and ovary vs somatic tissue (454-up and 683-down). Finally, functional annotation identified 22 key sex-related DEGs, including 13 testis-biased DEGs (dmrt1, cyp11b1, sox9, spata4, spata22, spata17, fshr, fem-1a, wt1, daz1, amh, vasa, and piwi1) and 9 ovary-biased DEGs (foxl2, gdf9, zp3, sox3, cyp19a, bmp15, fem-1b, fig. la, and piwi2). This result was further confirmed by the tissue expression detection via RT-PCR and RT-qPCR. Protein-protein interacting (PPI) network analysis revealed that the testis-specific dmrt1 interacts directly with the testis-biased DEGs (cyp11b1 and spata4) and the ovary-biased DEGs (foxl2, gdf9, zp3, sox3, cyp19a, and bmp15), suggesting that the dmrt1 as a sex-determining gene can play a dual role through inducing the testis-biased DEGs and inhibiting the ovary-biased DEGs during the testicular development. Our present results provide useful molecular data for a better understanding of sexual development in the largemouth bass.


Telehealth Strategies to Support Referral Management to Secondary Care in Brazil: A Cost-Effectiveness Analysis.
This study aimed to assess the cost-effectiveness of a remotely operated referral management system (RORMS) compared with a conventional referral management system (CRMS) in Brazil. This is a model-based cost-effectiveness analysis under the perspective of the Unified Healthcare System (Sistema Único de Saúde [SUS]) in Brazil. A Markov microsimulation model was developed to compare costs and referral outcomes of the RORMS and the CRMS. Model consisted of 4 states representative of sequential stepwise assessments of referral suitability, 3 states representative of referral outcomes, and 1 exit model state. Target population represented cases being referred from primary healthcare units to specialized care in SUS. Model inputs related to costs and effectiveness in the RORMS arm were obtained from the data set of a RORMS between July and December 2019. Model inputs for the CRMS model arm were obtained from administrative data sets of 2 Brazilian localities for the year 2019. Relative effect size of RORMS in comparison with CRMS in SUS was obtained from published studies. Effectiveness outcome was unnecessary referrals averted. The incremental cost-effectiveness ratio was calculated for the base case. Probabilistic sensitivity analysis was conducted. In the base-case analyses, RORMS dominated CRMS, with expected cost-savings from $50.42 to $80.62 per unnecessary referral averted. RORMS was the dominant strategy in 83.7% of 100 000 simulations in the probabilistic sensitivity analysis. In 16.2% of simulations, incremental cost-effectiveness ratio was between $0 and $222 per unnecessary referral averted. Model-based simulations indicate that the RORMS is likely to be cost saving in comparison with the CRMS.


Transcutaneous oximetry in evaluation of the initial peripheral artery disease in diabetics.
This study was performed to evaluate the reliability of transcutaneous oximetry as compared with strain gauge plethysmography and with Doppler in the assessment of the initial peripheral vascular disease in diabetics who are still asymptomatic. Twenty-five diabetics (38 lower extremities) with different degrees of peripheral vascular disease, classified according to Fontaine, were investigated. Ten healthy subjects (16 lower extremities) served as controls. In the first group of patients (still asymptomatic) it was possible to select by transcutaneous oximetry and by plethysmography a subpopulation that presented a significant reduction in the arterial flow of the limbs. Moreover, a significant correlation between data obtained by strain gauge plethysmography and transcutaneous oximetry was found (p less than 0.001), whereas correlation with data from Doppler was lacking.


Pediatric hernia repair: 1-stop shopping.
Multiple visits for the evaluation, treatment, and follow-up of straightforward surgical problems are inconvenient, can result in lost work for the parents, and missed school for the child. We hypothesized that with proper previsit screening, patients with select diagnoses can be evaluated in an outpatient clinic setting and undergo operation the same day. Criteria were developed to identify straightforward referrals to our surgical practice for umbilical, epigastric, or inguinal hernias. Scripting was created to offer families the option of consultation and, if indicated, surgical treatment on the same day. Data collected included number of patients, cases performed, insurance status, and consultation reimbursement and surgical fees. Families were surveyed postoperatively. Sixty-one patient candidates participated. The diagnosis and indication for surgery were confirmed in 56 (92%), of which 50 underwent repair the day of their consultation. Seventy-two percent of patients had commercial insurance, whereas 28% had Medicaid. The preoperative consultation fee was reimbursed in 39 (78%) of 50 encounters (57% Medicaid, 86% commercial). All surgical cases were reimbursed. Patient and family satisfaction was high. We conclude that it is feasible to provide same-day evaluation and service for straightforward pediatric hernias with acceptable financial reimbursement and high parent satisfaction.


Synthesis and evaluation of selegiline derivatives as monoamine oxidase inhibitor, antioxidant and metal chelator against Alzheimer's disease.
A series of compounds with monoamine oxidase inhibition and biometal chelation activities were designed, synthesised and evaluated as agents against Alzheimer's disease. The in vitro assay shows that most target compounds exhibit good MAO-B activities with submicromolar IC50 values and antioxidant activity (1.49-5.67 ORAC-FL values). The selected compounds were used to determine the biometal chelating ability using UV-vis spectrometry and high-resolution mass spectrometry, which confirm that they can effectively interact with copper(II), iron(II) and zinc(II). The ThT fluorescence binding assay indicates that the synthetic compounds can inhibit Cu(II)-induced Aβ1-42 aggregation. The parallel artificial membrane permeation assay shows that most target compounds can cross the BBB. Based on these results, compound 8a was selected as a potential multifunctional agent for the treatment of AD.


Effective Deep Brain Stimulation for Obsessive-Compulsive Disorder Requires Clinical Expertise.
Deep brain stimulation (DBS) is an innovative treatment for severe obsessive-compulsive disorder (OCD). Electrodes implanted in specific brain areas allow clinicians to directly modulate neural activity. DBS affects symptomatology in a completely different way than established forms of treatment for OCD, such as psychotherapy or medication. To understand the process of improvement with DBS in patients with severe OCD. By means of open-ended interviews and participant observation we explore how expert clinicians involved in the post-operative process of DBS optimization evaluate DBS effects. Evaluating DBS effect is an interactive and context-sensitive process that gradually unfolds over time and requires integration of different sources of knowledge. Clinicians direct DBS optimization toward a critical point where they sense that patients are being moved with regard to behavior, emotion, and active engagement, opening up possibilities for additional cognitive behavioral therapy (CBT). Based on the theoretical framework of radical embodied cognitive science (RECS), we assume that clinical expertise manifests itself in the pattern of interaction between patient and clinician. To the expert clinician, this pattern reflects the patient's openness to possibilities for action ("affordances") offered by their environment. OCD patients' improvement with DBS can be understood as a change in openness to their environment. The threshold for patients to engage in activities is decreased and a broader range of daily life and therapeutic activities becomes attractive. Movement is improvement.


Functional implications of major surgery for intraoral cancer.
A group of 41 patients were questioned about functional problems and concern for appearance, experienced following major surgery for intraoral malignancy. Twenty-five per cent of the group reported significant difficulties. Spouses reported a higher incidence of problems. The effects of primary tumour site and type of reconstruction on functional outcome are discussed.


Dietitian services are associated with improved patient outcomes and the MEDFICTS dietary assessment questionnaire is a suitable outcome measure in cardiac rehabilitation.
The purposes of this study were to (a) examine the effectiveness of registered dietitian (RD) education and counseling on diet-related patient outcomes compared with general education provided by the cardiac rehabilitation (CR) staff, and (b) evaluate the effectiveness of the Meats, Eggs, Dairy, Fried foods, In baked goods, Convenience foods, Table fats, Snacks (MEDFICTS) score as an outcome measure in CR. Observational study data examined from 426 CR patients discharged between January 1996 and February 2004. Groups were formed based on education source: (a) RD and (b) general education from CR staff. Baseline characteristics were compared between groups; pre/post diet-related outcomes (lipids, waist circumference, body mass index, MEDFICTS score) were compared within groups. Controlling for baseline measures and lipid-lowering medication, associations were examined between (a) RD education and diet-related outcomes and (b) ending MEDFICTS score and diet-related outcomes. Mean age was 62+/-11 years, 30% of patients were female, and 28% were nonwhite. At baseline, the RD group (n=359) had more dyslipidemia (88% vs 76%), more obesity (47% vs 27%), a larger waist (40+/-6 vs 37+/-5 inches), a higher body mass index (calculated as kg/m(2); 30+/-6 vs 27+/-5), a higher diet score (32+/-28 vs 19+/-19), and lower self-reported physical activity (7+/-12 vs 13+/-18 metabolic equivalent hours) (all P<.05) than the general education group (n=67). RD education was associated with improved low-density lipoprotein (r=0.13; P=.04), triglycerides (r=0.48; P=.01), and MEDFICTS score (r=0.18; P=.01). Improvements in MEDFICTS scores were correlated with improved total cholesterol, triglycerides, and waist measurements (all r=0.19; P=.04). Dietary education by an RD is associated with improved diet-related outcomes. The MEDFICTS score is a suitable outcome measure in CR.


[Reduction of Days in Inpatient Care in Psychiatric Hospitals with Flexible and Integrated Treatment for Patient-Centered Care with a Global Budget - Results with Three-Year Follow-up from the Evaluation Study EVA64].
This analysis describes the development of the duration of inpatient and daycare treatment as well as contacts in outpatient PIA in hospitals with flexible and integrated treatment (FIT) over a three-year follow-up period. Patients with treatment in the first year after FIT-onset and a follow-up period of three years were examined for 12 FIT-hospitals and compared with matched patients from hospitals providing routine care. 11,536 patients were analyzed. In the year after first treatment, the number of inpatient days was lower in almost all FIT-hospitals compared to routine care. On the other hand, the number of daycare treatment days was mostly higher than in routine care. FIT hospitals with a pre-existing FIT-like structure showed stronger effects. PIA utilization differed between FIT-hospitals. This analysis supports evidence-based health policy decisions on the adoption of patient-centered global budget care concepts.


Sustainable phosphorus management in soil using bone apatite.
Soil fertility and phosphorus management by bone apatite amendment are receiving increasing attention, yet further research is needed to integrate the physicochemical and mineralogical transformation of bone apatite and their impact on the supply and storage of phosphorus in soil. This study has examined bone transformation in the field over a span of 10-years using a set of synchrotron-based microscopic and spectroscopic techniques. Transmission X-ray microscopy (TXM) observations reveal the in-situ deterioration of bone osteocyte-canaliculi system and sub-micron microbial tunneling within a year. Extensive organic decomposition, secondary mineral formation and re-mineralization of apatite are evident from the 3rd year. The relative ratio of (v1 + v3) PO43- to v3 CO32- and to amide I increase, and the v3c PO43- peak exhibits a blue-shift in less than 3 years. The carbonate substitution of bone hydroxyapatite (HAp) to AB-type CHAp, and phosphate crystallographic rearrangement become apparent after 10 years' aging. The overall CO32- peak absorbance increases over time, contributing to a higher acid susceptibility in the aged bone. The X-ray Photoelectron Spectroscopy (XPS) binding energies for Ca (2p), P (2p) and O (1s) exhibit a red-shift after 1 year because of organo-mineral interplay and a blue-shift starting from the 3rd year as a result of the de-coupling of mineral and organic components. Nutrient supply to soil occurs within months via organo-mineral decoupling and demineralization. More phosphorus has been released from the bones and enriched in the associated and adjacent soils over time. Lab incubation studies reveal prominent secondary mineral formation via re-precipitation at a pH similar to that in soil, which are highly amorphous and carbonate substituted and prone to further dissolution in an acidic environment. Our high-resolution observations reveal a stage-dependent microbial decomposition, phosphorus dissolution and immobilization via secondary mineral formation over time. The active cycling of phosphorus within the bone and its interplay with adjacent soil account for a sustainable supply and storage of phosphorus nutrients.


A behavior change model to address caregiver hesitancy around COVID-19 vaccination in pediatrics.
Many families express hesitancy around immunizing their children against COVID-19. We sought to better understand the perspectives of vaccine hesitant caregivers, and develop targeted recommendations for health care workers and policymakers to engage in more effective vaccine discussions. We conducted semi-structured telephone interviews with 23 caregivers recruited from a pediatric infectious diseases clinic, including a subset of patients referred to discuss vaccine hesitancy. Thematic analysis of the interviews identified themes that were mapped using behavior change models to identify perceived barriers and facilitators towards COVID-19 immunization. Barriers and facilitators were mapped to the WHO (World Health Organization) 3C's (confidence, complacency, convenience) model of vaccine hesitancy as well as the COM-B (capability, opportunity, motivation) behavior change model. Barriers included mistrust in authorities, misperception of the risk of COVID-19 in children, and perceived health contraindications and negative previous vaccine experiences. Facilitators included positive relationships with healthcare workers, the promise of a "return to normal", and societal pressures to immunize. Efforts to increase vaccine uptake in the pediatric population must target specific barriers and facilitators to immunization expressed by caregivers. To address these concerns, we suggest: 1. Educating hesitant caregivers by highlighting the long-term pandemic effects on children and the threat of COVID-19 to children's health, 2. Building on the trust caregivers have in healthcare workers by involving frontline workers in public health policy, and 3. Harnessing the power of peer pressure by mobilization of societal pressures and establishing COVID-19 vaccination as the norm in children.


First 100 early endometrial cancer cases treated with laparoendoscopic single-site surgery: a multicentric retrospective study.
We sought to assess feasibility and perioperative outcomes for laparoendoscopic single-site surgery (LESS) in early endometrial cancer. This was a retrospective multicentric study of 100 early endometrial cancer cases undergoing LESS from July 2009 through July 2011. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy by LESS. Pelvic and paraaortic lymphadenectomy were performed in 48 and 27 patients, respectively. A median of 16 pelvic lymph nodes (range, 1-33) and 7 paraaortic lymph nodes (range, 2-28) were retrieved. Both median operative time (129 minutes; range, 45-321) and estimated blood loss (70 mL; range, 10-500) were greater when staging lymphadenectomy was performed (P values = .001). Four intraoperative and 4 postoperative complications were observed. Conversion to standard laparoscopy and laparotomy was necessary for completion of 1 case each. Patients responded positively regarding cosmetic result and minimal postoperative pain control. LESS further minimizes the invasive nature of surgery and is feasible for treatment of early-stage endometrial cancer.


Fluorescence methods for measuring the A, B, and H isoantigens on cytological material from bladder carcinoma.
Fluorescence methods for determining ABH isoantigens on transitional cells were developed for the study of cytologic material. Indirect immunofluorescence was used for A- and B-antigens, fluorescein-labeled Ulex Europaeus lectin for the H-antigen. Isoantigens of 151 patients with bladder carcinoma were studied. Patients with a malignant cytology showed deletion in 31/65 cases compared to 12/62 cases when the cytology was benign. Cyto-flow ploidy determinations were abnormal in 41/120 cases measured; cells from 21 of these 41 had isoantigen deletion compared to 25/79 cases with a diploid pattern. The ABH isoantigen deletion shows some relation to malignant cytology, abnormal ploidy and a visible tumor, but is probably an independent parameter.


Reconsideration of drug release from temperature-sensitive liposomes.
The liposomal phase transition temperature was monitored in unstirred suspensions using a differential scanning calorimeter. The main and pre-transition temperatures under conditions of stirring were measured by the change in 90 degrees light scattering using a fluorescence spectrophotometer. Both methods show the same main transition temperature either with or without stirring. Temperature sensitive liposomes were made of DPPC (dipalmitoylphosphatidylcholine), DMPC (dimylisitoylphosphatidylcholine) or DSPC (distearoylphosphatidylcholine). The calcein release profile from the liposomes depends on the stirring time of the liposome suspension at the main transition temperature. For 1 h incubation, the leakage profile with and without stirring is similar. It had been hypothesized that temperature sensitive liposomes released drug at the main-transition temperature. However, calcein leakage from liposomes is observed also at the pre-transition temperature. Thus, a liposomal encapsulated drug will likely leak from DPPC liposomes at body temperature (37 degrees C), even if the liposomes were designed to have a higher main transition temperature.


A bacteriostatic hemostatic dressing prepared from l-glutamine-modified chitosan, tannic acid-modified gelatin and oxidized dextran.
In this study, porous hemostatic sponges (CGS1, CGS2 and CGS3) with proper absorption (38-43×) and air permeability (2214 g/m2·day) were prepared from l-glutamine-modified chitosan (CG), tannic acid-modified gelatin (GTA), and oxidized dextran (ODEX) by Schiff base crosslinking reaction. Among them, CGS2 was proved to have high porosity (88.98 %), durable water retention (>6 h), strong antibacterial activity, proper mechanical quality, and suitable tissue adhesion. In addition, CGS2 had good biocompatibility, mainly manifested in low hemolysis rate (<0.4 %), low cytotoxicity (relative cell activity>90 %), and good biodegradability in vitro. The hemostatic time and blood loss in CGS2 group were much lower than those in commercial gelatin sponge group in three animal injury models. Moreover, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) results indicated that CGS2 promoted coagulation by activating the endogenous coagulation pathway. These results suggested that CGS2 had great potential for rapid hemostasis and avoidance of wound infection.


Supplemental description of Nyctotheroides pyriformis n. comb. (=Macrocytopharynxa pyriformis (Nie, 1932) Li et al. 2002) from frog hosts with consideration of the validity of the genus Macrocytopharynxa (Armophorea, Clevelandellida).
The morphological revisions of Macrocytopharynxa pyriformis (Nie, 1932) Li et al., 2002; collected from the rectum of Fejervarya limnocharis (=Rana limnocharis), are presented in this paper: (1) two surfaces of the organism are not identical - left side narrower and convex, right broader and flat or slightly concave; (2) infundibulum is large and well-developed with no "fold" or "plicature" present in the middle or posterior portion; (3) micronucleus is tiny and ovoid shaped and always embedded in the middle concavity of macronucleus, which can be well revealed by ammoniacal silver staining. Our phylogenetic analysis based on SSU-rDNA showed that M. pyriformis fell into the Nyctotheroides clade, within which four definite Nyctotheroides species were involved - N. cordiformis, N. deslierresae, N. parvus and N. hubeiensis. In combination with their morphological features, we discussed the reliability of using karyophore organelles or kinetal suture patterns as the generic taxonomic criteria. Besides, we considered that the genus Macrocytopharynxa is a junior synonym of Nyctotheroides and we transfer its type species to Nyctotheroides as Nyctotheroides pyriformis n. comb. The phylogenetic pattern of the family Nyctotheridae was also indicated in our work, but it will be necessary to analyze more species from fishes and reptiles before coming to a sound conclusion.


Integrated Multi-Tumor Radio-Genomic Marker of Outcomes in Patients with High Serous Ovarian Carcinoma.
Purpose: Develop an integrated intra-site and inter-site radiomics-clinical-genomic marker of high grade serous ovarian cancer (HGSOC) outcomes and explore the biological basis of radiomics with respect to molecular signaling pathways and the tumor microenvironment (TME). Method: Seventy-five stage III-IV HGSOC patients from internal (N = 40) and external factors via the Cancer Imaging Archive (TCGA) (N = 35) with pre-operative contrast enhanced CT, attempted primary cytoreduction, at least two disease sites, and molecular analysis performed within TCGA were retrospectively analyzed. An intra-site and inter-site radiomics (cluDiss) measure was combined with clinical-genomic variables (iRCG) and compared against conventional (volume and number of sites) and average radiomics (N = 75) for prognosticating progression-free survival (PFS) and platinum resistance. Correlation with molecular signaling and TME derived using a single sample gene set enrichment that was measured. Results: The iRCG model had the best platinum resistance classification accuracy (AUROC of 0.78 [95% CI 0.77 to 0.80]). CluDiss was associated with PFS (HR 1.03 [95% CI: 1.01 to 1.05], p = 0.002), negatively correlated with Wnt signaling, and positively to immune TME. Conclusions: CluDiss and the iRCG prognosticated HGSOC outcomes better than conventional and average radiomic measures and could better stratify patient outcomes if validated on larger multi-center trials.


IL-2 production by dendritic cells is not critical for the activation of cognate and innate effectors in draining lymph nodes.
Dendritic cells (DC) are unique antigen-presenting cells capable of triggering NK cell effector functions and priming naive T cells in vivo. Microbial stimulation induces early IL-2 production by mouse DC. Previous reports demonstrated that IL-2 is enriched at the site of DC/T cell interaction and promotes allogeneic T cell proliferation. However, the direct role of DC-derived IL-2 in the differentiation of cytotoxic T lymphocytes and in NK cell triggering in vivo has not been investigated. Lipopolysaccharide (LPS) stimulation of mouse bone marrow-derived DC results in early IL-2 production unless IL-4 is introduced in DC cultures. Here we show that IL-2 produced by LPS-activated DC is dispensable for cognate T cell responses since IL-2 loss of function DC elicit OVA-specific Tc1 effector and memory lymphocytes in draining lymph nodes in a setting where ex vivo cultured DC do not transfer antigens to host DC. Moreover, adoptively transferred IL-2 loss of function DC maintain their capacity to trigger NK cell proliferation/recruitment in lymph nodes. Therefore, immediate inducible IL-2 production by DC following microbial infection might play a regulatory role at ports of entry rather than in secondary lymphoid organs.


Measurement of the average radiation dose to the local skin and thyroid gland during intracranial aneurysm coil embolization.
Intracranial aneurysm coil embolisation is a fluoroscopically guided procedure associated with high radiation dose. The increase in the number of coil embolisation procedures raises concern for the amount of radiation and the associated radiation risks to the patients. This research study was conducted to determine the average radiation dose to patients' thyroid glands and local skin during intracranial aneurysm coil embolisation and to establish preliminary local diagnostic reference levels for this procedure. In this paper, local skin dose refers to the absorbed radiation dose on the areas of the skin exposed to radiation during intracranial aneurysm coil embolisation, namely neck, face and scalp. This study employed air-kerma area product meters to determine the local skin dose and diagnostic reference levels during intracranial aneurysm coil embolisation. In addition, thyroid radiation doses were measured using thermo-luminescent dosimeters on a phantom during simulation of embolisation procedures. The local skin doses as determined by air-kerma area product ranged between 33 and 125 Gy.cm2. The mean thyroid dose was 9.87 mGy. The established local diagnostic reference level was 52.1 Gy cm2, 17.8 min' fluoroscopy time and 503 image frames. The average air-kerma area product values and the proposed diagnostic reference levels were lower than most published values for intracranial aneurysm coil embolisation. The established local diagnostic reference levels are recommended for use as radiation dose optimisation tool at the research site. The findings of this study cannot be generalised or applied to other hospitals. The complexity of the embolisation procedures was not classified for this study. Further research on diagnostic reference levels for intracranial aneurysm coil embolisation, taking into account the complexity of the procedures, is recommended.