Reverse shoulder arthroplasty in obese patients: analysis of functionality in the medium-term.
Obesity is an epidemic nowadays and this fact conditions results in orthopaedic surgery. Very few studies evaluates if obesity is a risk factor for reverse shoulder arthroplasty. The aim of this study is to confirm if there are differences with regard to the outcomes in patients undergoing reverse shoulder arthroplasty according to their body mass index (BMI). A total of 35 patients were enrolled in the study. Then divided into subpopulations according to their BMI and analyzed twice. First analysis set a division 30 of BMI and second set it in 35. ASES score, major complications, length of the hospital stay, radiolucent lines in components as well as scapular notching were assessed. No major complications were described in our patients. No differences were found related to hospital stay, radiolucent lines or scapular notching. However, in the second analysis (BMI < 35 and ≥ 35) statistical differences were found regarding ASES score. Poorer functional outcomes were described in the type-II obese and morbidly obese population. Functional outcomes of reverse shoulder arthroplasty are worse in patients with a BMI over 35.


45,X/47,XYY mosaicism in a patient with Turner's syndrome.
A patient with classical Turner's syndrome and a 45,X/47,XYY mosaicism is described. Each cell line was present in approximately equal amounts in the peripheral blood lymphocytes, while in fibroblasts derived from skin and both gonads only the 45,X karyotype was present. It is suggested that the latter fact is responsible for the patient not having the mixed gonadal dysgenesis syndrome or tumor formation in both streak gonads.


Religiousness and disordered eating: does religiousness modify family risk?
The purpose of this study was to evaluate the role of intrinsic and extrinsic religiousness in modifying family risk on disordered eating among women. We hypothesized that intrinsic religiousness would buffer the impact of family risk whereas extrinsic religiousness would increase the risk. In a survey of 876 college women between the ages of 18 and 29, the results showed that, when intrinsic religiousness was higher, there was no relationship between family risk and disordered eating. When intrinsic religiousness was lower, there was a significant positive relationship between family risk and disordered eating. These findings support the hypothesized buffering effect of intrinsic religiousness. For extrinsic religiousness, there was a stronger relationship between family risk and disordered eating when extrinsic religiousness was higher than when it was lower, supporting the hypothesized enhanced vulnerability effect. Future research should actively explore other moderating variables as well as aspects of religiousness that may contribute to risk and resiliency in disordered eating.


A rare case of a pedunculated lipoma in the pharynx.
While lipomas on the trunk and limbs are common, they are rare in the upper aerodigestive tract. A case is reported of an 18 cm long pedunculated lipoma arising from the hypopharynx in a 73 year old man. The tumour was asymptomatic until it appeared in the mouth of the patient after a coughing episode.


Correlations between ATP hydrolysis, ATP synthesis, generation and utilization of delta pH in mitochondrial ATPase-ATP synthase.
Using fluorescence quenching of 9-amino-6-chloro-2- methoxyacridine induced either by ATP hydrolysis in the ATPase-ATP synthase complex or by succinate oxidation in inverted submitochondrial particles, correlation have been established between ATP hydrolysis, ATP synthesis and the generation and utilization of delta pH. The results obtained are best explained in terms of local circuits of protons.


Frequencies of phosphorylcholine-specific and T15-associated 10/13 idiotope-positive B cells within lipopolysaccharide-reactive B cells of adult BALB/c mice.
The frequencies of lipopolysaccharide-reactive B lymphocytes in adult BALB/c spleen cells were determined by limiting dilution experiments to be between 1 in 50 and 1 in 100. Within this reactive population, the frequencies of B lymphocytes specific for phosphorylcholine (PC) and/or binding a TEPC 15-associated idiotope-specific monoclonal antibody (10/13) were found to be between 1 in 50 and 1 in 500. Binding of these antibodies to immobilized PC or to monoclonal idiotope-specific antibodies could be inhibited by soluble PC in a solid-phase radioimmunoassay. Around half the PC-specific B cell clones were found to also bind 10/13 idiotope-specific monoclonal antibody, while the rest were either PC specific, but idiotope-negative or idiotope-positive, and unable to bind immobilized PC.


Approach to chronic obstructive pulmonary disease in primary care.
To review the diagnosis, assessment of severity, and management of chronic obstructive pulmonary disease (COPD) and to address the systemic manifestations associated with COPD. PubMed was searched from January 2000 to December 2007 using the key words COPD, practice guidelines, randomized controlled trials, therapy, and health outcomes. The Canadian Thoracic Society guideline on management of COPD was carefully reviewed. The authors, who have extensive experience in care of patients with COPD, provided expert opinion. Chronic obstructive pulmonary disease is a common systemic disease caused primarily by smoking. Spirometry is essential for diagnosis of COPD and should be integrated into primary care practice. Pharmacologic and nonpharmacologic therapy improves symptoms, capacity for exercise, and quality of life. Smoking cessation is the only intervention shown to slow disease progression. The systemic manifestations and comorbidity associated with COPD need to be identified and addressed to optimize health and quality of life. An evidence-based approach to managing COPD along with a primary care chronic disease management model could improve quality of life for patients with COPD.


A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes.
Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects. We conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible. There were 78 trials (81 comparisons; 13 175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91-1.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70-1.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49-40.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04-2.46)]. In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients.


Internal hydrocephalus and associated periventricular encephalitis in young dogs.
Six dogs that had a sudden onset and rapid progression of neurological signs with enlargement of the cranial vault at 6--8 weeks old were believed to have congenital hydrocephalus. There were severe inflammatory and necrotizing lesions in periventricular sites in the brain. A bacterial infection may have been the cause of this process.


[Complex regional pain syndrome].
Complex regional pain syndrome (CRPS) is not a very common yet typical complication of extremity trauma in the daily practice of a trauma surgeon. The pathophysiology of this puzzling disease is still not completely understood and its impact on the patient cannot be overestimated. However, advantages have been made in diagnostics and therapy. While a multitude of different diagnostic systems has led to confusion in the past, we now have an internationally accepted, validated and easy to reproduce diagnostic algorithm in the form of the Budapest criteria. The adequate therapy is still a field for debate, but there is now a broad choice of conservative and interventional treatments for the out- and inpatient setting.


Temperature induced dimorphism in Microsporum gypseum.
The biochemical mutant of Microsporum gypseum requiring adenine shows characteristic dimorphism dependent upon temperature. At 37 degrees C it produces faviform aconidial colonies with spherical swollen cells similar to thin-walled chlamydospores. At 26 degrees C it yields the usual mycelium with conidia. Conversion of the faviform and mycelial forms is controlled by temperature and reversible.


The comparative effectiveness of the "brown and blue reactions" for tracing neuronal processes of cells injected intracellularly with horseradish peroxidase.
The comparative advantages and disadvantages of diaminobenzidine (DAB) and benzidine di--HCl (BDHC) procedures for tracing processes of cells injected intracellularly with horseradish peroxidase (HRP) have been studied. The DAB reaction gives a good definition of membranes and appears more suitable for visualizing the fine structure of dendrites. The BDHC procedure, being more sensitive, induces crystal formation and heavily filled processes appear frosted. This last procedure is, however, much more appropriate for tracing the axonal system of injected cells.


Visible-light promoted de Mayo reaction by zirconium catalysis.
Zirconium catalysis with ZrCl4 was developed to facilitate a de Mayo reaction under visible light conditions without any external photosensitizer and additive.


Palliative care in the era of health care reform.
Research shows that early access to palliative care can significantly improve the quality of care for patients with chronic and advanced illnesses and reduce the overall costs of care. However, factors such as poor provider reimbursement mechanisms, inadequate formal education and training, workforce shortages, and low provider acceptance and patient engagement have created barriers to the widespread uptake of palliative care. Expanding access to these services requires their integration into new models of payment and delivery, such as Accountable Care Organizations, an overhaul of formal palliative care education and training, and improved messaging about these services to patients and providers.


Health items with a novel patient-centered approach provided information for preference-based transplant outcome measure.
Patient-reported outcome measures (PROMs) are widely applied to assess perceived health status. To date, no transplant-specific PROM is available for generating a single, standardized score regarding the health status of transplant recipients. The objective of this study is to generate health items for a new patient-centered PROM for organ recipients: the Transplant PROM (TXP). A five-phase, mixed-method approach was applied to identify and select the health items: scoping literature review, expert meetings, focus-group meetings with organ recipients, a special judgmental task within an online survey, and expert meetings for final selection of health items. Based on a previously published scoping literature review, a first round of expert meetings, and a total of four focus-group meetings with kidney, lung, and liver transplant recipients (N = 18), a list of 83 relevant health items relating to post-transplant life was selected. In an online survey, 183 transplant recipients selected the 10 most important health items from this list. After evaluating the frequency of selected health items and combining items that assess closely related or similar concepts in the second round of expert meetings, nine health items were chosen to be included in TXP: fatigue, skin, worry/anxiety, self-reliance, activities, weight, sexuality, stooling, and memory/concentration. The nine TXP health items reflect the most prominent issues transplant recipients experience. The TXP can be administered by means of a mobile phone app.


Pulsation artifact in short TR MR imaging and angiography: exacerbation with signal averaging.
Averaging the signals from more than one excitation per phase-encoding view increases the signal-to-noise ratio and, in conventional spin-echo magnetic resonance imaging, reduces most motion artifacts. To determine the effects of signal averaging on two-dimensional gradient-echo images, acquisitions with different TRs and with no averaging versus multiple-signal averaging were compared in a pulsatile flow phantom and the human abdominal aorta. Intraview (each view repeated before changing the phase-encoding value) and interview (obtaining all views sequentially and then repeating the entire set) averaging methods were used. Pulsation artifacts were present on all images of the flow phantom and the aorta. Intraview signal averaging, the method most commonly used, exacerbated rather than ameliorated pulsation artifacts with short TR sequences. Pulsation artifacts on two-dimensional images obtained with a short TR can be minimized by completing the acquisition as rapidly as possible, avoiding signal averaging. If signal averaging is used for short TR images, it should be interview averaging.


Case report of abuse of Orlistat.
A case report of abuse of the anti-obesity drug, Orlistat, is reported in a normal-weight woman with an eating disorder and stimulant dependence. The case is discussed with reference to the availability of prescription drugs on the Internet, abuse of nonamphetamines and the side effect profile of Orlistat versus laxatives.


EMF recommendations specific for children?
When discussing health risks for children due to electromagnetic fields it is crucial to translate scientific knowledge both into adequate protection and precautionary measures for the general public and, more particularly into specific recommendations for children. It is often aimed at influencing health-related attitudes and behaviour by means of information about health affecting behaviour, health risk factors, and health promoting possibilities. Children have to be treated differently from adults in addressing their ability and willingness to modify behaviour and their competence to comprehend cognitively the sense of behavioural recommendations. Research has shown that adults can be motivated to adjust their own behaviour in order to protect their children or to be role models for their children. Hence one way to modify children's behaviour is to address the parents and care persons. Generally education in the family, the social environment and in peer groups, nursery school and at school plays an important role in forming and influencing individual behaviour. The age of the target group has also to be taken into consideration. An important question is how to deal with scientific uncertainties when expressing EMF recommendations for children. Accentuating scientific uncertainties may under certain circumstances raise risk awareness. This can be an intended effect. But the expression of scientific uncertainties can also lead to unintended consequences in parent's behaviour or even senseless dealing with the respective EMF source. The paper points out relevant aspects of risk communication regarding EMF and children and suggests how recommendations for children might be designed.


Comparison of endoscopy and radiographic imaging for detection of esophageal inflammation and remodeling in adults with eosinophilic esophagitis.
Eosinophil predominant mucosal inflammation is central to the diagnosis and activity assessment of eosinophilic esophagitis (EoE). Esophageal mural remodeling is an important consequence of EoE that is responsible for adverse events of dysphagia, food impaction, and esophageal stenosis. The aim of this study was to compare upper endoscopy (EGD) with barium upper GI study (UGI) for the detection of esophageal inflammation and remodeling in adults with EoE. A retrospective review on a single-center database of adults with confirmed EoE identified those with EGD and UGI performed within 6 months of each another. Studies were reviewed for mucosal inflammatory and remodeling abnormalities. Seventy patients were included. Initial UGI results were consistent with EoE in 10% and suggestive of EoE in 39%. Review of UGI by a senior GI radiologist increased detection of changes consistent with EoE (34%). EGD identified characteristic abnormalities in 93%, which was significantly greater than UGI (67%). Inflammatory features were more frequently appreciated on EGD (74%) compared with UGI (21%). There was no significant difference in fibrostenotic changes observed on EGD (84%) versus UGI (73%). EGD and UGI have similar sensitivity for identifying the remodeling consequences of EoE; however, inflammatory features are better assessed on EGD. Inadequate sensitivity of UGI for composite features of EoE limits its capabilities as a diagnostic test, although radiologists' awareness significantly increases the diagnostic yield of UGI. UGI and EGD may identify fibrostenotic changes unappreciated by its counterpart and thus provide complementary information in select patients.


Environmental evaluation for workplace violence in healthcare and social services.
Federal policy recommends environmental strategies as part of a comprehensive workplace violence program in healthcare and social services. The purpose of this project was to contribute specific, evidence-based guidance to the healthcare and social services employer communities regarding the use of environmental design to prevent violence. A retrospective record review was conducted of environmental evaluations that were performed by an architect in two Participatory Action Research (PAR) projects for workplace violence prevention in 2000 and, in the second project in 2005. Ten facility environmental evaluation reports along with staff focus group reports from these facilities were analyzed to categorize environmental risk factors for Type II workplace violence. Findings were grouped according to their impact on access control, the ability to observe patients (natural surveillance), patient and worker safety (territoriality), and activity support. The environmental assessment findings reveal design and security issues that, if corrected, would improve safety and security of staff, patients, and visitors and reduce fear and unpredictability. Healthcare and social assistance employers can improve the effectiveness of violence prevention efforts by including an environmental assessment with complementary hazard controls.


Flux across [corrected] microneedle-treated skin is increased by increasing charge of naltrexone and naltrexol in vitro.
The purpose of this investigation was to evaluate the in vitro microneedle (MN) enhanced percutaneous absorption of naltrexone hydrochloride salt (NTX x HCl) compared to naltrexone base (NTX) in hairless guinea pig skin (GP) and human abdominal skin. In a second set of experiments, permeability of the major active metabolite 6-beta-naltrexol base (NTXOL) in the primarily unionized (unprotonated) form at pH 8.5 was compared to the ionized form (pH 4.5). In vitro fluxes of NTX, NTX.HCl and ionized and unionized NTXOL were measured through microneedle treated or intact full thickness human and GP skin using a flow through diffusion apparatus. Solubility and diffusion samples were analyzed by HPLC. Both GP and human skin show significant increases in flux when treated with 100 MN insertions as compared to intact full thickness skin when treated with NTX.HCl or ionized NTXOL (pH 4.5; p < 0.05). MN increased GP skin permeability for the hydrophilic HCL salt of NTX by tenfold and decreased lag time by tenfold too. Similar results were found using human skin, such that skin permeability to NTX.HCl was elevated to 7.0 x 10(-5) cm/h. Permeability of the primarily unionized (unprotonated) form of NTXOL at pH 8.5 was increased by MN only threefold and lag time was only modestly reduced. However, MN treatment with the primarily ionized (protonated) form of NTXOL at pH 4.5 increased skin permeability fivefold and decreased lag time fourfold. Enhancement was observed in vitro in both GP and human skin treated with MN compared to intact skin with the salt form of NTX and the ionized form of NTXOL. We conclude that transdermal flux can be optimized by using MN in combination with charged (protonated) drugs that have increased solubility in an aqueous patch reservoir and increased permeability through aqueous pathways created by MN in the skin.


Evaluation of an Interactive Case-based Online Network (ICON) in a problem based learning environment.
This study sought to assess the introduction of a web-based innovation in medical education that complements traditional problem-based learning curricula. Utilizing the case method as its fundamental educational approach, the Interactive Case-based Online Network (ICON) allows students to interact with each other, faculty and a virtual patient in difficult neurological cases. Given the paucity of available metrics to benchmark online systems, we complement user perceptions with data on system utilization. We describe a case study of distinct, small group tutorials over 2 years as part of the Human Nervous System and Behavior (HNSB) course at the Harvard Medical School. Participating students and faculty were interviewed following completion of the course and their utilization of the system was recorded and examined. Students each spent 3.2+/-1.3 h (mean+/-SD) through 8.6+/-2.8 accessions per week using ICON outside of required tutorial time. Faculty each spent 4.8+/-3.4 h through 16.6+/-8.9 accessions per week on ICON. Students identified real-time engagement, stronger relationships with faculty, increased accountability to the tutorial group and self-selected pace as the most beneficial characteristics of the ICON-based tutorial in comparison to traditional problem based learning (PBL) tutorials. Faculty identified enhanced collaboration with students and more realistic student experiences as the most beneficial characteristics. Both students and faculty reported that limitations of ICON included increased time investment for faculty and increased reliance on good faculty mentorship. This is the first study of the ICON learning system in undergraduate medical education, a platform designed to facilitate collaboration outside of the classroom. Data on user perceptions and system utilization suggest that both faculty and students chose to adopt this online learning system as a means for collaboration. The study also outlines future avenues for research in assessing novel online technologies.


[Sudy on the activation of early growth response factor-1 by silica dioxide and its signal pathway].
To discuss the role of early growth response factor (Egr)-1 and it's upstream signaling pathway in the development of silicosis. The expression and localization of Egr-1 were analyzed by immunofluorescence and in-situ hybridization. The activity of Egr-1 was observed in treated cells by using a reporter plasmid and EMSA, the activity of ERK1/2 in RAW264.7 incubated with SiO(2) by using a kinase assay, and further by using a kinase inhibitor assay to investigate the role of upstream kinase in the signal pathway of the activation of Egr-1. The obvious increase of expression and transcription of Egr-1 was observed shortly after being treated by silica and its activity increased abruptly. There was an increase of the activity of ERK1/2 in RAW264.7 cells treated, which reached a peak at 30 minutes. The expression and transcription of Egr-1 decreased maniferstly after using kinase inhibitors. Egr-1 expression can be induced by silica dioxide in RAW264.7 cells, and the ERK1/2, p38 kinases may take part in this process which suggest the pathway of SiO(2), ERK1/2, p38 and Egr-1 may play an important role in the development of silicosis.


Evaluation of tubulointerstitial injury by Doppler ultrasonography in glomerular diseases.
While Doppler ultrasonography is used commonly in various renal diseases, its clinical value in diagnosis of renal parenchymal diseases, especially glomerular diseases, remains controversial. We investigated whether Doppler ultrasonography in glomerular diseases could discriminate tubulointerstitial lesions, which correlated closely with long-term prognosis for renal function. Sixty patients with primary or secondary glomerular diseases were examined by Doppler ultrasonography immediately before renal biopsy. The resistive index was calculated, as was the atrophic index (a newly proposed parameter defined as renal sinus length/renal length). These were compared with histologic changes in biopsy specimens. Receiver operator characteristic analysis showed a resistive index of 0.65 to be the optimal for discriminating tubulointerstitial changes with specificity of 100% and sensitivity of 57.1%. Tubulointerstitial injury scores were significantly higher in patients with resistive indices exceeding 0.65 than in patients with a lower value. An atrophic index of 0.70 was also shown to be optimal with specificity 100% and sensitivity 61.9%. In combination, the 2 indices showed improved sensitivity; when the patients were divided into groups where both resistive and atrophic indices were normal (respectively < or = 0.65 and < or = 0.70) or where either or both were high, sensitivity rose to 85.7%, while specificity remained 94.4%. In combination, the resistive and atrophic indices discriminated tubulointerstitial injury in glomerular diseases with high specificity and sensitivity.


Transcoding zeros within complex numerals.
This paper describes a patient (LD) showing a selective syntactic deficit in the production of Arabic numerals. Unlike in previously reported cases, LD's syntactic difficulties result in deletions rather than insertions of zeros, with a reduction of the number magnitude. The pattern of errors highlighted a distinction between "lexical zeros", i.e. the zeros in tens, that are semantically derived, and "syntactic zeros" that are syntactically produced as the result of specific production rules. In LD, only syntactic zeros were affected. Furthermore, the processing of numerals with final zeros was found to be easier than the processing of numerals with internal zeros. This pattern of errors is compatible with the lexical-semantic model of Power and Dal Martello. In this model, in fact, lexical zeros originate from a numerical concept, while syntactic zeros originate from a concatenation operation, plus an overwriting operation leaving one or more intermediary zeros. Thus, lexical zeros may be easier to manipulate than syntactic zeros that merely represent a null quantity associated to a specific power of 10.


Flow cytometry of ethanol-fixed versus fresh bladder barbotage specimens.
Saline bladder barbotage specimens were obtained from 99 patients for comparison of flow cytometric deoxyribonucleic acid analyses using fresh versus ethanol-fixed cell preparation techniques. The analyses were consistent for the 2 methods in 87 (88 per cent) of the 99 cases (p less than 0.0001, Kappa statistic for agreement). Since accurate, reproducible results are obtainable on fixed bladder washings, samples may be sent to flow cytometry centers for analysis.


Dental Implants Survival After Nasal Floor Elevation: A Systematic Review.
The aim of this work is to assess the clinical outcomes of implants placed after a nasal floor elevation procedure. A systematic review was conducted using 4 electronic databases: MEDLINE (PubMed), Cochrane Library, Directory of Open Access Journals, and Scopus, following the PRISMA (Preferred Reporting Items for Systematic Reviews) statement recommendations to answer the PICO (Population, Intervention, Comparison, Outcome) question: "In patients undergoing dental implant placement in the maxillary anterior region (P), Do implants placed after nasal floor elevation (I) have a different survival (O) from those implants placed without grafting procedures (C)? The study was pre-registered in PROSPERO (CRD42021229479). Included article quality was assessed using the "NIH quality assessment tool", "The Newcastle-Ottawa scale," and "JBI critical appraisal tools for case reports." Twelve articles were finally selected, including 151 patients and 460 implants. The weighted mean follow-up was 32.2 months, and the weighted survival rate after this period was 97.64% (range: 89.2%-100%). No statistical differences could be inferred between the treatments performed in 1- or 2-stage, following a lateral approach or a transcrestal approach or using different grafting materials. A great heterogeneity was found in study design and methodological aspects. For this reason, a quantitative analysis followed by meta-analysis was not possible. Within the limitations of this study, implants placed after a nasal floor elevation present a good survival and a low range of complications. In absence of randomized studies, the level of evidence was low, attending the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) system and based on the study quality level, the strength of evidence attending the SORT (Strength Of Recommendation Taxonomy) was B.


Accelerated fractionation radiotherapy for advanced head and neck cancer.
Between 1981 and 1986, 89 patients with advanced head and neck squamous cancer were treated with a continuous accelerated fractionation radiotherapy (AFRT) regimen. Three fractions of 1.80 Gy, 4 h apart, were given on three treatment days per week (Monday, Wednesday, Friday), and the tumour dose was taken to 59.40 Gy in 33 fractions in 24-25 days. Acute mucosal reactions were generally quite severe, but a split was avoided by providing the patient with intensive support, often as an in-patient, until the reactions settled. Late radiation effects have been comparable to those obtained with conventional fractionation. The probability of local-regional control was 47% at 3 years for 69 previously untreated patients, whereas it was only 12% at one year for 20 patients treated for recurrence after radical surgery. Fifty-eight previously untreated patients with tumours arising in the upper aero-digestive tract were analysed in greater detail. The probability of local-regional control at 3 years was 78% for 17 Stage III patients and 15% for 31 Stage IV patients. This schedule of continuous AFRT is feasible and merits further investigation.


Identification of dual Acetyl-CoA carboxylases 1 and 2 inhibitors by pharmacophore based virtual screening and molecular docking approach.
Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme that plays a vital role in obesity-induced type 2 diabetes and fatty acid metabolism. To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed. The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features. The best pharmacophore hypotheses were validated by various methods such as test set, decoy set and Cat-Scramble methodology. The validated pharmacophore models were used to screen several small-molecule databases, including Specs, NCI, ChemDiv and Natural product databases to identify the potential dual ACC inhibitors. The virtual hits were then subjected to several filters such as estimated [Formula: see text] value, quantitative estimation of drug-likeness and molecular docking analysis. Finally, three novel compounds with diverse scaffolds were selected as potential starting points for the design of novel dual ACC inhibitors.


Activation of muscarinic K+ current by beta-adrenergic receptors in cultured atrial myocytes transfected with beta1 subunit of heterotrimeric G proteins.
Muscarinic K+ channels (IK(ACh)) in native atrial myocytes are activated by betagamma subunits of pertussis toxin (Ptx)-sensitive heterotrimeric G proteins coupled to different receptors. betagamma subunits of Ptx-insensitive Gs, coupled to beta-adrenergic receptors, do not activate native IK(ACh). In atrial myocytes from adult rats transfected with rat brain beta1 subunit IK(ACh) can be activated by stimulation of beta-adrenergic receptors using isoprenaline. This effect is insensitive to Ptx. These findings demonstrate for the first time promiscuous (Ptx-insensitive) coupling of Gsbetagamma to GIRK channels in their native environment.


Clinical Outcomes of Left Main Coronary Artery PCI With Rotational Atherectomy.
Data regarding rotational atherectomy percutaneous coronary intervention (RA PCI) angioplasty in the left main (LM) coronary artery are scarce, and mostly outdated. We aimed to describe clinical outcomes of RA PCI in LM. Patients requiring RA in 8 European countries and 19 centers were prospectively and consecutively included in the European registry of Cardiac Care of Calcified and Complex patients registry. In-hospital data collection and 1-year follow-up were performed for each patient. Between October 2016 and July 2018, 966 patients with complete data were included. Among them, 241 presented with an LM lesion, and 171 required an LM lesion preparation by RA. The latter, allocated to the LM-RA group, were compared with the 725 patients in the non-LM-RA group. Clinical success of the RA procedure was comparable in both groups, but in-hospital major adverse cardiac events were higher in the RA-LM group (7.6% vs 3.2%, adjusted p = 0.04), mainly driven by a higher in-hospital mortality rate (5.3 vs 0.3%, adjusted p = 0.005). At 1-year follow-up, mortality and major adverse cardiac event rates were comparable in both groups (12.9% vs 8.0%, adjusted p value: 0.821, and 15.8% vs 10.9%, adjusted p value: 0.329, respectively), but the rate of target vessel revascularization remained higher in the RA-LM group (5.3% vs 3.2%, adjusted p = 0.021). In conclusion, RA PCI is an efficient option for calcified LM lesions, providing acceptable outcomes regarding this population with high risk at 1 year, and yields comparable outcomes with RA PCI performed on non-LM lesions.


Mn-doped Co3O4 for acid, neutral and alkaline electrocatalytic oxygen evolution reaction.
This work reports the application of Mn-doped Co3O4 oxides in the electrocatalytic oxygen evolution reaction (OER). The materials were characterized by structural, morphological, and electrochemical techniques. The oxides with higher Co : Mn molar ratio presented a lower electron transfer resistance, and consequently the most promising OER activities. Pure Co3O4 shows an overpotential at j = 10 mA cm-2 of 761, 490, and 240 mV, at pH 1, 7, and 14, respectively, and a high TOF of 1.01 × 10-1 s-1 at pH 14. Tafel slopes around 120 mV dec-1 at acidic pH and around 60 mV dec-1 at alkaline pH indicate different OER mechanisms. High stability for Co3O4 was achieved for up to 15 h in all pHs, and no change in the structure and morphology after the electrocatalysis was observed. The reported excellent OER activity of the Mn-Co oxides in a wide pH range is important to broaden the practical applicability in different electrolyte solutions.


Spermatotoxicity of a protein isolated from the root of Achyranthes aspera: a comparative study with gossypol.
A previous study showed that 50% ethanolic extracts of the roots of Achyranthes aspera possess spermatotoxic effects. A 58-kDa protein (Ap) was isolated, and its spermatotoxic effects were studied in comparison with gossypol. Ap (25 mg/kg body weight a day) and gossypol (40 mg/kg body weight a day) were administered orally to Swiss male albino mice for 35 days. Sperm motility, sperm count, sperm abnormality, toxicity markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) in the liver and serum, testicular activities of hydroxyl methyl glutaryl CoA reductase (HMG CoA reductase), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase(17β-HSD), glucose-6-phosphate dehydrogenase, cholesterol level and serum testosterone were assayed. Spermicidal action of the proteolytic digests of Ap was also studied in vitro. Treated mice showed significant spermatotoxicity. Significant differences were also observed in the testicular activities of HMG CoA reductase, 3β-HSD, 17β-HSD and glucose-6-phosphate dehydrogenase and in the levels of cholesterol and serum testosterone. The nontoxic nature of Ap was indicated by the insignificant alterations in the activities of AST and ALT. Ap possessed spermicidal activity even after proteolysis. The 58-kDa protein isolated from A. aspera possesses spermatotoxic effects comparable to gossypol.


The global burden of trauma during the COVID-19 pandemic: A scoping review.
Purpose; The COVID-19 pandemic has necessitated profound adaptations in the delivery of healthcare to manage a rise in critically unwell patients. In an attempt to slow the spread of the virus nationwide lockdown restrictions were introduced. This review aims to scope the literature on the impact of the pandemic and subsequent lockdown on the presentation and management of trauma globally. Methods; A scoping review was conducted in accordance with PRISMA-ScR guidelines. A systematic search was carried out on the Medline, EMBASE and Cochrane databases to identify papers investigating presentation and management of trauma during the COVID-19 pandemic. All studies based on patients admitted with orthopaedic trauma during the COVID-19 pandemic were included. Exclusion criteria were opinion-based reports, reviews, studies that did not provide quantitative data and papers not in English. Results; 665 studies were screened, with 57 meeting the eligibility criteria. Studies reported on the footfall of trauma in the UK, Europe, Asia, USA, Australia and New Zealand. A total of 29,591 patients during the pandemic were considered. Mean age was 43.7 years (range <1-103); 54.8% were male. Reported reductions in trauma footfall ranged from 20.3% to 84.6%, with a higher proportion of trauma occurring secondary to interpersonal violence, deliberate self-harm and falls from a height. A decrease was seen in road traffic collisions, sports injuries and trauma occurring outdoors. There was no significant change in the proportion of patients managed operatively, and the number of trauma patients reported to be COVID-19 positive was low. Conclusion; Whilst the worldwide COVID-19 pandemic has caused a reduction in the number of trauma patients; the services managing trauma have continued to function despite infrastructural, personnel and pathway changes in health systems. The substantial effect of the COVID-19 pandemic on elective orthopaedics is well described, however the contents of this review evidence minimal change in the delivery of effective trauma care despite resource constraints during this global COVID-19 pandemic.


The p53 codon 72 polymorphism in Thai nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is a serious cancer in Thailand. To address on the genetic risk factor for NPC, we investigated association between the p53 codon 72 polymorphism (Pro/Arg) and NPC susceptibility in the Thai. The genotype frequency of this polymorphism in 102 NPC patients and 148 age-matched healthy controls was determined by using a PCR-RFLP assay. No statistically significant difference in the overall genotype frequencies or allele frequencies between cases and controls was observed. Among NPC patients, no statistical significant difference in p53 genotype frequencies between sex, histological types and clinical stages was observed. When cases and controls were categorized into 3 groups of age, >40, >45 and >50 years, the frequencies of p53 genotype in the cases were significantly different from those of the controls (P<0.05). The p53 Pro homozygotes with age of >40 years had twofold to threefold higher risk to develop NPC and the risk was increased with age (Odds Ratio (OR) increased from 2.01 to 2.63 by age >40 to >50 years). Individuals of age >40, >45 and >50 years with an Arg/Arg genotype and of age >45 and >50 years with combined Arg/Arg or Arg/Pro genotype had lower risk to develop NPC than those with Pro/Pro genotype (P<0.05). Collectively, we suggest that the p53 gene polymorphism may associate with NPC susceptibility in Thai population, particularly the Pro/Pro genotype carriers with age of >40 years. The detection of this p53 polymorphism may be a useful tool for screening of early stage and diagnosis of NPC.


Ascribing quantitative value to community participation: a case study of the Roll Back Malaria (RBM) initiative in five African countries.
There are two objectives. The first is to outline the processes involved in the estimation and use of quantitative values to measure community participation. The community participation value (Cp value) is a new concept being introduced in this study. The second is to compare the levels of community participation in the RBM programmes in five African countries, namely, Burkina Faso, Ghana, Nigeria, Tanzania and Uganda. The study design is based on the Rifkin and Pridmore Spidergram model for assessing the level of community participation in a development programme. The methods involved a structured review of web-based and published secondary data. Appropriate indices were used to capture the extent of malaria control in the respective countries. Comparisons were then made between the Cp values and the results obtained for malaria control in order to arrive at a judgement of the significance of community participation to the success of the RBM programmes. The findings from this study showed that community participation was present in varying degrees in the RBM programmes of the different countries. The computed Cp values for the five countries under consideration were as follows: Uganda (12.5), Ghana (10.5), Tanzania (10.0), Nigeria (9.0) and Burkina Faso (8.0). Based on a maximum attainable Cp value of 25, it was observed that the level of community participation in the RBM initiative is still generally low in the countries studied. Although community participation was present and relevant to the Roll Back Malaria initiative, other factors appeared to have more significant influence on the success, or otherwise, of the initiative. Such factors include the availability of financial resources for malaria control, competent health personnel, and the general health infrastructure available in a given country.


Regioselective Ni-Catalyzed reductive alkylsilylation of acrylonitrile with unactivated alkyl bromides and chlorosilanes.
Transition-metal catalyzed carbosilylation of alkenes using carbon electrophiles and silylmetal (-B, -Zn) reagents as the nucleophiles offers a powerful strategy for synthesizing organosilicones, by incorporating carbon and silyl groups across on C-C double bonds in one step. However, to the best of our knowledge, the study of silylative alkenes difunctionalization based on carbon and silyl electrophiles remains underdeveloped. Herein, we present an example of silylative alkylation of activated olefins with unactivated alkyl bromides and chlorosilanes as electrophiles under nickel catalysis. The main feature of this protocol is employing more easily accessible substrates including primary, secondary and tertiary alkyl bromides, as well as various chlorosilanes without using pre-generated organometallics. A wide range of alkylsilanes with diverse structures can be efficiently assembled in a single step, highlighting the good functionality tolerance of this approach. Furthermore, successful functionalization of bioactive molecules and synthetic applications using this method demonstrate its practicability.


A model of the neuro-musculo-skeletal system for human locomotion. I. Emergence of basic gait.
The generation of human locomotion was examined by linking computational neuroscience with biomechanics from the perspective of nonlinear dynamical theory. We constructed a model of human locomotion, which includes a musculo-skeletal system with 8 segments and 20 muscles, a neural rhythm generator composed of 7 pairs of neural oscillators, and mechanisms for processing and transporting sensory and motor signals. Using a computer simulation, we found that locomotion emerged as a stable limit cycle that was generated by the global entrainment between the musculo-skeletal system, the neural system, and the environment. Moreover, the walking movements of the model could be compared quantitatively with those of experimental studies in humans.


Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange.
In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA)< or =0.40ng/mL after nadir. Patients with metastatic prostate cancer or hormone refractory disease without obvious metastases who died of any cause were classified as died of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival. At 9 years, Agent Orange-exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange-exposed, nonexposed veterans, and nonveterans, respectively, p=0.012). No significant differences in cause-specific (CSS) (p=0.832) or overall survival (OS) (p=0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D(90), whereas Gleason Score, % positive biopsies, and D(90) predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D(90). In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one). In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.


Mycorrhiza in sedges--an overview.
Most terrestrial plants associate with root-colonising mycorrhizal fungi, which improve the fitness of both the fungal and plant associates. However, exceptions exist both between and within plant families failing to associate with mycorrhizal fungi or in the incidence and the extent of mycotrophy, which may vary greatly. Sedges are important pioneers of disturbed habitats and often dominate vegetations like wetlands, and arctic and alpine vegetations, in which the mycorrhizal inoculum in the soil is often low or absent. In the past, sedges were often designated as non-mycorrhizal, though limited reports indicated the presence of mycorrhiza in certain species. However, studies since 1987 indicate widespread occurrence of mycorrhiza in sedges. Based on these studies, the family Cyperaceae is no longer a non-mycorrhizal family, but the mycorrhizal status of its members is greatly influenced by environmental conditions. Further, sedges appear to have several morphological adaptations to thrive in the absence of mycorrhizal association. Though mycorrhizal associations have been noted in many sedge species, the ecological role of this association is not well documented and no clear generalisation can be drawn. Similarly, the role of mycorrhizal fungi on sedge growth and nutrient uptake or non-nutritional benefits has yet to be fully ascertained. This paper reviews the current information available on the incidence of mycorrhiza in sedges and the possible reasons for low mycotrophy observed in this family.


Heterogeneity among isolates of rapidly growing mycobacteria responsible for infections following augmentation mammaplasty despite case clustering in Texas and other southern coastal states.
Thirty-seven cases of rapidly growing mycobacterial wound infections following augmentation mammaplasty were identified between 1979 and 1988. The infections were usually unilateral and had a narrow geographic distribution: almost 60% were from Texas and 92% from five southern coastal states. In Texas a seasonal incidence was observed; 45% of all previously reported and current patients had undergone mammaplasty in April, May, or June. Although these findings suggested a possible common source, analysis of 35 available isolates revealed 19 different phenotype patterns. Five different taxonomic groups were represented, although most isolates (70%) were Mycobacterium fortuitum biovar fortuitum. Plasmid bands were identified in 10 of 15 strains studied, with nine different profiles. An additional 11 cases of breast infection due to rapidly growing mycobacteria not associated with augmentation were also identified, of which nine came from the same states that contributed mammaplasty cases. Rapidly growing mycobacterial infections of the breast are endemic in Texas and other southern coastal states, and the heterogeneity of the isolates suggests that most cases are unrelated.


Estimating the date corresponding to the horizon of the first detection of 137Cs and 239+240Pu in sediment cores.
The anthropogenic bomb fallout nuclides 137Cs and plutonium isotopes (240Pu, 239Pu) are important chronometers for the determination of recent sediment accumulation rates using sediment cores collected from various water bodies. One of the crucial time horizons used to date sediment core profiles corresponds to the date of first detection of these nuclides. Although atmospheric nuclear testing began during the mid-1940s, the year corresponding to a nuclide's first detection when measured in 2006 depends on a number of factors including fallout history, radioactive half-life, gamma/alpha detection limits, geographic latitude and the accumulated thickness of the sediment section. This paper reports estimations of the year of first detection in sediment profiles of fallout 137Cs and Pu measured by gamma and alpha spectrometry, respectively. We find that for the latitude 30-40 degrees south of the equator the year of first detection for 137Cs is 1955. The date is earlier in the northern hemisphere due to higher fallout rates. Due to better measurement sensitivity first detection of Pu is generally earlier than 137Cs by 1-2 years.


[Determinants of the intention of post-secondary students to eat at least five servings of vegetables and fruit daily].
Vegetable and fruit consumption helps reduce the occurrence of overweight, obesity, and other chronic diseases. However, only 50% of young adults eat at least five servings of these foods daily. Based on the construct of the Theory of planned behaviour of Ajzen (1991) to which other constructs were added (descriptive norm, perceived regularity of the behaviour and past behaviour), this study aims at identifying the determinants in the intention of young adults in postsecondary education institutions to eat at least five servings of vegetables and fruit daily during the next three months. A sample of 385 students in two CEGEP (junior college institutions) in the Quebec City area participated in this correlation study on a volunteer basis. While attending class, they completed a self-administered questionnaire. Hierarchical regression analyses showed that perceived behavioural controls and the perceived weight of facilitating factors and barriers to the behaviour, explained 75% of the intention variance. Another 4% was explained when the perceived regularity of the behaviour, the descriptive norm, and past-behaviour, were added to the analysis. Logistic regression analyses show that individuals presenting weak/strong intention can be differentiated among themselves as to the perception of benefits derived from a daily consumption of vegetables and fruit (such as maintaining good health, eating foods that taste good), and as to facilitating factors/barriers that assist or inhibit such consumption (possessing more information on the nutritional value and taste of vegetables and fruit, or disposing of sufficient time to prepare them). To our knowledge, this is the first study done in Quebec using a recognized theoretical model to identify the determinants of the intention to eat at least five servings of vegetables and fruit daily in a sample of young adults in postsecondary education institutions. The results may be helpful in designing the contents of interventions aimed at maintaining and increasing daily consumption of vegetables and fruit by young adults.


Ror2 mediates chronic post-thoracotomy pain by inducing the transformation of A1/A2 reactive astrocytes in rats.
Ror2 plays an important role in neuronal development, neuronal plasticity, and neuropathic pain. In our previous pilot study, we found that Ror2 and GFAP (a marker of astrocytes) protein levels increased in thoracic dorsal root ganglia from postoperative day (POD) 7 to POD 21 in rats with chronic post-thoracotomy pain (CPTP). In the present study, we aimed to further explore the roles of Ror2 and activated astrocytes during CPTP development. Ror2, c-JUN, and C3aR levels increased and the activated astrocytes were mainly expressed as the A1 phenotype in the spinal cord dorsal horn of the rats with CPTP. The knockdown of Ror2 in the spinal cord astrocytes alleviated thoracotomy-induced mechanical hyperalgesia and cold allodynia as well as reverted the A1/A2 ratio of the reactive astrocytes, downregulating the expression of c-JUN and C3aR in rats with CPTP. These results suggest that Ror2 in the spinal cord astrocytes mediates the transformation of A1/A2 reactive astrocytes via regulating the expressions of the c-JUN and C3aR in CPTP. Furthermore, the suppression of Ror2 could be utilized as a new strategy to help prevent CPTP.


An investigation to offer conclusive recommendations on suitable benefit/cost criteria-based normalization methods for TOPSIS.
Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) is a popular multi-criteria decision-making method that ranks the available alternatives by examining the ideal-positive and ideal-negative solutions for each decision criterion. The first step of using TOPSIS is to normalize the presence of incommensurable data in the decision matrix. There are several normalization methods, and the choice of these methods does affect TOPSIS results. As such, some efforts were made in the past to compare and recommend suitable normalization methods for TOPSIS. However, such studies merely compared a limited collection of normalization methods or used a noncomprehensive procedure to evaluate each method's suitability, leading to equivocal recommendations. This study, therefore, employed an alternate, comprehensive procedure to evaluate and recommend suitable benefit/cost criteria-based normalization methods for TOPSIS (out of ten methods extracted from past literature). The procedure was devised based on three evaluation metrics: the average Spearman's rank correlation, average Pearson correlation, and standard deviation metrics, combined with the Borda count technique.•The first study examined the suitability of ten benefit/cost criteria-based normalization methods over TOPSIS.•Users should combine the sum-based method and vector method into the TOPSIS application for safer decision-making.•The maximum method (version I) or Jüttler's-Körth's method has an identical effect on TOPSIS results.


Three-Dimensional Evaluation of Aortic Valve Annular Shape in Children With Bicuspid Aortic Valves and/or Aortic Coarctation Compared With Controls.
Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality, occurring in 1% to 2% of the general population. Adults with degenerative aortic valve (AV) disease have been shown to have an elliptical shaped AV annulus. The goal of this study was to investigate the shape of the aortic annulus in children with BAV, coarctation of the aorta (CoA) with or without BAV, and normal controls with trileaflet AVs using 3-dimensional echocardiography (3DE). We reviewed echocardiograms of children with isolated BAV (n = 40), CoA (n = 26), and controls (n = 40) that included 3DE of the AV. Eccentricity index (EI) was defined as the ratio between the smaller and larger annular dimension. ΔD was defined as the difference between the larger and smaller annular dimension. Patients with BAV had an eccentric AV annulus compared with controls (BAV EI 0.85 ± 0.05 and control EI 0.96 ± 0.03; p <0.001). Subjects with CoA also had a more eccentric annulus than controls regardless of AV morphology (CoA 0.84 ± 0.06; p <0.001). EI was not associated with somatic growth parameters or gender. Among all patients with BAV, AV dysfunction was associated with fusion of the right and noncoronary (R-N) cusps (p <0.001), but there was no association between valve dysfunction and EI. ΔD was higher in both the BAV and CoA groups compared with the control group (BAV 3.4 ± 1.9 mm, CoA 2.8 ± 1.8 mm, and control 0.6 ± 0.4 mm; p <0.001 each). Although there was no significant correlation of ΔD with age in the control group during childhood, ΔD increased with age in the BAV and CoA groups. In conclusion, children with BAV and/or CoA have an elliptical shaped AV annulus by 3DE, which is independent of age, gender, or body surface area. AV annular eccentricity may lead to inaccurate measurement of AV annular size if measured by 2DE alone. Considering AV annular eccentricity when balloon sizing the annulus before valvuloplasty may help improve interventional results in some patients.


Inhibition of human drug metabolizing cytochrome P450 enzymes by plant isoquinoline alkaloids.
The human cytochrome P450 (CYP) enzymes play a major role in the metabolism of endobiotics and numerous xenobiotics including drugs. Therefore it is the standard procedure to test new drug candidates for interactions with CYP enzymes during the preclinical development phase. The purpose of this study was to determine in vitro CYP inhibition potencies of a set of isoquinoline alkaloids to gain insight into interactions of novel chemical structures with CYP enzymes. These alkaloids (n=36) consist of compounds isolated from the Papaveraceae family (n=20), synthetic analogs (n=15), and one commercial compound. Their inhibitory activity was determined towards all principal human drug metabolizing CYP enzymes: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4. All alkaloids were assayed in vitro in a 96-well plate format using pro-fluorescent probe substrates and recombinant human CYP enzymes. Many of these alkaloids inhibited the CYP3A4 form, with 30/36 alkaloids inhibiting CYP3A4 with at least moderate potency (IC₅₀ < 10 μM) and 15/36 inhibiting CYP3A4 potently (IC₅₀ < 1 μM). Among them corydine, parfumine and 8-methyl-2,3,10,11-tetraethoxyberbine were potent and selective inhibitors for CYP3A4. CYP2D6 was inhibited with at least moderate potency by 26/34 alkaloids. CYP2C19 was inhibited by 15/36 alkaloids at least moderate potently, whereas CYP1A2, CYP2B6, CYP2C8, and CYP2C9 were inhibited to a lesser degree. CYP2A6 was not significantly inhibited by any of the alkaloids. The results provide initial structure-activity information about the interaction of isoquinoline alkaloids with major human xenobiotic-metabolizing CYP enzymes, and illustrate potential novel structures as CYP form-selective inhibitors.


Renal manifestations of a mutation in the uromodulin (Tamm Horsfall protein) gene.
Uromodulin (Tamm Horsfall glycoprotein) is the most abundant protein found in normal human urine. Its function has yet to be determined. Identifying mutations in the uromodulin gene may be helpful in understanding the function of uromodulin. There has been 1 report of 4 families suffering from mutations in the uromodulin gene, resulting in the autosomal dominant transmission of hypouricosuric hyperuricemia and chronic renal failure. This case report describes another family with similar clinical manifestations. A family was identified with clinical characteristics of hypouricosuric hyperuricemia and renal failure occurring in a mother and daughter. Clinical characteristics were identified, and laboratory studies were obtained in the proband and the proband's daughter. A genetic analysis was performed to evaluate for mutations in the uromodulin gene. The proband suffered from hyperuricemia at an early age and progressive renal failure with end-stage renal disease developing at age 49 years. The proband's daughter suffered from hyperuricemia, a reduced fractional excretion of uric acid, and mild renal insufficiency. A g.2105G > A mutation in exon 4 of the uromodulin gene resulting in a substitution of tyrosine for cysteine was identified in both the proband and the proband's daughter. The clinical characteristics were similar to those of other patients suffering from uromodulin mutations and to those of patients suffering from medullary cystic kidney disease type 2 and familial juvenile hyperuricemic nephropathy. Uromodulin associated kidney disease results in hyperuricemia and renal failure. The specific uromodulin mutation found in this family is consistent with the hypothesis that mutations disrupt highly conserved cysteine residues in the uromodulin protein. Potential mechanisms for these pathologic changes are discussed. The authors would appreciate referral of other families for screening for mutations.


Change of genetic determinants of left ventricular structure in adolescence: longitudinal evidence from the Georgia cardiovascular twin study.
Genetic contribution to left ventricular (LV) structure is generally recognized, but whether and how this influence varies by ethnicity or with age is unknown. Participants were 517 European-American (EA) and African-American (AA) twin pairs (mean age: 14.6 +/- 3.0) at visit 1 and 422 EA and AA twin pairs at follow-up 4.1 years later. Echocardiograms were obtained on both visits. Data were analyzed using the structural equation modeling software Mx. Body mass index (BMI) was a strong predictor for all LV measures at both visits 1 and 2, accounting for 3.5-24.2% of the total variance. Hemodynamics explained up to 4.5% additional LV measures variance. After adjusting for BMI, LV measures showed substantial heritability (range: 21-71%). Best-fitting longitudinal models revealed considerable novel genetic effects on the interventricular septum, posterior wall-, and relative wall thickness (RWT) (but not LV internal diameter), accounting for 32-41% of the phenotypic variance at visit 2, with no significant gender and ethnic effects. There was a gender difference for LV mass index in AAs (P < 0.01), with a significant influence of novel genetic effects in males (47%), but not in females. No gender difference was seen in EAs, with 34% of the phenotypic variance at visit 2 attributable to novel genetic effects. The heritability of cardiac structure and geometry was equally substantial in both AAs and EAs. Significant novel genetic influences were detected for all measures but LV inner diameter and LV mass index in AA females. Further developmental genetic studies are warranted to elucidate the nature of the emerging gene effects during the transition from adolescence to adulthood.


Cervical adeno-carcinoma and partial hydatidiform mole.
Partial hydatidiform mole was found in a 39-year-old grand-multiparous Jewish woman, having a polypoid cervical adeno-carcinoma. The patient was treated by surgery followed by internal and external pelvic irradiation, with excellent results. Four and a half years after the initial diagnosis she is very well. This is the first reported case of a rare combination. The literature regarding the association between pregnancy and cervical malignancies is reviewed briefly and the possible pathogenetic relationship between hydatidiform mole and carcinoma of the cervix is discussed.


Are the results of patient reported outcome measures after spine surgery influenced by recall of preoperative scores? A randomized controlled trial.
Patient reported outcome measures (PROMs) are of utmost importance to clinical practice as they permit a patient-focused evaluation of surgical outcomes. However, recall bias can limit an adequate interpretation of PROMs. To assess the impact of recall bias of preoperative status on postoperative PROMs of patients submitted to surgery due to degenerative spine disease. Randomized controlled trial in a tertiary care neurosurgical unit in Portugal PATIENT SAMPLE: All patients submitted to surgery at our institution from January 2019 to April 2020 due to degenerative lumbar or cervical spine disease with valid PROMs questionnaires were enrolled, and 2 computer generated randomized groups were created. The study´s primary endpoint was the median postoperative Core Outcome Measure Index (COMI) score. The intervention group was sent postoperative questionnaires including preoperative answers, while patients in the control group were sent the same PROMs without the preoperative answers. Randomization was applied to 236 patients (118 for each group) and valid results were obtained for 147 patients (81 lumbar, 44 from the intervention group; and 66 cervical, 29 from the intervention group), from which 88 (60%) were females, with a median age of 58 years. Both groups shared similar baseline clinical characteristics and preoperative scores. Median postoperative COMI scores and interquartile ranges (IQR) were 4.20 (IQR: 2.30-6.00) and 5.45 (IQR: 3.75-7.40) for the intervention and control groups, respectively (Wilcoxon, p=.02). This difference was reached mainly due to cervical spine patients as median postoperative COMI score was 3.95 (IQR: 2.20-5.32) in the intervention group and 5.1 (IQR: 4.0-8.4) in the control group (Wilcoxon, p=.01). No significant difference was reached for lumbar patients. Better PROMs scores were obtained for degenerative cervical spine patients to whom the preoperative results were provided. Therefore, providing preoperative scores to patients upon postoperative PROMs fulfilment might influence postoperative results. Further research is necessary to increase the reliability of PROMs in clinical practice.


Cerebral embolic stroke after disappearing takotsubo cardiomyopathy.
Takotsubo cardiomyopathy can induce cerebral embolic stroke because of intracardiac thrombosis, but the timing of cardiogenic embolism relating to takotsubo cardiomyopathy has not been well described. We evaluated a 71-year-old woman with takotsubo cardiomyopathy, who developed cardiogenic cerebral embolism after recovery of cardiac wall motion. Nevertheless, we treated her with anticoagulation therapy. The present clinical observation suggests that attention should be paid to the timing when takotsubo cardiomyopathy resolves against risk of cardiogenic cerebral embolism.


Sex differences in stroke incidence and survival in Hong Kong, 2000-2007.
Few studies have examined the impact of sex across different age groups and over time on chronic diseases in Asia. The objective of this study was to explore the effect of sex across different age groups and over time on stroke incidence and 30-day case fatality in Hong Kong. Over 90% first hospitalizations for stroke in Hong Kong (from 2000 to 2007) were identified from the Clinical Management System of the Hospital Authority. Age-specific rate ratios (RRs; women to men) for incidence of first hospitalization and the 30-day case fatality were estimated based on Poisson regression models after adjustment for year of hospitalization. Women below the age of 85 years had a lower incidence of first hospitalization than men, and the effect size varied with age [35-44 years: RR = 0.56, 95% confidence interval (CI) = 0.49-0.64; 45-54 years: 0.65, 0.53-0.79; 55-64 years: 0.58, 0.48-0.71; 65-74 years: 0.71, 0.58-0.85; 75-84 years: 0.83, 0.68-1.00)]. Women aged ≥85 years had a stroke incidence similar to men, but the adjusted 30-day case fatality was significantly higher than that of men aged ≥85 years (RR = 1.14, 95% CI = 1.05-1.23). Lower rates of incidence were observed in women than men aged 35-84 years in Hong Kong but short-term case fatality is greater in women aged ≥85 years.


"Broken"-How Identities as Women, Mothers and Partners Are Intertwined with the Experience of Living with and Seeking Treatment for Pelvic Organ Prolapse.
Pelvic Organ Prolapse (POP) occurs when one or more pelvic organs descend into or through the vaginal opening, significantly impacting physical and mental health. POP affects the female reproductive tract and, overwhelmingly, people who identify as women. However, little research has examined the impact of gendered expectations on women's treatment-seeking for POP and their decision-making around surgery for POP. To address this gap, we conducted semi-structured interviews with 26 women seeking surgery for POP in Alberta, Canada. Data were analyzed from a gender-based lens, using the Framework Method. Participants reported the need to balance their identities as women, partners, and mothers in their pursuit of treatment and faced many barriers to treatment related to their gendered responsibilities. Findings highlight the gendered experiences of prolapse in the context of healthcare needs and can inform policies and practices which promote more equitable access to prolapse treatment.


Automatic Intraoperative Correction of Brain Shift for Accurate Neuronavigation.
Unreliable neuronavigation owing to inaccurate patient-to-image registration and brain shift is a major problem in conventional magnetic resonance imaging-guided neurosurgery. We performed a prospective intraoperative validation of a system for fully automatic correction of this inaccuracy based on intraoperative three-dimensional ultrasound and magnetic resonance imaging-to-ultrasound registration. The system was tested intraoperatively in 13 tumor resection cases, and performance was evaluated intraoperatively and postoperatively. Intraoperatively, the system was accurate enough for tumor resection guidance in 9 of 13 cases. Manually placed anatomic landmarks showed improvement of alignment from 5.12 mm to 2.72 mm (median) after intraoperative correction. Postoperatively, the limitations of the current system were identified and modified for the system to be sufficiently accurate in all cases. Automatic and accurate correction of spatially unreliable neuronavigation is feasible within the constraints of surgery. The current limitations of the system were also identified and addressed.


Quantifying the beliefs of key players in the UK sheep industry on the efficacy of two treatments for footrot.
Clinical trials have demonstrated that sheep with footrot treated with parenteral and topical antibiotics without foot trimming (treatment A), cure faster than sheep treated with foot trimming and topical antibiotics (treatment B). We investigated how key players in the UK sheep industry recommended treating footrot, and tested whether reviewing the evidence surrounding treatment of footrot changed their beliefs. Eight key players attended a workshop to investigate their current practices, and their perceived efficacy of treatments, using probabilistic elicitation. At the start of the study, all participants recommended use of antibiotic injection but only four recommended not foot trimming feet with footrot. Initial beliefs in the difference in cure rate within five days of treatment ranged from 30 to 97% in favour of treatment A (true difference 60%); this heterogeneity reduced after reviewing the evidence. Participants who believed the cure rate differed by >60% over-estimated the cure rate of treatment A whilst participants who believed the difference was <60% over-estimated the efficacy of treatment B. During discussions, participants stated that parenteral antibiotics had always been recommended as a treatment for footrot but that the new research clarified when to use them. In contrast, it was highly novel to hear that foot trimming was detrimental to recovery, and key players and farmers are taking longer to accept this evidence. Three months after the workshop, two participants stated that they now placed greater emphasis on rapid individual antibiotic treatment of lame sheep and one was no longer recommending trimming feet.


Inhibitory action of (+/-)CP-96,345 on the cardiovascular responses to intrathecal substance P and neuropeptide K in the conscious freely moving rat.
(+/-)CP-96,345, a nonpeptide and highly selective NK-1 receptor antagonist, was tested acutely and chronically as an inhibitor of the cardiovascular responses induced by the intrathecal (i.t.) injection of substance P (SP) and neuropeptide K (NPK) in the conscious rat. When given at T-9 spinal cord level, NPK (0.65, 3.25 and 6.5 nmol) and SP (6.5, 16.25 and 32.5 nmol) produced increases in mean arterial pressure and heart rate. The cardiovascular responses to NPK were greater in intensity and duration than those produced by SP. The prior i.t. injection of (+/-)CP-96,345 (0.65 and 6.5 nmol, 15 min earlier) inhibited in a dose-dependent manner the pressor response and the tachycardia induced by 6.5 nmol SP while 65 nmol of the antagonist was required to reduce the effects of 3.25 nmol NPK. However, both the SP and NPK-induced cardiovascular changes were blocked 2 days after the i.t. injection of 6.5 nmol (+/-)CP-96,345. Five days after a single i.t. injection of 6.5 nmol (+/-)CP-96,345, the cardiovascular response to SP remained unaffected while that of NPK was partially attenuated. Moreover, (+/-)CP-96,345 was active as an antagonist when given i.v. at the dose of 0.13 mg/kg. Conversely, (+/-)CP-96,345 failed to block the cardiovascular effect caused by the i.t. injection of 81 pmol bradykinin and did not produce any changes on resting blood pressure and heart rate when given alone either i.t. or i.v.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional and phylogenetic implications of molar flare variation in Miocene hominoids.
Comparative analyses of molar shape figure prominently in Miocene hominoid evolutionary studies, and incomplete understanding of functional and phylogenetic influences on molar shape variation can have direct consequences for the interpretation of fossil taxa. Molar flare is a shape trait whose polarity, phylogenetic distribution, and functional significance have been sources of contention. To clarify the determinants of molar flare variation in the hominoid radiation, a combination of statistical methods was employed to investigate the effects of diet, phylogeny, and geologic age upon several measures of molar shape, to identify interactions among these factors, and to estimate their relative influence. Classic indices of molar crown shape and cusp relief are highly significantly associated with diet and show no clear phylogenetic or temporal patterning. Correlations with diet are insignificant when phylogenetic effects are controlled, a result which is interpreted as an artifact of the distribution of folivory in the Miocene hominoid radiation. Possession of pronounced molar flare was found to be the primitive condition for Miocene hominoids, but molar flare reduction cannot be considered a crown hominoid synapomorphy. Molar flare is strongly correlated with geologic age but differs significantly among dietary categories when the effects of time are controlled. Among contemporaneous taxa, hard-object feeders consistently show the highest levels of flare. Molar flare reduction is hypothesized to arise from realignment of cusp positions to maximize molar shearing and increase working occlusal surface area, while variation in flare among contemporaneous taxa may be due, at least in part, to enamel thickness variation. The pronounced molar flare of Otavipithecus is interpreted as a primitive retention, although alternative dietary and phylogenetic interpretations cannot be excluded. A dramatic reversal of molar flare reduction in Mio-Pliocene hominins is interpreted as a synapomorphy of the crown hominin clade, thus supporting the hominin status of the Lukeino hominine. The last common ancestor of the Pan-Homo clade is predicted to have possessed relatively non-flaring molars, and implications of this hypothesis for early hominin recognition are discussed.


Standards for European training requirements in interventional neuroradiology : Guidelines by the Division of Neuroradiology/Section of Radiology European Union of Medical Specialists (UEMS), in cooperation with the Division of Interventional Radiology/UEMS, the European Society of Neuroradiology (ESNR), and the European Society of Minimally Invasive Neurological Therapy (ESMINT).
This document sets out standards for training in Interventional Neuroradiology (INR) in Europe. These standards have been developed by a working group of the European Society of Neuroradiology (ESNR) and the European Society of Minimally Invasive Neurological Therapy (ESMINT) on the initiative and under the umbrella of the Division of Neuroradiology/Section of Radiology of the European Union of Medical Specialists (UEMS).


Comparison of electron beam computed tomography and technetium stress testing in differentiating cause of dilated versus ischemic cardiomyopathy.
The current reference standard for differentiating between nonischemic versus ischemic cardiomyopathy (CM) is angiography. The diagnostic accuracy of nuclear stress testing and electron beam tomography (EBT) was evaluated to differentiate between nonischemic and ischemic CM, using coronary angiography as the reference standard. A total of 56 patients who underwent technetium stress testing and coronary angiography for the evaluation of CM were enrolled. Patients then underwent EBT coronary scanning for coronary calcification (CC). Of the 56 patients, 34 (61%) had angiographically significant disease. Using the criteria of ischemia (reversible defect) or infarct (fixed defect) to define a patient with ischemic CM, nuclear stress testing had a sensitivity of 97% (33 of 34 patients) but a specificity of only 18% (4 of 22 patients). Using the criteria of reversible ischemia only, the specificity of nuclear stress testing improved to 50% (P < 0.001); however, the sensitivity decreased to 56%. An EBT score >0 had a sensitivity of 97% (33 of 34 patients) and a specificity of 68% (15 of 22 patients) for defining ischemia. Overall diagnostic accuracy was significantly higher with EBT as compared with nuclear stress testing in this study of patients with reduced ejection fractions (84% vs. 64%; P = 0.009). Given the high sensitivity of nuclear testing and EBT, these tests may prove to be an effective screen before angiography in patients with congestive heart failure of unclear cause.


Influenza specific antibodies in the female genital tract of mice after oral administration of live influenza vaccine.
In order to investigate the possible stimulation of antibodies in the genital tract by immunization female NMRI-mice were given orally a live influenza vaccine (A/PR/8/34, H1N1) on two occasions which were 10 days apart. Subsequently, virus specific IgA antibodies measured by an enzyme immunoassay in homogenates of urinary bladder, uterus and vagina and also in uterine washings. Specific IgA antibodies were not detectable in the sera of immunized mice. The high IgA titer in uterine washings, and in the homogenates suggests enhancement by vaccine of IgA antibody production in the genital tract.


Insulin-like growth factors 1 and 2 regulate gene expression and enzymatic activity of cyp17a1 in ovarian follicles of the yellowtail, Seriola quinqueradiata.
There is accumulating evidence that insulin-like growth factors (IGFs), primary mediators of somatic growth, play an important role in fish reproduction. Previously, we showed that IGF-1 and IGF-2 are expressed in the ovarian follicle cells of the yellowtail (Seriola quinqueradiata) during the vitellogenic phase, suggesting that IGFs may be involved in ovarian steroidogenesis. In this study, we examined the effects of IGF-1 and IGF-2 on gene expression and activity of steroidogenic enzymes in yellowtail ovary in vitro. IGF-1 and IGF-2 had no effect on mRNA levels of several steroidogenesis-related genes (star, cyp11a1, hsd3b, cyp17a2, and cyp19a1). However, both IGFs enhanced the transcription of cyp17a1 in vitellogenic ovaries, although such up-regulation was not found in the ovary at the pre-vitellogenic stage. The stage-dependent effects of IGFs were correlated with changes in ovarian cyp17a1 mRNA levels during the reproductive cycle: transcript abundances increased in conjunction with ovarian development. In addition, IGF-induced cyp17a1 gene expression was significantly inhibited by wortmannin, suggesting that PI3 kinase plays an essential role in IGF-mediated ovarian steroidogenesis. Furthermore, IGF-1 and IGF-2 promoted the conversion of both progesterone and 17α-hydroxyprogesterone to androstenedione in vitellogenic ovaries, suggesting that both IGFs stimulated 17α-hydroxylase and C17-20 lyase activities. Taken together, these findings suggest that IGF-1 and IGF-2 act directly on follicle cells to stimulate steroid production through an increase in gene expression and enzymatic activity of cyp17a1 via induction of PI3 kinase.


Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts.
The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.


HSV-1 interaction to 3-O-sulfated heparan sulfate in mouse-derived DRG explant and profiles of inflammatory markers during virus infection.
The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry. Finally, a cytokine array profile generated during HSV-1 infection in DRG explant indicated an enhanced expression of chemokines (LIX, TIMP-2, and M-CSF)-known regulators of HS. Taken together, these results highlight the significance of HS during HSV-1 entry in DRG explant. Further investigation is needed to understand which isoforms of 3-O-sulfotransferase (3-OST)-generated HS contributed during HSV-1 infection and associated cell damage.


Crystal structure and conformation of a DNA-RNA hybrid duplex with a polypurine RNA strand: d(TTCTTBr5CTTC)-r(GAAGAAGAA).
. DNA-RNA hybrids are substrates for RNase H. This enzyme catalyzes the hydrolysis of the RNA strand in the hybrid form. The polypurine tract (PPT) in human immunodeficiency virus 1 (HIV-1) is a short stretch of purines ( approximately 15 bases) located at the 3'-end of the U3 region of the RNA genome. The PPT has the unique ability to resist digestion by RNase H and serves as a primer for plus-strand DNA synthesis. . The crystal structure of a DNA-RNA hybrid duplex containing a polypurine RNA strand, d(TTCTTBr5CTTC)-r(GAAGAAGAA), has been determined at 1.8 A resolution. The structure was solved by molecular replacement methods and refined to a final R factor of 20.1% (R free 23.7%). The hybrid duplex adopts a standard A-form conformation. All of the sugar rings and glycosidic torsion angles are found in the standard C3'-endo/anti conformation, as seen in A-RNA or A-DNA. The crystal packing is dominated by the DNA strand, where the terminal base pairs of the hybrid abut the neighboring A-DNA sugar-phosphate backbone on the minor groove side. . The present DNA-RNA hybrid duplex containing a polypurine RNA strand exhibits standard A-form geometry. This observation might suggest that the RNA PPT resists the RNase H activity of HIV reverse transcriptase as a result of its A-form conformation. In addition, there appears to be a correlation between the percentage purine content of the RNA and the DNA backbone conformation.


Evaluation of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata: A randomized observer-blinded, placebo-controlled, split-head pilot study.
Platelet-rich plasma has shown some promise in the treatment of alopecia areata. To evaluate the effect of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata. This was a randomized, placebo-controlled, split-head study involving 27 patients with alopecia areata (Severity of Alopecia Tool score ≥25%). Alopecia patches on either side of the scalp were randomized to receive 3 intradermal injections of platelet-rich plasma or normal saline at monthly intervals and evaluated 3 months after the last session. Lesional T-cell cytokine messenger RNA expression was compared pre- and posttreatment in the platelet-rich plasma-treated sites. The mean Severity of Alopecia Tool score did not change significantly compared with baseline with either platelet-rich plasma or placebo injections at any visit; however, the mean percentage reduction in the score in the platelet-rich plasma arm was more than in the placebo arm (9.05% ± 36.48% vs 4.99% ± 33.88%; P = .049) at final assessment. The mean interferon gamma (P = .001) and interleukin 17 cytokine (P = .009) messenger RNA expression decreased, whereas the mean interleukin 10 (P = .049) and FOXP3 (P = .011) messenger RNA expression increased significantly after platelet-rich plasma treatment. Small sample size and a relatively short follow-up. Platelet-rich plasma was found to have limited efficacy in alopecia areata. However, it may play a role in restoring immune balance in the alopecic patches.


Ensuring quality in postgraduate medical education: competency testing is the key.
The changes made to the curricula and assessment systems in the UK have resulted in pathology specialty-training programmes which assess trainees on a regular (weekly or monthly) basis. An end of first year assessment tests their aptitude for the specialty, the FRCPath examinations taking place after at least one to two (part 1) and three to four (part 2) years of training respectively, and multi-source feedback is undertaken in years 1, 3 and 5. With regular educational appraisal, this constitutes cohorts of well-assessed and supported trainees. The assessments are blueprinted to the curriculum, ensuring adequate assessment coverage of curriculum content within workplace-based assessments (WPBA), objective structured pathology examinations and the FRCPath examinations. Notably, generic non-clinical attributes and behavioural skills such as leadership and management skills can be covered in the WPBA. Many of these changes are evolutionary in nature, but some have been imposed by continuously increasing regulatory requirements. Whilst additional information is generated, the increased amount of assessment of trainees has led to complaints that trainees do not acquire enough practical experience in the laboratory. It will be important to find the balance between didactic teaching with formal assessment, and apprenticeship-style, practical hands-on learning.


Beauvericin, a bioactive compound produced by fungi: a short review.
Beauvericin is a cyclic hexadepsipeptide mycotoxin, which has insecticidal, antimicrobial, antiviral and cytotoxic activities. It is a potential agent for pesticides and medicines. This paper reviews the bioactivity, fermentation and biosynthesis of the fungal product beauvericin.


Sacha inchi (Plukenetia volubilis L.): An emerging source of nutrients, omega-3 fatty acid and phytochemicals.
Sacha inchi (Plukenetia volubilis) (SI) is an oleaginous plant producing oil and protein-rich seeds. It has been cultivated for centuries and is native to the tropical rainforest of the Amazon region of South America including parts of Peru and northwestern Brazil. At present, SI seeds are emerging as a potential source of macro- and micronutrients, α-linolenic acid and phytochemicals. This review attempts to elucidate the nutrients, phytonutrients, safety, toxicity, health benefits and food applications of SI seed. Recent scientific studies have associated the consumption of SI seed/oil with reduced risk of chronic inflammatory diseases. However, lack of awareness and in-depth understanding has resulted in it being neglected both at the consumer and industrial level. In all, SI is an underutilized and undervalued oleaginous crop which not only has the potential to mitigate food and nutritional insecurity but also offers humongous opportunities for the development of novel value-added food products.


Development of a stir bar sorptive extraction method to study different beer styles volatile profiles.
A stir bar sorptive extraction method coupled to Gas Chromatography-Mass Spectrometry for the analysis of 52 volatile compounds in beer has been developed. The final optimized conditions were: 50 mL sample volume, 180 min extraction time, 25% (w/v) NaCl content and polydimethylsyloxane stir bars. Good values of linearity (R2 > 0.99) were achieved for the calibration lines of all the compounds. The limits of detection and quantification obtained were low enough for the determination of the volatile compounds in the samples and the recovery values obtained for the majority of the compounds were between 80% and 120%. The precision of the method was also studied and acceptable values for this type of extraction technique were obtained (<20%). 30 samples of different styles of beers (ale, lager, stout and wheat) were analysed and their aromatic profile was characterised. Multivariate statistical techniques allowed the correct classification of the samples according to their volatile composition.


Entropic Origin of Pseudogap Physics and a Mott-Slater Transition in Cuprates.
We propose a new approach to understand the origin of the pseudogap in the cuprates, in terms of bosonic entropy. The near-simultaneous softening of a large number of different q-bosons yields an extended range of short-range order, wherein the growth of magnetic correlations with decreasing temperature T is anomalously slow. These entropic effects cause the spectral weight associated with the Van Hove singularity (VHS) to shift rapidly and nearly linearly toward half filling at higher T, consistent with a picture of the VHS driving the pseudogap transition at a temperature ~T*. As a byproduct, we develop an order-parameter classification scheme that predicts supertransitions between families of order parameters. As one example, we find that by tuning the hopping parameters, it is possible to drive the cuprates across a transition between Mott and Slater physics, where a spin-frustrated state emerges at the crossover.


Repeat heart-lung transplantation outcome in the United States.
This study compared risk-adjusted survival between primary and repeat heart-lung transplantation. Data for 799 primary heart-lung and 19 repeat heart-lung transplants were extracted from the United Network Organ Sharing (UNOS) registry. Analyses were based on propensity score matching in which 1, 2, and 3 primary transplant patients were matched with 19 repeat transplant patients. The matching variables were sex of recipient and donor, ethnicity, race, age of recipient and donor, cytomegalovirus status, ABO match, human leukocyte antigen mismatch, medical condition (hospitalized), ventilator, employment status, functional status, UNOS transplant status, and ischemic time. Propensity score matching revealed incomplete overlap of covariate distributions between primary and repeat transplant patients. The 19 repeat heart-lung transplant patients were more severely impaired at the time of transplant, and 4 did not have an adequate primary transplant match. For 15 repeat transplant patients, survival time was not significantly different from matched primary transplant controls. For repeat transplant patients, being Hispanic, having longer ischemic time, poor functional status (needing assistance), being hospitalized, and requiring ventilator support were all associated with decreased survival time; however, only being on a ventilator was statistically significant. By contrast, being female, and younger were associated with increased survival, but were not statistically significant. When matched for a set of potential confounding variables, no difference in survival benefit was observed between primary and repeat heart-lung transplant patients. The only predictor significantly associated with decreased survival time among repeat transplant patients was being on a ventilator.


Is elevated triglyceride/high-density lipoprotein cholesterol ratio associated with poor prognosis of coronary heart disease? A meta-analysis of prospective studies.
Elevated triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C) are recognized as essential and independent hazard factors for total death and major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD). However, whether the increased TG/HDL-C forecasted the prognosis of CHD is still unknown. Therefore, we performed a meta-analysis to investigate the relationship between the elevated TG/HDL-C ratio and poor prognosis of CHD. A systematic literature search was conducted in PubMed, Web of Science, EMBASE, and The Cochrane Library, until August 30, 2021. Prospective observational studies regarding the association between TG/HDL-C and long-term mortality/MACEs in CHD patients were included. In total, 6 independent prospective studies of 10,222 participants with CHD were enrolled in the systematic and meta-analysis. Our outcomes of the meta-analysis indicated that the elevated TG/HDL-C group had a significantly increased risk of long-term all-cause mortality (hazard ratio [HR] = 2.92, 95% confidence interval [CI]: 1.75-4.86, P < .05) and long-term MACEs (HR = 1.56, 95%CI 1.11-2.18, P < .05). In patients with CHD, the present study showed that the high TG/HDL-C was associated with increased risk of long-term all-cause mortality and MACE.


Centrosome amplification-related signature correlated with immune microenvironment and treatment response predicts prognosis and improves diagnosis of hepatocellular carcinoma by integrating machine learning and single-cell analyses.
Centrosome amplification is a well-recognized oncogenic driver of tumor initiation and progression across a variety of malignancies and has been linked with tumor aggressiveness, metastasis, and adverse prognosis. Nevertheless, the significance of centrosome amplification in HCC is not well understood. The TCGA dataset was downloaded for centrosome amplification-related signature construction using the LASSO-penalized Cox regression algorithm, while the ICGC dataset was obtained for signature validation. Single-cell RNA sequencing from GSE149614 was analyzed to profile gene expression and the liver tumor niche. A total of 134 centrosome amplification-related prognostic genes in HCC were detected and 6 key prognostic genes (SSX2IP, SPAG4, SAC3D1, NPM1, CSNK1D, and CEP55) among them were screened out to construct a signature with both high sensitivity and specificity in diagnosis and prognosis of HCC patients. The signature, as an independent factor, was associated with frequent recurrences, high mortality rates, advanced clinicopathologic features, and high vascular invasions. Moreover, the signature was intimately associated with cell cycle-related pathways and TP53 mutation profile, suggesting its underlying role in accelerating cell cycle progression and leading to liver cancer development. Meanwhile, the signature was also closely correlated with immunosuppressive cell infiltration and immune checkpoint expression, making it a vital immunosuppressive factor in the tumor microenvironment. Upon single-cell RNA sequencing, SSX2IP and SAC3D1 were found to be specially expressed in liver cancer stem-like cells, where they promoted cell cycle progression and hypoxia. This study provided a direct molecular link of centrosome amplification with clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of centrosome amplification in liver cancer development and therapy resistance, thereby providing valuable insights into prognostic prediction and therapeutic response of HCC.