[Schizophrenic patients' length of stay: clinical factors of variability and consequences].
Schizophrenia is characterized by profound disruption in cognition and emotion, affecting the most fundamental human attributes: language, thought, perception, affect and sense of self. The clinical picture is further complicated by the multiple secondary consequences of the disorder; notably disrupted education, unemployment, impoverished social relationships, isolation, legal difficulties, family stress and substance abuse. Not surprisingly, the disorder is also associated with suicidal behaviour. The management of schizophrenia is thus extremely difficult with high rates of relapse, treatment refusal and poor treatment outcome. In Europe and the United States there has been a general trend towards decreasing the former long duration of hospital care in favour of short-term pharmacological stabilization in the hospital setting, followed by longer multidisciplinary follow-up within the community. This change reflects, on the one hand, the evolution in aetiological conceptions towards a predominantly neurobiological model of the disorder, with complex social consequences and also social and economic constraints. The clinical consequences of these changes were not, however, evaluated prior to the implementation of these changes. Several studies have shown a clear relationship between reductions in duration of stay and increases in readmission rates and suggest that the development of community services may not in fact significantly improve clinical outcome, and may also possibly increase relapse rates due to the instability of the clinical condition at first discharge. There has been some unsettling evidence to suggest that shortening hospital stays may not be a general panacea. Authors reported in 1999 that deinstitutionalization policies in Denmark had led to premature discharge and subsequently a 100% increase in suicide, a doubling of the rates of criminal acts committed by psychotic patients, and increases of 80 to 100% in acute admission rates. A large follow-up study of psychotic patients in the USA found that hospital stays of less than 14 days were significantly associated with increased suicide risk; on the other hand, shortening hospital stays appears to be linked to higher rates of care satisfaction. Indeed, studies of patients returning to the community compared to those remaining in institutions show not only better quality of life and larger friendship networks, but also reductions in dependence on pharmacotherapy and lower mortality rates. The essential question of whether shortened hospital care may lead to premature discharge or, on the other hand, decreased patient dependency and social deviance, has not been adequately addressed.


A blocking peptide stabilizes lysophosphatidic acid receptor 1 and promotes lysophosphatidic acid-induced cellular responses.
G protein-coupled receptors regulate a variety of cellular responses and have been considered as therapeutic targets for human diseases. Lysophosphatidic acid receptor 1 (LPA1) is a receptor for bioactive lysophospholipid, LPA. LPA/LPA1-mediated signaling contributes to inflammatory and fibrotic responses in lung diseases; thus understanding regulation of LPA1 stability is important for modulating LPA/LPA1 signaling. Our previous study has shown that LPA1 is degraded in the Nedd4 like (Nedd4L) E3 ubiquitin ligase-mediated ubiquitin-proteasome system. In the current study, we attempt to identify a peptide that stabilizes LPA1 through disrupting LPA1 association with Nedd4L. LPA treatment induces both endogenous and overexpressed LPA1 degradation, which is attenuated by a proteasome inhibitor, suggesting that LPA1 is degraded in the proteasome. LPA increases phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and I-κB kinase in lung epithelial cells, and this effect is promoted by overexpression of a peptide (P1) that mimics C-terminal of LPA1. P1, not a control peptide, attenuates LPA-induced LPA1 ubiquitination and degradation, suggesting that P1 stabilizes LPA1. Further, P1 diminishes Nedd4L-mediated degradation of LPA1 and Nedd4L/LPA1 association. In addition to increasing LPA1 signaling, P1 enhances LPA-induced cell migration and gene expression of Elafin, matrix metallopeptidase 1, and serpin family B member 2 in lung epithelial cells. These data suggest that disruption of LPA1 interaction with Nedd4L by P1 increases LPA1 stability and LPA/LPA1 signaling.


Clinical diagnosis of ocular sarcoidosis.
To assess the value of raised serum angiotensin converting enzyme (ACE) levels in making a clinical diagnosis of ocular sarcoidosis in patients with intraocular inflammation, compatible with sarcoidosis, in whom tissue biopsy is either not practical or not possible. The ocular manifestations and clinical course of 22 patients with intraocular inflammation compatible with sarcoidosis and elevated ACE level (including 11 patients with abnormal chest radiograph) were compared with those of a group of 18 patients with intraocular inflammation due to biopsy-proven sarcoidosis. The mean follow-up (+/- SD) was 4.5 +/- 3.4 years in the presumed ocular sarcoidosis group and 7.8 +/- 5.3 years in the biopsy-proven sarcoidosis group. There was no difference in sex, race and age distribution between the two groups. No statistically significant difference could be found between the ocular manifestations seen in each group. The most common finding was retinal vasculitis with panuveitis, seen in 86.4% of the presumed ocular sarcoidosis group and in 83.3% of the biopsy-proven sarcoidosis group. These results suggest that intraocular inflammation compatible with sarcoidosis in conjunction with raised ACE levels would be accordant with a diagnosis of sarcoidosis in patients in whom histological diagnosis is either not practical or not possible.


The effect of nutritional habits and addictions on the incidence of thyroid carcinoma in the Olsztyn province of Poland.
The aim of this study was to investigate the roles of nutritional habits and addictions in the incidence of thyroid carcinoma. The study of risk factors affecting the incidence of thyroid carcinoma was conducted in patients included in a register of thyroid carcinoma. For that purpose, a questionnaire was prepared. The questionnaire covered: personal information, medical history, individual risk factors of thyroid carcinoma such as nutritional habits, alcohol consumption and smoking. Statistical analysis was conducted. The register comprised 297 patients with thyroid carcinoma (89% women) and 589 healthy subjects. 46% of patients declared frequent consumption of milk and dairy products. The patients with thyroid carcinoma consumed cruciferous plants significantly more often than healthy subjects (p = 0.0001) whereas egg consumption among both groups of patients was similar. Low consumption of fish and average table salt consumption was typical of both groups. Alcohol consumption was similar in both groups and was, respectively, 42.18% and 47.59%. The patients with thyroid cancer smoked less frequently than subjects from the control group. Logistic regression analysis showed that carcinoma risk increased in patients who consumed cruciferous vegetables (brassicas). Their regular intake was related to a 1.5-fold (CI 1.19-1.96) higher risk of thyroid carcinoma incidence. Despite the demonstrated decreased risk of thyroid cancer, smoking (OR 0.54) was not considered a protective factor. 1. It is not possible to determine unequivocally the causative factors for the growth in the incidence of thyroid cancer in Olsztyn province. 2. It appears that one of the environmental factors causing the increase is overconsumption of cruciferous vegetables.


Lipoblastomatosis appearing as an unusual symmetric upper lip deformity.
We report an unusual case of a bilateral, symmetric upper lip deformity. The submucosal tissue of the resected redundant portion of the lip was occupied by a mass that was diagnosed histopathologically as lipoblastomatosis. Differential diagnoses of lesions with symmetric upper lip deformity and current controversy regarding the surgical treatment are discussed here.


In silico investigation of potential small molecule inhibitors of the SARS-CoV-2 nsp10-nsp16 methyltransferase complex.
The COVID-19 pandemic caused by SARS-CoV-2 has resulted in an international health emergency. The SARS-CoV-2 nsp16 is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase, and with its cofactor nsp10, is responsible for RNA cap formation. This study aimed to identify small molecules binding to the SAM-binding site of the nsp10-nsp16 heterodimer for potential inhibition of methyltransferase activity. By screening a library of 300 compounds, 30 compounds were selected based on binding scores, side-effects, and availability. Following more advanced docking, six potential lead compounds were further investigated using molecular dynamics simulations. This revealed the dietary compound oleuropein as a potential methyltransferase inhibitor.


The relationship between job stress and patient safety culture among nurses: a systematic review.
Work stress is one of the leading causes of physical and mental problems among nurses and can affect patient safety. Nurses experiencing stress are more prone to make errors, which has consequences for the safety culture. This study aimed to describe the findings of studies that examined the relationship between job stress and patient safety culture among nurses. A systematic review of published English-language articles from 2017 to 2021 was obtained through an electronic search of three large online databases (i.e., CINAHL through EBSCOhost, Medline through PubMed, and Embase). We used the Statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to guide the undertaking of this review. In addition, data extraction and quality assessment were performed for the final seven quantitative articles. This review showed a significant relationship between job-related stress in its different factors, patient safety culture, and patient safety. Three studies of the seven reviewed articles examined the relationship. The rest of the studies examined the relationship indirectly, discussing factors that impacted job stress and how they affected patient safety culture. However, differences in working conditions and study characteristics affected the results of these studies and the significance of this relationship. This review suggests that nursing managers and administrators should consider actions to minimize nursing job stress to the minimum levels and improve their work environment to provide the best possible patient care. Future studies are needed to develop interventions to reduce workplace stress and improve nurses' safety. Furthermore, nurses' managers and educators should train nurses on resilience and how to work in trauma-informed care.


The emergence of infections with community-associated methicillin resistant Staphylococcus aureus.
Recently there have been reports indicating an increased incidence of MRSA infections, afflicting individuals with no apparent risk factors for hospital acquisition. Patients with community-associated (CA) MRSA are significantly younger and had different distributions of clinical infections compared with HA-MRSA patients. CA-MRSA infections have mostly been associated with staphylococcal strains bearing the SCCmec type IV element and PVL genes. These strains are more frequently susceptible to a variety of non-beta-lactam antibiotics. Clinicians must be aware of the wide and, in some cases, unique spectrum of disease caused by CA-MRSA. Continued emergence of MRSA in the community is a public-health problem that warrants increased vigilance in the diagnosis and management of suspected and confirmed staphylococcal infections.


A de novo mutation of the SOX10 gene associated with inner ear malformation in a Guangxi family with Waardenburg syndrome type II.
Waardenburg syndrome type 2 (WS2) is a rare neural-crest disorder, characterized by heterochromic irides or blue eyes and sensorineural hearing loss. The aim of this study was to analyze the clinical features and investigate the genetic cause of WS2 in a small family from Guangxi Zhuang Autonomous region. Whole-exome sequencing and mutational analysis were used to identify disease-causing genes in this family. A de novo missense mutation, C.355C > T (p. Arg119Cys), in exon 2 of SOX10 was related to inner ear malformation in the proband and identified by whole exon sequencing, but this mutation was absent in normal controls and any public databases. According to nucleic acid sequence and protein bioinformatic analysis, this mutation is considered the cause of WS2 without neurologic involvement in the proband. Our findings provide an accurate genetic diagnosis, counseling, and rehabilitation for family members and may contribute to further genotype-phenotype correlation studies of the SOX10 gene.


Receptor-targeted co-transport of DNA and magnetic resonance contrast agents.
Ligand molecules conjugated to polylysine can be electrostatically bound to DNA and can bind receptors or antigens on the surface of cells, delivering the DNA into specific cells and tissues. Several researchers have used this approach to generate non-viral vehicles for the efficient delivery of DNA to specific cells. We have attempted to adopt this general approach to the cell-specific delivery of magnetic contrast agents for use in magnetic resonance imaging (MRI). We have synthesized a new class of agents capable of both transfecting genes into cells and enhancing the contrast of the targeted cells for MRI. DNA is used both to encode a marker gene and as a molecular scaffold, which electrostatically binds polylysine conjugated to transferrin, an iron uptake protein, and polylysine modified with gadolinium chelated to diethylenetriaminepetaacetic acid. When cells displaying the transferrin receptor are treated with these particles, high levels of gene expression are observed, higher than with control particles composed only of transferrin, polylysine and DNA. The treated cells show specific MRI contrast enhancement, which did not require expression of the marker gene. The development of this class of particles permits the use of novel protocols by which genes for genetic therapy and agents for MRI contrast are co-transported. These protocols may allow non-invasive MRI monitoring of DNA delivery for gene therapy in real time.


Evaluation of Circular Saw Injuries in a Reference Center in Microsurgery and Reimplantation.
Objective To evaluate the epidemiologic profile, the time until care, and the type of conduct taken regarding patients who are victims of accidents with circular saws and their resulting injuries, and to make a comparison with the literature. Methods A cross-sectional descriptive study reviewing the medical records of patients cared for from April to December 2018, analyzing age, gender, injured side, affected fingers, month and time of the accident, type of injuries, procedures performed in the emergency room, time elapsed between trauma and admission to the operating room, and reapproach during hospitalization. Results A total of 54 male patients aged between 15 and 72 years were care for. The left side was more affected, and the most frequent type of lesion involved the thumb, which had to be amputated in many cases. In total, 23 patients underwent reimplantation, 3 of which were macroreimplantations. Regarding the time of trauma, 26 cases occurred between noon and 4 p.m., and the time elapsed between the accident and the admission to the operating room was ≥ 6 hours in 84% of the patients. Conclusion Circular saw lesions are predominantly severe, with a potential for leaving permanent sequelae, and they affect mainly the thumb. The characterization of the type of injury and the initial care conditions obtained in the present study may contribute to the policy of prevention and care of patients who are victims of circular saw injuries. Level of Evidence IV; Case Series.


Comparison of machine learning algorithms for predicting diesel/biodiesel/iso-pentanol blend engine performance and emissions.
In this study, machine learning techniques, namely artificial neural network (ANN), support vector machine (SVM), and extreme gradient boosting (XGBoost), were used to comprehensively evaluate engine performance and exhaust emissions for different fuel blends. To obtain valuable insights on optimizing engine performance and emissions for alternative fuel blends and thus contribute to the advancement of knowledge in this field, we focused on iso-pentanol ratios while maintaining the biodiesel ratios constant. The maximum brake thermal efficiency (BTE) values for the diesel (30.13 %), D85B10P5 (29.92 %), D80B10P10 (29.89 %), and D70B10P20 (29.79 %) blends were achieved at 1600 rpm. At 1600 rpm, the brake-specific fuel consumption (BSFC) values for the diesel, D85B10P5, D80B10P10, and D70B10P20 blends were 189.93, 200.93, 202.93, and 203.95 g kWh-1, respectively. In engine performance prediction, the ANN model exhibited superior performance, yielding regression coefficient (R2), root mean square error, and mean absolute error values of 0.984, 0.411 %, and 0.112 %, respectively, in BTE prediction, and 0.958 %, 6.9 %, and 2.95 %, respectively, in BSFC prediction. In exhaust gas temperature prediction, the SVM model exhibited the best performance, yielding an R2 value of 0.981. Although all models successfully predicted NOx emissions, the ANN model exhibited the best performance, achieving an R2 value of 0.959. In CO2 and hydrocarbon estimation, the XGBoost model exhibited the best performance, yielding R2 values of 0.956 and 0.973, respectively. Therefore, the ANN model can be used to accurately predict engine performance, and the XGBoost model can be used to accurately predict emission parameters.


Evolution in the structure and function of carboxyl proteases.
A model for the structure and function of extracellular carboxyl (acid) proteases can be established from three amino acid sequences and four crystal structures of these enzymes. The carboxyl proteases from gastric and fungal origins are very homologous in both primary and tertiary structures. The molecules consist of about 320 residues organized with a secondary structure which is primarily comprised of beta-strands and very similar tertiary structures. An apparent binding cleft, which can accommodate a substrate with about eight amino acid residues, contains near its midpoint the active center residues Asp-215, Asp-32, and Ser-35. These three residues are hydrogen bonded to each other. An intracellular carboxyl protease, cathepsin D, is very homologous to the extracellular enzymes in N-terminal amino acid sequence and primary structure location of active center residues. The tertiary structure of cathepsin D is probably similar, as well. However, cathepsin D contains a unique hydrophobic "tail" made up of about 100 residues added on the C-terminal side. Cathepsin D precursor is over 100,000 daltons in molecular weights, as contrasted to the gastric carboxyl protease zymogens, which are about 40,000 daltons. Carboxyl proteases contain two lobes symmetrical in peptide chain conformations. Each of the lobes also consists of two homologous structural units. These structural characteristics suggest that the original gene was coded for only about eighty amino acid residues and that gene duplication and fusion has taken place twice to produce a single chain carboxyl protease with four basic structural units in two symmetrical lobes. The formation of the zymogens and the cathepsin D "tail" must have resulted from various gene fusions. Partial sequence comparisons also suggest that cathepsin D may be an evolutionary ancestral chain for gastric carboxyl proteases.


Alternative splicing gives rise to a nuclear protein tyrosine phosphatase in Drosophila.
A novel Drosophila protein tyrosine phosphatase gene (dPTP61F) undergoes alternative splicing to encode two non-receptor-like proteins of 61,000 daltons. This splice selection occurs at the 3' end of the message, altering the carboxyl termini of the encoded proteins. These carboxyl-terminal sequences govern the targeting of each protein tyrosine phosphatase either to a cytoplasmic membrane or to the nucleus. The catalytic activity of the two protein products is indistinguishable, suggesting that substrate specificity is modulated by the protein's subcellular location.


Reduced ELANE and SLPI expression compromises dental pulp cell activity.
Patients with ELANE variants and severe congenital neutropenia (SCN) commonly develop oral complications. Whether they are caused only by low neutrophil count or the combination of neutropenia and aberrant dental cells is unknown. Genetic variant was identified with exome sequencing. Dental pulp cells isolated from the SCN patient with an ELANE mutation were investigated for gene expression, enzyme activity, proliferation, colony formation, wound healing, apoptosis, ROS, attachment, spreading and response to lipopolysaccharide. ELANE cells had diminished expression of ELANE and SLPI and reduced neutrophil elastase activity. Moreover, ELANE cells exhibited impaired proliferation, colony forming, migration, attachment and spreading; and significantly increased ROS formation and apoptosis, corresponding with increased Cyclin D1 and MMP2 levels. The intrinsic levels of TGF-β1 and TNF-α were significantly increased; however, IL-6, IL-8 and NF-kB1 were significantly decreased in ELANE cells compared with those in controls. After exposure to lipopolysaccharide, ELANE cells grew larger, progressed to more advanced cell spreading stages and showed significantly increased SLPI, TNF-α and NF-kB1 and tremendously increased IL-6 and IL-8 expression, compared with controls. This study, for the first time, suggests that in addition to neutropenia, the aberrant levels and functions of ELANE, SLPI and their downstream molecules in pulp cells play an important role in oral complications in SCN patients. In addition, pulp cells with diminished neutrophil elastase and SLPI are highly responsive to inflammation.


Calcineurin signaling as a target for the treatment of alcohol abuse and neuroinflammatory disorders.
Converging lines of evidence point to a significant role of neuroinflammation in a host of psychiatric conditions, including alcohol use disorder, TBI, and PTSD. A complex interaction of both peripheral and central signaling underlies processes involved in neuroinflammation. Calcineurin is a molecule that sits at the nexus of these processes and has been clearly linked to a number of psychiatric disorders including alcohol use disorder (AUD). Like its role in regulating peripheral immune cells, calcineurin (CN) plays an integral role in processes regulating neuroimmune function and neuroinflammatory processes. Targeting CN or elements of its signaling pathways at critical points may aid in the functional recovery from neuroinflammatory related disorders. In this review we will highlight the role of neuroinflammation and calcineurin signaling in AUD, TBI and stress-induced disorders and discuss recent findings demonstrating a therapeutic effect of immunosuppressant-induced calcineurin inhibition in a pre-clinical model of binge alcohol drinking.


Standing Ultrasound Adds Clinical Utility for the Diagnosis of Varicoceles.
We assessed the role of standing vs supine scrotal ultrasound (SUS) for varicocele assessment by evaluating differences in clinical outcomes. We retrospectively reviewed men from 2008-2020 diagnosed with varicocele who had documented SUS with both supine and standing assessments with and without Valsalva. Clinical outcomes (semen parameters, TUNEL and serum testosterone [T]) after microsurgical varicocelectomy were compared among men who had varicoceles diagnosed by standing SUS (vein size >2.5 mm, vein size >3.0 mm or reversal of flow) to those who would have been missed on supine SUS only. A total of 349 men underwent varicocelectomy (right: 5 [1.4%]; left: 118 [33.8%]; bilateral: 226 [64.8%]). Disagreement between those with abnormal standing vs normal supine for vein size >2.5 mm was: 56 men (16.1%) on the right and 31 men (8.9%) on the left, for vein size >3.0 mm was: 64 men (18.3%) on the right, and 56 men (16.1%) on the left, and for flow reversal was: 36 (14.0%) on the right and 40 (15.4%) on the left. For those >2.5 mm, only T had significant improvements on the left (p=0.05). For those >3.0 mm significant differences were seen for sperm motility on the right (p=0.04), and TUNEL (p=0.04) and T (p <0.01) on the left. For flow reversal, significant differences were seen for sperm concentration (p <0.01), morphology (p=0.03) and volume (p=0.05) on the right and TUNEL on the left (p=0.02). Standing SUS identifies a greater number of men who would have been missed using supine SUS only.


Parenting Practices during Childhood and Later Adolescent Sexual Outcomes.
Limited empirical evidence exists regarding longitudinal connections between parenting during childhood and adolescents' sexual development. Using structural equation mediation modeling, this study examined how mothers' parenting practices during childhood (ages 8 to 11) directly related to adolescent sexual outcomes (ages 12 to 16) and whether relationships were mediated by parenting practices persisting over time. Two waves of data were used from a large longitudinal national sample including 687 mother-adolescent pairs (Mage = 10.02, SD = 1.15, 50% female, 64% White) in 2002 and 2007. For boys, mothers' knowledge of whereabouts and warmth during childhood had negative direct connections to later frequency of intercourse. However, no parallel connections were found for girls. For both boys and girls, mothers' warmth during childhood was associated with an increased likelihood of sexual debut in adolescence. The findings highlight that parenting practices during childhood directly and indirectly (through parenting trajectories) shape sexual development of children.


Survival and CTG repeat expansion in adults with myotonic dystrophy type 1.
An association is observed between the severity of myotonic dystrophy type 1 (DM1) and the genetic abnormality of cytosine-thymine-guanine (CTG) repeat expansion. It is unknown whether an association exists between survival and CTG repeat expansion. In an adult 406-patient DM1 cohort, the phenotype, including survival age, was evaluated in relation to CTG repeat expansion. At study entry, age was 42 ± 12 (range 18-78) years, with a CTG repeat length of 629 ± 386 (range 54-1965). An inverse correlation was observed between CTG repeat length and the age at onset and younger DM1 phenotype. Over a follow-up of 9.2 ± 3.1 years, 118 (29.1%) patients died, including 60 of neuromuscular respiratory failure, 41 of cardiac causes, and 17 of non-neuromuscular, non-cardiac causes. There was an inverse relationship between all-cause survival and CTG length (relative risk 5.4 per log repeat, 95% confidence interval 2.9-10.2, P < 0.001). The data demonstrate a genotype-mortality association in DM1.


Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Added to Dual or Triple Treatment in Patients with Type 2 Diabetes Mellitus.
We evaluated the effectiveness and safety of sodium-glucose cotransporter 2 inhibitor (SGLT2i) add-on treatment in patients with type 2 diabetes mellitus (T2DM) in the real-world setting. This single-center retrospective study used the clinical database of Seoul National University Hospital in South Korea. Patients who received metformin monotherapy or combination therapy with ≥ 1 other oral hypoglycemic medication and had a baseline glycosylated hemoglobin (HbA1c) between 7.0% and 10.5% were included. Propensity score matching was applied between patients treated with and without SGLT2 inhibitors (SGLT2i and non-SGLT2i groups, respectively). Changes in HbA1c from baseline to week 26 were compared between the SGLT2i and non-SGLT2i groups, and risk of adverse events (AE) were also assessed. A total of 1106 patients were included. At week 26, HbA1c was significantly more reduced by 0.35 percentage points in the SGLT2i group than in the non-SGLT2i group (95% CI 0.30-0.41, P < 0.001). Likewise, the proportion of patients achieving HbA1c < 7% was also significantly higher (51.9% vs. 37.6%, P < 0.05) in the SGLT2i group than in the non-SGLT2i group. The risk of adverse events in the SGLT2i group was mostly comparable with those in the non-SGLT2i group except for diseases of the liver, pain, hypertensive diseases, and metabolic disorders, which showed significantly higher odds in the SGLT2i group. SGLT2i add-on treatment is an effective and safe therapeutic option for patients with T2DM in the real-world practice setting.


Can serum fibrosis markers predict medium/large oesophageal varices in patients with liver cirrhosis?
Non-invasive predictors of medium/large oesophageal varices (LOVs) could reduce the number of screening endoscopies. As portal hypertension is a consequence of liver fibrosis, serum fibrosis markers were evaluated together with other variables as possible non-invasive predictors of medium OV/LOV. A total of 154 cirrhotic patients with splenomegaly and 30 healthy control subjects were recruited in a prospective study in two gastroenterology centres in Upper Egypt. Clinical parameters assessed included Child-Pugh class, liver size and ascites. Laboratory parameters included complete blood count, liver function tests, and aspartate aminotransferase (AST)/platelet ratio. Transforming growth factor-β(1) (TGF-β(1)), alpha(2) macroglobulin (A(2)M) and hyaluronic acid (HA) were assayed. Ultrasonographic examination was done for assessment of liver span, portal vein diameter and detection of minimal ascites. Oesophageal varices were diagnosed and graded by oesophagogastroduodenoscopy. Fifty-four patients (35%) had no or small varices and 100 (65%) patients had medium OV/LOV by endoscopy. On multivariate analysis, the independent predictors of medium OV/LOV were the presence of ascites (β=0.258, p=0.047) and serum HA (β=0.449, p=0.009). The receiver operating characteristic curve for HA showed the area under the curve to be 0.916. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of HA at a cut-off value of 207μgl(-1) were 94%, 77.8%, 88.7%, 87.5% and 88.3%, respectively. The presence of ascites and serum HA level higher than 207μgl(-1) can predict the presence of medium OV/LOV in cirrhotic patients. This would help physicians to identify patients who would most likely benefit from screening endoscopy and thus, reduce costs and discomfort from unnecessary endoscopic procedures.


Noninvasive measurement of stroke volume changes in critically ill patients by means of electrical impedance tomography.
Previous animal experiments have suggested that electrical impedance tomography (EIT) has the ability to noninvasively track changes in cardiac stroke volume (SV). The present study intended to reproduce these findings in patients during a fluid challenge. In a prospective observational study including critically ill patients on mechanical ventilation, SV was estimated via ECG-gated EIT before and after a fluid challenge and compared to transpulmonary thermodilution reference measurements. Relative changes in EIT-derived cardiosynchronous impedance changes in the heart ([Formula: see text]) and lung region ([Formula: see text]) were compared to changes in reference SV by assessing the concordance rate (CR) and Pearson's correlation coefficient (R). We compared 39 measurements of 20 patients. [Formula: see text] did not show to be a reliable estimate for tracking changes of SV (CR = 52.6% and R = 0.13 with P = 0.44). In contrast, [Formula: see text] showed an acceptable trending performance (CR = 94.4% and R = 0.72 with P < 0.0001). Our results indicate that ECG-gated EIT measurements of [Formula: see text] are able to noninvasively monitor changes in SV during a fluid challenge in critically ill patients. However, this was not possible using [Formula: see text]. The present approach is limited by the influences induced by ventilation, posture or changes in electrode-skin contact and requires further validation.


BION microstimulators: a case study in the engineering of an electronic implantable medical device.
The BION (Bionic Neuron) is a single channel implantable neurostimulator of unique design that can be delivered by injection. The development of the BION injectable neurostimulators exemplifies a challenging, but well posed medical design problem addressed with a successful strategy for prioritizing and resolving the biomedical and technological challenges. Though some performance requirements required post-evaluation revision, all fundamental goals were realized. A small number of significant design corrections occurred because the device requirements did not include the full scope of environmental demands. The design has spawned a number of variants optimized for diverse biomedical applications, and its clinical applications continue to evolve. The BION development history demonstrates design successes worth emulating and design pitfalls that may be avoidable for future medical device development teams. This paper serves as an introduction to the BION microstimulator technology and as an analysis of the design process used to develop the early clinical devices.


Validation of Cancer Diagnosis Based on the National Health Insurance Service Database versus the National Cancer Registry Database in Korea.
This study aimed to assess the feasibility of operational definitions of cancer patients in conducting cancer-related studies using the claims data from the National Health Insurance Service (NHIS). Cancer incidence data were obtained from the Korean Central Cancer Registry, the NHIS primary diagnosis, and from the rare and intractable disease (RID) registration program. The operational definition with higher sensitivity for cancer patient verification was different by cancer type. Using primary diagnosis, the lowest sensitivity was found in colorectal cancer (91.5%; 95% confidence interval [CI], 91.7 to 92.0) and the highest sensitivity was found in breast cancer (97.9%; 95% CI, 97.8 to 98.0). With RID, sensitivity was the lowest in liver cancer (91.9%; 95% CI, 91.7 to 92.0) and highest in breast cancer (98.1%; 95% CI, 98.0 to 98.2). In terms of the difference in the date of diagnosis in the cancer registration data, > 80% of the patients showed a < 31-day difference from the RID definition. Based on the NHIS data, the operational definition of cancer incidence is more accurate when using the RID registration program claims compared to using the primary diagnosis despite the relatively lower concordance by cancer type requires additional definitions such as treatment.


A dimensional approach to functional movement disorders: Heresy or opportunity.
Functional movement disorders (FMD) are a common and disabling neuropsychiatric condition, part of the spectrum of functional neurological/conversion disorder. FMD represent one of the most enigmatic disorders in the history of medicine. However, in the twenty years after the first report of distinctive abnormal brain activity associated with functional motor symptoms, there have been tremendous advances in the pathophysiologic understanding of these disorders. FMD can be characterized as a disorder of aberrant neurocircuitry interacting with environmental and genetic factors. These developments suggest that research on FMD could be better served by an integrative, neuroscience-based approach focused on functional domains and their neurobiological substrates. This approach has been developed in 'Research Domain Criteria' (RDoC) project, which promotes a dimensional approach to psychiatric disorders. Here, we use the RDoC conceptualization to review recent neuroscience research on FMD, focusing on the domains most relevant to these disorders. We discuss how the adoption of a similar integrative framework may facilitate the identification of the mechanisms underlying FMD and could also have potential clinical applicability.


A coupled optimization of groundwater remediation alternatives screening under health risk assessment: An application to a petroleum-contaminated site in a typical cold industrial region in Northeastern China.
Contaminated sites have been recognized as posing serious comprehensive social and environmental issues and have earned worldwide attention. China is becoming one of the largest contaminated sites remediation markets in the world and the contaminated sites in northeastern China need to rehabilitate urgently. However, remediation planning is often hindered by high financial costs resulting from incomplete assessments of pollution and inappropriate remediation plans. In-depth contaminated site assessments can provide the necessary baseline data for remediation alternatives screening. Therefore, risk assessments and remediation decisions will play crucial roles in the rehabilitation and reconstruction of contaminated sites in China. The main objectives of this study were to present a novel method for health risk assessment (HRA) and to demonstrate a multicriteria decision analysis (MCDA) based on this method to select the most suitable remediation alternatives of groundwater and to prioritize management of contaminated site. To demonstrate the HRA and MCDA processes, a typical contaminated site in Longtan, Jilin province, China, was used. The results of this research indicated that Benzene (PhH) and 1,2-Dichloroethylene (1,2-DCE) were the main organic pollutants and the vanillin plant in the north of the site was main pollution source. Pollution migrated from the north to the south and the health risk range in winter was significantly greater than in summer. Four remediation alternatives were proposed on the basis of the HRA results. The MCDA results showed that PRB was the most suitable technology for integrating the relevant environmental, social, economic, and technical aspects required for remediation. This study may help responsible agencies to strengthen local risk-based program screening frameworks for contaminated sites, to promote reconstruction projects, and to increase local public confidence of contaminated sites remediation.


Polyglyconate suture in pediatric surgery.
The authors have clinically evaluated a synthetic monofilament suture and have found it very satisfactory for all wound closures, esophageal and intestinal anastomoses, and bronchial closures.


Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40.
Genetic analysis of eukaryotic transcriptional promoters has revealed that protein-coding genes often contain a complex array of cis-control elements consisting of upstream activator sequences and enhancer elements. The metallothionein genes provide a useful example for dissecting the action of multiple interspersed control elements that govern both basal level and regulated expression in animal cells. The human metallothionein (hMTIIA) promoter has been analysed in detail and found to contain no less than five distinct control elements in the 5' flanking regions of the gene that mediate specificity and regulation of transcription. These different control elements can be functionally subdivided into two categories: basal and induced elements. There are several distinct basal recognition sequences, which include a TATA-box, a GC-box, and at least two basal level enhancer (BLE) sequences, that function like classical enhancer elements. The hMTIIA gene also responds to induction by heavy metals and by steroid hormones through the action of metal regulatory elements (MRE) and glucocorticoid responsive elements (GRE). Here we report the identification of two cellular DNA-binding proteins that interact selectively with sequences governing the basal level expression of hMTIIA. One of these factors is a novel activator protein (AP1) that interacts with sequences in the BLE of hMTIIA and also binds to a site within the 72-base pair (bp) repeats of the simian virus 40 (SV40) enhancer region. The second protein has been purified to homogeneity and shown to be transcription factor Sp1 which recognizes and binds to a single GC-box element within the hMTIIA promoter.


Insulin and brain metabolism. Absence of direct action of insulin on K+ and Na+ transport in mouse brain.
This is a study of the effect of insulin on the transport of K+ and Na+ from the blood into the brains of normal mice. Despite profound reductions in plasma and brain glucose levels, reduction of plasma K+ concentration and progressive deterioration of neurologic function 30-120 minutes after insulin injection, in 20-22-day-old animals there was no increase in brain K+ and Na+ concentrations. In fact, at 120 minutes, when the brain water content increased 0.7 per cent, brain K+ concentration was significantly reduced, not elevated. The effect of insulin on brain electrolyte and water content in adult mice was also studied. Although brain water increased 0.5 per cent at 120 minutes, there was no changes in brain Na+ or K+ concentrations at any time after insulin injection. The data from mice do not support a role of insulin in electrolyte transport in brain.


Magnetic Resonance Elastography of the Liver: A Single-Institution Review of Cases Performed in a 5-Year Interval.
This study aimed to assess the diagnostic accuracy of magnetic resonance elastography (MRE) in detecting hepatic fibrosis and determining clinically relevant stiffness cutoff values per stage of fibrosis. This retrospective study assessed 1488 hepatic MRE evaluations performed at a single institution for 5 years. Mean liver stiffness measurements were collected from 282 patients who had an MRE study within 1 year of histopathologic analysis. Areas under receiver operating characteristic curves were calculated for each stage of fibrosis with nonparametric ordinal measures of accuracy, and Youden Index was determined. Mean liver stiffness measurement values were as follows: F0, 2.5± 0.55 kPa; F1, 3.1± 0.80 kPa; F2, 3.4±0.95 kPa; F3, 4.7±1.44 kPa; and F4, 7.9± 2.64 kPa. Nonparametric ordinal measures of accuracy per fibrosis stage were as follows: F0: 0.934, P < 0.001; F0-F1: 0.917, P < 0.001; F0-F2: 0.944, P < 0.001; and F0-F3: 0.941, P < 0.001. Youden Index values for fibrosis stages F2, F3, and F4 were 3.9, 4.0, and 4.5 kPa, respectively. Magnetic resonance elastography is an accurate diagnostic tool in assessing liver fibrosis.


Comparison of screen time and digital gaming habits of Turkish children before and during the coronavirus disease 2019 pandemic.
The aim of this study is to compare the screen time and digital gaming habits of Turkish children before and during the coronavirus disease 2019 (COVID-19) pandemic. This cross-sectional descriptive study was carried out in a university hospital between May 7, 2020 and June 27, 2020. Healthy children aged 3-10 years who applied to the pediatrics clinics for outpatient care were included in the study. A structured survey was applied to the parents who agreed to participate. A total of 253 children were included in the study. It was found that the ratio of children with screen time of ≥1 hour during the pandemic was significantly higher than before the pandemic (p<0.001). It was determined that the ratio of children watching both adult and children's programs increased during the pandemic (p<0.001). The ratio of children playing digital games during the pandemic was also found to be increased significantly compared with that before the pandemic (p<0.001). This study demonstrated that screen and digital gaming time increased independently of sociodemographic characteristics during the COVID-19 pandemic compared with before the pandemic.


Associations Between a History of Depression and Cognitive Performance Among Older Adults in Shandong, China.
This study investigates the relationships between depression and cognitive performance among older adults living in Shandong province. Data were derived from the World Health Organization's Study on global AGEing and adult health (WHO-SAGE) China Wave 1 aged 50 and over residing in Shandong province (n = 1926). Cognitive performance was assessed by overall cognitive score. Data were analysed by multivariate linear regression. In rural Shandong, having a history of depression (- 4.0; p < 0.001), female (- 9.3; p < 0.001), and poor household wealth (- 8.9; p < 0.001) and primary level of education (- 6.4; p < 0.001) were main factors associated with their poor cognitive performance. Notably, in urban Shandong, lowest household wealth (- 12.5; p < 0.001) and not having health insurance (- 9.7; p < 0.001) were significant predictors of adverse cognitive performance. Findings could help inform policy in monitoring depressive symptoms and cognitive performance among older adults in China.


Serum insulinlike growth factor 1 as possible marker for risk and early diagnosis of Parkinson disease.
The level of serum insulinlike growth factor 1 (IGF-1) is increased in idiopathic Parkinson disease (PD). To assess whether the (1) IGF-1 level is increased in patients with PD at the time of diagnosis, (2) increased IGF-1 level is related to impaired motor function in healthy individuals, and (3) detection of increased IGF-1 level will help to identify persons at risk for PD. Cross-sectional cohort study. Serum IGF-1 was measured in 15 patients with newly diagnosed untreated PD and 139 healthy elderly individuals. Participants at risk for PD (n = 11) were defined as having altered motor function according to the Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III), and dopaminergic dysfunction as indicated by sonographically determined substantia nigra hyperechogenicity. The IGF-1 level was higher in patients with PD compared with healthy participants (P = .004) and inversely correlated with the UPDRS-III score (ρ = -0.77). The IGF-1 level was not related to motor function in the healthy group. However, there was no significant difference between the IGF-1 level in the at-risk subgroup vs the PD patients (corrected P = .15), and the IGF-1 level was positively correlated with the UPDRS-III score (ρ = 0.80). Serum IGF-1 monitoring may be valuable in the diagnosis of PD and for the identification of individuals with a putatively increased risk for PD.


The complete mitogenome of giant freshwater prawn (Macrobrachium rosenbergii) from two different selective breeding populations in China.
The giant freshwater prawn (GFP), Macrobrachium rosenbergii, is one of the largest freshwater shrimps in the world, being widely cultured because of its high economic value. In this study, complete mitogenomes of two GFP individuals from different selective breeding populations, 'South Taihu No.2' (ST) and 'Shufeng' (SF), were newly sequenced, compared with each other, and with those of other published Macrobrachium species. The total length is 15,767 bp (ST) and 15,766 bp (SF), including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and one control region. The phylogenetic analyses based on whole mitogenome sequences suggest that 'Shufeng' has a slightly distant relationship with 'South Taihu No.2', with a pairwise genetic distance of 0.011. This study can provide a genetic background for the GFP selective breeding, and add significantly to the knowledgebase regarding crustacean biology and aquaculture as well.


Neoadjuvant progesterone therapy for primary breast cancer: rationale for a clinical trial.
The hormonal milieu at the time of surgery may influence mortality and disease-free survival in patients with primary breast cancer. Indeed, there is evidence that circulating unopposed estrogen is detrimental and that the presence of circulating progesterone results in an improved disease-free and overall survival rate. Thus patients who receive neoadjuvant progesterone therapy may have a better outcome. A randomized controlled trial in which women with primary breast cancer receive either progesterone or placebo before surgery is urgently needed to confirm this hypothesis.


PBPK modeling of the metabolic interactions of carbon tetrachloride and tetrachloroethylene in B6C3F1 mice.
Potential exists for widespread human exposure to low levels of carbon tetrachloride (CT) and tetrachloroethylene (TET). These halocarbons are metabolized by the cytochrome P450 system. CT is known to inhibit its own metabolism (suicide inhibition) and to cause liver injury by generation of metabolically derived free radicals. The objective of this research was to use develop a physiologically based pharmacokinetic (PBPK) model to forcast the metabolic interactions between orally administered CT and TET in male B6C3F1 mice. Trichloroacetic acid (TCA), a stable metabolite of TET, was used as a biomarker to assess inhibition of the cytochrome P450 system by CT. Metabolic constants utilized for CT were 1.0mg/kg/h for Vmaxc_CT and 0.3 for Km_CT (mg/l). Values for TET (based in TCA production), were 6.0mg/kg/h for Vmaxc_TET was 3.0mg/l for Km_TET. The rate of loss of metabolic capacity for CT (suicide inhibition) was describe as: Vmaxloss ( mg / h )=- Kd ( RAM × RAM ) , where Kd (h/kg) is a second-order rate constant, and RAM (mg/h) is the Michaelis-Menten description of the rate of metabolism of CT. For model simplicity, CT was assumed to damage the primary enzymes responsible for metabolism of CT (CYP2E1) and TET (CYP2B2) in an equal fashion. Thus, the calculated fractional loss of TET metabolic capacity was assumed to be equivalent to the calculated loss in metabolic capacity of CT. Use of a Kd value of 400h/kg successfully described serum TCA levels in mice dosed orally with 5-100mg/kg of CT. We report, for the first time, suicide inhibition at a very low dose of CT (1mg/kg). The PBPK model under-predicted the degree of metabolic inhibition in mice administered 1mg/kg of CT. This PBPK model is one of only a few physiological models available to predict the metabolic interactions of chemical mixtures involving suicide inhibition. The success of this PBPK model demonstrates that PBPK models are useful tools for examining the nature of metabolic interactions of chemical mixtures, including suicide inhibition. Further research is required to compare the inhibitory effects of inhaled CT vapors with CT administered by oral bolus dosing and determine the interaction threshold for CT-induced metabolic inhibition.


The metabolic fate of high density lipoprotein (HDL) in the diabetic rat.
Diabetic rats, pre-fed and maintained on a sucrose-rich diet, have marked hyperlipoproteinaemia, with an increase in both very low density (VLDL) and high density lipoproteins (HDL). HDL obtained from both diabetic and non-diabetic rats and labelled with 125I or 135I was injected simultaneously into diabetic and non-diabetic rats. The half life of the two HDL preparations was similar in both diabetic and non-diabetic rats and ranged between 11.4 to 12.0 hours. A-I apolipoprotein had a disappearance rate parallel to the whole HDL, in contrast to the apo-C peptides which had a faster rate of removal. Although the fractional catabolic rate (FCR) of HDL preparations was slower in the diabetic rats, there was a 16% increase in the calculated synthetic rate (SR) of HDL-protein. These observations could explain the increased plasma HDL levels in the sucrose-fed, streptozotocin-induced diabetic rat.


Rapid proteolysis of brain MAP-1 related cytoskeleton-associated 350kd protein by purified calpain.
Microtubule associated protein-1 of brain and its intracellular 350kd analogues were highly sensitive to purified Ca2+-dependent cysteine proteinase (calpain). After 15 second digestion, we detected intermediate degradation products of MAP-1 by immunoblotting using anti-MAP-1 antibody as 290, 260, 220, 170, 140, 112, 80, 68, and 32kd polypeptides. These values corresponded to the molecular weights of the immunoreactive polypeptides of microtubule-enriched cytoskeletons isolated from HeLa and SV-3Y1 cells, suggesting the action of endogenous calpain on intracellular MAP-1 analogues in vivo or during the course of preparation.


Leishmania donovani glycosphingolipid facilitates antigen presentation by inducing relocation of CD1d into lipid rafts in infected macrophages.
NKT cells respond to presentation of specific glycolipids with release of both Th1- and Th2-type cytokines. Leishmania donovani (LD)-infected splenic macrophages (sMϕ(I)) and bone marrow-derived dendritic cells (BMDC(I)) failed to activate NKT cells in response to α-galactosyl ceramide (α-GalCer). The defective antigen presentation could be corrected by treating the cells with the immunostimulating glycosphingophospholipid (GSPL) of LD parasites. In vitro pulsing of BMDC(I) or sMϕ(I) with GSPL, caused the activation of the Vα14(+) CD1d1-specific NKT cell hybridoma DN32.D3. Localization of MHC II and CD1d molecules to membrane lipid rafts has been suggested to play an important role in antigen presentation. Confocal analysis clearly demonstrated that LD infection changed the pattern of CD1d distribution to the non-lipid raft regions and this change could be reversed by GSPL treatment. Isoelectric focusing gel shift assay indicated that GSPL binds to CD1d. GSPL-treated but not untreated BMDC(I) formed immune synapses with NKT cells and this was associated with calcium mobilization. In conclusion, GSPL treatment was associated with modification of BMDC(I)/sMϕ(I) lipid raft structure, which is a site for immune regulation.


Tonic eye movements induced by bilateral and unilateral galvanic vestibular stimulation (GVS) in guinea pigs.
Galvanic vestibular stimulation (GVS) stimulates primary vestibular afferents innervating the semicircular canals (SCCs) and otoliths found in the inner ear of humans and other mammals, including guinea pigs. To determine which pathways contribute to eye movements generated by this artificial vestibular stimulation in guinea pigs, low current intensities of GVS were passed either bilaterally between the tensor-tympani muscles of the two ears (up to 30 μA) or unilaterally between one tensor-tympani electrode and an indifferent on the back of the neck (up to 60 μA). Both forms of GVS were found to selectively generate tonic eye movements without nystagmus, characteristic of the otolith-ocular reflex; the axis of eye rotation did not align with any semicircular canal plane, but was oriented close to the expected axis of eye rotation that would occur in response to the net stimulation of otolith afferents. The induced eye rotation was predominantly vertical with a smaller horizontal deviation and very little torsion. Consistent with the results of previous human studies, the tonic eye movements were found to exhibit bilateral gain enhancement, whereby bilateral GVS generated twice the amplitude of eye rotation as unilateral anodal or cathodal stimulation alone. Eye movement responses to unilateral GVS were symmetrical in amplitude during equivalent intensities of anodal and cathodal stimulation, consistent with the known responses of more regularly and intermediately discharging primary vestibular afferents to GVS. These results together suggest that more regularly discharging otolith-ocular projections may mediate the tonic changes in eye position induced during maintained, low-intensity GVS in guinea pigs.


A systematic review of psychological treatments to manage fatigue in patients with inflammatory bowel disease.
Fatigue is highly prevalent, debilitating and associated with poor mental health in people with inflammatory bowel disease (IBD). However, little is known about the efficacy of psychological interventions to manage IBD fatigue. This systematic review aimed to establish the efficacy of psychological interventions to manage IBD fatigue. Studies were identified by systematically searching MEDLINE, PsychINFO, CINAHL, EMBASE, Cochrane CENTRAL, Google Scholar and Open Grey. Included studies needed to employ a randomised control trial (RCT) design with a psychological intervention targeted at reducing fatigue in patients with IBD and include a measure of fatigue. All screening, as well as data extraction and quality appraisals, were conducted by two researchers independently. Four RCTs were included in this systematic review. Psychological interventions including psychoeducation, cognitive behaviour therapy and solution-based approach showed preliminary efficacy for fatigue, however the studies were small and largely underpowered. CBT was the most efficacious psychotherapy trialled, with a greater reduction in fatigue severity (g = 0.91, CI 95% [- 0.30, 2.11]) and impact (g = 0.87, CI 95% [- 0.22, 2.07]) seen in the intervention group between baseline and 12-months follow-up when compared to the control group using the IBD-F scale. However, while these effect sizes are strong, they were non-significant due to being underpowered. While the evidence is scant and low quality, psychological interventions show promise in improving IBD fatigue. Future studies should examine larger samples and employ longer follow-up to better determine efficacy of psychological interventions for fatigue in people with IBD.


Fangchinoline Exerts Anticancer Effects on Colorectal Cancer Cells by Evoking Cell Apoptosis via Endoplasmic Reticulum Stress.
We studied the anti-tumor effect of fangchinoline (FAN) against human colorectal cancer cell lines CCL-244 and SW480 and analyzed the mechanism of FAN action. The cell viability and apoptosis were assessed by MTT test and Annexin V-PI staining; caspase-3 activity was measured by Western blotting. The expression of endoplasmic reticulum stress-related proteins was assessed by real-time PCR, Western blotting, and gene transfection. It was found that FAN inhibited cell growth and induced apoptosis in human colorectal cancer cell lines CCL-244 and SW480 in a dose-dependent manner. The caspase-3 inhibitor Ac-DEVD-CHO could reverse the inhibitory effect of FAN. Moreover, FAN significantly increased the expression of endoplasmic reticulum stress-related proteins p-PERK, p-eIF2α, ATF4, and CHOP in CCL-244 and SW480 cells. In addition, endoplasmic reticulum stress inhibitor 4-phenylbutyric acid or CHOP knockdown could prevent FAN-induced apoptosis. Thus, FAN induced apoptosis of human colorectal cancer through activation of endoplasmic reticulum stress.


A topology-based investigation of protein interaction sites using Hydrophobic Cluster Analysis.
Hydrophobic clusters, as defined by Hydrophobic Cluster Analysis (HCA), are conditioned binary patterns, made of hydrophobic and non-hydrophobic positions, whose limits fit well those of regular secondary structures. They were proved to be useful for predicting secondary structures in proteins from the only information of a single amino acid sequence and have permitted to assess, in a comprehensive way, the leading role of binary patterns in secondary structure preference towards a particular state. Here, we considered the available experimental 3D structures of protein globular domains to enlarge our previously reported hydrophobic cluster database (HCDB), almost doubling the number of hydrophobic cluster species (each species being defined by a unique binary pattern) that represent the most frequent structural bricks encountered within protein globular domains. We then used this updated HCDB to show that the hydrophobic amino acids of discordant clusters, i.e. those less abundant clusters for which the observed secondary structure is in disagreement with the binary pattern preference of the species to which they belong, are more exposed to solvent and are more involved in protein interfaces than the hydrophobic amino acids of concordant clusters. As amino acid composition differs between concordant/discordant clusters, considering binary patterns may be used to gain novel insights into key features of protein globular domain cores and surfaces. It can also provide useful information on possible conformational plasticity, including disorder to order transitions.


Adjuvant chemotherapy and survival among patients 70 years of age and younger with node-negative breast cancer and the 21-gene recurrence score of 26-30.
The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18-30, particularly those with RS 26-30, are not known. Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18-30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox's proportional hazards model. Among the breast cancer patients with the RS 18-30, 21% of them had RS 26-30. Compared to breast cancer patients with RS 18-25, patients with RS 26-30 had more aggressive tumor characteristics and chemotherapy use and increased risk of breast cancer-specific mortality and overall mortality. In breast cancer patients who were aged ≤ 70 years and had RS of 26-30, chemotherapy administration was associated with a 32% lower risk of breast cancer-specific mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47-0.99) and a 42% lower risk of overall mortality (HR, 0.58; 95% CI, 0.44-0.76). Survival benefits were most pronounced in breast cancer patients who were younger or had grade III tumor. The 21-gene RS of 18-30 showed heterogeneous outcomes, and the RS 26-30 was a significant prognostic factor for an increased risk of mortality. Adjuvant chemotherapy could improve the survival of node-negative, hormone receptor-positive, and HER2-negative breast cancer patients with the 21-gene RS 26-30 and should be considered for patients, especially younger patients or patients with high-grade tumors.


The impact of suboptimal bowel preparation on adenoma miss rates and the factors associated with early repeat colonoscopy.
There are no guidelines for the recommended interval to the next examination after colonoscopy with suboptimal bowel preparation. To identify factors associated with early repeat colonoscopy after initial examinations with suboptimal preparations and to measure adenoma miss rates in this context. Retrospective study. Hospital-based endoscopy unit. Bowel preparation quality was recorded in 12,787 patients. Of 12,787 colonoscopies, preparation quality was suboptimal (poor or fair) in 3047 patients (24%). Among these 3047 patients, repeat examination was performed in <3 years in 505 (17%). Factors associated with early repeat colonoscopy included lack of cecal intubation (odds ratio [OR] 3.62, 95% confidence interval [CI], 2.50-5.24) and finding a polyp (OR 1.55, 95% CI, 1.17-2.07). Among 216 repeat colonoscopies with optimal preparation, 198 adenomas were identified, of which 83 were seen only on the second examination, an adenoma miss rate of 42% (95% CI, 35-49). The advanced adenoma miss rate was 27% (95% CI, 17-41). For colonoscopies repeated in <1 year, the adenoma and advanced adenoma miss rates were 35% and 36%, respectively. Single-center, retrospective study. Although a minority of patients undergo early repeat examination after colonoscopies done with suboptimal bowel preparation, the miss rates for colonoscopies done with suboptimal bowel preparation were high, suggesting that suboptimal bowel preparation substantially decreases colonoscopy effectiveness and may mandate an early follow-up examination.


Effects of 24-hr fasting on methamphetamine- and apomorphine-induced locomotor activities, and on monoamine metabolism in mouse corpus striatum and nucleus accumbens.
The effects of 24-hr fasting on the vertical (VMA) and horizontal (HMA) locomotor activities, on cage climbing activity and on brain monoamine-related substances, were examined using male ddY mice. Both the VMA and HMA increased with fasting, but not the cage climbing activity. Methamphetamine (2 mg/kg, SC) increased the VMA and HMA in both the feeding and fasting mice, whereas with apomorphine (0.1 mg/kg, SC) both decreased. Furthermore, pretreatment with haloperidol (0.025 mg/kg, SC) showed no influence on the methamphetamine-induced VMA increase in both the feeding and fasting mice. However, pretreatment with haloperidol inhibited the methamphetamine-induced HMA increase in both the feeding and fasting mice and showed a higher level of HMA in fasting mice than in feeding mice. When measuring brain monoamine-related substances, the DA, NE, 5-HT, and 5-HIAA levels in the corpus striatum increased, whereas the 3-MT levels decreased. The monoamine levels in the nucleus accumbens of fasting mice were the same as those in feeding mice, except for a decrease of the 3-MT level. These results suggest that the locomotor activity in fasting mice may be increased by a change in the sensitivity of dopaminergic neurons in the corpus striatum.


The relationship between J waves and contact of lung cancer with the heart.
J waves result mainly from an increased density of transient outward current (Ito ). Mechanical stretch to the heart activates multiple signal transduction pathways, in which Ito may be involved. The purpose of this study was to test the hypothesis that mechanical contact of lung cancer with the heart may manifest J waves. We reviewed 12-lead electrocardiograms to examine whether J waves were associated with contact of lung cancer with the heart. J waves were defied as an elevation of ≥0.1 mV at the junction between QRS complex and ST segment with either notching or slurring morphology. The locational interaction between lung cancer and the heart was determined by computed tomography image. A total of 264 patients (176 men; mean 68.5 ± 10.7 years) with lung cancer were evaluated. The prevalence of J waves was 25.4% in the total population. J waves were present in 40 of 44 (90.9%) patients with the contact. In contrast, J waves were present in 25 of 220 (11.4%) patients without the contact. The sensitivity and specificity of the contact for J waves were 90.9% and 88.6%, respectively. The odds ratio of the contact with the heart to the presence of J waves was 78 (95% confidence interval 25.7-236.4). The appearance of J waves that coincided with the development of lung cancer was observed in 12 patients. The presence of J waves was associated with the contact of lung cancer with the heart.


Voice onset time of voiceless bilabial and velar stops in 3-year-old bilingual children and their age-matched monolingual peers.
This study investigates aspects of voice onset time (VOT) of voiceless bilabial and velar stops in monolingual and bilingual children. VOT poses a special challenge for bilingual Spanish- and English-speaking children because although this VOT distinction exists in both languages, the values differ for the same contrast across Spanish and English. Twenty-four 3-year-olds participated in this study (8 bilingual Spanish-English, 8 monolingual Spanish and 8 monolingual English). The VOT productions of /p/ and /k/ in syllable-initial stressed singleton position were compared across participants. Non-parametric statistical analyses were performed to examine differences (1) between monolinguals and bilinguals and (2) between English and Spanish. The main findings of the study were that monolingual and bilingual children generally differed on VOT in English, but not in Spanish. No statistically significant differences were found between the Spanish and the English VOT of the bilingual children, but the VOT values did differ significantly for monolingual Spanish- versus monolingual English-speaking participants. Our findings were interpreted in terms of Flege's Speech Learning Model, finding possible evidence for equivalence classification.


Herpes simplex virus isolates with reduced adefovir susceptibility selected in vivo by foscarnet therapy.
Sequential herpes simplex virus (HSV) isolates from AIDS patients receiving foscarnet therapy were evaluated for susceptibility to adefovir. Foscarnet-resistant isolates with DNA polymerase mutations in regions II, VI, and between I and VII were also associated with an important decrease in susceptibility to adefovir (mean IC50 increase: 4.6-fold compared to pre-foscarnet or wild-type isolates) suggesting that adefovir-resistant HSV could be selected in vivo by foscarnet therapy.


A prospective randomized study comparing exclusion technique and endoaneurysmorrhaphy for treatment of infrarenal aortic aneurysm.
The retroperitoneal approach used in aortic replacement for infrarenal aortic aneurysm has become an important part of the vascular surgeon's armamentarium. Use of the exclusion and bypass technique, however, remains controversial. Although benefits may include reduced blood loss, less operative dissection, and a smoother intraoperative and postoperative course, critics of this technique have alluded to potential drawbacks. In this study the results of the exclusion technique and open endoaneurysmorrhaphy for surgical treatment of abdominal aortic aneurysm were compared. One hundred patients were randomized to either exclusion (EXC) or open endoaneurysmorrhaphy (OP) procedures. A posterolateral left retroperitoneal approach was used in all patients. During surgery, autotransfusion devices were used when needed. Doppler flow and pressures in the excluded aneurysm sac were determined during surgery in EXC to evaluate the completeness of the exclusion. Patient demographics were similar between the two groups. The mean age was 70 years (range, 53 to 89 years). The operative mortality rates were 0% and 1.9% (1 of 51) in the EXC and OP groups, respectively. Nonfatal postoperative complications occurred in 10.2% (5 of 49) of the EXC group and in 23.5% (12 of 51) of the OP group (p < 0.05). Aneurysm sacs were opened in two EXC procedures. Blood loss (mean +/- SD) was 703 +/- 570 ml in the EXC group and 1031 +/- 703 ml in the OP group (p < or = 0.01). The intensive care unit stay (mean +/- SD) was 1.9 +/- 1.2 days in the EXC group and 3.2 +/- 6.9 days in the OP group (p = NS). The hospital stay (mean +/- SD) was 9.8 +/- 5.8 days and 12.1 +/- 17 days in the EXC and OP groups, respectively (p = NS). There has been persistent flow in the excluded sac in two patients, with sac enlargement in one of these patients on postoperative follow-up by duplex scan or clinical examination. The exclusion and bypass technique for repair of infrarenal aortic aneurysm appeared to be an acceptable technique and was associated with less operative blood loss and fewer postoperative complications than those of open aortic endoaneurysmorrhaphy. Exclusion bypass may contribute to a smoother perioperative course and postoperative treatment of these patients.


The Walking Classroom: Measuring the Impact of Physical Activity on Student Cognitive Performance and Mood.
The Walking Classroom is an education program that provides students with an opportunity to accumulate physical activity without losing instructional time. This research tests Kuczala's application of kinesthetic learning theory through measuring knowledge retention, postactivity information processing, and mood in students who engage in a short bout of physical activity while listening to Walking Classroom podcasts about language arts, science, and history, and those who remain seated during a podcast, compared with baseline levels. Students from 9 high-poverty fourth- and fifth-grade classrooms (n = 319) in a North Carolina county comprised the sample. Utilizing multivariate analysis of covariance, the results demonstrate significantly higher levels of learning while walking compared with learning while sitting. Measures of mood utilizing the 10-item version of the Positive and Negative Affect Scale also demonstrated a significant effect in predicted directions. The results support that coupling physical activity with instruction leads to increased performance and mood for elementary school students.


The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels.
Endothelium-independent vasoconstrictor responses in isolated segments of human internal thoracic artery (ITA) and saphenous vein (SV) were used as a bioassay system for the vasoinhibitory activity of bovine chromogranin A (CGA). Preincubation with vasostatin (0.8 micrograms/ml), containing the N-terminal domain of CGA, (CGA1-76, CGA1-113 and CGA1-143ff), inhibited the contractile responses evoked by 80 mM K+, 2.6 microM noradrenaline (NA), or 65 nM endothelin-1 (ET-1) in Ca(2+)-free solution in SV but not in ITA. The results demonstrate a vasoinhibitory activity in vasostatin and show that there is a marked difference between the arterial and venous segments in the Ca2+ independent component of the inhibitory response. A vascular role for the N-terminal domain of CGA is indicated, presumably by inhibiting Ca2+ release from intracellular stores in the human vein but not the artery.


20-Hydroxyecdysone induced aggregation of Drosophila S3 cells is inhibited by antibodies to a hormone-dependent extracellular glycoprotein.
The S3 cell line of Drosophila exhibits numerous responses to the molting hormone 20-hydroxyecdysone, including mitotic arrest, cell aggregation and extensive changes in cell surface and extracellular glycoproteins. We have produced polyclonal antibodies to a major hormone induced extracellular glycoprotein to investigate the role of this molecule in cell aggregation. This glycoprotein with a molecular weight of 110 kD (P110) is found primarily in the culture medium of hormone-induced cells. Upon reduction, the electrophoretic mobility of P110 is decreased, indicating the presence of internal disulfide bonds. Results from treatment of medium proteins with a cross-linking reagent indicate that the molecule is part of a higher molecular weight oligomer (300-400 kD). Fab fragments of anti P110 effectively inhibit the reaggregation of hormone-treated S3 cells, while preimmune Fab fragments have no effect. On the basis of these results, we propose that the P110 glycoprotein complex in the medium of hormone-treated cells functions in hormone-dependent cell-cell adhesion.


Novel mechanisms underlying inhibition of inflammation-induced angiogenesis by dexamethasone and gentamicin via PI3K/AKT/NF-κB/VEGF pathways in acute radiation proctitis.
Acute radiation proctitis (ARP) is one of the most common complications of pelvic radiotherapy attributed to radiation exposure. The mechanisms of ARP are related to inflammation, angiogenesis, and so on. In this study we evaluated the effect of dexamethasone (DXM) combined with gentamicin (GM) enema on ARP mice, and explored its possible mechanisms by transcriptome sequencing, western blot and immunohistochemistry. C57BL/6 mice were randomly divided into 3 groups: healthy control group, ARP model group, and DXM + GM enema treatment group. ARP mice were established by using a single 6 MV X-ray dose of 27 Gy pelvic local irradiation. Transcriptome sequencing results showed that 979 genes were co-upregulated and 445 genes were co-downregulated in ARP mice compared to healthy mice. According to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, we firstly found that PI3K/AKT/NF-κB/VEGF pathways were mostly correlated with the inflammation-induced angiogenesis in ARP mice. PI3K/AKT pathway leads to the activation of NF-κB, which promotes the transcription of VEGF and Bcl-2. Interestingly, symptoms and pathological changes of ARP mice were ameliorated by DXM + GM enema treatment. DXM + GM enema inhibited inflammation by downregulating NF-κB and upregulating AQP3, as well as inhibited angiogenesis by downregulating VEGF and AQP1 in ARP mice. Moreover, DXM + GM enema induced apoptosis by increasing Bax and suppressing Bcl-2. The novel mechanisms may be related to the downregulation of PI3K/AKT/NF-κB/VEGF pathways.


Inter-limb coupling in bimanual rhythmic coordination in Parkinson's disease.
Recently, it has been shown that rhythmic inter-limb coordination is disturbed in patients with Parkinson's disease (PD). The present study aims to investigate whether this coordination deficit is primarily the result of an impaired coupling, related to hypoactivation of the supplementary motor area (SMA), or primarily the indirect result of an asymmetrical distribution of PD symptoms over the left and right limbs (a peripheral process). Thirty PD patients and 30 matched control participants tapped with the index fingers anti-phase and left and right leading gallop patterns in four visual feedback conditions. Symmetrically affected participants performed significantly worse than asymmetrically affected and control participants in the gallop patterns. This result suggested that the central deficit has a stronger effect on inter-limb coupling in PD than the neuromuscular and biomechanical asymmetry between the limbs. Detailed analysis of inter-tap intervals (variability and correlation) suggested that this deficit leads to a compensatory asymmetrical inter-limb coupling in the primarily right-affected patient group, and under specific circumstances also in the primarily left-affected patient group. The difference in coordination strategy between left- and right-affected patients suggested that pre-morbid hand preference is an important structural constraint on the coupling strategies available to the participants.


Ru360 protects against vitrification-induced oocyte meiotic defects by restoring mitochondrial function.
Oocyte vitrification has been widely application in female fertility preservation. Recent studies found that vitrification of immature (germinal vesicle stage, GV) oocytes increased the risk of aneuploidy during meiotic maturation; however, the underlying mechanisms and the strategies to prevent this defect remain unexplored. In this study, we found that vitrification of GV oocytes decreased the first polarbody extrusion rate (90.51 ± 1.04% vs. 63.89 ± 1.39%, p < 0.05) and increased the aneuploid rate (2.50% vs. 20.00%, p < 0.05), accompanied with a series of defects during meiotic maturation, including aberrant spindle morphology, chromosome misalignment, incorrect Kinetochore-Microtubule attachments (KT-MTs) and weakened spindle assembly checkpoint protein complex (SAC) function. We also found that vitrification disrupted mitochondrial function by increasing mitochondrial Ca2+ levels. Importantly, inhibition of mitochondrial Ca2+ entry by 1 μM Ru360 significantly restored mitochondrial function and rescued the meiotic defects, indicating that the increase of mitochondrial Ca2+, at least, was a cause of meiotic defects in vitrified oocytes. These results shed light on the molecular mechanisms of oocyte vitrification-induced adverse effects of meiotic maturation and provided a potential strategy to improve oocyte cryopreservation protocols further.


Patient and surgeon comfort in vitreoretinal surgery performed with Sub-Tenon's Anaesthesia.
Background. Since Stevens first introduced Sub-Tenon's anaesthesia into cataract surgery it has shown itself to be a safe, simple, and efficient technique. The advantages of this type of block are comparable to those of sharp needle anaesthesia and complications are minimal. Several studies have found that the anaesthesia provided by Sub-Tenon's capsule injection is as good as or better for cataract surgery than that achieved by retrobulbar injection, but the efficacy of Sub-Tenon's block in vitreoretinal surgery is less well established. Methods. We performed 50 vitreoretinal procedures; 50 eyes received a Sub-Tenon's injection of a 5 ml mixture (50:50) of lidocaine and ropivacaine, plus 15 IU mL-1 of Hyaluronidase. Results. In 45 cases, only one injection was needed to achieve sufficient anaesthesia and akinesia; in 5 cases a second injection was performed five minutes after the first. Mean surgical time was 45.7 minutes. After surgery, each patient was asked to indicate his value on the VAS pain scale. Mean VAS degree was 2.4. In 7 cases, VAS was > 3 and the pain was successfully managed with the administration of paracetamol in the postoperative period. No light perception was detected at the end of surgery in 33 patients. All cases with 2 injections had no light perception at the end of surgery. Anaesthesia lasted throughout the surgery in all cases. The surgeon performed all surgery comfortably and with no difficulty. Conclusions. According to our experience and to a growing body of evidence, Sub-Tenon's anaesthesia appears to be a safe, simple, versatile, and effective technique and should be considered as a real alternative method of anaesthesia in vitreoretinal surgery.


Silicone exposure associated with breast papillary lesion: A case report.
We described a breast papillary lesion related to silicone breast implant exposure. The case report is in accordance with our initial publication, where we proposed that silicone particles may trigger a process of reverse morphogenesis in pericapsular tissue resulting in metaplasia of the epithelial cells. The relationship between breast metaplasia and silicone implants is still little discussed in the literature. Our current study is based on evidence obtained from the files of a patient with a six-year-old history of silicone breast implant, which resulted in a diagnosis of a papillary lesion after a percutaneous breast biopsy. Currently, the main complications related to implants reported in the literature are intra- and extra-capsular ruptures, capsular contracture, and the most severe, breast implant-associated anaplastic large cell lymphoma. However, another complication not yet widely accepted in the literature is breast implant illness, resulting from silicone induced granuloma of breast implant capsule. Many medical specialists are skeptical about silicone disease potential and argue the lack of scientific evidence to support its existence. We believe that presenting these findings and the appropriate discussion of the results should contribute to a better understanding of the pathologies related to breast implants. It is worth mentioning that the safety of breast implants must be questioned.


Unveiling the dermatological potential of marine fungal species components: Antioxidant and inhibitory capacities over tyrosinase.
Marine fungi are a rich source of biologically active molecules, but a poorly explored bioresource for cosmeceutical products. This study evaluates the phytochemistry, antioxidant, and antityrosinase effects of the organic extracts of marine fungi isolated from various marine environments in India. Out of 35 screened fungal strains, methanol extracts of strains P2, Talaromyces stipitatus, and D4, Aspergillus terreus exhibited antityrosinase activity of 45% and 43%, respectively, at the lowest concentration of 0.5 mg/mL. The highest free radicals scavenging activity of 94% and 97% was observed at 500 mg/mL, respectively, of the same fungal extracts. The total phenolic content ranged from 8.20 to 20.30 mg/g of the dry weight of extract, expressed as gallic acid equivalent. GC-MS analysis of T. stipitatus and A. terreus extract identified seven and 10 major compounds, respectively. Some of the major compounds included azetidine, (3E)-3-[(3,5-dimethoxybenzoyl)hydrazono]-N-isobutyl butanamide, aziridine, and 3-methylcyclopentanone, 1,1-dimethylcyclohexane, cyclopentane carboxylic acid, N-allyl-4,5,6,7-tetrahydro-2-benzothiophene-1-carboxamide, cyclo(l-Pro-l-Val), and 3-phenylpropionitrile. In conclusion, this study showed abundant fungal resources in Indian marine environments. A correlation between total phenolic contents of the extracts confirmed that phenolic compounds play an important role in antioxidant as well as antityrosinase activity of the marine fungal extracts and can be viewed as new potential antityrosinase and antioxidant resources.


[The effect of modern therapy on the course of purulent meningitides (author's transl)].
No fundamental change in the pathogen spectrum of purulent meningitis in adults has occurred between 1951 and 1974. It should be noted, however, that there is an increase in gram-negative pathogens. The lethality has in fact decreased during the period of observation, but the prognosis of pneumococcal meningitis has not been decisively improved by high dosage therapy with penicillin or ampicillin.


Modifications in the production of cytokines and growth factors in drainage fluids following mesh implantation after incisional hernia repair.
The aim of this study was to evaluate changes in the production of some cytokines (interleukins [ILs]-6, -10, -1, and -1ra), vascular endothelial growth factor, and beta-fibroblast growth factor after polypropylene mesh implantation. Twenty female patients were divided into 2 groups. In 1 group, hernia repair was performed with conventional sutures (CR), whereas in the other group polypropylene mesh (MR) was used. Growth factors and cytokines production was analyzed in wound drain fluids based on the amount produced during 24 hours. IL-1 increased substantially in MR patients on postoperative days 1 and 2. IL1-ra and IL-10 production was always significantly higher in CR patients. IL-6 production did not show any considerable difference between the 2 groups. Vascular endothelial growth factor production was significantly higher in the MR than the CR group at all time points, whereas beta-fibroblast growth factor production was higher in the MR than the CR group only on postoperative day 1. Our data suggest that different surgical procedures induce various levels of inflammation and that implantation of prostheses significantly stimulates the inflammatory response.


Missed opportunities in hypertension risk factors screening in Indonesia: a mixed-methods evaluation of integrated health post (POSBINDU) implementation.
To assess the implementation and contextual barriers of POSBINDU, a community-based activity focusing on screening of non-communicable diseases (NCDs), mainly hypertension and diabetes, in Indonesia. This was a concurrent mixed-methods study, with a cross-sectional analysis of secondary data and focus group discussions (FGDs) on stakeholder of POSBINDU. The study was conducted in seven districts in three provinces in Indonesia, with approximately 50% of the primary healthcare (PHC) were selected as areas for data collection (n PHC=100). From 475 POSBINDU sites, we collected secondary data from 54 224 participants. For the qualitative approach, 21 FGDs and 2 in-depth interviews were held among a total of 223 informants. Proportion of POSBINDU visitors getting the hypertension screening and risk factors' assessment, and barriers of POSBINDU implementation. Out of the 114 581 POSBINDU visits by 54 224 participants, most (80%) were women and adults over 50 years old (50%) showing a suboptimal coverage of men and younger adults. Approximately 95.1% of visitors got their blood pressure measured during their first visit; 35.3% of whom had elevated blood pressure. Less than 25% of the visitors reported to be interviewed for NCDs risk factors during their first visit, less than 80% had anthropometric measurements and less than 15% had blood cholesterol examinations. We revealed lack of resources and limited time to perform the complexities of activities and reporting as main barrier for effective hypertension screening in Indonesia. This study showed missed opportunities in hypertension risk factors screening in Indonesia. The barriers include a lack of access and implementation barriers (capability, resources and protocols).


Real-world bleeding in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and prescribed different combinations of dual antiplatelet therapy (DAPT) in England: a population-based cohort study emulating a 'target trial'.
To estimate the incidence and HRs for bleeding for different dual antiplatelet therapies (DAPT) in a real-world population with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in England. A retrospective, population-based cohort study emulating a target randomised controlled trial (tRCT). Linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). Primary and secondary care. Patients ≥18 years old with ACS undergoing emergency PCI. Aspirin and clopidogrel (AC, reference) versus aspirin and prasugrel (AP) or aspirin and ticagrelor (AT); AP evaluated only in patients with ST-elevation myocardial infarction (STEMI). Primary: any bleeding up to 12 months after the index event (HES- or CPRD- recorded). Secondary: HES-recorded bleeding, CPRD-recorded bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular and cerebrovascular events (MACCE). In ACS, the rates of any bleeding for AC and AT were 89 per 1000 person years and 134 per 1000 person years, respectively. In STEMI, rates for AC, AP and AT were 93 per 1000 person years, 138 per 1000 person years and 143 per 100 person years, respectively. In ACS, compared with AC, AT increased the hazard of any bleeding (HR: 1.47, 95% CI 1.19 to 1.82) but did not reduce MACCE (HR: 1.06, 95% CI 0.89 to 1.27). In STEMI, compared with AC, AP and AT increased the hazard of any bleeding (HR: 1.77, 95% CI 1.21 to 2.59 and HR: 1.50, 95% CI 1.10 to 2.05, respectively) but did not reduce MACCE (HR: 1.10, 95% CI 0.80 to 1.51 and HR: 1.21, 95% CI 0.94 to 1.51, respectively). Non-adherence to the prescribed DAPT regimen was 28% in AC (29% in STEMI only), 31% in AP (STEMI only) and 33% in AT (32% in STEMI only). In a real-world population with ACS, DAPT with ticagrelor or prasugrel are associated with increased bleeding compared with DAPT with clopidogrel. ISRCTN76607611.


Immunolocalization of β-catenin and Lef-1 during postnatal hair follicle development in mice.
It is well recognized that the Wnt pathway, in which β-catenin and Lef-1 are important factors, is associated with many physiological processes, including embryogenesis and postnatal development. The Wnt pathway also plays a critical role in the development of skin. It regulates the formation of the dorsal dermis and epidermal appendages in the skin and the activity of epithelial stem cells. In this study, we investigated the presence and localization of β-catenin and Lef-1 in murine hair follicles through the first postnatal month, which encompasses the first hair cycle in mice, using Western blotting and immunohistochemistry. Our results show that β-catenin and Lef-1 are expressed during all stages in a hair cycle, most strongly in the anagen and weakly in the catagen and telogen phases. The results also suggest that the β-catenin-Lef-1 complex may regulate hair follicle cycling. This process will be of considerable interest to future studies.


Radiographic demonstration of small intestinal villi on routine clinical studies.
The radiographic demonstration of the small intestinal villi is reported. The villi were demonstrable with both single- and double-contrast methods on routine clinical studies. The primary requirement for their delineation appears to be employment of a high-resolution radiographic system.


Autograft remodeling after the Ross procedure by cardiovascular magnetic resonance imaging: Aortic stenosis versus insufficiency.
Studies suggest that patients undergoing the Ross procedure for aortic insufficiency are at greater risk of autograft dilatation than those with aortic stenosis. By using a tailored Ross technique to mitigate autograft dilatation in patients with aortic insufficiency, we aimed to compare the biomechanical and morphologic remodeling of the autograft at 1 year between patients with aortic insufficiency and patients with aortic stenosis. A total of 210 patients underwent a Ross procedure (2011-2016). Of those, 86 patients (mean age 43 ± 13 years; 32% were female) completed preoperative and postoperative cardiovascular magnetic resonance imaging. A total of 71 studies were suitable for analysis: 41 patients with aortic stenosis and 30 patients with aortic insufficiency. Nine healthy adults were used as controls. Autograft root dimensions, individual sinus volumes, and distensibility were measured using cardiovascular magnetic resonance. At 1 year, there was no difference in autograft root dimensions between patients with aortic stenosis (mean annulus 25.1 ± 3.1 mm and sinus diameters 35 ± 4.1 mm) and patients with aortic insufficiency (26.6 ± 3 mm and 37.1 ± 3.5 mm; P = .12 and .06, respectively). Relative sinus of Valsalva volumes were symmetrical in the aortic stenosis (right 34.8% ± 4%, left 33.7% ± 3.5%, noncoronary 31.4% ± 3.2%) and aortic insufficiency groups (34.8% ± 3.9%, 33.8% ± 2.8%, 31.3% ± 3.7%, P = .85, .92, and .82), and similar to those of healthy adults. Aortic root distensibility was reduced in both groups compared with healthy adults (P = .003), but was similar between aortic stenosis (3.12 ± 1.58 × 10-3 mm Hg-1) and aortic insufficiency (3.04 ± 1.15 × 10-3 mm Hg-1; P = .9). Using a tailored technique, there were no differences in the morphologic or biomechanical remodeling of the autograft root 1 year after the Ross procedure between patients with aortic stenosis and patients with aortic insufficiency. However, autograft roots are stiffer than native aortic roots.


Sense of impending doom: inhibitory activity in waiting blood donors who subsequently experience vasovagal symptoms.
This study examined autonomic and hemodynamic processes associated with the development of naturally occurring vasovagal responses. Data from a study assessing the physiological correlates of an intervention to reduce vasovagal responses in blood donors were examined (Ditto et al., 2009). Ninety-eight participants were assigned randomly to groups that either practiced applied tension or not. Dependent variables included ratings of vasovagal symptoms, heart rate, blood pressure, and other parameters derived from ambulatory impedance cardiography. Participants who subsequently experienced vasovagal symptoms had a lower ratio between low and high frequency components (LF/HF HRV) of heart rate variability (HRV) before blood donation, suggesting lower sympathetic nervous system activity. They also showed sharper decreases in total peripheral resistance and lower respiration rates. The results suggest that vasovagal reactions that begin during anticipation of a medical procedure may be characterized by an inhibitory process from the outset and do not support the belief that reactions follow a diphasic pattern.


Surgical management of long urethral strictures.
A total of 25 patients with a long urethral stricture involving the bulbomembranoprostatic urethra underwent excision of the afflicted region via the perineal approach with end-to-end anastomosis. Liberation of the distal urethra provided sufficient length for anastomosis without tension of the healthy urethra. Satisfactory results were obtained in 23 of the 25 patients without any functional disturbance of sphincter control.


Successful establishment of partial denitrification by introducing hydrolytic acidification of slowly biodegradable organic matter.
Partial denitrification (PD, nitrate → nitrite) was successfully established in this study by introducing hydrolytic acidification (HA) of slowly biodegradable organic matter (SBOM). A high selectivity for the nitrate over nitrite as electron acceptors was obtained during a 178-day long-term operation, with the nitrate to nitrite transformation ratio climbing to 81.3% at an influent SBOM of 286 mg/L and low-strength nitrate of 40 mg/L. Acetate (33.9%) and dissolved saccharide (19.3%), as the major SBOM HA products, indeed facilitated high-efficiency nitrite production by serving as favorable electron donors. This was well explained by the metagenomic analysis that the dominant Dechloromonas and Thauera denitrifying genera, which hold 3.9 times higher abundance of nitrate reductase than nitrite reductase, also played a key role in carbon glycolysis and acidification. This study provides new insight into PD development in multiple types of wastewater for the versatile carbon/nitrogen metabolism of functional bacteria.


Thriving among Primary Care Physicians: a Qualitative Study.
Burnout is high in primary care physicians and negatively impacts the quality of patient care. While many studies have evaluated burnout, there have been few which investigate those physicians who are satisfied with their careers and life-a phenomenon we term "thriving." To identify factors contributing to both career and life satisfaction through qualitative interviews. The subjects were primary care physicians. Qualitative interviews were performed between July 2018 and March 2020. Physicians were identified by snowball sampling and were asked to complete validated instruments to identify job/life satisfaction and lack of burnout. Semi-structured interviews were conducted, focused on aspects of participants' career and life which contributed to their thriving, including work environment, social networks, family life, institutional support, coping strategies, and extracurricular activities. Transcripts were analyzed using thematic content analysis using a grounded theory approach. Personal, professional, and life factors that contributed to achieving career and life satisfaction in primary care physicians and potential solutions for burnout. Thirty-two physicians were interviewed (9.4% family physicians, 9.4% combined internists-pediatricians, 40.6% internists, and 40.6% pediatricians) with a mean age 54.7 years and 23.8 years in practice. No physicians included met the criteria for burnout. All met the criteria for career and life satisfaction. Five themes were identified as critical to thriving: an intrinsic love for the work, a rich social network, a fulfilling doctor-patient relationship, a value-oriented belief system, and agency in the work environment. Several factors contribute to professional fulfillment and life satisfaction among primary care physicians, which we propose as a model for physicians thriving. Some factors were intrinsic, such as having value-oriented beliefs and inherent love for medicine, while others were extrinsic, such as having a fulfilling social network. Barriers and opportunities to apply these lessons for the wider physician community are discussed.